DNA from hunter-gatherer teeth reveals secrets of ancient plague
Analysis shows evidence of deadly outbreaks 5,500 years ago — plus, a prototype dark-matter detector. Hear the biggest stories from the world of science | 17 June 2026
Academic Intelligence · Curated Daily
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Analysis shows evidence of deadly outbreaks 5,500 years ago — plus, a prototype dark-matter detector. Hear the biggest stories from the world of science | 17 June 2026
arXiv:2508.03506v5 Announce Type: replace Abstract: We present a systematic Magnus expansion treatment of the quantum Rabi model beyond the Rotating Wave Approximation. We show that at the second order of Magnus series, the second-order evolution operator contains a term that induces conditional squeezing of the field mode depending on the state of the atom, in addition to the energy shifts. We analyze the scaling behavior of the conditional squeezing coefficient for $^{87}\mathrm{Rb}$ $5^2S_{1/2}\rightarrow5^2P_{1/2}$ transition line and show that the slow envelope of the squeezing coefficient is maximized at half-detuning cycles, and that it scales with $\frac{4g^2}{\omega_0|\Delta|}$. We also show that the quadrature squeezing angle suggests a possible route towards quantum non-demolition readouts, while further investigation is required for a full first-order suppression. We then connect our work to the well-studied AC-Stark shift and Bloch-Siegert shift using the effective Hamiltonian theory. Finally, we show how the energy shifts and the conditional squeezing arise, as a whole $\mathrm{SU}(1,1)$ algebra, and how they can be disentangled as individual unitary evolutions.
Introduction The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide, in certain areas exceeding hospital capacities and human resources. This has underscored the importance of having better tools to predict the outcome of potentially severe respiratory infections such as SARS-CoV-2. Predicting COVID-19 severity may allow physicians to better manage ICU beds and increase the chances of patient survival through appropriate management. During the toughest months of the pandemic, most physicians tried to identify patients that might develop severe forms based primarily on clinical features on admission (e.g., BMI, age). In this context, significant research has focused on identifying comorbidities, clinical manifestations, and routine blood biomarkers to predict disease severity. However, despite the demonstrated value of untargeted metabolomics in assessing severity, limited data exist on its use for identifying novel metabolite biomarkers that could improve both the sensitivity and specificity of outcome prediction. Our goal is to identify metabolite biomarkers that could enhance the predictive accuracy of standard medical biology data and clinical parameters. Methods and analysis This is a retrospective, observational, monocentric cohort study conducted at the Centre Hospitalier Universitaire Grenoble Alpes (CHUGA). The maximum number of eligible patients admitted for PCR-confirmed COVID-19 between March and December 2020 will be included. Severity outcome is defined using the WHO 10-category ordinal scale (mild: categories 4-5; severe: >5). Blood samples were collected within 48 hours of admission and analyzed for 62 routine blood tests and untargeted multiplatform LC-MS/MS metabolomics across four national platforms. Statistical analysis will include logistic regression with variable selection for the primary aim, and multi-block chemometric integration of clinical, biological, and metabolomics data as a secondary aim. Ethics and dissemination A study steering committee has been formed to ensure the accuracy of the collected data by thoroughly reviewing it prior to the data lock. All aspects of the study comply with ethical standards, including approval by the CHUGA institutional review board and adherence to CNIL Reference Methodology MR004 for the protection of participants' rights, privacy, and confidentiality. This study is registered on the French Health Data Hub (number F20210218154851). Results will be disseminated through peer-reviewed publications, presentations at national and international scientific and clinical conferences, and reports shared with key healthcare system stakeholders.
arXiv:2606.17978v1 Announce Type: new Abstract: Trajectory similarity is a fundamental task in analyzing mobility patterns, essential for applications such as route pattern extraction, mobility prediction, and anomaly detection. Traditional distance-based measures for computing similarity incur high computational cost, driving the adoption of lightweight learning-based approaches. Supervised methods rely on extensive labels derived from traditional distance measures and often reproduce these metrics, which limits generalization. While self-supervised learning addresses this issue through contrastive learning, it lacks a unified framework, making it difficult to compare deep learning (DL) models for consistent trajectory representation. Accordingly, this paper presents MoCo-AIS, a unified framework for learning vessel trajectory embeddings based on the Momentum Contrast (MoCo) paradigm, which formulates similarity learning through positive and negative trajectory pairs. Within this framework, we evaluate a diverse set of leading DL models on large-scale, real-world vessel-tracking AIS datasets that capture diverse navigation behaviors and operating conditions. Results demonstrate that our framework significantly improves similarity learning over existing baselines, while providing a benchmarking platform for evaluating trajectory representation models.
