Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.

The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites and their dynamic turnover rates. CBP/p300 acetylates thousands of sites, including signature histone sites and a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Time-resolved acetylome analyses identified a subset of CBP/p300-regulated sites with very rapid (<30 min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation. Quantification of acetylation, mRNA, and protein abundance after CBP/p300 inhibition reveals a kinetically competent network of gene expression that strictly depends on CBP/p300-catalyzed rapid acetylation. Collectively, our in-depth acetylome analyses reveal systems attributes of CBP/p300 targets, and the resource dataset provides a framework for investigating CBP/p300 functions and for understanding the impact of small-molecule inhibitors targeting its catalytic and bromodomain activities.

Nuclear export of circular RNA.

Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1-5, are formed by back-splicing of precursor mRNAs in the nucleus6-10. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export.

Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release.

The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a "recruit-and-release" mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Dynamic lineage priming is driven via direct enhancer regulation by ERK.

Central to understanding cellular behaviour in multi-cellular organisms is the question of how a cell exits one transcriptional state to adopt and eventually become committed to another. Fibroblast growth factor-extracellular signal-regulated kinase (FGF -ERK) signalling drives differentiation of mouse embryonic stem cells (ES cells) and pre-implantation embryos towards primitive endoderm, and inhibiting ERK supports ES cell self-renewal1. Paracrine FGF-ERK signalling induces heterogeneity, whereby cells reversibly progress from pluripotency towards primitive endoderm while retaining their capacity to re-enter self-renewal2. Here we find that ERK reversibly regulates transcription in ES cells by directly affecting enhancer activity without requiring a change in transcription factor binding. ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. Though the binding of mediator components responds directly to signalling, the persistent binding of pluripotency factors to both induced and repressed genes marks them for activation and/or reactivation in response to fluctuations in ERK activity. Among the repressed genes are several core components of the pluripotency network that act to drive their own expression and maintain the ES cell state; if their binding is lost, the ability to reactivate transcription is compromised. Thus, as long as transcription factor occupancy is maintained, so is plasticity, enabling cells to distinguish between transient and sustained signals. If ERK signalling persists, pluripotency transcription factor levels are reduced by protein turnover and irreversible gene silencing and commitment can occur.

Protecting Caribbean patients diagnosed with cancer from compounding disasters.

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.

crANKing up the infection: ankyrin domains in Rickettsiales and their role in host manipulation.

Intracellular bacteria use secreted effector proteins to modify host biology and facilitate infection. For many of these microbes, a particular eukaryotic domain-the ankyrin repeat (ANK)-plays a central role in specifying the host proteins and pathways targeted by the microbe. While we understand much of how some ANKs function in model organisms like Legionella and Coxiella, the understudied Rickettsiales species harbor many proteins with ANKs, some of which play critical roles during infection. This minireview is meant to organize and summarize the research progress made in understanding some of these Rickettsiales ANKs as well as document some of the techniques that have driven much of this progress.

A review of biomedical datasets relating to drug discovery: a knowledge graph perspective.

Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritization. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, while relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data are required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorized according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and an evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, while also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.

Multimodal Analgesia and Small Opioid Prescriptions are the New Standard in Total Joint Arthroplasty: A Survey of the AAHKS Membership.

INTRODUCTION: The purpose of this survey study was to assess the current analgesia and anesthesia practices used by total joint arthroplasty (TJA) surgeon members of the American Association of Hip and Knee Surgeons (AAHKS) as well as identify changes in practice made by AAHKS members over time. METHODS: A survey of 37 questions was created and approved by the AAHKS Research Committee. The survey was distributed to all 3,243 practicing adult reconstruction surgeon members of AAHKS in May 2023. Results were compared to a nearly identical survey sent out to all board-certified adult reconstruction surgeon members of AAHKS five years previously in November 2018. RESULTS: There were 527 responses (16%) to the survey. Since 2018, the mean number of opioid pills prescribed after TJA has declined significantly from 49 to 32 pills after TKA and from 44 to 18 pills after THA. The use of multimodal analgesics in addition to opioids has also increased over the past five years from 74 to 93%. The most common medications utilized include nonsteroidal anti-inflammatories (98%), acetaminophen (80%), and gabapentinoids (32%). A majority of surgeons (78%) still use a spinal for total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, there has been an increase in the number of surgeons using peripheral nerve blocks for TKA from 69% in 2018 to 84% in 2023. The routine use of periarticular injection or local infiltration anesthesia in THA and TKA has also increased over the past 5 years from 80 to 86%. CONCLUSION: Since 2018, there has been increased adoption of multimodal analgesia and anesthesia, and improved consensus regarding the optimal regimen among surveyed arthroplasty surgeon members of AAHKS. The number of opioid pills prescribed after THA and TKA has declined significantly over the past 5 years.

