Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.360
Filtrar
1.
Front Psychol ; 15: 1417047, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135864

RESUMO

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.

2.
Front Microbiol ; 15: 1439204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39176281

RESUMO

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.

3.
J Biomed Semantics ; 15(1): 15, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39160586

RESUMO

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.


Assuntos
Ontologias Biológicas
4.
Artigo em Inglês | MEDLINE | ID: mdl-39189891

RESUMO

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.

5.
Development ; 151(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39101673

RESUMO

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.


Assuntos
Artérias , Proteínas Proto-Oncogênicas c-akt , Receptores Notch , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Artérias/embriologia , Artérias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células Endoteliais/metabolismo , Transdução de Sinais , Mutação/genética , Embrião não Mamífero/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
6.
Pharmaceutics ; 16(8)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39204358

RESUMO

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.

7.
Sensors (Basel) ; 24(16)2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39204861

RESUMO

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.

8.
Stat Theory Relat Fields ; 8(1): 69-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206429

RESUMO

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.

9.
Psychophysiology ; : e14678, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210245

RESUMO

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.

10.
Implement Sci Commun ; 5(1): 88, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113160

RESUMO

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.

11.
Sleep Adv ; 5(1): zpae040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022590

RESUMO

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.

12.
Int J Psychol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39030767

RESUMO

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.

13.
Adv Sci (Weinh) ; : e2400586, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984490

RESUMO

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.

14.
bioRxiv ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38979347

RESUMO

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.

15.
Diabetologia ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080045

RESUMO

AIMS/HYPOTHESIS: Homozygous mutations in RFX6 lead to neonatal diabetes accompanied by a hypoplastic pancreas, whereas heterozygous mutations cause MODY. Recent studies have also shown RFX6 variants to be linked with type 2 diabetes. Despite RFX6's known function in islet development, its specific role in diabetes pathogenesis remains unclear. Here, we aimed to understand the mechanisms underlying the impairment of pancreatic islet development and subsequent hypoplasia due to loss-of-function mutations in RFX6. METHODS: We examined regulatory factor X6 (RFX6) expression during human embryonic stem cell (hESC) differentiation into pancreatic islets and re-analysed a single-cell RNA-seq dataset to identify RFX6-specific cell populations during islet development. Furthermore, induced pluripotent stem cell (iPSC) lines lacking RFX6 were generated using CRISPR/Cas9. Various approaches were then employed to explore the consequences of RFX6 loss across different developmental stages. Subsequently, we evaluated transcriptional changes resulting from RFX6 loss through RNA-seq of pancreatic progenitors (PPs) and endocrine progenitors (EPs). RESULTS: RFX6 expression was detected in PDX1+ cells in the hESC-derived posterior foregut (PF). However, in the PPs, RFX6 did not co-localise with pancreatic and duodenal homeobox 1 (PDX1) or NK homeobox 1 (NKX6.1) but instead co-localised with neurogenin 3, NK2 homeobox 2 and islet hormones in the EPs and islets. Single-cell analysis revealed high RFX6 expression levels in endocrine clusters across various hESC-derived pancreatic differentiation stages. Upon differentiating iPSCs lacking RFX6 into pancreatic islets, a significant decrease in PDX1 expression at the PF stage was observed, although this did not affect PPs co-expressing PDX1 and NKX6.1. RNA-seq analysis showed the downregulation of essential genes involved in pancreatic endocrine differentiation, insulin secretion and ion transport due to RFX6 deficiency. Furthermore, RFX6 deficiency resulted in the formation of smaller islet organoids due to increased cellular apoptosis, linked to reduced catalase expression, implying a protective role for RFX6. Overexpression of RFX6 reversed defective phenotypes in RFX6-knockout PPs, EPs and islets. CONCLUSIONS/INTERPRETATION: These findings suggest that pancreatic hypoplasia and reduced islet cell formation associated with RFX6 mutations are not due to alterations in PDX1+/NKX6.1+ PPs but instead result from cellular apoptosis and downregulation of pancreatic endocrine genes. DATA AVAILABILITY: RNA-seq datasets have been deposited in the Zenodo repository with accession link (DOI: https://doi.org/10.5281/zenodo.10656891 ).

16.
J Voice ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043532

RESUMO

PURPOSE: This clinical tutorial will present the concept of applying auditory-perceptual prompts (implicit instruction) typically used in voice therapy to the anatomy and physiology of the voice production system (explicit instruction) via the Estill Voice Model (EVM) and the Rehabilitation Treatment Specification System (RTSS). METHODS: EVM offers an integrated implicit-explicit instructional approach to voice training allowing for isolated practice of vocal structures (explicit) that interact to produce functional voice qualities (implicit), such as modal speech and louder projected voice qualities. In EVM, voice quality is correlated with the specific anatomy and physiologic adjustments via 13 Estill Figures and Options (eg, Larynx Figure has three options: High, Mid, and Low). RTSS provides a framework to connect client change in functioning (ie, target) with clinician action (ie, ingredients). Mechanisms of action connect the target to the ingredients by hypothesizing how the treatment is expected to work. RESULTS: Evidence is provided for connecting auditory-perpetual voice prompts with the anatomy and physiology of voice and supporting an integrated implicit-explicit approach to voice therapy. The concept of linking commonly used implicit auditory-perceptual prompts used in voice therapy (eg, humming, loud "aahh") to explicit anatomy and physiology training (eg, 13 Estill Figures and Options) is demonstrated using EVM and the RTSS framework with case studies and video examples. CONCLUSIONS: Clinicians may choose to use anatomy and physiology of voice to define and provide explicit instruction for typically used implicit auditory-perceptual prompts. Future research is warranted to test the concept applied to voice therapy models in the literature across prevention and treatment of voice disorders.