Retrieval-Augmented Generation (RAG) has shown substantial promise in improving factual accuracy by grounding model responses with external knowledge relevant to queries. However, most existing approaches are limited to a text-only corpus, and while recent efforts have extended RAG to other modalities such as images and videos, they typically operate over a single modality-specific corpus. In contrast, real-world queries vary widely in the type of knowledge they require, which a single type of knowledge source cannot address. To address this, we introduce UniversalRAG, an any-to-any RAG framework designed to retrieve and integrate knowledge from heterogeneous sources with diverse modalities and granularities. Specifically, motivated by the observation that forcing all modalities into a unified representation space derived from a single aggregated corpus causes a modality gap, where the retrieval tends to favor items from the same modality as the query, we propose modality-aware routing, which dynamically identifies the most appropriate modality-specific corpus and performs targeted retrieval within it, and further justify its effectiveness with a theoretical analysis. Moreover, beyond modality, we organize each modality into multiple granularity levels, enabling fine-tuned retrieval tailored to the complexity and scope of the query. We validate UniversalRAG on 10 benchmarks of multiple modalities, showing its superiority over various modality-specific and unified baselines.
arXiv:2512.18123v2 Announce Type: replace Abstract: We investigate the interplay between quantum thermodynamics, quantum correlations, and quantum coherence within the framework of the Unruh-DeWitt (UdW) detector model. By analyzing both the steady and dynamical states of various quantum resources (including steerability, entanglement, quantum discord, and coherence), we study how these resources evolve under Markovian and non-Markovian environments. Furthermore, we investigate the impact of both the Unruh temperature and the energy levels on three key quantum phenomena: thermodynamic evolution, quantum correlations, and quantum coherence, considering different initial state preparations. The hierarchical structure relating quantum correlations and quantum coherence is determined. We further examine the thermodynamic performance of a quantum heat engine, highlighting the influence of memory effects and classical correlations on heat exchange, work extraction, and efficiency. Our results reveal that non-Markovian dynamics can enhance the preservation of quantum correlations and improve the engine's efficiency compared to purely Markovian regime. These findings provide insights into the role of quantum correlations and quantum coherence in quantum thermodynamic processes and open avenues for optimizing quantum devices operating in relativistic or open-system settings.
Nature asked a football-journal chief about emerging trends in the sport, from AI tools to PhD students embedded with teams. Nature asked a football-journal chief about emerging trends in the sport, from AI tools to PhD students embedded with teams.
arXiv:2606.13194v1 Announce Type: new Abstract: Deep learning has become the dominant paradigm in Wearable Human Activity Recognition (WHAR), yet progress is obscured by a comparability crisis. Results are often reported using inconsistent datasets, custom data processing, and varying evaluation protocols, making state-of-the-art claims fragile. We address this with a large-scale, open-source benchmark that integrates 30 diverse datasets under standardized processing, unified model interfaces, and a shared cross-subject evaluation protocol. Evaluating 17 representative architectures across 4760 training runs, we jointly measure predictive performance alongside on-device latency, peak memory, and model size on an Android reference device. Our results reveal that the WHAR state of the art is distributed rather than dominated by a single architecture. While CNN-HAR achieves the highest mean macro-F1, top-performing models cluster tightly, indicating contemporary architectures have converged near a predictive performance ceiling. When accounting for deployment efficiency, compact neural models, such as TinierHAR, and classical Random Forests define the practically relevant Pareto frontier, whereas larger recurrent and hybrid models incur high hardware costs without corresponding performance gains. Consequently, while predictive performance has plateaued, substantial potential for future progress remains in optimizing deployment efficiency and improving adaptation to domain shifts. We release our full framework to support transparent reuse and extension.
