The neocortical infrastructure for language involves region-specific patterns of laminar gene expression.

The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain's language network.

Structural insights reveal interplay between LAG-3 homodimerization, ligand binding, and function.

Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function. Additionally, we found a previously unidentified key protein-glycan interaction in the dimer interface that affects the spatial orientation of the neighboring D1 domain. Mutation of LAG-3 D2 residues reduced dimer formation, dramatically abolished LAG-3 binding to both MHCII and FGL1 ligands, and consequentially inhibited the role of LAG-3 in suppressing T cell responses. Intriguingly, we showed that antibodies directed against D1, D2, and D3 domains are all capable of blocking LAG-3 dimer formation and MHCII and FGL-1 ligand binding, suggesting a potential allosteric model of LAG-3 function tightly regulated by dimerization. Furthermore, our work reveals unique epitopes, in addition to D1, that can be targeted for immunotherapy of cancer and other human diseases.

Correction of Ito in human induced pluripotent stem Cell-derived cardiomyocyte carrying DPP6 mutation in early repolarization syndrome by CRISPR/Cas9 genome editing.

Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (Ito) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the Ito, whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased Ito and lengthen APD, which maybe lay the electrophysiological foundation of ERS.

Ion transport in nanofluidics under external fields.

Nanofluidic channels with tailored ion transport dynamics are usually used as channels for ion transport, to enable high-performance ion regulation behaviors. The rational construction of nanofluidics and the introduction of external fields are of vital significance to the advancement and development of these ion transport properties. Focusing on the recent advances of nanofluidics, in this review, various dimensional nanomaterials and their derived homogeneous/heterogeneous nanofluidics are first briefly introduced. Then we discuss the basic principles and properties of ion transport in nanofluidics. As the major part of this review, we focus on recent progress in ion transport in nanofluidics regulated by external physical fields (electric field, light, heat, pressure, etc.) and chemical fields (pH, concentration gradient, chemical reaction, etc.), and reveal the advantages and ion regulation mechanisms of each type. Moreover, the representative applications of these nanofluidic channels in sensing, ionic devices, energy conversion, and other areas are summarized. Finally, the major challenges that need to be addressed in this research field and the future perspective of nanofluidics development and practical applications are briefly illustrated.

Metalation of metal-organic frameworks: fundamentals and applications.

Metalation of metal-organic frameworks (MOFs) has been developed as a prominent strategy for materials functionalization for pore chemistry modulation and property optimization. By introducing exotic metal ions/complexes/nanoparticles onto/into the parent framework, many metallized MOFs have exhibited significantly improved performance in a wide range of applications. In this review, we focus on the research progress in the metalation of metal-organic frameworks during the last five years, spanning the design principles, synthetic strategies, and potential applications. Based on the crystal engineering principles, a minor change in the MOF composition through metalation would lead to leveraged variation of properties. This review starts from the general strategies established for the incorporation of metal species within MOFs, followed by the design principles to graft the desired functionality while maintaining the porosity of frameworks. Facile metalation has contributed a great number of bespoke materials with excellent performance, and we summarize their applications in gas adsorption and separation, heterogeneous catalysis, detection and sensing, and energy storage and conversion. The underlying mechanisms are also investigated by state-of-the-art techniques and analyzed for gaining insight into the structure-property relationships, which would in turn facilitate the further development of design principles. Finally, the current challenges and opportunities in MOF metalation have been discussed, and the promising future directions for customizing the next-generation advanced materials have been outlined as well.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

High-Nuclearity Ln210Al140 Clusters: Neonates of Open Hollow Dodecahedral Cage Families.

Open hollow dodecahedral cage clusters have long been a coveted target in synthetic chemistry, yet their creation poses immense challenges. Here we report two open hollow dodecahedral lanthanide-aluminum (Ln-Al) heterometallic cage clusters, namely, [Ln210Al140(µ2-OH)210(µ3-OH)540(OAc)180(H2O)156](ClO4)120·(MeCN)x·(H2O)y, (Ln = Dy and x = 27, y = 300 for 1; Ln = Y and x = 28, y = 420 for 2). Remarkably, the 350 metal atoms in 1 and 2 display a Keplerate-type four-shell structure of truncated icosidodecahedron@dodecahedron@dodecahedron@icosidodecahedron. The diameter of the cationic cluster in 1 is approximately 5.0 nm, with an inner cavity diameter of about 2.8 nm and a window diameter of roughly 0.66 nm. The cluster in 1 boasts an accessible inner void volume of up to 15,000 Å3. Notably, these cage clusters maintain stability in water, and the truncated icosidodecahedrons in 1 and 2 are the first of their kind synthesized to date. Given that the open hollow dodecahedral Ln-Al cage cluster has never been reported before, this work represents a member in the family of hollow open dodecahedral cages.