17.
Heliyon ; 10(13): e34014, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39055844

RESUMO

To understand how many kinds of mRNAs in female adults can be transferred into the eggs and the molecular basis of embryonic axis specification in Sogatella furcifera, we performed de novo transcriptome sequencing of six cDNA libraries of female adults and unfertilized eggs. Total 60,306 unigenes were obtained, with an average length of 1114.51 bp and N50 length of 2112 bp. Total 2900 differentially expressed genes with 496 upregulated and 2404 downregulated were found in unfertilized egg compared to female adult. Most of mRNAs in female adult could be passed into its eggs. Total 65 maternal effect genes were identified, including many homologous genes involved in embryonic axis specialization of D. melanogaster. This study provide transcriptome resources to elucidate the functions of maternal effect genes and the molecular basis of embryonic axis specification in S. furcifera in the future.

18.
J Biomech ; 173: 112235, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39059333

RESUMO

Slips are the leading cause of falls, and understanding slip biomechanics is crucial for preventing falls and mitigating their negative consequences. This study analyses human biomechanical responses to slips, including kinetic, kinematic, spatiotemporal, and EMG variables. We reviewed 41 studies investigating slip-induced falls in lab settings, computational models, and training approaches. Our analysis focused on reactions and effects of factors like age, fatigue, strength, perturbation intensity, and gait speed. Trailing limbs' hip extension and knee flexion interrupt the swing phase earlier, increasing the support base. The slipping leg responds with two phases: hip extension and knee flexion, then hip flexion and knee extension. Furthermore, our analysis revealed that the medial hamstring muscles play an active role in slip recoveries. Their activation in the slipping limb allows for hip extension and knee flexion, while in the trailing limb, their activation results in the foot touching down. Additionally, successful slip recoveries were associated with co-contraction of the Tibialis Anterior (TA) and Medial Gastrocnemius (MG), which increases ankle joint stability and facilitates foot contact with the ground. Our review identifies various factors that influence biomechanical and muscular responses to slips, including age, perturbation intensity, gait speed, muscular fatigue, and muscular strength. These findings have important implications for designing interventions to prevent slip-related falls, including cutting-edge technology devices based on a deeper understanding of slip recoveries. Future research should explore the complex interplay between biomechanics, muscle activation patterns, and environmental factors to improve slip-fall prevention strategies.


Assuntos
Acidentes por Quedas , Músculo Esquelético , Humanos , Fenômenos Biomecânicos , Acidentes por Quedas/prevenção & controle , Músculo Esquelético/fisiologia , Marcha/fisiologia , Articulação do Joelho/fisiologia
19.
Cell Mol Life Sci ; 81(1): 305, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012348

RESUMO

Lentiviral vectors have markedly enhanced gene therapy efficiency in treating congenital diseases, but their long-term safety remains controversial. Most gene therapies for congenital eye diseases need to be carried out at early ages, yet the assessment of related risks to ocular development posed by lentiviral vectors is challenging. Utilizing single-cell transcriptomic profiling on human retinal organoids, this study explored the impact of lentiviral vectors on the retinal development and found that lentiviral vectors can cause retinal precursor cells to shift toward photoreceptor fate through the up-regulation of key fate-determining genes such as PRDM1. Further investigation demonstrated that the intron and intergenic region of PRDM1 was bound by PHLDA1, which was also up-regulated by lentiviral vectors exposure. Importantly, knockdown of PHLDA1 successfully suppressed the lentivirus-induced differentiation bias of photoreceptor cells. The findings also suggest that while lentiviral vectors may disrupt the fate determination of retinal precursor cells, posing risks in early-stage retinal gene therapy, these risks could potentially be reduced by inhibiting the PHLDA1-PRDM1 axis.


Assuntos
Diferenciação Celular , Vetores Genéticos , Lentivirus , Retina , Células-Tronco , Fatores de Transcrição , Humanos , Retina/metabolismo , Retina/citologia , Lentivirus/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Vetores Genéticos/metabolismo , Vetores Genéticos/genética , Diferenciação Celular/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Organoides/metabolismo , Organoides/citologia , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Terapia Genética/métodos
20.
Psychometrika ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971882

RESUMO

The Ising model has become a popular psychometric model for analyzing item response data. The statistical inference of the Ising model is typically carried out via a pseudo-likelihood, as the standard likelihood approach suffers from a high computational cost when there are many variables (i.e., items). Unfortunately, the presence of missing values can hinder the use of pseudo-likelihood, and a listwise deletion approach for missing data treatment may introduce a substantial bias into the estimation and sometimes yield misleading interpretations. This paper proposes a conditional Bayesian framework for Ising network analysis with missing data, which integrates a pseudo-likelihood approach with iterative data imputation. An asymptotic theory is established for the method. Furthermore, a computationally efficient Pólya-Gamma data augmentation procedure is proposed to streamline the sampling of model parameters. The method's performance is shown through simulations and a real-world application to data on major depressive and generalized anxiety disorders from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA