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01.
medRxiv (Medicine) 2026-06-11

Polygenic risk scores associate with asthma phenotypes and proteomic analyses implicate IL1R1 in two family-based studies

Authors:
Lee↗Moll↗Mendez↗Prince↗Lasky-Su↗Lutz↗S. M↗Weiss↗S. T↗Lange↗Kelly↗R. S↗…

Despite its high prevalence and the discovery of hundreds of genetic associations, the genetic determinants and heterogeneous manifestations of asthma remain incompletely understood. Incorporating polygenic risk scores (PRS) into asthma research offers a powerful approach to quantify inherited susceptibility, refine risk profiles, and advance mechanistic understanding of disease development. For this study, we leveraged whole-genome sequencing (WGS) data from two family-based cohorts of childhood asthma - the Genetics of Asthma in Costa Rica Study (GACRS) and the Childhood Asthma Management Program (CAMP) - to examine the transmission profiles of externally derived asthma PRS and their associations with clinical phenotypes in children with asthma. To further elucidate molecular mechanisms, we integrated large-scale external genome-wide association study (GWAS) summary statistics and genetic prediction models of protein abundance in a two-step proteome-wide association study (PWAS) of asthma. Our findings provide robust evidence supporting the validity of externally derived asthma PRS (asthma PRS association p-value p={10}^{-24} [GACRS and CAMP trios combined] for the Global Biobank Meta-analysis Initiative [GBMI]) and reveal consistent associations with spirometry measures and atopy markers across both studies, as 13 of 21 traits (62%) were significantly associated with the GBMI-PRS in the meta-analysis after multiple-testing correction. Moreover, the results of the integrative proteomic analysis implicate IL-1 signaling in the etiology of asthma, reinforcing the candidacy of IL1R1 antagonists for drug repurposing.

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02.
Nature (Science) 2026-06-17

Emergent decadal predictability in Antarctic contribution to sea-level rise

Authors:
Felicity S. McCormack↗

Despite large uncertainties associated with future mass loss from the Antarctic Ice Sheet, ice-sheet models show that the rate of sea-level rise from Antarctic ice loss in 2025 is strongly predictive of the rate for the next several decades, regardless of emission pathway or model complexity. This finding is robust across all models that were considered in the Intergovernmental Panel on Climate Change Sixth Assessment Report global mean sea-level projections, including the low-likelihood, high-impact scenarios of sea-level rise. Given this strong near-term decadal predictability, ice-sheet models that can accurately reproduce present-day ice-mass loss provide a reliable basis for near-term sea-level planning and adaptation through to mid-century. The predictability breaks down by the end of the twenty-first century as feedbacks, such as those related to marine ice-sheet retreat, begin to emerge, leading to accelerating ice loss. Drawing on these results, we identify key feedback mechanisms that can account for the transition between near-term decadal predictability and the longer-term, feedback-driven evolution, and suggest priorities for ice-sheet model development aimed at resolving long-term sea-level rise uncertainty. Although Antarctic ice loss projections diverge widely by 2100, this Perspective shows that present-day rates robustly predict mid-century sea level rise, providing a firm basis for near-term planning, while highlighting priorities for model development aimed at resolving longer-term sea level rise uncertainty.

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03.
medRxiv (Medicine) 2026-06-16

Development of an automated, imaging-based preoperative screening model for early identification of malnutrition in an abdominal surgery cohort

Authors:
Gershuni↗V. M↗Damani↗R. A↗Vasisht↗Sharma↗Rowe↗Compher↗Duda↗Sagreiya↗Kelz↗Lee↗…

Background: Clinical malnutrition affects one in five abdominal surgery patients and increases postoperative complications and mortality. Current screening occurs after admission, closing the window for preoperative nutritional intervention. No objective, scalable preoperative screening tool exists. Objective: To determine whether automated volumetric CT-based body composition analysis improves preoperative identification of surgical patients at risk for clinical malnutrition compared to clinical variables or single slice imaging alone. Methods: Retrospective cohort study of adults undergoing elective abdominal surgery at a quaternary academic medical center (2018 to 2021) with a preoperative CT scan within 90 days and complete nutrition assessment. Clinical malnutrition was diagnosed by a registered dietitian using ASPEN/AND criteria. Three sex stratified Elastic Net models were compared: (1) base clinical variables; (2) base plus L3 single slice skeletal muscle index and attenuation; and (3) base plus comprehensive 3D volumetric quantification of five muscle groups and two fat depots. Discrimination (AUROC), calibration (Brier score), and clinical utility (decision curve analysis) were assessed via 10-fold cross-validation. Results: Among 1,143 patients (52.4% female; mean age 60.5 years), 231 (20.2%) were diagnosed with malnutrition. Malnourished patients had significantly higher complication rates (36.4% vs. 15.4%, p

