Lithium-ion battery components are at the nexus of sustainable energy and environmental release of per- and polyfluoroalkyl substances.

Lithium-ion batteries (LiBs) are used globally as a key component of clean and sustainable energy infrastructure, and emerging LiB technologies have incorporated a class of per- and polyfluoroalkyl substances (PFAS) known as bis-perfluoroalkyl sulfonimides (bis-FASIs). PFAS are recognized internationally as recalcitrant contaminants, a subset of which are known to be mobile and toxic, but little is known about environmental impacts of bis-FASIs released during LiB manufacture, use, and disposal. Here we demonstrate that environmental concentrations proximal to manufacturers, ecotoxicity, and treatability of bis-FASIs are comparable to PFAS such as perfluorooctanoic acid that are now prohibited and highly regulated worldwide, and we confirm the clean energy sector as an unrecognized and potentially growing source of international PFAS release. Results underscore that environmental impacts of clean energy infrastructure merit scrutiny to ensure that reduced CO2 emissions are not achieved at the expense of increasing global releases of persistent organic pollutants.

Impact of Chemotherapy Educational Videos for Patients with Acute Myeloid Leukemia.

Patient education in acute myeloid leukemia (AML) has become increasingly complex with the introduction of new treatments and chemotherapy regimens. Video education presents an opportunity to supplement traditional patient education and address some of the gaps associated with standard methods. This single-center study sought to assess the potential impact of supplemental video education on patients receiving induction chemotherapy for AML. Participants were consented to be randomized to receive their education with or without a supplemental video designed for their treatment regimen. We then provided a survey to each participant to assess knowledge retention, anxiety, and overall satisfaction with their care. Patients that received video education were found to have significantly improved knowledge retention compared to those that did not. There were no differences detected in anxiety or patient satisfaction. Video education appears to be an effective supplemental method for patient education in AML. Limitations include the single-center nature of the study at an urban academic medical center with a relatively well-educated, primarily Caucasian, younger population. Future research is warranted to assess the video in a diverse set of languages and to explore its broader benefits.

Comparative Anatomy of the Contralateral Transmaxillary Approach Alone and With Ipsilateral Transpterygoid Extension: Quantitative Insights on Surgical Exposure and Maneuverability in the Petroclival Region.

BACKGROUND AND OBJECTIVES: Beyond qualitative evidence legitimizing endoscopic corridors through contralateral transmaxillary (CTM) and endonasal ipsilateral transpterygoid (ITP) corridors to the petrous apex and petroclival region, surgical feasibility by direct quantitative comparative anatomy is sparse. Our cadaveric study addresses this by performing the CTM approach followed by ITP extension to quantify the extent of petrous apex resection, instrument maneuverability, and working distance to petrous apex. METHODS: Anatomic dissections were performed bilaterally on 5 latex-injected human cadaveric heads (10 petrous bones). After CTM dissections were quantified, the ITP approach was added enlarging initial exposure. Differences were measured with statistical significance when P values are < .05. RESULTS: The mean petrosectomy volume was 0.958 cm3 with CTM and 1.987 cm3 with CTM + ITP, corresponding to 14.53% and 30.52% petrous apex resection, respectively. Craniocaudal instrument mobility was more limited in the lateral extent of dissection compared with the midline for both CTM (8.062° vs 14.416°) and CTM + ITP (5.4° vs 14.4°). The CTM approach achieved the lateral-most dissection at the body of the petrous apex (15.936 mm), with lateralization more limited in the superior petroclival region (9.628 mm) and the inferior petroclival region (8.508 mm). Angle of surgical maneuverability increased superiorly vs inferiorly in the CTM approach (mean 12.596° vs 8.336°, respectively). The CTM approach offered the shortest mean working distance (88.624 mm) to the petroclival region compared with the bi-nares approach (100.5 mm). CTM + ITP achieved greater lateralization in the superior (21.237 mm) and inferior (22.087 mm) aspects of the petroclival region compared with the CTM approach. CONCLUSION: Operative considerations are discussed in accessing target neurovascular structures through the uniquely shaped corridors formed by the CTM or combined CTM + ITP. Allowing mobilization of the internal carotid artery laterally and eustachian tube inferiorly, addition of the ITP allowed for larger petrosectomy than CTM alone, especially in the inferior and lateral aspects of the petrous bone.

Resident and Fellow Performance and Supervision in Surgical Oncology Procedures.

