Surgical clipping and endovascular treatments for small or very small anterior communicating artery aneurysms: A comparative pooled analysis.

INTRODUCTION: Small and very small anterior communicating artery (ACoA) aneurysms pose a complex challenge in neurosurgery and interventional neuroradiology due to their critical location and potential for severe consequences upon rupture. Surgical clipping has been a traditional approach, but it presents challenges requiring precision and expertise. Endovascular treatment has emerged as an alternative, offering minimally invasive techniques with potential advantages. This study aims to comprehensively compare outcomes and efficacy between surgical clipping and endovascular treatment for small or very small ACoA aneurysms. OBJECTIVES: We aimed to perform a meta-analysis of small or very small anterior communicating artery aneurysms comparing surgical clipping and endovascular treatments. METHODS: A systematic review and meta-analysis were conducted, including studies reporting on both treatment modalities. Eligible studies were identified through PubMed, Cochrane Library, and Embase databases. Pooled analyses with 95% confidence intervals were used to compare treatment effects, and statistical analysis followed PRISMA guidelines. RESULTS: Thirteen studies with 637 patients were included. Endovascular treatment, predominantly coiling, was performed in 60.3% of patients, while 39.7% underwent surgical management. Endovascular treatment exhibited an 18% retreatment rate, contrasting with 0% in the surgery group. Mortality rates were 3% and 6% for endovascular and surgical treatments, respectively. Overall complications occurred in 1.8% of patients, with intraoperative rupture and cerebral infarction being the most common. CONCLUSION: In summary, our study indicates a comparable outcome between surgical clipping and endovascular treatment for small ACoA aneurysms, with the former showing a lower retreatment rate. Decision factors include surgeon expertise, healthcare context, and patient age. Further research is needed to refine treatment strategies, considering variations in aneurysm status and evolving techniques.

Modulation of anxiety-like behavior in galactooligosaccharide-fed mice: A potential role for bacterial tryptophan metabolites and reduced microglial reactivity.

Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice and humans. However, the biological pathways behind these behavioral changes are not well understood. To begin to study these pathways, we utilized C57BL/6 mice that were fed a standard diet with or without GOS supplementation for 3 weeks prior to testing on the open field. After behavioral testing, colonic contents and serum were collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS significantly reduced anxiety-like behavior (i.e., increased time in the center) and decreased cytokine gene expression (Tnfa and Ccl2) in the prefrontal cortex. Notably, time in the center of the open field was significantly correlated with serum methyl-indole-3-acetic acid (methyl-IAA). This metabolite is a methylated form of indole-3-acetic acid (IAA) that is derived from bacterial metabolism of tryptophan. Sequencing analyses showed that GOS significantly increased Lachnospiraceae UCG006 and Akkermansia; these taxa are known to metabolize both GOS and tryptophan. To determine the extent to which methyl-IAA can affect anxiety-like behavior, mice were intraperitoneally injected with methyl-IAA. Mice given methyl-IAA had a reduction in anxiety-like behavior in the open field, along with lower Tnfa in the prefrontal cortex. Methyl-IAA was also found to reduce TNF-α (as well as CCL2) production by LPS-stimulated BV2 microglia. Together, these data support a novel pathway through which GOS reduces anxiety-like behaviors in mice and suggests that the bacterial metabolite methyl-IAA reduces microglial cytokine and chemokine production, which in turn reduces anxiety-like behavior.

Assessing genomics confidence and learning needs in Australian nurses and midwives: an educational program evaluation.

Introduction: The mainstreaming of genomics across healthcare specialties necessitates that all nurses and midwives have a high literacy in genomics. Methods: We aimed to design, develop, implement and evaluate a genomics education workshop for nurses and midwives using action research principles. Results: Registered nurses and midwives completed an online survey regarding genomics confidence and learning needs (n = 274). The results of this survey were used to develop the genomics education workshop. The workshop was run three times (n = 105) with evaluation data being collected both before and after each workshop. Significant improvements in confidence across all learning domains was found following the workshops (p < 0.001). A desire for more education across all learning domains except for genetics knowledge was also identified (p < 0.001). Discussion: Genomics education workshops were found to increase the confidence of nurses and midwives across a range of specialties. Nurses and midwives also expressed a desire for further education in genomics.