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04.
medRxiv (Medicine) 2026-06-11

Genetic Susceptibility to Incisional Hernia: Evaluation of Hernia Polygenic Risk Scores

Authors:
Pregnall↗A. M↗Hornick↗M. M↗Broach↗R. B↗Judy↗DePaolo↗Yuan↗Levin↗Fischer↗J. P↗…

Objectives: Incisional hernia (IH) affects 13-30% of people after abdominal surgery, resulting in substantial morbidity and costs. While clinical risk factors have been studied extensively, genomic risk for IH is incompletely understood. We aimed to evaluate the impact of polygenic risk scores (PRS) on IH risk prediction. Methods] We created and evaluated three PRS for abdominal hernia, ventral hernia and latent hernia susceptibility for prediction of IH in an institutional biobank. The primary outcome was defined as the diagnosis or repair of an IH based on ICD-9/10-CM/PCS and CPT codes. Clinical covariates included age, sex, body mass index (BMI), smoking status, index procedure type, and perioperative surgical site infection. A phenome-wide association study (PheWAS) was performed to assess clinical associations with increased PRS. We then tested the ability of the PRS to improve prediction for IH by modeling clinical covariates with and without PRS in patients who underwent abdominal surgery. Model performance was assessed using 10 iterations of 5-fold cross-validation to estimate Brier scores and area under the receiver operating characteristic curve (AUROC), which were compared using cross-model Bayesian analysis of variance. Results: In 55,809 subjects, assessed PRS was significantly associated with incisional, umbilical, and ventral hernia on PheWAS, with 1.19 greater odds of developing IH per 1-SD increase in PRS (95% CI: 1.13-1.25, P < 0.001). Of 9,909 subjects who underwent qualifying abdominal surgery, 706 developed IH. In this cohort, the latent hernia susceptibility PRS was associated with a 16% increased hazard of developing IH per 1-SD increase (HR 1.16; 95% CI: 1.07-1.26; P < 0.001). Compared to a predictive model using clinical covariates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC = 0.660, 95% CI: 0.653-0.666), addition of the PRS showed similar Brier score and AUROC estimates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC: 0.667, 95% CI: 0.661-0.673) at five years. Cross-model Bayesian analysis demonstrated >99% probability of practical equivalence when trying to detect a difference of [&ge;] 0.02. Conclusion: All three PRS for hernia were independently associated with IH, suggesting that genomic factors contribute significantly to IH development. However, none of the three PRS meaningfully improved clinical IH risk prediction in patients who underwent abdominal surgery. This suggests that clinical comorbidities and surgical techniques may be equally as important as genomic architecture.

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05.
arXiv (CS.AI) 2026-06-16

LLM4RTL: Tool-Assisted LLM for RTL Generation

Authors:
Jing Jin↗Robert Chu↗Ning Yan↗Masood S. Mortazavi↗

arXiv:2606.15500v1 Announce Type: cross Abstract: Large language models (LLMs) have facilitated impressive progress in software engineering, code generation, tooling, and systems. Concurrently, a significant body of research has developed which explores a growing variety of methods and systems for applying LLMs to hardware and chip design (e.g., systems for RTL code generation based on functional description). However, when it comes to open Verilog/RTL code-generation, we need high-quality training samples to build specialized and more effective LLM systems through fine-tuning or low-rank adaptation. Here, we propose a ``judge-renew-check-renew-check'' (JRCRC) pipeline which updates a current public dataset using a hierarchy of state-of-the-art commercial LLM models differing in their costs and capabilities in RTL code generation. This approach achieves a cost-effective mechanism for filtering and refining code-generation samples into a higher-quality training dataset. Our experiments also identify some common weaknesses of LLMs in rule-based reasoning and logic, and consequently, in RTL code-generation. Having identified these weaknesses, we develop an architecture for incorporating pre-processing tools to dynamically assist the LLMs in inferring logical relationships from tabular data formats. With our tools-assisted architecture for RTL code generation, we achieve significant overall performance gains in the VerilogEval benchmark and outperform many state-of-the-art methods. Our LLM4RTL system achieves performance comparable to that of GPT-4O using a significantly much smaller LLM.

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06.
arXiv (CS.CV) 2026-06-19

HypOProto: Hyperbolic Ordinal Prototypes for Left Ventricular Filling Pressure Classification

Authors:
Victoria Wu↗Nima Hashemi↗Hooman Vaseli↗Christina Luong↗Purang Abolmaesumi↗Teresa S. M. Tsang↗

Echocardiography (echo) is a widely used imaging modality for assessing cardiac function, with Left Ventricular Filling Pressure (LVFP) serving as a critical physiological marker for conditions such as heart failure. Standard LVFP classification into normal vs elevated categories relies on the Doppler-derived $E/e'$ ratio, which is operator-dependent and often unavailable in resource-limited settings, motivating methods that infer LVFP directly from B-mode echo. Existing deep learning approaches achieve high performance but remain largely black-box, limiting clinical interpretability. We propose HypOProto, a hyperbolic, ordinal prototype-based framework for interpretable LVFP classification using a frozen, explainable foundation model backbone. HypOProto arranges prototypes along the physiological $E/e'$ scale, placing borderline cases near the hyperboloid root where small angular differences separate similar cases, while normal and elevated cases occupy outward positions reflecting increasing diagnostic certainty. This hyperbolic geometry encodes clinically meaningful ordinal relationships and improves interpretability. We also introduce a novel Hyperbolic Prototype Angular Separation (HyperPAS) loss, enforcing inter-class prototype separation in hyperbolic space. HypOProto achieves SOTA performance while maintaining transparency, and highlights clinically relevant regions in visualizations. This work represents the first prototype-based framework for LVFP classification in echo. Our code can be found at https://github.com/DeepRCL/HypOProto.

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07.
arXiv (quant-ph) 2026-06-17

DRAG-Compatible Leakage Suppression in Landau–Zener Control via Isoprobability Twins

Authors:
Ivo S. Mihov↗Nikolay V. Vitanov↗

arXiv:2506.19572v4 Announce Type: replace Abstract: Analytically solvable models – particularly the Landau-Majorana-Stückelberg-Zener (LMSZ) and Allen-Eberly-Hioe (AEH) models – underpin many quantum-gate implementations and population-transfer protocols. However, their canonical pulse shapes are incompatible with modern leakage-suppression techniques and some systems. Most notably, the constant Rabi envelope of the LMSZ pulse prevents many leakage-suppression approaches, which require smoothness. We address both limitations by developing the concept of isoprobability twin models: distinct pairs of Rabi frequency $\Omega(t)$ and detuning $\Delta(t)$ that yield identical post-pulse transition probabilities based on the Delos-Thorson transformation. In this work, we formalise the method by experimentally demonstrating the equivalence of multiple LMSZ and AEH twin models on IBM's ibm_kyiv processor. Finally, we show a staggering leakage reduction by more than 3 orders of magnitude using a custom DRAG implementation of a cosine LMSZ isoprobability model.

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08.
arXiv (quant-ph) 2026-06-24

The Saturable Electronic Reluctance Switch: Switchable low-power and low-noise generation of magnetic fields using permanent magnets

Authors:
P. D. Taylor-Burdett↗C. A. Burhan↗S. Mason↗F. R. Lebrun-Gallagher↗S. Weidt↗W. K. Hensinger↗

arXiv:2605.05158v2 Announce Type: replace Abstract: Across many areas of science, there is a need to generate magnetic fields that are both ultra-stable and switchable on and off. Current-carrying wire configurations are switchable but are susceptible to current noise. Existing current-controlled approaches to switching the field produced by a permanent magnet involve altering the magnets magnetisation, which typically requires large field pulses and produces excessive power dissipation in high frequency applications. We present a hybrid technique to switch the field of any arbitrary magnet through use of a non-linear ferromagnetic circuit, named the Saturable Electronic Reluctance Switch (SERS). The circuit achieves a linear and monotonic ramp of the magnetic field up to a current threshold, above which the field becomes constant. Crucially, the applied current has minimal influence on the magnetic field stability and demagnetisation of the magnet is avoided. The power dissipated in each switching cycle is expected to be many orders of magnitude less than for existing permanent magnet switching approaches. SERS is also robust to fabrication errors, suppressing noise in the control current by several orders of magnitude in a non-ideal device. To illustrate its application, a SERS-driven device is proposed for generating ultra-stable magnetic field gradients in a scalable trapped-ion quantum computer. We find this device offers an order of magnitude reduction in power dissipation compared to state-of-the-art current carrying wires, while reducing magnetic field noise originating from current fluctuations by up to five orders of magnitude.