BACKGROUND: Previous research has highlighted concerns among trainees and attendings that general surgery training and fellowship are inadequately preparing trainees for practice. Providing trainees with supervision that matches their proficiency may help bridge this gap. We sought to benchmark operative performance and supervision levels among senior surgery residents (post-graduate year 4 or 5) and fellows performing general surgical oncology procedures. STUDY DESIGN: Observational data were obtained from the Society for Improving Medical Procedural Learning (SIMPL) OR application for core general surgical oncology procedures performed at 103 unique residency and fellowship programs. Procedures were divided into breast and soft tissue, endocrine, and hepatopancreatobiliary (HPB). Case evaluations completed by trainees and attendings were analyzed to benchmark trainee operative performance and level of supervision. RESULTS: There were 4,907 resident cases and 425 fellow cases. Practice-ready performance, as assessed by trainees and faculty, was achieved by relatively low proportions of residents and fellows for breast and soft tissue cases (residents: 38%, fellows: 48%), endocrine cases (residents: 22%, fellows: 41%), and HPB cases (residents: 10%, fellows: 40%). Among cases in which trainees did achieve practice-ready performance, supervision only was provided for low proportions of cases as rated by trainees (residents: 17%, fellows: 18%) and attendings (residents: 21%, fellows 25%). CONCLUSION: In a sample of 103 residency and fellowship programs, attending surgeons rarely provided senior residents and fellows with levels of supervision commensurate to performance for surgical oncology procedures, even for high performing trainees. These findings suggest a critical need for surgical training programs to prioritize providing greater levels of independence to trainees that have demonstrated excellent performance.

Pathogenic differences of cynomolgus macaques after Taï Forest virus infection depend on the viral stock propagation.

Taï Forest virus (TAFV) is a negative-sense RNA virus in the Filoviridae family. TAFV has caused only a single human infection, but several disease outbreaks in chimpanzees have been linked to this virus. Limited research has been done on this human-pathogenic virus. We sought to establish an animal model to assess TAFV disease progression and pathogenicity at our facility. We had access to two different viral stock preparations from different institutions, both originating from the single human case. Type I interferon receptor knockout mice were inoculated with TAFV stock 1 or stock 2 by the intraperitoneal route. Inoculation resulted in 100% survival with no disease regardless of viral stock preparation or infectious dose. Next, cynomolgus macaques were inoculated with TAFV stock 1 or stock 2. Inoculation with TAFV stock 1 resulted in 100% survival and robust TAFV glycoprotein-specific IgG responses including neutralizing antibodies. In contrast, macaques infected with TAFV stock 2 developed disease and were euthanized 8-11 days after infection exhibiting viremia, thrombocytopenia, and increased inflammatory mediators identified by transcriptional analysis. Histopathologic analysis of tissue samples collected at necropsy confirmed classic filovirus disease in numerous organs. Genomic differences in both stock preparations were mapped to several viral genes which may have contributed to disease severity. Taken together, we demonstrate that infection with the two TAFV stocks resulted in no disease in mice and opposing disease phenotypes in cynomolgus macaques, highlighting the impact of viral stock propagation on pathogenicity in animal models.

Cardiac computed tomography-derived coronary artery volume to myocardial mass in patients with severe coronary artery disease.

BACKGROUND: Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium. METHODS: The V, M and V/M were obtained from the coronary computed tomography angiography (CCTA) of patients in the FAST-TRACK CABG study, the first-in-human trial of coronary artery bypass grafting (CABG) guided solely by CCTA and fractional flow reserve derived from CCTA (FFRCT) in patients with complex coronary artery disease (CAD). The correlations between V/M ratios and baseline characteristics were determined and compared with those from the ADVANCE registry, an unselected cohort of historical controls with chronic CAD. RESULTS: The V/M ratio was obtained in 106 of the 114 pre-CABG CCTAs. Mean age was 65.6 years and 87% of them were male. The anatomical SYNTAX score from CCTA was significantly higher than the functional SYNTAX score derived using FFRCT [43.1 (15.2) vs 41.1 (16.5), p â€‹< â€‹0.001]. Mean V, M, and V/M were 2204 â€‹mm3, 137 â€‹g, and 16.5 â€‹mm3/g, respectively. There were weak negative correlations between V and anatomical and functional SYNTAX scores (Pearson's r â€‹= â€‹-0.26 and -0.34). V and V/M had a strong correlation (r â€‹= â€‹0.82). The V/M ratio in the current study was significantly lower than that in the ADVANCE registry (median 16.1 vs. 24.8 [1st quartile 20.1]). CONCLUSION: Systematically smaller V/M ratios were found in this population with severe CAD requiring CABG compared to an unselected cohort with chronic CAD. The V/M ratio could provide additional non-invasive assessment of CAD especially when combined with FFRCT.

