Ontology-based decision support systems for diabetes nutrition therapy: A systematic literature review.

Diabetes is a non-communicable disease that has reached epidemic proportions, affecting 537 million people globally. Artificial Intelligence can support patients or clinicians in diabetes nutrition therapy - the first medical therapy in most cases of Type 1 and Type 2 diabetes. In particular, ontology-based recommender and decision support systems can deliver a computable representation of experts' knowledge, thus delivering patient-tailored nutritional recommendations or supporting clinical personnel in identifying the most suitable diet. This work proposes a systematic literature review of the domain ontologies describing diabetes in such systems, identifying their underlying conceptualizations, the users targeted by the systems, the type(s) of diabetes tackled, and the nutritional recommendations provided. This review also delves into the structure of the domain ontologies, highlighting several aspects that may hinder (or foster) their adoption in recommender and decision support systems for diabetes nutrition therapy. The results of this review process allow to underline how recommendations are formulated and the role of clinical experts in developing domain ontologies, outlining the research trends characterizing this research area. The results also allow for identifying research directions that can foster a preeminent role for clinical experts and clinical guidelines in a cooperative effort to make ontologies more interoperable - thus enabling them to play a significant role in the decision-making processes about diabetes nutrition therapy.

Laser ultrasonic frequency-domain imaging and phase weighted optimization based on full matrix capture.

Far-field laser technology has greatly promoted the progress of nondestructive ultrasonic imaging of bulk structures. However, under thermoelastic excitation, the body waves exhibit a relatively low signal-to-noise ratio, resulting in images with low resolution and contrast. Based on the motivation, this paper developed a frequency-domain phase weighted imaging method to improve the quality of laser ultrasonic defect imaging. Firstly, laser ultrasonic scanning was performed on the sample with artificial transverse hole defects. The cylindrical lens focused line source was used to improve the intensity of the body wave signals, and ensure that there was no damage on the material surface under high laser energies. Then, the frequency-domain phase shift migration (PSM) algorithm was used to perform multimode imaging of defects, achieving frequency-domain synthetic aperture focusing technique (F-SAFT) and total focused method (F-TFM) imaging based on full matrix capture. Furthermore, the phase circular statistical vector (PCSV) was proposed for weighted optimization, which improved the image quality, suppressed the background noise and multimode artifacts. Finally, the imaging quality of several algorithms were discussed. The results indicate that frequency-domain images were superior to time-domain results. After phase weighting, the imaging quality can be further improved, and the detection blind zone was significantly reduced. This work will contribute to the rapid and high-quality defect imaging of laser ultrasonic.

Semi-supervised model based on implicit neural representation and mutual learning (SIMN) for multi-center nasopharyngeal carcinoma segmentation on MRI.

BACKGROUND: The issue of using deep learning to obtain accurate gross tumor volume (GTV) and metastatic lymph nodes (MLN) segmentation for nasopharyngeal carcinoma (NPC) on heterogeneous magnetic resonance imaging (MRI) images with limited labeling remains unsolved. METHOD: We collected 918 patients with MRI images from three hospitals to develop and validate models and proposed a semi-supervised framework for the fine delineation of multi-center NPC boundaries by integrating uncertainty-based implicit neural representations named SIMN. The framework utilizes the deep mutual learning approach with CNN and Transformer, incorporating dynamic thresholds. Additionally, domain adaptive algorithms are employed to enhance the performance. RESULTS: SIMN predictions have a high overlap ratio with the ground truth. Under the 20 % labeled cases, for the internal test cohorts, the average DSC in GTV and MLN are 0.7981 and 0.7804, respectively; for external test cohort Wu Zhou Red Cross Hospital, the average DSC in GTV and MLN are 0.7217 and 0.7581, respectively; for external test cohorts First People Hospital of Foshan, the average DSC in GTV and MLN are 0.7004 and 0.7692, respectively. No significant differences are found in DSC, HD95, ASD, and Recall for patients with different clinical categories. Moreover, SIMN outperformed existing classical semi-supervised methods. CONCLUSIONS: SIMN showed a highly accurate GTV and MLN segmentation for NPC on multi-center MRI images under Semi-Supervised Learning (SSL), which can easily transfer to other centers without fine-tuning. It suggests that it has the potential to act as a generalized delineation solution for heterogeneous MRI images with limited labels in clinical deployment.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A promotes the inclusion of amyloid precursor protein exon 7.