TRPM4-Inspired Polymeric Nanochannels with Preferential Cation Transport for High-Efficiency Salinity-Gradient Energy Conversion.

Biological ion channels exhibit switchable cation transport with ultrahigh selectivity for efficient energy conversion, such as Ca2+-activated TRPM4 channels tuned by cation-π interactions, but achieving an analogous highly selective function is challenging in artificial nanochannels. Here, we design a TRPM4-inspired cation-selective nanochannel (CN) assembled by two poly(ether sulfone)s, respectively, with sulfonate acid and indole moieties, which act as cation-selective activators to manage Na+/Cl- selectivity via ionic and cation-π interactions. The cation selectivity of CNs can be activated by Na+, and thereby the Na+ transference number significantly improves from 0.720 to 0.982 (Na+/Cl- selectivity ratio from 2.6 to 54.6) under a 50-fold salinity gradient, surpassing the K+ transference number (0.886) and Li+ transference number (0.900). The TRPM4-inspired nanochannel membrane enabled a maximum output power density of 5.7 W m-2 for salinity-gradient power harvesting. Moreover, a record energy conversion efficiency of up to 46.5% is provided, superior to most nanochannel membranes (below 30%). This work proposes a novel strategy to biomimetic nanochannels for highly selective cation transport and high-efficiency salinity-gradient energy conversion.

Strong NIR-II Magneto-Optical Activity of a Chiral Sm15Cu54 Cage.

The magneto-optical response of chiral materials holds significant potential for applications in physics, chemistry, and biology. However, exploration of the near-infrared (NIR) magneto-optical response remains limited. Herein, we report the synthesis and strong NIR-II magneto-optical activity of three pairs of chiral 3d-4f clusters of R/S-Ln15Cu54 (Ln = Sm, Gd, and Dy). Structural analysis reveals that R/S-Ln15Cu54 features a triangular prism cage with C3 symmetry. Interestingly, magnetic circular dichroism (MCD) spectra exhibit remarkable magneto-optical response in the NIR-II region, driven by the f-f transition. The maximum g-factor of R/S-Sm15Cu54 reaches 5.5 × 10-3 T-1 around 1300-1450 nm, surpassing values associated with DyIII and CuII ions. This remarkable NIR-II magneto-optical activity may be attributed to strong magnetic-dipole-allowed f-f transitions and helix chirality of the structure. This work not only presents the largest Ln-Cu clusters to date but also demonstrate the key role of magnetic-dipole-allowed transitions on magneto-optical activity.

Enhancement of Magneto-Chiral Dichroism Intensity by Chemical Design: The Key Role of Magnetic-Dipole Allowed Transitions.

Here we report on the strong magneto-chiral dichroism (MChD) detected through visible and near-infrared light absorption up to 5.0 T on {Er5Ni6} metal clusters obtained by reaction of enantiopure chiral ligands and NiII and ErIII precursors. Single-crystal diffraction analysis reveals that these compounds are 3d-4f heterometallic clusters, showing helical chirality. MChD spectroscopy reveals a high gMChD dissymmetry factor of ca. 0.24 T-1 (T = 4.0 K, B = 1.0 T) for the 4I13/2 ← 4I15/2 magnetic-dipole allowed electronic transition of the ErIII centers. This record value is 1 or 2 orders of magnitude higher than that of the d-d electronic transitions of the NiII ions and the others f-f electric-dipole induced transitions of the ErIII centers. These findings clearly show the key role that magnetic-dipole allowed transitions have in the rational design of chiral lanthanide systems showing strong MChD.

Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

CD38 deficient mice are not protected from atherosclerosis.

CD38 is a multifunctional enzyme implicated in chemotaxis of myeloid cells and lymphocyte activation, but also expressed by resident cells such as endothelial and smooth muscle cells. CD38 is important for host defense against microbes. However, CD38's role in the pathogenesis of atherosclerosis is controversial with seemingly conflicting results reported so far. To clarify the discrepancy of current literature on the effect of CD38 ablation on atherosclerosis development, we implanted a shear stress modifier around the right carotid artery in CD38-/- and WT mice. Hypercholesterolemia was induced by human gain-of-function PCSK9 (D374Y), introduced using AAV vector (serotype 9), combined with an atherogenic diet for a total of 9 weeks. Atherosclerosis was assessed at the aortic root, aortic arch and the right carotid artery. The findings can be summarized as follows: i) CD38-/- and WT mice had a similar atherosclerotic burden in all three locations, ii) No significant differences in monocyte infiltration or macrophage content could be seen in the plaques, and iii) The amount of collagen deposition in the plaques were also similar between CD38-/- and WT mice. In conclusion, our data suggest that CD38-/- mice are neither protected against nor prone to atherosclerosis compared to WT mice.

