Bundibugyo Ebola without vaccines or therapeutics: why public health fundamentals matter more than border closures
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Academic Intelligence · Curated Daily
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Deep neural networks (DNNs) frequently fail to generalize to out-of-distribution (OOD) medical images because of variations in scanners and acquisition protocols. Retraining DNN models to address these distribution shifts is often impractical due to the high cost of acquiring and annotating new medical datasets. To address this, we introduce VarDeepPCA, a novel lightweight variational DNN framework designed to restore/refine degraded segmentation maps by leveraging intrinsic geometric priors. Unlike existing approaches that require target-domain data or extensive pre-training, our VarDeepPCA explicitly learns a distribution of valid anatomical geometries using only small in-distribution (ID) datasets. Theoretically, our novel variational learning framework leverages a reinterpretation of the softmax mapping to implicitly perform exact distribution modeling, thereby enabling computationally efficient, sampling-free learning and inference. This also enables VarDeepPCA to provide uncertainty estimates associated with its restored segmentation maps. We empirically validate our framework across 4 distinct clinical applications, using 14 publicly available datasets, involving segmentation of the myocardium, neuroretinal rim, prostate, and fetal head. Comparisons against 15 existing methods demonstrate that VarDeepPCA consistently restores segmentation maps produced by the existing methods on OOD data to (i) significantly improve anatomical plausibility of geometries and clinical utility of the segmentations, and (ii) significantly reduce errors, without needing any more training data than that used by existing methods.
Reward models for text-to-video (T2V) generation guide post-training but often fail at fine-grained semantic alignment. We trace this to two structural weaknesses in existing reasoning-based reward models: they do not systematically verify every condition described in the prompt, and the visual evidence supporting each judgment remains implicit in their free-form reasoning. We propose SG-PVR, a video reward model that addresses these limitations through plan-and-verify reasoning grounded in spatio-temporal scene graphs. The verification plan decomposes the prompt into atomic claims, ensuring every requirement is checked. The spatio-temporal scene graph, encoding entities, attributes, and temporally-grounded relations, is extracted from the video and maintained as a persistent structured visual reference throughout reasoning. Each claim is verified against both the video and the scene graph, anchoring judgments in explicit visual evidence. SG-PVR achieves strong performance on semantic alignment, including fine-grained temporal semantics. As a test-time reranker, it further enhances compositional alignment in T2V generation.
arXiv:2606.12404v1 Announce Type: cross Abstract: Neutrino evolution in dense astrophysical environments is typically described either within a quantum kinetic framework, which neglects the build-up of multi-body correlations, or through simplified many-body calculations that allow significant entanglement to develop. In this work, we compare these two approaches in a simple neutrino-gas configuration, with particular emphasis on the role of non-forward scattering processes. These effects are incorporated either through a collision term in the kinetic description, or by considering the full neutrino-neutrino many-body Hamiltonian. We highlight differences between the two descriptions in both their characteristic timescales and asymptotic behavior. Motivated by the natural suitability of quantum computing for many-body calculations, we further investigate the non-classicality of neutrino evolution, discussing Trotter error scaling, along with the associated costs of constructing quantum circuits in terms of entangling gates and non-Clifford gates. We find that the resources needed for neutrino many-body evolution are on the low end of typical high-energy physics problems and on the mid to high end with respect to quantum chemistry problems. For the full Hamiltonian, resource requirements increase relative to the truncated version. We emphasize the importance of efficient fermion-to-qubit encodings, which are essential for reducing the substantial computational resources required for such simulations.
Large language models (LLMs) are increasingly used for clinical text tasks such as summarization and revision. While most studies evaluate the fluency and coherence of LLM-generated text, whether LLMs correctly preserve diagnostic uncertainty remains underexplored. In clinical practice, phrases such as ``possible pneumonia'' communicate the strength of available evidence and directly guide decisions about follow-up testing and treatment. Altering these uncertainty expressions can change the clinical meaning entirely. In this paper, we systematically evaluated this problem in two steps. First, we constructed a benchmark of 1,200 clinical documents with 9,184 uncertainty annotations across five levels. Second, we evaluated three LLMs on this benchmark. Our results show that (1) LLMs preserve the original uncertainty cues poorly, often less than half the time; (2) LLMs struggle with nuanced distinctions between adjacent levels. This work reveals a failure mode not captured by standard evaluation metrics and provides implications for the safe deployment of LLMs in clinical workflows.
