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01.
arXiv (CS.AI) 2026-06-24

Can Scale Save Us From Plasticity Loss in Large Language Models?

arXiv:2606.24752v1 Announce Type: new Abstract: The loss of plasticity - the ability of a network to learn new information after having already learned older information - is a fundamental challenge in creating artificial neural networks capable of continual learning. Although this phenomenon has been known for decades, it has mostly been studied in older, relatively small architectures and rarely in natural-language domains. To determine whether loss of plasticity remains a problem in the modern transformer-based LLM paradigm, we study plasticity loss in GPT-style Transformer models trained on a multilingual continual learning problem. Consistent with prior work, we find evidence of plasticity loss across models ranging from 5M to 314M non-embedding parameters, as measured by deterioration on a held-out Vietnamese probing task. We further find that the onset of plasticity loss follows a predictable scaling law, growing sublinearly with model size. These results suggest that larger models may delay the measurable effects of plasticity loss, but that increasing parameter count alone is likely to be insufficient to completely prevent it. We also find evidence of plasticity loss under stationary multilingual training, challenging the view that the phenomenon is exclusive to continual learning with abrupt task changes. Overall, our results suggest that even large Transformer language models trained on natural-language will eventually lose the ability to efficiently adapt to new data after sufficiently long training, in both continual and stationary settings.

02.
medRxiv (Medicine) 2026-06-19

Hyperleukocytosis and outcomes in pediatric B-cell acute lymphoblastic leukemia: A report from the REDIAL Consortium

Hyperleukocytosis (white blood cell [WBC] count >100 000/uL) at diagnosis is an important prognostic risk factor in pediatric acute lymphoblastic leukemia (ALL), though its significance with contemporary therapy is unclear. We analyzed 1 826 pediatric ALL patients from a multi-institution cohort to determine whether hyperleukocytosis independently predicts outcomes using multivariable Cox proportional hazard modeling. Hyperleukocytosis occurred in 211 patients (12%), with 121 having B-ALL, and showed no prognostic significance in T-ALL patients. In B-ALL, 5-year event-free survival (EFS) was 65% versus 89% for non-hyperleukocytosis patients, and overall survival (OS) was 78% versus 93%. After adjustment for age, cytogenetic risk, central nervous system disease status, and treatment site, hyperleukocytosis remained an independent predictor of end-of-induction minimal residual disease (MRD) positivity (odds ratio 2.53 [95% confidence interval [CI]: 1.71-3.94; p

03.
arXiv (CS.CL) 2026-06-11

SOMA-SQL: Resolving Multi-Source Ambiguity in NL-to-SQL via Synthetic Log and Execution Probing

Natural language interfaces to databases aim to translate user questions into executable SQL, yet remain brittle in real-world settings where questions are underspecified and schemas are large and ambiguous. Ambiguity across user questions, database schemas, and model interpretations are central failure modes in NL2SQL, leading to misaligned intent, incorrect schema grounding, and erroneous SQL generation. Existing approaches rely on human clarification or treat ambiguity as a schema representation problem, but these do not scale nor resolve ambiguity autonomously. We propose SOMA-SQL to automatically resolve ambiguity via targeted synthetic query log and ambiguity-driven probing. SOMA-SQL constructs synthetic query log to ground schema interpretation and guide candidate SQL generation; it then executes targeted probing queries, driven by a structured ambiguity taxonomy and candidate disagreements, to produce disambiguation evidence for final SQL selection and repair. This active approach to ambiguity discovery and resolution generalizes across unseen schemas and query distributions without human-in-the-loop. Experiments on six public benchmarks demonstrate that SOMA-SQL improves execution accuracy by 13.0% on average over state-of-the-art baselines, with gains of up to 16.7% on ambiguous questions.

04.
arXiv (quant-ph) 2026-06-16

Exact Many-body Quantum Dynamics in One-Dimensional Baths via Collective Spins

arXiv:2505.00588v2 Announce Type: replace Abstract: Computing the exact dynamics of many-body quantum systems becomes intractable as system size grows. Here, we present a symmetry-based method that provides an exponential reduction in the complexity of a broad class of such problems $\unicode{x2014}$ qubits coupled to one-dimensional electromagnetic baths. We identify conditions under which partial permutational symmetry emerges and exploit it to group qubits into collective multi-level degrees of freedom, which we term ''superspins.'' These superspins obey a generalized angular momentum algebra, reducing the relevant Hilbert space dimension from exponential to polynomial. Using this framework, we efficiently compute many-body superradiant dynamics in large arrays of qubits coupled to waveguides and ring resonators, showing that $\unicode{x2014}$ unlike in conventional Dicke superradiance $\unicode{x2014}$ the total spin length is not conserved. At long times, dark states become populated. We identify configurations where these states exhibit metrologically useful entanglement. Our approach enables exact treatment of complex dissipative dynamics beyond the fully symmetric limit and provides a rigorous benchmark for approximate numerical methods.

