Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases.

Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestral ribonuclease (AncRNase) from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions.

Simulation dataset of thermal and epithermal neutron self-shielding correction factors for 186W(n,γ)187W reaction rate experiments using tungsten foil targets.

In the experiments of neutron interaction with research samples, the incident neutron energy spectrum, distribution inside the irradiating sample volume, is affected by the unexpected neutron self-shielding effects. The nature of these effects is due to the formation and thickness of the irradiating sample, which significantly causes neutron self-absorption and multiple scattering inside the sample volume. The datasets presented in this article showed the thermal (Gth) and epithermal (Gepi) neutron self-shielding correction factors for the 186W(n,γ)187W neutron capture reaction rate in irradiating tungsten (W) foil samples with different thicknesses. The simulations were performed for three models of surface neutron source's geometries and relative orientations of the irradiating foil samples of isotropic cylinder surface neutron source with foil sample along to the center line, isotropic cylinder neutron source with foil sample flat to the center line, and isotropic spherical neutron source with foil sample placed at the center point. The range of sample thicknesses was from 10 µm to 2.5 mm. The uncertainties for each data point are also reported in the data table, making it more convenient for reuse in related experiments or evaluations.

Characterisation of the mating-type loci in species of Elsinoe causing scab diseases.

The genus Elsinoe includes many aggressive plant pathogens that infect various economically important agricultural, horticultural and forestry plants. Significant diseases include citrus scab caused by E. fawcettii and E. australis, grapevine spot anthracnose by E. ampelina, and the emerging Eucalyptus scab and shoot malformation disease caused by the recently described E. necatrix. Despite their importance as plant pathogens, little is known regarding the biology of many Elsinoe spp. To gain insights into the reproductive biology of these fungi, we characterized the mating-type loci of seven species using whole genome sequence data. Results showed that the MAT1 locus organization and its flanking genes is relatively conserved in most cases. All seven species manifested a typical heterothallic mating system characterized by having either the MAT1-1 or MAT1-2 idiomorph present in an isolate. These idiomorphs were defined by the MAT1-1-1 or the MAT1-2-1 gene, respectively. A unique MAT1-1 idiomorph containing a truncated MAT1-2-1 gene, and a MAT1-1-1 gene, was identified in E. necatrix and E. fawcettii genomes. Additionally, two idiomorph-specific proteins were found in the MAT1-1 and MAT1-2 idiomorphs of E. australis. Universal mating-type markers confirmed heterothallism across 21 Elsinoe spp., are poised to advance future studies regarding the biology of these fungi.

Corrigendum to "Multiband rabi antenna using nest microstrip add-drop filter (NMADF) for relativistic sensing applications" [Heliyon 9(2) (February 2023) e13611].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13611.].

Complete genome sequence of a novel lytic phage of Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice.

Bacteriophage L522, which infects Xanthomonas oryzae pv. oryzae, was isolated from a paddy leaf sample collected in Long An province, Vietnam. The phage shows myovirus morphology based on transmission electron microscopy. It displays a latent period and burst size of approximately 3 h and 63 new virions per infected cell (PFU/infected cell), respectively. The genome of L522 is 44,497 bp in length, with 52% GC content. Of the 63 genes identified, functions were predicted for 26. No virulence or antibiotic-resistance genes were detected. The results of a BLASTn search showed similarity to a previously reported Xanthomonas phage, with 85% average nucleotide sequence identity and 87.15% query coverage. Thus, this L522 is a representative of a new species in the genus Xipdecavirus.

RENEB Inter-Laboratory Comparison 2021: The Cytokinesis-Block Micronucleus Assay.

