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Cost analysis of a sequential antimicrobial therapy protocol in patients with pneumonia: A multicenter study

PLoS ONE Flaviane Gecler Parreira, Juan Vicente da Cunha Leal, Aline Correa de Araujo et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354476

Pneumonia is one of the leading causes of hospitalization and mortality due to infectious diseases and is also responsible for a substantial proportion of antimicrobial prescriptions. This study aimed to analyze the clinical outcomes and the economic implications associated with a sequential antimicrobial in hospitalized patients with pneumonia. This was a multicenter, retrospective, observational cost analysis study conducted in four private Brazilian hospitals between January 2022 and December 2023. A total of 185 medical records from patients undergoing the sequential therapy protocol were included. Clinical outcomes, length of hospital stay, acceptability among physicians of pharmacist-led interventions for switching the route of administration, and the direct costs related to medications and human resources were assessed according to a microcosting methodology. Among the included patients, 74.6% transitioned to the oral route, and 88.4% showed a positive clinical outcome. Sequential therapy was associated with a significant reduction in mean length of stay (10.1 vs. 14.7 days; p = 0.024) and was associated with 55% lower treatment costs, corresponding to an estimated cost avoidance of US$ 4,529.96. The findings suggest that sequential antimicrobial therapy is an safe and economically advantageous strategy that contributes to the rational use of antimicrobials and the optimization of hospital resources.

Intentional incisions on Neolithic Obsidian arrowheads from Central Anatolia: A techno-functional and iconographic approach

PLoS ONE Alice Vinet, Denis Guilbeau Jul 28, 2026 DOI: 10.1371/journal.pone.0354715

Incised obsidian arrowheads form a rare and geographically restricted artifact class, known exclusively from Neolithic Central Anatolia between the late 8th and 7th millennia BCE. These artifacts, marked by deliberate incisions, have been variously interpreted as symbolic or identity-related. This study presents a comprehensive techno-functional and iconographic analysis of eleven newly identified specimens from Tepecik-Çiftlik (Cappadocia, Türkiye), adding to the regional corpus of 43 known examples. The incised arrowheads were found in dwelling sites, a chipped stone workshop, and during surveys.Provenance analysis by macroscopic characterization confirms their production from local Cappadocian obsidian sources (Göllüdağ, Nenezi Dağ). The incisions are highly variable, and show no correlation with raw material, chaîne opératoire , typology, or use-wear. Incisions were executed both before and after final retouching, suggesting no fixed production stage. Comparative analysis reveals parallels between sites, indicating a possible shared but flexible iconographic repertoire. The rarity of these artifacts, their relation to domestic contexts, and their absence beyond Central Anatolia point to the hypothesis of a shared cultural practice. The analysis of these incised arrowheads, along with the limited archaeological and ethnographic comparisons available, calls for a cautious interpretation. While they have been suggested as personal or collective markers (e.g., hunters’ marks), this hypothesis requires further evidence. The expanded dataset from Tepecik-Çiftlik refines the understanding of this peculiar practice, highlighting its persistence despite broader cultural change.

The unique Efg1 fungal virulence regulon in the catheterized bladder environment

Proceedings of the National Academy of Sciences Alyssa Ann La Bella, Nicholas C. Gervais, Kurt N. Kohler et al. Jul 28, 2026 DOI: 10.1073/pnas.2533309123

Urinary catheterization, a frequent procedure in hospitals, nursing homes, and other healthcare facilities, is a primary driver of nosocomial infections. The most common of these are catheter-associated urinary tract infections (CAUTIs), which often progress to severe complication, sepsis, and ultimately death. The fungus Candida albicans is a primary causative agent of CAUTIs; yet, its tissue-specific pathogenesis remains poorly understood, which complicates development of efficient treatments. While Efg1 is a known virulence driver in CAUTI, its specific downstream targets within the unique bladder environment have not been defined. Here, we identify and validate the EFG1 regulon that is active during conditions that mimic the human catheterized bladder and, additionally, confirm the regulon by transcriptional profiling of catheters retrieved from patients with C. albicans infection. We found that this urine-specific signature is highly conserved in clinical samples, with Efg1-dependent genes being among the most robustly induced transcripts during active human infection. Furthermore, we characterized two of these key factors, ECE1 and EED1 , validating their roles in infection both in vitro in human urine and in vivo using a CAUTI mouse model. Elucidating this tissue-specific regulon offers a strategic roadmap for the development of targeted therapies to mitigate these ever-increasing life-threatening fungal infections.