05.
arXiv (CS.CL) 2026-06-24

PETRA: Transforming Web Text for Petroleum-Engineering Domain Adaptation

Petroleum-engineering search exposes a supervision gap for strong general retrievers: relevant evidence exists in public web text, but domain relevance labels are scarce. To address this gap, we propose PETRA, a large-scale Petroleum Engineering Text for Retrieval Adaptation dataset and pipeline that converts noisy public web data into a curated domain corpus and synthetic supervision for dense retrieval and reranking. PETRA contains 1.36M curated chunks, approximately 2B token equivalents, $\approx$859k, embedding training rows from $\approx$224k anchors, and roughly 400k teacher-scored reranker candidate rows. Its construction combines high-recall energy-domain curation, an energy-domain classifier with 98.4% test accuracy, chunk-grounded query generation, LLM-written hard negatives, and retrieval-mined candidate lists. PETRA improves first-stage in-domain Normalized Discounted Cumulative Gain (nDCG) from 0.703 to 0.763 through score fusion. Reranker adaptation improves the public Earth Science benchmark by 44% relative and a six-task reasoning-intensive panel by 23%. Failed training recipes show that high train-holdout accuracy on synthetic labels does not predict retrieval gains; retrieval-mined data helps only after being repackaged as teacher-scored candidate lists sampled from the inference-time candidate distribution.

06.
medRxiv (Medicine) 2026-06-16

Doctors, Wellness Influencers, and Probiotic Gummies: A Cross-Sectional Analysis of Gut Health Claims and Financial Conflicts on TikTok

TikTok has emerged as a major source of health information, yet concerns persist regarding the accuracy of content and influence of financial conflicts. Gut health content is particularly vulnerable to misinformation. This study examined the relationship between creator profession ("medical" versus "non-medical") and the quality of gut health claims and the presence of financial conflicts on TikTok. We conducted a cross-sectional study of 412 TikTok creator accounts identified using the search terms "guthealth," "gutcleansing," and "digestion." One video per creator was analyzed. Creator profession was categorized as medical or non-medical. Health claim quality was coded as high, moderate, or poor. Financial conflicts (Showcase, Subscription, external links) were assessed. Modified Poisson regression was used to estimate prevalence ratios (PRs) of health claim quality (high versus poor- or moderate-quality) and financial conflicts between medical and non-medical creators, and negative binomial regression was used to evaluate associations between claim quality and number of video likes. Non-medical creators were more likely than medical creators to present poor- or moderate-quality health claims (adjusted PR: 2.33; 95% CI: 1.50-3.62). Most creators (92%) exhibited at least one financial conflict, and Showcase use was greater among non-medical creators (adjusted PR: 1.57; 95% CI: 1.02-2.42). Videos containing moderate- and poor-quality health claims received three times as many likes as videos containing high-quality claims. Non-medical creators disproportionately produced lower-quality gut health content on TikTok, and misleading claims received greater engagement. These findings highlight a misalignment between information quality and visibility, emphasizing the need for interventions promoting evidence-based health communication.

08.
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

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.

09.
medRxiv (Medicine) 2026-06-11

The impact of pre-stroke statin use on baseline corrected infarct volume and collateral perfusion

