Ontogeny and associated changes of the extinct sloth Simomylodon uccasamamensis (Xenarthra, Mylodontidae) from the Pliocene of the eastern Puna, Argentina.

Within Xenarthra (Eocene-Recent), Folivora developed (late Eocene-Recent) a remarkable diversity with respect to ecology and taxonomy over its evolutionary history. Knowledge of the diversity achieved by members of this clade in high-altitude areas of South America (i.e., Altiplano and Puna regions of Peru, Bolivia, and northwestern Argentina) has been improved in recent decades. A particular example involves the late Neogene Mylodontidae Simomylodon uccasamamensis, known mostly from multiple specimens recovered from the Bolivian Altiplano. Although several anatomical descriptions of this ground sloth have been published, almost nothing is known about its ontogenetic development and the associated morphological changes. Here we describe and compare new specimens of S. uccasamamensis from the upper level of the Tafna Formation (Pliocene) in the eastern Puna (ca. 3800 masl), Argentina, representing the southernmost record of this species. The new material is represented by specimens showing different ontogenetic stages, from infant to adult. One subadult specimen reached an estimated body mass of ca. 232 kg. The comparative study of external and internal morphology (the latter obtained from CT scans and radiography) shows remarkable changes in the mandible and molariforms associated with ontogeny; in addition, evidence suggests that the mfs2-3 are the first functional teeth, followed by mf1 and cf1. Based on our body mass estimates (ca. 232 kg.), we inferred an average lifespan of 14 years, 9-month gestation time, and sexual maturation at 4.1 years, quite similar to the values we obtained based on estimated body masses of adult specimens from Bolivia published by previous authors. Along its latitudinal distribution (ca. 14° S-21° S) S. uccasamamensis co-occurred with other ground sloths (e.g., Megatheriinae, Thalassocninae, and Scelidotheriinae), suggesting niche partitioning. The presence of this medium-sized ground sloth is consistent with the similarity between the faunas of eastern Puna and the Bolivian Altiplano during the Pliocene, which is also concordant with what was observed in other clades, such as Rodentia and Notoungulata.

Calcium and phosphorus digestibility in broilers as affected by varying phytate concentrations from corn.

Dietary phytate P (PP) concentration impacts Ca and P digestibility in broilers. Research was conducted to determine the impact of increasing concentration of dietary PP, with and without phytase, on broiler standardized ileal digestibility (SID) of Ca and P. Digestible (Dig) Ca and P were calculated by multiplying SID and the analyzed dietary Ca and P concentrations. The experiment was a factorial arrangement of 2 phytase (0 and 1,000 U/kg) and 4 PP (0.16, 0.23, 0.29, and 0.34%) concentrations. Treatments were fed for 36 h from 20 to 22 d of age (4 b/pen, n ≥ 7 replicate pens/treatment). Different ratios of corn and corn germ were used to achieve the desired PP concentrations. A limestone with 800 µm geometric mean diameter was used as the sole Ca source to achieve 0.7% Ca in the final diets (96% Ca from limestone). An additional diet was fed that was N, Ca- and P-free, for the determination of endogenous losses of each nutrient. Distal ileal digesta were pooled from all birds in a pen. There were no interactions between PP and phytase on SID Ca or Dig Ca from limestone. Irrespective of phytase inclusion, increasing PP from 0.16 to 0.34% decreased SID Ca from 53.8 to 38.1% (P < 0.05). The SID Ca averaged 41.5 and 51.4% in diets containing 0 and 1000 U phytase/kg, respectively, across all PP concentrations (P < 0.05). Interactions were seen between PP and phytase on SID and Dig P (P < 0.05) with SID P of 31.1, 24.0, 20.1, and 16.3% for broilers fed 0.16, 0.23, 0.29, and 0.34% PP diets without phytase, respectively. When phytase was included at 1000 U/kg, SID P was 89.9, 87.5, 73.9 and 60.4% for diets containing 0.16, 0.23, 0.29 and 0.34% PP, respectively (P < 0.05). Overall, phytase improved SID Ca and P independent of PP concentration. However, with increasing PP concentration, both SID Ca and P were negatively affected.

Task-based assessment for neural networks: evaluating undersampled MRI reconstructions based on human observer signal detection.