The goal of the RENEB inter-laboratory comparison 2021 exercise was to simulate a large-scale radiation accident involving a network of biodosimetry labs. Labs were required to perform their analyses using different biodosimetric assays in triage mode scoring and to rapidly report estimated radiation doses to the organizing institution. This article reports the results obtained with the cytokinesis-block micronucleus assay. Three test samples were exposed to blinded doses of 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 13 mA, ∼75 keV, 1 Gy/min). These doses belong to 3 triage categories of clinical relevance: a low dose category, for no exposure or exposures inferior to 1 Gy, requiring no direct treatment of subjects; a medium dose category, with doses ranging from 1 to 2 Gy, and a high dose category, after exposure to doses higher than 2 Gy, with the two latter requiring increasing medical attention. After irradiation the test samples (no. 1, no. 2 and no. 3) were sent by the organizing laboratory to 14 centers participating in the micronucleus assay exercise. Laboratories were asked to setup micronucleus cultures and to perform the micronucleus assay in triage mode, scoring 500 binucleated cells manually, or 1,000 binucleated cells in automated/semi-automated mode. One laboratory received no blood samples, but scored pictures from another lab. Based on their calibration curves, laboratories had to provide estimates of the administered doses. The accuracy of the reported dose estimates was further analyzed by the micronucleus assay lead. The micronucleus assay allowed classification of samples in the corresponding clinical triage categories (low, medium, high dose category) in 88% of cases (manual scoring, 88%; semi-automated scoring, 100%; automated scoring, 73%). Agreement between scoring laboratories, assessed by calculating the Fleiss' kappa, was excellent (100%) for semi-automated scoring, good (83%) for manual scoring and poor (53%) for fully automated scoring. Correct classification into triage scoring dose intervals (reference dose ±0.5 Gy for doses ≤2.5 Gy, or reference dose ±1 Gy for doses >2.5 Gy), recommended for triage biodosimetry, was obtained in 79% of cases (manual scoring, 73%; semi-automated scoring, 100%; automated scoring, 67%). The percentage of dose estimates whose 95% confidence intervals included the reference dose was 58% (manual scoring, 48%; semiautomated scoring, 72%; automated scoring, 60%). For the irradiated samples no. 2 and no. 3, a systematic shift towards higher dose estimations was observed. This was also noticed with the other cytogenetic assays in this intercomparison exercise. Accuracy of the rapid triage modality could be maintained when the number of manually scored cells was scaled down to 200 binucleated cells. In conclusion, the micronucleus assay, preferably performed in a semi-automated or manual scoring mode, is a reliable technique to perform rapid biodosimetry analysis in large-scale radiation emergencies.

Critical Appraisal of Artificial Intelligence-Enabled Imaging Tools Using the Levels of Evidence System.

Clinical adoption of an artificial intelligence-enabled imaging tool requires critical appraisal of its life cycle from development to implementation by using a systematic, standardized, and objective approach that can verify both its technical and clinical efficacy. Toward this concerted effort, the ASFNR/ASNR Artificial Intelligence Workshop Technology Working Group is proposing a hierarchal evaluation system based on the quality, type, and amount of scientific evidence that the artificial intelligence-enabled tool can demonstrate for each component of its life cycle. The current proposal is modeled after the levels of evidence in medicine, with the uppermost level of the hierarchy showing the strongest evidence for potential impact on patient care and health care outcomes. The intended goal of establishing an evidence-based evaluation system is to encourage transparency, foster an understanding of the creation of artificial intelligence tools and the artificial intelligence decision-making process, and to report the relevant data on the efficacy of artificial intelligence tools that are developed. The proposed system is an essential step in working toward a more formalized, clinically validated, and regulated framework for the safe and effective deployment of artificial intelligence imaging applications that will be used in clinical practice.

Sinus arrest in familial hypokalemic periodic paralysis caused by SCN4A mutation: a case report.

BACKGROUND: Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation. CASE REPORT: A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet. CONCLUSIONS: No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.

Microfungi associated with dying Euphorbia mauritanica in South Africa and their relative pathogenicity.

Euphorbia mauritanica is a succulent shrub that is indigenous to South Africa and widely distributed throughout the country. Dying plants have been observed in their natural habitat in the Northern and Western Cape Provinces of South Africa in recent years. Stems displaying lesions were collected and the emerging cultures were identified based on ITS, LSU, ACT, RPB2, TEF1 and/or TUB2 sequence data. Four filamentous fungi were consistently observed and isolated. One was identified as Alanphillipsia (Ala.) aloes, and the other three were new to science and are described here as Cytospora euphorbiicola sp. nov., Nothomicrosphaeropsis namakwaensis sp. nov. and Austrophoma (Aus.) euphorbiae gen. et sp. nov. These new species and Ala. aloes were the most commonly encountered, and their pathogenicity was tested on E. mauritanica plants in a greenhouse trial. All four species gave rise to lesions that were significantly larger than those associated with the controls, but they were not significantly different to each other. Although the lesions associated with the inoculations were well-developed, they did not give rise to plant death, suggesting that they are not responsible for the large-scale die-off of E. mauritanica in the field. The primary cause of the death of E. mauritanica in the studied area remains unknown and could be due to environmental factors such as has been found with the die-off of Euphorbia ingens in South Africa. Citation: Marincowitz S, Pham NQ, Wingfield BD, Roets F, Wingfield MJ (2023). Microfungi associated with dying Euphorbia mauritanica in South Africa and their relative pathogenicity. Fungal Systematics and Evolution 12: 59-71. doi: 10.3114/fuse.2023.12.04.

