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Tanya M Laidlaw1,2 *, Andrew Menzies-Gow3 *, Scott Caveney,4 Joseph K Han,5 Nicole Martin,6,7 Elliot Israel,8 Jason K Lee,9,10 Jean-Pierre Llanos,11 Neil Martin,12,13 Ayman Megally,14 Bhavini Parikh,14 Sylvia Vong,15 Tobias Welte,16 Jonathan Corren17 1Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Medicine, Harvard Medical School, Boston, MA, USA; 3Royal Brompton and Harefield Hospitals, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA; 5Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA; 6Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA; 7Cytel Inc, Waltham, MA, USA; 8Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 9Evidence Based Medical Educator Inc., Toronto, ON, Canada; 10Toronto Allergy and Asthma Clinic, Toronto, ON, Canada; 11Global Medical Affairs, Amgen, Thousand Oaks, CA, USA; 12Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 13University of Leicester, Leicester, UK; 14Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 15Translational Science and Experimental Medicine, Early Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 16Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany; 17David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Tanya M Laidlaw, Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA, 02115, USA, Email tlaidlaw@bwh.harvard.eduPurpose: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR.Methods: Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc).Results: Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (– 12.57 points [– 19.40, – 5.73]) and 52 weeks (– 10.58 points [– 17.75, – 3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status.Conclusion: Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.Graphical Abstract: Plain Language Summary: Asthma is a long-term condition caused by ongoing inflammation of the lower airways. The main symptoms are difficulty breathing, coughing, wheezing and shortness of breath. Approximately 41% of patients with severe asthma also have chronic rhinosinusitis with nasal polyps, a condition that affects the upper airways and sinuses. Nasal polyps are painless soft growths inside your nose that can keep growing if not treated. Symptoms include nasal congestion with mucus, facial pain and a reduced sense of smell or taste. People with both severe asthma and nasal polyps often have severe symptoms.Thymic stromal lymphopoietin (TSLP) is a signaling molecule released by cells lining the airways in response to airborne triggers, such as smoke, pollen and viruses. TSLP activates several pathways that cause inflammation in the airways, leading to asthma symptoms. Tezepelumab is a biologic treatment that targets the very start of these inflammatory pathways by blocking TSLP.The 1-year-long clinical trial called “NAVIGATOR” reported that tezepelumab reduced asthma attacks and improved lung function and asthma symptom control compared with placebo in patients with severe asthma that was not controlled with their current medicines. This analysis of data from NAVIGATOR looked at patients with both severe asthma and nasal polyps, showing that tezepelumab treatment improved sino-nasal symptoms compared with placebo. Tezepelumab also reduced asthma attacks and improved asthma symptoms, regardless of a patient’s medical history of nasal polyps. The effects of tezepelumab in patients with severe nasal polyps are being investigated in another clinical trial called “WAYPOINT”.Keywords: chronic rhinosinusitis, nasal polyps, SNOT-22, thymic stromal lymphopoietin

The par (partitioning defective) genes are required for the organization of cellular asymmetry in polarized cells such as C. elegans embryo and mammalian epithelium. We have analyzed the expression patterns of Xenopus par-6 mRNA and protein during early Xenopus embryogenesis. While the Xpar-6 mRNA is expressed both maternally and zygotically at relatively constant levels, its protein gradually increases throughout early Xenopus development, suggesting that translation of Xpar-6 protein is carefully regulated. The maternal Xpar-6 mRNA and protein are localized to the animal hemisphere of the fertilized egg and blastula. At the gastrula stage, the expressions of its zygotic transcripts and protein are restricted to not only the involuting mesoderm, dorsal and ventral, but also ectoderm, neural and epidermal, leading to their later localizations being associated with the mesodermal and ectodermal derivatives including neural tube, neural crest, somites, pronephros, heart and epidermal layer. At the cellular level, Xpar-6 protein appears to be localized to the cell cortex of epithelia. The cellular localizations of Xpar-6 protein within adult organs were also examined. In all organs studied, the specific staining is associated with epithelial cells of either a columnar or a cuboidal type that are organized in tubular structures. The smooth muscle cells also show positive staining for Xpar-6 protein.

Xretpos is a novel family of LTR-retrotransposons in Xenopus laevis whose complete elements are present in multiple copies in the genome. It contains long terminal repeats (LTRs) that can be subdivided into U3, R and U5 region, and one long open reading frame (ORF) encoding the CCHC motif conserved in retroviral gag proteins and leucine zipper motif. Xretpos transcript is zygotically activated, increases during gastrulation and neurulation, and then declines. It is restricted to ventro-posterior specific regions and induced by UV-irradiation or BMP-4 overexpression in cycloheximide-dependent way. Using an antibody directed against Xretpos protein, we have found that the expression of Xretpos is temporally regulated corroborating that of its transcript, and is localized to ventral mesoderm, heart, and neural tube. Using luciferase assay, we demonstrated that LTR and 5' untranslated region (UTR) contain all the necessary sequences for the temporal expression and induction by BMP-4 signal. We also showed that U3 region in the LTR has promoter activity and 5' part of the R region and 5' UTR positively regulate gene expression, while 3' part of the R region and U5 region negatively influence gene expression. We are currently searching for the specific cis-acting elements that are responsive to BMP-4 signal, and nuclear proteins that bind these sequences. These results would provide a good experimental tool in studying the regulatory mechanism of gene expression in early body patterning of Xenopus.