Photo-Driven Ion Directional Transport across Artificial Ion Channels: Band Engineering of WS2 via Peptide Modification.

Biological photo-responsive ion channels play important roles in the important metabolic processes of living beings. To mimic the unique functions of biological prototypes, the transition metal dichalcogenides, owing to their excellent mechanical, electrical, and optical properties, are already used for artificial intelligent channel constructions. However, there remain challenges to building artificial bio-semiconductor nanochannels with finely tuned band gaps for accurately simulating or regulating ion transport. Here, two well-designed peptides are employed for the WS2 nanosheets functionalization with the sequences of PFPFPFPFC and DFDFDFDFC (PFC and DFC; P: proline, D: aspartate, and F: phenylalanine) through cysteine (Cys, C) linker, and an asymmetric peptide-WS2 membrane (AP-WS2M) could be obtained via self-assembly of peptide-WS2 nanosheets. The AP-WS2M could realize the photo-driven anti-gradient ion transport and vis-light enhanced osmotic energy conversion by well-designed working patterns. The photo-driven ion transport mechanism stems from a built-in photovoltaic motive force with the help of formed type II band alignment between the PFC-WS2 and DFC-WS2. As a result, the ions would be driven across the channels of the membrane for different applications. The proposed system provides an effective solution for building photo-driven biomimetic 2D bio-semiconductor ion channels, which could be extensively applied in the fields of drug delivery, desalination, and energy conversion.

Tuning Electrocatalytic Water Oxidation Activity: Insights from the Active-Site Distance in LnCu6 Clusters.

Atomically precise metal clusters serve as a unique model for unraveling the intricate mechanism of the catalytic reaction and exploring the complex relationship between structure and activity. Herein, three series of water-soluble heterometallic clusters LnCu6, abbreviated as LnCu6-AC (Ln = La, Nd, Gd, Er, Yb; HAC = acetic acid), LnCu6-IM (Ln = La and Nd; IM = Imidazole), and LnCu6-IDA (Ln = Nd; H2IDA = Iminodiacetic acid) are presented, each featuring a uniform metallic core stabilized by distinct protected ligands. Crystal structure analysis reveals a triangular prism topology formed by six Cu2+ ions around one Ln3+ ion in LnCu6, with variations in Cu···Cu distances attributed to different ligands. Electrocatalytic oxygen evolution reaction (OER) shows that these different LnCu6 clusters exhibit different OER activities with remarkable turnover frequency of 135 s-1 for NdCu6-AC, 79 s-1 for NdCu6-IM and 32 s-1 for NdCu6-IDA. Structural analysis and Density Functional Theory (DFT) calculations underscore the correlation between shorter Cu···Cu distances and improves OER catalytic activity, emphasizing the pivotal role of active-site distance in regulating electrocatalytic OER activities. These results provide valuable insights into the OER mechanism and contribute to the design of efficient homogeneous OER electrocatalysts.

Transfemoral transcatheter aortic valve replacement with VitaFlowTM valve for pure native aortic regurgitation in patients with high surgical risk: Rationale and design of a prospective, multicenter, and randomized SEASON-AR trial.

BACKGROUND: Previous studies primarily demonstrated that transfemoral transcatheter aortic valve replacement (TAVR) with self-expanding valve appeared to be a safe and feasible treatment for patients with pure native aortic regurgitation (AR). However, the routine application of transfemoral TAVR for pure AR patients lacks support from randomized trials. TRIAL DESIGN: SEASON-AR trial is a prospective, multicenter, randomized, controlled, parallel-group, open-label trial, involving at least 20 sites in China, aiming to enroll 210 patients with pure native severe AR and high surgical risk. All enrolled patients are randomly assigned in a 1:1 fashion to undergo transfemoral TAVR with VitaFlowTM valve and receive guideline-directed medical therapy (GDMT) or to receive GDMT alone. The primary endpoint is the rate of major adverse cardiac events (MACE) at 12 months after the procedure, defined by the composite of all-cause mortality, disabling stroke, and rehospitalization for heart failure. The major secondary endpoints encompass various measures, including procedure-related complications, device success, 6-minute walk distance, and the occurrence of each individual component of the primary endpoint. After hospital discharge, follow-up was conducted through clinical visits or telephone contact at 1, 6, and 12 months. The follow-up will continue annually until 5 years after the index procedure to assess the long-term outcomes. CONCLUSION: SEASON-AR trial is the first study designed to investigate the clinical efficacy and safety of transfemoral TAVR with a self-expanding valve in patients with pure native severe AR with inoperable or high-risk, as compared to medical treatment only.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

The therapeutic effect of a novel GAPDH inhibitor in mouse model of breast cancer and efficacy monitoring by molecular imaging.