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09.
arXiv (CS.AI) 2026-06-24

The Measurable Majority

Authors:
Lawrence S. Moss↗Arthur Paul Pedersen↗

arXiv:2606.23853v1 Announce Type: cross Abstract: This paper studies strict majority reasoning in finite electorates using so-called $social decision frames$: finite sets of voters equipped with distinguished families of coalitions interpreted as those voting blocs evaluated to form a strict majority. A coherence criterion for qualitative majority judgments is identified and shown to give an exact characterization for representability of strict majorities by finitely additive measures. In addition, a minimal natural logic for reasoning about strict majorities is shown to be sound and complete. These developments motivate examination of associated combinatorial questions concerning incoherence in finite families of sets; partial results and a conjecture are given. Finally, the results of this paper are applied to correct a classical representation theorem for weak qualitative probability structures due to Patrick Suppes and to establish a May-type characterization for ordinary strict majority rule for social decision frames.

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10.
arXiv (CS.AI) 2026-06-16

Combining Retrieval-Augmented Text Generation with LLMs for Reading Content Recommendations

Authors:
Sooyeon Kim↗Piotr S. Maci\k{a}g↗

arXiv:2606.14817v1 Announce Type: cross Abstract: This work presents the design, implementation, and evaluation of a system for generating personalized reading content using Large Language Models (LLMs) combined with Retrieval-Augmented Generation (RAG). The proposed architecture consists of four modules: Input, RAG, Generation, and Judging and enables users to specify both a question and a target reading content complexity. RAG is employed to retrieve relevant information from the Internet, enriching and grounding the content produced by three modern LLMs: Meta LLaMA 4 Scout, LLaMA 3.1 8B Instant, and Google Gemma2 9B. Reading materials are generated using three prompting strategies (Chain-of-Thought, zero-shot, and few-shot), and the LLM-as-a-Judge module automatically evaluates answer quality and alignment with the desired readability level. Experimental results show that RAG consistently improves system performance across all models and prompting techniques, increasing relevance and particularly groundedness by up to 26-35 percentage points. Overall, the findings demonstrate that the RAG-augmented architecture effectively produces reading content tailored to user queries and desired textual complexity.

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11.
arXiv (CS.CV) 2026-06-16

Detect Before You Leap: Mirage Detection in Vision-Language Models

Authors:
Sayeed Shafayet Chowdhury↗Md. Shaown Miah↗S. M. Taiabul Haque↗Syed Ishtiaque Ahmed↗

Vision-language models (VLMs) can produce confident visual answers even when the required visual evidence is missing, blank, or unrelated to the question. This failure mode, recently described as mirage (mirage2026), is especially concerning in medical and document VQA, where a plausible but visually ungrounded answer may be mistaken for image-based evidence. We study the complementary problem of pre-release mirage detection: given an image-question pair, determine whether the VLM should answer or abstain before generation. To that end, we propose a novel model-agnostic Text-Conditioned Layer-wise Internal Alignment (TC-LIA) method that probes patch-token representations across the layers of a CLIP ViT-H/14 vision encoder. The key idea is to project layer-wise image patch tokens into the final CLIP embedding space and measure their similarity with the question embedding, thereby tracking whether question-relevant visual evidence emerges across vision layers. TC-LIA summarizes this alignment trajectory using final image-text cosine similarity, late-layer top-k patch-text alignment, early-to-late gain, and layer-wise slope. These features are combined with pixel-statistic based blank/noise detection, zero-shot domain routing, and structured VLM self-assessment in an ensemble. Across five VQA domains with related, unrelated-real, and blank/noise inputs, and across twelve VLM backbones, Qwen2.5-VL-32B achieves the highest three-class detection accuracy of 94.7% with a 3.0% mirage rate, while Qwen2.5-VL-72B achieves 94.6% accuracy with a lower 2.8% mirage rate. Baseline mirage rates span 21.7-66.6%.

