• Educational strategies to improve health literacy for people with type 2 diabetes in low socio-economic communities: A realist review protocol.
    2 weeks ago
    Type 2 diabetes (T2D) has emerged among the top ten causes of disability and mortality worldwide. Health literacy is crucial for effective self-management to reduce the burden associated with T2D. Studies have reported the effectiveness of educational strategies for improving health literacy to promote good health and well-being. However, contextual factors influence the effectiveness of these strategies. Therefore, this paper intends to explain how and why context shapes the mechanisms through which educational strategies work to improve health literacy for adults with type 2 diabetes in low socioeconomic communities.

    Theory-driven realist review methods will explain how and why contexts activate different mechanisms through which educational strategies work to produce intended or unintended outcomes in low socioeconomic communities. The following five steps of realist review, which are non-linear and iterative, will be undertaken: (i) Define the scope of the review and locate existing theories on educational strategies to improve health literacy, (ii) Develop the initial programme theories, (iii) Search for evidence, (iv) Select papers and appraise, and (v) Extract data and synthesis. The following databases will be searched, but not limited to, PubMed, Education Resource Information Centre (ERIC), and PsycINFO. Papers will be selected based on relevance, richness, and rigour. Data extraction will follow both inductive and deductive approaches. The Intervention-Context-Actor-Mechanism Outcome (ICAMO) configurations will be utilised to analyse and synthesise data using retroductive reasoning. Finally, the revised programme theories, which explain how the educational strategies are expected to work across different contexts in low socioeconomic communities, will be prepared and disseminated.

    The findings may inform practice, influence policy, and contribute to the design of health literacy programmes in similar settings. The realist review is registered with the Open Science Framework: (https://osf.io/9w867).
    Diabetes
    Diabetes type 2
    Care/Management
    Advocacy
    Education
  • Single-cell transcriptomic integrated with machine learning reveals human retinal cell-specific biomarkers in diabetic retinopathy.
    2 weeks ago
    Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, yet the cell-type-specific molecular alterations associated with disease progression remain incompletely understood. This study aimed to characterize transcriptional changes across retinal cell types in diabetes and DR and identify candidate disease-associated biomarkers using single-cell transcriptomics and machine-learning approaches.

    We generated a single-cell RNA sequencing (scRNA-seq) atlas comprising 297 121 high-quality retinal cells from 20 eyes of 13 Chinese donors, including non-diabetic controls (NON), diabetes without retinopathy (DM), and DR samples. Following quality control, batch correction, clustering, and cell-type annotation, differential expression analyses were performed across disease states within each retinal cell type. Candidate biomarkers were further prioritized using a machine-learning framework incorporating L1-regularized logistic regression, recursive feature elimination with cross-validation, and stability selection.

    We identified 10 major retinal cell populations and characterized extensive cell-type-specific transcriptional alterations associated with diabetes and DR. Pathway enrichment analyses consistently highlighted immune activation, oxidative stress, neurodegeneration, and synaptic dysfunction across multiple retinal cell types. A total of 707 cell-type-specific candidate marker genes were identified, providing a comprehensive resource for investigating disease-associated molecular mechanisms and potential therapeutic targets.

