Optimal design of synthetic circular RNAs.

Circular RNAs are an unusual class of single-stranded RNAs whose ends are covalently linked via back-splicing. Due to their versatility, the need to express circular RNAs in vivo and in vitro has increased. Efforts have been made to efficiently and precisely synthesize circular RNAs. However, a review on the optimization of the processes of circular RNA design, synthesis, and delivery is lacking. Our review highlights the multifaceted aspects considered when producing optimal circular RNAs and summarizes the available options for each step of exogenous circular RNA design and synthesis, including circularization strategies. Additionally, this review describes several potential applications of circular RNAs.

Prognostic Value of Electroneuronography in Severe Cases of Facial Palsy.

OBJECTIVE: To examine the prognostic value of electroneuronography (ENoG) in predicting functional recovery in severe cases of acute facial palsy. METHODS: Patients with severe degrees of facial palsy (initial House-Brackmann [HB] grades IV to VI) with available electrodiagnostic studies conducted 2-4 weeks after symptom onset were reviewed retrospectively. The patients were categorized into "good recovery" and "poor recovery" groups, with the former showing mild to no dysfunction (HB I to III) and the latter exhibiting moderate to severe dysfunction (HB IV to VI) on follow-up evaluation, 2 months after onset. ENoG amplitudes in four facial muscles (frontalis, nasalis, orbicularis oculi, and orbicularis oris), as well as age, sex, affected side, disease etiology, comorbidities, and laboratory findings, were compared between the two groups. RESULTS: Thirty-seven patients were included. Twenty-nine of the patients showed "good recovery," and eight showed "poor recovery" at 2 months after symptom onset. Univariate analysis yielded no significant difference in age, sex, affected side, disease etiology, comorbidities, and laboratory findings between the two groups. Preserved ENoG amplitudes (individual, average, and trimmed means) were significantly higher in the good recovery group than in the poor recovery group (p<0.005). Sex (p=0.038) and the ENoG of the nasalis muscle, acquired 2-4 weeks from symptom onset (p=0.004), showed significant differences in multivariate regression analysis. CONCLUSION: This study suggests that the female sex and lower ENoG of the nasalis muscle, acquired 2-4 weeks from symptom onset, have negative prognostic value for the 2-month functional outcome of severe facial palsy cases.

Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis.

OBJECTIVE: : To systematically review the effects of protein supplementation in older adults with sarcopenia. METHODS: : A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. RESULTS: : Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24-0.58; p<0.001; I2=1%), while handgrip strength (SMD=0.37; 95% CI, -0.32-1.07; p=0.29; I2=94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47-1.18; p=0.40; I2=94%) showed a tendency for improvement. CONCLUSION: : Nutritional supplementation with protein increased appendicular muscle mass in older adults with sarcopenia and improved handgrip strength and SPPB scores.

Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation.

Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation.

Scrub Typhus and Abnormal Electrocardiography.

This study compared the frequency of abnormal electrocardiogram (ECG) types between scrub typhus patient group and age- and gender-matched health checkup group and their associations with disease severity in scrub typhus patient. Demographic characteristics and ECG and laboratory findings of patients with scrub typhus admitted to Chosun University Hospital, and normal subjects visiting the hospital for health checkup from January 2008 to December 2012 were retrospectively studied. Electrocardiogram abnormalities at admission were observed in 72 of 165 (43.6%) scrub typhus confirmed patients. The following ECG abnormalities were observed: arrhythmic group (31 cases, 18.8%), ischemic change group (25 cases, 15.1%), prolonged QT group (32 cases, 19.4%).Compared with the age and gender-matched health checkup group, ECG abnormalities were more commonly observed in scrub typhus patient group (13.9% versus 43.6%, P < 0.001). In addition, when compared with the normal ECG group, scrub typhus in the abnormal ECG group showed greater disease severity and this phenomenon was particularly prominent in the prolonged QT group. Based on our study prolonged QT observed in approximately 20% of patients with scrub typhus, clinicians should pay additional attention to drugs that affect QT interval.

En bloc and segmental deletions of human XIST reveal X chromosome inactivation-involving RNA elements.

