All UK children could be offered screening for type 1 diabetes using a simple finger-prick blood test, say researchers who have been running a large study. Currently, many young people go undiagnosed and risk developing a life-threatening complication called diabetic ketoacidosis that needs urgent hospital treatment. Identifying diabetes earlier could help avoid this and mean treatments to control problematic blood sugar levels can be given sooner. Some 17,000 children aged three to 13 have already been checked as part of the ELSA (Early Surveillance for Autoimmune diabetes) study, funded by diabetes charities. Imogen, who is 12 and from the West Midlands, is one of those found to have diabetes thanks to the screening.

Feature selection (FS) is essential for biomarker discovery and in the analysis of biomedical datasets. However, challenges such as high-dimensional feature space, low sample size, multicollinearity, and missing values make FS non-trivial. Moreover, FS performances vary across datasets and predictive tasks. We propose roofs, a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. Roofs benchmarks multiple FS methods on the user's data and generates reports that summarize a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, reliability of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of roofs on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. The PIONeeR dataset contained 374 multi-source blood and tumor biomarkers from 435 patients. A reduced subset of 214 features was obtained through iterative variance inflation factor pre-filtering. Of the 34 FS methods gathered in roofs, we evaluated 23 in combination with 11 classifiers (253 models in total) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including the widely used LASSO. We conclude that comprehensive benchmarking with roofs has the potential to improve the robustness and reproducibility of FS discoveries and increase the translational value of clinical models.

Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregres-sive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.

The development of vaccines and immunotherapies against infectious diseases and cancers has been one of the major achievements of medical science in the last century. Subunit vaccines offer key advantages over whole-inactivated or attenuated-pathogen-based vaccines, as they elicit more specific Band T-cell responses with improved safety. However, developing subunit vaccines is often cost and timeconsuming and may not predict fast, strong, and long-lasting immunity, limiting their ability to rapidly counter apparent growing emerging pandemics and cancers. In the past, the development of vaccines and immunotherapeutics relied heavily on trial-and-error experimentation and extensive in vivo testing, often requiring years of pre-clinical and clinical trials. Today, artificial intelligence (AI) and deep learning (DL) are actively transforming vaccine and immunotherapeutic design, by (i) offering predictive frameworks that support rapid, data-driven decision-making; (ii) increasingly being implemented as time-and resourceefficient strategies that integrate computational models; systems vaccinology and multi-omics data to better phenotype, differentiate, and classify patients diseases and cancers; predict patients' immune responses and identify the factors contributing to optimal vaccine and immunotherapeutic protective efficacy; (iii) refining the selection of Band T-cell antigen/epitope targets to enhance efficacy and durability of immune protection; and (iv) enabling a deeper understanding of immune regulation, immune evasion, immune checkpoints, and regulatory pathways. The future of AI and DL points toward (i) replacing animal preclinical testing of drugs, vaccines, and immunotherapeutics with computational-based models, as recently proposed by the United States FDA; and (ii) enabling real-time in vivo modeling for immunobridging and prediction of protection in clinical trials. This may result in a fast and transformative shift for the development of personal vaccines and immunotherapeutics against infectious pathogens and cancers.

Language models (LMs) capabilities have grown with a fast pace over the past decade leading researchers in various disciplines, such as biomedical research, to increasingly explore the utility of LMs in their day-to-day applications. Domain specific language models have already been in use for biomedical natural language processing (NLP) applications. Recently however, the interest has grown towards medical language models and their understanding capabilities. In this paper, we investigate the medical conceptual grounding of various language models against expert clinicians for identification of hallmarks of immunotherapy in breast cancer abstracts. Our results show that pre-trained language models have potential to outperform large language models in identifying very specific (low-level) concepts.

