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In recent years, there has been significant advancement in virtual reality (VR) technology development. VR headsets have become lighter, offer higher resolution, and possess more powerful computational capabilities. Previous research has indicated that the level of immersion in operating technological products can positively impact user experiences. This study explores the effects of interaction, vividness, embodiment, and media novelty on immersion, perceived usefulness, satisfaction, and continuance intention. This study collected data from 150 users of virtual reality devices with the help of a survey methodology and analyzed the data with the help of the Partial Least Square – Structural Equation Model (PLS-SEM) technique. The results indicate that interaction and vividness do not directly influence immersion. However, embodiment and media novelty indirectly affect perceived usefulness, satisfaction, and continuance intention by increasing immersion. Our findings underscore the importance of embodiment and media novelty for users in virtual environments. When users can experience a genuine sense of embodiment and novelty in the virtual environment, their perception of usefulness, satisfaction, and intention to continue using VR is enhanced. These results provide valuable guidance for designing and applying virtual reality, aiming to improve user experiences and continuance intention. This study contributes to analyzing the antecedents and consequences of immersion and offers insights that can assist academic research, VR-related development, and businesses’ marketing efforts.

BackgroundMicrophthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.ResultsQuery of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.ConclusionsUsing genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

BackgroundThe diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property.MethodsHere we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project.ResultsWe found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts.ConclusionsInformation on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases.

MotivationHigh-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors.ResultsHere we introduce 'soft windowing', a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources.Availability and implementationThe method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin.Supplementary informationSupplementary data are available at Bioinformatics online.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.].

[This corrects the article DOI: 10.1038/s42003-018-0226-0.].

Audiovestibular dysfunction in patients with systemic lupus erythematosus has been underestimated for decades. Systemic lupus erythematosus can affect both the auditory and vestibular systems simultaneously. Several potential pathophysiological mechanisms behind systemic lupus erythematosus-related audiovestibular dysfunction have been proposed, including antibody-mediated immune responses, cell-mediated cytotoxicity, immune complex deposition in microvessels, central involvement in the audiovestibular pathway, and ototoxicity from medications used in systemic lupus erythematosus treatment. Currently available tests to evaluate audiovestibular function in systemic lupus erythematosus patients are neither specific nor sensitive. Nevertheless, there is no consensus regarding the efficacy of treatments for audiovestibular dysfunction in such patients. In this systematic review, we electronically searched the PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect platforms to find eligible articles. The first inspection date was on 29 December 2023 and the final update search date was on 11 June 2024. Further, we rated the quality of the included articles with Newcastle–Ottawa Scale. Based upon the aforementioned systematic review process, we have summarized the currently available evidence on the characteristics, pathophysiology, examination, and treatment of audiovestibular dysfunction related to systemic lupus erythematosus. Furthermore, we have proposed a specific steroid treatment protocol to manage audiovestibular dysfunction related to systemic lupus erythematosus. Audiovestibular dysfunction related to systemic lupus erythematosus may be responsive to adequate treatments, potentially allowing for reversibility if the disease is recognized and managed in a timely manner. Therefore, to provide clinically relevant evidence to clinicians, we have organized this literature review article to summarize the available evidence on the characteristics, pathophysiology, examination, and treatment of audiovestibular dysfunction in patients with systemic lupus erythematosus. Finally, based on our modified steroid treatment protocol, we would like to provide a new treatment strategy to clinicians to manage systemic lupus erythematosus-related audiovestibular dysfunction. [ABSTRACT FROM AUTHOR]

Despite advances in next generation sequencing technologies, determining the genetic basis of ocular disease remains a major challenge due to the limited access and prohibitive cost of human forward genetics. Thus, less than 4,000 genes currently have available phenotype information for any organ system. Here we report the ophthalmic findings from the International Mouse Phenotyping Consortium, a large-scale functional genetic screen with the goal of generating and phenotyping a null mutant for every mouse gene. Of 4364 genes evaluated, 347 were identified to influence ocular phenotypes, 75% of which are entirely novel in ocular pathology. This discovery greatly increases the current number of genes known to contribute to ophthalmic disease, and it is likely that many of the genes will subsequently prove to be important in human ocular development and disease.

This corrects the article DOI: 10.1038/nature19356.

This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly improved the global QoR score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% confidence interval: 0.70—1.78; p < 0.00001). It also enhanced specific QoR dimensions, with substantial effects on pain (SMD: 1, p < 0.00001) and physical comfort (SMD: 0.85, p < 0.0001), a moderate effect on emotional state (SMD: 0.65, p = 0.002), and small improvements in physical independence (SMD: 0.43, p < 0.00001) and psychological support (SMD: 0.37, p < 0.0001). In addition, magnesium sulfate reduced the intraoperative opioid consumption (SMD: −0.66, p < 0.0001), postoperative pain severity, and the incidence of postoperative nausea and vomiting (risk ratio: 0.48, p = 0.008). The extubation times were unaffected, whereas the post-anesthesia care unit stay was slightly prolonged. These findings highlight the potential of magnesium sulfate as a valuable adjunct for multimodal analgesia and enhanced recovery. Future studies should aim to elucidate the optimal dosing strategies, timing of administration, and specific surgical populations that may derive maximum benefits. [ABSTRACT FROM AUTHOR]

In recent years, there has been significant advancement in virtual reality (VR) technology development. VR headsets have become lighter, offer higher resolution, and possess more powerful computational capabilities. Previous research has indicated that the level of immersion in operating technological products can positively impact user experiences. This study explores the effects of interaction, vividness, embodiment, and media novelty on immersion, perceived usefulness, satisfaction, and continuance intention. This study collected data from 150 users of virtual reality devices with the help of a survey methodology and analyzed the data with the help of the Partial Least Square – Structural Equation Model (PLS-SEM) technique. The results indicate that interaction and vividness do not directly influence immersion. However, embodiment and media novelty indirectly affect perceived usefulness, satisfaction, and continuance intention by increasing immersion. Our findings underscore the importance of embodiment and media novelty for users in virtual environments. When users can experience a genuine sense of embodiment and novelty in the virtual environment, their perception of usefulness, satisfaction, and intention to continue using VR is enhanced. These results provide valuable guidance for designing and applying virtual reality, aiming to improve user experiences and continuance intention. This study contributes to analyzing the antecedents and consequences of immersion and offers insights that can assist academic research, VR-related development, and businesses' marketing efforts. [ABSTRACT FROM AUTHOR]

Aim: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well‐studied. Method: In the first step, we compared the performance of ChatGPT GPT‐4, Bard, and Llama‐2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis. Result: Only GPT‐4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama‐2 scored 25. GPT‐4 outperformed Bard and Llama‐2, especially in the areas of 'Pathophysiology & Epidemiology' (χ2 = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ2 = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT‐4 (5), Bard (3), and Llama‐2 (1). Conclusion: Compared to Bard and Llama‐2, GPT‐4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT‐4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT‐4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs. [ABSTRACT FROM AUTHOR]

Background: Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods: We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results: Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations: Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion: The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo., Introduction Depressive disorders after traumatic brain injury (TBI) are not uncommon, with an estimated incidence of 16% to 60%, (1-3) and the prevalence of post-TBI major depression has been reported [...]