论文检索

Applications · Health / Medicine

Chunlei Li, Zixuan Zheng, Yilei Shi, Guanglu Dong, Pengfei Li, Jingliang Hu, Xiao Zhu, Lichao Mou

Mislabeled samples in training datasets severely degrade the performance of deep networks, as overparameterized models tend to memorize erroneous labels. We address this challenge by proposing a novel approach for mislabeled data detection that leverages training dynamics. Our method is grounded in the key observation that correctly labeled samples exhibit consistent entropy decrease during training, while mislabeled samples maintain relatively high entropy throughout the training process. Building on this insight, we introduce a signed entropy integral (SEI) statistic that captures both the magnitude and temporal trend of prediction entropy across training epochs. SEI is broadly applicable to classification networks and demonstrates particular effectiveness when integrated with contrastive language-image pretraining (CLIP) architectures. Through extensive experiments on three medical imaging datasets---a domain particularly susceptible to labeling errors due to diagnostic complexity---spanning diverse modalities and pathologies, we demonstrate that SEI achieves state-of-the-art performance in mislabeled data identification, outperforming existing methods while maintaining computational efficiency and implementation simplicity.

Applications · Health / Medicine

Yucheng Xing, ling huang, Jingying Ma, Ruping Hong, Jiangdong Qiu, Pei Liu, Kai He, Huazhu Fu, Mengling Feng

Whole-slide images (WSIs) are widely used for cancer survival analysis because of their comprehensive histopathological information at both cellular and tissue levels, enabling quantitative, large-scale, and prognostically rich tumor feature analysis. However, most existing WSI survival analysis methods struggle with limited interpretability and often overlook predictive uncertainty in heterogeneous slide images. In this paper, we propose DPsurv, a dual-prototype whole-slide image evidential fusion network that outputs uncertainty-aware survival intervals, and enables interpretable survival results through patch prototype distribution assignment, component prototype evidence reasoning, and component-wise relative risk aggregation. Experiments on five publicly available datasets demonstrate strong discriminative performance and well-calibrated predictions, validating its effectiveness and reliability. The interpretation of survival results provides transparency at the feature, reasoning, and decision levels, thereby enhancing the trustworthiness and interpretability of DPsurv.

Applications · Health / Medicine

Yiqi Su, Ray Lee, Jiaming Cui, Naren Ramakrishnan

Epidemiological forecasting from surveillance data is a hard problem and hybridizing mechanistic compartmental models with neural models is a natural direction. The mechanistic structure helps keep trajectories epidemiologically plausible, while neural components can capture non-stationary, data-adaptive effects. In practice, however, many seemingly straightforward couplings fail under partial observability and continually shifting transmission dynamics driven by behavior, waning immunity, seasonality, and interventions. We catalog these failure modes and show that robust performance requires making non-stationarity explicit: we extract multi-scale structure from the observed infection series and use it as an interpretable control signal for a controlled neural ODE coupled to an epidemiological model. Concretely, we decompose infections into trend, seasonal, and residual components and use these signals to drive continuous-time latent dynamics while jointly forecasting and inferring time-varying transmission, recovery, and immunity-loss rates. Across seasonal and non-seasonal settings—including early outbreaks and multi-wave regimes—our approach reduces long-horizon RMSE by 15–35%, improves peak timing error by 1–3 weeks, and lowers peak magnitude bias by up to 30% relative strong time-series, neural ODE, and hybrid baselines, without relying on auxiliary covariates.

Applications · Health / Medicine

Shiva Kaul, Anjum Khurshid

Medical AI has rapidly improved its ability to perform diagnostic and prognostic tasks that lead to treatment decisions. But understanding of treatment itself is still inadequately trained and evaluated, using human opinions and syntheses (especially texts such as biomedical publications and clinical practice guidelines) rather than actual underlying data on treatment outcomes. This neglect seriously limits the long-term potential of medical AI, and is already causing deficiencies in both frontier models and major benchmarks, as argued in this position paper. Real treatment outcomes, drawn from sources such as observational databases and randomized experiments, should be substantially incorporated into both training and evaluation. Improving these outcomes should be reemphasized as the goal of all medical AI.