Extracellular amyloid plaques made of Amyloid-ß (Aß) derived from amyloid precursor protein (APP) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). There are three major isoforms of APP, APP770, APP751, and APP695 generated by alternative splicing of exons 7 and 8. Exon 7 encodes the Kunitz protease inhibitor (KPI) domain. Its inclusion generates APP isoforms containing KPI, APPKPI+, which is elevated in AD and Down syndrome (DS) brains and associated with increased Aß deposition. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) phosphorylates many splicing factors and regulates the alternative splicing of pre-mRNA. It is upregulated in DS and AD brain. However, it is not yet clear whether Dyrk1A could regulate APP alternative splicing. In the present study, we overexpressed or knocked down Dyrk1A in cultured cells and observed that Dyrk1A promoted the inclusion of both APP exons 7 and 8. Moreover, a significant increase in APP exon7 inclusion was also detected in the forebrain and hippocampus of human Dyrk1A transgenic mice - Tg/Dyrk1A. Screening for splicing factors regulated by Dyrk1A revealed that serine/arginine-rich protein 9G8 inhibited APP exon7 inclusion and interacted with APP pre-mRNA. In vitro, expression of exon 7 facilitated APP cleavage. In human Dyrk1A transgenic mice, we also found an increase in Aß production. These findings suggest that Dyrk1A inhibits the splicing factor 9G8 and promotes APP exon 7 inclusion, leading to more APPKPI+ expression and APP cleavage and potentially contributing to Aß production in vivo.

THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma.

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation.

Biology System Description Language (BiSDL): a modeling language for the design of multicellular synthetic biological systems.

BACKGROUND: The Biology System Description Language (BiSDL) is an accessible, easy-to-use computational language for multicellular synthetic biology. It allows synthetic biologists to represent spatiality and multi-level cellular dynamics inherent to multicellular designs, filling a gap in the state of the art. Developed for designing and simulating spatial, multicellular synthetic biological systems, BiSDL integrates high-level conceptual design with detailed low-level modeling, fostering collaboration in the Design-Build-Test-Learn cycle. BiSDL descriptions directly compile into Nets-Within-Nets (NWNs) models, offering a unique approach to spatial and hierarchical modeling in biological systems. RESULTS: BiSDL's effectiveness is showcased through three case studies on complex multicellular systems: a bacterial consortium, a synthetic morphogen system and a conjugative plasmid transfer process. These studies highlight the BiSDL proficiency in representing spatial interactions and multi-level cellular dynamics. The language facilitates the compilation of conceptual designs into detailed, simulatable models, leveraging the NWNs formalism. This enables intuitive modeling of complex biological systems, making advanced computational tools more accessible to a broader range of researchers. CONCLUSIONS: BiSDL represents a significant step forward in computational languages for synthetic biology, providing a sophisticated yet user-friendly tool for designing and simulating complex biological systems with an emphasis on spatiality and cellular dynamics. Its introduction has the potential to transform research and development in synthetic biology, allowing for deeper insights and novel applications in understanding and manipulating multicellular systems.

Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension.

