MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

Learning together for better health using an evidence-based Learning Health System framework: a case study in stroke.

BACKGROUND: In the context of expanding digital health tools, the health system is ready for Learning Health System (LHS) models. These models, with proper governance and stakeholder engagement, enable the integration of digital infrastructure to provide feedback to all relevant parties including clinicians and consumers on performance against best practice standards, as well as fostering innovation and aligning healthcare with patient needs. The LHS literature primarily includes opinion or consensus-based frameworks and lacks validation or evidence of benefit. Our aim was to outline a rigorously codesigned, evidence-based LHS framework and present a national case study of an LHS-aligned national stroke program that has delivered clinical benefit. MAIN TEXT: Current core components of a LHS involve capturing evidence from communities and stakeholders (quadrant 1), integrating evidence from research findings (quadrant 2), leveraging evidence from data and practice (quadrant 3), and generating evidence from implementation (quadrant 4) for iterative system-level improvement. The Australian Stroke program was selected as the case study as it provides an exemplar of how an iterative LHS works in practice at a national level encompassing and integrating evidence from all four LHS quadrants. Using this case study, we demonstrate how to apply evidence-based processes to healthcare improvement and embed real-world research for optimising healthcare improvement. We emphasize the transition from research as an endpoint, to research as an enabler and a solution for impact in healthcare improvement. CONCLUSIONS: The Australian Stroke program has nationally improved stroke care since 2007, showcasing the value of integrated LHS-aligned approaches for tangible impact on outcomes. This LHS case study is a practical example for other health conditions and settings to follow suit.

Dynamic structural evolution of MgO-supported palladium catalysts: from metal to metal oxide nanoparticles to surface then subsurface atomically dispersed cations.

Supported noble metal catalysts, ubiquitous in chemical technology, often undergo dynamic transformations between reduced and oxidized states-which influence the metal nuclearities, oxidation states, and catalytic properties. In this investigation, we report the results of in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, and other physical characterization techniques, bolstered by density functional theory, to elucidate the structural transformations of a set of MgO-supported palladium catalysts under oxidative treatment conditions. As the calcination temperature increased, the as-synthesized supported metallic palladium nanoparticles underwent oxidation to form palladium oxides (at approximately 400 °C), which, at approximately 500 °C, were oxidatively fragmented to form mixtures of atomically dispersed palladium cations. The data indicate two distinct types of atomically dispersed species: palladium cations located at MgO steps and those embedded in the first subsurface layer of MgO. The former exhibit significantly higher (>500 times) catalytic activity for ethylene hydrogenation than the latter. The results pave the way for designing highly active and stable supported palladium hydrogenation catalysts with optimized metal utilization.

Protocol to develop human alveolar macrophage-like cells from mononuclear cells or purified monocytes for use in respiratory biology research.

Human alveolar macrophages are a unique myeloid subset critical for understanding pulmonary diseases and are difficult to access. Here, we present a protocol to generate human alveolar macrophage-like (AML) cells from fresh peripheral blood mononuclear cells or purified monocytes. We describe steps for cell isolation, incubation in a defined cocktail of pulmonary surfactant and lung-associated cytokines, phenotype analysis, and validation with human alveolar macrophages. We then detail procedures for quality control and technical readouts for monitoring microbial response. For complete details on the use and execution of this protocol, please refer to Pahari et al.1 and Neehus et al.2.

Anatomy beyond the pandemic: A Q-methodology study exploring student perceptions toward a hybrid curriculum.