The artificial intelligence advantage: Supercharging exploratory data analysis.

Explorative data analysis (EDA) is a critical step in scientific projects, aiming to uncover valuable insights and patterns within data. Traditionally, EDA involves manual inspection, visualization, and various statistical methods. The advent of artificial intelligence (AI) and machine learning (ML) has the potential to improve EDA, offering more sophisticated approaches that enhance its efficacy. This review explores how AI and ML algorithms can improve feature engineering and selection during EDA, leading to more robust predictive models and data-driven decisions. Tree-based models, regularized regression, and clustering algorithms were identified as key techniques. These methods automate feature importance ranking, handle complex interactions, perform feature selection, reveal hidden groupings, and detect anomalies. Real-world applications include risk prediction in total hip arthroplasty and subgroup identification in scoliosis patients. Recent advances in explainable AI and EDA automation show potential for further improvement. The integration of AI and ML into EDA accelerates tasks and uncovers sophisticated insights. However, effective utilization requires a deep understanding of the algorithms, their assumptions, and limitations, along with domain knowledge for proper interpretation. As data continues to grow, AI will play an increasingly pivotal role in EDA when combined with human expertise, driving more informed, data-driven decision-making across various scientific domains. Level of Evidence: Level V - Expert opinion.

Minimally invasive keyhole craniotomies for microsurgical clipping of cerebral aneurysms: comparative meta-analysis of the mini-pterional and supraorbital keyhole approaches.

OBJECTIVE: Axel Perneczky is responsible for conceptualizing the "keyhole" philosophy as a new paradigm of minimal invasiveness within cranial neurosurgery. Keyhole neurosurgery aims to limit approach-related traumatization and minimize brain retraction while still enabling the neurosurgeon to achieve operative goals. The supraorbital keyhole craniotomy (SOKC) and minipterional (pterional keyhole, PKC) approaches have become mainstays for clipping intracranial aneurysms. While studies have compared these approaches to the traditional pterional craniotomy for clipping cerebral aneurysms, head-to-head comparisons of these workhorse keyhole approaches remain limited. METHODS: The authors queried three databases per PRISMA guidelines to identify all studies comparing the SOKC to the PKC for microsurgical clipping of cerebral aneurysms. Of 148 unique studies returned on initial query, a total of 5 studies published between 2013 and 2019 met inclusion criteria. Where applicable, quantitative meta-analysis was performed via the Mantel-Haenszel method using Review Manager v5.4 (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Risk of bias (ROB) was assessed using the Cochrane ROBINS-I tool, and all studies were assigned a Level of Evidence (I-V). RESULTS: Across all five studies, the mean age ranged from 53.0 to 57.5 years old, and the cohort consisted of more females (n = 403, 60.6%) than males. The proportion of patients presenting with ruptured aneurysmal SAH was comparable between the SOKC and PKC cohorts (p = 0.43). Clipping rate [defined as the rate of successful aneurysm clip deployment with successful intraoperative occlusion] (OR 1.52 [0.49, 4.71], I2 = 0%, p = 0.47), final occlusion rates (OR 1.27 [0.37, 4.32], p = 0.70), and operative durations (SMD 0.33 [-0.83. 1.49], I2 = 97%, p = 0.58) were comparable regardless of approach used. Furthermore, rates of intraoperative rupture (OR 1.51 [0.64, 3.55], I2 = 0, p = 0.34), postoperative hemorrhage (OR 1.49 [0.74, 3.01], I2 = 0, p = 0.26), postoperative vasospasm (OR 0.94 [0.49, 1.80], I2 = 63, p = 0.86), and postoperative infection (OR 0.70 [0.16, 2.99], I2 = 0%, p = 0.63) were equivocal across SOKC and PKC cohorts. CONCLUSION: The PKC and SOKC approaches appear to afford comparable outcomes when used for open microsurgical clipping of cerebral aneurysms in select patients with both ruptured and unruptured aneurysms. Both are associated with excellent clipping and occlusion rates, minimal perioperative complication profiles, and favorable postoperative neurologic outcomes. Further investigations are merited so clinicians can further parse out the indications and contraindications for each keyhole approach.