Applications · Health / Medicine

Jingbo Yang, Yunfeng Zhao, Chao Qiu, Yulin Sun, Xiuyun Liu, Xiaofei Wang

Stereotactic electroencephalography (sEEG) provides temporally precise intracranial recordings but is inherently constrained by sparse and irregular spatial sampling due to clinical limitations on electrode implantation. Signal reconstruction under this setting aims to infer neural activity at unmonitored locations, potentially expanding the coverage of neural recordings without increasing the number of implanted electrodes. However, most existing sEEG reconstruction methods underutilize the spatial information of electrode contacts in both encoding and modeling, and rely on deterministic objectives that favor average patterns, leading to over-smoothed reconstructions. We propose EpiTwin, a conditional spatial graph transformer for sEEG signal reconstruction, comprising three key components. Hybrid Spatial Positional Encoding (HSPE) constructs explicit spatial identities from electrode coordinates, graph topology, and anatomical priors. Geometry–Functional Biased Attention (GFBA) incorporates geometric distance and data-driven functional similarity biases into attention computation. Adversarial Refinement Training employs a multi-scale discriminator to counter reconstruction over-smoothing. Experiments on real-world clinical sEEG data demonstrate that EpiTwin consistently achieves lower reconstruction error under electrode series-level masking, outperforming recent foundation models such as LaBraM with a 16.8\% relative reduction in RMSE. Furthermore, EpiTwin effectively mitigates spectral over-smoothing and improves reconstruction fidelity.

Applications · Health / Medicine

Yuting Yan, Yinghao Fu, Wendi Ren, Haozhou Gao, Shuang Li

Diagnosing rare diseases remains a persistent challenge, often hindered by *cognitive anchoring*: once clinicians settle on a common diagnosis, they often discount alternative explanations, including rare conditions. To address this, we propose a human-centered counterfactual reasoning framework using a Denoising Masked AutoEncoder (DMAE) to simulate *what-if* diagnostic scenarios that disrupt clinicians’ initial assumptions. Our model jointly learns (1) the true distribution of diseases and symptoms, and (2) human diagnostic behavior, revealing critical gaps between *medically possible* and *clinically considered* diagnoses. By strategically perturbing latent patient representations, it generates *contrastive counterfactuals* that highlight rare yet plausible diseases that cognitive bias often obscures. Unlike traditional decision-support tools, our system *proactively* suggests rare diseases not because they are statistically probable, but because they are *cognitively neglected*. Across four public and three private rare-disease datasets, our approach outperforms standard machine learning classifiers in detecting rare conditions while maintaining strong performance on common diagnoses. Beyond boosting accuracy, the counterfactual evidence encourages *hypothesis-driven reasoning* and supports clinical learning.

Applications · Health / Medicine

Sirui Li, Shuhan Xiao, Mihir Joshi, Ahmed Metwally, Daniel McDuff, Wei Wang, Yuzhe Yang

The rise of large language models (LLMs) has shifted time series analysis from narrow analytics to general-purpose reasoning. Yet, existing benchmarks cover only a small set of health time series modalities and tasks, failing to reflect the diverse domains and extensive temporal dependencies inherent in real-world physiological modeling. To bridge these gaps, we introduce HEARTS (Health Reasoning over Time Series), a unified benchmark for evaluating hierarchical reasoning capabilities of LLMs over general health time series. HEARTS integrates 16 real-world datasets across 12 health domains and 20 signal modalities, and defines a comprehensive taxonomy of 110 tasks grouped into four core capabilities: Perception, Inference, Generation, and Deduction. Evaluating 14 state-of-the-art LLMs on more than 20K test samples reveals intriguing findings. First, LLMs substantially underperform specialized models, and their performance is only weakly related to general reasoning scores. Moreover, LLMs often rely on simple heuristics and struggle with multi-step temporal reasoning. Finally, performance declines with increasing temporal complexity, with similar failure modes within model families, indicating that scaling alone is insufficient. By making these gaps measurable, HEARTS provides a standardized testbed and living benchmark for developing next-generation LLM agents capable of reasoning over diverse health signals.

