Topochemical Synthesis of LiCoF3 with a High-Temperature LiNbO3-Type Structure.

A novel perovskite fluoride, LixCoF3, which has an exceptionally low tolerance factor (0.81), has been synthesized via low-temperature lithium intercalation into a distorted ReO3-type fluoride CoF3 using organolithium reagents. Interestingly, this reaction is completed within 15 min at room temperature. Synchrotron X-ray diffractometry and optical second harmonic generation at room temperature have revealed that this compound shows a high-temperature LiNbO3-type structure (space group: R3̅c) involving Li-Co antisite defects and A-site splitting along the c direction. A-site splitting is consistent with the prediction based on hybrid Hartree-Fock density functional theory calculations. Co-L2,3 edge X-ray absorption spectroscopy, as well as bond valence sum analysis, has verified the divalent oxidation state of Co ions in the lithiated phase, suggesting that its composition is close to LiCoF3 (x ≈ 1). This compound exhibits a paramagnetic-to-antiferromagnetic transition at 36 K on cooling, accompanied by weak ferromagnetic ordering. The synthetic route based on low-temperature lithiation of metal fluorides host paves the way for obtaining a new LiNbO3-type fluoride family.

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.

BACKGROUND: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. METHODS: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. RESULTS: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. CONCLUSIONS: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.

Serum anti-LRPAP1 is a common biomarker for digestive organ cancers and atherosclerotic diseases.

Some cancers are related to atherosclerotic diseases; therefore, these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method, which incorporates glutathione donor beads and anti-human IgG acceptor beads, was used to evaluate serum antibody levels. SEREX screening identified low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) as a target antigen of serum IgG antibodies in the sera of patients with ESCC or AIS. Antigens, including recombinant glutathione S-transferase-fused LRPAP1 protein, were prepared to examine serum antibody levels. AlphaLISA revealed significantly higher antibody levels against the LRPAP1 protein in patients with solid cancers such as ESCC and colorectal carcinoma and some atherosclerosis-related diseases such as AIS and diabetes mellitus compared with healthy donors. Correlation analysis revealed that the elevated serum antibody levels against LRPAP1 were associated with smoking, a well-known risk factor for both cancer and atherosclerosis. Serum LRPAP1 antibody is therefore a common marker for the early diagnosis of some cancers and atherosclerotic diseases and may reflect diseases caused by habitual smoking.

Resistive switching memory performance in oxide hetero-nanocrystals with well-controlled interfaces.

For realization of new informative systems, the memristor working like synapse has drawn much attention. We developed isolated high-density Fe3O4 nanocrystals on Ge nuclei/Si with uniform and high resistive switching performance using low-temperature growth. The Fe3O4 nanocrystals on Ge nuclei had a well-controlled interface (Fe3O4/GeOx/Ge) composed of high-crystallinity Fe3O4 and high-quality GeOx layers. The nanocrystals showed uniform resistive switching characteristics (high switching probability of ~90%) and relatively high Off/On resistance ratio (~58). The high-quality interface enables electric field application to Fe3O4 and GeOx near the interface, which leads to effective positively charged oxygen vacancy movement, resulting in high-performance resistive switching. Furthermore, we successfully observed memory effect in nanocrystals with well-controlled interface. The experimental confirmation of the memory effect existence even in ultrasmall nanocrystals is significant for realizing non-volatile nanocrystal memory leading to neuromorphic devices.

Cost Effectiveness of Drive and Retrieve System in Hokkaido for Acute Ischemic Stroke Patient Treatment Using Geographic Information System.

