YEASTRACT+: a portal for the exploitation of global transcription regulation and metabolic model data in yeast biotechnology and pathogenesis.

YEASTRACT+ (http://yeastract-plus.org/) is a tool for the analysis, prediction and modelling of transcription regulatory data at the gene and genomic levels in yeasts. It incorporates three integrated databases: YEASTRACT (http://yeastract-plus.org/yeastract/), PathoYeastract (http://yeastract-plus.org/pathoyeastract/) and NCYeastract (http://yeastract-plus.org/ncyeastract/), focused on Saccharomyces cerevisiae, pathogenic yeasts of the Candida genus, and non-conventional yeasts of biotechnological relevance. In this release, YEASTRACT+ offers upgraded information on transcription regulation for the ten previously incorporated yeast species, while extending the database to another pathogenic yeast, Candida auris. Since the last release of YEASTRACT+ (January 2020), a fourth database has been integrated. CommunityYeastract (http://yeastract-plus.org/community/) offers a platform for the creation, use, and future update of YEASTRACT-like databases for any yeast of the users' choice. CommunityYeastract currently provides information for two Saccharomyces boulardii strains, Rhodotorula toruloides NP11 oleaginous yeast, and Schizosaccharomyces pombe 972h-. In addition, YEASTRACT+ portal currently gathers 304 547 documented regulatory associations between transcription factors (TF) and target genes and 480 DNA binding sites, considering 2771 TFs from 11 yeast species. A new set of tools, currently implemented for S. cerevisiae and C. albicans, is further offered, combining regulatory information with genome-scale metabolic models to provide predictions on the most promising transcription factors to be exploited in cell factory optimisation or to be used as novel drug targets. The expansion of these new tools to the remaining YEASTRACT+ species is ongoing.

Effects of the pyriproxyfen and fenthion on the gonadal morphology of Nile tilapia (Oreochromis niloticus: Perciformes, Cichlidae).

Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. Forty-five juvenile male Nile tilapias (Oreochromis niloticus) were divided into control, pyriproxyfen-exposed (0.01 g/L), and fenthion-exposed (0.001 g/L) groups. They were evaluated in three moments (30, 60, and 90 days). The variables analyzed were the gonadosomatic index (GSI), weight to length ratio, seminiferous tubules morphometry (diameter and height), tissue damage, and immunohistochemical analysis for caspase-3, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Pyriproxyfen and fenthion injured the seminiferous tubule tissue, and the damage progressed according to the exposure time. In addition, the GSI gradually reduced over time in all groups compared with the first moment (30 days), while caspase-3, TNF-α, and VEGF values increased only in the fenthion-exposed group. Therefore, pyriproxyfen and fenthion changed the gonadal morphology of male Oreochromis niloticus, which may affect their reproduction in the wild or captivity.

Aberrant Splicing Caused by a Novel VPS16 Variant Linked to Dystonia Type 30.

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent involuntary muscle contractions, causing abnormal postures and/or repetitive movements. In this report, we identified a novel heterozygous splice-site variant in VPS16 (NM_022575.4:c.240+3G>C) in a patient with cervical and upper limb dystonia without other neurological or extra-neurological features. Analysis of patient's blood mRNA showed disruption of exon 3/intron 3 donor splice-site, leading to exon 3 skipping, which predictably results in a frameshift [p.(Ala48Valfs*14)]. Despite the scarcity of splice-affecting variants described in VPS16-related dystonia, our report contributes with the first fully characterized variant at the mRNA level.

Stress response mechanisms in protein misfolding diseases: Profiling a cellular model of Huntington's disease.

Stress response pathways like the integrated stress response (ISR), the mitochondrial unfolded protein response (UPRmt) and the heat shock response (HSR) have emerged as part of the pathophysiology of neurodegenerative diseases, including Huntington's disease (HD) - a currently incurable disease caused by the production of mutant huntingtin (mut-Htt). Previous data from HD patients suggest that ISR is activated while UPRmt and HSR are impaired in HD. The study of these stress response pathways as potential therapeutic targets in HD requires cellular models that mimic the activation status found in HD patients of such pathways. PC12 cells with inducible expression of the N-terminal fragment of mut-Htt are among the most used cell lines to model HD, however the activation of stress responses remains unclear in this model. The goal of this study is to characterize the activation of ISR, UPRmt and HSR in this HD cell model and evaluate if it mimics the activation status found in HD patients. We show that PC12 HD cell model presents reduced levels of Hsp90 and mitochondrial chaperones, suggesting an impaired activation or function of HSR and UPRmt. This HD model also presents increased levels of phosphorylated eIF2α, the master regulator of the ISR, but overall similar levels of ATF4 and decreased levels of CHOP - transcription factors downstream to eIF2α - in comparison to control, suggesting an initial activation of ISR. These results show that this model mimics the ISR activation and the impaired UPRmt and HSR found in HD patients. This work suggests that the PC12 N-terminal HD model is suitable for studying the role of stress response pathways in the pathophysiology of HD and for exploratory studies investigating the therapeutic potential of drugs targeting stress responses.

Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis.

INTRODUCTION: Replication of the nuclear genome is an essential step for cell division. Pathogenic variants in genes coding for highly conserved components of the DNA replication machinery cause Meier-Gorlin syndrome (MGORS). OBJECTIVE: Identification of novel genes associated with MGORS. METHODS: Exome sequencing was performed to investigate the genotype of an individual presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. The analysis of the candidate variants employed bioinformatic tools, in silico structural protein analysis and modelling in budding yeast. RESULTS: A novel homozygous missense variant NM_016095.2:c.341G>T, p.(Arg114Leu), in GINS2 was identified. Both non-consanguineous healthy parents carried this variant. Bioinformatic analysis supports its classification as pathogenic. Functional analyses using yeast showed that this variant increases sensitivity to nicotinamide, a compound that interferes with DNA replication processes. The phylogenetically highly conserved residue p.Arg114 localises at the docking site of CDC45 and MCM5 at GINS2. Moreover, the missense change possibly disrupts the effective interaction between the GINS complex and CDC45, which is necessary for the CMG helicase complex (Cdc45/MCM2-7/GINS) to accurately operate. Interestingly, our patient's phenotype is strikingly similar to the phenotype of patients with CDC45-related MGORS, particularly those with craniosynostosis, mild short stature and patellar hypoplasia. CONCLUSION: GINS2 is a new disease-associated gene, expanding the genetic aetiology of MGORS.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Cost-effectiveness of hypofractionated versus conventional fractionated radiotherapy for the treatment of men with early glottic cancer: a study in the Brazilian public and private health system.

BACKGROUND: This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems. METHODS: Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values. RESULTS: In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.

3% polidocanol foam sclerotherapy versus hemorrhoidal artery ligation with recto anal repair in hemorrhoidal disease grades II-III: a randomized, pilot trial.

PURPOSE: Polidocanol foam sclerotherapy (SP) versus doppler-guided hemorrhoidal artery ligation with recto-anal repair (HAL-RAR) in the treatment of hemorrhoidal disease (HD) was analyzed. METHODS: A prospective, randomized study including patients with HD grades II and III was performed. Participants were randomly assigned (1:1) into SP or HAL-RAR, during a recruitment period between September 2019 and February 2020. Therapeutic success (Sodergren's and bleeding scores) was the primary outcome. Other outcomes evaluated included complications and implication in the professional life. Efficacy and safety outcomes were evaluated during the 8 weeks after surgery or the final SP session. RESULTS: Forty-six patients were allocated either to SP (n=22) or HAL-RAR (n=24). Most patients achieved therapeutic success (SP 100% vs. HAL-RAR 90.9%, p=0.131). Complete success was higher in the SP group (91.7% vs. 68.2%, p=0.045) and SP patients had less complications (25% vs. 68.2%, p=0.003). HAL-RAR had a greater negative impact on work activity of the patient. CONCLUSION: SP was more effective and safer than HAL-RAR. SP patients had less impact on their work activity. Clinical trials identifier NCT04675177.

Congenital heart defects associated with pathogenic variants in WAC gene: Expanding the phenotypic and genotypic spectrum of DeSanto-Shinawi syndrome.

WAC-related intellectual disability, also known as DeSanto-Shinawi syndrome, is a rare autosomal dominant genetic disorder caused by pathogenic variants in WAC gene. This syndrome is characterized by developmental delay, intellectual disability, behavioral abnormalities, and dysmorphic facial features, including deep-set eyes, flat nasal bridge, bulbous nasal tip, and synophrys. Chromosomal deletions at 10p12p11 encompassing WAC gene have been described in patients with a similar phenotype, presenting with developmental delay, intellectual disability, visual impairments, abnormal behavior, and dysmorphic features. An important clinical difference between the two groups of patients, is that those with large deletions frequently present with congenital cardiac defects, which were rarely reported in patients with pathogenic variants in WAC. The genes underlying heart defects in patients with the deletion have not yet been fully clarified. Here, we describe two unrelated Portuguese patients with de novo pathogenic variants in WAC gene, previously unreported in the literature. Both patients present with microcephaly, developmental delay, intellectual disability, behavioral problems, and facial dysmorphisms. Interestingly, the youngest patient has a severe congenital cardiac malformation, showing that intragenic pathogenic WAC variants can also be associated with heart defects. Therefore, this report expands the phenotypic and genotypic spectrum of this rare syndrome and provides deeper insights by comparing the clinical features of our patients with previously reported cases.