Factors affecting lung cancer stage at diagnosis and receipt of surgery in Ontario: A population-based analysis

PLoS ONE Nader M. Hanna, Saad Shakeel, Gileh-Gol Akhtar-Danesh et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354330

Lung cancer is the leading cause of cancer mortality in Canada, with most cases diagnosed at advanced stage. Despite universal healthcare, social determinants of health may impact stage at diagnosis and access to treatment. We examined the association between these factors, stage at diagnosis, and receipt of surgery in Ontario. We conducted a population-based retrospective cohort study of adults diagnosed with lung cancer in Ontario from 2007–2023 using linked administrative health data. Stage was obtained from the Ontario Cancer Registry. Factors included income, primary care attachment, immigration status, geographic region, and distance to the nearest cancer centre. Logistic regression identified factors associated with stage IV diagnosis. Among 106,867 patients with available stage data, 52.6% were diagnosed with stage IV disease; 19.1% were stage I. Patients without a family physician were significantly more likely to present with stage IV cancer compared with those fully rostered (62.1% vs 51.5%; adjusted OR 1.55, p < 0.001). Females had lower likelihood of stage IV diagnosis than males (OR 0.85, p < 0.001). Increasing household income was associated with reduced likelihood of stage IV disease (OR 0.92 for highest vs lowest quintile, p < 0.001). Immigrants were less likely to be diagnosed with stage IV cancer than non-immigrants (OR 0.77, p = 0.001). Frailty was associated with higher odds of stage IV disease (OR 1.01, p = 0.009). Surgical resection was performed in 56.1% of patients with stage I disease and 1.4% with stage IV disease. Receipt of surgery decreased with advancing age (27.0% < 50 years vs 7.3% ≥ 80 years), higher comorbidity burden (25.4% with 0 vs 5.0% with ≥5 comorbidities), and lack of primary care attachment. Marked social inequities in lung cancer stage at diagnosis and surgical treatment persist in Ontario. Interventions addressing primary care attachment and upstream social determinants may improve early detection and access to curative therapy.

Statutory construction and interpretation for AI

Proceedings of the National Academy of Sciences Luxi He, Nimra Nadeem, Michel Liao et al. Jul 28, 2026 DOI: 10.1073/pnas.2509766123

AI systems are increasingly governed by natural language rules, yet a key challenge arising from reliance on language remains underexplored: interpretive ambiguity. As in legal systems, ambiguity arises both from how these rules are written and how they are applied. But while legal systems use institutional safeguards to manage such ambiguity, such as transparent appellate review policing interpretive constraints, rule-based AI alignment pipelines lack comparable protections. Different interpretations of the same rule can lead to inconsistent model behavior. Drawing on U.S. legal theory, we identify key gaps in current rule-based alignment pipelines by examining how legal systems constrain ambiguity at both the rule creation and rule application steps. We then propose a computational framework that formalizes interpretive ambiguity as constrained entropy minimization and introduces two law-inspired mechanisms: 1) a rule refinement pipeline that minimizes interpretive disagreement by revising ambiguous rules (analogous to agency rulemaking or iterative legislative action), and 2) prompt-based interpretive constraints that reduce disagreement during rule application (analogous to legal canons that guide judicial discretion). We evaluate our framework on a 5,000-scenario subset of the WildChat dataset and show that both interventions significantly improve judgment consistency across a panel of reasonable interpreters. Our approach offers a step toward systematically managing interpretive ambiguity, an essential step for building more robust, law-following AI systems.

Preoperative anxiety: Is it affected by preoperative counseling and surgical technique?

