Glucose transporters and sodium glucose co-transporters cooperatively import glucose into energy-demanding organs in carcinogenic liver fluke Clonorchis sinensis.

BACKGROUND: The liver fluke Clonorchis sinensis imports large amounts of glucose to generate energy and metabolic intermediates through glycolysis. We hypothesized that C. sinensis absorbs glucose through glucose transporters and identified four subtypes of glucose transporter (CsGTP) and one sodium glucose co-transporter (CsSGLT) in C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS: Expressed sequence tags encoding CsGTPs were retrieved from the C. sinensis transcriptome database, and their full-length cDNA sequences were obtained by rapid amplification of cDNA ends (RACE). The tissue distribution of glucose transporters in C. sinensis adults was determined using immunohistochemical staining. Developmental expression was measured using RT-qPCR. The transport and distribution of glucose into living C. sinensis were monitored using confocal microscopy. Membrane topology and key functional residues of CsGTPs were homologous to their counterparts in animals and humans. CsGTP1, 2, and 4 were transcribed 2.4-5.5 times higher in the adults than metacercariae, while CsGTP3 was transcribed 2.1 times higher in the metacercariae than adults. CsSGLT transcription was 163.6 times higher in adults than in metacercariae. In adults, CsSGLT was most abundant in the tegument; CsGTP3 and CsSGLT were localized in the vitelline gland, uterine wall, eggs, mesenchymal tissue, and testes; CsGTP4 was found in sperm and mesenchymal tissue; and CsGTP1 was mainly in the sperm and testes. In C. sinensis adults, exogenous glucose is imported in a short time and is present mainly in the middle and posterior body, in which the somatic and reproductive organs are located. Of the exogenous glucose, 53.6% was imported through CsSGLT and 46.4% through CsGTPs. Exogenous glucose import was effectively inhibited by cytochalasin B and phlorizin. CONCLUSIONS/SIGNIFICANCE: We propose that CsSGLT cooperates with CsGTPs to import exogenous glucose from the environmental bile, transport glucose across mesenchymal tissue cells, and finally supply energy-demanding organs in C. sinensis adults. Studies on glucose transporters may pave the way for the development of new anthelmintic drugs.

12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.

Background and Purpose: Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods: SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results: In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions: Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.

Does Cognitive Function Affect Performance and Listening Effort During Bilateral Wireless Streaming in Hearing Aid Users?

Background and Objectives: : Wireless streaming technology (WT), designed to transmit sounds directly from a mobile phone to hearing aids, was developed to enhance the signal-to-noise ratio. However, the advantages of WT during phone use and the specific demographic that can fully benefit from this technology has not been thoroughly evaluated. We aimed to investigate the benefits and identify predictive factors associated with bilateral wireless streaming among hearing aid users. Subjects and Methods: : Eighteen adults with symmetrical, bilateral hearing loss participated in the study. To assess the benefits of wireless streaming during phone use, researchers assessed sentence/word recognition and listening effort in two scenarios: a noisy background with WT turned "OFF" or "ON." Listening effort was evaluated through self-reported measurements. Cognitive function was also assessed using the Montreal Cognitive Assessment (MoCA) score. Results: : Participant mean age was 57.3 years (range 27-70), and the mean MoCA score was 27.0 (23-30). The activation of WT demonstrated a significant improvement in the sentence/word recognition test and reduced listening effort. The MoCA score showed a significant correlation with WT (ρ=0.59, p=0.01), suggesting a positive association between cognitive function and the benefits of WT. Conclusions: : Bilateral wireless streaming may enhance sentence/word recognition and reduce listening effort during phone use in hearing aid users, with these benefits potentially linked to cognitive function.

Enzymatically Oxidized Carbohydrates As Dicarbonyl Biobased Cross-Linkers for Polyamines.