Applications · Health / Medicine

Wenkang Jiang, Yuhang Liu, Yichao Cai, Erdun Gao, Jiayi Dong, Ehsan Abbasnejad, Lina Yao, Javen Qinfeng Shi

Single-cell perturbation modeling is fundamental for understanding and predicting cellular responses to genetic perturbations. However, existing approaches, from causal representation learning to foundation models, often struggle with an overlooked challenge: gene expression is dominated by perturbation-invariant information, while perturbation-specific signals are intrinsically sparse. As a result, learned representations either entangle invariant and perturbation-specific information, leading to spurious and non-generalizable predictors, or suppress perturbation-specific signals altogether, rendering them ineffective for prediction. To address this, we propose PerturbedVAE, a general framework designed to resolve this signal imbalance. The framework explicitly separates perturbation-specific information from dominant invariant structure and recovers causal representations to effectively utilize such information for prediction. We further provide an identifiability analysis that characterizes the conditions under which sparse perturbation effects can be reliably recovered, thereby clarifying how the framework can be concretely specified under such conditions. Empirically, PerturbedVAE achieves state-of-the-art performance on a widely used benchmark across multiple evaluation settings, yielding significant gains on out-of-distribution combinatorial predictions and uncovering interpretable perturbation-response programs.

Applications · Health / Medicine

Yu Zhao, Hao Guan, Yongcheng Jing, Ying Zhang, Dacheng Tao

Large Language Models (LLMs) have shown strong potential in complex medical reasoning yet face diminishing gains under inference scaling laws. While existing studies augment LLMs with various knowledge types, it remains unclear how effectively the additional costs translate into accuracy. In this paper, we explore how meta-cognition of LLMs, i.e., their self-awareness of their own knowledge states, can regulate the reasoning process. Specifically, we propose MedCoG, a Medical Meta-Cognition Agent with Knowledge Graph, where the meta-cognitive assessments of task complexity, familiarity, and knowledge density dynamically regulate utilization of procedural, episodic, and factual knowledge. The LLM-centric on-demand reasoning aims to mitigate scaling laws by (1) reducing costs via avoiding indiscriminate scaling, (2) improving accuracy via filtering out distractive knowledge. To validate this, we empirically characterize the scaling curve and introduce inference density to quantify inference efficiency, defined as the ratio of theoretically effective cost to actual cost. Experiments demonstrate the effectiveness and efficiency of MedCoG on five hard sets of medical benchmarks, yielding $5.5\times$ inference density. Furthermore, the Oracle study highlights the significant potential of meta-cognitive regulation.

Applications · Health / Medicine

Pengkai Wang, Pengwei Liu, Qi Zuo, Zhijie Sang, Congkai Xie, Hongxia Yang

Reinforcement learning (RL) has powered many of the recent breakthroughs in large language models (LLMs), especially for tasks where rewards can be computed automatically, such as code generation. However, these methods deteriorate in open-ended domains like medical consultation, where feedback is inherently ambiguous, highly context-dependent, and cannot be reduced to a reliable scalar signal. In such settings, RL must either rely on supervision-intensive reward models that often fail to generalize, or it falls into pathological behaviors such as reward hacking—an especially troubling risk for high-stakes medical dialogue. To address these limitations, we introduce ORBIT, an open-ended rubric-based incremental training framework for high-stakes medical dialogue. ORBIT integrates synthetic dialogue generation with dynamically constructed rubrics that serve as adaptive guides for incremental RL. Instead of relying on external medical knowledge bases or handcrafted rule sets, ORBIT uses rubric-driven feedback to steer the learning process. Its judge component can be instantiated with general-purpose instruction-following LLMs, removing the need for any task-specific fine-tuning. Applied to the Qwen3-4B-Instruct model, ORBIT raises the HealthBench-Hard score from 7.0 to 27.5 using only 2k training samples, achieving SOTA performance for models at this scale. With larger rubric datasets, ORBIT-trained models further compete with the strongest open-source baselines on HealthBench-Hard. Our analysis shows that rubric-guided RL consistently improves consultation quality across diverse medical scenarios. We also apply such rubric generation and training pipeline to InfoBench, where ORBIT enhances instruction-following performance, highlighting the generality of rubric-based feedback.