PLoS ONE Syed F. Javaid, Hamed Aljanaahi, Saleh AlSeiari et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354701

Background Preoperative anxiety (PA) is a common psychological response that can adversely affect patient satisfaction and surgical complications and outcomes. To reduce these effects, several studies were conducted to identify the factors that influence the severity of PA; however; none of the studies have examined the relationship between the PA and factors related to preoperative surgical and anesthetic counseling and the type of surgical technique. Methods A cross-sectional questionnaire-based study was carried out between November 2023-January 2024, involving patients aged 18 years or older who were scheduled for surgical procedures at our institute. Anxiety levels were assessed using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). PA was stratified into low (<11) and high (≥11) anxiety based on the total anxiety (both anesthesia- and surgery-related) scores. Results The prevalence of clinically significant PA was 39.7%. In addition to the previously identified factors such as female gender, younger age and unemployment status, other factors which were also associated with higher PA included fewer pre-operative surgical consultations, longer duration of each surgical consultation, undergoing laparoscopic procedures instead of open surgery, referral to an internist for further evaluation of preexisting medical conditions and use of general anesthesia or uncertainty about the type of anesthesia (P < 0.05 for all). However, the number of anesthetic consultations and the surgeon’s level of experience were not significantly associated with PA. Interestingly, using illustrations and figures during consultations was also associated with higher PA (P < 0.05) while searching the internet for more information, did not have an effect. Conclusions Preoperative anxiety remains a significant concern and was associated with factors related to gender, employment status, preoperative surgical and anesthetic counseling, surgical technique and type of anesthesia. These findings might help in formulating targeted interventions to reduce preoperative anxiety and improve surgical outcomes.

Glucocorticoid receptors in oligodendrocyte precursor cells regulate hippocampal network plasticity and stress-induced behavior in mice

Proceedings of the National Academy of Sciences Lorenzo Mattioni, Giulia Poggi, Celine Gallagher et al. Jul 28, 2026 DOI: 10.1073/pnas.2614867123

Glucocorticoid receptors (GRs) are key mediators of how the stress hormone glucocorticoids (GCs) shape postnatal brain development and adaptive plasticity. Because GC signaling is critical during this period, postnatal GC concentrations are tightly regulated in the brain, whereas excessive levels of circulating GCs can disrupt developmental trajectories and increase the risk of psychiatric disorders later in life. GR function influences multiple neural cell types, but its cell-specific roles, particularly early in development, remain poorly understood. Oligodendrocyte precursor cells (OPCs), which generate myelinating oligodendrocytes and actively modulate neuronal networks, express GRs and can therefore respond to fluctuations in GC levels. Although excessive GC exposure during early life adversity has been linked to changes in OPC development, the physiological role of GR signaling specifically within OPCs remains unclear. To address this, we conditionally deleted GRs in postnatal OPCs in mice to investigate the role of physiological GC signaling in OPC proliferation and maturation, as well as in neuronal network activity and behavior. This deletion resulted in reduced oligodendrocyte and myelinated axon density in the hippocampus, sex-specific alterations in hippocampal activity and long-term potentiation following acute challenge, and impairments in memory formation in adulthood. Our findings reveal an OPC-specific role for GRs and suggest that physiological GR activity in the oligodendrocyte lineage contributes to normal hippocampal plasticity, learning, and memory.

Beyond speed and strategy: A configurational analysis of collective attention to post-match institutional discourse in the UEFA Champions League

PLoS ONE Zhichen Ling, Xinlei Ren, Bingquan Luo Jul 28, 2026 DOI: 10.1371/journal.pone.0354175

Post-match institutional communication has become a visible component of elite football events, yet comparable official messages can receive very different levels of public attention. This study examines UEFA Champions League post-match communication as a configurational problem rather than as a linear consequence of response speed or message strategy. Using 25 theoretically selected focal club-event observations from the 2017–2018–2022–2023 seasons, it calibrates one outcome set, High_News, from a Raw_Mentions-derived media-visibility proxy and four causal-condition sets: High_Delay, High_Shock, High_Stakes, and High_TemplateDeviation. The analysis uses conservative coding of template deviation, separating response latency from communication form. The intermediate solution identifies one stable high-stakes legacy pathway and one sensitivity-dependent crisis-minimalism pathway. The stable pathway combines non-delayed response, low outcome shock, high match stakes, and trophy/legacy-oriented template deviation. The crisis-minimalism pathway is retained in the baseline solution but is interpreted cautiously because it depends on medium-confidence coding and changes under strict recoding. The analysis of ~High_News confirms causal asymmetry: non-membership in the high-attention set is not simply the inverse of the pathway(s) associated with High_News. The findings contribute to sport communication research by showing how event structure and institutional discourse combine to produce bounded media visibility, while avoiding population-level claims about all football matches or internal platform algorithms.

