α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

The relationship between medication beliefs, patient activation, and self-rated health in patients taking oral anticancer agents.

PURPOSE: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. METHODS: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. RESULTS: The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). CONCLUSION: The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.

Linking artificial sweetener intake with kidney function: insights from NHANES 2003-2006 and findings from Mendelian randomization research.

Background: The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function. Methods: We utilized data from the National Health and Nutrition Examination Survey from 2003-2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust adjusted profile score were the primary analytical methods employed. Results: A total of 20,470 participants were included in the study, with 1,257 participants ultimately included in the analysis. In all adjusted logistic regression models, no significant association was found between the intake of artificial sweeteners and CKD risk. Similarly, the summary odds ratios (OR) for each unit change in genetically predicted CKD risk were 2.14 (95% CI: 0.83, 5.21, p = 0.092), 1.41 (95% CI: 0.54, 3.63, p = 0.482), and 1.50 (95% CI: 0.50, 4.52, p = 0.468) for the impact of artificial sweeteners added to cereals, tea, and coffee, respectively. It was only observed that adding artificial sweeteners to coffee was associated with a modest reduction in urinary albumin-to-creatinine ratio (OR = 0.94, 95% CI: -0.108, -0.022, p = 0.003), the effect appeared to be relatively small and may not directly impact the individual level. Conclusion: Our study does not support a causal relationship between artificial sweetener intake and the risk of CKD. However, due to the limitations and potential confounding factors, these findings need to be further validated through larger sample sizes in observational studies and Mendelian randomization analyses.

The role of ATP-binding cassette subfamily G member 1 in tumor progression.

BACKGROUND: ATP-binding cassette subfamily G member 1 is mostly known as a transporter for intracellular cholesterol efflux, and a number of studies indicate that ABCG1 also functions actively in tumor initiation and progression. This review aimed to provide an overall review of how ABCG1 acts in tumor progression. METHOD: A comprehensive searching about ABCG1 and tumor was conducted up to November 2023 using proper keywords through databases including PubMed and Web of Science. RESULT: Overall, ABCG1 plays a crucial role in the development of multiple tumorigenesis. ABCG1 enhances tumor-promoting ability through conferring stem-like properties to cancer cells and mediates chemoresistance in multiple cancers. Additionally, ABCG1 may act as a kinase to phosphorylate downstream molecules and induces tumor growth. In tumor microenvironment, ABCG1 plays a substantial role in immunity response through macrophages to create a tumor-favoring circumstance. CONCLUSION: High expression of ABCG1 is usually associated with poor prognosis, which means ABCG1 may be a potential biomarker for early diagnosis and prognosis of various cancers. ABCG1-targeted therapy may provide a novel treatment for cancer patients.

High-density genetic map construction and QTL mapping of a zigzag-shaped stem trait in tea plant (Camellia sinensis).

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.

Oncology patients' willingness to report their medication safety concerns from home: a qualitative study.

PURPOSE: Oncology patients often struggle to manage their medications and related adverse events during transitions of care. They are expected to take an active role in self-monitoring and timely reporting of their medication safety events or concerns to clinicians. The purpose of this study was to explore the factors influencing oncology patients' willingness to report adverse events or concerns related to their medication after their transitions back home. METHODS: A qualitative interview study was conducted with adult patients with breast, prostate, lung, or colorectal cancer who experienced care transitions within the previous year. A semi-structured interview guide was developed to understand patients' perceptions of reporting mediation-related safety events or concerns from home. All interviews were conducted via phone calls, recorded, and transcribed for thematic data analysis. RESULTS: A total of 41 individuals participated in the interviews. Three main themes and six subthemes emerged, including patients' perceived relationship with clinicians (the quality of communication and trust in clinicians), perceived severity of adverse medication events (perceived severe vs. non-severe events), and patient activation in self-management (self-efficacy in self-management and engagement in monitoring health outcomes). CONCLUSION: The patient-clinician relationship significantly affects patients' reporting behaviors, which can potentially interact with other factors, including the severity of adverse events. It is important to engage oncology patients in medication safety self-reporting from home by enhancing health communication, understanding patients' perceptions of severe events, and promoting patient activation. By addressing these efforts, healthcare providers should adopt a more patient-centered approach to enhance the overall quality and safety of oncological care.