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12.
arXiv (CS.CL) 2026-06-24

SURGELLM: Rethinking Multi-Task Evaluation through Task-Aware Feature Gating with Class-Balanced Normalization

Authors:
Noor Islam S. Mohammad↗Ulug Bayazit↗

Fine-tuned encoders deployed across heterogeneous NLP tasks face three compounding problems: mismatched inductive biases, class-imbalance corruption of feature statistics, and no mechanism to condition attention on external lexical knowledge. We introduce \surgellm, a unified transformer framework that addresses each with a dedicated lightweight module: a surgical feature gate (learned per-dimension sigmoid over curated lexical indicators and \texttt{[CLS]}; provably degenerates to identity when features are uninformative), task-conditioned prefix tokens (quantized feature values and task identity prepended to every input), and Instance-Weighted Normalization (IWN; removes class-prior bias from gate statistics). We prove an excess-risk bound linking gate benefit to surgical feature alignment. Across four tasks, SST-2, multi-hop retrieval, LLM-prompt attribution, and authorship detection, covering 17,830 examples and eleven model variants over three seeds, the IWN variant achieves macro-F1 0.940 ($+0.036$ over the strongest non-IWN baseline; $+0.130$ on authorship detection). A random-vocabulary control ($-0.028$ avg.\ F1) confirms gains are lexical, not parametric. Code, vocabularies, and a $99.5\%$-recovery auto-extraction recipe are released.

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13.
arXiv (CS.AI) 2026-06-16

Learning Earthquake Wave Arrival Time Picking from Labels with Inaccuracies

Authors:
Sen Li↗Xu Yang↗S. Mostafa Mousavi↗Anye Cao↗Keting Fan↗Yaoqi Liu↗Changbin Wang↗Qiang Niu↗

arXiv:2606.15377v1 Announce Type: cross Abstract: Inaccurately labeled training data, or "label noise", poses a significant threat to the integrity of supervised machine learning models. This corruption directly degrades performance by teaching the model erroneous mappings between features and labels, which leads to poor generalization and reduced accuracy on properly labeled validation and test data. Current seismological applications mainly rely on large-scale training sets or data augmentation to reduce the label-noise impact, which can be labor-intensive and costly. Here, we introduce a Label Noise-Contrastive Robust Learning (LaNCoR) approach that can effectively handle noisy labels in seismic signal processing tasks, without requiring large-scale training datasets. In this approach, the input waveform feature and label representation distributions are aligned in the feature space to correct mislabeling and reduce its impact on the training process. We present LaNCoR's performance on the task of P-phase arrival-time picking of real microseismic data using two baseline models and training approaches. Our results indicate that LaNCoR can improve performance by up to 28.8% across performance metrics. This approach holds great promise for model training in seismology and geosciences.

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14.
medRxiv (Medicine) 2026-06-23

Estimating vaccine-prevented disease outcomes when vaccination has only direct effects

Authors:
Yang↗Magee↗Morris↗S. E↗Mathis↗S. M↗Wiegand↗Iuliano↗D. A↗Biggerstaff↗Olesen↗S. W↗…

Vaccination can be a useful intervention for reducing infectious disease burden. Estimating numbers of vaccine-prevented health outcomes is one approach to quantifying the benefits of vaccination. Here we improve a method described by Foppa et al. (1) that assumes vaccination has only direct effects, that is, it cannot prevent infection or onward transmission of the disease. We rederive this method and derive an improved method that increases estimation accuracy with minimal additional analytical complexity. To evaluate the improved method, we simulated disease outbreaks and compared the accuracy of the two methods for estimating prevented disease outcomes. In 84% of simulations performed over a wide parameter space, the improved method had an equal or smaller estimation error compared to the original Foppa method, with 7.9-fold smaller mean error and 44-fold smaller standard deviation of errors. Our study improves a method for estimating prevented burden when assuming vaccination has only direct effects.