Identification of a conserved gene family with an essential role in <i>Leishmania</i> parasite–insect vector adhesion

Proceedings of the National Academy of Sciences Barrack O. Owino, Ryuji Yanase, Katerina Pruzinova et al. Jul 28, 2026 DOI: 10.1073/pnas.2603653123

Adhesion to tissues and surfaces is used by pathogens to avoid clearance, maintain infections, and facilitate transmission. An important example is the adhesion of the Leishmania parasite to the stomodeal valve of its insect vector, the sand fly, which is important for life cycle progression, and occurs through its flagellum via a cytoskeletal adhesion complex. While three essential kinetoplastid-insect adhesion proteins (KIAPs) are known, the overall proteome of the adhesion complex is obscure. Using TurboID-tagged KIAP3 combined with proteomics and light microscopy, we have identified additional proteins associated with the adhered flagellum, including multiple members of the Adhesion Related NTPase-like Domain (ARND) family, of which the canonical member is KIAP4, described here. Phylogenetic analysis of the ARND family showed it is conserved across the kinetoplastids, and we demonstrate that Trypanosoma congolense paralogs localize to the adhered flagellum in that parasite. Deletion of KIAP4 severely impaired haptomonad adhesion, with the mutant parasites unable to colonize the sand fly stomodeal valve. Our work provides details of the molecular machinery essential for vector colonization and shows that these proteins have a conserved function in other kinetoplastid parasites.

Distribution and efficacy of ingested dsRNA targeting tissue-specific genes in the Argentine ant, Linepithema humile

PLoS ONE Mathew A. Dittmann, Grzegorz Buczkowski, Brock A. Harpur Jul 28, 2026 DOI: 10.1371/journal.pone.0323988

With the increasing availability of genomic and transcriptomic information within Formicidae, the investigation of gene function has become possible within ants. However, eusocial life history renders the generation of mutagenic strains of ants difficult outside of specific ant lineages that can induce reproductive behavior in workers. RNA interference (RNAi) remains a practical option to investigate gene function within their genomic context in ant lineages that do not exhibit reproductive behavior in workers. This method can be leveraged to investigate the large odorant receptor (OR) gene families present in ant clades. However, ORs tend to be expressed in a tissue-specific fashion, and the capability of dsRNA to achieve knockdown of genes exhibiting localized expression remains uncertain. In this study, we use fluorescently labelled dsRNA to track the spread of dsRNA through the worker body, qPCR to verify that dsRNA can knockdown gene expression in the antennae, and behavioral trials to verify that knockdown of ORs affects nestmate recognition. Our results show ingested dsRNA is able to reach the antennae and knock down odorant coreceptor ( orco ) expression in the antennae. We determined that orally-administered dsRNA is capable of being spread systemically and knocking down tissue-specific genes. These findings show that RNAi may be useful in investigating the influence of ORs in eusocial insect nestmate recognition.

Correction for Fassl et al., Regulation of the immune CD155–CD226–TIGIT axis by cyclin D-CDK4/6

Proceedings of the National Academy of Sciences Jul 28, 2026 DOI: 10.1073/pnas.2623204123

A dual self-regulatory platform for programmable biosynthesis of L-lysine-derived alkaloids

Proceedings of the National Academy of Sciences Pingxin Lin, Sang Yup Lee Jul 28, 2026 DOI: 10.1073/pnas.2612082123