A Comparison of Three Executive Function Batteries in a Preschool-Aged Sample.

There is great interest in the development of executive function (EF) in the preschool period. Accordingly, multiple performance-based measures of EF have been developed for this age group, yet little is known about how they compare to one another. This study used a large and diverse sample of 3-to-5-year-old children (N = 846), who completed subtests of the National Institutes of Health's Toolbox Cognition Battery (NTCB), the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV), and the EF Touch battery. Scores across the three batteries were compared and associations with age, income, and race/ethnicity were examined. Results revealed that (1) the three tasks were moderately correlated (r = 0.44-0.51, all p < 0.001), but children had higher mean accuracy scores on EF Touch than on the NTCB or the WPPSI-IV. (2) Mean accuracy scores on all batteries were linearly associated with child age (all F > 32.68, all p < 0.0001). (3) Comparisons by income and race/ethnicity showed lower accuracy for low-income children on the WPPSI-IV and lower accuracy for White children on the NTCB. Across all batteries, there was consistently lower accuracy for Hispanic children. In conclusion, the three batteries we examined performed similarly across several metrics. EF Touch may be more appropriate for younger children, while the NTCB performed well with older children.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

OBJECTIVES: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. TRIAL REGISTRATION NUMBER: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Tracking neuroinflammatory biomarkers in Alzheimer's disease: a strategy for individualized therapeutic approaches?

BACKGROUND: Recent trials of anti-amyloid-ß (Aß) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. MAIN BODY: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aß reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aß deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aß ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I"). CONCLUSIONS: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.

A Novel Two-Step Method for Converting Lumbar Cortical Screw to Pedicle Screw: A Case Report.

The cortical bone trajectory (CBT) technique has emerged as a minimally invasive approach for lumbar fusion but may result in pseudoarthrosis and hardware failure. This report presents a case of successful pedicle screw revision in a patient with previous failed L2 and L3 fusion using a novel "two-step" technique, including (1) drilling a new trajectory with Medtronic EM800N Stealth MIDAS Navigated MR8 drill system (Medtronic, Dublin, Ireland) and (2) placement of Solera 4.75 ATS (awl-tapped screws) with navigated POWEREASE™ (Medtronic), described here for the first time. This method involves utilizing neuronavigation and specialized instruments to safely place pedicle screws through the path of the old cortical screw trajectory, addressing the challenges associated with CBT hardware failure.

Liver surface depressions in the presence of diaphragmatic muscular bands on trans-illumination.

Traditional descriptions of liver anatomy refer to a smooth, convex surface contacting the diaphragm. Surface depressions are recognized anatomic variants. There are many theories to explain the cause of the depressions. We discuss the theory that these are caused by hypertrophic muscular bands in the diaphragm.

Hepatic grooves: An observational study at laparoscopic surgery.

BACKGROUND: In traditional descriptions, the upper surface of the liver is smooth and convex, but deep depressions are variants that are present in 5%-40% of patients. We sought to determine the relationship between surface depressions and the diaphragm. AIM: To use exploratory laparoscopy to determine the relationship between surface depressions and the diaphragm. METHODS: An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1, 2023 and January 20, 2024. A thirty-degree laparoscope was used to inspect the liver and diaphragm. When surface depressions were present, we recorded patient demographics, presence of diaphragmatic bands, rib protrusions and/or any other source of compression during inspection. RESULTS: Of 394 patients, 343 had normal surface anatomy, and 51 (12.9%) had prominent surface depressions on the liver. There was no significant relationship between the presence of surface depressions and gender nor the presence of rib projections. However, there was significant association between the presence of surface depressions and diaphragmatic muscular bands (P < 0.001). CONCLUSION: With these data, the diaphragmatic-band theory has gained increased importance over other theories for surface depressions. Further studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from All of Us cohort.