Bulked Segregant RNA-Seq Reveals Different Gene Expression Patterns and Mutant Genes Associated with the Zigzag Pattern of Tea Plants (Camellia sinensis).

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.

Assessing the Reproducibility of Research Based on the Food and Drug Administration Manufacturer and User Facility Device Experience Data.

OBJECTIVE: This article aims to assess the reproducibility of Manufacturer and User Facility Device Experience (MAUDE) data-driven studies by analyzing the data queries used in their research processes. METHODS: Studies using MAUDE data were sourced from PubMed by searching for "MAUDE" or "Manufacturer and User Facility Device Experience" in titles or abstracts. We manually chose articles with executable queries. The reproducibility of each query was assessed by replicating it in the MAUDE Application Programming Interface. The reproducibility of a query is determined by a reproducibility coefficient that ranges from 0.95 to 1.05. This coefficient is calculated by comparing the number of medical device reports (MDRs) returned by the reproduced queries to the number of reported MDRs in the original studies. We also computed the reproducibility ratio, which is the fraction of reproducible queries in subgroups divided by the query complexity, the device category, and the presence of a data processing flow. RESULTS: As of August 8, 2022, we identified 523 articles from which 336 contained queries, and 60 of these were executable. Among these, 14 queries were reproducible. Queries using a single field like product code, product class, or brand name showed higher reproducibility (50%, 33.3%, 31.3%) compared with other fields (8.3%, P = 0.037). Single-category device queries exhibited a higher reproducibility ratio than multicategory ones, but without statistical significance (27.1% versus 8.3%, P = 0.321). Studies including a data processing flow had a higher reproducibility ratio than those without, although this difference was not statistically significant (42.9% versus 17.4%, P = 0.107). CONCLUSIONS: Our findings indicate that the reproducibility of queries in MAUDE data-driven studies is limited. Enhancing this requires the development of more effective MAUDE data query strategies and improved application programming interfaces.

The Acceptance and Use of Digital Technologies for Self-Reporting Medication Safety Events After Care Transitions to Home in Patients With Cancer: Survey Study.

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.

A Quantitative Analysis of Patient-Facing Technologies for Patient Self-Reporting.

Dramatic improvements in patient-facing technologies have demonstrated the potential to transform healthcare delivery for a 360-degree holistic view of care. A key question regarding how such technologies affect patient self-reporting still needs to be answered. This study presents the technologies and their associated key variables via quantitative analysis. Associations were found between single-platform and web-based applications (apps), Android apps and physician view, mental health disease, and user feedback. The results are intended to inform future design, development, and evaluation of patient-facing technologies. More systematic, theory-driven, framework-based design and evaluation are necessary to fully characterize the effectiveness and maintenance of patient-facing technologies toward a sustainable strategy.

Exploring a Mechanism Toward Automated Feedback for Cancer Patient Self-Reporting.

"Infobuttons" spearheaded electronic health records (EHR) based decision support by offering automated knowledge resources to physicians. However, how such a mechanism could be leveraged to provide optimal resources to patients remains unanswered. Informatics approaches are expected to utilize more relevant information beyond EHR, such as patient-reported outcomes, to support clinical decisions. This pilot study is intended to explore how patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in EHR can be incorporated and how to recommend tailored content to cancer patients via automated feedback.

Challenges in Selecting Patient-Reported Outcome Measures for Use in a Patient-Facing Technology.

Patient-reported outcome measures (PROMs) have been increasingly integrated into patient-facing technologies to engage and empower patients in cancer self-management at home. However, researchers and developers face several challenges in selecting the best-suited PROMs for patient-facing technologies, due to the complex nature of the disease, the multitude of PROMs with high psychometric quality, and the lack of clear standards for PROM utilization. In this paper, we have discussed these challenges, illustrated by breast cancer instruments.

User-Centered Data Display for Clinicians to Diagnose and Manage Hypertension.

The accurate diagnosis and effective treatment of hypertension are hindered by challenges stemming from limited access to comprehensive blood pressure (BP) data and the need for clinical context surrounding BP readings. Using handwritten tables for home-monitored BP exacerbates issues related to integration of electronic health records (EHRs) and trend analysis. This study employs user-centered design principles to develop prototypes for BP data visualization, with the primary goal of harmonizing disparate BP data sources to empower clinicians in precise hypertension diagnosis and management.