L-lysine-derived alkaloids represent a structurally diverse and pharmacologically significant class of nitrogen-containing natural products with broad utility as pharmaceutical agents and industrial platform chemicals. However, their microbial biosynthesis has been persistently hindered by precursor imbalance and the rigid regulatory architecture of native metabolic pathways. Here, we report a programmable biosynthetic platform for the de novo production of L-lysine-derived alkaloids directly from glucose in Corynebacterium glutamicum . Through systematic metabolic rewiring, we developed a high-flux cadaverine-producing chassis that achieves robust accumulation of the central nitrogenous precursor required for downstream alkaloid assembly. Leveraging this chassis, we designed a dual metabolite-responsive regulatory circuit that autonomously orchestrates malonate assimilation, malonyl-CoA supply, and alkaloid formation without external inducers. This self-regulating strategy enabled the production of pelletierine at 6.11 ± 0.06 g/L in fed-batch fermentation, representing the highest reported microbial titer to date. Extending this platform through selective short-chain dehydrogenase/reductase catalysis, we further achieved the stereoselective conversion of 1-piperideine and pelletierine into piperidine (8.60 ± 0.16 g/L) and sedridine (3.71 ± 0.19 g/L), respectively—constituting a heterologous microbial production of either compound. Collectively, this work establishes a versatile, programmable, and industrially tractable platform for L-lysine-derived alkaloid biosynthesis, providing a compelling foundation for the sustainable microbial production of diverse alkaloid intermediates and drug leads.

Continuity and change in US legal tradition: Evidence from judicial citation communities

Proceedings of the National Academy of Sciences Elliott Ash, Caterina Chiopris, Robert Mahari et al. Jul 28, 2026 DOI: 10.1073/pnas.2509763123

Legal doctrine is often described as evolving case by case while preserving coherent legal traditions. We introduce a method for identifying and tracing such traditions by applying the Louvain community-detection algorithm to the complete U.S. federal judicial citation graph (1790–2024; 760,000 opinions linked by 8.3 million citations). The resulting citation communities are unsupervised, blind to court labels and topical taxonomies, yet they form meaningful empirical groupings: In validation exercises, they recover known institutional structure and capture coherent substantive and procedural approaches to law. Using these communities as empirical units, we study how legal traditions evolve and respond to legislative change. We show that the introduction of pivotal federal statutes shifts citation patterns toward newer precedent, indicating that legislation can disrupt established traditions and redirect the development of case law.

When children shape their families: Evocative effects analysis of 40,000 trios from the Norwegian Mother, Father and Child Cohort Study

Proceedings of the National Academy of Sciences Evelina T. Akimova, Agnes Fauske, Ruth Eva Jørgensen et al. Jul 28, 2026 DOI: 10.1073/pnas.2532642123

Family demographic behavior is often studied as a response to structural conditions or parental characteristics, yet children may themselves shape key family trajectories through evocative gene–environment correlations. This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). By analyzing ~ 40,000 genotyped mother–father–child trios, we test whether children’s polygenic indices (PGIs) predict parents’ subsequent fertility, partnership dissolution, and transition to marriage. Accounting for parental PGIs, we found limited evidence for evocative effects across most traits. The exception was that higher child ADHD PGI predicted increased parental partnership dissolution (7% [CI = 2.9 to 11.8%] per SD), especially in families with daughters (11% [CI = 4.9 to 18%] per SD), higher socioeconomic status (15% [CI = 7.7 to 23.2%] per SD), and older maternal age at first birth (10% [CI = 3 to 17%] per SD). The main source of variation is the socioeconomic dimension where child-driven effects are stronger in higher-SES families. The study provides evidence for evocative gene–environment correlations in family demography, demonstrating the importance of child-to-parent effects in shaping family trajectories.

A phosphorylation cascade involving ZmSnRK2.10–ZmRIPK2–ZmWRKY38 attenuates drought response by derepressing <i>ZmSUS2</i> in maize

Proceedings of the National Academy of Sciences Tingting Wang, Aifang Ma, Jinkui Cheng et al. Jul 28, 2026 DOI: 10.1073/pnas.2602740123

