Evolvability of cancer-associated genes under APOBEC3A/B selection.

Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and genetic variation. Mutations generated by APOBEC3 contribute to genetic variation and tumor evolvability. However, the influence of APOBEC3 on the evolvability of the genome and its differential impact on cancer genes versus non-cancer genes remains unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer and non-cancer genes, suggesting unique associations with cancer. Studying a bat species with numerous APOBEC3 genes, we found distinct motif patterns in orthologs of cancer genes compared to non-cancer genes, as in humans, suggesting APOBEC3 evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC3-induced heterogeneity enhances cancer evolution through bimodal patterns of mutations in certain classes of genes. Our results suggest the bimodal distribution of APOBEC-induced mutations can significantly increase cancer heterogeneity.

Evolvability of cancer-associated genes under APOBEC3A/B selection.

Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and, ultimately, genetic variation. Mutations generated by APOBEC3 cytidine deaminases can contribute to genetic variation and the consequences of APOBEC activation differ depending on the stage of cancer, with the most significant impact observed during the early stages. However, how APOBEC activity shapes evolutionary patterns of genes in the host genome and differential impacts on cancer-associated and non-cancer genes remain unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer-related genes and controls, suggesting unique associations with cancer. Studying a bat species with many more APOBEC3 genes, we found diverse motif patterns in orthologs of cancer genes compared to controls, similar to humans and suggesting APOBEC evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC-induced heterogeneity enhances cancer evolution, shaping clonal dynamics through bimodal introduction of mutations in certain classes of genes. Our results suggest that a major consequence of the bimodal distribution of APOBEC affects greater cancer heterogeneity.

A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation.

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species and 114 metabolites from the gutMgene database. Further, we used different online-based database platforms to predict 1890 gene targets associated with metabolites. Moreover, DisGeNET, OMIM, and Genecard databases were used to consider 13,104 disease-related gene targets. We used a Venn diagram and various protein-protein interactions (PPIs), KEGG pathways, and GO analyses for the functional analysis of gene targets. Moreover, the subnetwork of protein-protein interactions (through string and cytoscape platforms) was used to select the top 20% of gene targets through degree centrality, betweenness centrality, and closeness centrality. To screen the possible candidate compounds, we performed an analysis of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of metabolites and then found the best binding affinity using molecular docking simulation. (3) Results: Finally, we found the key gene targets that interact with suitable compounds and function against kidney cancer and inflammation, such as MTOR (with glycocholic acid), PIK3CA (with 11-methoxycurvularin, glycocholic acid, and isoquercitrin), IL6 (with isoquercitrin), PTGS2 (with isoquercitrin), and IGF1R (with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, isoquercitrin), showed a lower binding affinity. (4) Conclusions: This study provides evidence to support the positive effects of SCFA-producing microbial metabolites that function against kidney cancer and inflammation and makes integrative research proposals that may be used to guide future studies.

Development of Parkinson Patient Generated Data Collection Platform Using FHIR and IoT Devices.

Internet of Things (IoT) devices can be effectively used in cases where continuous observation of patients is required, such as Parkinson's disease. This is due to the characteristics of the IoT (Internet of Things), which allows data to be measured and transmitted at any time, anywhere. In this study, we developed a health data collection platform that stores and transmits the foot pressure data of Parkinson patients using FHIR (Fast Healthcare Interoperability Resources). The platform can be used to collect the foot pressure of a large number of Parkinson's patients. Based on the accumulated data, it is possible to identify abnormal behaviors such as walking pattern, tilt and instability of stride length in patients with Parkinson's disease. Based on the results of this study, accurate diagnosis and treatment of Parkinson's disease can be made.

Distinct immune tones are established by Lactococcus lactis BFE920 and Lactobacillus plantarum FGL0001 in the gut of olive flounder (Paralichthys olivaceus).