    This study establishes a single-cell transcriptomic atlas of the Chinese diabetic retina and reveals cell-type-specific molecular signatures associated with DR progression. These findings provide biological insights into retinal disease mechanisms and nominate candidate biomarkers for future functional and translational studies.
    Diabetes
    Cardiovascular diseases
    Care/Management
  • Heat-treatment-programmed NiTi-5Cu (AH) bioactive orthodontic alloy enables Cu release for antibiofilm and periodontal protection in diabetic oral microenvironment.
    2 weeks ago
    Diabetes-associated hyperglycemia reshapes the oral microenvironment, aggravates biofilm-driven inflammation, and compromises the safety and efficacy of orthodontic treatment. Here, we develop a heat treatment-programmed bioactive orthodontic alloy, named NiTi-5Cu (AH), which combines structural functionality with microenvironment-responsive biological activity. By applying a solution-quench-aging process to NiTi-5Cu, we induce near-surface Cu enrichment and a more uniformly active electrochemical state, thereby enabling sustained Cu release. The resulting alloy maintains functional recoverability while exhibiting robust antibacterial and antibiofilm activities against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. In parallel, NiTi-5Cu (AH) exhibited no cytotoxicity toward human oral epithelial cells, vascular endothelial cells, and macrophages. Moreover, it induced M2-like macrophage polarization, shows favorable hemocompatibility isn both healthy and diabetic rabbits, and does not induce overt developmental or inflammatory toxicity in zebrafish assays. In a type 2 diabetic periodontitis rat model, intraoral placement of the alloy alleviates alveolar bone loss, inflammatory infiltration, and osteoclast activation. Moreover, 16S rRNA sequencing showed treatment-associated differences in oral-swab microbiota composition, while transcriptomic and metabolomic analyses revealed associative changes in inflammatory and metabolic pathways. Collectively, this work establishes a bioactive platform in which heat-treatment-engineered Cu release enables simultaneous antibiofilm regulation and periodontal protection, offering a promising metallic biomaterial strategy for diabetic oral care.
    Diabetes
    Policy
  • Leveraging expression quantitative trait loci information in single-cell resolution to identify cell-specific genes for gestational diabetes.
    2 weeks ago
    Gestational diabetes mellitus (GDM) is a common pregnancy complication with long-term metabolic consequences for both mother and offspring. While genome-wide association studies (GWAS) have identified risk loci, the cell-type-specific genetic architecture remains poorly characterized due to the limitations of bulk-tissue analyses.

    We integrated GWAS summary statistics from FinnGen (12,332 cases, 131,109 controls) with single-cell expression quantitative trait loci (sc-eQTL) data from 12 immune cell types in the OneK1K cohort. Using the OTTERS framework and ACAT-O omnibus testing, we performed single-cell transcriptome-wide association studies (scTWAS) to identify GDM-associated genes. We performed bulk-level TWAS as a sensitivity analysis. To investigate the function of significant genes, we performed functional enrichment.

    We detected 14 unique genes significantly associated with GDM across immune cell types (FDR < 0.05), with the strongest signals in CD4+ T cells and monocytes. Notably, ERAP1 and ERAP2 showed associations in 10 of 12 cell types (ACAT. P = 2.17 × 10-5), and RIOK2 emerged as a shared regulator. Gene Ontology analysis consistently highlighted "antigen processing and presentation via MHC class I" as the top enriched pathway (FDR < 10-5). In contrast, traditional bulk TWAS using GTEx whole blood identified only two genes with nominal associations.

    Our sc-TWAS identifies cell-type-specific GDM-associated genes that are not detected in bulk tissue, highlighting dysregulated antigen presentation in peripheral immune cells. Colocalization prioritizes monocytic LNPEP as the primary causal candidate, while associations for ERAP1, ERAP2, and RIOK2 likely reflect complex LD or tissue-specific effects.
    Diabetes
    Advocacy
  • Real-World Prognostic Analysis of Clinical Characteristics in Extensive-Stage Small Cell Lung Cancer: A Nomogram for Survival Prediction in Patients Receiving First-Line Immunochemotherapy With Serplulimab.
    2 weeks ago
    Extensive-stage small cell lung cancer (ES-SCLC) has limited treatment options, with first-line immunochemotherapy providing modest survival benefits.

    This single-center, retrospective study aimed to develop a prognostic nomogram using real-world data from ES-SCLC patients treated with serplulimab-based immunochemotherapy to identify key factors influencing overall survival (OS).

