Respiratory Syncytial Virus Risk Profile in Hospitalized Infants and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. METHODS: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. CONCLUSIONS: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6-24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.

Formation of the interatrial septum: Insights obtained from cardiac computed tomographic angiography.

We previously described a septal variant termed left atrial septal pouch (LASP). Present in a third of hearts, it results from incomplete fusion of the septum primum (SP) and septum secundum (SS). We assessed the prevalence of LASP using 64-section multidetector computed tomography and further characterized the different variants. Among 864 scans, 770 were of sufficient quality for assessment (428 male, aged 59.2 ± 11.7 years). They were classified on the basis of the degrees of fusion of the SP and SS into a completely fused septum (CFS), patent foramen ovale (PFO), or LASP. The lengths of the SS, SP, and overlapping SP, the maximal length of the foramen ovale (FO) floor, and the atrial dimensions were compared. A PFO was seen in 181 patients (23.5%), a LASP in 242 (31.4%), and a CFS in 339 (44.0%). There were significant differences in the length of the SS (PFO-13.6 ± 4.3 mm, LASP-17.6 ± 4.8 mm, CFS-14.3 ± 7.7 mm, p < 0.001). Hearts with LASPs had a longer overlapping SP than those with PFOs (PFO-6.3 ± 4.5 mm, LASP-13.1 ± 5.2 mm, p < 0.001). The maximal lengths of the FO floor showed differences in short axis (SAX) view (PFO-21.7 ± 4.5 mm, LASP-15.3 ± 4.3 mm, CFS-16.3 ± 4.3 mm, p < 0.001). Hearts with PFO and LASP showed similar SP lengths (27.3 ± 6.6 mm vs. 26.4 ± 6.6 mm, p = 0.10). There was a positive linear correlation between the length of the SS and the overlapping SP (R2 = 0.28, p < 0.001) with a weaker negative correlation between the SS length and maximal length of the FO floor (R2 = 0.02, p < 0.001). The groups showed similar atrial dimensions and volumes. Present in a third of patients, hearts with LASP have longer SS and overlapping SP.

Challenges Reconciling Theory and Experiments in the Prediction of Lattice Thermal Conductivity: The Case of Cu-Based Sulvanites.

The exploration of large chemical spaces in search of new thermoelectric materials requires the integration of experiments, theory, simulations, and data science. The development of high-throughput strategies that combine DFT calculations with machine learning has emerged as a powerful approach to discovering new materials. However, experimental validation is crucial to confirm the accuracy of these workflows. This validation becomes especially important in understanding the transport properties that govern the thermoelectric performance of materials since they are highly influenced by synthetic, processing, and operating conditions. In this work, we explore the thermal conductivity of Cu-based sulvanites by using a combination of theoretical and experimental methods. Previous discrepancies and significant variations in reported data for Cu3VS4 and Cu3VSe4 are explained using the Boltzmann Transport Equation for phonons and by synthesizing well-characterized defect-free samples. The use of machine learning approaches for extracting high-order force constants opens doors to charting the lattice thermal conductivity across the entire Cu-based sulvanite family-finding not only materials with κ l values below 2 W m-1 K-1 at moderate temperatures but also rationalizing their thermal transport properties based on chemical composition.

Outflow Graft Tamponade: An Underrecognized Cause of Obstruction.

BACKGROUND: Left ventricular assist device (LVAD) outflow graft obstruction can result in severe clinical deterioration. Underlying mechanisms may vary depending on the location. Outflow graft tamponade due to external compression can be under recognized. Management of this complication varies across institutions and a uniform approach has yet to be elucidated. OBJECTIVES: Report a single center experience with outflow graft tamponade in patients with LVAD with the purpose of developing an optimal algorithm for the diagnosis and treatment of LVAD-related outflow graft tamponade. METHODS AND RESULTS: Retrospective chart review between July 2011 and July 2020. A total of 351 LVADs were implanted at our center, with outflow graft tamponade identified in 26 patients with LVAD. Fourteen (53.8%) had HeartMate II™, 8 (30.8%) had HeartMate3™ and 4 (15.4%) had HeartWare™. Individuals presented with heart failure symptoms, an audible precordial murmur and LVAD alarms after a median duration of 862 days of support (IQR 327 - 1455). Of the 26 patients, 15 (57.7%) underwent mini thoracotomy with outflow graft relief, 4 had percutaneous balloon dilatation and stenting, 2 were bridged directly to transplant and 1 had a pump exchange. No intervention was made on the remaining due to mild symptoms (n = 4). CONCLUSIONS: Conclusions: Outflow graft tamponade is a form outflow graft obstruction with a variable presentation that can result in significant hemodynamic compromise. It is amenable to both surgical and percutaneous interventions that restore LVAD function.

