Despite theoretical advantages, causal methods for Gene Regulatory Network (GRN) inference from single-cell RNA-seq data consistently fail to match or outperform correlation-based baselines in many realistic benchmarks, a persistent puzzle which casts doubt on the value of causality for this task. We argue that existing benchmarks are insufficiently controlled to answer this question because they evaluate on real or semi-real data where multiple pathologies co-occur, confounding failure modes, and obscuring the specific conditions under which different inference methods excel or fail. To address this gap, we introduce a controlled diagnostic framework that isolates seven biologically motivated pathologies (dropout, latent confounders, cell-type mixing, feedback loops, network density, sample size, and pseudotime drift) and measure how six representative methods spanning three inference paradigms degrade as each pathology intensifies. Across 6,120 controlled experiments, we find that causal methods genuinely dominate in clean and structurally favorable regimes, but specific pathologies (notably dropout and latent confounders) selectively neutralize their advantages. We further introduce an errortype decomposition that reveals methods with similar aggregate accuracy commit qualitatively different errors. To probe whether single-pathology effects persist when multiple stressors co-occur, we perform an interaction sweep over the three most impactful pathologies and find that their joint effects are sub-additive, while also exposing density-conditional cross-overs invisible to single-dial analysis. Our findings offer a nuanced understanding of when and why different methods succeed or fail for GRN inference, providing actionable insights for method development and practical guidance for practitioners.3

Magnification shift is a major obstacle to robust histopathology classification, because models trained on one imaging scale often generalize poorly to another. Here, we evaluated this problem on the BreaKHis dataset using a strict patient-disjoint leave-one-magnification-out protocol, comparing supervised baseline, baseline augmented with DCGAN-generated patches, and a gradient-reversal domain-general model designed to preserve discriminative information while suppressing magnification-specific variation. Across held-out magnifications, the domain-general model achieved the strongest overall discrimination and its clearest gain was observed when 200X was held out. By contrast, GAN augmentation produced inconsistent effects, improving some folds but degrading others, particularly at 400X. The domain-general model also yielded the lowest Brier score at 0.063 vs 0.089 at baseline. Sparse embedding analysis further revealed that domain-general training reduced average signature size more than three-fold (306 versus 1,074 dimensions) while preserving equivalent predictive performance (AUC: 0.967 vs 0.965; F1: 0.930 vs 0.931). It also increased cross-fold signature reproducibility from near-zero Jaccard overlap in the baseline to 0.99 between the 100X and 200X folds. These findings show that calibrated, compact, and transferable representations can be learned without added architectural complexity, with clear implications for the reliable deployment of computational pathology models across heterogeneous acquisition settings.

Varied number of bit split: To generate the samples in this split, we first sampled the number ofbits, then sampled each bitindividually from auniform Bernoulli distribution. Variednumberofonessplit: Here, we fixed the number of bits at30. NaturalLanguageParityDataset: Inorder totapinto thenatural language understanding capabilities of pretrained language models, we situated the parity task as a"coin flip problem". We trained baseline models with the same parameter count on a modified version of the variable assignment dataset where the order of the operations were randomly shuffled. We used greedy decoding in all of our experiments (including few-shot scratchpad ones).

We define an easy and hard split.

Moreover,doctors explicitly explore severepathologies before potentially ruling them out from the differential, especially in acute care settings. Finally, for doctors to trust a system's recommendations, they need to understand how the gathered evidences led to the predicted diseases.