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Identification of priorities for medication safety in neonatal intensive care.

BACKGROUND: Although neonates are reported to be at greater risk of medication error than infants and older children, little is known about the causes and characteristics of error in this patient group. Failure mode and effects analysis (FMEA) is a technique used in industry to evaluate system safety and identify potential hazards in advance. The aim of this study was to identify and prioritize potential failures in the neonatal intensive care unit (NICU) medication use process through application of FMEA. METHODS: Using the FMEA framework and a systems-based approach, an eight-member multidisciplinary panel worked as a team to create a flow diagram of the neonatal unit medication use process. Then by brainstorming, the panel identified all potential failures, their causes and their effects at each step in the process. Each panel member independently rated failures based on occurrence, severity and likelihood of detection to allow calculation of a risk priority score (RPS). RESULTS: The panel identified 72 failures, with 193 associated causes and effects. Vulnerabilities were found to be distributed across the entire process, but multiple failures and associated causes were possible when prescribing the medication and when preparing the drug for administration. The top ranking issue was a perceived lack of awareness of medication safety issues (RPS score 273), due to a lack of medication safety training. The next highest ranking issues were found to occur at the administration stage. Common potential failures related to errors in the dose, timing of administration, infusion pump settings and route of administration. Perceived causes were multiple, but were largely associated with unsafe systems for medication preparation and storage in the unit, variable staff skill level and lack of computerised technology. CONCLUSION: Interventions to decrease medication-related adverse events in the NICU should aim to increase staff awareness of medication safety issues and focus on medication administration processes.

Clinical Competence↗

The effect of social support on educational outcomes.

A review of the social support literature identified the theoretical framework for this prospective descriptive correlational study. The relationship of social support to educational outcomes was investigated in a convenience sample of 67 junior and 60 senior nursing students. Social support was measured by the Inventory of Socially Supportive Behavior (ISSB), indicating the frequency with which respondents were recipients of supportive actions from their total support network. Outcomes included the cumulative grade point averages of all participants and the NCLEX scores of graduating seniors. Social Support was also examined in relation to self-esteem, measured by the Coopersmith Self-Concept scale and test anxiety, measured by the Spielberger Test Anxiety Inventory. Hypotheses tested were: (1) There is a positive relationship between social support and both cumulative grade point average and NCLEX scores. (2) There is a positive relationship between social support and self-esteem. (3) Social support will have greater influence on outcomes under conditions of stress, defined as high test anxiety. Hypotheses 1 and 3 were not supported. Hypothesis 2 was supported at the .05 significance level, using a Pearson Correlation Coefficient. Additional information included a significant inverse correlation for test anxiety and both grade point average (p = .01) and NCLEX results (p = .05). Implications for educational experiences and future research are discussed.

Achievement↗

Dynamic Protein Structure Paradox: An Integrative Framework for Endpoint-Conditioned Evidentiary Sufficiency in Structure-to-Function Claims.

Accurate coordinates for a represented protein state do not, by themselves, establish activity or any other condition-specific function. This article defines the Dynamic Protein Structure Paradox (DPSP) as the apparent conflict between structural accuracy and functional underdetermination and develops it as an integrative evidentiary assessment framework rather than a new theory or paradigm. The underlying problem has been longstanding, since structural genomics, function annotation, allostery, and disorder research each established that fold does not determine function and that function does not determine fold. DPSP consolidates those results into one endpoint-conditioned rule. Once a measurable endpoint is defined, it assesses four coupled dimensions: relevant-state completeness, context completeness, ensemble or kinetic dependence, and chemical dependence. A rubric rates each dimension as adequate, uncertain, or missing, and a materiality test determines which gaps influence the stated decision. The outcome is one of three mutually exclusive modes of utilization: geometry-led, conditional, or function-measured. The deliverable is a concise evidence statement delineating what the structure supports, which decisive variable remains unmeasured, and what corroboration is necessary. DPSP complements, rather than replaces, existing structural, ensemble, and computational approaches. The framework remains unvalidated, its thresholds are provisional, and the studies necessary to confirm or refute it are specified.