BACKGROUND: Previous studies have indicated that neutrophil extracellular traps (NETs) play a pivotal role in pathogenesis of pulmonary arterial hypertension (PAH). However, the specific mechanism underlying the impact of NETs on pulmonary artery smooth muscle cells (PASMCs) has not been determined. The objective of this study was to elucidate underlying mechanisms through which NETs contribute to progression of PAH. METHODS: Bioinformatics analysis was employed in this study to screen for potential molecules and mechanisms associated with occurrence and development of PAH. These findings were subsequently validated in human samples, coiled-coil domain containing 25 (CCDC25) knockdown PASMCs, as well as monocrotaline-induced PAH rat model. RESULTS: NETs promoted proliferation of PASMCs, thereby facilitating pathogenesis of PAH. This phenomenon was mediated by the activation of transmembrane receptor CCDC25 on PASMCs, which subsequently activated ILK/ß-parvin/RAC1 pathway. Consequently, cytoskeletal remodeling and phenotypic transformation occur in PASMCs. Furthermore, the level of NETs could serve as an indicator of PAH severity and as potential therapeutic target for alleviating PAH. CONCLUSION: This study elucidated the involvement of NETs in pathogenesis of PAH through their influence on the function of PASMCs, thereby highlighting their potential as promising targets for the evaluation and treatment of PAH.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Concomitant Light-Reversible Magnetic Response in Multiferroic Oxide Heterostructures for Multiphysics Applications.

The concept of multiphysics, where materials respond to diverse external stimuli, such as magnetic fields, electric fields, light irradiation, stress, heat, and chemical reactions, plays a fundamental role in the development of innovative devices. Nanomanufacturing, especially in low-dimensional systems, enhances the synergistic interactions taking place on the nanoscale. Light-matter interaction, rather than electric fields, holds great promise for achieving low-power, wireless control over magnetism, solving two major technological problems: the feasibility of electrical contacts at smaller scales and the undesired heating of the devices. Here, we shed light on the remarkable reversible modulation of magnetism using visible light in epitaxial Fe3O4/BaTiO3 heterostructure. This achievement is underpinned by the convergence of two distinct mechanisms. First, the magnetoelastic effect, triggered by ferroelectric domain switching, induces a proportional change in coercivity and remanence upon laser illumination. Second, light-matter interaction induces charged ferroelectric domain walls' electrostatic decompensations, acting intimately on the magnetization of the epitaxial Fe3O4 film by magnetoelectric coupling. Crucially, our experimental results vividly illustrate the capability to manipulate magnetic properties using visible light. This concomitant mechanism provides a promising avenue for low-intensity visible-light manipulation of magnetism, offering potential applications in multiferroic devices.

Multi-branch myocardial infarction detection and localization framework based on multi-instance learning and domain knowledge.

Objective. Myocardial infarction (MI) is a serious cardiovascular disease that can cause irreversible damage to the heart, making early identification and treatment crucial. However, automatic MI detection and localization from an electrocardiogram (ECG) remain challenging. In this study, we propose two models, MFB-SENET and MFB-DMIL, for MI detection and localization, respectively.Approach. The MFB-SENET model is designed to detect MI, while the MFB-DMIL model is designed to localize MI. The MI localization model employs a specialized attention mechanism to integrate multi-instance learning with domain knowledge. This approach incorporates handcrafted features and introduces a new loss function called lead-loss, to improve MI localization. Grad-CAM is employed to visualize the decision-making process.Main Results.The proposed method was evaluated on the PTB and PTB-XL databases. Under the inter-patient scheme, the accuracy of MI detection and localization on the PTB database reached 93.88% and 67.17%, respectively. The accuracy of MI detection and localization on the PTB-XL database were 94.89% and 85.83%, respectively.Significance. Our method achieved comparable or better performance than other state-of-the-art algorithms. The proposed method combined deep learning and medical domain knowledge, demonstrates effectiveness and reliability, holding promise as an efficient MI diagnostic tool to assist physicians in formulating accurate diagnoses.

Conformational and dynamic properties of the KH1 domain of FMRP and its fragile X syndrome linked G266E variant.

