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01.
arXiv (CS.CL) 2026-06-12

LLMs Can Better Capture Human Judgments–With the Right Prompts

Are large language models (LLMs) bad at capturing human judgment? Two commonly stated limitations are that LLMs fail to capture full distributions of responses, and that their judgments are unstable across wording variations. We demonstrate simple prompting strategies that mitigate these limitations. Across two datasets–a U.S.-representative set of 144 moral scenarios and 38 moral beliefs from the International Social Survey Programme's Family and Changing Gender Roles module covering 32 countries–we show how simple elicitation techniques help improve AI-human alignment. First, prompting models to report standard deviations and response proportions recovers the full range of human responses better than common strategies. Second, ensuring scenarios are clear to human participants–as reflected in human confusion ratings–boosts model alignment, and LLMs can track human confusion ratings. At the same time, we find that LLMs' estimates of their own error are poorly calibrated, though they can predict human variability relatively well. These results suggest that asking better questions to LLMs can yield better answers.

02.
arXiv (CS.CL) 2026-06-18

Retell, Reward, Repeat: Reinforcement Learning for Narrative Theory-Informed Story Retelling

Counterfactual story retelling exposes LLM shortcomings in constrained narrative solution spaces where they can no longer rely on recalling memorised training data. Ground-truth-based post-training, such as SFT, fails to teach LLMs how to generate logical and rational narrative events. In this paper, we introduce Retell, Reward, Repeat (RRR), an RL-based pipeline synthesising Structuralist Narratology with scalar narrativity to teach storytelling structure. We extend the TimeTravel dataset with human-annotated stages of narrative equilibrium to evaluate reward models. By using d-RLAIF, RRR derives training signals from the narrativity of textual features without the need for reference outputs. Evaluations demonstrate that RRR-trained LLMs outperform few-shot and SFT baselines in logic, rationality, and completeness, with output quality additionally validated by blind human preference. Relying on a small, query-only dataset, RRR provides a linguistically grounded, cost-effective post-training mechanism for storytelling–a domain currently lacking effective post-training methods. RRR highlights the continued relevance of integrating established linguistic theories into contemporary NLP.

03.
medRxiv (Medicine) 2026-06-18

Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4,770 PE, 8,020 controls; 10,808 maternal, 1,982 fetal, including 1,848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across class I loci showed a protective effect in preterm PE (OR=0.82, 95%CI:0.69-0.97), with a similar pattern for HLA-A heterozygosity (OR=0.78, 95%CI:0.64-0.96). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR=1.36, 95%CI:1.03-1.79) and preterm PE (OR=1.73, 95%CI:1.13-2.73). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE etiology.

04.
medRxiv (Medicine) 2026-06-18

Guiding the development of climate counterfactuals for health impact attribution studies

Climate change detection and attribution (D&A) methods have become vital for quantifying the influence of anthropogenic forcing on the Earth's systems, including human health. Health impact attribution (HIA) studies seek to disentangle climate-driven health effects from natural variability yet are often constrained by the availability of accessible counterfactual climate scenarios. This tutorial paper presents a flexible, reproducible framework for developing counterfactual climates without reliance on computationally intensive global circulation models. We provide practical, R-based methodologies for constructing both trend-based (temperature and non-temperature) and event-based counterfactual, using a variety of techniques including model residual detrending, data-driven decomposition (e.g., Singular Spectrum Analysis and Empirical Mode Decomposition) and stochastic weather generators. The tutorial also explores the incorporation of greenhouse gas concentrations as forcing variables, rather than global mean temperature anomalies. By operationalising these methods through worked examples and an open code repository, this paper aims to build capacity within the HIA community, enhance methodological transparency, and foster interdisciplinary collaboration between climate and health researchers.

05.
PLOS Medicine 2026-05-21

Novel symptoms associated with eclampsia could improve detection and save lives

by Alice Beardmore-Gray, Andrew Shennan Eclampsia is a life-threatening complication of pre-eclampsia, yet remains difficult to predict. In this Perspective, Alice Beardmore-Gray and Andrew Shennan highlight a recent study that identifies 10 novel prodromal symptoms of eclampsia, with potential to better predict which women are at risk and therefore reduce delays in intervention.