Proteins↗

A contextual analysis of attention to chronic pain: what the patient does with their pain might be more important than their awareness or vigilance alone.

UNLABELLED: It is often believed that to feel greater pain is to experience greater effects of that pain, and that attention and awareness represent the transmission mechanism in this relationship. By implication, it is assumed that if attention and awareness can be lessened, the effects of pain will likewise reduce. Despite conceptual work and data suggesting more complex processes might indeed be in place, these long-standing and intuitively appealing ideas remain, either explicitly or implicitly, in both research and clinical applications. The purpose of this study was to compare the role of attentional processes in chronic pain with a process that is more contextual, functional, and behavior-focused, namely, acceptance. The hypothesis tested is whether it is more important to understand the amount of contact an individual has with pain, in this case awareness and vigilance to pain, or the degree of influence on behavior brought with that contact, in this case acceptance. Data from 227 patients seeking treatment for chronic pain were examined. Results from correlation analyses showed that acceptance scores achieved stronger correlations than scores for the attention variables with measures of cognitive, emotional, social, and physical functioning. When acceptance of pain was taken into account in multiple regression analyses, scores from the attention measures accounted for little or no variance in measures of patient functioning. The value of various mental, mechanical, behavior-focused, and contextual models of attention in chronic pain is discussed. PERSPECTIVE: Attention, awareness, and vigilance appear immediately applicable for understanding chronic pain. These processes, however, might be incomplete in accounting for pain-related suffering and disability. Acceptance is proposed as a process that expands the framework of attention to include varying cognitive, emotional, and social influences exerted by pain on patient behavior.

Adaptation, Psychological↗

A multi-criteria approach to Great Barrier Reef catchment (Queensland, Australia) diffuse-source pollution problem.

This paper presents a multi-criteria based tool for assessing the relative impact of diffuse-source pollution to the Great Barrier Reef (GBR) from the river basins draining into the GBR lagoon. The assessment integrates biophysical and ecological data of water quality and pollutant concentrations with socio-economic information pertaining to non-point source pollution and (potential) pollutant impact. The tool generates scores for each river basin against four criteria, thus profiling the basins and enabling prioritization of management alternatives between and within basins. The results support policy development for pollution control through community participation, scientific data integration and expert knowledge contributed by people from across the catchment. The results specifically provided support for the Reef Water Quality Protection Plan, released in October 2003. The aim of the plan is to provide a framework for reducing discharge of sediment, nutrient and other diffuse-source loads and (potential) impact of that discharge and for prioritising management actions both between and within river basins.

Agriculture↗

The validity and reliability of the measurement of the concept 'expressed emotion' in the family members and nurses of Hong Kong patients with schizophrenia.

This study aimed to test the validity and reliability of three measures of expressed emotion in a sample of family members and nurses of Hong Kong Chinese people with schizophrenia. Little research has been done in Hong Kong in relation to family expressed emotion (EE) and schizophrenia so the present study set out to pilot some measures that could become reliable and valid measures for future clinical studies. The Adjective Check List (ACL) and the Family Attitude Scale (FAS) were compared to EE ratings obtained after a brief interview. The ratings were made based on the conceptual framework of the Camberwell Family Interview, which includes the dimensions of criticism, hostility and emotional over-involvement. Twenty-one family members and their primary nurses participated in the study which revealed that 13 of the family members and 10 of the primary nurses were rated as high EE, either in terms of criticism, emotional over-involvement or both, based on the interview. The differences in the mean FAS scores between the high EE groups and the low EE group was large but not statistically significant, and there was a significant correlation between the FAS and the brief interview. The ACL revealed some interesting results in terms of the way relatives and nurses see themselves responding to the person with schizophrenia and vice versa. Recommendations for future studies and family education strategies are made.

Adult↗

Measurement properties and interpretability of the Chronic respiratory disease questionnaire (CRQ).

