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Effects of a 12-week multicomponent exercise programme on physical function in older adults with cancer: Study protocol for the ONKO-FRAIL randomised controlled trial
Introduction Cancer in older adults is often associated with functional limitations, geriatric syndromes, poor self-rated health, vulnerability, and frailty, and these conditions might worsen treatment-related side effects. Recent guidelines for patients with cancer during and after treatment have documented the beneficial effects of exercise to counteract certain side effects; however, little is known about the role of exercise during cancer treatment in older adults. Materials and Methods This is a multicentre randomised controlled trial in which 200 participants will be allocated to a control group or an intervention group (the sample size has been calculated to detect a clinical difference of 1 point in Short Physical Performance Battery (SPPB) score, assuming an α error of 0.05, a β error of 0.20, and a 10 % loss rate). Patients aged ≥70 years, diagnosed with any type of solid cancer and candidates for systemic treatment are eligible. Subjects in the intervention group are invited to participate in a 12-week supervised multicomponent exercise programme in addition to receiving usual care. Study assessments are conducted at baseline and three months. The primary outcome measure is physical function as assessed by the SPPB. Secondary outcome measures include comprehensive geriatric assessment scores (including social situation, basic and instrumental activities of daily living, cognitive function, depression, nutritional status, polypharmacy, geriatric syndromes, pain, and emotional distress), anthropometric characteristics, frailty status, physical fitness, physical activity, cognitive function, quality of life, fatigue, and nutritional status. Study assessments also include analysis of inflammatory, endocrine, and nutritional mediators in serum and plasma as potential frailty biomarkers at mRNA and protein levels and multiparametric flow cytometric analysis to measure immunosenescence markers on T and NK cells. Discussion This study seeks to extend our knowledge on exercise interventions during systemic anticancer treatment in patients over 70 years of age. Results from this research will guide the management of older adults during systemic treatment in hospitals seeking to enhance the standard of care.
SPE-ECG: An Ontology-Guided Knowledge Representation Framework for Enhancing LLM-Based Code Generation
Large Language Models (LLMs) can translate natural-language instructions into code, but when the input is unstructured clinical protocol text, the generated code may omit doses, monitoring intervals, or safety thresholds that the text states. Such omissions matter because they can propagate into software that supports clinical monitoring. We propose SPE-ECG (Structured Prompt Engineering for Enhanced Code Generation), a transparent, rule-based pipeline that converts unstructured domain text into a JSON prompt using text cleaning, part-of-speech tagging, bigram matching, and hand-built domain dictionaries, without fine-tuning any model. In a case study of 43 rheumatoid arthritis DMARD monitoring protocols, we compared raw and structured prompts on three LLMs (GPT-3.5, LLaMA 2, and Gemma), scoring the generated Python code using version 3.15.1 with BLEU against the raw-prompt code of the other two models. Mean BLEU rose for all three models (relative gains of 55.1%, 32.5%, and 19.9%); the paired differences were significant for GPT-3.5 and LLaMA 2 but not, after correction for multiple comparisons, for Gemma. These results suggest that lightweight input structuring can change how closely different models’ outputs agree, and that it could serve as a low-cost, auditable preparation step for protocol-to-code tools built on free or open models. BLEU does not measure correctness, no ablation or state-of-the-art baseline was run, and clinical validation is required before any use.