    109 ES-SCLC patients treated with first-line immunochemotherapy were analyzed. Baseline clinicopathological characteristics and hematological markers were assessed, and four prognostic factors - liver metastasis, maintenance therapy, albumin level, and neutrophil-to-lymphocyte ratio (NLR) - were identified by LASSO regression. A nomogram was constructed to predict 6-, 12-, and 24-month OS rates. The model's performance was validated with C-index, AUC, calibration curves, and decision curve analysis.

    The nomogram effectively stratified patients into low-, intermediate-, and high-risk groups with significant OS differences (log-rank p < 0.001). Patients with liver metastasis, no maintenance therapy, low albumin levels, and high NLR had worse outcomes. The C-index for the training and internal validation sets was 0.698 and 0.832, respectively, with AUC values exceeding 0.7 across most time points, suggesting favorable discrimination within this exploratory cohort.

    The identified nomogram provides an exploratory real-world tool for OS estimation in ES-SCLC patients receiving first-line serplulimab-based immunochemotherapy. By integrating baseline clinical factors and treatment-course information, the model may support dynamic risk stratification and help inform follow-up intensity, supportive care optimization, and prognostic counseling during routine clinical practice. Further prospective, multicenter external validation and time-dependent analyses are warranted to confirm and optimize its clinical applicability.
    Cancer
    Chronic respiratory disease
    Access
    Care/Management
    Advocacy
  • Impact of prior sexual trauma on patient experience and comfort in breast cancer radiation therapy.
    2 weeks ago
    Most women with breast cancer undergo radiation therapy (RT) as part of treatment, but the impact of prior sexual trauma on their RT experience remains unclear. We sought to understand the patient experience and comfort during breast RT with a focus on how sexual trauma may negatively affect the RT experience of patients.

    Between May and October 2022, IRB-approved surveys were distributed to female breast cancer patients treated with radiation at Sidney Kimmel Cancer Center. The 35-question survey assessed demographics, treatment details, body image satisfaction, comfort during various times throughout the RT process, and trauma history. Statistical analysis was performed using chi-square.

    Of the 505 surveys collected, 420 met the inclusion criteria. At the time of their radiation treatment, most patients surveyed were over 60 (70%), postmenopausal (75%), and had at least a college degree (63%). Most patients had localized breast cancer (69%), had undergone a lumpectomy prior to radiation (79%), were treated by a female physician (53%), and had completed radiation therapy less than five years prior (61%) at the time of the survey. Although most patients reported general comfort during RT, notable discomfort was associated with gender dynamics. Fewer patients felt uncomfortable changing for treatment (9.8%), waiting in the general area (20%), or being set up for RT (22%), but many more expressed discomfort in waiting rooms with men (43%) or when treated by male radiation therapists (38%). A history of trauma exposure was prevalent: 38% had experienced verbal harassment, 39% an unwanted sexual advance, 33% unwanted sexual touching, and 19% an unwanted sexual encounter. Trends towards greater discomfort were associated with body exposure during treatment (p = 0.29), setup (p = 0.18) and being left alone in the treatment room (p = 0.29), though none of these differences reached statistical significance.

    This study underscores the potential negative influence of prior sexual trauma on the RT experience for breast cancer patients. Although most patients reported overall comfort, those with a trauma history experienced trends toward greater distress related to exposure during treatment.

    Adopting trauma-informed practices to increase provider training, gender considerations, and patient-centered modifications could enhance patient comfort, adherence, and satisfaction for breast cancer treatment.
    Cancer
    Access
    Care/Management
    Advocacy
  • Dermatology patient-derived health utility of facial angiofibroma associated with tuberous sclerosis complex.
    2 weeks ago
    The majority of patients with Tuberous Sclerosis Complex have cutaneous manifestations, the most common being facial angiofibroma (FA). The impact of facial angiofibroma on quality of life has not been comprehensively evaluated, and a health state utility has not previously been determined. The purpose of this study was to calculate the health utility of facial angiofibroma from the perspective of dermatology patients and explore any associations between participants' sociodemographic characteristics and the perceived utility of facial angiofibroma.