The chronic respiratory questionnaire, available as an interviewer and a self-administered instrument, includes 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). When completing this instrument, patients rate their experience on a 7-point scale ranging from 1 (maximum impairment) to 7 (no impairment). The Chronic Respiratory Questionnaire has demonstrated excellent measurement properties for both discriminative and evaluative purposes and served as a model in numerous methodological studies in chronic airflow limitation and patients with chronic obstructive pulmonary disease. We performed a systematic review of the literature on the chronic respiratory questionnaire to summarize the key qualities of the chronic respiratory questionnaire and to appraise the work regarding the minimal important difference of the chronic respiratory questionnaire. This paper includes a revision of our initial definition of the minimal important difference and a methodological framework for using anchor based approaches to establish the minimal important difference pioneered by Jaeschke and colleagues. Other approaches to evaluate the minimal important difference include distribution-based methods and panel-based methods. Investigators have used all of these approaches to establish the minimal important difference for the chronic respiratory questionnaire and the results are in general agreement with the minimal important difference of 0.5 for the mean domain scores of the chronic respiratory questionnaire. As a result of this literature review and discussion at the workshop, we established several research objectives. These objectives include the exploration of presentation of quality of life information and prospective anchor-based approaches.

Chronic Disease↗

Evaluation of a computer-based approach to teaching acid/base physiology.

Because acid/base physiology is a difficult subject for most medical and veterinary students, the first author designed a software program, Acid/Base Primer, that would help students with this topic. The Acid/Base Primer was designed and evaluated within a conceptual framework of basic educational principles. Seventy-five first-year veterinary students (of 81; 93% response rate) participated in this study. Students took both a pre- and posttest of content understanding. After completing the Acid/Base Primer in pairs, each student filled out a survey evaluating the features of the program and describing his/her use and experience of it. Four pairs of students participated in interviews that elaborated on the surveys. Scores improved from 53 +/- 2% on the pretest to 74 +/- 1% on an immediate posttest. On surveys and in interviews, students reported that the program helped them construct their own understanding of acid/base physiology and prompted discussions in pairs of students when individual understandings differed. The case-based format provided anchors and a high degree of relevance. Repetition of concepts helped students develop a more complex network of understanding. Questions in the program served to scaffold the learning process by providing direction, accentuating the relevant features of the cases, and provoking discussion. Guidelines for software development were generated on the basis of the findings and relevant educational literature.

Acid-Base Equilibrium↗

Social support for school-aged siblings of children with cancer: a comparison between parent and sibling perceptions.

This descriptive, exploratory study investigated the social support interventions received by school-aged siblings of children with cancer and which of those interventions are perceived as being helpful. A comparison between the siblings' and parents' perceptions was made. The conceptual framework was guided by House's (1981) work on social support, which includes major categories of support variables including emotional, informational, instrumental, and appraisal support. A nonprobability purposive sample consisted of 50 school-aged siblings of children with cancer and their parents. Subjects completed either the sibling or parent version of the Nurse-Sibling Social Support Questionnaire (NSSSQ). Descriptive statistical analyses were performed to examine NSSSQ helpfulness and frequency scores for both siblings and parents. Paired t tests were used to test the difference between the responses given by siblings and by their parents on the NSSSQ helpfulness and frequency scales. Results demonstrated that siblings perceive interventions aimed at providing emotional and instrumental support as the most helpful. Parents perceived interventions aimed at meeting the siblings' need for emotional and informational support the most beneficial. Parents reported that siblings receive emotional, informational, and appraisal support more frequently than siblings did.

Adult↗

Differences in neuropsychological performance associated with ethnicity in children with HIV-1 infection: preliminary findings.

This study investigated the relationship between ethnicity (African American and European American) and neuropsychological performance in two specific neuropsychological domains (language and speed of information processing) in a group of HIV-1+ children. The Expressive One-Word Picture Vocabulary Test-Revised and the Rapid Color Naming subtest of the Comprehensive Test of Phonological Processing were administered to 5- to 7-year-old children (n = 22) as part of a comprehensive research or clinical protocol. African American children scored lower than European American children (p < .05) on both procedures. The observed performance difference emerged despite the fact that there were no group differences in age, immunologic clinical categories, intellect, level of maternal education, or CD4+ percentage and after using stringent exclusionary criteria, including history of enrollment in special education services and the presence of other chronic medical conditions. The implications of such findings are discussed within biological and demographic frameworks.