Purpose: Recent research explores using neural networks to reconstruct undersampled magnetic resonance imaging. Because of the complexity of the artifacts in the reconstructed images, there is a need to develop task-based approaches to image quality. We compared conventional global quantitative metrics to evaluate image quality in undersampled images generated by a neural network with human observer performance in a detection task. The purpose is to study which acceleration (2×, 3×, 4×, 5×) would be chosen with the conventional metrics and compare it to the acceleration chosen by human observer performance. Approach: We used common global metrics for evaluating image quality: the normalized root mean squared error (NRMSE) and structural similarity (SSIM). These metrics are compared with a measure of image quality that incorporates a subtle signal for a specific task to allow for image quality assessment that locally evaluates the effect of undersampling on a signal. We used a U-Net to reconstruct under-sampled images with 2×, 3×, 4×, and 5× one-dimensional undersampling rates. Cross-validation was performed for a 500- and a 4000-image training set with both SSIM and MSE losses. A two-alternative forced choice (2-AFC) observer study was carried out for detecting a subtle signal (small blurred disk) from images with the 4000-image training set. Results: We found that for both loss functions, the human observer performance on the 2-AFC studies led to a choice of a 2× undersampling, but the SSIM and NRMSE led to a choice of a 3× undersampling. Conclusions: For this detection task using a subtle small signal at the edge of detectability, SSIM and NRMSE led to an overestimate of the achievable undersampling using a U-Net before a steep loss of image quality between 2×, 3×, 4×, 5× undersampling rates when compared to the performance of human observers in the detection task.

Chromosome-scale pearl millet genomes reveal CLAMT1b as key determinant of strigolactone pattern and Striga susceptibility.

The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

Study Protocol for the Opioid and Pain Treatment in Indigenous Communities Trial: A Systems Level Intervention for Enhanced Screening and Brief Intervention and Referral for Co-Occurring Chronic Pain and Opioid Use Disorder.

American Indian/Alaska Native (AI/AN) individuals have the highest rates of opioid overdose mortality and chronic pain (CP) compared to other racial/ethnic groups in the United States. These individuals also report higher rates of pain anxiety and pain catastrophizing, which are both associated with poorer outcomes and risk for opioid misuse (OM) and opioid use disorder (OUD) among individuals with CP. Yet, no prior studies have examined rates of comorbid pain and OUD among AI/AN adults. This commentary describes an implementation research partnership of 3 AI/AN-serving clinics and a university team that utilizes an implementation hybrid type III design to examine the impact of implementation strategies on adoption and sustainability of evidence-based screening and brief intervention for CP and OM/OUD among AI/AN clients. As part of our community-engaged approach, we embrace both AI/AN models and Western models, and a collaborative board of 10 individuals guided the research throughout. We hypothesize that our culturally centered approach will increase rates of screening and brief intervention and improve identification of and outcomes among AI/AN clients with CP and OUD who receive treatment at participating sites. Each site convenes a workgroup to evaluate and set goals to culturally center screening and brief interventions for CP and OM/OUD. Data collected include deidentified electronic health records to track screening and brief interventions and rates of CP and OUD; provider and staff surveys beginning prior to implementation and every 6 months for 2 years; and a subset of clients will be recruited (N = 225) and assessed at baseline, 6, and 12 months to examine biopsychosocial and spiritual factors and their experiences with culturally centered screening and brief intervention. Cultural adaptations to the measures and screening and brief intervention as well as barriers and facilitators will be addressed. Recommendations for successful Tribal health clinic-university partnerships are offered.

From Acyclic Intramolecular-[4 + 2]- to Transannular Bis-[4 + 2]-Cycloaddition of the Macrodiolide for the Stereoselective Synthesis of the Octahydronaphthalene Core of Polyenic Macrolactam Sagamilactam.

The strategy for the synthesis of the octahydronaphthalene core of natural macrolide sagamilactam has unintentionally evolved from the acyclic intramolecular (IMDA) to the transannular (TADA) Diels-Alder reaction. Lewis acid-promoted IMDA of a protected 2Z,8E,10E-4,6,12-trihydroxy-2,8,10-decatrienal model with a diol of 4,6-anti relative configuration, as proposed by DP4+-based computational studies, afforded the cis-octahydronaphthalene diastereomer through the Re-endo approach. The 26-membered macrodiolide generated, under thermal reaction conditions, the trans-octahydronaphthalene by a double TADA reaction along the desired Si-exo orientation.