As a result of the COVID-19 pandemic, anatomy education was forced to adopt online modes of delivery. Previous research on student views revealed areas of strong preference (asynchronous lectures) and strong dislike (virtual specimens) in online anatomy courses. The current study seeks to compare the views of a single cohort of students experiencing both online and in-person undergraduate introductory anatomy and physiology courses. This comparison can highlight what students consider beneficial to their education and can inform future hybrid course offerings. Q-methodology was used to assess the opinions of students. Students sorted 41 statements on anatomy education in a quasi-normally distributed grid based on their degree of agreement with the statements. The rankings underwent a by-person factor analysis which categorized students with shared perceptions into groups. Data were collected from 246 students in the primarily online fall semester and 191 students in the primarily in-person winter semester. Analysis revealed three distinct factors (groups) in the cohort. Factor one (n = 113 (fall), n = 93 (winter)), was satisfied overall with the course materials and delivery. Factor two (n = 52 (fall), n = 18 (winter)) had a deep dislike of online learning, and factor three (n = 37 (fall), n = 49 (winter)) had a strong preference for online learning. While many students were comfortable in both online and in-person learning environments, this was not the case for all learners. The strengths and weaknesses of each teaching modality suggest the opportunity to explore hybrid learning as an option for future course offerings and specifically highlight valuable aspects to incorporate from each environment.

Reversible Intrapore Redox Cycling of Platinum in Platinum-Ion-Exchanged HZSM-5 Catalysts.

Isolated platinum(II) ions anchored at acid sites in the pores of zeolite HZSM-5, initially introduced by aqueous ion exchange, were reduced to form platinum nanoparticles that are stably dispersed with a narrow size distribution (1.3 ± 0.4 nm in average diameter). The nanoparticles were confined in reservoirs within the porous zeolite particles, as shown by electron beam tomography and the shape-selective catalysis of alkene hydrogenation. When the nanoparticles were oxidatively fragmented in dry air at elevated temperature, platinum returned to its initial in-pore atomically dispersed state with a charge of +2, as shown previously by X-ray absorption spectroscopy. The results determine the conditions under which platinum is retained within the pores of HZSM-5 particles during redox cycles that are characteristic of the reductive conditions of catalyst operation and the oxidative conditions of catalyst regeneration.

Endovascular thrombectomy with versus without intravenous thrombolysis in patients with acute basilar artery occlusion: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The benefit and safety of intravenous thrombolysis before endovascular thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion (BAO) remains unclear. This article aims to investigate the clinical outcomes and safety of endovascular thrombectomy with versus without intravenous thrombolysis in acute BAO stroke patients. METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases to identify relevant literature pertaining to patients with acute BAO who underwent endovascular thrombectomy alone or intravenous thrombolysis bridging with endovascular thrombectomy (bridging therapy), until January 10, 2024. The primary outcome was functional independence, defined as a score of 0-2 on the modified Rankin Scale at 90 days. The safety outcome was mortality at 90 days and symptomatic intracranial hemorrhage within 48 h. Effect sizes were computed as risk ratio (RR) with random-effect models. This study was registered in PROSPERO (CRD42023462293). RESULTS: A total of 528 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded. Finally, 2 RCTs and 10 cohort studies met the inclusion criteria. The findings revealed that the endovascular thrombectomy alone group had a lower rate of functional independence compared to the bridging therapy group (29% vs 38%; RR 0.78, 95% CI 0.68-0.88, p < 0.001), lower independent ambulation (39% vs 45%; RR 0.89, 95% CI 0.82-0.98, p = 0.01), and higher mortality (36% vs 28%, RR 1.22, 95% CI 1.08-1.37, p = 0.001). However, no differences were detected in symptomatic intracranial hemorrhage between the two groups (6% vs 4%; RR 1.12, 95% CI 0.74-1.71, p = 0.58). CONCLUSION: Intravenous thrombolysis plus endovascular thrombectomy seemed to led to better functional independence, independent ambulation, and lower risk of mortality without increasing the incidence of intracranial hemorrhage compared to endovascular thrombectomy alone. However, given the non-randomized nature of this study, further studies are needed to confirm these findings.

A toxicology study of Csf2ra complementation and pulmonary macrophage transplantation therapy of hereditary PAP in mice.