Cardiac Magnetic Resonance for Structural Aortic Valve Stenosis Procedures.

The number of structural aortic valve procedures has increased significantly in recent years. Pre-procedural planning and follow-up with noninvasive testing are essential. Although cardiac magnetic resonance (CMR) is the gold standard for assessing left ventricular mass, volume, and function, it is not performed routinely in patients undergoing structural interventions. CMR can provide useful information for pre- and post-procedural assessment, including quantification of cardiac function, myocardial assessment, grading of the severity of valvular heart disease, and evaluation of extracardiac anatomy while avoiding the limitations of other non-invasive modalities. Here, we review the use cases, future perspectives, and limitations of CMR for patients undergoing structural aortic valve procedures.

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

Design and Proof of Concept of a Web-Based Questionnaire to Identify Patients at Risk for HIV and HCV Infection.

Despite remarkable improvement in the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) care continuum, the rate of late diagnosis of HIV and HCV in high-income countries remains unacceptably high. Testing relies mainly on primary care physicians' identification of risk factors. We aimed to adapt an analogic to an online questionnaire to help HIV and HCV screening and perform a pilot study to assess its accuracy and acceptability. We used the Delphi method to adapt a previously validated analogical questionnaire to a user-friendly online tool. It aimed to identify participants who should be screened for HIV or HCV and those who should be referred for pre-exposure prophylaxis (PrEP). We then designed a proof-of-concept pilot study from July to October 2022 to test its feasibility and suitability for use on a larger scale and to assess its accuracy in identifying patients at risk for HIV or HCV or with indication for PrEP. The final questionnaire consisted of 37 questions. A total of 142 participants provided informed consent, and 102 completed the questionnaire: 41 random patients recruited at the primary care level, 10 participants recently diagnosed with HIV, 20 participants with HIV on follow-up, 21 participants from the PrEP program, and 10 patients diagnosed with HCV. The tool adequately indicated the need for testing in more than 98% of participants with confirmed HIV/HCV infections or in the PrEP program. Furthermore, it adequately assessed PrEP referral in 94% of participants already on PrEP or with known HIV infection. Participants were highly satisfied with the tool, and 98% of them recommended its use. A self-administered web-based tool to identify patients who should be tested for HIV or HCV or referred to PrEP could simplify patient selection and help reduce late diagnosis.

RSV Risk Profile in Hospitalized Adults and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. METHODS: This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30 days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p = < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p = < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjusted OR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38-84%) lower odds of experiencing any severe outcome compared to COVID-19. CONCLUSIONS: RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation.

BACKGROUND: Adding functional information by CT-derived fractional flow reserve (FFRct) to coronary CT angiography (CCTA) and assessing its temporal change may provide insight into the natural history and physiopathology of cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients. We assessed FFRct changes as well as CAV progression over a 2-year period in HTx patients undergoing serial CT imaging. METHODS: HTx patients from Erasmus MC and Mount Sinai Hospital, who had consecutive CCTAs 2 years apart were evaluated. FFRct analysis was performed for both scans. FFRct values at the most distal point in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) were measured after precisely matching the anatomical locations in both analyses. Also, the number of anatomical coronary stenoses of > 30% was scored. RESULTS: In total, 106 patients (median age 57 [interquartile range 47-67] years, 67% male) at 9 [6-13] years after HTx at the time of the baseline CCTA were included. Median distal FFRct values significantly decreased from baseline to follow-up for the LAD from 0.85 [0.79-0.90] to 0.84 [0.76-0.90] (p = 0.001), LCX from 0.92 [0.88-0.96] to 0.91 [0.85-0.95] (p = 0.009), and RCA from 0.92 [0.86-0.95] to 0.90 [0.86-0.94] (p = 0.004). The number of focal anatomical stenoses of > 30% increased from a median of 1 [0-2] at baseline to 2 [0-3] at follow-up (p = 0.009). CONCLUSIONS: The distal coronary FFRct values in post-HTX patients in each of the three major coronary arteries decreased, and the number of focal coronary stenoses increased over a 2-year period. Temporal FFRct change rate may become an additional parameter in the follow-up of HTx patients, but more research is needed to elucidate its role. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve (FFRct) is important post-heart transplant because of additional information on coronary CT angiography for cardiac allograft vasculopathy (CAV) detection. The decrease and degree of reduction in distal FFRct value may indicate progression in anatomic CAV burden. KEY POINTS: CT-derived fractional flow reserve (FFRct) is important for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients. Over time, transplant patients showed a decrease in distal FFRct and an increase in coronary stenoses. Temporal changes in FFRct could be crucial for transplant follow-up, aiding in CAV detection.

Phage display identification of high-affinity ligands for human TSG101-UEV: A structural and thermodynamic study of PTAP recognition.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disrupting TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of novel host-oriented antivirals with a broad spectrum of action. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood. Here we present a detailed thermodynamic, structural, and dynamic characterization viral PTAP Late domain recognition by TSG101-UEV, combining isothermal titration calorimetry, X-ray diffraction structural studies, molecular dynamics simulations, and computational analysis of intramolecular communication pathways. Our analysis highlights key contributions from conserved hydrophobic contacts and water-mediated hydrogen bonds at the PTAP binding interface. We have identified additional electrostatic hotspots adjacent to the core motif that modulate affinity. Using competitive phage display screening we have improved affinity by 1-2 orders of magnitude, producing novel peptides with low micromolar affinities that combine critical elements found in the best natural binders. Molecular dynamics simulations revealed that optimized peptides engage new pockets on the UEV domain surface. This study provides a comprehensive view of the molecular forces directing TSG101-UEV recognition of PTAP motifs, revealing that binding is governed by conserved structural elements yet tuneable through targeted optimization. These insights open new venues to design inhibitors targeting TSG101-dependent pathways with potential application as novel broad-spectrum antivirals.

Transition times across the HIV care continuum in Spain from 2005 to 2022: a longitudinal cohort study.

BACKGROUND: Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. METHODS: We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. FINDINGS: We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. INTERPRETATION: The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. FUNDING: Instituto de Salud Carlos III and Spanish AIDS Research Network.

Theoretical Investigation of the Lattice Thermal Conductivities of II-IV-V2 Pnictide Semiconductors.

Ternary pnictide semiconductors with II-IV-V2 stoichiometry hold potential as cost-effective thermoelectric materials with suitable electronic transport properties, but their lattice thermal conductivities (κ) are typically too high. Insights into their vibrational properties are therefore crucial to finding strategies to reduce κ and achieve improved thermoelectric performance. We present a theoretical exploration of the lattice thermal conductivities for a set of pnictide semiconductors with ABX2 composition (A = Zn, Cd; B = Si, Ge, Sn; and X = P, As) using machine-learning-based regression algorithms to extract force constants from a reduced number of density functional theory simulations and then solving the Boltzmann transport equation for phonons. Our results align well with available experimental data, decreasing the mean absolute error by ∼3 W m-1 K-1 with respect to the best previous set of theoretical predictions. Zn-based ternary pnictides have, on average, more than double the thermal conductivity of the Cd-based compounds. Anisotropic behavior increases with the mass difference between A and B cations, but while the nature of the anion does not affect the structural anisotropy, the thermal conductivity anisotropy is typically higher for arsenides than for phosphides. We identify compounds such as CdGeAs2, for which nanostructuring to an affordable range of particle sizes could lead to κ values low enough for thermoelectric applications.

SwissGenVar: A Platform for Clinical-Grade Interpretation of Genetic Variants to Foster Personalized Healthcare in Switzerland.

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows. This includes extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUSs) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of the standards used to describe genetic variants and the associated phenotypes when searching for relevant information to support clinical decision making. To address this, all five Swiss academic institutions for Medical Genetics joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its aim is to provide a protected environment for expert evidence sharing about individual variants to harmonize and upscale their significance interpretation at the clinical grade according to international standards. To corroborate the clinical assessment, the variant-related data will be combined with consented high-quality clinical information. Broader visibility will be achieved by interfacing with international databases, thus supporting global initiatives in personalized healthcare.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.

BACKGROUND: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. METHODS: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). RESULTS: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. CONCLUSION: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.

A 12-week multicomponent exercise program enhances frailty by increasing robustness, improves physical performance, and preserves muscle mass in older adults with HIV: MOVIhNG study.