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

10.
arXiv (CS.AI) 2026-06-18

EMORSION: Examining the Impact of Audio Parameters on Emotional Responses and Immersion in Film

arXiv:2606.18266v1 Announce Type: cross Abstract: EMORSION is an exploratory proof-of-concept study examining how film audio design shapes audience emotion and immersion in acinema setting. Four film scenes were selected across the horror (2) and drama (2) genres, balanced between mainstream and independent productions. For each scene, multiple alternative audio mixes were created by systematically manipulating three core aspects of audio design, frequency (pitch), dynamics (loudness), and directionality (spatial placement). Three audience groups viewed the scenes, with each group exposed to one manipulated mix alongside a control mix for each scene. Audience responses were assessed through a triangulated multimodal framework combining self-reported emotion and immersion via a questionnaire, physiological measures including heart rate monitoring, and video-based motion tracking. The protocol successfully captured measurable, interpretable differences across audio conditions, indicating that even subtle changes in audio design can shape emotional perception and immersion. Unconventional mixes tended to produce greater variability in audience interpretation, while conventional immersive mixes were associated with stronger cross-audience agreement. These findings establish the feasibility of the EMORSION protocol and motivate larger-scale studies to characterise the role of specific audio parameters in shaping audience experience.

11.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

12.
medRxiv (Medicine) 2026-06-16

High-Risk Anti-Seizure Medication Use in Childbearing-Age People with Epilepsy in a Taenia solium Endemic Region

Background: People of childbearing potential with epilepsy in regions endemic for Taenia solium, where neurocysticercosis (NCC) is highly prevalent, represent a vulnerable population due to the elevated burden of epilepsy and resource limitations. Clinical practice in these settings remains poorly characterized. This study characterized anti-seizure medication (ASM) prescribing patterns by medication risk profiles among people of childbearing potential with epilepsy in Northern Peru, a region highly endemic for T. solium. Methods: Participants were drawn from a prospective, population-based epilepsy cohort in Tumbes, Peru (2006 to 2020). The analytic population included females with epilepsy aged 15 to 49 years. The primary outcome was pregnancy-associated ASM risk of congenital malformations and adverse neurodevelopmental outcomes. ASMs were classified as ''Established Low Risk'' (lamotrigine, levetiracetam), ''Possible Risk/Inadequate Data'' (carbamazepine, phenobarbital, phenytoin), and ''Established High Risk'' (valproic acid). Prescription patterns were examined in relation to demographic and clinical characteristics. Results: Among 1,975 individuals with epilepsy, 685 were people of childbearing potential. Approximately 34.9% met criteria for probable or definite NCC. Most ASM prescriptions were in the ''Possible Risk/Inadequate Data'' category (87.0%), and 12.8% received ''Established High Risk'' medications. In multivariable analysis, high-risk prescribing was associated with prior ASM use and polytherapy. Discussion: People of childbearing potential with epilepsy were predominantly treated with carbamazepine, phenytoin, phenobarbital, and valproate, reflecting local ASM availability. Despite evidence supporting lamotrigine and levetiracetam in pregnancy, prescribing patterns reflect local formulary constraints. These findings highlight a gap between guideline recommendations and real-world prescribing in resource-limited settings, underscoring the need for context-specific treatment strategies.

13.
bioRxiv (Bioinfo) 2026-06-18

Accounting for allelic diversity and multicopy gene detection improves the accuracy of antibiotic resistance genotypic determination

Background Genomic prediction of antimicrobial resistance (AMR) relies on the accurate detection of resistance genes or allelic variants of core genes from raw or assembled genomes sequences. For several bacterial species and antibiotics, AMR genotype-phenotype discrepancies are common, indicating that important sources of error remain unresolved. For Enterococcus faecium, we focused on identifying the sources of discrepancies for tetracycline resistance, for which genotypic detection had shown particularly low accuracy. We investigated the effect of structural variation in antibiotic resistance genes (ARGs), including gene duplications, truncations, interruptions, and mixed configurations of complete and partial gene copies, as a source of genotype-phenotype discrepancies from short-read data. We conduct further extended investigations to other antibiotic families and into another bacterial species: Escherichia coli. Methods We analyzed collections of E. faecium and E. coli genomes, integrating high-quality complete assemblies, simulated Illumina short reads, and matched AMR phenotypic data. The integrity, copy number, and allelic diversity of ARGs were examined for multiple antibiotic classes, and their impact on ARG detection and accuracy of AMR determination was assessed using several commonly used bioinformatic tools (SRST2, ARIBA and AMRFinderPlus). Results For E. faecium, after ruling out the effect of specific tet allelic variants on tetracycline susceptibility, we found that the integrity and copy number of tet(M) had a major effect on detection accuracy. Duplicated and incomplete ARGs are also common in E. faecium genomes, particularly for macrolides (erm(B)) and aminoglycosides (ant(6)-Ia and aph(3')-IIIa). In E. coli, similar patterns were observed for tet(A), erm(B) and aminoglycoside-associated genes (aph(3')-IIIa and ant(6)-Ia). Across ARGs in both species, short-read mapping methods wrongly reported interrupted genes as complete in some instances, while assembly-based methods often failed to resolve complete copies of duplicated genes. Detection accuracy improved when tools were adapted to account for gene integrity and when extended AMR databases incorporating species-specific alleles were included. Conclusions Our findings reveal that bioinformatic limitations in dealing with ARG copy number and completeness, and in accounting for allelic variation, underly a substantial source of genotype-phenotype errors, highlighting the need for improved AMR databases and bioinformatic tools that consider these factors to achieve reliable genomic prediction of AMR.