Drought stress severely limits crop productivity, with transcription factors (TFs) playing pivotal roles in plant adaptation. Here, we identify the maize TF ZmWRKY38 as a positive regulator of drought tolerance. CRISPR/Cas9-mediated knockout of ZmWRKY38 increased plant sensitivity to drought compared with the wild type. We demonstrate that ZmWRKY38 binds to the promoter of the sucrose synthase gene ZmSUS2 and represses its transcription. Conversely, ZmSUS2 functions as a negative regulator of drought tolerance, as zmsus2 mutants displayed enhanced drought resistance. Moreover, we identified ZmRIPK2 (RPM1-induced protein kinase 2), a plasma membrane-localized receptor-like cytoplasmic kinase that also negatively regulates drought responses. Under abscisic acid (ABA) or drought stress, ZmSnRK2.10 phosphorylates and activates ZmRIPK2, triggering its partial translocation into the nucleus. Within the nucleus, ZmRIPK2 interacts with and phosphorylates ZmWRKY38, impairing its DNA-binding capacity and thereby alleviating transcriptional repression of ZmSUS2 . Together, our results reveal a negative feedback loop in which ZmRIPK2-mediated phosphorylation of ZmWRKY38 fine-tunes the drought stress response through modulation of ZmSUS2 expression. This mechanism illustrates how ABA signaling attenuates drought responses to balance stress adaptation with normal growth.

Magnetotaxis in an anaerobic ciliate via tripartite syntrophy

Proceedings of the National Academy of Sciences Mitali Chitnis, Leon Kaub, Peter Vďačný et al. Jul 28, 2026 DOI: 10.1073/pnas.2609513123

Magnetotaxis has evolved independently numerous times in bacteria, whereby genetically controlled biomineralization of nano-crystalline magnets results in swimming along Earth’s magnetic field lines. Compared to magnetotactic bacteria (MTB), evolutionary mechanisms of magnetotaxis as a trait in eukaryotes remain poorly understood. Here, we report a magnetotactic ciliate, Tropidoatractus magnetotacticus sp. nov., that acquires magnetotaxis via syntrophy. T. magnetotacticus exhibits magnetotaxis due to the magnetic moment of internal ferrimagnetic magnetite (Fe 3 O 4 ) nanoparticles forming ellipsoidal “necklace-shaped” parallel chains. Electron microscopy revealed T. magnetotacticus hosts numerous internal rod-shaped bacteria containing these magnetosome chains. Consistent with this, a genomic population of MTB (Thermodesulfobacteriota) in magnetically sorted T. magnetotacticus cells was found that encoded and expressed a magnetosome gene cluster responsible for magnetosome Fe 3 O 4 biomineralization closely related to that of the ectosymbiont “ Candidatus Desulfarcum epimagneticum.” T. magnetotacticus also housed a second genomic population affiliated with the endosymbiotic methanogen Methanoregula . Metatranscriptomes of sorted T. magnetotacticus cells show eukaryotic hydrogenosomal Fe-hydrogenase gene expression, and expression of genes encoding proteins in an electron transport chain indicative of H 2 -producing mitochondria-related organelles. Active gene expression of energy metabolism pathways indicates a tripartite syntrophic network whereby anaerobic fermentation products from T. magnetotacticus are consumed by two syntrophic partners: MTB producing the magnetosome chains and hydrogenotrophic methanogens. Our findings show how magnetotaxis can emerge as a trait in eukaryotes via syntrophic cooperation.

Ligand regulation and function of preformed EGFR dimers

Proceedings of the National Academy of Sciences Yuhong Zuo, Hillel T. Schwartz, Kahlil Walker et al. Jul 28, 2026 DOI: 10.1073/pnas.2602436123

Receptor tyrosine kinases (RTKs) are key therapeutic targets in cancer, diabetes, and other diseases. With only one transmembrane α-helix—compared with seven in G-protein-coupled receptors—RTKs are thought to be activated by ligand-induced dimerization. Complicating this view, however, one of the best-studied RTKs, the insulin receptor (IR), forms allosterically regulated covalent dimers. Moreover, noncovalent “preformed” dimers have frequently been reported for the sequence-related epidermal growth factor receptor (EGFR), one of the first RTKs for which ligand-induced dimerization was described. Here, we describe a detailed structural view of a preformed EGFR dimer. Using cryo-EM, we describe how the Caenorhabditis elegans EGFR (LET-23) dimerizes without ligand. We show that preformed dimer formation modulates ligand sensitivity in vivo, but is not required for signaling itself. We also elucidate substantial ligand-induced conformational changes in LET-23 required for signaling. Our structures reveal unexpected similarities between regulation of LET-23 and the IR, suggesting that LET-23 may represent an evolutionary “missing link” between the IR and EGFR families. In the absence of ligand, intermolecular interactions within preformed receptor dimers hold the extracellular juxtamembrane regions far apart to separate the intracellular kinase domains so that they remain inactive. Ligand binding disrupts these interactions to remove the restraints on the kinase domains, which then can associate to become activated. Our analysis further suggests a unified model for the allosteric activation of preformed RTK dimers that has important implications for understanding cell-surface EGFR.

