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Code archive corresponding to the manuscript submission: "Quantifying the Optimism of Naive Cross-Validation for Binary Outcome Prediction with Repeated-Measures Predictors: A Simulation Study and Clinical Illustration."
The editors of BMC Medical Research Methodology would like to thank all our reviewers who have contributed to the journal in Volume 15 (2015).
The automation of scientific research through large language models (LLMs) presents significant opportunities but faces critical challenges in knowledge synthesis and quality assurance. We introduce Feedback-Refined Agent Methodology (FRAME), a novel framework that enhances medical paper generation through iterative refinement and structured feedback. Our approach comprises three key innovations: (1) A structured dataset construction method that decomposes 4,287 medical papers into essential research components through iterative refinement; (2) A tripartite architecture integrating Generator, Evaluator, and Reflector agents that progressively improve content quality through metric-driven feedback; and (3) A comprehensive evaluation framework that combines statistical metrics with human-grounded benchmarks. Experimental results demonstrate FRAME's effectiveness, achieving significant improvements over conventional approaches across multiple models (9.91% average gain with DeepSeek V3, comparable improvements with GPT-4o Mini) and evaluation dimensions. Human evaluation confirms that FRAME-generated papers achieve quality comparable to human-authored works, with particular strength i
Advanced radiotherapy approaches such as FLASH irradiation and spatially fractionated radiotherapy (SFRT) show potential to improve the therapeutic ratio, yet their biological mechanisms and optimal delivery parameters remain uncertain. Progress requires accessible proton research platforms with flexible temporal and spatial dose delivery. We report on the adaptation of the Beam Transfer Line (BTL) of the Bern Medical Cyclotron (BMC) for radiobiology research with FLASH and proton minibeam capabilities. The BMC is optimized for the production of radionuclides for medical imaging, and is able to extract currents up to 150 $ \mathrm{μA}$. The 18 MeV proton beam was passively shaped using collimators, scattering foils, and extended drift space to generate irradiation fields. A dosimetric framework was implemented using an in-beam ionization chamber and radiochromic film with LET-dependent corrections. Beam uniformity and SFRT profiles with various grid spacings were evaluated at realistic target distances. The developed beamline enables stable delivery under controlled conditions in both conventional and FLASH regimes, spanning dose rates from 0.01 to 100 Gy/s. Dose uniformity within
BACKGROUND: An observed decrease of physician scientists in medical practice has generated much recent interest in increasing the exposure of research programs in medical school. The aim of this study was to review the experience and attitudes regarding research by medical students in Canada. METHODS: An anonymous, cross-sectional, self-report questionnaire was administered to second and fourth year students in three medical schools in Ontario between February and May of 2005. Questions were primarily closed-ended and consisted of Likert scales. Descriptive and correlative statistics were used to analyze the responses between students of different years and previous research experience. RESULTS: There was a 47% (327/699) overall response rate to the questionnaire. Despite 87% of respondents reporting that they had been involved in some degree of research prior to medical school, 43% report that they have not been significantly involved in research activity during medical school and 24% had no interest in any participation. There were significant differences in the attitudes towards research endeavors during medical school between students in their fourth year compared to second year. The greatest barriers to involvement in research in medical school appear to be time, availability of research mentors, formal teaching of research methodology and the perception that the student would not receive appropriate acknowledgement for work put towards a research project. CONCLUSION: The results of this self-report survey outline the significant differences in attitudes towards mandatory research as a component of critical inquiry and scholarship in the undergraduate curriculum in Ontario medical schools.