The XIST RNA is a non-coding RNA that induces X chromosome inactivation (XCI). Unlike the mouse Xist RNA, how the human XIST RNA controls XCI in female cells is less well characterized, and its functional motifs remain unclear. To systematically decipher the XCI-involving elements of XIST RNA, 11 smaller XIST segments, including repeats A, D and E; human-specific repeat elements; the promoter; and non-repetitive exons, as well as the entire XIST gene, were homozygously deleted in K562 cells using the Cas9 nuclease and paired guide RNAs at high efficiencies, followed by high-throughput RNA sequencing and RNA fluorescence in situ hybridization experiments. Clones containing en bloc and promoter deletions that consistently displayed no XIST RNAs and a global up-regulation of X-linked genes confirmed that the deletion of XIST reactivates the inactive X chromosome. Systematic analyses of segmental deletions delineated that exon 5 harboring the non-repeat element is important for X-inactivation maintenance, whereas exons 2, 3 and 4 as well as the other repeats in exon 1 are less important, a different situation from that of mouse Xist. This Cas9-assisted dissection of XIST allowed us to understand the unique functional domains within the human XIST RNA.

The small peptide world in long noncoding RNAs.

Long noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200 nucleotides (nt) without coding potential. Over the past decade, tens of thousands of novel lncRNAs have been annotated in animal and plant genomes because of advanced high-throughput RNA sequencing technologies and with the aid of coding transcript classifiers. Further, a considerable number of reports have revealed the existence of stable, functional small peptides (also known as micropeptides), translated from lncRNAs. In this review, we discuss the methods of lncRNA classification, the investigations regarding their coding potential and the functional significance of the peptides they encode.

TERIUS: accurate prediction of lncRNA via high-throughput sequencing data representing RNA-binding protein association.

BACKGROUND: LncRNAs are long regulatory non-coding RNAs, some of which are arguably predicted to have coding potential. Despite coding potential classifiers that utilize ribosome profiling data successfully detected actively translated regions, they are less sensitive to lncRNAs. Furthermore, lncRNA annotation can be susceptible to false positives obtained from 3' untranslated region (UTR) fragments of mRNAs. RESULTS: To lower these limitations in lncRNA annotation, we present a novel tool TERIUS that provides a two-step filtration process to distinguish between bona fide and false lncRNAs. The first step successfully separates lncRNAs from protein-coding genes showing enhanced sensitivity compared to other methods. To eliminate 3'UTR fragments, the second step takes advantage of the 3'UTR-specific association with regulator of nonsense transcripts 1 (UPF1), leading to refined lncRNA annotation. Importantly, TERIUS enabled the detection of misclassified transcripts in published lncRNA annotations. CONCLUSIONS: TERIUS is a robust method for lncRNA annotation, which provides an additional filtration step for 3'UTR fragments. TERIUS was able to successfully re-classify GENCODE and miTranscriptome lncRNA annotations. We believe that TERIUS can benefit construction of extensive and accurate non-coding transcriptome maps in many genomes.

Stroke or left atrial thrombus prediction using antithrombin III and mean platelet volume in patients with nonvalvular atrial fibrillation.

BACKGROUND: CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke) and CHA2 DS2 -VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke, vascular disease, age 65 to 74 years, sex category) scores showed just moderate discrimination ability in predicting thromboembolic complications in patients with nonvalvular atrial fibrillation (AF). HYPOTHESIS: To determine the association of antithrombin III (AT-III) deficiency and mean platelet volume (MPV) with the development of stroke or left atrial (LA) thrombus in patients with AF. METHODS: AT-III and MPV were analyzed in 352 patients with AF. The primary endpoint was a composite of ischemic stroke event and incidental LA thrombus. RESULTS: There were 50 events (14.2%) during a mean 35.4 months of follow-up. A significantly higher stroke or LA thrombus rate was observed in the low-AT-III group (<70%) than that in the high-AT-III group (≥70%). A significantly higher stroke or LA thrombus rate was observed in the high-MPV group (≥7.0 fL) than that in the low-MPV group (<7.0 fL). AF patients with an MPV ≥7.0 fL and AT-III deficiency had higher stroke or LA thrombus risk than those without an MPV ≥7.0 fL and AT-III deficiency. In the Cox proportional hazard analysis, high MPV was found to be an independent predictor of stroke or LA thrombus risk (hazard ratio: 6.408; 95% confidence interval: 2.874-14.286). Although AT-III deficiency was not an independent predictor of stroke or LA thrombus risk, a trend was observed. CONCLUSIONS: High MPV and AT-III deficiency were predictive markers for stroke or LA thrombus. Their predictive power for stroke was independent of antiplatelet treatment, anticoagulation therapy, and a high CHA2 DS2 -VASc score in patients with AF.