Pulmonary macrophage transplantation (PMT) is a gene and cell transplantation approach in development as therapy for hereditary pulmonary alveolar proteinosis (hPAP), a surfactant accumulation disorder caused by mutations in CSF2RA/B (and murine homologs). We conducted a toxicology study of PMT of Csf2ra gene-corrected macrophages (mGM-Rα+Mϕs) or saline-control intervention in Csf2raKO or wild-type (WT) mice including single ascending dose and repeat ascending dose studies evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics. Lentiviral-mediated Csf2ra cDNA transfer restored GM-CSF signaling in mGM-Rα+Mϕs. Following PMT, mGM-Rα+Mϕs engrafted, remained within the lungs, and did not undergo uncontrolled proliferation or result in bronchospasm, pulmonary function abnormalities, pulmonary or systemic inflammation, anti-transgene product antibodies, or pulmonary fibrosis. Aggressive male fighting caused a similarly low rate of serious adverse events in saline- and PMT-treated mice. Transient, minor pulmonary neutrophilia and exacerbation of pre-existing hPAP-related lymphocytosis were observed 14 days after PMT of the safety margin dose but not the target dose (5,000,000 or 500,000 mGM-Rα+Mϕs, respectively) and only in Csf2raKO mice but not in WT mice. PMT reduced lung disease severity in Csf2raKO mice. Results indicate PMT of mGM-Rα+Mϕs was safe, well tolerated, and therapeutically efficacious in Csf2raKO mice, and established a no adverse effect level and 10-fold safety margin.

Effects of ingesting large prey on the kinematics of rectilinear locomotion in Boa constrictor.

Large and stout snakes commonly consume large prey and use rectilinear crawling; yet, whether body wall distention after feeding impairs rectilinear locomotion is poorly understood. After eating large prey (30-37% body mass), all Boa constrictor tested could perform rectilinear locomotion in the region with the food bolus despite a greatly increased distance between the ribs and the ventral skin that likely lengthens muscles relevant to propulsion. Unexpectedly, out of 11 kinematic variables, only two changed significantly (P<0.05) after feeding: cyclic changes in snake height increased by more than 1.5 times and the longitudinal movements of the ventral skin relative to the skeleton decreased by more than 25%. Additionally, cyclic changes in snake width suggest that the ribs are active and mobile during rectilinear locomotion, particularly in fed snakes, but also in unfed snakes. These kinematic changes suggest that rectilinear actuators reorient more vertically and undergo smaller longitudinal excursions following large prey ingestion, both of which likely act to reduce elongation of these muscles that may otherwise experience substantial strain.

Anion Binding to Ammonium and Guanidinium Hosts: Implications for the Reverse Hofmeister Effects Induced by Lysine and Arginine Residues.

Anions have a profound effect on the properties of soluble proteins. Such Hofmeister effects have implications in biologics stability, protein aggregation, amyloidogenesis, and crystallization. However, the interplay between the important noncovalent interactions (NCIs) responsible for Hofmeister effects is poorly understood. To contribute to improving this state of affairs, we report on the NCIs between anions and ammonium and guanidinium hosts 1 and 2, and the consequences of these. Specifically, we investigate the properties of cavitands designed to mimic two prime residues for anion-protein NCIs─lysines and arginines─and the solubility consequences of complex formation. Thus, we report NMR and ITC affinity studies, X-ray analysis, MD simulations, and anion-induced critical precipitation concentrations. Our findings emphasize the multitude of NCIs that guanidiniums can form and how this repertoire qualitatively surpasses that of ammoniums. Additionally, our studies demonstrate the ease by which anions can dispense with a fraction of their hydration-shell waters, rearrange those that remain, and form direct NCIs with the hosts. This raises many questions concerning how solvent shell plasticity varies as a function of anion, how the energetics of this impact the different NCIs between anions and ammoniums/guanidiniums, and how this affects the aggregation of solutes at high anion concentrations.

Tubular Injury Biomarkers to Predict Chronic Kidney Disease and Hypertension at 3-Months Post-Cisplatin in Children.