A novel species of Microsphaeropsis causing cankers on Rafnia amplexicaulis in South Africa.

Cankers leading to branch, stem and plant death were observed on the South African endemic Rafnia amplexicaulis (Fabaceae) in the Cederberg Wilderness Area, South Africa, during September 2021. Conidiomatal pycnidia were found developing on the cankers, and isolations consistently yielded a Microsphaeropsis species. Phylogenetic analysis based on partial nucleotide sequences of the internal transcribed spacers (ITS), the nuclear large subunit (LSU) and RNA polymerase II second largest subunit (RPB2) regions showed that the fungus represented an undescribed species. Based on the multigene phylogeny and morphological characteristics, we describe the species here as M. rafniae sp. nov. Pathogenicity tests and the fulfilment of Koch's postulates confirmed that M. rafniae sp. nov. is the cause of the cankers of R. amplexicaulis. Presently, this disease is known from a single location in South Africa, and further surveys are required to determine its distribution and relative importance. Citation: Paap T, Marincowitz S, Pham NQ, Roets F, Basson RJ, Wingfield BD, Oberlander K, Wingfield MJ (2023). A novel species of Microsphaeropsis causing cankers on Rafnia amplexicaulis in South Africa. Fungal Systematics and Evolution 12: 73-80. doi: 10.3114/fuse.2023.12.05.

Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.

Background: Patients with heart failure with reduced ejection fraction (HFrEF) in Asia exhibit many differences from those in other parts of the world. Objectives: This study sought to investigate the efficacy and safety of dapagliflozin, compared with placebo, in HFrEF patients in Asia, compared with those elsewhere, enrolled in the DAPA-HF (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure) trial. Methods: Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for the DAPA-HF trial. The primary outcome in the DAPA-HF trial was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results: Of the 4,744 patients in the DAPA-HF trial, 1,096 (23.1%) were enrolled in Asia; 721 (15.2% overall, 65.8% of patients in Asia) were enrolled in East Asia (237 in China, 343 in Japan, and 141 in Taiwan), 138 (2.9% overall, 12.6% in Asia) in South-East Asia (Vietnam), and 237 (5.0% overall, 21.6% in Asia) in South Asia (India). Patients from Asia had similar rates of worsening HF events and mortality compared with patients elsewhere. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients from Asia (HR: 0.65; 95% CI: 0.49 to 0.87) as elsewhere (HR: 0.77; 95% CI: 0.66 to 0.89) (P for interaction = 0.32). Consistent benefits were observed for the other prespecified outcomes and among the regions of Asia. Study drug discontinuation and prespecified adverse events did not differ between regions. Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events and cardiovascular death to the same extent in Asian patients as elsewhere. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

Preoperative Determination of the Size of the Semitendinosus and Gracilis Tendon by Multidetector Row CT Scanner for Anterior Cruciate Ligament Reconstruction.

Accurately measuring the length and diameter of the hamstring tendon autograft preoperatively is important for planning anterior cruciate ligament (ACL) reconstructive surgery. The purpose of this study was to assess the reliability of three-dimensional computed tomography (3D CT) scanning technique to produce the actual measurement of the gracilis and semitendinosus (GT and ST, respectively) tendon grafts' length and diameter for surgery. Ninety patients were scheduled for ACL reconstruction with hamstring autograft. Before the surgery, patients were examined under the multidetector row CT scanner and the ST and GT tendons were qualitatively measured by a volume-rendering technique. The length of ST and GT was measured with 3D CT compared with the length of the harvested ST and GT. The cross-sectional area (CSA) of ST and GT measured with 3D CT compared with the ST and GT graft diameter. Tendon size measured preoperatively and during surgery were statistically compared and correlated. The GT tendons length and cross-sectional area measured during surgery was both shorter and smaller compared with the ST tendon. GT and ST tendon length were correlated to patients' body index such as the height and weight (p < 0.05). However, the correlation levels were low to medium (r = 0.23-0.49). There was strong correlation between the lengths of GT (r = 0.76; p < 0.001) and ST (r = 0.87; p < 0.001) measured with the 3D CT and tendon length at surgery. There was a moderate correlation between graft diameter measured at surgery and 3D CT cross-sectional area (r = 0.31; p < 0.05). A multidetector row CT scanner can determine the ST and GT tendons' length and diameter. These measurements can be used for preoperative planning to help determine the surgical method and counsel patients on appropriate graft choices prior to surgery.