14.
medRxiv (Medicine) 2026-06-22

Reliable quantification of renal function from frozen blood samples

BACKGROUND: Differences in renal function may affect Alzheimer disease (AD) blood biomarker levels independent of AD pathology. Although renal function was unaccounted for in foundational AD blood biomarker studies, there is potential to address this through quantification of estimated glomerular filtration rate (eGFR) from frozen serum and plasma samples. However, the validity of eGFR evaluation from long-term frozen blood samples is unknown. METHODS: Adults aged 50-85 with at least 2 vascular risk factors were recruited from vascular surgery or cardiology clinics in Tucson, Arizona from 2022-2025. Individuals with creatinine assessments in point-of-care whole blood (POC-WB) and frozen serum and plasma samples using the iSTAT (Abbott) were included. eGFR was calculated using the 2021 CKD-EPI creatinine equation without race. Agreement between POC-WB and frozen blood samples was assessed using Cohen's kappa with linear weights. RESULTS: 134 participants (mean [SD] age: 72.6 [7.5] years, 39.6% female, 23.1% chronic kidney disease) had POC-WB eGFR available. Frozen serum and plasma samples had strong agreement with POC-WB for eGFR (Kw= 0.90-0.95, P

15.
arXiv (CS.AI) 2026-06-11

Irresponsible AI: big tech's influence on AI research and associated impacts

arXiv:2512.03077v2 Announce Type: replace-cross Abstract: The accelerated development, deployment and adoption of artificial intelligence systems has been fuelled by the increasing presence of big tech in the AI field. This trend has been accompanied by growing ethical concerns and intensified societal and environmental impacts. This position paper argues that irresponsible AI development is strongly driven by big tech's influence and involvement in the field. First, we examine the growing and disproportionate influence of big tech in AI research and argue that its drive for scaling and general-purpose systems is fundamentally at odds with the responsible, ethical, and sustainable development of AI. Second, we review key current environmental and societal negative impacts of AI and trace their connections to big tech's influence. Third, we discuss the underlying economic forces driving big tech's actions. Finally, as a call to action, we invite AI researchers to counter big tech's influence in irresponsible AI development through strategies that build on the responsibility of implicated actors and collective action.

16.
arXiv (quant-ph) 2026-06-25

Coherent Control of Quantum-Dot Spins with Cyclic Optical Transitions

arXiv:2509.14445v2 Announce Type: replace Abstract: Solid-state spins are promising as interfaces from stationary qubits to single photons for quantum communication technologies. Semiconductor quantum dots have excellent optical coherence, exhibit near unity collection efficiencies when coupled to photonic structures, and possess long-lived spins for quantum memory. However, the incompatibility of performing optical spin control and single-shot readout simultaneously has been a challenge faced by almost all solid-state emitters. To overcome this, we leverage light-hole mixing to realize a highly asymmetric lambda system in a negatively charged heavy hole exciton in Faraday configuration. By compensating GHz-scale differential Stark shifts, induced by unequal coupling to Raman control fields, and by performing nuclear-spin cooling, we achieve quantum control of an electron-spin qubit with a $\pi$-pulse contrast of 97.4% while preserving spin-selective optical transitions with a cyclicity of 471 (50). We demonstrate this scheme for both GaAs and InGaAs quantum dots, and show that it is compatible with the operation of a nuclear quantum memory. Our approach thus enables repeated emission of indistinguishable photons together with qubit control, as required for single-shot readout, photonic cluster-state generation, and quantum repeater technologies.