arXiv:2606.17338v1 Announce Type: new Abstract: Adiabatic quantum flux parametron (AQFP) gate is a promising approach to scale up the cryogenic microwave electronics for superconducting qubit multiplexed control. However, the performance of these circuits depends on the quality of the Josephson junctions which are ideally superconductor-insulator-superconductor (SIS) type following the ideal sinusoidal relation between current and quantum phase. We demonstrate how the non-sinusoidal current-phase relation in Superconductor-Normal metal-Superconductor (SNS) and weak link (WL) junctions affects the speed, delay, and margin of the AQFP gates. The JJ models are defined in the Keysight ADS simulator using symbolically defined device (SDD) method.
arXiv:2606.19060v1 Announce Type: cross Abstract: We study the vorticity formulation of the 3D Navier-Stokes equation driven by transport noise in a periodic channel with Navier-slip boundary conditions. We consider both non-degenerate transport noise and degenerate tangential transport noise. For any prescribed $T>0$ and $\epsilon>0$, we prove that, by choosing the noise intensity sufficiently large and concentrating the noise on sufficiently high modes, the solution exists up to $T$ with probability at least $1-\epsilon$. A main contribution of this work is to identify and analyze the interaction between enhanced dissipation induced by transport noise and physical boundary effects. The no-flux condition breaks the isotropy of the noise and changes the scaling limit of the Itô-Stratonovich corrector. In the non-degenerate case, a boundary feedback term appears in the limiting effective operator; in the degenerate case, the limiting operator is a nonlocal anisotropic tangential dissipation. The proof is based on a combination of a boundary correction operator, a Meyers-type estimate, a scaling-limit analysis of the Itô-Stratonovich corrector, and resolvent estimates for the deterministic limiting equations.
arXiv:2602.00482v2 Announce Type: replace Abstract: Reinforcement learning (RL)-based post-training for large language models (LLMs) is computationally expensive, as it generates many rollout sequences that frequently share long token prefixes. Existing RL frameworks usually process these sequences independently during policy training, i.e., repeatedly recomputing identical prefixes in both the forward and backward passes of policy gradient computation, leading to substantial inefficiencies in computation resources and memory usage. Although prefix sharing naturally induces a tree structure over rollouts, packed tree-mask approaches scale poorly in RL settings. In this paper, we introduce AReaL-DTA, which efficiently exploits prefix sharing in RL training. AReaL-DTA employs a depth-first search (DFS)-based execution strategy that dynamically traverses the rollout prefix tree during both forward and backward computation, materializing only a single root-to-leaf path at a time. To further improve scalability, AReaL-DTA incorporates a load-balanced distributed batching mechanism that dynamically constructs and processes prefix trees across multiple GPUs. On $\tau^2$-bench, AReaL-DTA improves training throughput by up to $8.31\times$ over dense training and up to $1.70\times$ over sparse training. Our code is available at https://github.com/areal-project/AReaL/tree/feat/dta.
arXiv:2606.15227v1 Announce Type: cross Abstract: We study pseudo entropy $\mathcal{S}$, a recent generalization of entanglement entropy, for scalar cosmological perturbations in de Sitter space with sound speed $0.024 \leq c_s \leq 1$, and in expanding and contracting FLRW backgrounds with varying equation-of-state parameter $w$. In de Sitter space, $\mathrm{Re}(\mathcal{S})$ grows after horizon exit while $c_s$ controls its onset and saturates at late times. A similar saturation occurs in expanding-accelerating and contracting-decelerating backgrounds. In contrast, expanding-decelerating and contracting-accelerating backgrounds show large early-time $\mathrm{Re}(\mathcal{S})$ followed by oscillations after horizon re-entry. This happens because while the squeezing freezes, the squeezing angle doesn't. Unlike entanglement entropy, pseudo entropy possesses an imaginary part, $\mathrm{Im}(\mathcal{S})$, as well, which can encode the relative phase. $\mathrm{Im}(\mathcal{S})$ decays to zero in de Sitter and expanding-accelerating cases, but forms dense sub-Hubble oscillation bands in expanding-decelerating and contracting-accelerating backgrounds. Compared with entanglement entropy, Krylov complexity, and Nielsen circuit complexity, pseudo entropy captures otherwise hidden phase information; in the unsaturated regime, its slope is $\sqrt{2}$ times that of Nielsen complexity. Unlike circuit complexity, whose saturation bound is $w$-independent, pseudo entropy is sensitive to $w$ during the transition regime, making it a finer information theoretic diagnostic of cosmological dynamics.
