RESUMEN

Dorsal neural tube-derived retinoic acid promotes the end of neural crest production and transition into a definitive roof plate. Here we analyze how this impacts the segregation of central and peripheral lineages, a process essential for tissue patterning and function. Localized in-ovo inhibition in quail embryos of retinoic acid activity followed by single cell transcriptomics unraveled a comprehensive list of differentially expressed genes relevant to these processes. Importantly, progenitors co-expressed neural crest, roof plate and dI1 interneuron markers indicating a failure in proper lineage segregation. Furthermore, separation between roof plate and dI1 interneurons is mediated by Notch activity downstream of retinoic acid, highlighting their critical role in establishing the roof plate-dI1 boundary. Within the peripheral branch, where absence of retinoic acid resulted in neural crest production and emigration extending into the roof plate stage, sensory progenitors failed to separate from melanocytes leading to formation of a common glia-melanocyte cell with aberrant migratory patterns. Together, the implementation of scRNA sequencing facilitated the discovery and characterization of a molecular mechanism responsible for the segregation of dorsal neural fates during development.

RESUMEN

OBJECTIVES: To examine whether somatisation, depression, anxiety, fatigue, coping dimensions, pain, physical and social function, or sociodemographic characteristics can differentiate fibromyalgia from low back pain in a cross-sectional cohort setting of our Zurzach Interdisciplinary Pain Programme. METHODS: Fibromyalgia and low back pain (not fulfilling the diagnostic criteria for fibromyalgia) were compared using the Symptom Checklist-90R (SCL-90R) Somatisation scale, the Quantification Inventory for Somatoform Syndromes (QUISS) Number of somatoform symptoms, and other standardised instruments. Standardised mean differences (SMDs) quantified the score differences, and binomial logistic regression modelling with various co-variates differentiated fibromyalgia from low back pain. RESULTS: The largest differences indicating worse health in fibromyalgia (n = 131) were in somatisation (SCL-90R: SMD=-0.971, QUISS: SMD=-0.960), followed by affective health, pain and coping (SMDs between -0.632 and -0.280). Physical and social functioning were comparable in the two conditions (n = 262 low back pain). The two somatisation scales both with odds ratios (OR)=0.966 (p≤ 0.002) plus female sex (OR = 3.396, p< 0.001) predicted 74.3% of the cases correctly (accuracy) with a positive predictive value of 65.3% and a specificity of 87.0% for fibromyalgia. In the female subsample (n = 280), the model remained stable with an accuracy of 71.9%. CONCLUSION: Somatisation stood out from all other somatic, psychosocial, and coping dimensions and sociodemographics as the one significant specific predictor distinguishing fibromyalgia from low back pain. The fibromyalgia phenotype is characterised by the generalisation of painful loci but equally prominently by generalised somatoform symptoms. Assessment of somatisation is recommended to ensure accurate identification and understanding of the multifaceted syndrome of fibromyalgia.

RESUMEN

Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a promising source of cardiac cells for disease modelling and regenerative medicine. However, current protocols invariably lead to mixed population of cardiac cell types and often generate cells that resemble embryonic phenotypes. Here we developed a combinatorial approach to assess the importance of extracellular matrix proteins (ECMP) in directing the differentiation of cardiomyocytes from human embryonic stem cells (hESC). We did this by focusing on combinations of ECMP commonly found in the developing heart with a broad goal of identifying combinations that promote maturation and influence chamber specific differentiation. We formulated 63 unique ECMP combinations fabricated from collagen 1, collagen 3, collagen 4, fibronectin, laminin, and vitronectin, presented alone and in combinations, leading to the identification of specific ECMP combinations that promote hESC proliferation, pluripotency, and germ layer specification. When hESC were subjected to a differentiation protocol on the ECMP combinations, it revealed precise protein combinations that enhance differentiation as determined by the expression of cardiac progenitor markers kinase insert domain receptor (KDR) and mesoderm posterior transcription factor 1 (MESP1). High expression of cardiac troponin (cTnT) and the relative expression of myosin light chain isoforms (MLC2a and MLC2v) led to the identification of three surfaces that promote a mature cardiomyocyte phenotype. Action potential morphology was used to assess chamber specificity, which led to the identification of matrices that promote chamber-specific cardiomyocytes. This study provides a matrix-based approach to improve control over cardiomyocyte phenotypes during differentiation, with the scope for translation to cardiac laboratory models and for the generation of functional chamber specific cardiomyocytes for regenerative therapies.