T cells use focal adhesions to pull themselves through confined environments.

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show that activated primary Th1 T cells require both confinement and extracellular matrix proteins to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal cell focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cells preferentially follow tracks of other T cells, suggesting that these adhesions modify the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated focal adhesions play a key role in T cell motility.

A glial circadian gene expression atlas reveals cell type and disease-specific reprogramming in response to amyloid pathology or aging.

While circadian rhythm disruption may promote neurodegenerative disease, how aging and neurodegenerative pathology impact circadian gene expression patterns in different brain cell types is unknown. Here, we used translating ribosome affinity purification methods to define the circadian translatomes of astrocytes, microglia, and bulk cerebral cortex, in healthy mouse brain and in the settings of amyloid-beta plaque pathology or aging. Our data reveal that glial circadian translatomes are highly cell type-specific and exhibit profound, context-dependent reprogramming of rhythmic transcripts in response to amyloid pathology or aging. Transcripts involved in glial activation, immunometabolism, and proteostasis, as well as nearly half of all Alzheimer Disease (AD)-associated risk genes, displayed circadian oscillations, many of which were altered by pathology. Amyloid-related differential gene expression was also dependent on time of day. Thus, circadian rhythms in gene expression are cell- and context dependent and provide important insights into glial gene regulation in health, AD, and aging.

Caught in the Act: Incipient Speciation at the Southern limit of Viburnum in the Central Andes.

A fundamental objective of evolutionary biology is to understand the origin of independently evolving species. Phylogenetic studies of species radiations rarely are able to document ongoing speciation; instead, modes of speciation, entailing geographic separation and/or ecological differentiation, are posited retrospectively. The Oreinotinus clade of Viburnum has radiated recently from north to south through the cloud forests of Mexico and Central America to the Central Andes. Our analyses support a hypothesis of incipient speciation in Oreinotinus at the southern edge of its geographic range, from central Peru to northern Argentina. Although several species and infraspecific taxa of have been recognized in this area, multiple lines of evidence and analytical approaches (including analyses of phylogenetic relationships, genetic structure, leaf morphology, and climatic envelopes) favor the recognition of just a single species, V. seemenii. We show that what has previously been recognized as V. seemenii f. minor has recently occupied the drier Tucuman-Bolivian forest region from Samaipata in Bolivia to Salta in northern Argentina. Plants in these populations form a well-supported clade with a distinctive genetic signature and they have evolved smaller, narrower leaves. We interpret this as the beginning of a within-species divergence process that has elsewhere in the neotropics resulted repeatedly in Viburnum species with a particular set of leaf ecomorphs. Specifically, the southern populations are in the process of evolving the small, glabrous, and entire leaf ecomorph that has evolved in four other montane areas of endemism. As predicted based on our studies of leaf ecomorphs in Chiapas, Mexico, these southern populations experience generally drier conditions, with large diurnal temperature fluctuations. In a central portion of the range of V. seemenii, characterized by wetter climatic conditions, we also document what may be the initial differentiation of the leaf ecomorph with larger, pubescent, and toothy leaves. The emergence of these ecomorphs thus appears to be driven by adaptation to subtly different climatic conditions in separate geographic regions, as opposed to parapatric differentiation along elevational gradients as suggested by Viburnum species distributions in other parts of the neotropics.

L-LOP/LOPP for the treatment of canine gastrointestinal/hepatosplenic lymphoma.

Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy and a very poor prognosis. Currently, there are no established effective chemotherapy protocols for canine GI/HS lymphomas. This case series aimed to retrospectively evaluate the efficacy of lomustine-based protocols L-LOP (L-asparaginase, lomustine, vincristine, and prednisolone) and L-LOPP (with the addition of procarbazine) for treatment of canine GI/HS lymphomas. Medical records of dogs with cytologically or histologically diagnosed lymphoma at CityU Veterinary Medical Centre from 2019 to 2022 were retrospectively reviewed. The L-LOP/LOPP treatment protocol was well tolerated with rare severe adverse events. Median progression-free survival for GI and HS lymphoma was 56 days (range, 10-274 days) and 57 days (range 8-135 days) respectively; while median survival time for GI and HS lymphoma was 93 days (range 10-325 days) and 210 days (range 8-240 days) respectively.

Sequence, structure prediction, and epitope analysis of the polymorphic membrane protein family in Chlamydia trachomatis.