Global rice production faces mounting challenges from abnormal temperature fluctuations and nitrogen-fertilizer-driven environmental pollution1–7. Developing varieties that balance chilling resilience and nitrogen-use efficiency (NUE) offers a promising solution, but the molecular networks coordinating these traits remain poorly understood. Here we identify CHILLING PHOENIX (CHPO), a major gene underlying the quantitative trait locus shared by both chilling tolerance and resilience. It encodes a MYB transcription factor that acts as a key regulator coordinating post-chilling recovery with nitrogen use in rice. Natural variation in a GCG-repeat-encoded polyalanine tract alters CHPO DNA-binding preference and redirects regulatory outputs between the japonica-type (CHPOjap) and indica-type (CHPOind), causing opposing effects on chilling tolerance and resilience. This allelic variation is shaped by domestication selection, with the CHPOjap allele probably derived from Chinese wild rice. CHPOjap directly targets OsTCP19 and OsNRT2.4 to fine-tune NUE, thereby enhancing chilling tolerance and resilience. These findings provide a mechanistic framework for a chilling-induced high-nitrogen-utilization module that alleviates the damage caused by chilling stress, and a potential molecular design strategy for breeding rice varieties with both chilling resilience and high NUE at the recovery stage. A rice gene, CHPO, links chilling resilience with nitrogen-use efficiency, revealing a domestication-shaped regulatory mechanism that could guide breeding of climate-resilient, sustainable rice varieties.
arXiv:2606.04573v2 Announce Type: replace-cross Abstract: Recently, Chen [Chen2026] proved that Talagrand's Boolean convolution conjecture holds up to the dimension-free factor \((\log\log\eta)^{3/2}\), namely for every fixed \(\tau>0\), \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{(\log\log\eta)^{3/2}}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \] We revisit the terminal testing-discrepancy step in Chen's perturbed reverse-heat coupling. Chen estimates this discrepancy globally in terms of the remaining gap to the terminal level. We keep the same coupling and the same reverse-heat formulations, but localize the terminal discrepancy on each remaining-gap layer before summing the layers. This changes the fixed-time anti-concentration cost from order \((\log L)^{3/2}/\sqrt L\) to order \((\log L)/\sqrt L\), where \(L=\log\eta\). Consequently, we obtain a \((\log\log\eta)^{1/2}\) improvement as \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{\log\log\eta}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \]
Multi-center studies are crucial for advancing medical and radiological research. Data exploration, collaboration discovery, and study progress monitoring are essential for maximizing their potential. However, in practice these processes often rely on manual communication and shared tables, which quickly become outdated and hinder efficient coordination in large distributed studies. This highlights the need for dedicated monitoring solutions that provide transparent and up-to-date insights into study progress. We propose a lightweight, open-source monitoring architecture for multi-center studies based on the widely used Grafana-Prometheus stack. The framework collects aggregated monitoring metrics from distributed study sites and visualizes them through configurable dashboards. As a real-world deployment example, the framework is integrated into the medical imaging platform Kaapana and evaluated within a large multi-center research network. By deploying our solution within the Germany-wide RACOON consortium, we demonstrate its ability to enable privacy-preserving data exploration and study progress monitoring across all 38 German university clinics. The monitoring framework supports transparent coordination of distributed research activities and can facilitate more efficient management of large-scale multi-center studies. The source code and Kaapana integration are publicly available at https://github.com/MIC-DKFZ/study-monitoring-kaapana.
arXiv:2604.16897v2 Announce Type: replace-cross Abstract: Tetraphenylpyrazine (TPP) and 2,3,4,5-tetraphenyl-1H-pyrrole (TePP) are closely related heterocycles bearing four phenyl substituents, whose structural similarity makes them a useful pair for comparing how intramolecular flexibility influences excited-state relaxation and emission in the gas phase and in the solid state. TPP is a prototypical solid-state luminescence enhancement (SLE) emitter, exhibiting a markedly increased quantum yield upon molecular aggregation. In contrast, TePP displays similar quantum yields in solution and solid state, characteristic of dual-state emission (DSE). This behaviour indicates that intramolecular rotations are already significantly hindered in the isolated-molecule regime, consistent with our previous observations for TPP and other solid-state emitters (Hernández-Rodríguez et al., ChemPhysChem, 2024, 25, e202400563). To unravel the excited-state dynamics underlying this contrasting behaviour, we performed mixed quantum-classical trajectory simulations on a single molecule of TPP and TePP employing the surface-hopping method. Twelve singlet states were included at the TD-B3LYP-D3/def2-SVP level, which were previously benchmarked against coupled cluster methods. Simulated observables such as gas phase ultrafast electron diffraction (GUED) and time-resolved fluorescence (TR-FL) signals allow us to dissect the distinct deactivation pathways operating in both systems in the gas phase, while also providing mechanistic insight into how these pathways are expected to evolve in solution and solid-state environments.