Sign language translation (SLT) converts sign language video into spoken language text and holds significant promise for improving accessibility and enabling communication between signing and non-signing communities. While large weakly-aligned datasets have enabled pre-training at scale and gloss-free methods have reduced reliance on expert annotation, high-quality parallel sign video-text pairs for fine-tuning remain scarce, limiting generalisation on long-tail vocabulary and unseen constructions. We propose a corpus augmentation approach that requires no additional human annotation, external sign-language video corpora, or generative video models, relying only on the existing gloss-annotated training corpus and an LLM for sentence generation: per-gloss clips are extracted from training videos via CTC forced-alignment, novel gloss-sentence pairs are generated by a corpus-anchored LLM, and synthetic sequences are assembled through random sentence sampling and clip assignment. The resulting synthetic RGB video-text pairs are architecture-agnostic at the downstream training stage and can be consumed directly by RGB-based SLT models, or converted into pose or feature representations by pipelines that derive such inputs from video. Sincan et al. re-evaluated five recent gloss-free methods under strictly identical conditions; the largest verified gain over the GFSLT-VLP baseline was only 0.98 BLEU-4. Our augmentation, applied within the same framework, achieves +2.92 BLEU-4 without any change to architecture or training protocol. We further identify that synthetic data harms vision-language pretraining despite improving its objectives, and that optimising clip transitions for visual smoothness is counter-productive under L2-based criteria; we propose that abrupt boundaries may act as a form of implicit regularisation. Code is available at https://github.com/robizso/slt-datagen.
Objective: Tracing the propagation of high-frequency oscillations (HFOs) aids in localizing epileptogenic regions and improving surgical outcomes. We examined how hippocampal epileptogenicity influences the propagation properties of the HFOs it generates. Methods: We analyzed non-REM sleep stereo-EEG from 49 patients (68 hemispheres) with verified hippocampal contacts. Hippocampi were stratified by excitability: 28 seizure onset zone (SOZ), 22 more-irritative non-SOZ (>6 interictal epileptiform discharges [IED]/min), and 18 less-irritative non-SOZ (
arXiv:2606.14398v1 Announce Type: new Abstract: Mixture-of-experts (MoE) layers enable the scaling of transformer models while keeping the inference compute fixed. While task-expert specialization has been observed in empirical studies of frontier MoE transformer models, existing theoretical work analyzes this using continuous mixture models that cannot be used to model natural language effectively. An important open question is to theoretically explain task-expert specialization in transformer MoE models using discrete models of language. To address this, we represent structured knowledge via syntactic templates and finite key-value dictionaries, and prove formally that a single-layer MoE transformer can encode knowledge by using experts that specialize in the corresponding tasks. Our construction shows how queries are routed to unique, task-specific experts whose size depends solely on the intrinsic complexity of the given task (i.e. the combined size of its syntactic templates and factual dictionary). Our construction provides a theoretical support for empirical results on localized knowledge circuits in MoE models. We support our theoretical findings with experiments evaluating model performance under varying MoE loss functions.
Existing computer-use agents remain fundamentally limited in professional software manipulation: GUI-based agents suffer from fragile visual grounding and long-horizon error accumulation, while API-basedapproaches struggle with heterogeneous protocols and inaccessible commercial interfaces. In this work,we identify the Component Object Model (COM) as a unified executable abstraction, proposing COM-as-Action: a new paradigm that reframes professional software interaction as deterministic program synthesisrather than sequential visual control. To validate this paradigm in the most demanding environments, weintroduce ComCADBench, the first benchmark for agents operating real industrial CAD software. Ourexperiments reveal a substantial paradigm gap: frontier proprietary models achieve near-zero successunder GUI-based interaction, whereas COM-based execution yields substantial immediate gains. Tobridge the remaining gap between syntactic correctness and geometric accuracy, we develop ComActor, aself-correcting agent trained through a progressive three-stage framework, alongside ComForge, a scalableplatform for large-scale training in Windows containers. Extensive experiments show that ComActorachieves state-of-the-art performance on ComCADBench, with strong resilience in long-horizon taskswhere baselines collapse, and generalizes to external CAD benchmark.
Reward models are central to text-to-image post-training, but visual preference is subjective and better represented as a distribution over rubric scores than as a deterministic scalar. Existing scalar, score-token, and pairwise reward models over-compress uncertainty and fine-grained score differences, while reasoning-based generative rewards provide stronger judgments but are costly to deploy and difficult to use as direct optimization signals. We propose Z-Reward, a teacher-student reward modeling framework that decouples reasoning-heavy judgment from efficient reward deployment. The teacher is a large VLM that uses reasoning to infer rubric-aligned score distributions, and is trained with Group-wise Direct Score Optimization (GDSO), which combines policy-gradient rewards from distribution expectations with direct pointwise and pairwise supervision on score distributions and score gaps. The student is trained with Reasoning-Internalized Score Distillation (RISD), which transfers the teacher's reasoning-conditioned score distribution into a compact VLM without requiring explicit reasoning chains at inference time. On our internally annotated evaluation set, the 27B GDSO teacher reaches 89.6% human preference accuracy, outperforming SFT, RewardDance, and GRPO, while the 9B RISD student reaches 88.6%, outperforming the OPD baseline and closely matching the larger teacher. We further show that Z-Reward can serve as a differentiable reward signal for text-to-image optimization, yielding a 41.3% net human-preference improvement over the SFT baseline.