17.
arXiv (CS.CV) 2026-06-15

Dual Cross-Attention Siamese Transformer for Rectal Tumor Regrowth Assessment in Watch-and-Wait Endoscopy

Increasing evidence supports watch-and-wait (WW) surveillance for patients with rectal cancer who show clinical complete response (cCR) at restaging following total neoadjuvant treatment (TNT). However, accurate methods to early detect local regrowth (LR) from follow-up endoscopy images during WW are essential to manage care and prevent distant metastases. Hence, we developed a Siamese Swin Transformer with Dual Cross-Attention (SSDCA) to combine longitudinal endoscopic images at restaging and follow-up and distinguish cCR from LR. SSDCA leverages pretrained Swin Transformers to extract domain agnostic features and enhance robustness to imaging variations. Dual cross attention is implemented to emphasize features from the paired scans without requiring any spatial alignment to predict response. SSDCA as well as Swin-based baselines were trained using image pairs from 135 patients and evaluated on a held-out set of image pairs from 62 patients. SSDCA produced the best balanced accuracy (81.76% $\pm$ 0.04), sensitivity (90.07% $\pm$ 0.08), and specificity (72.86% $\pm$ 0.05). Robustness analysis showed stable performance irrespective of artifacts including blood, stool, telangiectasia, and poor image quality. UMAP clustering of extracted features showed maximal inter-cluster separation (1.45 $\pm$ 0.18) and minimal intra-cluster dispersion (1.07 $\pm$ 0.19) with SSDCA, confirming discriminative representation learning. Code and weights available at: https://github.com/Jotanator/SSDCA

18.
arXiv (quant-ph) 2026-06-17

Closest Accessible Symmetry reduction: a tool for Hamiltonian interpolation analysis

arXiv:2606.18161v1 Announce Type: new Abstract: We introduce a framework for analysing the spectrum of Hamiltonian interpolations without heavily relying on discretising the interpolation parameter. The method is based on the concept of accessible symmetries: a problem-class-dependent family of certifiable reflections that induce bipartitions of the Hilbert space. At each step, the interpolation Hamiltonian is projected onto the sectors of the accessible symmetry that is closest to being satisfied, yielding a hierarchy of weakly coupled pseudo-eigenspaces together with explicit residual couplings between them. We show that this representation captures qualitative signatures of quantum phase transitions, provides estimates of their location, and offers insights into their nature. The quality of the approximation is controlled by the compatibility between the accessible symmetry family and the problem instance. Although motivated in spirit by adiabatic quantum computation, our approach applies more broadly to the study of Hamiltonian phase diagrams, providing a new perspective on the spectral reorganisation of many-body quantum systems.

19.
bioRxiv (Bioinfo) 2026-06-22

Dynamic balance of sparse flux vectors for efficient simulation of culture dynamics and metabolic network reduction

Dynamic Flux Balance Analysis (DFBA) enables simulation of microbial culture dynamics under changing environmental conditions, but remains computationally expensive for tasks such as parameter calibration and fermentation optimization when applied using genome-scale metabolic models (GEMs). To address this challenge, we introduce Dynamic Flux Vector Balancing (DFVB), a reformulation of DFBA that solves an equivalent problem using a pre-computed, sparse basis of flux solutions that reduces the dimensionality of the internal optimization problem without information loss. Notably, DFVB provides a compact, interpretable representation of flux states that can readily identify dynamically inactive pathways and enable simulation-based automatic metabolic network reduction. We showed that DFVB produces the same culture dynamics as DFBA across multiple model scales and conditions, and identifies inactive reactions more accurately than Flux Variability Analysis (FVA) when compared to transcriptomic data profiles. Furthermore, computational performance analyses demonstrated that integrating DFVB with solver warm-start strategies and model reduction enhances computational efficiency relative to DFBA, yielding up to 3-fold reductions in simulation time for large-scale metabolic models. Finally, kinetic parameter estimation of culture dynamics with DFVB in two fermentation scenarios using a large-scale yeast GEM reached equal or higher prediction fidelity and narrower confidence intervals than DFBA, indicating improved parameter identifiability and robustness. Together, these results position DFVB as a scalable, robust, and biologically coherent framework for dynamic metabolic modeling, easing the integration of GEMs for culture dynamics simulation.