The polymorphic membrane proteins (Pmps) are a family of autotransporters that play an important role in infection, adhesion and immunity in Chlamydia trachomatis. Here we show that the characteristic GGA(I,L,V) and FxxN tetrapeptide repeats fit into a larger repeat sequence, which correspond to the coils of a large beta-helical domain in high quality structure predictions. Analysis of the protein using structure prediction algorithms provided novel insight to the chlamydial Pmp family of proteins. While the tetrapeptide motifs themselves are predicted to play a structural role in folding and close stacking of the beta-helical backbone of the passenger domain, we found many of the interesting features of Pmps are localized to the side loops jutting out from the beta helix including protease cleavage, host cell adhesion, and B-cell epitopes; while T-cell epitopes are predominantly found in the beta-helix itself. This analysis more accurately defines the Pmp family of Chlamydia and may better inform rational vaccine design and functional studies.

Experiences of Deployed Physicians in Support of Operation Allies Refuge/Operation Allies Welcome: Lessons to Inform Improvements in Training.

INTRODUCTION: Stability operations, including humanitarian assistance and disaster relief missions, are key functions of U.S. Military medicine and the Military Medical Humanitarian Assistance Course (MMHAC) is a 2-day course widely used to prepare military medical personnel for such missions. It focuses on caring for those most vulnerable in the wake of disasters, particularly children. The large-scale humanitarian deployment of military medical providers in support of Operation Allies Welcome/Operation Allies Refuge (OAW/OAR) presents an opportunity to evaluate the preparedness of these providers to care for the needs of the Afghan travelers, so we explored the experiences of military medical providers deployed in support of OAW/OAR to inform improvements in the MMHAC. MATERIALS AND METHODS: We conducted a qualitative study of military medical providers who were deployed in support of OAW/OAR using a series of three virtual focus groups. Focus group questions were structured around the main topics covered in the MMHAC (patient care, ethical considerations, logistical concerns, and preventive and public health) and explicitly asked about adaptive leadership challenges faced and strategies used to overcome them. We analyzed transcripts using inductive thematic analysis within a constructivist paradigm, with adaptive leadership as a sensitizing concept. The study was approved by the Institutional Review Board of Uniformed Services University. RESULTS: We constructed 4 themes from participant responses, each addressing challenges that medical providers faced during their mission: (1) Medical providers navigated tension between medical and public health priorities and military mission priorities; (2) Chronic and complex care needs posed unique challenges for medical personnel; (3) Challenges in patient care were compounded by logistical and system-based barriers; and (4) Cultural barriers led to ethical dilemmas that physicians felt inadequately prepared to handle, most notably with respect to gender-related concerns. Within each theme, participants described which aspects of MMHAC training were most helpful and which areas were inadequate. CONCLUSIONS: Physicians found the OAR/OAW mission meaningful but also identified challenges related to medical care provision, public health, logistics, and ethical dilemmas that hindered their ability to carry out their medical mission. Lessons learned from OAW/OAR highlight several areas in which the MMHAC training could be augmented and improved to further mitigate these challenges.

Interfacial Stabilization by Prelithiated Trithiocyanuric Acid as an Organic Additive in Sulfide-based All-Solid-State Lithium Metal Batteries.

Sulfide-based all-solid-state battery (ASSB) with a lithium metal anode (LMA) is a promising candidate to surpass conventional Li-ion batteries owing to their inherent safety against fire hazards and potential to achieve a higher energy density. However, the narrow electrochemical stability window and chemical reactivity of the sulfide solid electrolyte towards the LMA results in interfacial degradation and poor electrochemical performance. In this direction, we introduce an organic additive approach, that is the mixing of prelithiated trithiocyanuric acid, Li3TCA, with Li6PS5Cl, to establish a stable interface while preserving high ionic conductivity. Including 2.5 wt% Li3TCA alleviates the decomposition of the electrolyte on the lithium metal interface, decreasing the Li2S content in the solid-electrolyte interface (SEI) thus forming a more stable interface. In Li|Li symmetric cells this enables a rise in the critical current density from 1.0 to 1.9 mA cm-2 and stable cycling for over 750 hours at a high current density of 1.0 mA cm-2. This approach also enables Li|NbO-NCM811 full cell to operate more than 500 cycles at 0.3C.

A multicenter randomized trial to compare automatic versus as-needed follow-up for children hospitalized with common infections: The FAAN-C trial protocol.