While mixed-language querying is ubiquitous in multilingual communities, the sensitivity of dense retrievers to such queries remains poorly understood. We present a ratio-controlled study on mMARCO that systematically evaluates retrieval performance by varying the mixing proportion of parallel query translations via embedding-level mixing – constructing mixed queries as an interpolation of monolingual embeddings. Experiments with BGE-M3 demonstrate that an optimal mixing ratio outperforms the best monolingual endpoint in 88/105 cases. We uncover a distinct asymmetry driven by English dominance: mixing is uniformly beneficial when retrieving from non-English document indices, whereas indices containing English are best served by pure English queries. Furthermore, English acts as the strongest mixing partner for every non-English document language. Finally, when controlling for English dominance, mixing gains correlate negatively with typological distance. We conclude that language-mix sensitivity is structured and predictable, and we validate the robustness of these patterns across model families and scales.
arXiv:2606.15350v1 Announce Type: cross Abstract: Many problems in modern scientific computing are challenging because of a curse of dimension, where their mathematical formulation involves objects whose dimension is exponential in the nominal "size" of the problem. Tensor networks can provide a compact representation for exponentially large vectors and matrices that arise in applications, but these representations do not always lead to reliable algorithms. This paper develops and analyzes techniques for randomized dimension reduction of tensor network data. These techniques support a suite of efficient algorithms for provably solving exponential-scale linear algebra problems, including trace estimation and eigenvalue approximation. The paper includes several stylized illustrations from quantum many-body physics with ambient dimension up to $2^{200}$.
Saliency-guided training is a paradigm in visual recognition that encourages models to focus on the most relevant image regions during learning. While its application in biometric presentation attack detection (PAD) has shown strong benefits in robustness and generalization, adoption is often limited by the high cost, domain specificity, and limited scalability of existing saliency acquisition methods, such as human annotations over a limited dataset. We present a novel, cost-efficient, and highly-scalable approach to saliency acquisition using maps inspired by classical dimensionality reduction techniques: PCA and LDA. Our proposed methods generate saliency maps directly from raw training data, requiring no human annotation nor domain knowledge. We contextualize the effectiveness of these saliency sources in three saliency-explored domains (iris PAD, synthetic face detection, fingerprint PAD) and demonstrate its scalability in two saliency-novel domains (fingerprint vein PAD and ID card PAD). Across all domains tested, models trained using dimensionality reduction-sourced saliency maps exceed baseline and sometimes SOTA saliency methods without any resource investment or domain-specific tooling. Our findings overcome an important yet unaddressed barrier to saliency-guided training for biometric attack detection and beyond.
arXiv:2606.11711v1 Announce Type: new Abstract: Online learning with delayed feedback typically assumes that the learner can track all pending rounds until their feedback arrives. In practice, tracking resources are finite, and feedback from untracked rounds is permanently lost. In this paper, we study delayed online convex optimization (OCO) under a hard capacity constraint, where at most $C$ pending rounds can be tracked at any time. To model delay information, we introduce a semi-clairvoyant model that refines the clairvoyant assumption from prior work: rather than requiring delays to be known at prediction time, the learner observes delay expirations online, consistent with the classical unconstrained delayed setting. Our approach proceeds via a reduction to a novel ``delayed and weighted'' OCO problem, using a scheduler that randomizes tracking decisions and importance-weights the resulting observations. For this base problem, we propose and analyze Delayed-Weighted FTRL and its bandit analogue, establishing regret bounds that explicitly characterize the interaction between time-varying weights and delayed feedback. Combining these base learners with our schedulers yields the first regret guarantees for capacity-constrained OCO under convex and strongly convex losses, for both first-order and bandit feedback. For first-order feedback, capacity $C = \Omega(\log T)$ suffices to recover standard delayed OCO rates up to logarithmic factors. For bandit feedback, the regret rates are modulated by powers of $(1 + \sigma_{max}/C)$, where $\sigma_{max}$ is the maximum number of pending observations at any time. This allows the regret bound to degrade gracefully when $C < \sigma_{max}$, while remaining sublinear.