Objective: To determine whether change in the apparent diffusion coefficient (ADC) before and after neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer (LARC) would more accurately predict pathological complete response (pCR) than analysing the pre- or post-CRT ADC individually.Methods: 76 patients with LARC (≥ T3 or lymph node-positive) underwent pre- and post-CRT, 1.5-T diffusion-weighted imaging. A blinded radiologist measured the tumour ADCs. The three measures were compared with regard to CR and non-CR. To calculate accuracy for determining pCR, receiver-operating characteristic curve (ROC) analysis was applied to the three measures.Results: The post-CRT ADC (1.43 ± 0.10) (× 10(-3) mm(2)/s) and the percentage change (70.0 ± 23.5%) in the CR (n = 11) were significantly higher than those in the non-CR (n = 65) (1.14 ± 0.18, 30.2 ± 21.7%, respectively)(both, P < 0.0001). The pre-CRT ADC (0.85 ± 0.10) of the pCR did not differ significantly from that of the non-pCR (0.88 ± 0.14)(P = 0.4094). The post-CRT ADC showed comparable relative accuracy for determining pCR to that of the percentage change (P = 0.788). However, overall accuracy of the former (87%) was higher than that of the latter (75%) (P = 0.049).Conclusion: Analyzing post-CRT ADC alone can reliably differentiate pCR from non-pCR in LARC. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of computer-aided detection (CAD) for CT colonography (CTC) with and without electronic cleansing (EC) in a high-risk population tagged with a faecal tagging (FT) protocol.Methods: Thirty-two patients underwent CTC followed by same-day colonoscopy. All patients underwent bowel preparation and FT with barium and gastrografin. Each CTC dataset was processed with colon CAD with and without EC. Per-polyp sensitivity was calculated. The average number of false-positive (FP) results and their causes were also analysed and compared.Results: Eighty-six polyps were detected in 29 patients. Per-polyp sensitivities of CAD with EC (93.8% and 100%) were higher than those without EC (84.4% and 87.5%) for polyps >or=6 mm and >or=10 mm, respectively. However, the differences were not significant. The average number (6.3) of FPs of CAD with EC was significantly larger than that (3.1) without EC. The distribution of FPs in both CAD settings was also significantly different. The most common cause of FPs was the ileocaecal valve in both datasets. However, untagged faeces was a significantly less common cause of FPs with EC, EC-related artefacts being more common.Conclusion: Electronic cleansing has the potential to improve per-polyp sensitivity of CTC CAD, although the significantly larger number of FPs with EC remains to be improved. [ABSTRACT FROM AUTHOR]

The purpose was to compare two-dimensional (2D) magnetic resonance pancreatography (MRP) with 3D MRP to evaluate intraductal papillary mucinous neoplasm (IPMN). Thirty-four patients (22 men, 12 women; age range, 45-80 years) with IPMN (n = 40) were examined with MRP on 2D and 3D sequences. Two readers independently reviewed the images to assess the overall image quality, artifacts, lesion location, communication with main pancreatic duct, and potential for malignancy. The readers assigned their confidence level (1-5) for predicting ductal communication of the lesion. The results of MRP were compared with endoscopic retrograde pancreatography and surgical and histopathologic findings. Studies obtained with 3D MRP were of significantly higher technical quality than those obtained with 2D MRP. Although 3D MRP showed higher area under the ROC curve (Az) values for predicting ductal communication of the lesion, there was no statistical significance between Az values of 2D and 3D MRP (Az for 2D = 0.821, 0.864 for readers 1 and 2, respectively, and Az for 3D= 0.964, 0.921). Accuracies for discriminating benign from malignant lesions were 70 and 67.5% (reader 1 and 2, respectively, for 2D) and 62.5 and 80.1% (3D). 3D MRP showed superior image quality to that of 2D MRP but did not increase the diagnostic accuracy for predicting ductal communication of the lesion. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Chronic sinusitis is primarily an inflammatory disorder characterized by hyperplasia of immune cells and sinus tissue. Nasal mucosal swelling or polyps can occlude the sinus ostia, decreasing the level of oxygen available to the sinus tissue. Hypoxia in many diseases results in increased recruitment of inflammatory cells and release of cytokines. The role of hypoxia in chronic sinusitis is unknown. We hypothesized that hypoxia induces production of mediators that recruit cells into the sinus tissue and are involved in remodeling of the nasal mucosa. Methods: We compared data from unstimulated nasal-polyp derived fibroblasts with those cultured in hypoxic (10% O2) and anoxic (0% O2) environments. Changes in mRNA expression and protein levels of cytokines and chemokines were measured along with changes in cellular proliferation. Results: Hypoxic conditions did not change the proliferative capacity of fibroblasts, whereas anoxia led to a 40% reduction in cellular proliferation (P < .05). Hypoxia led to increases in secretion of many cytokines including vascular endothelial growth factor and CCL11. As a marker of remodeling, procollagen and fibronectin production were significantly increased under hypoxic conditions. Conclusions: Hypoxic conditions present in the sinus tissue could increase production of proinflammatory and remodeling cytokines that contribute to the inflammation observed in sinusitis. Surgical intervention may help decrease inflammation by allowing reoxygenation of the sinus cavity and decrease the hypoxic induction of cytokines and remodeling factors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the diagnostic value of color Doppler twinkling artifacts (CDTAs) in the evaluation of gallbladder adenomyomatosis with differently colored Doppler frequencies. An ultrasound was performed by an experienced radiologist in 17 patients with typical gallbladder adenomyomatosis. Two abdominal radiologists retrospectively evaluated the anatomic locations, the intensity of 69 CDTAs on 1.8 MHz and 4.0 MHz Doppler frequencies, and the intensity of the corresponding comet-tail artifacts. Statistical analysis was performed using the Friedman and Kruskal-Wallis test. The intensity of the CDTAs was significantly greater than that of the comet-tail artifacts, regardless of the color Doppler frequency and anatomic location (p < 0.001). The intensity of the CDTAs on 1.8 MHz was significantly higher than that on 4.0 MHz color Doppler frequency (p < 0.05). In conclusion, CDTAs may be useful in recognizing gallbladder adenomyomatosis, and 1.8 MHz color Doppler frequency is more highly recommended than 4.0 MHz for the visualization of CDTAs. [ABSTRACT FROM AUTHOR]