Outpatient Total Joint Arthroplasty in the "Unhealthy": Staying Safe Using Institutional Protocols.

BACKGROUND: Recent expansion in the indications for outpatient total joint arthroplasty has led to debates over patient selection. The purpose of this study was to compare early clinical outcomes and complications of same-day discharge (SDD) hip and knee arthroplasties from a high-volume institution based on the American Society of Anesthesiologists (ASA) physical status classification. METHODS: Prospectively collected data were reviewed for all SDD primary joint arthroplasties between January 2013 and August 2023. There were 8 surgeons who performed 7,258 cases at hospital outpatient (n = 4,288) or ambulatory surgery centers (n = 2,970). This included 3,239 total hip arthroplasties, 1,503 total knee arthroplasties, and 2,516 unicompartmental knee arthroplasties. The ASA 1 group comprised 506 subjects, compared to 5,005 for ASA 2 and 1,736 for ASA 3. The primary outcomes included emergency department (ED) visits, readmissions, complications, and revisions within 24 hours and 90 days of surgery. The ASA 3 group was older (ASA 1 = 55 versus ASA 2 = 63 versus ASA 3 = 66 years; P < .01) and had a higher body mass index (ASA 1 = 25.4 versus ASA 2 = 28.5 versus ASA 3 = 32.7; P < .01). RESULTS: There were no differences between ASA groups in joint-related ED visits, readmissions, and complications within 24 h and 90 days of surgery (P > .05). Subjects in the ASA 3 group experienced greater 90-day revisions compared to the other groups (ASA 1 = 1 of 506, 0.2% versus ASA 2 = 15 of 5,005, 0.3% versus ASA 3 = 15 of 1,736, 0.9%; P = .01). Regarding systemic events, ASA 1 subjects experienced significantly greater 24-hour complications (8 of 506, 1.6%) and ED visits (5 of 506, 1.0%), and the ASA 3 subjects had a higher incidence of 90-day readmissions (19 of 1,736, 1.1%) compared to the other groups (P < .05). Within 24 hours of discharge, urinary retention and syncope were the most frequent complications that required additional health care utilization. CONCLUSIONS: Medically optimized patients categorized as ASA 3 can safely undergo SDD hip and knee arthroplasty without increased risk of 24-hour or 90-day complications. Patient preference for outpatient care, reliable social support, and independent functional status are imperative for a successful outpatient program.

The Effect of the COVID Pandemic on the Rate of Same-Day Discharge in Primary Hip and Knee Arthroplasty.

BACKGROUND: Same-day discharge (SDD) following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) started increasing prior to 2020. The purpose of this study was to evaluate the change in the rate of SDD after the pandemic and determine whether those changes became permanent. METHODS: The annual rate of SDD for 15,208 primary THA and TKA cases performed between January 1, 2015, and September 9, 2022, at a single institution was determined. We also examined changes in SDD patient demographics as well as differences in the 90-day complication rates of SDD and overnight patients. RESULTS: In 2015, the rate of SDD for primary arthroplasty was 24%, which grew annually to 29% in 2019. Postpandemic, the rate of SDD jumped above 50% and continued up to 64% by 2022. The biggest increase was in TKA, which went from under 10% SDD prepandemic to 50% by 2022. The average age and body mass index of SDD cases prepandemic increased significantly to 62 ± 9 years and 29.4 ± 5.3 (P < .01). Overnight patients had higher rates of 90-day postoperative complications (8.4 versus 4.2%, P < .00001). CONCLUSIONS: The pandemic caused major changes in the rate of SDD for primary THA and TKA, increasing in subsequent years. The SDD patients became older and heavier due to the expanded criteria for SDD cases. The 90-day postoperative complication rate was lower for SDD patients since higher risk patients were kept overnight. At the prepandemic rate, 29% of patients currently being sent home would have stayed overnight.

Outcomes Following Intraoperative Calcar Fractures During Cementless Total Hip Arthroplasty.