arXiv:2606.15054v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) detect features via inner product, so a feature's activation scales with both its directional alignment and the input's norm. Under BatchTopK, high-norm tokens inflate all pre-activations simultaneously, claiming dictionary slots regardless of content alignment. This matters because sublayer normalization has already discarded the magnitude the score measures, so the encoder detects a quantity the model does not read. We replace the score with a learned blend of cosine similarity and input magnitude, letting the optimizer choose how much norm to use; a per-feature extension lets each feature decide independently. In both regimes, training is free to recover inner product but never does, with no feature ever choosing more than half-magnitude dependence. At matched reconstruction, the cosine encoder learns features that align with human-recognizable concepts far more often than standard, filling dictionary slots that inner product wastes on norm detectors. Loss reweighting that equalizes gradients barely closes the gap, confirming forward-pass score geometry as the lever. The advantage is not universal across tasks or depths, but we believe cosine scoring should be the default for dictionary learning on normalized representations.
arXiv:2606.19595v1 Announce Type: cross Abstract: Voice agents deployed in structured workflows (customer service, healthcare scheduling, account management) must handle frequent user interruptions while maintaining progress through multi-step procedures. Existing benchmarks for speech-capable models focus on the timing of interruptions: barge-in detection, endpointing, and turn-taking dynamics. They leave unmeasured what happens after the interruption: does the agent resume the workflow at the correct step? Does it address the user's interjection? Does it avoid re-delivering content the user already heard? We introduce IHBench (Interruption Handling Benchmark), a benchmark that evaluates post-interruption recovery in voice agents executing state-machine-driven workflows across 10 enterprise domains. Six interruption types are injected at controlled points mid-utterance, with per-interruption evaluation rubrics generated alongside the data. Each interruption is scored on two axes: task fulfillment and recovery quality. We evaluate 27 audio-language model configurations from OpenAI, Google, and the open-weight community. Models vary widely, and recovery quality depends strongly on the interruption type. Across our experiments, closed-weight models are consistently more robust to interruptions than open-weight ones: they win far more often on task fulfillment, degrade roughly 3.3x more slowly as conversations grow longer, and show no audio-versus-text modality gap, whereas the open-weight models lose ground on all three. A human study validates the LLM judge against human annotators, and a cross-benchmark analysis against AudioMultiChallenge indicates that recovery quality is a largely distinct capability axis.
arXiv:2606.18733v1 Announce Type: cross Abstract: Realistic coding-agent benchmarks often replay public GitHub issues and pull requests, making them vulnerable to overlap with model pretraining, fine-tuning, synthetic-data generation, or benchmark-driven model selection. Fully synthetic tasks avoid direct historical replay, but can drift away from real repository needs. We propose SWE-Future, a forecast-conditioned data synthesis method for future-oriented coding tasks. Given a forecast snapshot at time $T_0$, the method uses only pre-$T_0$ repository evidence to forecast future feature implementation/enhancement, bugfix, and refactor task families. We first validate this forecasting step retrospectively: after forecasts are fixed, later pull requests are used only to measure whether the predicted task families match future repository work. In an 80-repository study, the forecaster achieves 58.1\% future-work relevance under the main semantic matching metric. We then use validated forecast families as conditioning signals to synthesize a 200-task coding-agent dataset across 61 repositories from a task-generation snapshot, rather than replaying the later pull requests used for validation. SWE-Future shows that repository-evolution forecasts can guide realistic, future-oriented coding-task synthesis while reducing direct dependence on historical pull-request replay.
arXiv:2602.12670v4 Announce Type: replace Abstract: Agent Skills are structured packages of procedural knowledge that augment large language model (LLM) agents at inference time. Despite rapid adoption, there is no standard way to measure whether they actually help. We present SkillsBench, a benchmark whose current inventory contains 87 tasks across 8 domains paired with curated Skills and deterministic verifiers. Our latest aggregate evaluation runs the 87-task benchmark under matched no-Skills and curated-Skills conditions for 18 model-harness configurations. Curated Skills raise the average pass rate from 33.9% to 50.5% (+16.6 percentage points; 25.5% normalized gain), with configuration-level gains ranging from +4.1 to +25.7 pp. Focused Skills with at most three modules outperform larger or exhaustive bundles, and smaller models with Skills can match larger models without them. SkillsBench establishes paired evaluation as the foundation for rigorous measurement of Skill efficacy on agentic, expertise-heavy work.