Generative world models for autonomous driving face two unresolved tensions: heterogeneous control injection, where free-form language, HD-maps, trajectories, and camera poses reside in incompatible representational spaces, and post-hoc cross-view fusion, where per-camera latents fail to encode global 3-D geometry. We trace both to a single root cause: the absence of a shared symbolic interlingua aligning language, geometry, and pixels at the latent-token level. We present DRIVE-CHOREO, an LLM-choreographed multi-agent world model that recasts controllable multi-view video generation as latent choreography. Three Qwen2.5-VL agents - a Director parsing user intent into a structured WorldScript, a Cartographer grounding it into spatially-anchored layout tokens, and an Auditor feeding cross-view critiques back as auxiliary supervision - jointly author a single position-aware token sequence. This sequence is co-compressed with the multi-view video via a view-time permutation that enforces inter-camera geometry within the convolutional receptive field of a 3-D VAE. On nuScenes, DRIVE-CHOREO sets new state-of-the-art multi-view consistency and BEV mAP (21.6) with competitive FVD (45.7); a detector trained purely on our synthetic data gains +2.4 NDS on the real validation split, validating downstream utility.
In service computing, video classification has become fundamental to many intelligent applications. While Deep Neural Networks (DNNs) have demonstrated excellent performance in recognizing video content, recent studies have shown that DNNs are highly vulnerable to adversarial examples. Thus, understanding adversarial attacks can better respond to emergency situations. In order to improve attack performance, many style-transfer-based attacks and patch-based attacks have been proposed. However, the global perturbation of the former will bring unnatural global colors, while the latter is difficult to achieve success in targeted attacks due to the limited perturbation space. Moreover, compared to a plethora of methods targeting image classifiers, video adversarial attacks remain relatively underexplored. Therefore, to generate adversarial examples with a low budget and to provide them with a higher verisimilitude, we propose a novel black-box video attack framework, called Stylized Logo Attack (SLA). SLA is conducted through three stages. The first stage involves building a style reference set for logos, which can not only make the generated examples more natural, but also carry more target class features in targeted attacks. Then, Reinforcement Learning is employed to determine the style reference and position parameters of the logo within the video, which ensures that the stylized logo is placed in the video with optimal attributes. Finally, perturbations are optimized in a step-by-step manner so as to improve the fooling rate. Experimental results indicate that SLA can achieve better performance than state-of-the-art methods and still maintain good deception effects when facing various defense methods. We believe SLA can raise awareness among the security community about the reliability and security of video classification systems and serve as a memorandum of possible attack methods.
arXiv:2606.18997v1 Announce Type: new Abstract: Uncovering the true informational architecture of real-world complex systems requires disentangling how their components uniquely store, redundantly share, and synergistically integrate information over time. Integrated Information Decomposition ($\Phi$ID) is a framework for decomposing the information dynamics of multivariate systems into sixteen non-overlapping atoms that characterize redundant, unique, and synergistic modes of information storage, transfer, and integration. Existing methods to compute $\Phi$ID are restricted to Gaussian or discrete systems, preventing its application to continuous non-Gaussian dynamical systems. We address this limitation by proposing DIPHINE (Diffusion-based $\Phi$-ID Neural Estimator), the first neural estimator that leverages score-based diffusion models to jointly estimate all the mutual information terms required by $\Phi$ID from a single amortized network, recovering the sixteen atoms through Möbius inversion. We provide a theoretical analysis of error propagation through the inversion, showing that the Jacobian of the mapping from mutual informations to atoms is integer-valued and that the synergy-to-synergy atom is provably the hardest to estimate. We demonstrate accurate recovery of ground-truth atoms on synthetic benchmarks, superior performance compared to established mutual information estimators, and the ability to extract physiologically interpretable information-dynamic structure on an application involving real data without any distributional assumptions.