Exercise in cancer patients: assistance levels and referral pathways-a position statement from the Spanish Society of Medical Oncology.

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

Modeling human observer detection for varying data acquisition in undersampled MRI for two-alternative forced choice (2-AFC) and forced localization tasks.

Undersampling in the frequency domain (k-space) in MRI enables faster data acquisition. In this study, we used a fixed 1D undersampling factor of 5x with only 20% of the k-space collected. The fraction of fully acquired low k-space frequencies were varied from 0% (all aliasing) to 20% (all blurring). The images were reconstructed using a multi-coil SENSE algorithm. We used two-alternative forced choice (2-AFC) and the forced localization tasks with a subtle signal to estimate the human observer performance. The 2-AFC average human observer performance remained fairly constant across all imaging conditions. The forced localization task performance improved from the 0% condition to the 2.5% condition and remained fairly constant for the remaining conditions, suggesting that there was a decrease in task performance only in the pure aliasing situation. We modeled the average human performance using a sparse-difference of Gaussians (SDOG) Hotelling observer model. Because the blurring in the undersampling direction makes the mean signal asymmetric, we explored an adaptation for irregular signals that made the SDOG template asymmetric. To improve the observer performance, we also varied the number of SDOG channels from 3 to 4. We found that despite the asymmetry in the mean signal, both the symmetric and asymmetric models reasonably predicted the human performance in the 2-AFC experiments. However, the symmetric model performed slightly better. We also found that a symmetric SDOG model with 4 channels implemented using a spatial domain convolution and constrained to the possible signal locations reasonably modeled the forced localization human observer results.

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α.

Many functional aspects of the protein kinase p38α have been illustrated by more than three hundred structures determined in the presence of reducing agents. These structures correspond to free forms and complexes with activators, substrates, and inhibitors. Here we report the conformation of an oxidized state with an intramolecular disulfide bond between Cys119 and Cys162 that is conserved in vertebrates. The structure of the oxidized state does not affect the conformation of the catalytic site, but alters the docking groove by partially unwinding and displacing the short αD helix due to the movement of Cys119 towards Cys162. The transition between oxidized and reduced conformations provides a mechanism for fine-tuning p38α activity as a function of redox conditions, beyond its activation loop phosphorylation. Moreover, the conformational equilibrium between these redox forms reveals an unexplored cleft for p38α inhibitor design that we describe in detail.

Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.

The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

Long-term performance of single-connector (DF4) implantable defibrillator leads.

AIMS: Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. METHODS AND RESULTS: We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. CONCLUSION: DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.

Scientific facts improve cannabis perception and public opinion: results from Sinaloa, México.

Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents "Using Evidence to Talk About Cannabis" and "State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa.

Mechanism substitution in preventive innovations: Dissecting the reproduction of health inequalities in the United States.

In the last three decades, numerous studies in different countries have corroborated the main postulates of the Fundamental Cause Theory (FCT), providing evidence showing how health inequalities are reproduced as society increases its capacity to control disease and/or avoid its consequences through preventive innovations. However, documenting the reproductive logic proposed by the theory requires the development of a dynamic analytical approach to consider socioeconomic disparities in the incorporation of multiple preventive innovations over time, which could act as mediating mechanisms of the durable relationship between socioeconomic status and health/mortality. This study draws on data from different waves of the National Health Interview Survey and the National Health and Nutrition Examination Survey to analyze the diffusion processes of various innovations in the U.S. The results of the study show that educational inequalities emerge, are amplified, and are reduced by the continuous diffusion of preventive innovations, supporting the meta-hypothesis of substitution of mediating mechanisms according to the interconnections of FCT and Diffusion of Innovation Theory.

Outcomes of leadless pacemaker implantation after cardiac surgery and transcatheter structural valve interventions.