Empirical substantive research, such as in the life or social sciences, is commonly categorized into the two modes exploratory and confirmatory, both of which are essential to scientific progress. The former is also referred to as hypothesis-generating or data-contingent research, while the latter is also called hypothesis-testing research. In the context of empirical methodological research in statistics, however, the exploratory-confirmatory distinction has received very little attention so far. Our paper aims to fill this gap. First, we revisit the concept of empirical methodological research through the lens of the exploratory-confirmatory distinction. Second, we examine current practice with respect to this distinction through a literature survey including 115 articles from the field of biostatistics. Third, we provide practical recommendations toward a more appropriate design, interpretation, and reporting of empirical methodological research in light of this distinction. In particular, we argue that both modes of research are crucial to methodological progress, but that most published studies -- even if sometimes disguised as confirmatory -- are essentially exploratory in na
Medical image analysis is essential to clinical diagnosis and treatment, which is increasingly supported by multi-modal large language models (MLLMs). However, previous research has primarily focused on 2D medical images, leaving 3D images under-explored, despite their richer spatial information. This paper aims to advance 3D medical image analysis with MLLMs. To this end, we present a large-scale 3D multi-modal medical dataset, M3D-Data, comprising 120K image-text pairs and 662K instruction-response pairs specifically tailored for various 3D medical tasks, such as image-text retrieval, report generation, visual question answering, positioning, and segmentation. Additionally, we propose M3D-LaMed, a versatile multi-modal large language model for 3D medical image analysis. Furthermore, we introduce a new 3D multi-modal medical benchmark, M3D-Bench, which facilitates automatic evaluation across eight tasks. Through comprehensive evaluation, our method proves to be a robust model for 3D medical image analysis, outperforming existing solutions. All code, data, and models are publicly available at: https://github.com/BAAI-DCAI/M3D.
Vision-language foundation models (VLMs) have shown great potential in feature transfer and generalization across a wide spectrum of medical-related downstream tasks. However, fine-tuning these models is resource-intensive due to their large number of parameters. Prompt tuning has emerged as a viable solution to mitigate memory usage and reduce training time while maintaining competitive performance. Nevertheless, the challenge is that existing prompt tuning methods cannot precisely distinguish different kinds of medical concepts, which miss essentially specific disease-related features across various medical imaging modalities in medical image classification tasks. We find that Large Language Models (LLMs), trained on extensive text corpora, are particularly adept at providing this specialized medical knowledge. Motivated by this, we propose incorporating LLMs into the prompt tuning process. Specifically, we introduce the CILMP, Conditional Intervention of Large Language Models for Prompt Tuning, a method that bridges LLMs and VLMs to facilitate the transfer of medical knowledge into VLM prompts. CILMP extracts disease-specific representations from LLMs, intervenes within a low-ra
Access to diverse, well-annotated medical images with interactive learning tools is fundamental for training practitioners in medicine and related fields to improve their diagnostic skills and understanding of anatomical structures. While medical atlases are valuable, they are often impractical due to their size and lack of interactivity, whereas online image search may provide mislabeled or incomplete material. To address this, we propose MIRAGE, a multimodal medical text and image retrieval and generation system that allows users to find and generate clinically relevant images from trustworthy sources by mapping both text and images to a shared latent space, enabling semantically meaningful queries. The system is based on a fine-tuned medical version of CLIP (MedICaT-ROCO), trained with the ROCO dataset, obtained from PubMed Central. MIRAGE allows users to give prompts to retrieve images, generate synthetic ones through a medical diffusion model (Prompt2MedImage) and receive enriched descriptions from a large language model (Dolly-v2-3b). It also supports a dual search option, enabling the visual comparison of different medical conditions. A key advantage of the system is that it
Digital healthcare generates vast amounts of clinical text that can support AI-assisted applications, yet German biomedical language models remain limited by older architectures or restricted training data. We present ChristBERT (Clinical- and Healthcare-Related Issues and Subjects Tuned BERT), a family of domain-specific German RoBERTa-based language models trained on a 13.5GB corpus of scientific publications, clinical texts, health-related web content, and translated clinical resources. To investigate the impact of domain adaptation strategies in German clinical NLP, we compare continued pre-training, training from scratch, and domain-specific vocabulary adaptation. The resulting models are evaluated on three medical named entity recognition tasks and two text classification tasks. ChristBERT consistently outperforms existing general-purpose and medical German language models on four of five benchmarks and establishes a new state of the art for German clinical language modeling. Our results show that the optimal adaptation strategy is task-dependent: in our evaluation, training from scratch is particularly effective for highly specialized clinical texts, whereas continued pre-tr
The Segment Anything Model (SAM) has recently gained popularity in the field of image segmentation due to its impressive capabilities in various segmentation tasks and its prompt-based interface. However, recent studies and individual experiments have shown that SAM underperforms in medical image segmentation, since the lack of the medical specific knowledge. This raises the question of how to enhance SAM's segmentation capability for medical images. In this paper, instead of fine-tuning the SAM model, we propose the Medical SAM Adapter (Med-SA), which incorporates domain-specific medical knowledge into the segmentation model using a light yet effective adaptation technique. In Med-SA, we propose Space-Depth Transpose (SD-Trans) to adapt 2D SAM to 3D medical images and Hyper-Prompting Adapter (HyP-Adpt) to achieve prompt-conditioned adaptation. We conduct comprehensive evaluation experiments on 17 medical image segmentation tasks across various image modalities. Med-SA outperforms several state-of-the-art (SOTA) medical image segmentation methods, while updating only 2\% of the parameters. Our code is released at https://github.com/KidsWithTokens/Medical-SAM-Adapter.