RESUMEN

This study aimed for a better understanding of the niche specification of bacteria carrying the tfd-genes for aerobic 2,4-dichlorphenoxyacetic acid (2,4-D) degradation in the rice paddy ecosystem. To achieve this, a dedicated microcosm experiment was set up to mimic the rice paddy system, with and without 2,4-D addition, allowing spatial sampling of the different rice paddy compartments and niches, i.e., the main anaerobic bulk soil and the aerobic surface water, surface soil, root surface and rhizosphere compartments. No effect of 2,4-D on the growth and morphology of the rice plant was noted. 2,4-D removal was faster in the upper soil layers compared to the deeper layers and was more rapid after the second 2,4-D addition compared to the first. Moreover, higher relative abundances of the 2,4-D catabolic gene tfdA and of the mobile genetic elements IncP-1 and IS1071 reported to carry the tfd-genes, were observed in surface water and surface soil when 2,4-D was added. tfdA was also detected in the root surface and rhizosphere compartment but without response to 2,4-D addition. While analysis of the bacterial community composition using high-throughput 16S rRNA gene amplicon sequencing did not reveal expected tfd-carrying taxa, subtle community changes linked with 2,4-D treatment and the presence of the plant were observed. These findings suggest (i) that the surface soil and surface water are the primary and most favorable compartements/niches for tfd-mediated aerobic 2,4-D biodegradation and (ii) that the community structure in the 2,4-D treated rice paddy ecosystem is determined by a niche-dependent complex interplay between the effects of the plant and of 2,4-D.

RESUMEN

Rationale: Regulatory processes of transcription factors (TFs) shape heart development and influence the adult heart's response to stress, contributing to cardiac disorders. Despite their significance, the precise mechanisms underpinning TF-mediated regulation remain elusive. Here, we identify that EBF1, as a TF, is highly expressed in human heart tissues. EBF1 is reported to be associated with human cardiovascular disease, but its roles are unclear in heart. In this study, we investigated EBF1 function in cardiac system. Methods: RNA-seq was utilized to profile EBF1 expression patterns. CRISPR/Cas9 was utilized to knock out EBF1 to investigate its effects. Human pluripotent stem cells (hPSCs) differentiated into cardiac lineages were used to mimic cardiac development. Cardiac function was evaluated on mouse model with Ebf1 knockout by using techniques such as echocardiography. RNA-seq was conducted to analyze transcriptional perturbations. ChIP-seq was employed to elucidate EBF1-bound genes and the underlying regulatory mechanisms. Results: EBF1 was expressed in some human and mouse cardiomyocyte. Knockout of EBF1 inhibited cardiac development. ChIP-seq indicated EBF1's binding on promoters of cardiogenic TFs pivotal to cardiac development, facilitating their transcriptional expression and promoting cardiac development. In mouse, Ebf1 depletion triggered transcriptional perturbations of genes, resulting in cardiac remodeling. Mechanistically, we found that EBF1 directly bound to upstream chromatin regions of cardiac hypertrophy-inducing genes, contributing to cardiac hypertrophy. Conclusions: We uncover the mechanisms underlying EBF1-mediated regulatory processes, shedding light on cardiac development, and the pathogenesis of cardiac remodeling. These findings emphasize EBF1's critical role in orchestrating diverse aspects of cardiac processes and provide a promising therapeutic intervention for cardiomyopathy.