A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as undifferentiated pleomorphic sarcoma in the left atrium.

RATIONALE: An intracardiac cystic mass is a rare type of mass found in the left atrium. The differential diagnosis of an intracardiac cystic mass includes hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some tumor types, including myxoma. PATIENT CONCERNS: We present the case of a 68-year-old woman who presented with episodic dyspnea. DIAGNOSES-INTERVENTIONS-OUTCOMES: Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass mimicking myxoma. However, in postoperative findings, it was determined that the mass was actually a hemorrhagic cyst. Eighteen months later, the patient presented with recurrent exertional dyspnea and TTE revealed the recurrence of a left atrial mass. Computed tomography showed that the mass extended into the right atrium, inferior vena cava, and coronary sinus. After re-operation, the final histological diagnosis was determined to be an undifferentiated pleomorphic sarcoma in the left atrium. LESSONS: An intracardiac hemorrhagic cyst was suspected during the operation of a benign-looking LA mass. As such, we recommend that other rare etiologies be considered and more biopsies be performed when possible.

Protein Tyrosine Phosphatase N2 Is a Positive Regulator of Lipopolysaccharide Signaling in Raw264.7 Cell through Derepression of Src Tyrosine Kinase.

T cell protein tyrosine phosphatase N2 (PTPN2) is a phosphotyrosine-specific nonreceptor phosphatase and is ubiquitously expressed in tissues. Although PTPN2 functions as an important regulator in different signaling pathways, it is still unclear what is specific target protein of PTPN2 and how is regulated in lipopolysaccharide (LPS)-induced inflammatory signaling pathway. Here, we found that PTPN2 deficiency downregulated the expression of LPS-mediated pro-inflammtory cytokine genes. Conversely, overexpression of PTPN2 in Raw264.7 cells enhanced the expression and secretion of those cytokines. The activation of MAPK and NF-κB signaling pathways by LPS was reduced in PTPN2-knockdowned cells and ectopic expression of PTPN2 reversed these effects. Furthermore, we found that PTNP2 directly interacted with Src and removed the inhibitory Tyr527 phosphorylation of Src to enhance the activatory phosphorylation of Tyr416 residue. These results suggested that PTPN2 is a positive regulator of LPS-induced inflammatory response by enhancing the activity of Src through targeting the inhibitory phosphor-tyrosine527 of Src.

Prediction of Long-Term Mortality Based on Neutrophil-Lymphocyte Ratio After Percutaneous Coronary Intervention.

BACKGROUND: The preprocedural neutrophil-lymphocyte ratio (NLR) is related to adverse outcomes in patients with coronary artery disease. We hypothesized that high NLR is a predictor of cardiac death after percutaneous coronary intervention (PCI). The objective of this investigation was to assess the associations of NLR, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the occurrence of cardiac death after PCI. MATERIALS AND METHODS: The NLR, hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary end point was cardiac death. RESULTS: The median NLR was 2.3 (interquartile range: 1.5-4.1). There were 21 cardiac death events during a mean follow-up duration of 25.8 months. With the NLR cutoff level set to 3.3 using the receiver-operating characteristic curve, the sensitivity and specificity for differentiating between the group with cardiac death and the group without cardiac death were 85.7% and 59.3%, respectively. Kaplan-Meier analysis revealed that the higher NLR group (≥3.3) had a significantly higher cardiac death rate than the lower NLR group (<3.3) (11.1% versus 1.4%, log-rank: P < 0.0001). This value was more useful in patients with heart failure (NT-proBNP ≥ 300ng/L) or myocardial injury (hs-cTnT ≥ 100ng/L). CONCLUSIONS: The outcomes of the current study demonstrate that high NLR is a predictor of cardiac death after PCI, especially in patients with heart failure or myocardial injury.

Incredible RNA: Dual Functions of Coding and Noncoding.