Carbonyl cross-linkers are used to modify textiles and form resins, and are produced annually in megatonne volumes. Due to their toxicity toward the environment and human health, however, less harmful biobased alternatives are needed. This study introduces carbonyl groups to lactose and galactose using galactose oxidase from Fusarium graminearum (FgrGalOx) and pyranose dehydrogenase from Agaricus bisporus (AbPDH1) to produce four cross-linkers. Differential scanning calorimetry was used to compare cross-linker reactivity, most notably resulting in a 34 °C decrease in reaction peak temperature (72 °C) for FgrGalOx-oxidized galactose compared to unmodified galactose. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and proton nuclear magnetic resonance (1H NMR) spectroscopy were used to verify imine formation and amine and aldehyde depletion. Cross-linkers were shown to form gels when mixed with polyallylamine, with FgrGalOx-oxidized lactose forming gels more effectively than all other cross-linkers, including glutaraldehyde. Further development of carbohydrate cross-linker technologies could lead to their adoption in various applications, including in adhesives, resins, and textiles.

Recent advances in earth-abundant transition metal-catalyzed dihydrosilylation of terminal alkynes.

Over the past few years, earth-abundant transition metal-catalyzed hydrosilylation has emerged as an ideal strategy for the synthesis of organosilanes. The success in this area of research has expanded to the advancements of alkyne dihydrosilylation reactions, offering broadened synthetic applications through the selective installation of two silyl groups. In particular, catalysts based on Fe, Co, and Ni have engendered enabling platforms for mild transformations with a range of distinct regioselectivity. This mini-review summarizes recent advances in this research field, highlighting the unique features of each system from both synthetic and mechanistic perspectives.

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Pleural metastasis is the most common cause of malignant diseases involving the pleura, and characterized by pleural effusion, nodules, and thickening. Pleuroparenchymal fibroelastosis (PPFE) is a disease characterized by apical pleural thickening and subjacent parenchymal fibrosis. We report a case of a 60-year-old male with lung cancer in the left lower lobe and underlying PPFE combined with left apical pleural metastasis. Initially, asymmetric left apical pleural thickening due to pleural metastasis was mistaken for PPFE. Additionally, we describe the imaging and histopathological findings of PPFE, including MRI findings.

Effects of temperature, pH, and relative humidity on the growth of Penicillium paneum OM1 isolated from pears and its patulin production.

Patulin is a mycotoxin produced by several species of Penicillium sp., Aspergillus sp., and Byssochlamys sp. on apples and pears. Most studies have been focused on Penicillium expansum, a common postharvest pathogen, but little is known about the characteristics of Penicillium paneum. In the present study, we evaluated the effects of temperature, pH, and relative humidity (RH) on the growth of P. paneum OM1, which was isolated from pears, and its patulin production. The fungal strain showed the highest growth rate at 25 °C and pH 4.5 on pear puree agar medium (PPAM) under 97 % RH, while it produced the highest amount of patulin at 20 °C and pH 4.5 on PPAM under 97 % RH. Moreover, RT-qPCR analysis of relative expression levels of 5 patulin biosynthetic genes (patA, patE, patK, patL, and patN) in P. paneum OM1 exhibited that the expression of the 4 patulin biosynthetic genes except patL was up-regulated in YES medium (patulin conducive), while it was not in PDB medium (patulin non-conducive). Our data demonstrated that the 3 major environmental parameters had significant impact on the growth of P. paneum OM1 and its patulin production. These results could be exploited to prevent patulin contamination by P. paneum OM1 during pear storage.

Nationwide Prevalence of Video Head Impulse Test Abnormality and its Risk Factors in South Korea.

OBJECTIVE: To identify the prevalence of and relevant information for video head impulse test (vHIT) abnormality in a large population. STUDY DESIGN: A cross-sectional design. SETTING: Korean National Health and Nutrition Examination Survey, 2021. METHODS: The sample was representative of the Korean population, with 2237 participants aged ≥40 years. A vHIT was performed to evaluate vestibular function. The vestibulo-ocular reflex (VOR) gain and the presence of reproducible catch-up saccades was assessed in a vHIT. Participants also completed questionnaires for demographics, socioeconomic status, and basic information regarding systemic diseases and dizziness and underwent hearing tests with automated pure-tone audiometry. RESULTS: The prevalence of vHIT abnormality was 22.5%, with unilateral (14.3%) being more common than bilateral (8.2%). The prevalence of vHIT abnormality increased significantly with age, with the highest rate observed in individuals aged >70 years (42.5%). Both hearing and VOR gain deteriorated with age, but the patterns of age-related progression were different. While hearing loss (HL) deteriorated gradually and progressively throughout adulthood, VOR gain deterioration was markedly evident after 70 years of age. CONCLUSION: Considering the high prevalence of vHIT abnormality, appropriate social and medical policies are needed to prevent associated injuries and improve patients' quality of life. The distinct age-related changes in HL and objective findings of vestibular dysfunction indicate the need for different approaches to address these social problems in aging countries.