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15.
medRxiv (Medicine) 2026-06-24

Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals

Authors:
Kosmicki↗J. A↗Ganel↗Watanabe↗Joseph↗Gaynor↗S. M↗Kessler↗M. D↗Backman↗J. D↗Mbatchou↗…

Highly heritable, polygenic, and easily measured, adult height has long been the model trait in human genetics. While the landscape of height-associated common genetic variation has been studied extensively, rare variation remains relatively unexplored. Using rare protein-altering variants in a discovery set of 826,066 exomes, we identify 207 height-associated genes - 98% of which replicate in an additional 624,567 individuals. The rarest and most deleterious class of variation, singleton (frequency

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16.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

Authors:
Eger↗S. J↗Lopez↗Gomez Navarro↗L. F↗Pena-Tauber↗Cochran↗J. N↗Hiatt↗S. M↗Gelvez↗Garcia-Garcia↗…

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

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17.
arXiv (CS.CV) 2026-06-17

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

Authors:
Zheng Chen↗Zongwei Wu↗Eduard Zamfir↗Kai Zhang↗Yulun Zhang↗Radu Timofte↗Xiaokang Yang↗Hongyuan Yu↗Cheng Wan↗Yuxin Hong↗Zhijuan Huang↗Yajun Zou↗…

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

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18.
arXiv (quant-ph) 2026-06-11

Tight Bounds for Quantum Phase Estimation and Related Problems

Authors:
Nikhil S. Mande↗Ronald de Wolf↗

arXiv:2305.04908v3 Announce Type: replace Abstract: Phase estimation, due to Kitaev [arXiv'95], is one of the most fundamental subroutines in quantum computing. In the basic scenario, one is given black-box access to a unitary $U$, and an eigenstate $\lvert \psi \rangle$ of $U$ with unknown eigenvalue $e^{i\theta}$, and the task is to estimate the eigenphase $\theta$ within $\pm\delta$, with high probability. The cost of an algorithm for us is the number of applications of $U$ and $U^{-1}$. We tightly characterize the cost of several variants of phase estimation where we are no longer given an eigenstate, but are required to estimate the maximum eigenphase of $U$, aided by advice in the form of states (or a unitary preparing those states) which are promised to have at least a certain overlap $\gamma$ with the top eigenspace. We give algorithms and nearly matching lower bounds for all ranges of parameters. We show that a small number of copies of the advice state (or of an advice-preparing unitary) are not significantly better than having no advice at all. We also show that having lots of advice (applications of the advice-preparing unitary) does not significantly reduce cost, and neither does knowledge of the eigenbasis of $U$. We immediately obtain a lower bound on the complexity of the Unitary recurrence time problem, resolving an open question of She and Yuen~[ITCS'23]. Lastly, we study how efficiently one can reduce the error probability in the basic phase-estimation scenario. We show that a phase-estimation algorithm with precision $\delta$ and error probability $\epsilon$ has cost $\Omega\left(\frac{1}{\delta}\log\frac{1}{\epsilon}\right)$, matching an easy upper bound. This contrasts with some other scenarios in quantum computing (e.g., search) where error-probability reduction costs only a factor $O(\sqrt{\log(1/\epsilon)})$. Our lower bound uses a variant of the polynomial method with trigonometric polynomials.

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19.
arXiv (CS.AI) 2026-06-18

Practical Anonymous Two-Party Gradient Boosting Decision Tree

Authors:
Chenyu Huang↗Fan Zhang↗Minxin Du↗Sherman S. M. Chow↗Huangxun Chen↗Huaming Rao↗Danqing Huang↗Bo Qian↗Peng Chen↗

arXiv:2605.26903v2 Announce Type: replace-cross Abstract: Structured data is well handled by gradient-boosted decision trees (GBDT), which are usually trained on vertically partitioned features across mutually distrustful parties. High speed and interpretability make GBDTs popular in finance and healthcare, where neural networks may fall short. Enabling secure computation for GBDTs poses unique challenges, requiring secure record alignment for comparison. Relying on private set intersection (PSI) is a de facto approach. Mistaking PSI for a safety measure actually exposes which record identifiers (IDs) are shared between the datasets. Although circuit-PSI could help, it is costly for generic uses. New ideas are needed to efficiently train in a "dark forest". Aiming to hide the IDs, we initiate the study of anonymous GBDT training on split data held by two parties. Dual circuit-PSI in our design lets the parties alternate as receiver to run pick-then-sum over local features. Via oblivious programmable pseudorandom functions, we propagate circuit-PSI outputs as shared state across runs. Avoiding universal alignment, we resolve the neglected dilemma that ID hiding incurs a cost that scales with domain size. Next, we halve the cost of ciphertext packing used to convert single-instruction multiple-data homomorphic encryption from (ring) learning with errors in prior secure GBDT (Usenix Security' 23) and related secure machine-learning computations. Comparative experiments show our protocol remains competitive with leaky approaches in efficiency. Enabling ID-hiding aggregation, our techniques can extend to other vertically partitioned analytics.