    In a structured interview format, participants recruited from dermatology clinics (n = 100) were asked to imagine themselves in each of four health states (monocular blindness, binocular blindness, almost-clear facial angiofibroma and moderate facial angiofibroma). Visual analogue scale, time trade-off and standard gamble were conducted for each health state and each outcome was converted into a health state utility.

    The adjusted mean health state utilities were 0.88 [0.84,0.92], 0.95 [0.91,0.99] and 0.94 [0.91,0.98] for almost-clear facial angiofibroma, by Visual Analogue Scale, Time Trade-Off and Standard Gamble, respectively, and 0.68 [0.64,0.72], 0.88 [0.84,0.92] and 0.91 [0.87,0.94] for moderate facial angiofibroma. Participants theoretically elected to sacrifice 6.8 years of their remaining 57 years of life (12%) and accept a 9% risk of immediate death to receive curative treatment for moderate facial angiofibroma.

    The health state utility of moderate facial angiofibroma was significantly poorer than almost-clear facial angiofibroma. This highlights that reducing the severity of facial angiofibroma can deliver potential gains in quality of life.
    Cancer
    Access
    Care/Management
    Advocacy
  • The Impact of the G8 Score on Survival Outcomes in Patients With Head and Neck Cancer Undergoing Concurrent Radiotherapy With Cetuximab due to Contraindications With Cisplatin.
    2 weeks ago
    Patients unable to receive cisplatin due to age, comorbidities, or reduced performance status are commonly treated with concurrent radiotherapy (RT) and cetuximab. This study evaluated the prognostic significance of the Geriatric 8 (G8) score and the Charlson Comorbidity Index (CCI) in predicting survival outcomes in this population.

    We retrospectively analyzed data from 52 patients with locally advanced or loco-regional recurrent head and neck squamous cell carcinoma (HNSCC) who were treated with RT and cetuximab between 2011 and 2024. Patients with p16-positive oropharyngeal or nasopharyngeal cancers were excluded. Overall survival (OS) and cancer-specific survival (CSS) were assessed according to G8 and CCI scores using ROC analysis, Kaplan-Meier curves, and Cox regression.

    The median follow-up was 50 months. A G8 cut-off of 9.75 was identified (AUC: 0.713, p < 0.01). Patients with G8 ≥ 9.75 showed significantly improved OS (median: 47 vs. 7 months, p < 0.01) and 4-year CSS (66% vs. 32%, p < 0.01). In the definitive treatment group, 4-year CSS was 68% in high-G8 patients vs. 42% in low-G8 patients. In the recurrence group, 4-year CSS was 63% among high-G8 patients, whereas no patient with a low G8 score survived beyond 4 years. Multivariate analysis identified G8 < 9.75 (HR: 4.72, p < 0.01) and RT dose < 60 Gy (HR: 3.01, p = 0.01) as independent predictors of poor OS. No significant association was observed between CCI and survival.

    The G8 score is a valuable prognostic tool for cisplatin-ineligible HNSCC patients treated with RT and cetuximab. Low G8 scores were strongly associated with worse outcomes, highlighting the need for alternative therapeutic strategies in this high-risk subgroup.
    Cancer
    Access
    Care/Management
    Advocacy
  • Baseline neutrophil-to-lymphocyte ratio and cumulative clinical pregnancy and obstetric/neonatal outcomes after IVF/ICSI in women with PCOS: exploratory analysis including sperm preservation method.
    2 weeks ago
    In women with polycystic ovary syndrome (PCOS), IVF/ICSI outcomes may be influenced by systemic inflammation (neutrophil-to-lymphocyte ratio, NLR) and by sperm preservation method.