There is no free benchmark: An institutional view of legal AI benchmarking

Proceedings of the National Academy of Sciences Neel Guha, Andy K. Zhang, Christine Tsang et al. Jul 28, 2026 DOI: 10.1073/pnas.2509757122

Despite substantial excitement around the use of AI in law, little information exists on the performance and associated risks of the domain’s widely marketed tools. Recent work, for instance, has demonstrated the significant potential for “hallucinations”—wherein models make up facts, law, and precedent—leading Chief Justice Roberts to spotlight this risk in his annual report on the judiciary. We argue that there is a need for public AI benchmarking in law. First, relative to other AI application domains, the legal AI ecosystem lacks legibility—there is little information about the design and performance of many commercial legal AI systems. Legal AI has not benefited from the types of benchmarking that have catalyzed, measured, and informed AI innovation and responsible use in other domains. Second, we articulate the challenges of the institutional design of benchmarking. We illustrate how benchmarks can be captured, watered down, and abused. Careful institutional design around the why, who, what, and how of benchmarking will be critical to navigate difficult tradeoffs of transparency, objectivity, expertise, and resources. Third, addressing legal AI’s illegibility requires matching institutional models to available resources and constraints. Rather than advocating for a single “best” approach to benchmarking, we show how benchmarking strategies depend on available resources.

Measuring disparate impact in human and machine decisions

Proceedings of the National Academy of Sciences Jongbin Jung, Sam Corbett-Davies, Johann D. Gaebler et al. Jul 28, 2026 DOI: 10.1073/pnas.2509765122

Empirical analyses have grown increasingly important in discrimination litigation with the greater availability of detailed data on individuals and decisions. A popular analytic strategy is to estimate disparities after adjusting for observed covariates, typically with a regression model, in hopes of ferreting out discriminatory intent. This approach, however, is ill-suited to auditing algorithms that are now commonly used to aid decisions, which typically do not include race or other legally protected factors as inputs. Motivated by legal understandings of disparate impact, we introduce an approach that aims to measure “unjustified” disparities in both human and machine decisions. Our method, which we call risk-adjusted regression, proceeds in three steps. In the first step, we combine all available information in a machine learning model to estimate the value, or inversely, the risk, of taking a certain action, such as approving a loan application or hiring a job candidate. Second, we measure disparities in decisions after adjusting for these risk estimates alone. Finally, in the third step, we assess the sensitivity of results to potential mismeasurement of risk. We demonstrate this approach on a detailed dataset of 2.2 million police stops of pedestrians in New York City, and show that traditional statistical tests of discrimination can substantially understate the magnitude of (risk-adjusted) racial disparities.

Continuity in geometric intuition between humans and monkeys

Proceedings of the National Academy of Sciences Jialin Li, Isabelle Boni, Logan R. Sandwick et al. Jul 28, 2026 DOI: 10.1073/pnas.2532934123

Geometric intuition is regarded as a hallmark of human intelligence. Humans hold a unique advantage in recognizing geometric shapes with Euclidean features (e.g., parallelism, symmetry) and have more sophisticated geometric concepts than nonhuman primates. A popular explanation for this human distinctiveness is that humans rely on discrete, symbolic features to encode geometric shapes, while other primates depend only on continuous perceptual features. The current study challenges this view. We used a match-to-sample task to test whether monkeys share geometric representations with humans. We found that monkeys combined high-level perceptual representations with abstract symbolic representations like humans, suggesting a graded, quantitative continuity in geometric intuition across species rather than a categorical, qualitative divide. Importantly, monkeys showed stronger reliance on symbolic features when processing rotated geometric shapes than preschoolers did with unrotated shapes, indicating that what appears to be symbolic representation may largely emerge from rotation-invariant encoding. These results challenge the hypothesis of human uniqueness in geometric intuition and suggest that its origins in humans are rooted in abstractions shared with primates.