Applications · Health / Medicine

Shizhao Yang, Yixin Wang, Kevin Lin

Deciphering how cells commit to future fates is essential for developing precision therapeutics that can reprogram stem cells or modulate immune functions. However, isolating these fate-determining signals in single-cell lineage tracing (scLT) remains challenging because differentiation programs are often confounded by unrelated processes like the cell cycle. To address this, we introduce Lineage-aware Contrastive Learning (LCL), a framework that treats inheritable lineage barcodes as a "natural" data augmentation to isolate subtle, lineage-specific signals. LCL utilizes a semi-supervised architecture to align unlabeled cells, facilitating the transfer of lineage structures to clinical datasets where explicit barcoding is unavailable. We demonstrate LCL’s utility by predicting future cell-type compositions from early-time points, effectively modeling longitudinal fate commitment from cross-sectional data. Benchmarking on hematopoietic and fibroblast systems shows that LCL significantly outperforms standard models like scVI, establishing contrastive learning as a scalable paradigm for understanding and potentially manipulating cellular differentiation.

Applications · Health / Medicine

Nikita Makarov, Maria Bordukova, Lena von Voithenberg, Estrella Pivel-Villanueva, Sabrina Mielke, Jonathan Wickes, Hanchen Wang, Mingyu Ma, Keunwoo Choi, Kyunghyun Cho 等

Precision oncology requires forecasting clinical events and trajectories, yet modeling sparse, multi-modal clinical time series remains a critical challenge. We introduce TwinWeaver, an open-source framework that serializes longitudinal patient histories into text, enabling unified event prediction as well as forecasting with large language models, and use it to build Genie Digital Twin (GDT) on 93,054 patients across 20 cancer types. In benchmarks, GDT significantly reduces forecasting errors, achieving a median Mean Absolute Scaled Error (MASE) of 0.87 compared to 0.97 for the strongest time-series baseline ($p<0.001$). Furthermore, GDT improves risk stratification, achieving an average concordance index (C-index) of 0.703 across survival, progression, and therapy switching tasks, surpassing the best baseline of 0.662. GDT also generalizes to out-of-distribution clinical trials, matching trained baselines at zero-shot and surpassing them with fine-tuning, achieving a median MASE of 0.75–0.88 and outperforming the strongest baseline in event prediction with an average C-index of 0.672 versus 0.648. Finally, TwinWeaver enables an interpretable clinical reasoning extension, providing a scalable and transparent foundation for longitudinal clinical modeling.

Applications · Health / Medicine

Yuhan Wang, Yuanyuan Zou, Jie Cheng, Bin Dai, Jinhong Guo

Accurately capturing local variations in long series has always been one of the most challenging problems in time-series forecasting especially in medical signals, where local variations often indicate pathological events. Our study reveals a previously overlooked key bottleneck in this field: traditional global and local branches learn similar representations, leading to strong feature coupling and reduced sensitivity to local variations. To address this challenge, we propose the novel Dual-Stream Enhancement Mechanism, which structurally enlarges the difference between global and local patterns, enabling weak interactions between the two. Based on this idea, we introduce a new baseline model for blood glucose prediction: Dual-Stream Enhancement Network (DSENet), which fundamentally alleviates the problem of excessively strong coupling between global and local features. Experimental results show that our model achieves SOTA performance on multiple public datasets. Moreover, benefiting from extremely low computational cost, our model demonstrates strong application potential and can serve as a baseline model in multiple domains in the future.

Applications · Health / Medicine

Erjian Zhang, Yatong Hao, Liejun Wang, Zhiqing Guo

While multi-task learning based automatic radiology report generation (RRG) is widely adopted to ensure clinical consistency, most focus on architectural designs yet remain limited to coarse linear scalarization strategies. These strategies can not effectively balance the hard constraints of discriminative clinical supervision with the smoothness requirements of report generation. To address these problems, we analyze the failure mechanism of linear scalarization from the perspective of gradient dynamics for the first time, utilizing the stochastic differential equation (SDE) framework to formalize it as a "Double Dilemma'' of drift term deviation and diffusion term decay. Based on this, we propose a backbone-agnostic optimizer named Conflict-Averse Magnitude-Enhanced Gradient Descent (CAME-Grad). Through conflict-averse direction rectification and magnitude-enhanced energy injection, the algorithm not only ensures geometric validity, but also avoids the local optimal solution. Then, the adaptive gradient fusion technology is used to establish a dynamic balance between the theoretical optimal direction and the task-specific inductive bias. Experiments show that as a universal plug-and-play optimizer, CAME-Grad brings substantial and consistent improvements across eight diverse RRG methods, elevating overall clinical efficacy performance by an average of 2.3% on MIMIC-CXR and 1.9% on IU X-Ray. Our code is available at https://anonymous.4open.science/r/CAME-Grad-04A7.