YEASTRACT+: a portal for cross-species comparative genomics of transcription regulation in yeasts.

The YEASTRACT+ information system (http://YEASTRACT-PLUS.org/) is a wide-scope tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in yeasts of biotechnological or human health relevance. YEASTRACT+ is a new portal that integrates the previously existing YEASTRACT (http://www.yeastract.com/) and PathoYeastract (http://pathoyeastract.org/) databases and introduces the NCYeastract (Non-Conventional Yeastract) database (http://ncyeastract.org/), focused on the so-called non-conventional yeasts. The information in the YEASTRACT database, focused on Saccharomyces cerevisiae, was updated. PathoYeastract was extended to include two additional pathogenic yeast species: Candida parapsilosis and Candida tropicalis. Furthermore, the NCYeastract database was created, including five biotechnologically relevant yeast species: Zygosaccharomyces baillii, Kluyveromyces lactis, Kluyveromyces marxianus, Yarrowia lipolytica and Komagataella phaffii. The YEASTRACT+ portal gathers 289 706 unique documented regulatory associations between transcription factors (TF) and target genes and 420 DNA binding sites, considering 247 TFs from 10 yeast species. YEASTRACT+ continues to make available tools for the prediction of the TFs involved in the regulation of gene/genomic expression. In this release, these tools were upgraded to enable predictions based on orthologous regulatory associations described for other yeast species, including two new tools for cross-species transcription regulation comparison, based on multi-species promoter and TF regulatory network analyses.

Generative models based on eigendecomposition for dense ray tracing.

In this work, we present an algorithm capable of emulating ray trajectories that obey the least action principle. The method is based on spectral decomposition of geometric shapes taken from a set of raypaths. As the proposed work relies on shape analysis, it is agnostic on the underlying physics of raypath generation. As such, it is independent of the ray tracing method used to generate the training paths. In cases of mildly heterogeneous media or scenarios with a limited number of geometrical scatters, we show that the algorithm is capable of efficiently populating a given scenario with a dense array of emulated rays whose trajectories are in close agreement with actual rays. We argue that the algorithm also serves as an effective method capable of detecting regions where ray variation is high, such as when possible shadow zones are present.

Transcriptome-wide differences between Saccharomyces cerevisiae and Saccharomyces cerevisiae var. boulardii: Clues on host survival and probiotic activity based on promoter sequence variability.

Although Saccharomyces cerevisiae and S. cerevisiae var. boulardii share more than 95% genome sequence homology, only S. cerevisiae var. boulardii displays probiotic activity. In this study, the transcriptomic differences exhibited by S. cerevisiae and S. cerevisiae var. boulardii in intestinal like medium were evaluated. S. cerevisiae was found to display stress response overexpression, consistent with higher ability of S. cerevisiae var. boulardii to survive within the human host, while S. cerevisiae var. boulardii exhibited transcriptional patterns associated with probiotic activity, suggesting increased acetate biosynthesis. Resorting to the creation of a S. cerevisiae var. boulardii genomic database within Yeastract+, a possible correlation between loss or gain of transcription factor binding sites in S. cerevisiae var. boulardii promoters and the transcriptomic pattern is discussed. This study suggests that S. cerevisiae var. boulardii probiotic activity, when compared to S. cerevisiae, relies, at least partially, on differential expression regulation, based on promoter variability.

Active Control System to Prevent Malfunctioning Caused by the Pressure Difference in Gasket Plate Heat Exchangers Applied in the Oil and Gas Industry.

In the oil and gas industry, heat exchangers are subject to loads that cause malfunctioning. These loads are divided into thermal and mechanical stresses; however, most efforts are focused on studying thermal stresses. The present work reduces mechanical stresses by mitigating pressure events in a gasket plate heat exchanger (GPHE). GPHE requires that the hot and cold stream branches have approximately the same pressure. Thus, the work focuses on controlling the pressure difference between the branches. A test bench was used to emulate, on a small scale, the typical pressure events of an oil production plant. A control valve was used in different positions to evaluate the controller. In the experiments, it was observed that the best option to control the pressure difference is to use a hydraulic pump and control valve in the flow of the controlled thermal fluid branch. The reduction in pressure events was approximately 50%. Actuator efforts are also reduced in this configuration.