INTRODUCTION: Permanent pacing indications are common after cardiac surgery and transcatheter structural valve interventions. Leadless pacemakers (LPs) have emerged as a useful alternative to transvenous pacemakers. However, current commercially available LPs are unable to provide atrial pacing or cardiac resynchronization and relatively little is known about LP outcomes after cardiac surgery and transcatheter valve interventions. METHODS: This retrospective study included patients who received a Micra VR (MicraTM MC1VR01) or Micra AV (MicraTM MC1AVR1) (Medtronic) leadless pacemaker following cardiac surgery or transcatheter structural valve intervention between September 2014 and September 2022. Device performance and clinical outcomes, including ventricular pacing burden, ejection fraction, and need for conversion to transvenous pacing systems, were evaluated during follow-up. RESULTS: A total of 78 patients were included, of whom 40 received a Micra VR LP implant, and 38 received a Micra AV LP implant. The mean age of the cohort was 65.9 ± 17.9 years, and 48.1% were females. The follow-up duration for the entire cohort was 1.3 ± 1.1 years: 1.6 ± 1.3 years for the Micra VR group and 0.8 ± 0.5 years for the Micra AV group. Among the cohort, 50 patients had undergone cardiac surgery and 28 underwent transcatheter structural valve interventions. Device electrical performance was excellent during follow-up, with a small but clinically insignificant increase in ventricular pacing threshold and a slight decrease in pacing impedance. The mean right ventricle pacing (RVP) burden significantly decreased over time in the entire cohort (74.3% ± 37.2% postprocedure vs. 47.7% ± 40.6% at last follow-up, p < .001), and left ventricle ejection fraction (LVEF) showed a modest but significant downward trend during follow-up (55.0% ± 10.6% vs. 51.5% ± 11.2% p < .001). Patients with Micra VR implants had significantly reduced LVEF during follow-up (54.1% ± 11.9% vs. 48.8% ± 11.9%, p = .003), whereas LVEF appeared stable in the Micra AV group during follow-up (56.1% ± 9.0% vs. 54.6% ± 9.7%, p = .06). Six patients (7.7%) required conversion to transvenous pacing systems, four who required cardiac resynchronization for drop in LVEF with high RVP burden and two who required dual-chamber pacemakers for symptomatic sinus node dysfunction. CONCLUSION: Leadless pacemakers provide a useful alternative to transvenous pacemakers in appropriately selected patients after cardiac surgery and transcatheter structural valve interventions. Device performance is excellent over medium-term follow-up. However, a significant minority of patients require conversion to transvenous pacing systems for cardiac resynchronization or atrial pacing support, demonstrating the need for close electrophysiologic follow-up in this cohort.

Humoral immune response to COVID-19 mRNA vaccines in patients with relapsing multiple sclerosis treated with ofatumumab.

BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab. METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined by local laboratory severe acute respiratory syndrome coronavirus-2 qualitative immunoglobulin G assays. Assay No. 1 was ≥14 days after the second or third vaccine dose. Assay No. 2 was 90 days thereafter. RESULTS: Of the 26 patients enrolled (median [range] age: 42 [27-54] years; median [range] ofatumumab treatment duration: 237 [50-364] days), HIR was achieved by 53.9% (14/26; 95% CI: 33.4 - 73.4%) at Assay No. 1 and 50.0% (13/26; 95% CI: 29.9 - 70.1%) at Assay No. 2. Patients who received 3 vaccine doses had higher HIR rates (Assay No. 1: 70.0% [7/10]; Assay No. 2: 77.8% [7/9]) than those who received 2 doses (Assay No. 1: 46.7% [7/15]; Assay No. 2: 42.9% [6/14]). Of patients aged <40 years without previous anti-CD20 therapy, HIR was achieved by 90.0% (9/10) at Assay No. 1 and 75.0% (6/8) at Assay No. 2. No serious adverse events were reported. CONCLUSION: Patients with RMS treated with ofatumumab can mount HIRs following COVID-19 vaccination. A plain language summary, infographic and a short video summarizing the key results are provided in supplementary material. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04847596 (https://clinicaltrials.gov/ct2/show/NCT04847596).

Prospective validation of a risk score to predict pacemaker implantation after transcatheter aortic valve replacement.

INTRODUCTION: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. METHODS: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. RESULTS: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001). CONCLUSIONS: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.