BACKGROUND AND PURPOSE: Although endovascular thrombectomy combined with recombinant tissue-type plasminogen activator is effective for treatment of acute ischemic stroke, regional disparities in implementation rates of those treatments have been reported. Drive and retrieve system, where a qualified neurointerventionist travels to another primary stroke center for endovascular thrombectomy, has been practiced in parts of Hokkaido, Japan. This study aims to simulate the cost effectiveness of the drive and retrieve system, which can be a method to enhance equality and cost effectiveness of treatments for acute ischemic stroke. MATERIALS AND METHODS: The number of patients who had acute ischemic stroke in 2015 is estimated. Those patients are generated according to the population distribution, and thereafter patient transport time is analyzed in the 3 scenarios (1) 60-minute drive scenario, (2) 90-minute drive scenario, in which the drive and retrieve system operates within 60-minute or 90-minute driving distance (3) without the system, using geographic information system. Incremental cost-effectiveness rate, quality-adjusted life years, and medical and nursing care costs are estimated from the analyzed transport time. FINDINGS: The incremental cost-effectiveness rate by implementing the system was dominant. Cost reductions of $213,190 in 60-minute drive scenario, and $247,274 in the 90-minute scenario were expected, respectively. Such benefits are the most significant in Soya, Emmon, Rumoi, and Kamikawahokubu medical areas. CONCLUSIONS: The drive and retrieve system could enhance regional equality and cost effectiveness of ischemic stroke treatments in Hokkaido, which can be achieved using existing resources. Further studies are required to clarify its cost effectiveness from hospital perspective.

Accessibility to Tertiary Stroke Centers in Hokkaido, Japan: Use of Novel Metrics to Assess Acute Stroke Care Quality.

BACKGROUND: Both the accessibility and availability of stroke specialists are major determinants of patient outcomes following acute ischemic stroke (AIS). The purpose of this study was to implement novel metrics to assess the accessibility of tertiary stroke centers as well as to evaluate regional disparities in stroke specialists. METHODS: Using network analysis in a geographic information system, we calculated areas within 30- and 60-minute travel times to facilities providing intravenous recombinant tissue-type plasminogen activator and mechanical thrombectomy. We further evaluated the accessibility for the proportion of the population aged 65 years or older that resided outside of these areas. Uniformity in the geographical distribution of stroke specialists was then evaluated using optimal statistical analysis. RESULTS: Accessibility varied widely from region to region, with low accessibility being concentrated in rural areas with low population density. Accessibility to facilities providing mechanical thrombectomy was especially low, and 17.8% of elderly individuals lived ≥60 minutes from treatment facilities. In addition, the distribution of stroke specialists was uneven compared with the distribution of hospital beds and full-time medical doctors. CONCLUSION: The results of this study revealed regional disparities in the spatial accessibility to treatment facilities, as well as in the distribution of stroke specialists in Hokkaido. These findings provide useful information that could be employed to appropriately allocate resources toward the formation of a medical supply system for patients with AIS.

Identification of stroke-associated-antigens via screening of recombinant proteins from the human expression cDNA library (SEREX).

BACKGROUND: Because circulating antibodies against a variety of antigens have been detected in patients with coronary heart disease, carotid atherosclerosis and those who have suffered a stroke, it is suspected that immune response may be one of the mechanisms of atherogenesis The objective of this study is to identify novel antibodies in ischemic stroke patients by screening the expressed recombinant proteins using a human cDNA library (SEREX). METHODS: To identify the candidate antigens, cDNA library was screened by SEREX using plasma from ten patients with ischemic stroke. Subsequently, via ELISA using recombinant proteins and synthetic peptides, the serum antibody levels were measured in two independent patient/healthy donor (HD) cohorts (142 and 78 in the 2nd screening and a validation cohort, respectively). RESULTS: The initial screening resulted in the identification of six candidate antigens. Of these antigens, replication protein A2 (RPA2) was determined to be the antigen associated with stroke (P < 0.05) by ELISA with 2nd screening and validation cohort. Multifactorial logistic regression analysis showed that the increased levels of the RPA2 antibodies (RPA2-Abs) associated with stroke independent of other risk factors for stroke (P < 0.05). Receiver operating curve analysis demonstrated that the area under the curve from ELISA using GST fusion RPA2 and synthetic peptides (bRPA2-132) were 0.867 (95% CI: 0.798-0.936) and 0.971 (95% CI: 0.940-1.00), respectively. If the cut-off value of the bRPA2-132-Ab level was determined to be 0.334, the sensitivity and specificity of the antibody level as the diagnostic marker for stroke were 0.323 (95% CI: 0.209-0.453) and 1.00 (95% CI: 0.713-1.00), respectively. CONCLUSIONS: SEREX identified RPA2 as the antigen associated with ischemic stroke and serum auto-antibodies against RPA2 elevates in stroke patients. RPA2-Abs could become a biomarker for the evaluation of ischemic stroke at risk.