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20.
arXiv (CS.AI) 2026-06-16

The Faithfulness Gap: Certifying Semantic Equivalence Between Natural-Language and Formal Mathematical Statements

Authors:
Noor Islam S. Mohammad↗Tamim Sheikh↗

arXiv:2606.16541v1 Announce Type: new Abstract: Autoformalization, translating natural-language mathematics into formal proof assistants, is bottlenecked not by translation fluency but by faithfulness: a formal statement can typecheck and be provable, yet still encode a different theorem than the source intended. We introduce Bidirectional Provability Fingerprinting (\bpf{}), a framework that certifies faithfulness by characterizing each candidate through its forward and backward consequence neighborhoods in the ambient theory and matching these against probes derived from the natural-language statement. We further introduce four novel components: (i) Counterfactual Probe Generation (\cpg{}), a contrastive procedure that synthesizes probes targeting specific drift directions; (ii) the Equivalence Spectrum, a continuous faithfulness score that replaces brittle binary verdicts; (iii) Adaptive Probe Budget Allocation (\apba{}), an information-theoretic budget router; and (iv) Faithfulness-Guided Decoding (\fgd{}), which uses \bpf{} signals as a reward during autoformalization. We prove a drift detection theorem and a PAC-faithfulness result establishing that the equivalence class of a natural language statement is learnable from $\mathcal{O}(\log(1/\delta)/\varepsilon)$ probes under mild assumptions. We release \driftbench{}, a benchmark of $2{,}183$ NL/Lean~4 pairs with controlled drift labels across six subfields of mathlib4. \bpf{}\,+\,\cpg{} detects $89.6\%$ of drifted formalizations at a $3.0\%$ false-positive rate-against $41.2\%$ for typecheck and $63.3\%$ for LLM-judge baselines, and \fgd{} reduces the rate at which a state-of-the-art autoformalizer emits drifted statements by $47\%$. https://pmlrbd.github.io/BPF/

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21.
bioRxiv (Bioinfo) 2026-06-19

Nickel-Driven Dynamics of Urease in Sporosarcina pasteurii: Integrated Computational and Experimental Insights

Authors:
Al-Thawadi↗S. M↗

Urease is a nickel-dependent enzyme that plays an important role in urea hydrolysis and in a process named as microbial-induced calcium carbonate precipitation (MICP), which is widely used in sustainable environmental biotechnology. Despite its ecological importance, urease powers Biogrout (biocementation), a promising green technology for soil stabilization and infrastructure repair. Yet, the relationship between nickel availability, enzyme activation, and bacterial fitness remains poorly understood. In this study, we reveal a striking dual effect of nickel on Sporosarcina pasteurii: while high Ni2+ concentrations strongly inhibit growth (IC50 {approx} 637.7 {micro}M), they simultaneously boost specific urease activity up to six-fold. This uncoupling between biomass and enzymatic efficiency highlights a previously overlooked adaptive strategy under metal stress. Using structural bioinformatics and molecular docking, we show that Ure1–the catalytic subunit–exhibits the strongest nickel affinity (-4.3 kcal{middle dot}mol-1), supported by highly conserved active-site residues, whereas accessory proteins UreE and UreG display moderate and weak binding, consistent with their roles in metal delivery and GTP-dependent maturation. In addition, microscopic observations confirmed that calcium carbonate precipitation was most pronounced at intermediate nickel concentrations (approximately 400-1000 {micro}M), whereas higher concentrations ([&ge;]1000-1300 {micro}M) led to reduced mineral formation due to loss viable cells. Taken together, these results indicates that nickel availability controls both urease activation and bacterial fitness, and that an optimal balance is required to maximize biomenerilization efficiency in environmental applications, particularly in biocementation technology.