Background: To assess the added value of 80 kVp images to weighted average 120 kVp images for detecting hepatocellular carcinomas (HCCs) using dual-source, dual-energy MDCT. Materials and Methods: Forty-one HCCs in 42 patients who underwent liver transplantation (LT) were included. All patients underwent quadruple-phase CT using a 64-row dual-source, dual-energy MDCT with 80 kVp and 140 kVp. For 120 kVp, a linear blending ratio of 0.3 was chosen. Interval reviews for both simulated 120 kVp images without and with pure 80 kVp data were performed independently by two radiologists. They detected HCCs using a 4-point confidence scale. Tumor-to-liver contrast-to-noise ratio (CNR) was calculated and compared between the 80 kVp and simulated 120 kVp images. The additional diagnostic value of 80 kVp images was evaluated by jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis. Results: There were 41 HCCs on pathology and 37 of the 41 HCCs were depicted on CT scan. The mean CNR of the 37 HCCs in late arterial and portal-phase images was significantly better in the 80 kVp images than in 120 kVp images. The average JAFROC figure of merit, however, was not significantly improved when 80 kVp was added. Furthermore, the number of false-positives was significantly increased in reader 1 when adding 80kVp data. Conclusion: The addition of 80 kVp CT images to simulated 120 kVp images did not significantly improve the detection of HCCs despite of the significantly better CNR of 80 kVp images. [ABSTRACT FROM AUTHOR]

Background: Real-world burden data on systemic corticosteroid (SCS) use in chronic rhinosinusitis with nasal polyps (CRSwNP) are limited., Objective: This study's objective was to describe the real-world burden of SCS in CRSwNP., Methods: This retrospective cohort study included commercial/Medicare Advantage with Part D health plan members from the Optum Research Database with a first medical claim (index) for CRSwNP (January 2015 to July 2020). Primary outcomes/variables included SCS use, healthcare resource utilization (HCRU) and costs during the 12-month follow-up period. Outcomes were analyzed overall (N=21,172) and stratified by baseline comorbid asthma status and sinus surgeries during follow-up., Results: Overall, 64.7% and 41.0% of patients used all-cause and CRSwNP-related SCS respectively, and 36.0% had ≥1 oral corticosteroid (OCS) burst (≥20 mg for 3-28 days); SCS use was higher in patients with asthma and those with a NP-related surgery (1, 2, ≥3) versus without. The mean (SD) all-cause cumulative OCS dose was 303.3 (675.0) mg/year and 23.5% had a cumulative annual dose ≥400 mg; these values were higher (p<0.001) in patients with versus without comorbid asthma (514.9 [956.1] vs. 247.5 [567.0]; 36.9% vs. 19.9%). All-cause and CRSwNP HCRU and costs increased with increasing number of surgeries; mean (SD) all-cause total medical costs were $14,472 (38,915), $26,909 (40,800), $29,816 (41,677), and $31,558 (37,143) with 0, 1, 2, and ≥3 surgeries, respectively., Conclusion: These data highlight the significant burden of SCS use in CRSwNP, particularly in patients with comorbid asthma and suggest a need to reduce SCS exposure., Competing Interests: Conflicts of interest Joseph K. Han received consultancy fees from Sanofi Genzyme, Regeneron, Genentech, Novartis, AstraZeneca, and GSK. Jared Silver was formerly employed by GSK and holds financial equities in GSK, they are currently employed by Amgen and hold financial equities in Amgen. Arijita Deb is employed by GSK and holds financial equities in GSK. Phani Veeranki is an employee of Optum and holds stocks/shares with Optum, which received funding from GSK to conduct this study. Indu Dhangar is a former employee of Optum, which received funding from GSK to conduct this study., (Copyright © 2024. Published by Elsevier Inc.)