The Fragile X messenger ribonucleoprotein (FMRP) is a multi-domain protein involved in interactions with various macromolecules, including proteins and coding/non-coding RNAs. The three KH domains (KH0, KH1 and KH2) within FMRP are recognized for their roles in mRNA binding. In the context of Fragile X syndrome (FXS), over-and-above CGG triplet repeats expansion, three specific point mutations have been identified, each affecting one of the three KH domains (R138QKH0, G266EKH1, and I304NKH2) resulting in the expression of non-functional FMRP. This study aims to elucidate the molecular mechanism underlying the loss of function associated with the G266EKH1 pathological variant. We investigate the conformational and dynamic properties of the isolated KH1 domain and the two KH1 site-directed mutants G266EKH1 and G266AKH1. Employing a combined in vitro and in silico approach, we reveal that the G266EKH1 variant lacks the characteristic features of a folded domain. This observation provides an explanation for functional impairment observed in FMRP carrying the G266E mutation within the KH1 domain, as it renders the domain unable to fold properly. Molecular Dynamics simulations suggest a pivotal role for residue 266 in regulating the structural stability of the KH domains, primarily through stabilizing the α-helices of the domain. Overall, these findings enhance our comprehension of the molecular basis for the dysfunction associated with the G266EKH1 variant in FMRP.

Factor VIII moiety of recombinant Factor VIII Fc fusion protein impacts Fc effector function and CD16+ NK cell activation.

Recombinant Factor VIII-Fc fusion protein (rFVIIIFc) is an enhanced half-life therapeutic protein product used for the management of hemophilia A. Recent studies have demonstrated that rFVIIIFc interacts with Fc gamma receptors (FcγR) resulting in the activation or inhibition of various FcγR-expressing immune cells. We previously demonstrated that rFVIIIFc, unlike recombinant Factor IX-Fc (rFIXFc), activates natural killer (NK) cells via Fc-mediated interactions with FcγRIIIA (CD16). Additionally, we showed that rFVIIIFc activated CD16+ NK cells to lyse a FVIII-specific B cell clone. Here, we used human NK cell lines and primary NK cells enriched from peripheral blood leukocytes to study the role of the FVIII moiety in rFVIIIFc-mediated NK cell activation. Following overnight incubation of NK cells with rFVIIIFc, cellular activation was assessed by measuring secretion of the inflammatory cytokine IFNγ by ELISA or by cellular degranulation. We show that anti-FVIII, anti-Fc, and anti-CD16 all inhibited indicating that these molecules were involved in rFVIIIFc-mediated NK cell activation. To define which domains of FVIII were involved, we used antibodies that are FVIII domain-specific and demonstrated that blocking FVIII C1 or C2 domain-mediated membrane binding potently inhibited rFVIIIFc-mediated CD16+ NK cell activation, while targeting the FVIII heavy chain domains did not. We also show that rFVIIIFc binds CD16 with about five-fold higher affinity than rFIXFc. Based on our results we propose that FVIII light chain-mediated membrane binding results in tethering of the fusion protein to the cell surface, and this, together with increased binding affinity for CD16, allows for Fc-CD16 interactions to proceed, resulting in NK cellular activation. Our working model may explain our previous results where we observed that rFVIIIFc activated NK cells via CD16, whereas rFIXFc did not despite having identical IgG1 Fc domains.

Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt.

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.

Offloading the computational complexity of transfer learning with generic features.

Deep learning approaches are generally complex, requiring extensive computational resources and having high time complexity. Transfer learning is a state-of-the-art approach to reducing the requirements of high computational resources by using pre-trained models without compromising accuracy and performance. In conventional studies, pre-trained models are trained on datasets from different but similar domains with many domain-specific features. The computational requirements of transfer learning are directly dependent on the number of features that include the domain-specific and the generic features. This article investigates the prospects of reducing the computational requirements of the transfer learning models by discarding domain-specific features from a pre-trained model. The approach is applied to breast cancer detection using the dataset curated breast imaging subset of the digital database for screening mammography and various performance metrics such as precision, accuracy, recall, F1-score, and computational requirements. It is seen that discarding the domain-specific features to a specific limit provides significant performance improvements as well as minimizes the computational requirements in terms of training time (reduced by approx. 12%), processor utilization (reduced approx. 25%), and memory usage (reduced approx. 22%). The proposed transfer learning strategy increases accuracy (approx. 7%) and offloads computational complexity expeditiously.