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.

PURPOSE: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. MATERIALS AND METHODS: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. RESULTS: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases. CONCLUSIONS: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

Taguchi Optimization of Wetting, Thermal and Mechanical Properties of Sn-1.0wt.%Ag-0.5wt.%Cu Alloys Modified with Bi and Sb.

This study was conducted on SAC105 (Sn-1wt.%Ag-0.5wt.%Cu) lead-free solder modified with Bi and Sb. The wetting, melting point, and mechanical properties were analysed with the addition of 1~5 wt.%Bi and 1~5 wt.%Sb for SAC105 base alloy. The wetting characteristics were assessed by wetting time (zero cross time, ZCT) obtained from wetting balance tests. The mechanical properties were analysed by tensile tests. Considering two factors (Bi, Sb), a three-level (0, 1, 2 wt.%) design of experiment (DOE) method array was applied for Taguchi optimization. The results indicated that the solder wetting increased as Bi content increased, while it decreased with Sb. The ZCT decreased with increasing Bi content up to 4 wt.%, while it increased proportionally to Sb content. The melting point, measured using a differential scanning calorimeter (DSC), showed that the melting point tended to decrease according to Bi increase, while it increases depending on the Sb content. Increase in Bi and Sb levels resulted in enhanced tensile strength in the mechanical properties tests, with Bi having a more noticeable impact. The Taguchi optimized conditions for the Bi and Sb studies were found to be 2 wt.%Bi and 2 wt.%Sb. This led to an optimal set of 0.9 s of wetting time, a 222.55 °C melting point, a 55 MPa tensile strength, and a 50% elongation.

Enhancing the Internet of Medical Things (IoMT) Security with Meta-Learning: A Performance-Driven Approach for Ensemble Intrusion Detection Systems.

This paper investigates the application of ensemble learning techniques, specifically meta-learning, in intrusion detection systems (IDS) for the Internet of Medical Things (IoMT). It underscores the existing challenges posed by the heterogeneous and dynamic nature of IoMT environments, which necessitate adaptive, robust security solutions. By harnessing meta-learning alongside various ensemble strategies such as stacking and bagging, the paper aims to refine IDS mechanisms to effectively counter evolving cyber threats. The study proposes a performance-driven weighted meta-learning technique for dynamic assignment of voting weights to classifiers based on accuracy, loss, and confidence levels. This approach significantly enhances the intrusion detection capabilities for the IoMT by dynamically optimizing ensemble IDS models. Extensive experiments demonstrate the proposed model's superior performance in terms of accuracy, detection rate, F1 score, and false positive rate compared to existing models, particularly when analyzing various sizes of input features. The findings highlight the potential of integrating meta-learning in ensemble-based IDS to enhance the security and integrity of IoMT networks, suggesting avenues for future research to further advance IDS performance in protecting sensitive medical data and IoT infrastructures.

Comparison of partial and total cystectomy for colorectal cancer with histologically confirmed bladder invasion.

BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.

A lipase from Lacticaseibacillus rhamnosus IDCC 3201 with thermostability and pH resistance for use as a detergent additive.