Anti-HIV Agents↗

Selective loss of HLA-A or HLA-B antigen expression in colon carcinoma.

A panel of colorectal carcinomas has been examined immunohistologically with mAb specific for allodeterminants of HLA-A or HLA-B, and with mAb reactive with HLA-A,B,C framework determinants or beta 2-microglobulin. Out of 85 carcinomas, 5 cases were completely negative for all class I Ag in the tumor cell population. Fifteen cases exhibited a differential expression of HLA-A and HLA-B products in all tumor cells or in a subset. Such tumor cells showed strong staining with monomorphic HLA antibodies but failed to stain with certain allospecific mAb. Negativity of tumor cells was scored only when normal stromal cells within the tumor mass were clearly labeled, indicating expression of the particular allodeterminant(s) in the given tissue. Four carcinomas showed a selective loss of HLA-A2 or a non-A2 HLA-A allospecificity in all tumor cells or a major subset, whereas HLA-B Ag were expressed. Seven cases showed a selective loss of the HLA-Bw6 superspecificity in the tumor cell population; HLA-Bw4 and HLA-A Ag were present. Three cases exhibited a combined loss of HLA-A2 and HLA-Bw6 Ag, with non-A2 HLA-A and HLA-Bw4 Ag being expressed. A further case was HLA-Bw6/Bw4 negative in a major tumor cell subset and HLA-A negative in the complementary minor subset. The results show that a considerable proportion of colorectal carcinomas is heterogeneous with regard to HLA-A and HLA-B expression. The reasons for the appearance of tumor subsets with complete loss of class I Ag or selective loss of only HLA-A or HLA-B Ag are not clear, but it is conceivable that some of them arose because they have escaped immunoselection.

Alleles↗

Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science.

STUDY DESIGN: A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. OBJECTIVES: To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. SUMMARY OF THE BACKGROUND DATA: No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). METHODS: A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. RESULTS: A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (kappa values, 0.49-0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age ( < 0.0001) and macroscopic grade of degeneration ( < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. CONCLUSIONS: Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.

Adolescent↗

Development of an instrument to measure pain in rheumatoid arthritis: Rheumatoid Arthritis Pain Scale (RAPS).

OBJECTIVE: To develop a valid and reliable clinical instrument for measuring pain in adult patients with rheumatoid arthritis. The resulting Rheumatoid Arthritis Pain Scale (RAPS) is a quantitative, single-score, self-report 24-item instrument. METHODS: Psychometric evaluation of RAPS was conducted following estimation of content validity and a pilot study. The actual study used a convenience sample of 120 adults, 18 years of age or older, with pain of at least 3 months duration. The setting was a large rheumatology private practice in a metropolitan southwestern city. The gate control and affective motivational theories of pain served as a framework guiding the development of RAPS, which includes items suggestive of the multidimensional pain experience in rheumatoid arthritis. Four subscales, physiological, affective, sensory-discriminative, and cognitive, evaluated numerous pain factors. RESULTS: Findings indicate a high estimate for internal consistency for the total scale and a moderate to high estimate of internal consistency for projected subscales. Data were analyzed using Cronbach's coefficient alpha, Pearson product-moment correlation coefficients, and exploratory factor analysis. Using Cronbach's coefficient alpha, RAPS showed an internal consistency reliability coefficient of 0.92, a strong indicator of reliability. Reliability assessments for the 4 subscales also indicate reliability, with Cronbach's coefficients ranging from 0.65 to 0.86. Exploratory factor analysis yielded 3 factors with criteria for factor loadings > or = 0.4. CONCLUSION: The study's findings provided support for RAPS as a reliable and valid measurement of rheumatoid arthritis pain. Assessment of rheumatoid arthritis pain and its relationship to treatment outcomes could significantly impact the treatment interventions.

Adult↗

The Risk Approach: unassailable logic?