BACKGROUND: Intraoperative calcar fractures (IOCFs) are an established complication of cementless total hip arthroplasty (THA). Prompt recognition and management may prevent subsequent postoperative complications. This study aimed to evaluate the outcomes and revision rates of THAs with IOCFs identified and managed intraoperatively. METHODS: There were 11,438 primary cementless THAs performed at a single institution from 2009 to 2022. Prospectively collected data on cases with an IOCF was compared to cases without the complication. The fracture group had a lower body mass index (26.9 versus 28.9 kg/m2; P = .01). Patient age, sex, and mean follow-up (3.2 (0 to 12.8) versus 3.5 years (0 to 14); P = .45) were similar between groups. RESULTS: An IOCF occurred in 62 of 11,438 (0.54%) cases. The THAs done via a direct anterior approach experienced the lowest rate of fractures (31 of 7,505, 0.4%) compared to postero-lateral (27 of 3,759, 0.7%; P = .03) and lateral (4 of 165, 2.4%; P < .01) approaches. Of the IOCFs, 48 of 62 (77%) were managed with cerclage cabling, 4 of 62 (6.5%) with intraoperative stem design change and cabling, 4 of 62 (6.5%) with restricted weight-bearing, and 6 of 62 (9.7%) with no modification to the standard postoperative protocol. The IOCF group experienced one case of postoperative component subsidence. No subjects in the IOCF cohort required revision, and rates were similar between groups (0 of 62, 0% versus 215 of 11,376, 1.9%; P = .63). Postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement scores were comparable (85.7 versus 86.4; P = .80). CONCLUSIONS: Cementless THA complicated by IOCF had similar postoperative revision rates and patient-reported outcome measures at early follow-up when compared to patients not experiencing this complication. Surgeons may use these data to provide postoperative counseling on expectations and outcomes following these rare intraoperative events.

Advanced Concepts in Outpatient Joint Arthroplasty.

As the adoption and utilization of outpatient total joint arthroplasty continues to grow, key developments have enabled surgeons to safely and effectively perform these surgeries while increasing patient satisfaction and operating room efficiency. Here, the authors will discuss the evidence-based principles that have guided this paradigm shift in joint arthroplasty surgery, as well as practical methods for selecting appropriate candidates and optimizing perioperative care. There will be 5 core efficiency principles reviewed that can be used to improve organizational management, streamline workflow, and overcome barriers in the ambulatory surgery center. Finally, future directions in outpatient surgery at the ASC, including the merits of implementing robot assistance and computer navigation, as well as expanding indications for revision surgeries, will be debated.

The CCJR® Charles A. Engh, Sr, MD. Excellence in Hip Research Award: The Evolution of Revision Hip Arthroplasty and Impact on the Trainee's Experience.

BACKGROUND: Advances in total hip arthroplasty (THA) have resulted in evolving revision indications and intraoperative techniques, which can influence the exposure of trainees to complex cases. We report 3 decades of revision experience from a tertiary referral center that trains fellows, comparing the reasons for revision and the complexity of revisions over time. METHODS: We retrospectively reviewed all revision THAs performed at our institution from 1990 to 2022. Revision diagnoses, components revised, types of revision implants used, and exposure techniques were collected. A "complex" revision was defined as a case that involved an extended trochanteric osteotomy, triflange and cup-cage construct, or acetabular augment. RESULTS: A total of 3,556 THA revisions were identified (108 revisions/year). Aseptic loosening was the most common indication in 1990 to 1999 (45 per year), but decreased to 28.3/year in 2010 to 2019. From 1990 to 1999 and 2010 to 2019, fracture increased from 3.1 to 7.3 per year, infection from 2.9/year to 16.9/year, and metallosis from 0.1 to 13.2 per year. Both component revision were common from 1990 to 1994 (42.6 per year), while polyethylene exchange was most common in 2010 to 2019 (43.3 per year). A decrease was observed in "complex" cases over time: 14.8 extended trochanteric osteotomies/year in 2000 to 2004 compared to 5.4 per year in 2018 to 2022, 4.5 triflange and cup-cage constructs/year in 2004 to 2007 compared to 0.8 per year in 2018 to 2022, and 4 acetabular augments per year in 2009 to 2012 compared to 1 per year in 2018 to 2022. CONCLUSIONS: Indications for revision have changed over the decades, while the number of "complex" revisions has gradually decreased, presumably due to advances in implants and materials. If this trend extends to other training institutions, the next generation of arthroplasty surgeons will have less exposure to complex revisions during their training.

Direct Anterior Total Hip Arthroplasty with VELYS™ Hip Navigation.

We describe the technique of total hip arthroplasty via a direct anterior approach using the Depuy Synthes (Raynham, MA) VELYS™ Hip Navigation system This technique allows one to accurately set the acetabular component position as well as recreate leg length and offset to meet the goals of hip reconstruction in a precise and efficient manner.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Vernal: a tool for mining fuzzy network motifs in RNA.