Applications · Health / Medicine

Jiusong Ge, Yingkang Zhan, Wenjie Zhao, Di Zhang, Ke Wang, Jiashuai Liu, Chunze Yang, Chengzu Li, Jian Zhang, Yuxin Dong 等

Traditional whole slide image (WSI) analysis methods typically rely on the multiple instance learning (MIL) paradigm, which extracts patch-level features at high magnification and aggregates them for slide-level prediction. However, such exhaustive patch-level processing is computationally expensive, severely limiting the efficiency and scalability of WSI analysis. To address this challenge, we propose \textbf{PathCTM} (a \textbf{\ul{Path}}ology-oriented \textbf{\ul{C}}ontinuous \textbf{\ul{T}}hought \textbf{\ul{M}}odel) that enables token-efficient scale-space continuous reasoning for gigapixel WSIs. PathCTM formulates diagnostic inference as a dynamic sequential information pursuit. It progressively transitions from low-magnification global to high-magnification local inspection, and adaptively terminates inference when sufficient evidence is gathered to effectively bound decision uncertainty. Specifically, it uses conditional computation for dynamic scale switching with attention-guided region pruning, coupled with confidence-aware early stopping. Extensive experiments demonstrate that compared with state-of-the-art MIL methods, PathCTM reduces the number of required image patches by 95.95\%, shortens inference time by approximately 95.62\%, and improves AUC by an average of 2.3\%. Code is available at \url{https://anonymous.4open.science/r/PathCTM}.

Applications · Health / Medicine

Ziyu Zhao, Yiyang Liu, Yajiao Wang, Xiaotao Wang, Yang Li, Yuyang Peng, Jiaheng Zhou, Jinqiao Wang, Yingying Chen, Ge Yang 等

Despite progress of Multimodal Large Language Models (MLLMs) in biomedical visual question answering (VQA), existing benchmarks provide limited assessment of their scientific reasoning capabilities. Most datasets adopt single-image question construction and outcome-oriented evaluation, where correctness is judged by answer plausibility rather than alignment with experimental evidence. Such formulations fail to capture the evidence-constrained, multi-step nature of biomedical reasoning, and obscure whether models can derive conclusions through causal interpretation of experimental observations. To address these critical gaps in reasoning evaluation, we propose a principled benchmark construction framework that reconstructs scientific reasoning paths directly from biomedical literature. By jointly modeling clusters of experimentally related images together with their captions and context, the framework generates tightly coupled question–reasoning–answer triples that require multi-image integration and explicit evidence-driven inference. Based on this framework, we introduce \textbf{SORBE} (\textbf{S}cientific \textbf{O}bservation \& \textbf{R}easoning for \textbf{B}iomedical \textbf{E}valuation), a large-scale multi-image biomedical VQA benchmark designed to evaluate evidence alignment and multi-step experimental reasoning. Under a process-oriented evaluation metric, state-of-the-art biomedical-specialized MLLMs exhibit substantial performance degradation, revealing systematic limitations in evidence grounding and causal reasoning that are not reflected by existing benchmarks.

Applications · Health / Medicine

Tianwei Lin, Zhongwei Qiu, Jie Cao, Jiang Liu, Wenjie Yan, Bo Zhang, Yu Zhong, Wenqiao Zhang, Yingda Xia, Ling Zhang

The advancement of Medical Vision-Language Models (VLMs) for 3D Computed Tomography (CT) analysis is hindered by a misalignment between optimization objectives and clinical rigor. Current Reinforcement Learning (RL) paradigms rely on lexical proxy signals that induce ``\textbf{evaluation hallucinations}'', where models prioritize linguistic fluency over factual accuracy, leading to fatal clinical errors. To bridge this gap, we introduce the \textbf{Clinical Abnormality Benchmarking Substrate (CABS)}, a structured system that decomposes radiology reports into verifiable semantic units. Using CABS, we identify a ``\textbf{mechanistic divergence}'' in standard RL, where surface-similarity rewards drive policy gradients to bypass medical facts. We therefore propose \textbf{Trajectory-Integral Feedback GRPO (TIF-GRPO)}, a novel framework integrating control-theoretic principles into policy optimization. By formulating clinical reasoning as a pseudo-temporal trajectory for anomaly discovery, TIF-GRPO regulates anatomy-aware rewards via an integral feedback loop that penalizes persistent omissions as cumulative state errors and suppresses hallucinations as excessive control effort. Experiments on 3D CT benchmarks demonstrate that our approach significantly enhances abnormality detection and clinical faithfulness, establishing a new paradigm for fine-grained regulation in medical VLMs.