BACKGROUND: Urine kidney injury biomarkers measured during cisplatin therapy may identify patients at risk for adverse subsequent kidney outcomes. We examined relationships between tubular injury biomarkers collected early (early visit [EV]: first or second cisplatin cycle) and late (late visit [LV]: last or second-last cisplatin cycle) during cisplatin therapy, with 3-month post-cisplatin chronic kidney disease (CKD) and hypertension. METHODS: We analyzed data from the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment Nephrotoxicity Study: twelve-center prospective cohort study of 159 children receiving cisplatin. We measured urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine, kidney injury molecule-1 (KIM-1)/creatinine, tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP-7) (TIMP-2 and IGFBP-7 expressed as their product, ng/ml^2/1000) at an EV and LV during cisplatin therapy with pre-infusion, post-infusion, and hospital discharge sampling. Area under the curve (AUC) was calculated for biomarkers to detect 3-month post-cisplatin CKD (KDIGO guidelines: low estimated glomerular filtration rate (eGFR) or elevated uACR for age) and hypertension (three blood pressures; per American Academy of Pediatrics guidelines). RESULTS: At median follow-up of 90 days, 52/118 (44%) and 17/125 (14%) developed CKD and hypertension, respectively. Biomarker prediction for 3-month CKD was low to modest; NGAL combined with KIM-1 at EV discharge yielded the highest AUC (0.67, 95% CI 0.57-0.77). Biomarker prediction of 3-month hypertension was stronger, but modest; the highest AUC was from combining EV pre-infusion NGAL and TIMP-2*IGFBP-7 (0.71, 95% CI 0.62-0.80). When EV pre-infusion NGAL and TIMP-2*IGFBP-7 were added to the 3-month hypertension clinical predictive model, AUCs increased from 0.81 (0.72-0.91) to 0.89 (0.83-0.95) (p<0.05). CONCLUSIONS: Tubular injury biomarkers we studied were individually not strong predictors of 3-month post-cisplatin kidney outcomes. Adding biomarkers to existing clinical prediction models may help predict post-therapy hypertension and identify higher kidney-risk patients.

Assessing Weak Anion Binding to Small Peptides.

Since Hofmeister's seminal studies in the late 19th century, it has been known that salts and buffers can drastically affect the properties of peptides and proteins. These Hofmeister effects can be conceived of in terms of three distinct phenomena/mechanisms: water-salt interactions that indirectly induce the salting-out of a protein by water sequestration by the salt, and direct salt-protein interactions that can either salt-in or salt-out the protein. Unfortunately, direct salt-protein interactions responsible for Hofmeister effects are weak and difficult to quantify. As such, they are frequently construed of as being nonspecific. Nevertheless, there has been considerable effort to better specify these interactions. Here, we use pentapeptides to demonstrate the utility of the H-dimension of nuclear magnetic resonance (NMR) spectroscopy to assess anion binding using N-H signal shifts. We qualify binding using these, demonstrating the upfield shifts induced by anion association and revealing how they are much larger than the corresponding downfield shifts induced by magnetic susceptibility and other ionic strength change effects. We also qualify binding in terms of how the pattern of signal shifts changes with point mutations. In general, we find that the observed upfield shifts are small compared with those induced by anion binding to amide-based hosts, and MD simulations suggest that this is so. Thus, charge-diffuse anions associate mostly with the nonpolar regions of the peptide rather than directly interacting with the amide N-H groups. These findings reveal the utility of 1H NMR spectroscopy for qualifying affinity to peptides─even when affinity constants are very low─and serve as a benchmark for using NMR spectroscopy to study anion binding to more complex systems.

Ecological inferences on invasive carp survival using hydrodynamics and egg drift models.

