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01.
medRxiv (Medicine) 2026-06-22

GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Introduction: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined. Objectives: To investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant. Methods: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n=22,372PD vs n=8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n=4,712PD vs 38,733Controls). Clinico-demographic details of affected variant carriers were collated. Results: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n=9/2,757; 0.33%) but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio:5.1; 95%CI:2.3-10.7; p=2.89x10-5). Affected carriers (mean age at onset:56.3+-12.5 years) had additional occurrence of dystonia, while dementia was rare. Conclusions: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.

02.
arXiv (CS.AI) 2026-06-19

The MAMA-MIA Challenge: Advancing Generalizability and Fairness in Breast MRI Tumor Segmentation and Treatment Response Prediction

arXiv:2603.01250v2 Announce Type: replace-cross Abstract: Breast cancer is the most frequently diagnosed malignancy among women worldwide and a leading cause of cancer-related mortality. Dynamic contrast-enhanced magnetic resonance imaging plays a central role in tumor characterization and treatment monitoring, particularly in patients receiving neoadjuvant chemotherapy. However, existing artificial intelligence models for breast magnetic resonance imaging are typically developed and evaluated using heterogeneous datasets, study populations, and assessment protocols, making direct comparison difficult and limiting understanding of model robustness across institutions and clinically relevant patient subgroups. The MAMA-MIA Challenge was designed to address these challenges by providing a standardized benchmark for the joint evaluation of primary tumor segmentation and prediction of pathologic complete response using pre-treatment magnetic resonance imaging only. The training cohort comprised 1,506 patients from multiple institutions in the United States, while evaluation was conducted on an external test set of 574 patients from three independent European centers to assess cross-continental and cross-institutional generalization. A unified scoring framework combined predictive performance with subgroup consistency across age, menopausal status, and breast density. Twenty-six international teams participated in the final evaluation phase. Results demonstrate substantial performance variability under a common external evaluation framework and reveal trade-offs between overall accuracy and subgroup fairness. The challenge provides standardized datasets, evaluation protocols, and public resources to promote the development of robust and equitable artificial intelligence systems for breast cancer imaging.

03.
arXiv (CS.CL) 2026-06-16

A Systematic Evaluation of Large Language Models for PTSD Severity Estimation: The Role of Contextual Knowledge and Modeling Strategies

Large language models (LLMs) are increasingly being used in a zero-shot (generative) fashion to assess mental health conditions, yet we have limited knowledge on what factors affect their accuracy. In this study, we use a clinical dataset of natural language narratives and self-reported PTSD severity scores from 1,437 individuals to comprehensively evaluate the performance of 11 state-of-the-art LLMs. To understand the factors affecting model's assessment accuracy, we systematically varied (i) contextual knowledge prompted to the models like subscale definitions, distribution summary, and interview questions, and (ii) modeling strategies including zero-shot vs few shot, amount of reasoning effort, model sizes, structured subscales vs direct scalar prediction, output rescaling and nine ensemble methods. Our findings indicate that (a) LLMs are most accurate when provided with detailed construct definitions and context of the narrative, even exceeding human raters agreement with self-reported scores; (b) increased reasoning effort leads to better estimation accuracy; (c) performance of open-weight models (Llama, DeepSeek) plateaus beyond 70B parameters while closed-weight (gpt-o3-mini, gpt-5) alternatives improve with newer generations; and (d) best performance is achieved when ensembling a supervised model with the zero-shot LLMs. Beyond agreement with self-reports, LLMs' estimates discriminated PTSD severity from depression, anxiety, and alcohol use, and prospectively predicted future mental healthcare expenditure. Together, these results suggest that contextual knowledge and modeling strategies meaningfully affect accuracy and clinical utility of LLM-based assessments of PTSD severity.