CAR T cell therapy can induce deep responses but also severe toxicities in patients with smoldering myeloma, an asymptomatic cancer precursor; given the potential risks and benefits, its success depends on careful patient selection.
arXiv:2606.13426v1 Announce Type: new Abstract: Speculative decoding speeds up LLM inference by using a draft model to generate tokens, with an acceptance-rejection scheme that ensures that the output matches the target distribution. Adapting this to continuous diffusions is difficult because speculative sampling requires drawing from a residual distribution. While straightforward in discrete spaces, efficiently sampling this residual in continuous space is non-trivial. Consequently, existing diffusion adaptations either use computationally inefficient sampling techniques or rely on an alternative scheme. In this work, we introduce a novel scheme that efficiently implements the original speculative sampling mechanism for diffusion models. Our approach offers a critical advantage over current methods: it enables us to adapt block verification from LLMs to diffusions – which provably improves the acceptance rate of drafts. Furthermore, we formalize and analyze the Free Drafter, a heuristic self-speculative drafter for diffusions that requires no training. By enabling block verification, our Free Drafter yields up to a 6.3% speedup over existing speculative methods with no additional training and negligible overhead beyond the existing parallel verification pass.
Making large language models (LLMs) deeply forget specific knowledge and values without sacrificing general capabilities remains a central challenge in unlearning. However, current methods are easily reversed by fine-tuning or few-shot prompting, suggesting their forgetting is only shallow. We identify the root cause. Existing methods target representations shared with both the retain set and the subspace recovered by a fine-tuning attacker, making unlearning both disruptive to general capabilities and easy to reverse. We propose RepSelect (Representation Selectivity), isolates forget-set-specific representations by collapsing top principal components of weight gradients before each update, leaving general capabilities intact while limiting what fine-tuning can recover. We evaluate across two forget categories, biohazardous knowledge and abusive tendencies, and four model families spanning dense and Mixture-of-Experts architectures (Llama 3, Qwen 3.5, Gemma 4 E4B, DeepSeek V2 Lite). Compared to five popular baselines (GradDiff, NPO, SimNPO, RMU, UNDIAL), RepSelect achieves a 4-50x larger reduction in post-relearning answer accuracy than the strongest baseline, and is near-perfectly robust to few-shot prompting attacks. Targeting selective representations is thus an important step towards deep and robust LLM forgetting.
arXiv:2606.19474v1 Announce Type: cross Abstract: The transition to Post Quantum Cryptography (PQC) introduces considerable implementation complexity, requiring strict adherence to constant-time execution, side channel resistance, and precise parametrisation. Simultaneously, large language models (LLMs) are heavily embedded in software development workflows, including cryptographic engineering. While LLMs improve productivity, evidence shows that they frequently generate insecure or suboptimal code, particularly in security critical domains. This paper introduces Secure Coding Drift in PQC, a novel socio technical vulnerability model capturing the gradual degradation of secure coding practices due to sustained reliance on LLM-generated code. Unlike prior work that focuses on static vulnerabilities, we conceptualise security risk as a longitudinal behavioural phenomenon rising from human AI interaction. To mitigate this, we propose a gamified, LLM augmented secure coding framework that embeds adversarial evaluation, behavioural feedback, and security scoring into development workflows. Our approach reframes LLMs from passive assistants into active security co-pilots, contributing toward safer PQC implementation in AI mediated environments.
Agentic reinforcement learning (RL) trains large language models to use tools, but its impact on alignment is poorly understood. We study how agentic RL for search affects the alignment of instruction-tuned (IT) models. We find that RL-trained models inherit refusal reasoning by deflecting harmful requests into benign search queries, but this breaks down under a simple diagnostic trigger that elicits a search call before refusal can occur. Under this condition, RL models produce multi-step unsafe search actions and reasoning, reducing search query safety by up to 68.6% in Qwen and Llama models relative to their IT counterparts. The effect generalises across model families, scales, and RL algorithms. To understand why, we identify linear directions in the residual stream that control search query safety, and show that RL training progressively shifts search behaviour toward the harmful end of this direction. We thus propose representation-guided RL training, which adds a reward penalty based on projection toward the harmful search direction. Training on benign data alone, it restores IT-level alignment without reducing task accuracy and requires no additional training data. Together, our work provides the first framework for diagnosing, mechanistically analysing, and mitigating alignment degradation in agentic RL for search.