Asunto(s)

RESUMEN

Over the past few years, more attention has been paid to jingle and jangle fallacies in psychological science. Jingle fallacies arise when two or more distinct psychological phenomena are erroneously labeled with the same term, while jangle fallacies occur when different terms are used to describe the same phenomenon. Jingle and jangle fallacies emerge due to the vague linkage between psychological theories and their practical implementation in empirical studies, compounded by variations in study designs, methodologies, and applying different statistical procedures' algorithms. Despite progress in organizing scientific findings via systematic reviews and meta-analyses, effective strategies to prevent these fallacies are still lacking. This paper explores the integration of several approaches with the potential to identify and mitigate jingle and jangle fallacies within psychological science. Essentially, organizing studies according to their specifications, which include theoretical background, methods, study designs, and results, alongside a combinatorial algorithm and flexible inclusion criteria, may indeed represent a feasible approach. A jingle-fallacy detector arises when identical specifications lead to disparate outcomes, whereas jangle-fallacy indicators could operate on the premise that varying specifications consistently yield overrandomly similar results. We discuss the role of advanced computational technologies, such as Natural Language Processing (NLP), in identifying these fallacies. In conclusion, addressing jingle and jangle fallacies requires a comprehensive approach that considers all levels and phases of psychological science.

RESUMEN

BACKGROUND: /Aims De-implementation, including the removal or reduction of unnecessary or inappropriate prescribing, is crucial to ensure patients receive appropriate evidence-based health care. The utilization of de-implementation efforts is contingent on the quality of strategy reporting. To further understand effective ways to de-implement medical practices, specification of behavioural targets and components of de-implementation strategies are required. This paper aims to critically analyse how well the behavioural targets and strategy components, in studies that focused on de-implementing unnecessary or inappropriate prescribing in secondary healthcare settings, were reported. METHODS: A supplementary analysis of studies included in a recently published review of de-implementation studies was conducted. Article text was coded verbatim to two established specification frameworks. Behavioural components were coded deductively to the five elements of the Action, Actor, Context, Target, Time (AACTT) framework. Strategy components were mapped to the nine elements of the Proctor's 'measuring implementation strategies' framework. RESULTS: The behavioural components of low-value prescribing, as coded to the AACTT framework, were generally specified well. However, the Actor and Time components were often vague or not well reported. Specification of strategy components, as coded to the Proctor framework, were less well reported. Proctor's Actor, Action target: specifying targets, Dose and Justification elements were not well reported or varied in the amount of detail offered. We also offer suggestions of additional specifications to make, such as the 'interactions' participants have with a strategy. CONCLUSION: Specification of behavioural targets and components of de-implementation strategies for prescribing practices can be accommodated by the AACTT and Proctor frameworks when used in conjunction. These essential details are required to understand, replicate and successfully de-implement unnecessary or inappropriate prescribing. In general, standardisation in the reporting quality of these components is required to replicate any de-implementation efforts. TRIAL REGISTRATION: Not registered.

RESUMEN

BACKGROUND: Within the Open Biological and Biomedical Ontology (OBO) Foundry, many ontologies represent the execution of a plan specification as a process in which a realizable entity that concretizes the plan specification, a "realizable concretization" (RC), is realized. This representation, which we call the "RC-account", provides a straightforward way to relate a plan specification to the entity that bears the realizable concretization and the process that realizes the realizable concretization. However, the adequacy of the RC-account has not been evaluated in the scientific literature. In this manuscript, we provide this evaluation and, thereby, give ontology developers sound reasons to use or not use the RC-account pattern. RESULTS: Analysis of the RC-account reveals that it is not adequate for representing failed plans. If the realizable concretization is flawed in some way, it is unclear what (if any) relation holds between the realizable entity and the plan specification. If the execution (i.e., realization) of the realizable concretization fails to carry out the actions given in the plan specification, it is unclear under the RC-account how to directly relate the failed execution to the entity carrying out the instructions given in the plan specification. These issues are exacerbated in the presence of changing plans. CONCLUSIONS: We propose two solutions for representing failed plans. The first uses the Common Core Ontologies 'prescribed by' relation to connect a plan specification to the entity or process that utilizes the plan specification as a guide. The second, more complex, solution incorporates the process of creating a plan (in the sense of an intention to execute a plan specification) into the representation of executing plan specifications. We hypothesize that the first solution (i.e., use of 'prescribed by') is adequate for most situations. However, more research is needed to test this hypothesis as well as explore the other solutions presented in this manuscript.