The immune tone is defined as an immunological state during which the readiness for immune response is potentiated. The establishment of immune tone in the gut of olive flounder (Paralichthys olivaceus) was investigated by feeding Lactococcus lactis BFE920 (LL) or Lactobacillus plantarum FGL0001 (LP). LL-fed flounder showed significantly increased levels of regulatory genes (FOXP3, IL-10, and TGF-ß1), CD18, and CD83 in the gut. In contrast, LP feeding drastically increased proinflammatory genes (T-bet, IL-1ß, and IFN-γ) and CD18. This indicates that LL and LP establish different types of local immune tones in the gut through differential activation of innate immune cells: LL activates both macrophages and dendritic cells while LP activates macrophages only. Both of the immune tones required at least a total of 6 probiotic feeds during 72 h for a stable establishment. Once established, the type of immune tone remained steady even up to 30 days (a total of 60 feeds) probiotics feeding. The LL-induced regulatory immune tone enhanced the level of occludin, a tight junction molecule, significantly more than that observed with the proinflammatory immune tone established by LP feeding. Consequently, LL-fed fish showed considerably lower gut permeability than that of the LP-fed group. Furthermore, when orally challenged by Edwardsiella tarda, LL-fed flounder survived at a significantly higher rate than LP-fed fish. The data clearly demonstrate that individual probiotics establish distinct types of immune tone in the fish gut, which in turn influences the immunological status as well as the physiology of the gut. Selection of proper probiotics may be essential for optimal effects in aquaculture farming.

Clinical Document Architecture integration system to support patient referral and reply letters.

Many Clinical Document Architecture (CDA) referrals and reply documents have been accumulated for patients since the deployment of the Health Information Exchange System (HIES) in Korea. Clinical data were scattered in many CDA documents and this took too much time for physicians to read. Physicians in Korea spend only limited time per patient as insurances in Korea follow a fee-for-service model. Therefore, physicians were not allowed sufficient time for making medical decisions, and follow-up care service was hindered. To address this, we developed CDA Integration Template (CIT) and CDA Integration System (CIS) for the HIES. The clinical items included in CIT were defined reflecting the Korean Standard for CDA Referral and Reply Letters and requests by physicians. CIS integrates CDA documents of a specified patient into a single CDA document following the format of CIT. Finally, physicians were surveyed after CIT/CIS adoption, and they indicated overall satisfaction.

Embedding the shapes of regions of interest into a Clinical Document Architecture document.

Sharing a medical image visually annotated by a region of interest with a remotely located specialist for consultation is a good practice. It may, however, require a special-purpose (and most likely expensive) system to send and view them, which is an unfeasible solution in developing countries such as Vietnam. In this study, we design and implement interoperable methods based on the HL7 Clinical Document Architecture and the eXtensible Markup Language Stylesheet Language for Transformation standards to seamlessly exchange and visually present the shapes of regions of interest using web browsers. We also propose a new integration architecture for a Clinical Document Architecture generator that enables embedding of regions of interest and simultaneous auto-generation of corresponding style sheets. Using the Clinical Document Architecture document and style sheet, a sender can transmit clinical documents and medical images together with coordinate values of regions of interest to recipients. Recipients can easily view the documents and display embedded regions of interest by rendering them in their web browser of choice.

Improving chronic disease management with mobile health platform.

In modern society, aging and chronic disease is becoming common phenomenon due to the increasing numbers of elderly patients. To best treat this growing segment of the population, medical care should be based on constant vital sign monitoring. In this study, we propose a mobile vital sign measurement and data collection system for chronic disease management.. And we implemented a middle ware using Multi-Agent platform in SOS (Self-Organizing System) platform that transmits patient clinical data for services. We also implemented a HL7 messaging interface for interoperability of clinical data exchange. We propose health services on a self-organized software platform.

Preliminary comparison of mHealth architectures based on MU2 criteria.

Mobile Health (MH) is a hot topic in the health IT industry because it can make a big difference in healthcare services. Before adopting Mobile Health technology, however, we must ensure that it provides safe and reliable services to users and it should be evaluated by authoritative criteria. In US, Electronic Health Record (EHR) systems are evaluated through Meaningful Use (MU). Although MU focuses on EHR systems, it can't be thought of without MH. So in this paper we derive proper evaluation criteria for MH from MU criteria and evaluate existing MH architectures that are currently being surveyed in ISO/AWI TR 17522 - Provisions for Health Applications on Mobile/Smart Devices.