MOTIVATION: RNA 3D motifs are recurrent substructures, modeled as networks of base pair interactions, which are crucial for understanding structure-function relationships. The task of automatically identifying such motifs is computationally hard, and remains a key challenge in the field of RNA structural biology and network analysis. State-of-the-art methods solve special cases of the motif problem by constraining the structural variability in occurrences of a motif, and narrowing the substructure search space. RESULTS: Here, we relax these constraints by posing the motif finding problem as a graph representation learning and clustering task. This framing takes advantage of the continuous nature of graph representations to model the flexibility and variability of RNA motifs in an efficient manner. We propose a set of node similarity functions, clustering methods and motif construction algorithms to recover flexible RNA motifs. Our tool, Vernal can be easily customized by users to desired levels of motif flexibility, abundance and size. We show that Vernal is able to retrieve and expand known classes of motifs, as well as to propose novel motifs. AVAILABILITY AND IMPLEMENTATION: The source code, data and a webserver are available at vernal.cs.mcgill.ca. We also provide a flexible interface and a user-friendly webserver to browse and download our results. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RNAglib: a python package for RNA 2.5 D graphs.

SUMMARY: RNA 3D architectures are stabilized by sophisticated networks of (non-canonical) base pair interactions, which can be conveniently encoded as multi-relational graphs and efficiently exploited by graph theoretical approaches and recent progresses in machine learning techniques. RNAglib is a library that eases the use of this representation, by providing clean data, methods to load it in machine learning pipelines and graph-based deep learning models suited for this representation. RNAglib also offers other utilities to model RNA with 2.5 D graphs, such as drawing tools, comparison functions or baseline performances on RNA applications. AVAILABILITY AND IMPLEMENTATION: The method is distributed as a pip package, RNAglib. Data are available in a repository and can be accessed on rnaglib's web page. The source code, data and documentation are available at https://rnaglib.cs.mcgill.ca. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Physical Versus Virtual Reality-Based Calm Rooms for Psychiatric Inpatients: Quasi-Randomized Trial.

BACKGROUND: Interest in sensory rooms or so-called "calm rooms" in psychiatric inpatient care has increased significantly. In a hospital setting, their purpose is to introduce a relaxing environment to increase well-being as well as to decrease anxiety and aggressive behaviors. Calm rooms can also be used as a tool to provide self-help through a convenient environment for the patients and, at the same time, strengthen the therapeutic relationship between the patient and the professional. Recent developments in virtual reality (VR) have made virtual calm rooms possible, but these have not yet been evaluated in psychiatric inpatient care. OBJECTIVE: This study aimed to compare the effects of VR and physical calm rooms on self-reported well-being and physiological markers of arousal. METHODS: The study was conducted in 2 inpatient psychiatric wards specializing in bipolar disorder from March 2019 to February 2021. Patients who were already admitted were asked if they were interested in using a calm room and willing to provide ratings. This study relied on the quasi-randomized allocation of patients to the wards, which either had a physical or VR calm room. Self-assessment scales (Montgomery-Åsberg Depression Rating Scale-Self Assessment [MADRS-S], Beck Anxiety Scale, and Clinical Global Impression) were used to determine the participants' baseline level of depressive and anxiety symptoms before their use of the physical or VR calm room. The study determined the state of well-being measured using an 11-point visual analog scale (VAS) as well as arousal measured by blood pressure (systolic and diastolic) and heart rate before and after the use of the calm rooms. The primary end point was self-reported well-being using the VAS. RESULTS: A total of 60 participants were included-40 used the VR calm room and 20 used the physical calm room. The mean age of participants was 39 years and the majority were women (35/60, 58%). Analysis of VAS measurement showed improved well-being at the group level from before to after the intervention (P<.05), with no statistically significant difference in effects between the 2 different interventions. Effects were not moderated by baseline depression levels (dichotomized as MADRS-S >20 or ≤20) despite an overall difference in reported well-being between subgroups. CONCLUSIONS: Although the power in this study was low, the findings of this first study indicate comparable effects with respect to well-being and arousal of a VR calm room and a physical calm room. This suggests that a VR calm room can be a viable alternative when the use of a physical calm room is not an option for logistic or other reasons. TRIAL REGISTRATION: ClinicalTrials.gov NCT03918954; https://clinicaltrials.gov/ct2/show/NCT03918954.