Thrombocytopenia-Absent Radius Syndrome: Descriptions of Three New Cases and a Novel Splicing Variant in RBM8A That Expands the Spectrum of Null Alleles.

Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by the bilateral absence of the radius and thrombocytopenia, and sometimes by other skeletal, gastrointestinal, cardiac, and renal abnormalities. The underlying genetic defect is usually the compound inheritance of a microdeletion in 1q21.1 (null allele) and a low-frequency, non-coding single nucleotide variant (SNV) in the RBM8A gene (hypomorphic allele). We report three new cases from two unrelated families. The two siblings presented the common genotype, namely the compound heterozygosity for a 1q21.1 microdeletion and the hypomorphic SNV c.-21G>A in RBM8A, whereas the third, unrelated patient presented a rare genotype comprised by two RBM8A variants: c.-21G>A (hypomorphic allele) and a novel pathogenic variant, c.343-2A>G (null allele). Of the eight documented RBM8A variants identified in TAR syndrome patients, four have hypomorphic expression and four behave as null alleles. The present report expands the RBM8A null allele spectrum and corroborates the particularities of RBM8A involvement in TAR syndrome pathogenesis.

Assessment of preschool-age executive functions: A systematic review.

Executive functions (EF) are higher-order cognitive processes present in the prefrontal cortex and are fundamental in planning, executing and monitoring goal-oriented behaviours. Evaluating EF in early stages of child development is essential for identifying any cognitive alterations in young children, given that it allows for early intervention and minimizes future complications. Additionally, it contributes to a better understanding of this construct in this age bracket, as well as its operational model. Study of EF has recently been the focus of multiple researchers; however, there is still a serious lack of instruments and measurements validated towards children's age bracket. This systematic review's main goal is to evaluate instruments and/or tasks that serve to evaluate and analyse EF and/or their components between the ages of 36 and 72 months. Forty-nine studies were analysed, containing multiple tasks and tools oriented towards EF and their constituent components. Results indicate the existence of various tasks that grade the different components independently from one another; nevertheless, they also confirm the lack of any global measurement instrument or method. Therefore, this systematic review presents itself as an important contribution in the study of EF, stressing not only the importance of further investing into constructing and validating new and better tools for evaluating the construct but also the study of operating models of executive functioning, especially in an age bracket where comprehending it is notoriously difficult.

From a genome assembly to full regulatory network prediction: the case study of Rhodotorula toruloides putative Haa1-regulon.

Numerous genomes are sequenced and made available to the community through the NCBI portal. However, and, unlike what happens for gene function annotation, annotation of promoter sequences and the underlying prediction of regulatory associations is mostly unavailable, severely limiting the ability to interpret genome sequences in a functional genomics perspective. Here we present an approach where one can download a genome of interest from NCBI in the GenBank Flat File (.gbff) format and, with a minimum set of commands, have all the information parsed, organized and made available through the platform web interface. Also, the new genomes are compared with a given genome of reference in search of homologous genes, shared regulatory elements and predicted transcription associations. We present this approach within the context of Community YEASTRACT of the YEASTRACT + portal, thus benefiting from immediate access to all the comparative genomics queries offered in the YEASTRACT + portal. Besides the yeast community, other communities can install the platform independently, without any constraints. In this work, we exemplify the usefulness of the presented tool, within Community YEASTRACT, in constructing a dedicated database and analysing the genome of the highly promising oleaginous red yeast species Rhodotorula toruloides currently poorly studied at the genome and transcriptome levels and with limited genome editing tools. Regulatory prediction is based on the conservation of promoter sequences and available regulatory networks. The case-study examined is focused on the Haa1 transcription factor-a key regulator of yeast resistance to acetic acid, an important inhibitor of industrial bioconversion of lignocellulosic hydrolysates. The new tool described here led to the prediction of a RtHaa1 regulon with expected impact in the optimization of R. toruloides robustness for lignocellulosic and pectin-rich residue biorefinery processes.

Novel KMT2B mutation causes cerebellar ataxia: Expanding the clinical phenotype.