Asunto(s)

RESUMEN

Background: This study aimed to investigate the effects of licorice processing of different Evodiae Fructus (EF) specifications on liver inflammation and oxidative stress associated with the intestinal mucosal microbiota. Materials and methods: The 25 Kunming mice were divided into control (MCN), raw small-flowered Evodiae Fructus (MRSEF), raw medium-flowered EF (MRMEF), licorice-processed small-flowered EF (MLSEF), and licorice-processed medium-flowered EF (MLSEF) groups. The EF intervention groups were given different specifications of EF extract solutions by gavage. After 21 days, indices of liver inflammation and oxidative stress and intestinal mucosal microbiota were measured in mice. Results: Compared with the MCN, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly increased in the MRMEF. Although the trends of oxidative stress and inflammatory indexes in the MLSEF and MLMEF were consistent with those in the raw EF groups, the changes were smaller than those in the raw EF groups. Compared to the raw EF groups, the MLSEF and MLMEF showed closer approximations of metabolic function to the MCN. The abundance of Corynebacterium in MRMEF was significantly lower than that in the MCN, and it was not significantly different from the MCN after licorice processing. The probiotic Candidatus Arthromitus was enriched in the MLSEF. The probiotic Lactobacillus was enriched in the MLMEF. Correlation analysis revealed significant negative correlations between IL-1ß, some metabolic functions and Corynebacterium. Conclusion: The effects of medium-flowered EF on oxidative stress and inflammatory factors in the liver of mice were stronger than those of small-flowered EF. The licorice processing can reduce this difference by modulating the abundance of Corynebacterium and intestinal mucosal metabolic function.

RESUMEN

Causal inference plays a crucial role in biomedical studies and social sciences. Over the years, researchers have devised various methods to facilitate causal inference, particularly in observational studies. Among these methods, the doubly robust estimator distinguishes itself through a remarkable feature: it retains its consistency even when only one of the two components-either the propensity score model or the outcome mean model-is correctly specified, rather than demanding correctness in both simultaneously. In this paper, we focus on scenarios where semiparametric models are employed for both the propensity score and the outcome mean. Semiparametric models offer a valuable blend of interpretability akin to parametric models and the adaptability characteristic of nonparametric models. In this context, achieving correct model specification involves both accurately specifying the unknown function and consistently estimating the unknown parameter. We introduce a novel concept: the relaxed doubly robust estimator. It operates in a manner reminiscent of the traditional doubly robust estimator but with a reduced requirement for double robustness. In essence, it only mandates the consistent estimate of the unknown parameter, without requiring the correct specification of the unknown function. This means that it only necessitates a partially correct model specification. We conduct a thorough analysis to establish the double robustness and semiparametric efficiency of our proposed estimator. Furthermore, we bolster our findings with comprehensive simulation studies to illustrate the practical implications of our approach.

RESUMEN

In some situations, for example, when we expect to gain a reward in case of good performance, goal-driven top-down attention is particularly strong. Little is known about the task specificity of such increases of top-down attention due to environmental factors. To understand to what extent performance-contingent reward prospects can result in specific and unspecific changes in cognitive processing, we here investigate reward effects under different levels of task specification. Thirty-two participants performed a visual or an auditory discrimination task cued by two consecutive visual stimuli: First, a reward cue indicated if good performance was rewarded. Second, a task cue announced either which of the two tasks would follow (precise cue) or that both tasks would follow equally likely (imprecise cue). Reward and task cue preciseness both significantly improved performance. Moreover, the response time difference between precisely and imprecisely cued trials was significantly stronger in rewarded than in unrewarded trials. These effects were reflected in event-related potential (ERP) slow wave amplitudes: Reward and preciseness both significantly enhanced the contingent negative variation (CNV) prior to the task stimulus. In an early CNV time interval, both factors also showed an interaction. A negative slow wave prior to the task cue was also significantly enhanced for rewarded trials. This effect correlated with the reward difference in response times. These results indicate that reward prospects trigger task-specific changes in preparatory top-down attention which can flexibly adapt over time and across different task requirements. This highlights that a reward-induced increase of cognitive control can occur on different specificity levels.

RESUMEN

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. Endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the arterial-to-capillary-to-vein axis. While our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease.

RESUMEN

Pharmacopeia monographs are not intended to establish biosimilarity. However, the US Food and Drug Administration (FDA) has stopped the US Pharmacopeia (USP) from creating monographs for biological drugs due to the need for side-by-side comparisons with the reference products. The USP can create Biological Product Specifications (BPS), not to be labeled as monographs, based on the analytical testing of reference products and validated test methods that will remove the need for side-by-side analytical testing of biosimilars with reference products. Scientific arguments confirm that this plan is logical and capable of creating global quality standards for biosimilars to allow their interchangeability with other biosimilars. While the regulatory agencies have waived many high-cost biosimilar tests, analytical assessment is the most sensitive test; reducing its cost will further enhance the entry of biosimilars with no clinically meaningful difference.

RESUMEN

Linear temporal logic (LTL) formalism can ensure the correctness of mobile robot planning through concise, readable, and verifiable mission specifications. For uneven terrain, planning must consider motion constraints related to asymmetric slope traversability and maneuverability. However, even though model checker tools like the open-source Simple Promela Interpreter (SPIN) include search optimization techniques to address the state explosion problem, defining a global LTL property that encompasses both mission specifications and motion constraints on digital elevation models (DEMs) can lead to complex models and high computation times. In this article, we propose a system model that incorporates a set of uncrewed ground vehicle (UGV) motion constraints, allowing these constraints to be omitted from LTL model checking. This model is used in the LTL synthesizer for path planning, where an LTL property describes only the mission specification. Furthermore, we present a specific parameterization for path planning synthesis using a SPIN. We also offer two SPIN-efficient general LTL formulas for representative UGV missions to reach a DEM partition set, with a specified or unspecified order, respectively. Validation experiments performed on synthetic and real-world DEMs demonstrate the feasibility of the framework for complex mission specifications on DEMs, achieving a significant reduction in computation cost compared to a baseline approach that includes a global LTL property, even when applying appropriate search optimization techniques on both path planners.

RESUMEN

This paper reports on two flash-mode experiments that test redundant descriptions of small (2-4) cardinalities, borderline (5-8) cardinalities, and color in referential communication. It provides further support for the idea that small cardinalities are more salient (due to subitizing), less sensitive to visual context, and therefore give rise to higher over-specification rates than color. Because of greater salience, Russian speakers more often use prenominal positions for numerals than for color adjectives. The paper also investigates borderline cardinalities and argues for the order factor that affects their salience, since ordered items can be perceived in small subitized parts. The ordered mode of presentation of the borderline cardinalities leads to higher over-specification rates and to higher percentages of prenominal positions than the unordered one. The paper provides further evidence for the consistency of small, borderline cardinalities, and color in people's choices to minimally specify or over-specify given objects in referential communication.

RESUMEN

The dorsal aorta (DA) is the first major blood vessel to develop in the embryonic cardiovascular system. Its formation is governed by a coordinated process involving the migration, specification, and arrangement of angioblasts into arterial and venous lineages, a process conserved across species. Although vascular endothelial growth factor a (VEGF-A) is known to drive DA specification and formation, the kinases involved in this process remain ambiguous. Thus, we investigated the role of protein kinase B (Akt) in zebrafish by generating a quadruple mutant (aktΔ/Δ), in which expression and activity of all Akt genes - akt1, -2, -3a and -3b - are strongly decreased. Live imaging of developing aktΔ/Δ DA uncovers early arteriovenous malformations. Single-cell RNA-sequencing analysis of aktΔ/Δ endothelial cells corroborates the impairment of arterial, yet not venous, cell specification. Notably, endothelial specific expression of ligand-independent activation of Notch or constitutively active Akt1 were sufficient to re-establish normal arterial specification in aktΔ/Δ. The Akt loss-of-function mutant unveils that Akt kinase can act upstream of Notch in arterial endothelial cells, and is involved in proper embryonic artery specification. This sheds light on cardiovascular development, revealing a mechanism behind congenital malformations.

Asunto(s)

RESUMEN

The large-scale experimental measures of variant functional assays submitted to MaveDB have the potential to provide key information for resolving variants of uncertain significance, but the reporting of results relative to assayed sequence hinders their downstream utility. The Atlas of Variant Effects Alliance mapped multiplexed assays of variant effect data to human reference sequences, creating a robust set of machine-readable homology mappings. This method processed approximately 2.5 million protein and genomic variants in MaveDB, successfully mapping 98.61% of examined variants and disseminating data to resources such as the UCSC Genome Browser and Ensembl Variant Effect Predictor.

RESUMEN

Sleep occurs in all animals but its amount, form, and timing vary considerably between species and between individuals. Currently, little is known about the basis for these differences, in part, because we lack a complete understanding of the brain circuitry controlling sleep-wake states and markers for the cell types which can identify similar circuits across phylogeny. Here, I explain the utility of an "Evo-devo" approach for comparative studies of sleep regulation and function as well as for sleep medicine. This approach focuses on the regulation of evolutionary ancient transcription factors which act as master controllers of cell-type specification. Studying these developmental transcription factor cascades can identify novel cell clusters which control sleep and wakefulness, reveal the mechanisms which control differences in sleep timing, amount, and expression, and identify the timepoint in evolution when different sleep-wake control neurons appeared. Spatial transcriptomic studies, which identify cell clusters based on transcription factor expression, will greatly aid this approach. Conserved developmental pathways regulate sleep in mice, Drosophila, and C. elegans. Members of the LIM Homeobox (Lhx) gene family control the specification of sleep and circadian neurons in the forebrain and hypothalamus. Increased Lhx9 activity may account for increased orexin/hypocretin neurons and reduced sleep in Mexican cavefish. Other transcription factor families specify sleep-wake circuits in the brainstem, hypothalamus, and basal forebrain. The expression of transcription factors allows the generation of specific cell types for transplantation approaches. Furthermore, mutations in developmental transcription factors are linked to variation in sleep duration in humans, risk for restless legs syndrome, and sleep-disordered breathing. This paper is part of the "Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches" collection.

RESUMEN

Even when guided by strong theories and sound methods, researchers must often choose a singular course of action from multiple viable alternatives. Regardless of the choice, it, along with all other choices made during the research process, individually and collectively affects study results, often in unpredictable ways. The inability to disentangle how much of an observed effect is attributable to the phenomenon of interest, and how much is attributable to what have come to be known as researcher degrees of freedom (RDF), slows theoretical progress and stymies practical implementation. However, if one could examine the results from a particular set of RDF (known as a universe) against a systematically and comprehensively determined background of alternative viable universes (known as a multiverse), then the effects of RDF can be directly examined to provide greater context and clarity to future researchers, and greater confidence in the recommendations to practitioners. This tutorial demonstrates a means to map result variability directly and efficiently, and empirically investigate RDF impact on conclusions via multiverse analysis. Using the R package multiverse, we outline best practices in planning, executing and interpreting of multiverse analyses.

RESUMEN

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.