Applications · Health / Medicine

Ana Sanchez Fernandez, Thomas Pinetz, Werner Zellinger, Günter Klambauer

Biomedical imaging data presents enormous potential for deep learning models to predict invaluable properties, such as diseases and drug effects. However, unavoidable alterations of the technical conditions cause *batch effects*: variations between groups of samples that are not due to any biological signal of interest. Batch effects greatly hinder the generalization abilities of deep learning models, preventing their practical use in the real world. Unsupervised Domain Adaptation (UDA) methods have been proposed to mitigate batch effects, but they usually assume that the data is comprised of only one source domain and one target domain, whereas biological datasets are comprised of multiple domains, both at training and at inference time. While Batch Normalization–based test-time and meta-learning adaptation methods offer a promising mechanism for domain alignment, we show that existing approaches exhibit degraded performance under the usual inference scenarios of small target batch sizes and label shift. We address these limitations by leveraging negative control samples, which are consistently present in every experimental batch in biological datasets, as stable context for adaptation. We propose CS-ARM-BN, a meta-learning BN adaptation method that uses controls both during training and inference to stabilize domain statistics. We perform a suite of experiments of Mechanism-Of-Action (MoA) classification, a crucial task for drug discovery, on the large JUMP-CP imaging dataset. Our experiments show that CS-ARM-BN substantially improves robustness to batch size and class distribution shifts, enabling practical use of deep learning models for biomedical images.

Applications · Health / Medicine

Ivan Svatko, Maxime Sanchez, Ihab Bendidi, Gilles Cottrell, Auguste Genovesio

Representation learning has driven major advances in natural image analysis by enabling models to acquire high-level semantic features. In microscopy imaging, however, it remains unclear what current representation learning methods actually learn. In this work, we conduct a systematic study of representation learning for the two most widely used and broadly available microscopy data types, representing critical scales in biology: cell culture and tissue imaging. To this end, we introduce a set of simple yet revealing baselines on curated benchmarks, including untrained models and simple structural representations of cellular tissue. Our results show that, surprisingly, state-of-the-art methods perform comparably to these baselines. We further show that, in contrast to natural images, existing models fail to consistently acquire high-level, biologically meaningful features. Moreover, we demonstrate that commonly used benchmark metrics are insufficient to assess representation quality and often mask this limitation. In addition, we investigate how detailed comparisons with these benchmarks provide ways to interpret the strengths and weaknesses of models for further improvements. Together, our results suggest that progress in microscopy image representation learning requires not only stronger models, but also more diagnostic benchmarks that measure what is actually learned.

Applications · Health / Medicine

Marcin Możejko, Adam Bielecki, Jurand Prądzyński, Marcin Traskowski, Antoni Janowski, Hyun-Su Lee, Marcelo Torres, Michal Kmicikiewicz, Paulina Szymczak, Karol Jurasz 等

Antimicrobial peptide discovery is challenged by the astronomical size of peptide space and the relative scarcity of active peptides. While generative models provide latent maps of this space, they typically ignore decoder-induced geometry and rely on flat Euclidean metrics, making exploration distorted and inefficient. Existing manifold-based approaches assume fixed intrinsic dimensionality, which fails for real peptide data. We introduce **PepCompass**, a geometry-aware framework based on a **Union of $\kappa$-Stable Riemannian Manifolds** that captures local decoder geometry while maintaining computational stability. PepCompass performs global interpolation via **Potential-minimizing Geodesic Search (PoGS)** to bias discovery toward promising seeds and enables local exploration through **Second-Order Riemannian Brownian Efficient Sampling** and **Mutation Enumeration in Tangent Space**, which together form **Local Enumeration Bayesian Optimization (LE-BO)**. PepCompass achieves a 100% *in-vitro* validation rate: PoGS identifies four novel seeds and LE-BO optimizes them into 25 highly active, broad-spectrum peptides, demonstrating that geometry-informed exploration is a powerful paradigm for antimicrobial peptide design.