The Risk Approach (RA) is a framework for selective provision of health care services advocated by the World Health Organization (WHO). Although the potential utility of RA is stressed in the WHO literature, the framework remains largely untested as a basis for resource deployment. Despite this, advocates claim the logic of RA is 'theoretically unassailable'. The purpose of this paper is to challenge this claim by critically examining some of the assumptions and proposed methods contained in the WHO literature concerning RA. Two areas of concern are discussed, relating to (i) prediction and the nature of relations between markers and outcomes, and (ii) marker measurement and scoring.

Calibration↗

Age, gender, quality of life and psychological distress in patients hospitalized with psoriasis.

BACKGROUND: Psoriasis has a great impact on the quality of life of patients, and the ageing population is an important public health issue. OBJECTIVES: To investigate whether older patients with psoriasis have a different impairment in quality of life compared with younger patients, considering level of severity, duration of disease, gender and psychological distress. METHODS: The study was performed between February 2000 and February 2002 at the inpatient wards of the Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large project on clinical, epidemiological, emotional and quality of life aspects of psoriasis (IMPROVE study). This is a hospital-based cross-sectional study, with measures of quality of life (Skindex-29, Dermatology Life Quality Index and Psoriasis Disability Index) and of psychological distress, generic (12-item General Health Questionnaire) and psoriasis-related (Psoriasis Life Stress Inventory), all self-assessed by patients. We compared the mean scores of each quality of life instrument in patients aged < 65 years and >/= 65 years, in subsets of patients based on clinical and sociodemographic characteristics. RESULTS: We analysed 936 patients hospitalized at IDI-IRCCS with a diagnosis of psoriasis. Quality of life was significantly more impaired in the older group for all the Skindex-29 scales, and psychological distress was higher in older patients. In particular, older women suffering from anxiety or depression had the greatest impairment in quality of life. The results were somewhat different using the other quality of life instruments. CONCLUSIONS: These results should alert dermatologists that similar levels of clinical severity in psoriasis may be associated with different levels of quality of life and psychological distress of patients. Particular attention should be devoted to older patients, and especially to older women.

Adolescent↗

Developing an assessment tool for evaluating community involvement.

BACKGROUND: Current UK policy has resulted in greater requirements for public and patient participation in health service planning and decision making. Organizations and services need to be able to monitor and evaluate the effectiveness and quality of their community involvement processes, but there are few appropriate evaluation tools or sets of indicators available. This paper reports on work within Bradford Health Action Zone to develop a self-assessment tool for organizations on community involvement. METHODS: A multi-agency working group developed the tool. A literature search was undertaken and evaluation resources were reviewed. A set of benchmarks for community involvement in regeneration was utilized in developing the assessment areas. A range of individuals with expertise on community involvement practice and performance management was consulted. The tool was then piloted in two primary care trusts prior to final modifications. RESULTS: The process resulted in the production of Well Connected--a self-assessment tool on community involvement designed for organizations to assess their progress and identify areas for improvement. A scoring system assesses evidence of a strategic approach to community involvement, good practice throughout the organization, and a range of opportunities and support. Feedback from the pilots revealed that the tool had facilitated assessment of the strengths and weaknesses of organizational practices. CONCLUSION: The paper discusses some of the methodological challenges pertaining to the measurement of community involvement. Notwithstanding those challenges, it is argued that Well Connected provides a robust and practical framework that health organizations and their partners can use to assess practice.

Community Participation↗

A per- and polyfluoroalkyl substances-based gene signature links prognosis to immune landscapes in thyroid cancer.