Lipases are important biocatalysts and ubiquitous in plants, animals, and microorganisms. The high growth rates of microorganisms with low production costs have enabled the wide application of microbial lipases in detergent, food, and cosmetic industries. Herein, a novel lipase from Lacticaseibacillus rhamnosus IDCC 3201 (Lac-Rh) was isolated and its activity analyzed under a range of reaction conditions to evaluate its potential industrial application. The isolated Lac-Rh showed a molecular weight of 24 kDa and a maximum activity of 3438.5 ± 1.8 U/mg protein at 60 °C and pH 8. Additionally, Lac-Rh retained activity in alkaline conditions and in 10% v/v concentrations of organic solvents, including glycerol and acetone. Interestingly, after pre-incubation in the presence of multiple commercial detergents, Lac-Rh maintained over 80% of its activity and the stains from cotton were successfully removed under a simulated laundry  setting. Overall, the purified lipase from L. rhamnosus IDCC 3201 has potential for use as a detergent in industrial applications. KEY POINTS: • A novel lipase (Lac-Rh) was isolated from Lacticaseibacillus rhamnosus IDCC 3201 • Purified Lac-Rh exhibited its highest activity at a temperature of 60 °C and a pH of 8, respectively • Lac-Rh remains stable in commercial laundry detergent and enhances washing performance.

Effect duration of lumbar sympathetic ganglion neurolysis in patients with complex regional pain syndrome: a prospective observational study.

Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P < 0.001). The median time to return to baseline temperature was 12 weeks (95% confidence interval [CI] 7.7-16.3) at the maximum pain site and 12 weeks (95% CI 9.4-14.6) at the plantar area. Pain intensity decreased significantly relative to baseline, at all-time points after LSGN. In conclusion, the median duration of the LSGN is estimated to be 12 weeks.

Lesion-aware cross-phase attention network for renal tumor subtype classification on multi-phase CT scans.

Multi-phase computed tomography (CT) has been widely used for the preoperative diagnosis of kidney cancer due to its non-invasive nature and ability to characterize renal lesions. However, since enhancement patterns of renal lesions across CT phases are different even for the same lesion type, the visual assessment by radiologists suffers from inter-observer variability in clinical practice. Although deep learning-based approaches have been recently explored for differential diagnosis of kidney cancer, they do not explicitly model the relationships between CT phases in the network design, limiting the diagnostic performance. In this paper, we propose a novel lesion-aware cross-phase attention network (LACPANet) that can effectively capture temporal dependencies of renal lesions across CT phases to accurately classify the lesions into five major pathological subtypes from time-series multi-phase CT images. We introduce a 3D inter-phase lesion-aware attention mechanism to learn effective 3D lesion features that are used to estimate attention weights describing the inter-phase relations of the enhancement patterns. We also present a multi-scale attention scheme to capture and aggregate temporal patterns of lesion features at different spatial scales for further improvement. Extensive experiments on multi-phase CT scans of kidney cancer patients from the collected dataset demonstrate that our LACPANet outperforms state-of-the-art approaches in diagnostic accuracy.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

scAI-SNP: a method for inferring ancestry from single-cell data.

Collaborative efforts, such as the Human Cell Atlas, are rapidly accumulating large amounts of single-cell data. To ensure that single-cell atlases are representative of human genetic diversity, we need to determine the ancestry of the donors from whom single-cell data are generated. Self-reporting of race and ethnicity, although important, can be biased and is not always available for the datasets already collected. Here, we introduce scAI-SNP, a tool to infer ancestry directly from single-cell genomics data. To train scAI-SNP, we identified 4.5 million ancestry-informative single-nucleotide polymorphisms (SNPs) in the 1000 Genomes Project dataset across 3201 individuals from 26 population groups. For a query single-cell data set, scAI-SNP uses these ancestry-informative SNPs to compute the contribution of each of the 26 population groups to the ancestry of the donor from whom the cells were obtained. Using diverse single-cell data sets with matched whole-genome sequencing data, we show that scAI-SNP is robust to the sparsity of single-cell data, can accurately and consistently infer ancestry from samples derived from diverse types of tissues and cancer cells, and can be applied to different modalities of single-cell profiling assays, such as single-cell RNA-seq and single-cell ATAC-seq. Finally, we argue that ensuring that single-cell atlases represent diverse ancestry, ideally alongside race and ethnicity, is ultimately important for improved and equitable health outcomes by accounting for human diversity.

Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results.

BACKGROUND AND OBJECTIVES: The popliteal artery is generally regarded as a "no-stent zone". Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. METHODS: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)-free rate. RESULTS: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. CONCLUSIONS: DCB treatment yielded favorable 12-month clinical primary patency and TLR-free survival outcomes in patients with popliteal artery disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698345.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).