Background: The optimal duration of dual antiplatelet therapy (DAPT) in patients with chronic kidney disease undergoing percutaneous coronary intervention (PCI), especially with third-generation drug-eluting stents (DES), remains unknown., Methods and Results: We conducted a prespecified post hoc analysis of the HOST-IDEA trial, randomizing patients undergoing PCI with third-generation DES to 3- to 6-month or 12-month DAPT. In all, 1,997 patients were grouped by their estimated glomerular filtration rate (eGFR): high (>90 mL/min/1.73 m 2 ), intermediate (60-90 mL/min/1.73 m 2 ), and low (<60 mL/min/1.73 m 2 ). The primary outcome was net adverse clinical events (NACE), a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding (Bleeding Academic Research Consortium Type 3 or 5) at 12 months. Secondary outcomes were target lesion failure (TLF) and major bleeding. The low eGFR group had the highest rates of NACE, TLF, and major bleeding compared with the other 2 groups (P<0.001). Rates of NACE were similar in the 3- to 6-month and 12-month DAPT in the high (2.9% vs. 3.2%; P=0.84), intermediate (2.1% vs. 2.8%, P=0.51), and low (8.9% vs. 9.1%; hazard ratio 0.99; P=0.97; P interaction =0.88) eGFR groups. TLF and major bleeding events showed similar trends., Conclusions: In patients undergoing PCI with third-generation DES, 3- to 6-month DAPT was comparable to 12-month DAPT for clinical outcomes regardless of renal function.

In-sensor computing has gained attention as a solution to overcome the von Neumann computing bottlenecks inherent in conventional sensory systems. This attention is due to the ability of sensor elements to directly extract meaningful information from external signals, thereby simplifying complex data. The advantage of in-sensor computing can be maximized with the sampling principle of a restricted Boltzmann machine (RBM) to extract significant features. In this study, a stochastic photo-responsive neuron is developed using a TiN/In-Ga-Zn-O/TiN optoelectronic memristor and an Ag/HfO 2 /Pt threshold-switching memristor, which can be configured as an input neuron in an in-sensor RBM. It demonstrates a sigmoidal switching probability depending on light intensity. The stochastic properties allow for the simultaneous exploration of various neuron states within the network, making identifying optimal features in complex images easier. Based on semi-empirical simulations, high recognition accuracies of 90.9% and 95.5% are achieved using handwritten digit and face image datasets, respectively. In addition, the in-sensor RBM effectively reconstructs abnormal face images, indicating that integrating in-sensor computing with probabilistic neural networks can lead to reliable and efficient image recognition under unpredictable real-world conditions.

This study explores the stochastic and binary switching behaviors of a Ta/HfO 2 /RuO 2 memristor to implement a combined data mining approach for outlier detection and data clustering algorithms in a multi-functional memristive crossbar array. The memristor switches stochastically with high state dispersion in the stochastic mode and deterministically between two states with low dispersion in the binary mode, while they can be controlled by varying operating voltages. The stochastic mode facilitates the parallel generation of random hyperplanes in a tree structure, used to compress spatial information of the dataset in the Euclidian space into binary format, still retaining sufficient spatial features. The ensemble effect from multiple trees improved the classification performance. The binary mode facilitates parallel Hamming distance calculation of the binary codes containing spatial information, which measures similarity. These two modes enable efficient implementation of the newly proposed minority-based outlier detection method and modified K -means method on the same hardware. Array measurements and hardware simulations investigate various hyperparameters' impact and validate the proposed methods with practical datasets. The proposed methods show linear O( n ) time complexity and high energy efficiency, consuming <1% of the energy compared to digital computing with conventional algorithms while demonstrating software-comparable performance in both tasks.

Polyphenols have been well-established to exert sedative-hypnotic effects in psychopharmacology. Lime (Citrus aurantifolia) peel is rich in biologically active polyphenols; however, the effects of lime peel extract on sleep have not yet been demonstrated. A comparison was conducted in mice, between the sleep-promoting effects of a standardized lime peel supplement (SLPS) and a well-known hypnotic drug, zolpidem, and its hypnotic mechanism was investigated using in vivo and in vitro assays. The effects of SLPS on sleep were assessed using a pentobarbital-induced sleep test and sleep architecture analysis based on recording electroencephalograms and electromyograms. Additionally, a GABA A receptor binding assay, electrophysiological measurements, and in vivo animal models were used to elucidate the hypnotic mechanism. SLPS (200 and 400 mg/kg) was found to significantly decrease sleep latency and increase the amount of non-rapid eye movement sleep without altering delta activity. The hypnotic effects of SLPS were attributed to its flavonoid-rich ethyl acetate fraction. SLPS had a binding affinity to the GABA-binding site of the GABA A receptor and directly activated the GABA A receptors. The hypnotic effects and GABA A receptor activity of SLPS were completely blocked by bicuculline, a competitive antagonist of the GABA A receptor, in both in vitro and in vivo assays. To the best of our knowledge, this study is the first to demonstrate the hypnotic effects of SLPS, which acts via the GABA-binding site of the GABA A receptor. Our results suggest that lime peel, a by-product abundantly generated during juice processing, can potentially be used as a novel sedative-hypnotic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Competing Interests: Disclosures J.K.H. receives moderate compensation for medical advisory to Abbott, Medtronic CMR, and iRhythm Technologies Inc.