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22.
arXiv (CS.AI) 2026-06-16

Protein Design with Agent Rosetta: A Case Study for Specialized Scientific Agents

Authors:
Jacopo Teneggi↗S. M. Bargeen A. Turzo↗Tanya Marwah↗Alberto Bietti↗P. Douglas Renfrew↗Vikram Khipple Mulligan↗Siavash Golkar↗

arXiv:2603.15952v2 Announce Type: replace Abstract: Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML) methods achieve strong results, these are largely restricted to canonical amino acids and narrow objectives, leaving unfilled need for a generalist tool for broad design pipelines. We introduce Agent Rosetta, an LLM agent paired with a structured environment for operating Rosetta, the leading physics-based heteropolymer design software, capable of modeling non-canonical building blocks and geometries. Agent Rosetta iteratively refines designs to achieve user-defined objectives, combining LLM reasoning with Rosetta's generality. We evaluate Agent Rosetta on design with canonical amino acids, matching specialized models and expert baselines, and with non-canonical residues – where ML approaches fail – achieving comparable performance. Critically, prompt engineering alone often fails to generate Rosetta actions, demonstrating that environment design is essential for integrating LLM agents with specialized software. Our results show that properly designed environments enable LLM agents to make scientific software accessible while matching specialized tools and human experts.

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23.
medRxiv (Medicine) 2026-06-24

Pembrolizumab, Temozolomide and HSPPC-96 Vaccine in Newly Diagnosed Glioblastoma Post-Chemoradiation: Results from a Multi-institutional, Phase 2, Randomized, Placebo-Controlled Trial

Authors:
Ozer↗B. H↗Lindhorst↗S. M↗Merrell↗R. T↗Trevino↗C. R↗Rudnick↗J. D↗Avgeropoulos↗N. G↗…

Background: GBM is one of the most common and most aggressive brain tumors in adults, and upfront standard of care treatment has limited efficacy. Immune checkpoint inhibitor strategies have significantly improved outcomes in various solid tumors but have not proven effective in GBM, suggesting other strategies may be needed to realize their full potential. Methods: GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation. Results: 90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe. Conclusions: Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy. Trials Registration: ClinicalTrials.gov identifier: NCT03018288

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24.
Nature Biotechnology 2026-06-23

Efficient generation of epitope-targeted antibodies with Germinal

Authors:
Luis S. Mille-Fragoso↗

Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Meanwhile, computational methods for antibody design have been limited by low success rates that require resource-intensive screening. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing. Our method co-optimizes antibody structure and sequence by integrating a structure predictor with an antibody-specific protein language model to perform de novo design of functional complementarity-determining regions onto a user-specified structural framework. When tested against four diverse protein targets, Germinal designed functional antibodies across all targets and binder formats, testing only 43–101 designs for each antigen. Validated designs also exhibited robust expression in mammalian cells and high sequence and structural novelty. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal achieves epitope-targeted, de novo complementarity-determining region design with high experimental success rates.

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25.
arXiv (quant-ph) 2026-06-17

Tungsten Germanide Superconducting Nanowire Single-Photon Detectors with Saturated Internal Detection Efficiency at Wavelengths up to 29 {\mu}m

Authors:
Benedikt Hampel↗Daniel Kuznesof↗Andrew S. Mueller↗Sahil R. Patel↗Robert H. Hadfield↗Emma E. Wollman↗Matthew D. Shaw↗Dirk Schwarzer↗Alec M. Wodtke↗Khalid Hossain↗Allison V. Mis↗Alexana Roshko↗…

arXiv:2511.20868v2 Announce Type: replace-cross Abstract: Superconducting nanowire single-photon detectors (SNSPDs) are among the most sensitive single-photon detectors available and have the potential to transform fields ranging from infrared astrophysics to molecular spectroscopy. However, extending their performance into the mid-infrared spectral region - crucial for applications such as exoplanet transit spectroscopy and vibrational fingerprinting of molecules - has remained a major challenge, primarily due to material limitations and scalability constraints. Here, we report on the development of SNSPDs based on tungsten germanide, a novel material system that combines high mid-infrared sensitivity with compatibility for large-scale fabrication. Our detectors exhibit saturated internal detection efficiency at wavelengths up to 29 {\mu}m, while using 2.7x thicker films (8 nm vs 3 nm) and up to 4.5x wider nanowires (360 nm vs 80 nm) compared to mid-infrared-optimized SNSPDs fabricated from tungsten silicide. This advance will enable scalable, high-performance single-photon detection in a spectral region that was previously inaccessible, opening new frontiers in remote sensing, thermal imaging, environmental monitoring, molecular physics, and astronomy.

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