Background: Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells by blocking inhibitory pathways. Despite their efficacy, these treatments can trigger immune-related adverse events (irAEs), such as acute kidney injury (ICI-AKI), complicating patient management. The genetic predispositions to ICI-AKI are not well understood, necessitating comprehensive genomic studies to identify risk factors and improve therapeutic strategies. Objective: To identify genetic predispositions for ICI-AKI using large-scale real-world data. Methods: A systematic literature search led to 14 candidate variants related to irAEs. We performed a candidate variant association study with these 14 variants using the All of Us cohort (AoU, v7, cutoff date: 7/1/2022). A cohort for cancer patients receiving ICI and a general cohort were established to evaluate ICI-AKI risk. Logistic regression, adjusted for sex, was used to evaluate the impact of each candidate genotype, separately for self-reported and ancestry-estimated race. Kaplan-Meier survival analysis assessed the genetic effects on AKI-free survival. Results: The ICI cohort (n=414) showed a one-year AKI incidence rate of 23.2%, significantly higher than the general cohort (6.5%, n=213,282). The rs16957301 variant (chr13:100324308, T>C) in the PCCA gene was a significant risk genotype for ICI-AKI among self-reported Caucasians (Beta=0.93, Bonferroni-corrected P-value=0.047) and ancestry estimated Caucasians (Beta = 0.94, Bonferroni-corrected P-value=0.044). Self-reported Caucasians with the rs16957301 risk genotypes (TC/CC) developed AKI significantly earlier (3.6 months) compared to the reference genotype (TT, 7.0 months, log-rank P=0.04). Consistent results were found in ancestry-estimated Caucasians. This variant did not present significant AKI risks in the general cohort (Beta: -0.008-0.035, FDR: 0.75-0.99). Conclusion: Real-world evidence from the All of Us cohort suggests that, in Caucasians, PCCA variant rs16957301 is a novel AKI risk genotype specific to ICI treatment. Additional studies are warranted to validate rs16957301 as risk marker for AKI in Caucasian patients treated with ICIs and to assess its risk in other ancestral populations.

The Proton Resonance Enhancement for CEST imaging and Shift Exchange (PRECISE) family of RF pulse shapes for Chemical Exchange Saturation Transfer MRI.

Purpose: To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice. Methods: A gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains ('PRECISE'). Gradient ascent optimizations were performed for exchange rates (k ca ) = 500 s -1 , 1,500 s -1 , 2,500 s -1 , 3,500 s -1 and 4,500 s -1 and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B 1 = 4 µT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration. Results: The most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s -1 optimized pulse with ∼2.7 x improvement over Gaussian and ∼1.3x's over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice. Conclusion: A new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.

Strand asymmetry in the repair of replication dependent double-strand breaks.

Single-strand breaks (SSBs) are one of the most common endogenous lesions and have the potential to give rise to cytotoxic double-strand breaks (DSBs) during DNA replication. To investigate the mechanism of replication fork collapse at SSBs and subsequent repair, we employed Cas9 nickase (nCas9) to generate site and strand-specific nicks in the budding yeast genome. We show that nCas9-induced nicks are converted to mostly double-ended DSBs during S-phase. We find that repair of replication-dependent DSBs requires homologous recombination (HR) and is independent of canonical non-homologous end joining. Consistent with a strong bias to repair these lesions using a sister chromatid template, we observe minimal induction of inter-chromosomal HR by nCas9. Using nCas9 and a gRNA to nick either the leading or lagging strand template, we carried out a genome-wide screen to identify factors necessary for the repair of replication-dependent DSBs. All the core HR genes were recovered in the screen with both gRNAs, but we recovered components of the replication-coupled nucleosome assembly (RCNA) pathway with only the gRNA targeting the leading strand template. By use of additional gRNAs, we find that the RCNA pathway is especially important to repair a leading strand fork collapse.

Rexinoids Induce Differential Gene Expression in Human Glioblastoma Cells and Protein-Protein Interactions in a Yeast Two-Hybrid System.

Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize, and these protein-protein interactions and subsequent transactivating potential lead to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or downregulated. Expression analysis was performed in the U87 human glioblastoma cell line treated with a panel of rexinoids, and our analysis demonstrated that rexinoids with similar RXR EC50 values can have pronounced differences in differential gene expression. Rexinoid binding likely leads to distinctive RXR conformations that cause major downstream gene expression alterations via modulation of RXR interacting proteins. Yeast two-hybrid analysis of RXR bait with two RXR interacting partners demonstrates that rexinoids drive differential binding of RXR to distinctive protein partners. Physiochemical analysis of the rexinoids reveals that the molecules cluster similarly to their gene expression patterns. Thus, rexinoids with similar RXR binding affinities drive differential gene expression by stimulating additional binding patterns in RXR and its homo- and heteropartners, driven by the physicochemical characteristics of these molecules.

Scientific experimental articles are modernist stories.

This paper attempts to revive the epistemological discussion of scientific articles. What are their epistemic aims, and how are they achieved? We argue that scientific experimental articles are best understood as a particular kind of narrative: i.e., modernist narratives (think: Woolf, Joyce), at least in the sense that they employ many of the same techniques, including colligation and the juxtaposition of multiple perspectives. We suggest that this way of writing is necessary given the nature of modern science, but it also has specific epistemic benefits: it provides readers with an effective way to grasp the content of scientific articles which increases their understanding. On the other hand, modernist writing is vulnerable to certain kinds of epistemic abuses, which can be found instantiated in modern scientific writing as well.

Comparative analysis of PD-L1 expression and tumor-infiltrating lymphocytes in metaplastic breast carcinoma and gynecologic carcinosarcoma: A single-institution retrospective study.

Metaplastic breast carcinoma (MBC) and gynecologic carcinosarcoma (GCS) are rare, clinically aggressive cancers that demonstrate epithelial components and mesenchymal or sarcomatoid components. In this study, we assessed PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in MBC and GCS. Overall, PD-L1 positivity using the SP142 clone was seen in 50 % of MBC and 51.9 % of GCS cases, with PD-L1 expression in tumor cells significantly higher in MBC cases (p = 0.034), and PD-L1 expression in immune cells similar in MBC and GCS cases. PD-L1 expression was significantly higher in epithelial components than in mesenchymal components in both MBC and GCS cases (p = 0.0005). TILs were low in the majority of MBC and GCS cases (≥ 10 %) and generally correlated with PD-L1 expression; however, many PD-L1 positive cases with low TILs were seen. PD-L1 expression using the 22C3 clone was additionally assessed, with positivity seen in 62.9 % of MBC cases and 30 % of GCS cases. Concordance between SP142 and 22C3 results was seen in 62.5 % of MBC cases and 80 % of GCS cases. Overall, our findings suggest that a subset of MBC and GCS cases may benefit from immune checkpoint inhibitor therapy. Our findings also illustrate unique aspects of PD-L1 expression patterns in these tumors which may harbor additional prognostic and therapeutic significance.

Hijacking limitations of working memory load to test for composition in language.

Although language depends on storage and composition, just what is stored or (de)composed remains unclear. We leveraged working memory load limitations to test for composition, hypothesizing that decomposed forms should particularly tax working memory. We focused on a well-studied paradigm, English inflectional morphology. We predicted that (compositional) regulars should be harder to maintain in working memory than (non-compositional) irregulars, using a 3-back production task. Frequency, phonology, orthography, and other potentially confounding factors were controlled for. Compared to irregulars, regulars and their accompanying -s/-ing-affixed filler items yielded more errors. Underscoring the decomposition of only regulars, regulars yielded more bare-stem (e.g., walk) and stem affixation errors (walks/walking) than irregulars, whereas irregulars yielded more past-tense-form affixation errors (broughts/tolded). In line with previous evidence that regulars can be stored under certain conditions, the regular-irregular difference held specifically for phonologically consistent (not inconsistent) regulars, in particular for both low and high frequency consistent regulars in males, but only for low frequency consistent regulars in females. Sensitivity analyses suggested the findings were robust. The study further elucidates the computation of inflected forms, and introduces a simple diagnostic for linguistic composition.