BACKGROUND: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

Global, regional and national burdens of depression in adolescents and young adults aged 10-24 years, from 1990 to 2019: findings from the 2019 Global Burden of Disease study.

BACKGROUND: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time. AIMS: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years. METHOD: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019. RESULTS: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males. CONCLUSIONS: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

Single-center experience with self-expanding transcatheter aortic valve system for symptomatic high-risk patients with severe aortic regurgitation: One-year outcomes.

AIMS: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for the treatment of aortic regurgitation (AR). METHODS: From September 2019 to February 2022, 62 patients who underwent transfemoral TAVI procedure for pure, symptomatic severe AR with the VitaFlow system were enrolled in the current study. The outcomes were assessed according to the Valve Academic Research Consortium 3 criteria. Procedural results and clinical outcomes for 1 year were analyzed. RESULTS: The mean age was 71.56 ± 7.34 years and 58.1% were male. The mean Society of Thoracic Surgeons score was 5.44 ± 3.22%. The device success rate was 79.0%. Only one patient was converted to open surgery. The in-hospital mortality rate was 1.6%. The 1-year all-cause mortality rate was 6.5%. The new permanent pacemaker implantation rate was 29.0% in-hospital and 30.7% at 1-year follow-up. The second valve implantation rate was 14.5%. No patient developed more than moderate paravalvular leakage during follow-up. The mean ejection fraction improved from 54.05 ± 10.83% at baseline to 59.32 ± 8.70% (p < 0.001 compared with baseline) at 12 months. Left ventricular end-diastolic diameter decreased from 61.62 ± 5.58 mm at baseline to 55.20 ± 4.51 mm (p < 0.001 compared with the baseline) at 12 months. CONCLUSIONS: Transfemoral TAVI procedure shows efficacy in treating patients with severe pure native AR. The safety is improved with the development of the VitaFlow system.

Cardiac MR Feature Tracking Derived Strain Analysis can Predict Return to Training following Exertional Heatstroke.

BACKGROUND: Exertional heatstroke (EHS) is increasingly common in young trained soldiers. However, the prognosis marker in EHS patients remains unclear. To evaluate cardiac MRI feature tracking (CMR-FT) derived left ventricle (LV) strain as a biomarker for return to training (RTT) in trained soldiers with EHS in a prospective CMR cohort. METHODS: Trained soldiers (participants) with EHS underwent cardiac MR cine sequences between June 2020 and August 2023. Two-dimensional (2D) LV strain parameters were derived. At 3 months after index CMR, the participants with persistent cardiac symptoms including chest pain, dyspnea, palpitations, syncope, and recurrent heat-related illness were defined as non-RTT. Multivariable logistic regression analysis is used to develop a predictive RTT model. The performance of different models was compared using the area under curve (AUC). RESULTS: A total of 80 participants (median age, 21 years; interquartile range (IQR), 20-23 years) and 27 health controls (median age, 21 years; IQR, 20-22 years) were prospectively included. Of the 77 participants, 32 (41.6%) had persistent cardiac symptoms and were not able to RTT at 3 months follow-up after experiencing EHS. The 2D global longitudinal strain (GLS) was significantly impaired in EHS participants compared to the healthy control group (-15.81 ± 1.67% vs -16.93 ± 1.22%, P =.001), which also showed significantly statistical differences between participants with RTT and non-RTT (-14.99 ± 3.54% vs -16.53 ± 1.43%, P <.001). 2D-GLS (≤ -15.00%) (odds ratio, 1.53; 95% confidence interval (CI): 1.08, 2.17; P =.016) was an independent predictor for RTT even after adjusting known risk factors. 2D-GLS provided incremental prognostic value over the clinical model and conventional CMR parameters model (AUCs: 0.72 vs 0.88, P =.013; 0.79 vs 0.88, P =.023; respectively). CONCLUSIONS: Two-dimensional global longitudinal strain (≤ -15.00%) is an incremental prognostic CMR biomarker to predict return to training in exertional heatstroke soldiers.