These authors contributed equally and are considered joint last authors Correspondence: melda.yeghaian@donders.ru.nl Abstract Purpose: Analyzing noninvasive longitudinal and multimodal data using artificial intelligence could potentially transform immunotherapy for cancer patients, paving the way towards precision medicine. Methods: In this study, we integrated pre-and on-treatment blood measurements, prescribed medications and CT-based volumes of organs from a large pan-cancer cohort of 694 patients treated with immunotherapy to predict short and long-term overall survival. By leveraging a combination of recent developments, different variants of our extended multimodal transformer-based simple temporal attention (MMTSimTA) network were trained end-to-end to predict mortality at three, six, nine and twelve months. These models were also compared to baseline methods incorporating intermediate and late fusion based integration methods. Results: The strongest prognostic performance was demonstrated using the extended transformer-based multimodal model with area under the curves (AUCs) of 0.84 0.04, 0.83 0.02, 0.82 0.02, 0.81 0.03 for 3-, 6-, 9-, and 12-month survival prediction, respectively. Conclusion: Our findings suggest that analyzing integrated early treatment data has potential for predicting survival of immunotherapy patients. Integrating complementary noninvasive modalities into a jointly trained model, using our extended transformer-based architecture, demonstrated an improved multimodal prognostic performance, especially in short term survival prediction. 1 Introduction During cancer treatment, non-invasive data, such as laboratory blood test results and radiological imaging, is routinely collected by clinicians to guide clinical decision-making.

Researching the specificity of TCR contributes to the development of immunotherapy and provides new opportunities and strategies for personalized cancer immunotherapy. Therefore, we established a TCR generative specificity detection framework consisting of an antigen selector and a TCR classifier based on the Random Forest algorithm, aiming to efficiently screen out TCRs and target antigens and achieve TCR specificity prediction. Furthermore, we used the k-fold validation method to compare the performance of our model with ordinary deep learning methods. The result proves that adding a classifier to the model based on the random forest algorithm is very effective, and our model generally outperforms ordinary deep learning methods. Moreover, we put forward feasible optimization suggestions for the shortcomings and challenges of our model found during model implementation.

Doctors believe Artificial Intelligence is now saving lives, after a major advancement in breast cancer screenings. A.I. is detecting early signs of the disease, in some cases years before doctors would find the cancer on a traditional scan. A chemotherapy alternative called immunotherapy is showing promise in treating cancer -- and a new artificial intelligence tool could help ensure that patients have the best possible experience. Immunotherapy, first approved in 2011, uses the cancer patient's own immune system to target and fight cancer. While it doesn't work for everyone, for the 15% to 20% who do see results, it can be life-saving.

PULSAR (personalized, ultra-fractionated stereotactic adaptive radiotherapy) is the adaptation of stereotactic ablative radiotherapy towards personalized cancer management. For the first time, we applied a transformer-based attention mechanism to investigate the underlying interactions between combined PULSAR and PD-L1 blockade immunotherapy based on a murine cancer model (Lewis Lung Carcinoma, LLC). The proposed approach is able to predict the trend of tumor volume change semi-quantitatively, and excels in identifying the potential causal relationships through both self-attention and cross-attention scores. Introduction The field of combining radiotherapy and immunotherapy is rapidly evolving, and one aspect of particular interest is determination of optimal timing and sequence to harness the potential synergy between radiation therapy and immune checkpoint blockade.

Gastric and oesophageal (OG) cancers are the leading causes of cancer mortality worldwide. In OG cancers, recent studies have showed that PDL1 immune checkpoint inhibitors (ICI) in combination with chemotherapy improves patient survival. However, our understanding of the tumour immune microenvironment in OG cancers remains limited. In this study, we interrogate multiplex immunofluorescence (mIF) images taken from patients with advanced Oesophagogastric Adenocarcinoma (OGA) who received first-line fluoropyrimidine and platinum-based chemotherapy in the PLATFORM trial (NCT02678182) to predict the efficacy of the treatment and to explore the biological basis of patients responding to maintenance durvalumab (PDL1 inhibitor). Our proposed Artificial Intelligence (AI) based marker successfully identified responder from non-responder (p < 0.05) as well as those who could potentially benefit from ICI with statistical significance (p < 0.05) for both progression free and overall survival. Our findings suggest that T cells that express FOXP3 seem to heavily influence the patient treatment response and survival outcome. We also observed that higher levels of CD8+PD1+ cells are consistently linked to poor prognosis for both OS and PFS, regardless of ICI.