Due to its area and energy efficiency, a memristive crossbar array (CBA) has been extensively studied for various combinatorial optimization applications, from network problems to circuit design. However, conventional approaches include heavily burdening software fine-tuning for the annealing process. Instead, this study introduces the "in-materia annealing" method, where the inter-layer interference of vertically stacked memristive CBA is utilized as an annealing method. When mapping combinatorial optimization problems into the configuration layer of the CBA, exponentially decaying annealing profiles are generated in nearby noise layers. Moreover, in-materia annealing profiles can be controlled by changing compliance current, read voltage, and read pulse width. Therefore, the annealing profiles can be arbitrarily controlled and generated individually for each cell, providing rich noise sources to solve the problem efficiently. Consequently, the experimental and simulation of Max-Cut and weighted Max-Cut problems achieve notable results with the minimum software burden., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: This randomised, double-blind, placebo-controlled, parallel-group, 52-week Phase III study (MERIT; NCT04607005) assessed mepolizumab efficacy and safety in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS (ECRS) in Japan, Russia, and China, for which data are limited., Methodology: Eligible patients (enrolled at 60 centres) had blood eosinophil count >2%, endoscopic bilateral NP score ≥5, nasal obstruction visual analogue scale (VAS) score >5, ≥2 sinonasal symptoms, and either previous sinus surgery or systemic corticosteroid use/intolerance. Patients were randomised (1:1) to receive mepolizumab 100 mg subcutaneously or placebo every 4 weeks, plus standard of care. Co-primary endpoints: change from baseline in total endoscopic NP score (ENPS) (Week 52) and nasal obstruction VAS score (Weeks 49-52). Post hoc analyses conducted in a modified intent-to-treat (mITT) population excluded patients from two study sites, related to Good Clinical Practice violations by the Site Management Organisation overseeing these sites. These were considered the primary efficacy analyses., Results: In the mITT population, mepolizumab (n=80) versus placebo (n=83) significantly improved nasal obstruction VAS score from baseline to Week 49-52 and was associated with a trend of total ENPS improvements at Week 52. Mepolizumab/placebo on-treatment adverse events (AEs) occurred in 68/84 and 65/85 patients in the safety population (treatment-related AEs: 2/84 and 5/85, respectively), and on-treatment serious AEs in 0/84 and 4/85 patients, respectively (no fatalities reported)., Conclusions: Mepolizumab was effective and well-tolerated in patients with CRSwNP/ECRS from Japan, Russia, and China.

Background and Objectives: The clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with diabetes mellitus (DM) patients. We sought to compare the prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM., Methods: A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on the angiographic image. The primary endpoint of this study was the patient-oriented composite outcome (POCO) defined as a composite of all-cause death, any myocardial infarction, and any revascularization within 3 years., Results: Overall, 3-year POCO was significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1,165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (hazard ratio, 0.52; 95% confidence interval, 0.36-0.75) only in the non-DM group., Conclusions: In AMI patients with multivessel disease, CR may have less clinical benefit in DM patients than in non-DM patients., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Background and Aims: Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients., Methods: This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events., Results: Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P < .001) and ischaemic events (33.8% vs. 14.4%, P < .001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04-3.21, P < .001] and for ischaemic events (HR 2.50, 95% CI 2.45-2.56, P < .001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66-3.79, P < .001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion., Conclusions: Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Frequently reported outcomes of clinical trials in chronic rhinosinusitis with nasal polyps (CRSwNP) may have limited relatability for patients., Objective: To enhance the patient relatability of outcomes in dupilumab clinical trials for CRSwNP, daily symptom scores were used to determine new patient‑centered end points: mild-to-no-symptom months (MSM) and symptom-free months (SFM)., Methods: This work is a post hoc analysis of patients receiving dupilumab 300 mg or placebo every 2 weeks for 24 weeks (SINUS-24 study; NCT02912468) or 52 weeks (SINUS‑52; NCT02898454). Patients recorded symptom severity scores daily for each of nasal congestion, loss of smell, and anterior and posterior rhinorrhea on a scale of 0 to 3 (0 = no symptoms; 1 = mild; 2 = moderate; 3 = severe). We assessed the proportions of patients reporting only MSM or SFM throughout the 28‑day period before randomization, week 24 (pooled studies), and week 52 (SINUS‑52)., Results: Significantly more dupilumab‑treated than placebo-treated patients achieved MSM for all 4 symptoms (week 24: 31.0% vs 4.4%; odds ratio [OR] 12.9 [95% CI 6.4-25.8]; week 52: 38.3% vs 2.6%; OR 15.6 [5.9-41.0]; both P < .0001). In addition, significantly more dupilumab-treated than placebo‑treated patients achieved SFM for at least 1 of the 4 symptoms (week 24: 35.4% vs 10.8%; OR 4.9 [95% CI 3.1-7.8]; week 52: 50.0% vs 9.2%; OR 9.1 [95% CI 4.6-17.9]; both P < .0001)., Conclusion: One-third of patients with severe CRSwNP treated with dupilumab achieved MSM for all 4 cardinal symptoms (nasal congestion, loss of smell, and anterior and posterior rhinorrhea). Moreover, half of the patients achieved SFM for at least 1 of the 4 symptoms. These results support the benefit of dupilumab in improving patient‑centered outcomes., Trial Registration: ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52)., Competing Interests: Disclosures Professor Bachert is an advisory board member for AstraZeneca, Novartis, and Sanofi. Professor Hopkins is an advisory board member for AstraZeneca, BioInspire Technologies, GlaxoSmithKline, and Sanofi. Professor Han is an advisory board member for AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals Inc, and Sanofi. Professor Fokkens has received research grants from BioInspire Technologies, GlaxoSmithKline, Mylan, Novartis, and Sanofi. Dr Khan, Dr Mannent, Mr Msihid, and Dr Rowe are employees of Sanofi and may hold stock and/or stock options in the company. Dr Borsos and Dr Jacob-Nara are former employees of Sanofi and may hold stock and/or stock options in the company. Mr Kamat, Dr Nash, and Dr Deniz are employees and shareholders of Regeneron Pharmaceuticals Inc. Dr Sacks is an employee of Regeneron Pharmaceuticals Inc and a shareholder in OptiNose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab and mepolizumab have shown efficacy and safety in treating chronic rhinosinusitis with nasal polyps (CRSwNP)., Objective: Without available results from head-to-head randomized control trials (RCTs) comparing dupilumab with other biologics, we conducted an indirect treatment comparison (ITC) with mepolizumab., Methods: A systematic literature review identified RCTs of biologics in CRSwNP. A Bucher ITC was performed, including nasal polyp score (NPS; range 0-8), nasal congestion (NC; 0-3), loss of smell (LOS; 0-3), University of Pennsylvania Smell Identification Test (UPSIT; 0-40), visual analog score (VAS; 0-10), Sino-Nasal Outcome Test (SNOT-22; 0-110), systemic corticosteroids (SCS) use or surgery for nasal polyps (NPs), and binary responder analyses for NPS and SNOT-22 improvement by ≥1/≥2 and ≥8.9, respectively. Matching-adjusted indirect comparisons (MAIC) were conducted as supporting analyses., Results: SINUS-24/-52 (SYNAPSE-like subpopulation only) and SYNAPSE were identified for ITC. At 24 weeks, change from baseline in NPS and proportion of patients with a binary responder outcome of NPS improvement ≥1 were significantly (P<0.05) greater in patients receiving dupilumab versus mepolizumab. At 52 weeks, improvements in NPS, NC, LOS, UPSIT, and VAS were significantly (P<0.05) greater for dupilumab versus mepolizumab. Proportion of patients achieving binary responder outcomes of NPS and SNOT-22 improvement by ≥1/≥2 and ≥8.9, respectively, was significantly (P<0.05) higher, while SCS use was significantly (P<0.05) reduced, for dupilumab versus mepolizumab. Surgery rate was numerically reduced with dupilumab versus mepolizumab. The MAIC analyses confirmed these results., Conclusions: Dupilumab was associated with greater improvements in CRSwNP-related outcomes versus mepolizumab., (Copyright © 2024. Published by Elsevier Inc.)