Hereditary cerebellar ataxias comprise a heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or cerebellar pathways. Next-generation sequencing techniques have contributed substantially to the expansion of ataxia-causing genes, including genes classically described in alternative phenotypes. Herein, we describe a patient with adult-onset cerebellar ataxia, minor dystonia, neuropathy, seizure and ophthalmological pathology, who bears a novel variant in KMT2B (NM_014727.2:c.3334 + 1G > A). Bioinformatic analysis suggested this variant completely abolished the splice-site at exon 8/intron 8, which was confirmed through analysis of mRNA extracted from fibroblasts. Exon 8 skipping would ultimately translate as an in-frame deletion at the protein level, corresponding to the loss of 91 aminoacids [p.(Gly1020_Asn1111del)]. So far, KMT2B disease causing variants have been described in patients with dystonia or neurodevelopmental delay, with no reports of a cerebellar predominant phenotype. Our findings highlight the possible role of KMT2B as a gene involved in hereditary cerebellar ataxias.

The N.C.Yeastract and CommunityYeastract databases to study gene and genomic transcription regulation in non-conventional yeasts.

Responding to the recent interest of the yeast research community in non-Saccharomyces cerevisiae species of biotechnological relevance, the N.C.Yeastract (http://yeastract-plus.org/ncyeastract/) was associated to YEASTRACT + (http://yeastract-plus.org/). The YEASTRACT + portal is a curated repository of known regulatory associations between transcription factors (TFs) and target genes in yeasts. N.C.Yeastract gathers all published regulatory associations and TF-binding sites for Komagataellaphaffii (formerly Pichia pastoris), the oleaginous yeast Yarrowia lipolytica, the lactose fermenting species Kluyveromyces lactis and Kluyveromyces marxianus, and the remarkably weak acid-tolerant food spoilage yeast Zygosaccharomyces bailii. The objective of this review paper is to advertise the update of the existing information since the release of N.C.Yeastract in 2019, and to raise awareness in the community about its potential to help the day-to-day work on these species, exploring all the information available in the global YEASTRACT + portal. Using simple and widely used examples, a guided exploitation is offered for several tools: (i) inference of orthologous genes; (ii) search for putative TF binding sites and (iii) inter-species comparison of transcription regulatory networks and prediction of TF-regulated networks based on documented regulatory associations available in YEASTRACT + for well-studied species. The usage potentialities of the new CommunityYeastract platform by the yeast community are also discussed.

Spasmodic cough preceding CANVAS phenotype in a family with biallelic repeat expansions in RFC1.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, multisystem ataxia that remained only clinically defined, until recently, when the discovery of biallelic repeat expansion in the RFC1 gene allowed the genetic link. We describe the first Portuguese familial CANVAS harboring the pathogenic RFC1 expansion. Detail clinical features and course of four affected members are provided. Phenotype characterizations are important as the novel RFC1 mutation is expected to be a major cause of idiopathic late-onset ataxia.

Virtual Reality Cognitive Training Among Individuals With Alcohol Use Disorder Undergoing Residential Treatment: Pilot Randomized Controlled Trial.

BACKGROUND: Alcohol use disorder (AUD) has been associated with diverse physical and mental morbidities. Among the main consequences of chronic and excessive alcohol use are cognitive and executive deficits. Some of these deficits may be reversed in specific cognitive and executive domains with behavioral approaches consisting of cognitive training. The advent of computer-based interventions may leverage these improvements, but randomized controlled trials (RCTs) of digital interactive-based interventions are still scarce. OBJECTIVE: The aim of this study is to explore whether a cognitive training approach using VR exercises based on activities of daily living is feasible for improving the cognitive function of patients with AUD undergoing residential treatment, as well as to estimate the effect size for this intervention to power future definitive RCTs. METHODS: This study consisted of a two-arm pilot RCT with a sample of 36 individuals recovering from AUD in a therapeutic community; experimental group participants received a therapist-guided, VR-based cognitive training intervention combined with treatment as usual, and control group participants received treatment as usual without cognitive training. A comprehensive neuropsychological battery of tests was used both at pre- and postassessments, including measurement of global cognition, executive functions, attention, visual memory, and cognitive flexibility. RESULTS: In order to control for potential effects of global cognition and executive functions at baseline, these domains were controlled for in the statistical analysis for each individual outcome. Results indicate intervention effects on attention in two out of five outcomes and on cognitive flexibility in two out of six outcomes, with effect sizes in significant comparisons being larger for attention than for cognitive flexibility. Patient retention in cognitive training was high, in line with previous studies. CONCLUSIONS: Overall, the data suggest that VR-based cognitive training results in specific contributions to improving attention ability and cognitive flexibility of patients recovering from AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04505345; https://clinicaltrials.gov/show/NCT04505345.