arXiv:2602.23242v3 Announce Type: replace Abstract: In general reinforcement learning, all established optimal agents, including AIXI, are model-based, explicitly maintaining and using environment models. This paper introduces Universal AI with Q-Induction (AIQI), the first model-free agent proven to be asymptotically $\varepsilon$-optimal in general RL. AIQI performs universal induction over distributional action-value functions, instead of policies or environments like previous works. Under a grain of truth condition, we prove that AIQI is strong asymptotically $\varepsilon$-optimal and asymptotically $\varepsilon$-Bayes-optimal. We also apply our novel proof techniques to show asymptotic $\varepsilon$-optimality of Self-AIXI without any ad-hoc assumptions. Our results significantly expand the diversity of known universal agents.
Structural ambiguity arises when a single sentence admits multiple valid interpretations due to its syntactic structure, posing a fundamental challenge for language understanding. Visual scenes serve as useful cues for resolving such ambiguity, and Vision and Language Models (VLMs) need to be capable of deriving possible semantic interpretations from visual scenes. We introduce Language and Vision Structural Ambiguity (LaViSA), a benchmark designed to evaluate the ability of VLMs to resolve structural ambiguity leveraging visual scenes. LaViSA consists of ambiguous sentences, their disambiguated sentences, and corresponding images of these disambiguated sentences across seven ambiguity categories. Using LaViSA, we conduct a comprehensive evaluation of diverse VLMs, including both proprietary and open-source models with varying parameter scales and reasoning capabilities. Experimental results show that although recent VLMs can leverage visual scenes to resolve structural ambiguity to a some extent, they still struggle with certain ambiguity types and visually subtle semantic distinctions, indicating remaining limitations in resolving structural ambiguity using visual scenes.
Exposure to adverse childhood experiences is a pervasive risk factor for psychosis, exhibiting a linear relationship across the psychosis spectrum from subclinical schizotypal traits to schizophrenia spectrum disorders. While this association is often conceptualised within the vulnerability-stress framework, the systemic mechanisms through which childhood trauma reconfigures the brain-personality interactome remain poorly understood. We examined clinical, neuropsychological, and neuroimaging data from a sample of low- and high-schizotypy individuals, and patients with a diagnosis of schizophrenia spectrum disorder (N=120). Our aim was to map how trauma reconfigures interactions between neurobiology and schizotypal phenomenology. We adopted a mixed graphical model approach to jointly estimate conditional dependencies between childhood trauma, regional brain morphometry, and schizotypal traits across the psychosis spectrum. Our results show that childhood trauma reconfigures the brain-personality network, shifting it from a state driven by cognitive processes to one anchored in emotional (limbic) reactivity. This transition is marked by the increased influence of impulsive traits and a significant strengthening of connections within the salience network. These changes converge with a reduced thickness of the frontal executive regions, the brain's control centres, identified in our models. Collectively, our results suggest a structural phenomenological decoupling, where trauma conditioned affective circuits may bypass weakened top-down regulatory controls. These findings highlight the necessity of using integrative frameworks to capture how trauma fundamentally reshapes the relationship between the brain and schizotypal personality.
arXiv:2504.20908v3 Announce Type: replace Abstract: Current subgroup identification methods typically follow a two-step approach: first estimate conditional average treatment effects and then apply thresholding or rule-based procedures to define subgroups. While intuitive, this decoupled approach fails to incorporate key constraints essential for real-world clinical decision-making, such as subgroup size and propensity overlap. These constraints operate on fundamentally different axes than CATE estimation and are not naturally accommodated within existing frameworks, thereby limiting the practical applicability of these methods. We propose a unified optimization framework that directly solves the primal constrained optimization problem to identify optimal subgroups. Our key innovation is a reformulation of the constrained primal problem as an unconstrained differentiable min-max objective, solved via a gradient descent-ascent algorithm. We theoretically establish that our solution converges to a feasible and locally optimal solution. Unlike threshold-based CATE methods that apply constraints as post-hoc filters, our approach enforces them directly during optimization. The framework is model-agnostic, compatible with a wide range of CATE estimators, and extensible to additional constraints like cost limits or fairness criteria. Extensive experiments on synthetic and real-world datasets demonstrate its effectiveness in identifying high-benefit subgroups while maintaining better satisfaction of constraints.