Perturbing dimer interactions and allosteric communication modulates the immunosuppressive activity of human galectin-7.

The design of allosteric modulators to control protein function is a key objective in drug discovery programs. Altering functionally essential allosteric residue networks provides unique protein family subtype specificity, minimizes unwanted off-target effects, and helps avert resistance acquisition typically plaguing drugs that target orthosteric sites. In this work, we used protein engineering and dimer interface mutations to positively and negatively modulate the immunosuppressive activity of the proapoptotic human galectin-7 (GAL-7). Using the PoPMuSiC and BeAtMuSiC algorithms, mutational sites and residue identity were computationally probed and predicted to either alter or stabilize the GAL-7 dimer interface. By designing a covalent disulfide bridge between protomers to control homodimer strength and stability, we demonstrate the importance of dimer interface perturbations on the allosteric network bridging the two opposite glycan-binding sites on GAL-7, resulting in control of induced apoptosis in Jurkat T cells. Molecular investigation of G16X GAL-7 variants using X-ray crystallography, biophysical, and computational characterization illuminates residues involved in dimer stability and allosteric communication, along with discrete long-range dynamic behaviors involving loops 1, 3, and 5. We show that perturbing the protein-protein interface between GAL-7 protomers can modulate its biological function, even when the overall structure and ligand-binding affinity remains unaltered. This study highlights new avenues for the design of galectin-specific modulators influencing both glycan-dependent and glycan-independent interactions.

Genotoxicity of Paragonimus heterotremus Infection in a Rat Model of Simultaneous Pulmonary and Hepatic Paragonimiasis.

Parasites cause numerous health issues in humans, eventually leading to significant social and economic damage; however, the mechanisms of parasite-mediated pathogenesis are not well understood. Nevertheless, it is clearly evidenced that cancerogenic fluke-induced chronic inflammations and cancer are closely associated with oxidative stress. (1) Methods: The Paragonimus heterotremus infection's genotoxic potential was assessed in a rat model of simultaneous pulmonary and hepatic paragonimiasis by the alkaline version of single-cell gel electrophoresis (comet assay). Statistical analysis of comet parameters was based on the non-parametric Mann-Whitney U test. (2) Results: A clear and statistically significant increase in DNA damage was detected in the helminth-exposed group versus the control rats and the tissue areas adjacent to the parasite capsule versus remote ones; however, differences in DNA damage patterns between different tissues were not statistically significant. Infection resulted in up to 40% cells with DNA damage and an increased genetic damage index. (3) Conclusions: The data obtained contribute to understanding the pathogenesis mechanisms of paragonimiasis, suggesting oxidative stress as the most likely reason for DNA breaks; these findings allow us to consider P. heterotremus as a potentially cancerogenic species, and they are important for the monitoring and treatment of paragonimiasis.

Striped catfish (Pangasianodon hypophthalmus) use air-breathing and aquatic surface respiration when exposed to severe aquatic hypercarbia.

We investigated the extent to which the facultative air-breathing fish, the striped catfish (Pangasianodon hypophthalmus), uses air-breathing to cope with aquatic hypercarbia, and how air-breathing is influenced by the experimental exposure protocol and level of hypercarbia. We exposed individuals to severe aquatic hypercarbia (up to Pw CO2 = 81 mmHg) using step-wise and progressive exposure protocols while measuring gill ventilation rate, heart rate, mean arterial blood pressure, and air-breathing frequency, as well as arterial blood pH and PCO2 . We confirm that P. hypophthalmus is tolerant of hypercarbia. Under both protocols gill ventilation rate, heart rate, and mean arterial blood pressure were maintained near control levels even at very high CO2 levels. We observed a marked amount of individual variation in the PwCO2 at which air-breathing was elicited, with some individuals not responding at all. The experimental protocol also influenced the onset of air-breathing. Air-breathing began at lower Pw CO2 in the step-wise protocol (23 ± 4.1 mmHg) compared with the progressive protocol (46 ± 7.8 mmHg). Air-breathing was often followed by aquatic surface respiration, at higher PCO2 (71 ± 5.2 mmHg) levels. On average, the blood PCO2 was approximately 43% lower (46 ± 2.5 mmHg) than water Pw CO2 (~81 mmHg) at our highest tested CO2 level. While this suggests that aerial CO2 elimination is an effective, and perhaps critical, respiratory strategy used by P. hypophthalmus to cope with severe hypercarbia, this observation may also be explained by a long lag time required for equilibration.