21.
medRxiv (Medicine) 2026-06-23

Attention and memory in Parkinson's disease: a discriminant analysis approach

Background. Cognitive impairment in Parkinson's disease (PD) is highly prevalent and heterogeneous. Assessing multiple cognitive domains is challenging and risks redundancy. This study evaluated whether a discriminant analysis approach could optimize the selection of specific tasks and measures for identifying attention and memory deficits in PD. Methods. Thirty PD patients and 25 cognitively unimpaired (CU) controls completed four experimental tasks: two assessing attention (flanker and spatial Stroop), one for recognition memory, one for working memory (n-back). Following group-level difference analyses, a discriminant analysis was performed to identify which tasks, and performance metrics possessed the highest sensitivity for distinguishing PD patients from CU individuals. Results. At the group level, PD patients exhibited significantly worse conflict costs in both attention tasks and lower sensitivity scores (d') in the recognition memory task compared to CU controls. The discriminant analysis revealed that time-based measures from the spatial Stroop task and the sensitivity score from the recognition memory task provided the highest discriminating power to differentiate between the two groups. Conclusion. These findings suggest that cognitive deficits in PD can be identified with high diagnostic accuracy using a targeted subset of metrics, eliminating the need for extensive and redundant neuropsychological testing batteries for attention and memory, without needing an extensive number of cognitive tasks for attention and memory.

22.
medRxiv (Medicine) 2026-06-22

Maternal-Fetal immune networks and viral signatures in the healthy amniotic cavity

The intrauterine environment has traditionally been viewed as a privileged site protected by the placental barrier. However, emerging evidence suggests that early in utero microbial exposure may prime the developing fetal immune system. Here, using target-enriched metagenomics and high-dimensional proteomics, we characterized the intra-amniotic viral landscape and immune networks in 114 healthy pregnancies including both normal and anomalous fetuses. We identify a sparse yet heterogeneous human viral signature in 26% of samples, predominantly composed of Herpesviridae, Polyomaviridae, and Picornaviridae. Although viral reads abundance was associated with fetal abnormalities, viral detection generally did not induce overt inflammatory activation, supporting a state of immune homeostasis within the amniotic cavity. Instead, viral presence was associated with subtle and selective immune modulation, including altered inducible antimicrobial peptide expression (HBD-2 and HBD-3), coupled with an attenuation of regulatory cytokines. Our results further reveal that the amniotic immune environment is primarily governed by gestational age, transitioning from a Th1-predominant "alert" phase to innate-readiness preceding parturition. These findings suggest that fragments of viral genetic material within the amniotic cavity may contribute to fetal immune instruction without triggering overt inflammation, providing a foundational framework for understanding how "silent" viral-exposure during gestation influences the developmental origins of neonatal immunity.

23.
arXiv (CS.AI) 2026-06-16

AnonShield: Scalable On-Premise Pseudonymization for CSIRT Vulnerability Data

arXiv:2606.15650v1 Announce Type: cross Abstract: We present AnonShield, a high-throughput, on-premise pseudonymization system that combines GPU-accelerated NER, streaming processing, caching, and schema-aware configuration. Evaluated on datasets up to 550 MB (70,951 records), AnonShield reduces processing time from over 92 hours to under 10 minutes (up to 738x speedup) while achieving up to 94.2% F1-score and 96.7% recall. Our results show that scalable pseudonymization of vulnerability data is feasible without sacrificing analytical utility, enabling compliant data sharing in operational CSIRT environments.

24.
bioRxiv (Bioinfo) 2026-06-24

Systematic benchmarking of multi-modal approaches for tumor-naive ctDNA detection and quantification

Longitudinal monitoring of circulating tumor DNA (ctDNA) has emerged as a promising framework for characterizing treatment response dynamics in cancer. Scalable tumor-naive approaches for quantifying ctDNA often involve whole-genome sequencing (WGS) or DNA methylation profiling, but their comparative performance and capacity for complementary integration remain poorly understood. Here we systematically benchmarked tumor-naive WGS- and methylation-based ctDNA quantification methods using plasma from 150 patients with colorectal, lung and breast cancer. Using paired high-depth WGS and EM-seq data, we generated 40,000 in silico samples and evaluated detection accuracy, limits of detection (LoD) and quantification (LoQ) across cancer types and sequencing depths (0.1x-30x). We further assessed single- and multimodal method combinations, identifying conditions under which integrated approaches enhance analytical performance for detection and quantification relative to single modalities. This benchmark delineates key performance trade-offs and provides a practical framework to support method development and guide future research applications in ctDNA-based biomarker studies.

25.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.