    We retrospectively studied 276 first eligible autologous PCOS IVF/ICSI cycles. NLR was dichotomized at 2.6 (low n = 136; high n = 140), whereas adjusted models used continuous NLR after exploratory spline assessment showed no convincing nonlinearity. Clinical pregnancy was defined cumulatively from the index retrieval cycle, including fresh or frozen transfer(s) derived from that cycle. Male-factor/semen characteristics were summarized by sperm method. Multivariable logistic regression evaluated cumulative clinical pregnancy in all cycles and an exploratory composite adverse pregnancy/neonatal outcome among 144 clinical pregnancies. Sensitivity analyses repeated the adjusted models using the dichotomized high-versus-low NLR grouping.

    Cumulative clinical pregnancy was lower with high versus low NLR (42.9% vs 61.8%; p = 0.002). Among clinical pregnancies, the exploratory composite adverse outcome was more frequent with high versus low NLR (58.3% vs 27.4%; p < 0.001). In adjusted analyses, each 1-unit increase in NLR was associated with lower odds of cumulative clinical pregnancy (aOR 0.71, 95% CI 0.53-0.95; p = 0.023) and higher odds of the exploratory composite adverse outcome (aOR 2.32, 95% CI 1.44-3.74; p < 0.001). Sensitivity models using dichotomized NLR were directionally consistent for cumulative clinical pregnancy (high vs low NLR: aOR 0.52, 95% CI 0.31-0.86; p = 0.011). Sperm preservation method was not independently associated with either outcome, and NLR × sperm interaction terms were not significant. Exploratory ROC analysis for the pregnancy cohort showed modest discrimination (AUC 0.67, 95% bootstrap CI 0.57-0.76); the Youden-derived cutoff of 3.16 yielded sensitivity 53.4% and specificity 84.9%.

    Higher baseline NLR was associated with lower cumulative clinical pregnancy and higher subsequent obstetric/neonatal risk in PCOS IVF/ICSI cycles. After accounting for baseline covariates and male-factor differences, fresh versus frozen ejaculated sperm was not independently associated with either outcome in this analysis. The ROC-derived cutoff should be viewed as exploratory only.
    Cancer
    Access
    Care/Management
    Advocacy
  • Effectiveness of Telerehabilitation for Upper-Limb Pain After Breast Cancer: Systematic Review.
    2 weeks ago
    Upper-limb pain is a frequent and disabling sequela following breast cancer treatment, often persisting beyond the acute postoperative period and substantially impairing function, self-management, and quality of life. Telerehabilitation has emerged as a strategy to expand access to physiotherapy-based care; however, its effectiveness for pain management in this population remains unclear.

    To systematically evaluate the effectiveness of telerehabilitation interventions in reducing upper-limb pain in women after breast cancer treatment.

    This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261332939). PubMed, CINAHL, Web of Science, and EMBASE were searched through December 2025. Randomized controlled trials evaluating telerehabilitation-based physiotherapy interventions and reporting outcomes related to upper-limb pain were included. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the certainty of evidence was evaluated using the GRADE framework.

    Six randomized controlled trials involving 517 women were included. Telerehabilitation interventions varied in delivery format (synchronous, asynchronous, app-based, or telephone-based), intensity, and duration. One trial demonstrated a significant reduction in the proportion of women reporting chronic arm pain, and another reported greater improvement in pain interference, but not pain intensity. The remaining studies showed pain outcomes comparable to usual care or no significant benefit. Methodological limitations included heterogeneity in pain assessment tools, limited individualization of interventions, attrition, lack of blinding, and inconsistent reporting of analgesic use. Overall certainty of evidence was rated as low.

    Telerehabilitation appears feasible and comparable to usual care for upper-limb pain management after breast cancer treatment; however, consistent superiority has not been demonstrated. Evidence of benefit is primarily associated with structured, high-frequency, and multimodal programs. Further well-designed trials with standardized pain-specific outcomes are needed.

    Management of upper-limb pain after breast cancer treatment through telerehabilitation requires coordinated input from multidisciplinary healthcare teams, including nurses and physical therapists. Telerehabilitation may facilitate remote pain monitoring, patient education, and self-management across survivorship care, provided that interventions are structured, clearly protocolized, and focused on pain-specific outcomes.
    Cancer
    Access