Protein context shapes the specificity of SH3 domain-mediated interactions in vivo.

Protein-protein interactions (PPIs) between modular binding domains and their target peptide motifs are thought to largely depend on the intrinsic binding specificities of the domains. The large family of SRC Homology 3 (SH3) domains contribute to cellular processes via their ability to support such PPIs. While the intrinsic binding specificities of SH3 domains have been studied in vitro, whether each domain is necessary and sufficient to define PPI specificity in vivo is largely unknown. Here, by combining deletion, mutation, swapping and shuffling of SH3 domains and measurements of their impact on protein interactions in yeast, we find that most SH3s do not dictate PPI specificity independently from their host protein in vivo. We show that the identity of the host protein and the position of the SH3 domains within their host are critical for PPI specificity, for cellular functions and for key biophysical processes such as phase separation. Our work demonstrates the importance of the interplay between a modular PPI domain such as SH3 and its host protein in establishing specificity to wire PPI networks. These findings will aid understanding how protein networks are rewired during evolution and in the context of mutation-driven diseases such as cancer.

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients

BackgroundIncreased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 may help define disease severity and guide care and decision making. MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining. ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified in COVID-19 plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death. ConclusionsCirculating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function may be potential COVID-19 disease biomarkers.

Phytophthora acaciivora sp. nov. associated with dying Acacia mangium in Vietnam.

Acacia mangium plantations account for more than 50 % of the exotic plantations in Vietnam. A new black butt symptom was discovered in 2012, followed by the wilting sign in Acacia seedlings in Tuyen Quang Province. Isolations recovered two Phytophthora species, the well-known Acacia pathogen P. cinnamomi, and an unknown species. The new species is described here as Phytophthora acaciivora sp. nov. Phylogenetically this species resides in clade 2d and is most closely related to P. frigida. Phytophthora acaciivora is a heterothallic species, oospores are aplerotic and antheridia are amphigynous. It produces predominantly elongated ovoid, semi papillate, persistent sporangia, no hyphal swellings and no chlamydospores. Optimum temperature for the growth is 25-30 °C and the maximum temperature is over 37.5 °C. Studies are underway to determine the impact of this new species on Acacia plantations in Vietnam.

The effectiveness of emotional wellness programs on mental health outcomes for adults with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: People with multiple sclerosis (MS) have a greater prevalence of depression and anxiety than the general population. Emotional wellness programs (any psychological or psychosocial interventions that focus on awareness, acceptance, managing, or challenging thoughts and feelings) could be important for people with MS. However, there have been no reviews on the effectiveness of emotional wellness programs for people with MS. The objective of this review was to determine the effectiveness of emotional wellness programs on mental health outcomes for adults with MS. INCLUSION CRITERIA: Randomised controlled trials (RCTs) and quasi-experimental trials evaluating emotional wellness programs for adults with any form of MS were included. Mental health outcomes included were depression, anxiety, quality of life, and stress. The comparator groups were waitlist controls, usual care, or another intervention. METHODS: This review was registered with PROSPERO (registration number CRD42019131082) and conducted in accordance with PRISMA guidelines. CINAHL, Cochrane, MEDLINE, PsycInfo, Web of Science, ProQuest Dissertations and Theses, Cochrane register of Controlled Trials, and Google Scholar were searched for English- language publications. Titles and abstracts were initially screened, followed by a screen of full text articles. Studies were critically appraised for methodological quality using the JBI standardised critical appraisal checklists. Data were extracted on intervention details, study outcome measures, behaviour change techniques, and results. Random effects meta-analyses were performed for outcomes assessed in at least five studies, with results reported as the standardised mean difference (SMD). RESULTS: This review comprised 25 RCTs and four quasi-experimental studies (n participants=2323); 21 were included in meta-analyses. Meta-analyses produced statistically significant results favouring the interventions (SMD (95% CI) for depression -0.55 (-0.87, -0.24); anxiety -0.42 (-0.70, -0.14); quality of life 0.28 (0.14, 0.43); and stress -1.00 (-1.58, -0.43)). The most commonly used behaviour change techniques were behaviour practice/rehearsal, social comparison, and social support. CONCLUSIONS: This review provides evidence to support the effectiveness of emotional wellness programs for improving mental health outcomes in adults with MS. However, these findings should be interpreted with caution given the high degree of heterogeneity between the studies, and potential for biases in analysis due to missing data and/or incomplete reporting.