Since the RNA world hypothesis was proposed, a large number of regulatory noncoding RNAs (ncRNAs) have been identified in many species, ranging from microorganisms to mammals. During the characterization of these newly discovered RNAs, RNAs having both coding and noncoding functions were discovered, and these were considered bifunctional RNAs. The recent use of computational and high-throughput experimental approaches has revealed increasing evidence of various sources of bifunctional RNAs, such as protein-coding mRNAs with a noncoding isoform and long ncRNAs bearing a small open reading frame. Therefore, the genomic diversity of Janus-faced RNA molecules that have dual characteristics of coding and noncoding indicates that the functional roles of RNAs have to be revisited in cells on a genome-wide scale. Such studies would allow us to further understand the complex gene-regulatory network in cells. In this review, we discuss three major genomic sources of bifunctional RNAs and present a handful of examples of bifunctional RNA along with their functional roles.

Prediction of Infarct Transmurality From C-Reactive Protein Level and Mean Platelet Volume in Patients With ST-Elevation Myocardial Infarction: Comparison of the Predictive Values of Cardiac Enzymes.

BACKGROUND: High C-reactive protein (CRP) and mean platelet volume (MPV) levels are associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the relationship between CRP level or MPV and infarct transmurality in patients with STEMI. METHODS: We retrospectively reviewed CRP level, MPV, and infarct transmurality in 112 STEMI patients who were assessed with contrast-enhanced cardiac magnetic resonance imaging. RESULTS: When the cut-off peak CRP level and MPV were set at 2.35 mg/dl and 7.3 fl using receiver operating characteristic curves analysis, the sensitivity was 67.3/69.2% and specificity was 76.7/76.7% for differentiating between the groups with and those without transmural involvement. Peak CRP level, MPV, peak creatine kinase-MB (CK-MB) level, and peak high-sensitivity cardiac troponin T (hs-cTnT) level had comparable predictive values for transmural involvement (area under the curve, 0.749, 0.761, 0.680, and 0.696, respectively). High peak CRP level and MPV were independent predictors of transmural involvement after adjusting for the peak CK-MB level, peak hs-cTnT level, baseline thrombolysis in myocardial infarction flow grade, and left ventricular ejection fraction (odds ratio: 5.16/5.42, 95% confidence interval: 1.84-14.50/2.03-14.47, P = 0.002/0.001, respectively) in the logistic regression analysis. CONCLUSION: The results of this study show that peak CRP level and MPV are predictive markers for transmural involvement. Their predictive power for transmural involvement is independent of and comparable to that of peak CK-MB and hs-cTnT levels.

Smad7 Modulates Epidermal Growth Factor Receptor Turnover through Sequestration of c-Cbl.

Epidermal growth factor (EGF) regulates various cellular events, including proliferation, differentiation, migration, and tumorigenesis. For the maintenance of homeostasis, EGF signaling should be tightly regulated to prevent the aberrant activation. Smad7 has been known as inhibitory Smad that blocks the signal transduction of transforming growth factor ß. In the process of cell proliferation or transformation, Smad7 has been shown the opposite activities as a promoter or suppressor depending on cell types or microenvironments. We found that the overexpression of Smad7 in human HaCaT keratinocyte cells and mouse skin tissues elevated EGF receptor (EGFR) activity by impairing ligand-induced ubiquitination and degradation of activated receptor, which is induced by the E3 ubiquitin ligase c-Cbl. The C-terminal MH2 region but not MH1 region of Smad7 is critical for interaction with c-Cbl to inhibit the ubiquitination of EGFR. Interestingly, wild-type Smad7, but not Smad6 or mutant Smad7, destabilized the EGF-induced complex formation of c-Cbl and EGFR. These data suggest a novel role for Smad7 as a promoter for prolonging the EGFR signal in keratinocyte and skin tissue by reducing its ligand-induced ubiquitination and degradation.

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction.

BACKGROUND/AIMS: The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). METHODS: We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. RESULTS: The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). CONCLUSIONS: The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity.

Clinical outcome prediction from mean platelet volume in patients undergoing percutaneous coronary intervention in Korean cohort: Implications of more simple and useful test than platelet function testing.