Telemedicine, e-Health, and Digital Health Equity: A Scoping Review.

Background: With the progressive digitization of people's lives and in the specific healthcare context, the issue of equity in the healthcare domain has extended to digital environments or e-environments, assuming the connotation of "Digital Health Equity" (DHE). Telemedicine and e-Health, which represent the two main e-environments in the healthcare context, have shown great potential in the promotion of health outcomes, but there can be unintended consequences related to the risk of inequalities. In this paper, we aimed to review papers that have investigated the topic of Digital Health Equity in Telemedicine and e-Health [definition(s), advantages, barriers and risk factors, interventions]. Methods: We conducted a scoping review according to the methodological framework proposed in PRISMA-ScR guidelines on the relationship between Digital Health Equity and Telemedicine and e-Health via Scopus and Pubmed electronic databases. The following inclusion criteria were established: papers on the relationship between Digital Health Equity and Telemedicine and/or e-Health, written in English, and having no time limits. All study designs were eligible, including those that have utilized qualitative and quantitative methods, methodology, or guidelines reports, except for meta-reviews. Results: Regarding Digital Health Equity in Telemedicine and e-Health, even if there is no unique definition, there is a general agreement on the idea that it is a complex and multidimensional phenomenon. When promoting Digital Health Equity, some people may incur some risk/s of inequities and/or they may meet some obstacles. Regarding intervention, some authors have proposed a specific field/level of intervention, while other authors have discussed multidimensional interventions based on interdependence among the different levels and the mutually reinforcing effects between all of them. Conclusion: In summary, the present paper has discussed Digital Health Equity in Telemedicine and e-Health. Promoting equity of access to healthcare is a significant challenge in contemporary times and in the near future. While on the one hand, the construct "equity" applied to the health context highlights the importance of creating and sustaining the conditions to allow anyone to be able to reach (and develop) their "health potential", it also raises numerous questions on "how this can happen". An overall and integrated picture of all the variables that promote DHE is needed, taking into account the interdependence among the different levels and the mutually reinforcing effects between all of them.

Optimal timing for drug delivery into the hippocampus by focused ultrasound: A comparison of hydrophilic and lipophilic compounds.

Aims: Previous studies have reported that focused ultrasound (FUS) helps modulate the blood-brain barrier (BBB). These studies have generally used the paracellular pathway owing to tight junction proteins (TJPs) regulation. However, BBB transport pathways also include diffusion and transcytosis. Few studies have examined transcellular transport across endothelial cells. We supposed that increased BBB permeability caused by FUS may affect transcytosis. We investigated drug delivery through transcytosis and paracellular transport to the brain after BBB modulation using FUS. Main methods: FUS and microbubbles were applied to the hippocampus of rats, and were euthanized at 1, 4, 24, and 48 h after sonication. To investigate paracellular transport, we analyzed TJPs, including zona occludens-1 (ZO-1) and occludin. We also investigated caveola-mediated transcytosis by analyzing caveola formation and major facilitator superfamily domain-containing 2a (Mfsd2a) levels, which inhibit caveola vesicle formation. Key findings: One hour after FUS, ZO-1 and occludin expression was the lowest and gradually increased over time, returning to baseline 24 h after FUS treatment. Compared with that of TJPs, caveola formation started to increase 1 h after FUS treatment and peaked at 4 h after FUS treatment before returning to baseline by 48 h after FUS treatment. Decreased Mfsd2a levels were observed at 1 h and 4 h after FUS treatment, indicating increased caveola formation. Significance: FUS induces BBB permeability changes and regulates both paracellular transport and caveola-mediated transcytosis. However, a time difference was observed between these two mechanisms. Hence, when delivering drugs into the brain after FUS, the optimal drug administration timing should be determined by the mechanism by which each drug passes through the BBB.