Learning from Non-Routine Events and Teamwork in Intensive Care Units: Challenges and Opportunities.

Patients admitted to intensive care units (ICUs) have profound and complex illnesses, often fraught with uncertainties in diagnoses, treatments, and care decisions. Clinicians often deviate from best practices to handle ICUs' myriad complexities and uncertainties. Non-routine events (NREs), defined as any aspect of care perceived by clinicians as deviations from optimal care, are latent and frequent safety threats that, if left unchecked, can be precursors to adverse events. Proper identification and analysis of NREs that represent latent safety threats have been proposed as a feasible and more effective approach for performance improvement than traditional root cause analysis for patient safety events. However, NRE studies to date have yet to show the holistic picture of NREs in the contexts of teamwork and time-dependent tasks that are frequently associated with NREs. NREs, an upstream interventional area to understand root causes, team performance, and human-computer interaction, still needs to be expanded. This article presents concepts of NREs, and the use of real-world data (RWD) and informatics methodology to investigate NREs in contexts and discusses the opportunities and challenges to enhance NREs research in teamwork and time-dependent tasks.

A Patient-Centered Approach to Collecting and Displaying Patient Identifiers.

Patient identifiers such as name, date of birth, or gender are the first line of defense to ensure the accuracy of the health data displayed in health information exchange. Health data display is the impetus for clinical decisions and patient outcomes and directly correlates with promoting interoperability and health information exchange. Therefore, constant monitoring of quality metrics is imperative for clinical leaders to keep a pulse on what is happening within their organizations. However, the electronic health records (EHRs) designer should also take precautions to ensure the visualizations are not misleading, given that EHRs have been shown in some studies to lead to increased patient safety events.

maresin2 fine-tunes ULK1 O-GlcNAcylation to improve post myocardial infarction remodeling.

BACKGROUND: Myocardial infarction (MI) is one of the common causes of hospitalization and death all over the world. Maresin2 (MaR2), a specialized pro-solving mediator of inflammation, has been consolidated to be a novel cytokine fine-tuning inflammatory cascade. However, the precise mechanism is still unknown. Here, we demonstrated that maresin2 relieved myocardial damage via ULK1 O-GlcNAc modification during MI. METHODS: The myocardial infarction model was established by ligating the left anterior descending artery (LAD). Echocardiography, histopathology, transmission electron microscope, and Western blot were used to evaluate cardiac function and remodeling. Furthermore, primary neonatal rat cardiomyocytes (NRCMs) were cultivated, and immunoprecipitation (IP) assays were performed to explore the specific mechanism. RESULTS: As suggested, maresin2 treatment protected cardiac function and ameliorated adverse cardiac remodeling. Furthermore, we found that maresin2 facilitated autophagy and inhibited apoptosis under the modulation of O-GlcNAcylation-dependent ULK1 activation. Meanwhile, we discovered that maresin2 treatment ameliorated the inflammation of myocardial cells by inhibiting the interaction of TAK1 and TAB1. CONCLUSIONS: Maresin2 is likely to promote autophagy while relieving apoptosis and inflammation of myocardial cells, thereby exerting a protective effect on the heart after MI.

Selecting patient-reported outcome measures for a patient-facing technology.

Objective: This article provides insight into our process and considerations for selecting patient-reported outcome measures (PROMs) designed for self-reporting symptoms and quality-of-life among breast cancer (BCA) patients undergoing oral anticancer agent treatment via a patient-facing technology (PFT) platform. Methods: Following established guidelines, we conducted a thorough assessment of a specific set of PROMs, comparing their content to identify the most suitable options for studying BCA patients. Results: We recommend utilizing the combination of EORTC QLQ-C30 + EORTC QLQ-BR45 as the preferred instrument, especially when developing a dedicated "breast cancer-only" application. Discussion: When developing and maintaining a dashboard for a PFT platform that includes multiple cancer types, it is important to consider the feasibility of interface design and workload. To achieve this, we recommend using PRO-CTCAE+PROMIS 10 GH for the PFT. Moreover, it is important to consider adding ad hoc items to complement the chosen PROM(s). Conclusion: This article describes our efforts to identify PROMs for self-reported data while considering patient and developer burdens, providing guidance to PFT developers facing similar challenges in PROM selection.

USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice.

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. CONCLUSIONS: USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.