INTRODUCTION: Physicians commonly recommend automatic primary care follow-up visits to children being discharged from the hospital. While automatic follow-up provides an opportunity to address postdischarge needs, the alternative is as-needed follow-up. With this strategy, families monitor their child's symptoms and decide if they need a follow-up visit in the days after discharge. In addition to being family centered, as-needed follow-up has the potential to reduce time and financial burdens on both families and the healthcare system. As-needed follow-up has been shown to be safe and effective for children hospitalized with bronchiolitis, but the extent to which hospitalized children with other common conditions might benefit from as-needed follow-up is unclear. METHODS: The Follow-up Automatically versus As-Needed Comparison (FAAN-C, or "fancy") trial is a multicenter randomized controlled trial. Children who are hospitalized for pneumonia, urinary tract infection, skin and soft tissue infection, or acute gastroenteritis are eligible to participate. Participants are randomized to an as-needed versus automatic posthospitalization follow-up recommendation. The sample size estimate is 2674 participants and the primary outcome is all-cause hospital readmission within 14 days of discharge. Secondary outcomes are medical interventions and child health-related quality of life. Analyses will be conducted in an intention-to-treat manner, testing noninferiority of as-needed follow-up compared with automatic follow-up. DISCUSSION: FAAN-C will elucidate the relative benefits of an as-needed versus automatic follow-up recommendation, informing one of the most common decisions faced by families of hospitalized children and their medical providers. Findings from FAAN-C will also have implications for national quality metrics and guidelines.

Insights Into Preaggregation Control of Y-Series Nonfullerene Acceptors in Liquid State for Highly Efficient Binary Organic Solar Cells.

Leveraging breakthroughs in Y-series nonfullerene acceptors (NFAs), organic solar cells (OSCs) have achieved impressive power conversion efficiencies (PCEs) exceeding 19%. However, progress in advancing OSCs has decelerated due to constraints in realizing the full potential of the Y-series NFAs. Herein, a simple yet effective solid additive-induced preaggregation control method employing 2-chloro-5-iodopyridine (PDCI) is reported to unlock the full potential of the Y-series NFAs. Specifically, PDCI interacts predominantly with Y-series NFAs enabling enhanced and ordered phase-aggregation in solution. This method leads to a notable improvement and a redshifted absorption of the acceptor phase during film formation, along with improved crystallinity. Moreover, the PDCI-induced preaggregation of NFAs in the solution enables ordered molecule packing during the film-formation process through delicate intermediate states transition. Consequently, the PDCI-induced preaggregated significantly improves the PCE of PM6:Y6 OSCs from 16.12% to 18.12%, among the best values reported for PM6:Y6 OSCs. Importantly, this approach is universally applicable to other Y-series NFA-based OSCs, achieving a champion PCE of 19.02% for the PM6:BTP-eC9 system. Thus, the preaggregation control strategy further unlocks the potential of Y-series NFAs, offering a promising avenue for enhancing the photovoltaic performance of Y-series NFA-based OSCs.

Differential transcriptional invasion signatures from patient derived organoid models define a functional prognostic tool for head and neck cancer.

Clinical outcome for patients suffering from HPV-negative head and neck squamous cell carcinoma (HNSCC) remains poor. This is mostly due to highly invasive tumors that cause loco-regional relapses after initial therapeutic intervention and metastatic outgrowth. The molecular pathways governing the detrimental invasive growth modes in HNSCC remain however understudied. Here, we have established HNSCC patient derived organoid (PDO) models that recapitulate 3-dimensional invasion in vitro. Single cell mRNA sequencing was applied to study the differences between non-invasive and invasive conditions, and in a collective versus single cell invading PDO model. Differential expression analysis under invasive conditions in Collagen gels reveals an overall upregulation of a YAP-centered transcriptional program, irrespective of the invasion mode. However, we find that collectively invading HNSCC PDO cells show elevated levels of YAP transcription targets when compared to single cell invasion. Also, collectively invading cells are characterized by increased nuclear translocation of YAP within the invasive strands, which coincides with Collagen-I matrix alignment at the invasive front. Using gene set enrichment analysis, we identify immune cell-like migratory pathways in the single cell invading HNSCC PDO, while collective invasion is characterized by overt upregulation of adhesion and migratory pathways. Lastly, based on clinical head and neck cancer cohorts, we demonstrate that the identified collective invasion signature provides a candidate prognostic platform for survival in HNSCC. By uncoupling collective and single cell invasive programs, we have established invasion signatures that may guide new therapeutic options.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

BACKGROUND: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. METHODS: We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. RESULTS: Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. CONCLUSIONS: We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.

LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial

BACKGROUND Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1•5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2­4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10•44% and assuming an event rate of 26•10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80•0 years (SD 5•7) for those treated with the Myval THV and 80•4 years (5•4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2•6% [IQR 1•7­4•0] vs contemporary 2•6% [1•7­4•0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of ­2•3% (one-sided upper 95% CI 3•8, pnon-inferiority<0•0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days.