One of the most noticeable trends in healthcare over the last years is the continuous growth of data volume produced and its heterogeneity. In the medical imaging field, the evolution of digital systems is supported by the PACS concept and the DICOM standard. These technologies are deeply grounded in medical laboratories, supporting the production and providing healthcare practitioners with the ability to set up collaborative work environments with researchers and academia to study and improve healthcare practice. However, the complexity of those systems and protocols makes difficult and time-consuming to prototype new ideas or develop applied research, even for skilled users with training in those environments. Dicoogle emerges as a reference tool to achieve those objectives through a set of resources aggregated in the form of a learning pack. It is an open-source PACS archive that, on the one hand, provides a comprehensive view of the PACS and DICOM technologies and, on the other hand, provides the user with tools to easily expand its core functionalities. This paper describes the Dicoogle framework, with particular emphasis in its Learning Pack package, the resources available a
Over the years, the Invariant Scattering Transform (IST) technique has become popular for medical image analysis, including using wavelet transform computation using Convolutional Neural Networks (CNN) to capture patterns' scale and orientation in the input signal. IST aims to be invariant to transformations that are common in medical images, such as translation, rotation, scaling, and deformation, used to improve the performance in medical imaging applications such as segmentation, classification, and registration, which can be integrated into machine learning algorithms for disease detection, diagnosis, and treatment planning. Additionally, combining IST with deep learning approaches has the potential to leverage their strengths and enhance medical image analysis outcomes. This study provides an overview of IST in medical imaging by considering the types of IST, their application, limitations, and potential scopes for future researchers and practitioners.
Large volumes of medical data remain underutilized because centralizing distributed data is often infeasible due to strict privacy regulations and institutional constraints. In addition, models trained in centralized settings frequently fail to generalize across clinical sites because of heterogeneity in imaging protocols and continuously evolving data distributions arising from differences in scanners, acquisition parameters, and patient populations. Federated learning offers a promising solution by enabling collaborative model training without sharing raw data. However, incorporating differential privacy into federated learning, while essential for privacy guarantees, often leads to degraded accuracy, unstable convergence, and reduced generalization. In this work, we propose an adaptive differentially private federated learning (ADP-FL) framework for medical image segmentation that dynamically adjusts privacy mechanisms to better balance the privacy-utility trade-off. The proposed approach stabilizes training, significantly improves Dice scores and segmentation boundary quality, and maintains rigorous privacy guarantees. We evaluated ADP-FL across diverse imaging modalities and s
The diagnosis and treatment of various diseases had been expedited with the help of medical imaging. Different medical imaging modalities, including X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Nuclear Imaging, Ultrasound, Electrical Impedance Tomography (EIT), and Emerging Technologies for in vivo imaging modalities is presented in this chapter, in addition to these modalities, some advanced techniques such as contrast-enhanced MRI, MR approaches for osteoarthritis, Cardiovascular Imaging, and Medical Imaging data mining and search. Despite its important role and potential effectiveness as a diagnostic tool, reading and interpreting medical images by radiologists is often tedious and difficult due to the large heterogeneity of diseases and the limitation of image quality or resolution. Besides the introduction and discussion of the basic principles, typical clinical applications, advantages, and limitations of each modality used in current clinical practice, this chapter also highlights the importance of emerging technologies in medical imaging and the role of data mining and search aiming to support translational clinical research, improve patient care, and