Background: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function., Methods and Results: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m 2 . The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status ( P for interaction=0.889)., Conclusions: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

In the big data era, the requirement for data clustering methods that can handle massive and heterogeneous datasets with varying distributions increases. This study proposes a clustering algorithm for data sets with heterogeneous density using a dual-mode memristor crossbar array for data clustering. The array consists of a Ta/HfO 2 /RuO 2 memristor operating in analog or digital modes, controlled by the reset voltage. The digital mode shows low dispersion and a high resistance ratio, and the analog mode enables precise conductance tuning. The local outlier factor is introduced to handle a heterogeneous density, and the required Euclidean and K -distances within the given dataset are calculated in the analog mode in parallel. In the digital mode, clustering is performed based on the connectivity among data points after excluding the detected outliers. The proposed algorithm boasts linear time complexity for the entire process. Extensive evaluations of synthetic datasets demonstrate significant improvement over representative density-based algorithms, and the datasets with heterogeneous density are clustered feasibly. Finally, the proposed algorithm is used to cluster the single-molecule localization microscopy data, demonstrating the feasibility of the suggested method for real-world problems.

Background: Temporary eosinophilia is a potential adverse reaction of monoclonal antibody therapies in the treatment of a variety of type 2 inflammatory conditions, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). The pathophysiology, epidemiology, and clinical significance of eosinophilia and eosinophilic adverse reactions following the initiation of biologic therapy are unclear., Objectives: To describe the postmarketing, eosinophilic adverse reactions with clinical significance in patients treated with the 3 biologic therapies approved by the U.S. Food and Drug Administration (FDA) for CRSwNP: dupilumab, omalizumab, and mepolizumab., Methods: The FDA Adverse Event Reporting System (FAERS) Public Dashboard was searched for eosinophilic adverse reactions related to dupilumab, omalizumab, and mepolizumab treatments from November 2004 to December 2022. Data regarding each of the eosinophilic adverse reactions were extracted and analyzed., Results: A total of 218, 270, and 134 reports of eosinophilic adverse reactions were reported among patients who were treated with dupilumab, omalizumab, and mepolizumab, respectively. The most common eosinophilic adverse reaction was eosinophilic granulomatosis with polyangiitis (338 patients), followed by eosinophilic respiratory tract reactions (158 patients). The most common indication for biological treatment among the reaction groups was asthma., Conclusions: Eosinophilic adverse reactions are rare but consequential complications of biological treatment. They are more common among patients treated for asthma and chronic rhinosinusitis with nasal polyposis. Measuring and monitoring blood eosinophil levels may be appropriate in specific clinical instances when patients are started on different biologic therapies for type 2 inflammatory conditions., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A self-powered mechanoreceptor array is demonstrated using four mechanoreceptor cells for recognition of dynamic touch gestures. Each cell consists of a triboelectric nanogenerator (TENG) for touch sensing and a bi-stable resistor (biristor) for spike encoding. It produces informative spike signals by sensing a force of an external touch and encoding the force into the number of spikes. An array of the mechanoreceptor cells is utilized to monitor various touch gestures and it successfully generated spike signals corresponding to all the gestures. To validate the practicality of the mechanoreceptor array, a spiking neural network (SNN), highly attractive for power consumption compared to the conventional von Neumann architecture, is used for the identification of touch gestures. The measured spiking signals are reflected as inputs for the SNN simulations. Consequently, touch gestures are classified with a high accuracy rate of 92.5%. The proposed mechanoreceptor array emerges as a promising candidate for a building block of tactile in-sensor computing in the era of the Internet of Things (IoT), due to the low cost and high manufacturability of the TENG. This eliminates the need for a power supply, coupled with the intrinsic high throughput of the Si-based biristor employing complementary metal-oxide-semiconductor (CMOS) technology., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Modern graph datasets with structural complexity and uncertainties due to incomplete information or data variability require advanced modeling techniques beyond conventional graph models. This study introduces a memristive crossbar array (CBA)-based probabilistic graph model (C-PGM) utilizing Cu 0.3 Te 0.7 /HfO 2 /Pt memristors, which exhibit probabilistic switching, self-rectifying, and memory characteristics. C-PGM addresses the complexities and uncertainties inherent in structural graph data across various domains, leveraging the probabilistic nature of memristors. C-PGM relies on the device-to-device variation across multiple memristive CBAs, overcoming the limitations of previous approaches that rely on sequential operations, which are slower and have a reliability concern due to repeated switching. This new approach enables the fast processing and massive implementation of probabilistic units at the expense of chip area. In this study, the hardware-based C-PGM feasibly expresses small-scale probabilistic graphs and shows minimal error in aggregate probability calculations. The probability calculation capabilities of C-PGM are applied to steady-state