Spontaneous Coronary Artery Dissection With Concomitant Coronary Vasospasm.

We herein describe a case of acute myocardial infarction due to spontaneous coronary artery dissection complicated by vasospastic angina. Given the need for different clinical management strategies of these cardiac manifestations, clinicians should consider the possibility of concomitant vasospasm in cases of spontaneous coronary artery dissection.

[Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer]. / ç»“ç›´è‚ ç™Œæ ¹æ²»æœ¯åŽæ‚£è€ Tim-3、galectin-9è¡¨è¾¾æ°´å¹³ä¸Žå ¶ä¸´åºŠç— ç†ç‰¹å¾åŠé¢„åŽçš„å ³ç³».

Objective: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer. Methods: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients. Results: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05). Conclusion: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

A new perspective on balancing life domains: work-nonwork balance crafting.

BACKGROUND: Self-initiated and proactive changes in working conditions through crafting are essential for shaping work and improving work-related well-being. Recently, the research stream of job crafting has been extended to other life domains. The present paper aims to study a novel crafting concept-work-nonwork balance crafting-investigating the role of its antecedents and identifying relevant outcomes. Work-nonwork balance crafting is defined as individuals' unofficial techniques and activities to shape their work-nonwork balance, here considering their life domain boundary preferences. METHODS: In the study, 1,060 employees in three European countries (Austria, Germany and Switzerland) were surveyed in a longitudinal three-wave study with three-month intervals. We explored the influences of job/home demands and resources as antecedents of work-nonwork balance crafting. Important constructs for employee health and well-being (i.e., work engagement, work-related burnout, mental well-being and detachment from work) were investigated as outcomes. RESULTS: The findings suggest that resources and demands in the context of work or home are key antecedents of work-nonwork balance crafting. Work-nonwork balance crafting was also predictive for important employee health and well-being outcomes over three months, mainly in a positive and health-promoting way. CONCLUSION: This study provides insights into the antecedents of proactive efforts to balance the complex interplay of life domains. By studying work-nonwork balance crafting, we provide a new perspective on crafting beyond job crafting, which may help maintain or improve employees' mental health and well-being.

Genetic and multi-omic risk assessment of Alzheimer's disease implicates core associated biological domains.

INTRODUCTION: Alzheimer's disease (AD) is the predominant dementia globally, with heterogeneous presentation and penetrance of clinical symptoms, variable presence of mixed pathologies, potential disease subtypes, and numerous associated endophenotypes. Beyond the difficulty of designing treatments that address the core pathological characteristics of the disease, therapeutic development is challenged by the uncertainty of which endophenotypic areas and specific targets implicated by those endophenotypes to prioritize for further translational research. However, publicly funded consortia driving large-scale open science efforts have produced multiple omic analyses that address both disease risk relevance and biological process involvement of genes across the genome. METHODS: Here we report the development of an informatic pipeline that draws from genetic association studies, predicted variant impact, and linkage with dementia associated phenotypes to create a genetic risk score. This is paired with a multi-omic risk score utilizing extensive sets of both transcriptomic and proteomic studies to identify system-level changes in expression associated with AD. These two elements combined constitute our target risk score that ranks AD risk genome-wide. The ranked genes are organized into endophenotypic space through the development of 19 biological domains associated with AD in the described genetics and genomics studies and accompanying literature. The biological domains are constructed from exhaustive Gene Ontology (GO) term compilations, allowing automated assignment of genes into objectively defined disease-associated biology. This rank-and-organize approach, performed genome-wide, allows the characterization of aggregations of AD risk across biological domains. RESULTS: The top AD-risk-associated biological domains are Synapse, Immune Response, Lipid Metabolism, Mitochondrial Metabolism, Structural Stabilization, and Proteostasis, with slightly lower levels of risk enrichment present within the other 13 biological domains. DISCUSSION: This provides an objective methodology to localize risk within specific biological endophenotypes and drill down into the most significantly associated sets of GO terms and annotated genes for potential therapeutic targets.