06.
bioRxiv (Bioinfo) 2026-06-13

ProtAff: Protein Binding Affinity Prediction via LoRA-Finetuned ESM-2

Predicting the binding affinity of protein–protein interactions remains a central challenge in computational biology. Structure prediction models such as AlphaFold3 (AF3) and Boltz-2 can produce high-quality docking poses, and their confidence scores indicate structure quality, but these same scores fail to rank binding affinity among confirmed binders. Here we present ProtAff, a sequence-only affinity prediction model built on ESM-2 (650M parameters) with low-rank adaptation (LoRA) fine-tuning and a cross-attention module. ProtAff is trained using a margin ranking loss on 362,567 affinity measurements spanning 20 heterogeneous data sources, and we removed all training samples whose target sequence exceeds 50% similarity to the test target EGFR. On the AdaptyvBio EGFR benchmark (N = 55), ProtAff achieves a Spearman correlation coefficient {rho} = 0.413, outperforming the best AF3 metric ({rho} = 0.054), the best Boltz-2 metric ({rho} = -0.046), and ML-based predictors MINT ({rho} = 0.242) and CrossAffinity ({rho} = 0.216). Applied to the AdaptyvBio Nipah virus binder design competition, a pipeline incorporating ProtAff for affinity ranking produced a design with KD = 0.132 nM (2 of 5 designs confirmed binding), a 2.8-fold improvement over the competition winner. On a cross-target discrimination benchmark of 91 VHH-antigen crystal structures, ProtAff underperforms structural methods for distinguishing cognate from non-cognate pairings, indicating that sequence-based affinity models are effective for within-target ranking but not for cross-target specificity.

07.
bioRxiv (Bioinfo) 2026-06-11

GermRL: Alleviating The Germline Bias In Autoregressive Antibody Language Models Through Reinforcement Learning

Antibodies are powerful therapeutics whose antigen specificity arises from sequence diversity shaped during development. Recently, language models trained on large antibody repertoire datasets have enabled the generation and screening of novel candidates, but these models retain a strong germline bias. As AI adoption increases in therapeutic workflows, it is crucial to develop models that harness the diversity of antibodies necessary for the discovery of mutations that encode desirable properties. Previous work explored the germline bias in masked antibody language models, yet the bias in generative autoregressive language models has not yet been addressed. Here, we present GermRL, a lightweight and modular reinforcement learning (RL) framework capable of alleviating the germline bias in pre-trained antibody autoregressive language models through group relative policy optimization (GRPO). GermRL achieves consistent one-shot generation of antibodies that satisfy specified mutation thresholds from germline while maintaining structural plausibility. Under the lowest and highest mutation thresholds tested (5 and 35 mutations from germline), GermRL scores 0.992 and 0.950 pass@1, respectively, compared to 0.398 and 0.034 for the pre-trained language model. Within GermRL, we introduce a key pair of modifications to GRPO that increase training efficiency by discouraging reward hacking under our antibody application. Furthermore, comparison of RL generated and natural antibody sequences reveals how RL based optimization can explore alternative evolutionary mutational patterns and residue compositional strategies while preserving key global properties of natural antibodies, including identifiable germline assignments, embedding-level similarity and comparable developability profiles. Thus, RL-trained generative models optimized to promote antibody mutations through diversity from germline provide a promising framework for navigating the antibody sequence landscape, enabling exploration of novel yet biologically plausible candidates for therapeutic design.

08.
arXiv (CS.AI) 2026-06-16

LiteOdyssey: A Lightweight Reasoning AI Agent for Interpretable Rare-Disease Diagnosis

arXiv:2606.16149v1 Announce Type: new Abstract: Most medical AI systems improve by scaling additional machinery: more fine-tuning data, more agents, and/or larger retrieval databases. In rare-disease diagnosis, however, such scaling can produce systems that are difficult to deploy, audit, and maintain. We asked whether state-of-the-art diagnostic performance could instead be achieved by extending the reasoning chain of a single AI agent: guiding it with a diagnostic policy, developed through human-AI collaboration and augmenting with freely available biomedical tools. We introduce LiteOdyssey, a lightweight rare-disease diagnostic framework that guides reasoning language model through a clinical genetics workflow. This framework was developed through Policy Iteration with Human Feedback (PIHF) and uses dynamic access to public biomedical tools. On two challenging benchmarks that provide only patient clinical features, LiteOdyssey achieved state-of-the-art performance, with an overall disease Recall@1 of 59.3% over the combined 1,243 cases of LIRICAL (n = 370) and the PhenoPacket Store (n = 873). Both benchmarks have a high proportion of ultra-rare disease (a prevalence below 1 in 1,000,000, with ultra-rare shares of approximately 45% and 52.8%, respectively). On the more difficult PhenoPacket subset, where causal diseases were not mapped to Orphanet in our rarity-mapping pipeline, LiteOdyssey achieved 60.7% Recall@1, compared with 10.7% for the same baseline model (GPT-5.4) without tools. This performance was achieved without fine-tuning, multi-agent ensembles, or a large case-retrieval database. Gains were also observed in the following: on cases never seen during development, on a private cohort of real-world rare disease patients, and on a smaller open-weights model. LiteOdyssey suggests a path toward rare-disease AI systems that are accurate, easier to deploy, and more transparent for physician review.