Determining whether two sets of images belong to the same or different distributions or domains is a crucial task in modern medical image analysis and deep learning; for example, to evaluate the output quality of image generative models. Currently, metrics used for this task either rely on the (potentially biased) choice of some downstream task, such as segmentation, or adopt task-independent perceptual metrics (e.g., Fréchet Inception Distance/FID) from natural imaging, which we show insufficiently capture anatomical features. To this end, we introduce a new perceptual metric tailored for medical images, FRD (Fréchet Radiomic Distance), which utilizes standardized, clinically meaningful, and interpretable image features. We show that FRD is superior to other image distribution metrics for a range of medical imaging applications, including out-of-domain (OOD) detection, the evaluation of image-to-image translation (by correlating more with downstream task performance as well as anatomical consistency and realism), and the evaluation of unconditional image generation. Moreover, FRD offers additional benefits such as stability and computational efficiency at low sample sizes, sensiti
Medical imaging is an essential tool for diagnosing and treating diseases. However, lacking medical images can lead to inaccurate diagnoses and ineffective treatments. Generative models offer a promising solution for addressing medical image shortage problems due to their ability to generate new data from existing datasets and detect anomalies in this data. Data augmentation with position augmentation methods like scaling, cropping, flipping, padding, rotation, and translation could lead to more overfitting in domains with little data, such as medical image data. This paper proposes the GAN-GA, a generative model optimized by embedding a genetic algorithm. The proposed model enhances image fidelity and diversity while preserving distinctive features. The proposed medical image synthesis approach improves the quality and fidelity of medical images, an essential aspect of image interpretation. To evaluate synthesized images: Frechet Inception Distance (FID) is used. The proposed GAN-GA model is tested by generating Acute lymphoblastic leukemia (ALL) medical images, an image dataset, and is the first time to be used in generative models. Our results were compared to those of InfoGAN a
This paper presents a methodology for measuring the technical efficiency of research activities. It is based on the application of data envelopment analysis to bibliometric data on the Italian university system. For that purpose, different input values (research personnel by level and extra funding) and output values (quantity, quality and level of contribution to actual scientific publications) are considered. Our study aims at overcoming some of the limitations connected to the methodologies that have so far been proposed in the literature, in particular by surveying the scientific production of universities by authors' name.
Deep learning becomes an elevated context regarding disposing of many machine learning tasks and has shown a breakthrough upliftment to extract features from unstructured data. Though this flourishing context is developing in the medical image processing sector, scarcity of problem-dependent training data has become a larger issue in the way of easy application of deep learning in the medical sector. To unravel the confined data source, researchers have developed a model that can solve machine learning problems with fewer data called ``Few shot learning". Few hot learning algorithms determine to solve the data limitation problems by extracting the characteristics from a small dataset through classification and segmentation methods. In the medical sector, there is frequently a shortage of available datasets in respect of some confidential diseases. Therefore, Few shot learning gets the limelight in this data scarcity sector. In this chapter, the background and basic overview of a few shots of learning is represented. Henceforth, the classification of few-shot learning is described also. Even the paper shows a comparison of methodological approaches that are applied in medical image
Medical image segmentation is critical for clinical diagnosis, treatment planning, and monitoring, yet segmentation models often struggle with uncertainties stemming from occlusions, ambiguous boundaries, and variations in imaging devices. Traditional test-time augmentation (TTA) techniques typically rely on predefined geometric and photometric transformations, limiting their adaptability and effectiveness in complex medical scenarios. In this study, we introduced Test-Time Generative Augmentation (TTGA), a novel augmentation strategy specifically tailored for medical image segmentation at inference time. Different from conventional augmentation strategies that suffer from excessive randomness or limited flexibility, TTGA leverages a domain-fine-tuned generative model to produce contextually relevant and diverse augmentations tailored to the characteristics of each test image. Built upon diffusion model inversion, a masked null-text inversion method is proposed to enable region-specific augmentations during sampling. Furthermore, a dual denoising pathway is designed to balance precise identity preservation with controlled variability. We demonstrate the efficacy of our TTGA through