estimation and the PageRank algorithm, which is implemented on a simulated large-scale C-PGM. The C-PGM-based steady-state estimation and PageRank algorithm demonstrate comparable accuracy to conventional methods while significantly reducing computational costs., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Electromechanical metal oxides, such as piezoceramics, are often incompatible with soft polymers due to their crystallinity requirements, leading to high processing temperatures. This study explores the potential of ceria-based thin films as electromechanical actuators for flexible electronics. Oxygen-deficient fluorites, like cerium oxide, are centrosymmetric nonpiezoelectric crystalline metal oxides that demonstrate giant electrostriction. These films, deposited at low temperatures, integrate seamlessly with various soft substrates like polyimide and PET. Ceria thin films exhibit remarkable electrostriction ( M 33 > 10 -16 m 2 V -2 ) and inverse pseudo-piezo coefficients ( e 33 > 500 pmV -1 ), enabling large displacements in soft electromechanical systems. Our study explores resonant and off-resonant configurations in the low-frequency regime (<1 kHz), demonstrating versatility for three-dimensional and transparent electronics. This work advances the understanding of oxygen-defective metal oxide electromechanical properties and paves the way for developing versatile and efficient electromechanical systems for applications in biomedical devices, optical devices, and beyond.

Background: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple outcomes of treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with dupilumab., Objective: Our aim was to gain a better understanding of dynamics of the response to dupilumab over 52 weeks., Methods: We used data from the SINUS-52 (ClinicalTrials.gov identifier NCT02898454) intention-to-treat population to perform a post hoc analysis of patients with severe CRSwNP who had received dupilumab, 300 mg once every 2 weeks, or placebo. Response, which was defined as an improvement from baseline of a least 1 point in Nasal Polyp Score (NPS), nasal congestion (NC) score, and loss of smell (LoS) score, as well as an improvement of at least 8.9 points on the 22-Item Sino-Nasal Outcome Test (SNOT-22), was assessed for rapidity, maintenance, and durability., Results: The study included 303 patients (150 of whom received dupilumab and 153 of whom received placebo). For each outcome measure, a greater proportion of patients achieved a first response by week 16 (rapidity) with dupilumab versus with placebo; specifically, the respective differences in indicators between the 2 groups by week 16 were as follows: NPS, 75.3% versus 39.2%; NC score, 60.0% versus 24.2%; LoS score, 60.7% versus 15.7%; and SNOT-22 score, 83.3% versus 66.0%. Of those patients given dupilumab who had a response by week 16, more than 80% maintained their response at week 52 (maintenance). Over 52 weeks, greater proportions of those patients given dupilumab were responders on at least 80% of time points; specifically, the respective differences in indicators between the 2 groups by week 16 were as follows: NPS, 46.7% versus 2.6%; NC score, 46.7% versus 9.2%; LoS score, 47.3% versus 3.9%; and SNOT-22 score, 62.0% versus 21.6% (durability)., Conclusion: Most patients with CRSwNP achieve clinically meaningful responses to dupilumab by week 16, and most such patients in our study had maintenance and durability of response with continued treatment over time., Competing Interests: Disclosure statement Supported by Sanofi, France, and Regeneron Pharmaceuticals, Inc, United States. Disclosure of potential conflict of interest: C. Bachert is an advisory board member of AstraZeneca, Novartis, and Sanofi. W. J. Fokkens reports research grants from BioInspire Technologies, GlaxoSmithKline, Mylan, Novartis, and Sanofi. C. Hopkins is an advisory board member of AstraZeneca, BioInspire Technologies, GlaxoSmithKline, and Sanofi. P. Gevaert reports clinical trial funding from and is an advisory board member of 3NT, Argenx, Genentech, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi, and Stallergenes Greer. J. K. Han is an advisory board member of AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, and Sanofi. P. W. Hellings is an advisory board member of Regeneron Pharmaceuticals and Sanofi. S. E. Lee reports receiving clinical trial funding from and being an advisory board member of AstraZeneca, Genentech, GlaxoSmithKline, and Sanofi and being an advisory board member of Novartis and Regeneron Pharmaceuticals. A. H. Khan, J. Msihid, J. A. Jacob-Nara, and P. J. Rowe are employees of Sanofi and may hold stock and/or stock options in the company. S. Nash and Y. Deniz are employees and shareholders of Regeneron Pharmaceuticals. H. Sacks is an employee of Regeneron Pharmaceuticals and a shareholder of Optinose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This work demonstrates a physical reservoir using a back-end-of-line compatible thin-film transistor (TFT) with tin monoxide (SnO) as the channel material for neuromorphic computing. The electron trapping and time-dependent detrapping at the channel interface induce the SnO·TFT to exhibit fading memory and nonlinearity characteristics, the critical assets for physical reservoir computing. The three-terminal configuration of the TFT allows the generation of higher-dimensional reservoir states by simultaneously adjusting the bias conditions of the gate and drain terminals, surpassing the performances of typical two-terminal-based reservoirs such as memristors. The high-dimensional SnO TFT reservoir performs exceptionally in two benchmark tests, achieving a 94.1% accuracy in Modified National Institute of Standards and Technology handwritten number recognition and a normalized root-mean-square error of 0.089 in Mackey-Glass time-series prediction. Furthermore, it is suitable for vertical integration because its fabrication temperature is <250 °C, providing the benefit of achieving a high integration density.