Bighead carp (Hypophthalmichthys nobilis), silver carp (H. molitrix), black carp (Mylopharyngodon piceus), and grass carp (Ctenopharyngodon idella), are invasive species in North America. However, they hold significant economic importance as food sources in China. The drifting stage of carp eggs has received great attention because egg survival rate is strongly affected by river hydrodynamics. In this study, we explored egg-drift dynamics using computational fluid dynamics (CFD) models to infer potential egg settling zones based on mechanistic criteria from simulated turbulence in the Lower Missouri River. Using an 8-km reach, we simulated flow characteristics with four different discharges, representing 45-3% daily flow exceedance. The CFD results elucidate the highly heterogeneous spatial distribution of flow velocity, flow depth, turbulence kinetic energy (TKE), and the dissipation rate of TKE. The river hydrodynamics were used to determine potential egg settling zones using criteria based on shear velocity, vertical turbulence intensity, and Rouse number. Importantly, we examined the difference between hydrodynamic-inferred settling zones and settling zones predicted using an egg-drift transport model. The results indicate that hydrodynamic inference is useful in determining the 'potential' of egg settling, however, egg drifting paths should be taken into account to improve prediction. Our simulation results also indicate that the river turbulence does not surpass the laboratory-identified threshold to pose a threat to carp eggs.

Evaluation of the X-ray/EUV Nanolithography Facility at AS through wavefront propagation simulations.

Synchrotron light sources can provide the required spatial coherence, stability and control to support the development of advanced lithography at the extreme ultraviolet and soft X-ray wavelengths that are relevant to current and future fabricating technologies. Here an evaluation of the optical performance of the soft X-ray (SXR) beamline of the Australian Synchrotron (AS) and its suitability for developing interference lithography using radiation in the 91.8 eV (13.5 nm) to 300 eV (4.13 nm) range are presented. A comprehensive physical optics model of the APPLE-II undulator source and SXR beamline was constructed to simulate the properties of the illumination at the proposed location of a photomask, as a function of photon energy, collimation and monochromator parameters. The model is validated using a combination of experimental measurements of the photon intensity distribution of the undulator harmonics. It is shown that the undulator harmonics intensity ratio can be accurately measured using an imaging detector and controlled using beamline optics. Finally, the photomask geometric constraints and achievable performance for the limiting case of fully spatially coherent illumination are evaluated.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

Cataplexy response with extended-release once-nightly sodium oxybate: Post hoc responder analyses from the phase 3 REST-ON clinical trial.

Background: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant (P < 0.001 at 6 g, 7.5 g, and 9 g) reductions in cataplexy episodes in participants in the phase 3 REST-ON clinical trial (NCT02720744). This post hoc analysis from REST-ON further characterized changes in cataplexy episodes in participants with narcolepsy type 1 (NT1). Methods: Participants with narcolepsy aged ≥16 years received ON-SXB (1 wk, 4.5 g; 2 wk, 6 g; 5 wk, 7.5 g; 5 wk, 9 g) or placebo. Percentages of participants with NT1 who had ≥25%, ≥50%, ≥75%, and 100% reductions from baseline in mean number of weekly cataplexy episodes were determined. Two-sided P values comparing ON-SXB vs placebo were calculated with Fisher exact test. Results: Participants with NT1 (ON-SXB, n = 73; placebo, n = 72; modified intent-to-treat population) had a baseline mean number of weekly cataplexy episodes of 18.9 (ON-SXB) and 19.8 (placebo). Of participants receiving the highest doses of ON-SXB (7.5 and 9 g), approximately half had a 50% reduction, one-third had a 75% reduction, and one-tenth had a 100% reduction in their cataplexy episodes vs placebo. Significantly greater proportions of participants receiving ON-SXB vs placebo had respective reductions in weekly cataplexy episodes of ≥25% at weeks 1 (4.5 g; P < 0.05), 3 (6 g; P < 0.001), 8 (7.5 g; P < 0.001), and 13 (9 g; P = 0.001). Conclusions: A significantly greater proportion of participants receiving ON-SXB vs placebo experienced reductions in weekly cataplexy episodes at all tested doses. Approximately 10% of participants taking the 2 highest ON-SXB doses had complete elimination of their cataplexy.