04.
arXiv (quant-ph) 2026-06-12

Toward quantum-noise-limited interferometric measurements of optical nonlinearity in vacuum

arXiv:2602.10896v2 Announce Type: replace-cross Abstract: Quantum Electrodynamics predicts that the vacuum must behave as a nonlinear optical medium: the vacuum optical index should increase when it is stressed by intense electromagnetic fields. The DeLLight (Deflection of Light by Light) project aims to measure it by using intense and ultra-short laser pulses. The experiment uses a Sagnac interferometer to amplify the tiny deflection signal of a low-intensity probe pulse crossing the vacuum refractive-index gradient produced by an external high-intensity pump pulse. The measurement of the amplified signal by a CCD camera requires a high spatial resolution, which is limited by the ultimate quantum noise of the CCD. However, interferometric phase noise induced by the mechanical vibrations of the interferometer is also amplified and degrades spatial resolution. To overcome this, we propose a new method named High-Frequency Phase Noise Suppression (HFPNS), based on the addition of a delayed replica (5 ns) of the probe pulse. The delayed pulse, which is not affected by the pump but is subject to the same vibration noise, enables offline subtraction of correlated phase noise. In this work, we present an experimental proof-of-concept on a prototype interferometer operating with a limited amplification factor ($\mathcal{A}\simeq25$), about 10 times smaller than the required value of the final experiment. We have succeeded in reducing phase noise by a factor of 40, resulting in a residual noise level 2.3 times higher than the expected quantum noise. The residual noise is linked to delay-line instabilities and incident beam pointing fluctuations present during these tests. This result validates HFPNS as a robust method for future quantum-noise-limited interferometric measurements of vacuum optical nonlinearity, though additional stabilization and higher interferometric amplification are still needed.

05.
arXiv (CS.AI) 2026-06-11

"That's AI Slop, You Bot!" Studying Accusations, Evidence, and Credibility in Online Discourse Towards LLM-Generated Comments

arXiv:2606.12073v1 Announce Type: cross Abstract: Generative AI has made fluent prose cheap to produce, breaking the old promise to readers that good writing meant real thinking. How have readers responded, and what can this tell us about changing anti-AI attitudes? We analyzed 25 million comments from Hacker News and Reddit (2023-2026), combining LLM judgment on 7,500 sampled accusations of AI use, sentiment trajectories, speech-act coding of 300 confirmed accusations of AI use, and a matched-control test of accused versus non-accused parent comments. We found that the pejorative-label share of accusations rose more than tenfold on both platforms while a placebo vocabulary of pre-2022 inauthenticity terms (shill, astroturf) did not. This shift reflected a fast-growing trend of branding any suspicious or seemingly inauthentic prose as "AI slop". The slop frame now constitutes 94 percent of pejorative mentions, with the dominant comments shifting in tone from mockery toward gatekeeping and structural protest. The key surprise comes from a matched-control test which found that prose features that statistically distinguish AI from human text do not predict which human text gets accused as AI. The new accusations work as social gatekeeping of perceived authenticity without actually screening for AI. This research extends signaling theory by showing that substitute signals used socially can grow even when inaccurate if the underlying detection problem cannot be solved at the non-expert level. It shows that AI's effects on writing from the reader side are distinct from those on the production (writer) side. Detection technology cannot resolve this dynamic because the social function of accusations is increasingly to perform social gatekeeping and in-group signaling as opposed to identifying AI-generated writing.

06.
medRxiv (Medicine) 2026-06-10

Prediction of immunotherapy response using live tumor fragments from routine clinical biopsies

Functional ex vivo assays using live tumor tissues have demonstrated strong predictive accuracy for response to immune checkpoint inhibitors (ICIs) but are not scalable, requiring manual processing of large resections collected at academic centers. Here, an ex vivo live tumor fragment (LTF) platform was developed using standard-of-care biopsies from 228 patients with suspected malignancy collected across prospective, multicenter observational trials and biobanks. Hierarchical clustering of ICI-mediated changes in cytokine production identified two groups: responders and nonresponders. A binary classifier (elive index) using 8 cytokines achieved an AUC of 0.99 for cluster prediction. elive index correctly predicted clinical benefit in 93% (26/28) of patients (P = 3.2x10-5) and accurately identified 83% (10/12) of objective responders. Critically, elive responders were identified among biomarker-negative patients, highlighting the platform as a scalable approach that complements existing companion diagnostics and expands the population of patients identified to benefit from ICI therapy.