Aims: Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial., Methods: Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators., Results: Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL -1 ); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm -2 at baseline to 0 cells mm -2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin-17 at week 56 (P < .05) with benralizumab., Conclusion: Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP., (© 2024 AstraZeneca. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Transcatheter aortic valve implantation (TAVI) is preferred for treating severe aortic stenosis in older, frail populations, yet the impact of frailty on economic and clinical outcomes of TAVI is not well studied., Methods: This retrospective cohort study included 2175 TAVI patients from 2015 to 2019, using Korea's National Health Insurance Service database, stratifying patients into low, intermediate, and high-frailty groups, using the Hospital Frailty Risk Score (HFRS). Health care costs, admissions, and total length of hospitalization were analyzed using Wilcoxon-rank test 12 months pre- and post-TAVI. Composite endpoint of death, stroke, and major bleeding, with individual outcomes, were compared using χ 2 tests and Kaplan-Meier analysis., Results: Mean age was 80.2 years, and 47.3% were male; 747 (34.3%) were low frailty, 1159 (53.3%) were moderate frailty, and 269 (12.4%) were high frailty. After TAVI, medical costs decreased in the intermediate- (pre-TAVI: 2,269,000 KRW [$1668 USD], post-TAVI: 1,607,000 KRW [$1181 USD]; P < 0.001) and high-frailty groups (pre-TAVI: 3,949,000 KRW [$2904 USD], post-TAVI: 2,188,000 KRW [$1609 USD]; P < 0.001). All frailty groups had shorter length of hospital stay post-TAVI (26 to 21 days in the low-frailty, 44 to 31 days in the intermediate-frailty, and 65 to 41 days in the high-frailty group; all P <0.001). The composite outcome was higher in the frailer groups (27.8% in the low-frailty vs 31.5% in the intermediate-frailty vs 37.9% in the high-frailty group; P = 0.008). All groups showed comparable rates of cardiovascular death, stroke, or bleeding., Conclusions: TAVI is clinically viable and cost-saving treatment option for frail patients with severe aortic stenosis., (Copyright © 2024. Published by Elsevier Inc.)

An ion-based synaptic transistor (synaptor) is designed to emulate a biological synapse using controlled ion movements. However, developing a solid-state electrolyte that can facilitate ion movement while achieving large-scale integration remains challenging. Here, a bio-inspired organic synaptor (BioSyn) with an in situ ion-doped polyelectrolyte (i-IDOPE) is demonstrated. At the molecular scale, a polyelectrolyte containing the tert-amine cation, inspired by the neurotransmitter acetylcholine is synthesized using initiated chemical vapor deposition (iCVD) with in situ doping, a one-step vapor-phase deposition used to fabricate solid-state electrolytes. This method results in an ultrathin, but highly uniform and conformal solid-state electrolyte layer compatible with large-scale integration, a form that is not previously attainable. At a synapse scale, synapse functionality is replicated, including short-term and long-term synaptic plasticity (STSP and LTSP), along with a transformation from STSP to LTSP regulated by pre-synaptic voltage spikes. On a system scale, a reflex in a peripheral nervous system is mimicked by mounting the BioSyns on various substrates such as rigid glass, flexible polyethylene naphthalate, and stretchable poly(styrene-ethylene-butylene-styrene) for a decentralized processing unit. Finally, a classification accuracy of 90.6% is achieved through semi-empirical simulations of MNIST pattern recognition, incorporating the measured LTSP characteristics from the BioSyns., (© 2024 Wiley‐VCH GmbH.)

Background: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES., Methods: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months., Results: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P =0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P =0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P =0.34) were comparable between the 2 groups., Conclusions: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157., Competing Interests: Dr Han reports grants from ChongKunDang and HanMi outside the submitted work. Dr K.W. Park reports speaker fees from Daiichi Sankyo, AstraZeneca, Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside the submitted work. Dr H.-S. Kim reports grants or speaker fees from Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Dio, Medtronic, Abbott Vascular, Edwards Life Science, Amgen, and Behringer Ingelheim outside of the submitted work. The other authors report no conflicts.