Modern Vision-Language Models (VLMs) benefit from chain-of-thought prompting and test-time scaling, but these gains often come with prohibitive inference cost due to large visual contexts and long decoding chains. We view this cost through two coupled axes: Visual Context Scaling (VCS), which controls how much visual evidence is passed to the language model, and Visual Reasoning Scaling (VRS), which controls how much inference-time reasoning search is performed. Existing methods typically optimize one axis at a time, leaving the joint allocation of compute across these axes underexplored. We introduce Adaptive Visual Inference Scaling (AVIS), a lightweight policy that adapts both VCS and VRS per query. AVIS realizes VCS through Key Diversity Visual (KDV) pruning, a training-free $O(N)$ key-based rule for removing redundant visual tokens before prefilling, and realizes VRS through adaptive self-consistency, using a learned difficulty predictor to select the number of reasoning rollouts. AVIS is deployment-friendly and compatible with shared-prefill inference, where all rollouts reuse a single prefilling pass and KV cache. Across diverse image and video reasoning benchmarks, AVIS improves the accuracy–compute trade-off relative to VCS-only and VRS-only baselines, and remains effective on top of RL post-trained VLMs while keeping compute and latency low.
In real-world applications, a machine learning model is required to handle an open-set recognition (OSR), where unknown classes appear during the inference, in addition to a domain shift, where the data distribution differs between the training and inference phases. Domain generalization (DG) aims to handle the domain shift situation where the target domain of the inference phase is inaccessible during the model training. Open domain generalization (ODG) considers DG and OSR. Domain-augmented meta-learning (DAML) is a method targeting ODG; however, it has a complicated learning process. By contrast, although various DG methods have been proposed, they have not been evaluated in ODG situations. In this study, we comprehensively evaluate the existing DG methods in ODG and show that the two simple DG methods, CORrelation ALignment (CORAL) and maximum mean discrepancy (MMD), are competitive with DAML in several cases. In addition, we propose simple extensions of CORAL and MMD by introducing the techniques used in DAML, such as ensemble learning and Dirichlet mixup data augmentation. The experimental evaluation demonstrates that the extended CORAL and MMD can perform comparably to DAML with lower computational costs. This suggests that the simple DG methods and their simple extensions are strong baselines for ODG.
arXiv:2606.19823v1 Announce Type: cross Abstract: Automatic speech recognition remains unreliable for dysarthric speech due to data scarcity and high inter-speaker variability. While synthetic data can address these gaps, traditional methods often require extensive speaker-specific data, reintroducing the collection bottleneck. We investigate zero-shot voice cloning as a low-burden augmentation strategy, using Higgs Audio V2 to clone speakers in the TORGO dataset. We fine-tune (FT) Whisper-medium on cloned, real, and hybrid data and evaluate on held-out real speech. Compared to the zero-shot (31.62%), Clone FT achieved a competitive 26.00% WER, nearly matching the 24.44% and 25.12% seen with Real and Hybrid FT, respectively. Notably, Clone and Hybrid FT outperform Real FT for moderate-severe speakers. Clone FT achieves the best results (11.45% relative) in cross-corpus evaluation on the SAP-1102. These results suggest that zero-shot cloning provides scalable training data that circumvents the costly data collection bottleneck.
Recent progress in modeling techniques and high-throughput screening has significantly enhanced the accessibility of protein engineering. Nevertheless, further progress gets hindered by the lack of robust benchmarks that capture the practical challenges for real-world protein engineering. Here, we introduced DeePEn, a Depth-sensitive benchmark for Protein Engineering that quantifies a models generalization capabilities when predicting protein fitness at increasing mutational distance from the wildtype or training data. We defined distance as the number of simultaneous point mutations, i.e., single amino acid variants (SAVs), moving from wild-type to mutant (edit distance in computer science jargon). Specifically selecting four deep mutational scanning (DMS) datasets with sufficient multi-mutation data points from ProteinGym, we assessed recent predictive models, including general and biophysics-informed protein Language Models (pLMs), and a non-transformer neural network. Our results highlight how the performance of all models deteriorates with increasing mutational distance and that no single metric sufficiently captures the diverse requirements of protein engineering. To overcome these shortcomings, DeePEn provides a readily available resource for multi-metric benchmarking that focuses on the prediction of distant variants.