The aim of this study was to determine the associations of the mean platelet volume (MPV) with the development of adverse outcomes after percutaneous coronary intervention (PCI) and platelet reactivity. MPV and platelet function testing were analysed in 208 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analysed was cardiovascular events (CVE): the composite of myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis (ST). The median MPV level, aspirin reaction unit (ARU), P2Y12 reaction units (PRU) and P2Y12% inhibition (PI%) of clopidogrel were 8.55 (IQR 8.00-9.18) fl, 401.0 (IQR 389.3-442.0) ARU, 222.0 (IQR 169.0-272.3) PRU and 22 (IQR 9-38) %, respectively. We observed that high values of MPV were associated with elevated ARU (r = 0.165, p = 0.017) and decreased PI% (r = -0.167, p = 0.016). There were 10 events of cardiac death, 3 MI (including 1 event of ST), and 8 TVR during a mean of 7.6 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (≥8.55 fl, median) had a significantly higher cardiac death rate compared to the lower MPV group (<8.55 fl) (7.7% vs. 1.9%, log-rank: p = 0.035). However, aspirin or clopidogrel resistance (>550 ARU, <40 PI%, respectively) did not predict cardiac death. When the MPV cut-off level was set to 8.55 fl using the receiver operating characteristic curve, the sensitivity was 80% and the specificity was 51.5% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with clinical diagnosis of acute coronary syndrome (ACS). Furthermore, ACS patients with an MPV over 8.55 fl had high cardiac death and CVE risk without atorvastatin loading before PCI (Log-Rank = 0.0031, 0.0023, respectively). The results of this study show that MPV was a predictive marker for cardiac death after PCI; its predictive power for cardiac death was more useful in patients with ACS.

Stroke or coronary artery disease prediction from mean platelet volume in patients with type 2 diabetes mellitus.

The aim of this study was to determine the association of mean platelet volume (MPV) with the development of stroke or coronary artery disease (CAD) in diabetes mellitus (DM). MPV was analyzed in 200 Korean patients with DM. The primary endpoint was composite of ischemic stroke/CAD events. The mean MPV was 7.6 ± 0.8 fl. There were 14 ischemic stroke events and 8 CAD events during a mean of 28.4 months of follow-up. The Kaplan-Meier analysis revealed that the higher tertile MPV group (≥7.9 fl) had a significantly higher stroke/CAD rate compared to the lower tertile MPV group (≤7.3 fl) (29.9% vs. 2.8%, log-rank: p < 0.001). Higher MPV was an independent predictor of stroke/CAD risk after adjusting for 10-year risk ≥10%, hypertension, dyslipidemia, and previous stroke or transient ischemic attack history (hazard ratio: 11.92, 95% confidence interval 2.68-52.92, p = 0.001) in the Cox proportional hazard analysis. When the MPV cut-off level was set to 7.95 fl using the receiver operating characteristic curve, the sensitivity was 91% and the specificity was 80% for differentiating between the group with stroke/CAD and the group without stroke/CAD. This value was more useful in patients with hypertension. The results of this study show that MPV is a predictive marker for stroke/CAD; its predictive power for stroke/CAD is independent of age, gender, hypertension, and hemoglobin A1C.

Predictive value of brachial-ankle pulse wave velocity for cardiovascular events.

BACKGROUND: The aim of this study was to determine the association of pulse wave velocity or left ventricular diastolic function with the development of cardiovascular (CV) events. METHODS: Brachial-ankle pulse wave velocity (baPWV) and E/E' were analyzed in 185 patients. The primary end point was CV events including ischemic stroke, coronary arterial disease (CAD), peripheral arterial disease and aortic dissection. RESULTS: There were 30 CV events during a mean follow-up period of 19.8 months. When the baPWV cutoff level was set to 1704 cm/s using the receiver operating characteristic curve, the sensitivity was 70/92% and the specificity 63/62% for differentiating between the group with and without CV events or ischemic stroke. In univariate analysis with the Cox proportional hazard model, higher baPWV was a predictor for CV events and ischemic stroke events. However, high E/E' (>15) was not a predictor for CV, ischemic stroke events or CAD. A higher baPWV was an independent predictor for CV and ischemic stroke risk after adjusting for age, sex, hypertension and diabetes in the Cox proportional hazard analysis. In subgroup analysis, diabetic patients with a baPWV >1704 cm/s had a high CV event and ischemic stroke risk. CONCLUSIONS: The results of this study show that higher baPWV was a predictive marker for CV events, especially ischemic stroke. The subgroup analysis suggests that antiplatelet therapy may be needed in diabetic patients with a high baPWV for prevention of ischemic stroke.