BACKGROUND: Thyroid cancer (THCA) is the most common endocrine malignancy with a rising global incidence and significant heterogeneity. Although per- and polyfluoroalkyl substances (PFAS) exposure is linked to thyroid dysfunction, the prognostic value of per- and polyfluoroalkyl substances-related genes (PFASRGs) and their role in the tumor immune microenvironment (TME) remain poorly understood. This study aims to systematically screen key PFASRGs and evaluate their prognostic value as biomarkers for THCA. METHODS: Utilizing The Cancer Genome Atlas (TCGA)-THCA transcriptomic data and PFASRGs, we constructed a prognostic model through differential expression analysis, univariate and multivariate Cox regression analyses, and the least absolute shrinkage and selection operator (LASSO). The model's robustness was validated using receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, and clinical nomograms. Furthermore, the TME, immunotherapy response, and drug sensitivities were systematically evaluated. Distinct molecular landscapes were characterized by stratifying the cohort via unsupervised consensus clustering analysis. RESULTS: The eight-gene prognostic model demonstrated robust performance, with area under the curve (AUC) values exceeding 0.85 across all validation cohorts. High-risk patients exhibited significantly shorter overall survival and an "inflamed" TME characterized by high immune scores and checkpoint expression. In contrast, the therapeutic efficacy of anti-programmed death-ligand 1 (PD-L1) agents was more pronounced in the low-risk category, as evidenced by a superior objective response. Furthermore, distinct molecular subtypes and risk-specific sensitivities to targeted agents, such as sorafenib and sunitinib, were identified, highlighting the model's clinical utility for personalized treatment. CONCLUSIONS: We established a novel THCA prognostic framework based on eight PFASRGs. This model exhibits superior performance in risk stratification, effectively distinguishing cohorts with divergent clinical trajectories, unique immune microenvironment features, and varied therapeutic responses. Our findings provide a powerful predictive tool for refining prognostic evaluation and facilitating the implementation of personalized management strategies for THCA patients.

Per- and polyfluoroalkyl substances-related genes ↗

Multimodal Analysis Reveals Aberrant Expression of SUMO2 and Its Significant Association With Key Mechanisms of Metabolic Pathways in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. However, the role of small ubiquitin-like modifier 2 (SUMO2), a core member of the small ubiquitin-like modifier (SUMO) family, regarding its expression patterns and metabolism-related functions in HCC remains inadequately understood. METHODS: A multidimensional analytical framework was applied, integrating immunohistochemistry (153 HCC vs. 21 non-HCC samples), proteomics (159 paired samples), bulk transcriptomics (3240 HCC vs. 2267 non-HCC samples), single-cell RNA sequencing (RNA-seq) (10 HCC vs. 8 non-HCC samples), spatial transcriptomics, and external CRISPR/Cas9 functional genomics data. Systematic analyses included standardized mean difference (SMD), pathway enrichment, pseudotime trajectory inference, in silico knockout, cell-cell communication, metabolic flux scoring, immune infiltration, clinical correlation, drug sensitivity prediction, and molecular docking. RESULTS: At the protein level, immunohistochemistry (nuclear positivity) and external proteomic data collectively demonstrated consistent SUMO2 overexpression in HCC. Consistent upregulation was also observed at the mRNA level across large-scale cohorts. Single-cell RNA-seq and spatial transcriptomics localized SUMO2 enrichment to malignant hepatocytes and tumor-dominant regions. CRISPR-mediated SUMO2 knockout suppressed proliferation in multiple HCC cell lines. Mechanistically, high SUMO2 expression was significantly associated with metabolic reprogramming involving glycolysis/gluconeogenesis, pyruvate metabolism, and the tricarboxylic acid cycle. SUMO2-high malignant hepatocyte subpopulations exhibited enhanced activity of the macrophage migration inhibitory factor signaling axis and enhanced iron-sensor interactions. Further, the immune infiltration analysis revealed a negative correlation between SUMO2 expression and M1 macrophages and a positive correlation between follicular helper T cells and regulatory T cells. Clinically, elevated SUMO2 levels were found to be associated with adverse prognostic features. Furthermore, high SUMO2 expression was associated with increased sensitivity to dasatinib, and molecular docking simulations predicted potential binding between SUMO2 and dasatinib, with a Vina score of -8.5 kcal/mol. CONCLUSIONS: SUMO2 is aberrantly expressed at the protein, mRNA, single-cell, and spatial transcriptomic levels in HCC and is significantly associated with metabolic reprogramming and altered migration inhibitory factor (MIF)-mediated intercellular communication, suggesting its potential as a novel biomarker for diagnosis and treatment.

Humans↗