Background: Our aim was to analyze the effects of a multicomponent exercise program (MEP) on frailty and physical performance in older adults with HIV (OAWH) since exercise can reverse frailty in the older population overall, but there is no data for OAWH. Methods: A prospective longitudinal study with intervention and control group was designed. Sedentary adults 50 or over with and without HIV were included. The intervention was a 12-week home-based MEP. Dependent variables were frailty (frailty phenotype), physical performance (Senior Fitness Test), muscle mass (ASMI) by bioimpedance. Pre- and postintervention measurements were analyzed using McNemar's test for categorical variables and the Wilcoxon signed-rank test for quantitative variables. Results: 40 OAWH and 20 OA without HIV. The median age was 56.5 years. 23.3% were women. The prevalence of frailty was 6.6% with no frail HIV-negative participants. Three of the four frail HIV-participants transitioned two (50%) from frail to prefrail and one (25%) to robust after the MEP. In participants with an adherence ≥50%, physical performance was significantly improved [basal vs. 12 week]: upper extremity strength [13 (13-15) vs. 16 (15-19), p = 0.0001], lower extremity strength [13 (11-16) vs. 15 (13-16), p = 0.004], aerobic endurance [62 (55-71) vs. 66 (58-80), p = 0.005]. Participants with low adherence experienced a significant worsening in ASMI [8.35 (7.44-9.26) vs. 7.09 (6.08-8.62), p = 0.03]. Conclusion: A 12-week MEP enhances frailty by increasing robustness in OAWH, and improves physical performance, and preserves muscle mass in older adults with good adherence to the MEP independently of HIV status.

Design Principles Guided by DFT Calculations and High-Throughput Frameworks for the Discovery of New Diamond-like Chalcogenide Thermoelectric Materials.

Rational design principles are one pathway to discovering new materials. However, technological breakthroughs rarely occur in this way because these design principles are usually based on incremental advances that seldom lead to disruptive applications. The emergence of machine-learning (ML) and high-throughput (HT) techniques has changed the paradigm, opening up new possibilities for efficiently screening large chemical spaces and creating on-the-fly design principles for the discovery of novel materials with desired properties. In this work, the approach is used to discover novel thermoelectric (TE) materials based on quaternary diamond-like chalcogenides. A HT framework that integrates density functional theory calculations, ML, and the solution of the Boltzmann transport equation is used to efficiently rationalize the transport properties of these compounds and identify those with potential as TE materials, achieving ZT values above 2.

Potential Effects on Elderly People From Nirsevimab Use in Infants.

Nirsevimab therapy has the potential to revolutionize infant respiratory syncytial virus (RSV) prophylaxis. But other populations suffering RSV, such the elderly or those over 60, may also be protected by using this novel antibody in the infant group. It is true that some studies link the use of nirsevimab to a reduction in the virus's ability to spread by lowering the viral load in infants as a result of the drug's long half-life. However, this protective effect may not be very significant because RSV transmission in the elderly typically comes from other elderly people or from school-aged children. Furthermore, RSV may be transmitted at any time of the year and not just during the period of nirsevimab protection due to its existence in human reservoirs. The reasons made here show that, even though nirsevimab treatment in infants may protect the elderly, this benefit would be limited and testimonial. Therefore, immunizing the elderly with currently licensed and developing vaccines should be a priority.

El uso de nirsevimab puede suponer una revolución en la prevención del virus respiratorio sincitial (VRS) en lactantes. Sin embargo, el uso de este nuevo anticuerpo en dicho grupo de edad podría proteger también a otros grupos que conviven con ellos, como por ejemplo las personas de edad avanzada o grupo de personas mayores de 60 años. Si bien es cierto que algunos estudios sugieren una disminución en la propagación del virus con el uso de nirsevimab, al reducir la carga viral en lactantes como consecuencia de la prolongada vida media del fármaco, este efecto protector podría ser de escasa relevancia, ya que la transmisión del VRS en personas de edad avanzada sucede en la mayor parte de los casos desde personas de la misma edad o desde niños en edad escolar. Adicionalmente, la presencia de VRS en reservorios humanos puede permitir que el VRS se transmita en cualquier época del año, no limitándose únicamente al periodo de protección de nirsevimab. Los argumentos aquí expuestos demuestran que, si bien el uso de nirsevimab en lactantes podría tener un efecto protector en las personas de edad avanzada, este solo sería testimonial y limitado. En consecuencia, debe priorizarse la inmunización de los pacientes de edad avanzada con las vacunas actualmente autorizadas y en desarrollo.

Stability properties of ultraholomorphic classes of Roumieu-type defined by weight matrices.

We characterize several stability properties, such as inverse or composition closedness, for ultraholomorphic function classes of Roumieu type defined in terms of a weight matrix. In this way we transfer and extend known results from J. Siddiqi and M. Ider, from the weight sequence setting and in sectors not wider than a half-plane, to the weight matrix framework and for sectors in the Riemann surface of the logarithm with arbitrary opening. The key argument rests on the construction, under suitable hypotheses, of characteristic functions in these classes for unrestricted sectors. As a by-product, we obtain new stability results when the growth control in these classes is expressed in terms of a weight sequence, or of a weight function in the sense of Braun-Meise-Taylor.