Cross-Dataset Generalization of Deep Learning for Retinal Vessel Segmentation in Fundus Images: External Evaluation from DRIVE to CHASE_DB1
Automated retinal vessel segmentation can support quantitative analysis of fundus photographs and facilitate measurement of vascular characteristics associated with ocular and systemic disease. Although deep-learning methods achieve high segmentation performance on benchmark datasets, their reliability may decrease when applied to images obtained under different acquisition conditions. This study evaluated the cross-dataset generalizability of a U-Net segmentation architecture incorporating an ImageNet-pretrained ResNet34 encoder. Sixteen images from the DRIVE dataset were used for model training and four were retained for in-domain validation. Images were resized to 256 × 256 pixels and processed using a consistent normalization pipeline, while spatial and photometric augmentation was applied during training. Without target-domain retraining or domain adaptation, the trained model was subsequently evaluated on the independent CHASE_DB1 dataset. Segmentation performance was assessed using the Dice coefficient, intersection over union (IoU), and sensitivity, together with qualitative examination of predicted vessel maps. On the held-out DRIVE images, the model achieved a Dice coefficient of 0.7263, IoU of 0.5703, and sensitivity of 0.7201. On CHASE_DB1, performance decreased to 0.6269, 0.4573, and 0.5502, respectively. The disproportionately larger reduction in sensitivity indicated an increased frequency of missed vessel pixels under cross-dataset evaluation. Qualitative examination showed greater fragmentation and omission of fine and peripheral vascular structures in CHASE_DB1 images. These findings demonstrate that within-dataset performance may overestimate the robustness of retinal vessel segmentation models when transferred to a different imaging domain. External evaluation should therefore form an important component of retinal imaging artificial intelligence research. Future work should investigate higher-resolution processing, vessel-width-specific evaluation, multi-domain training, domain-adaptation strategies, and larger multicentre datasets to improve model generalizability.
Thermal degradation mechanism of myricetin in palmitic acid
Dietary polyphenols are susceptible to degradation during high-temperature cooking, yet their transformation behavior in lipid-rich frying systems remains poorly understood. The thermal stability and degradation of myricetin in a simplified palmitic acid model under frying-relevant conditions was investigated. Myricetin degraded rapidly at 180 °C but remained relatively stable at 120 °C. UPLC–QTOF–MS/MS, supported by density functional theory calculations, suggested that myricetin transformation is temperature-dependent but primarily governed by lipid oxidation–derived radical and carbonyl chemistry. Vitamin C markedly delayed myricetin degradation by suppressing radical initiation and limiting o-quinone–centered downstream reactions. These findings highlight lipid oxidation as a key determinant of polyphenol stability during frying and clarify the protective role of antioxidants in lipid-rich thermal processing systems.
Hybrid deep learning and CNN-Isotonic Regression framework for accurate global mean sea level rise prediction using multi-source atmospheric and oceanic data
Keeping track of Global Mean Sea Level (GMSL) over long periods is important for assessing coastal risk. However, deep learning models may produce predictions that exhibit short-term increases and decreases, potentially conflicting with expected long-term physical behavior. In this study, we propose a combined Convolutional Neural Network and Isotonic Regression framework, termed CNN-ISO, for modeling and forecasting annual GMSL changes over the period 1880–2024. The framework uses 11 predictors representing atmospheric, oceanic, and cryospheric conditions. To provide longer temporal sequences, the original 144 annual observations are linearly interpolated into 1728 monthly observations. Model evaluation follows a strict chronological split, with training data from 1880–1979, validation data from 1980–1999, and test data from 2000–2024. All preprocessing transformations and the isotonic mapping are fitted exclusively on the training set to prevent information leakage from later periods. On the unseen test period, CNN-ISO achieves R 2 = 0.997 with a 95% confidence interval of [ 0.995,0.999 ] , together with an MAE of 0.56 mm and an RMSE of 0.72 mm. For comparison, linear regression achieves R 2 = 0.982 . Although the predictive improvement over linear regression is relatively modest, CNN-ISO provides an additional constraint by producing monotonic out-of-sample projections, which is consistent with the assumed long-term behavior of GMSL. Under statistical trend extrapolation to 2050, CNN-ISO estimates a GMSL increase of 184.10 mm relative to the baseline. However, estimates vary substantially across models, with linear regression and LSTM producing 116.60 mm and 299.19 mm, respectively. These results should therefore be interpreted as trend-based statistical extrapolations rather than comprehensive climate projections, as the framework does not explicitly model ice-sheet dynamics, changes in ocean circulation, or future emission pathways. Nevertheless, the proposed approach provides a transparent framework for examining model uncertainty and may support early-stage coastal adaptation planning.