Unlocking the chemical environment of nitrogen in perovskite-type oxides.

Nitrogen (N) doping of perovskite-type oxides is an effective method for enhancing their photocatalytic performance. Quantitative and qualitative analyses of the doped N species are essential for a deeper understanding of the catalytic activity enhancement mechanism. However, examining the N environment in perovskite-type oxides, particularly in the bulk, using conventional analytical techniques, such as X-ray photoelectron spectroscopy (XPS), is challenging. In this study, we propose a new analytical technique, advanced temperature-programmed desorption (TPD) up to 1600 °C, to complement the conventional methods. TPD can quantify all N species in bulk oxides. Moreover, it facilitates chemical speciation of N environments, such as substitutional and interstitial N species. This is verified by XPS, CHN elemental analysis, X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier-transform spectroscopy. This study demonstrates the feasibility of advanced TPD as a new analytical method that offers comprehensive information on the N species within N-doped oxide materials at the bulk level.

Redox Reaction in Ti-Mn Redox Flow Battery Studied by X-ray Absorption Spectroscopy.

We performed X-ray absorption studies for the electrolytes of a Ti-Mn redox flow battery (RFB) to understand the redox reaction of the Ti/Mn ions and formation of precipitates in charged catholyte, because suppression of the disproportionation reaction is a key to improve the cyclability of Ti-Mn RFB and enhance the energy density. Hard X-ray absorption spectroscopy with a high transmittance and soft X-ray absorption spectroscopy to directly observe the 3d orbitals were complementarily employed. Moreover, the Ti/Mn 3d electronic structure for each precipitate and solution in the charged catholyte was investigated by using scanning transmission X-ray microscopy: the valence of Mn in the precipitate is mostly attributed to 4+, and the solution includes only Mn2+ . This charge disproportionation reaction should occur after the Mn ions in the catholyte should be oxidized from Mn2+ to Mn3+ by charge.

Thermoresponsive mobility of liquid crystals and reactive mesogens during photopolymerization-induced phase separation.

Molecular interactions between liquid crystals (LCs) and reactive mesogens (RMs) at temperatures across the phase transition regions were comprehensively studied during photopolymerization-induced phase separation (PPIPS) beginning with raw mixtures until the formation of polymer network liquid crystals (PNLCs). Then, the molecules were found to be nonuniformly more and less mobile in response to temperature as PPIPS progressed. Optical birefringence and infrared absorption were carefully measured throughout PPIPS, using 4-cyano-4'-hexylbiphenyl (6CB) and 1,4bis-[4-(3-acryloyloxypropyloxy) benzoyloxy]-2-methylbenzene (RM257) as typical LCs and RMs. Microscopic views of thermoresponsive changes in the molecular orientation order of both LCs and RMs were obtained: LCs and RMs in raw mixtures interacted with one another but uniformly transformed their molecular orientation. Such interactions continuously change to become nonuniform with progress in PPIPS. At the incipient stages of PPIPS, RMs, which are polymerized but not completely networked, inhibit LCs from changing their molecular orientation and vice versa. As PPIPS progresses, some LCs become more mobile and some less mobile owing to RM constraints. The domain configuration of the submicrometer phase separation affects the thermoresponsive mobility of LCs and RMs, that is, LCs become more mobile in LC-richer areas. The quantitative knowledge here provides comprehensive insight that LCs and RMs are mutually constrained and that such interactive behavior varies nonuniformly as PPIPS progresses.

Ruptured bilateral middle cerebral artery aneurysms diagnosed based on cerebral vasospasm-associated ischemic symptoms: A case report.

We report a case of subarachnoid hemorrhage presenting with ischemic symptoms due to cerebral vasospasm. A 64-year-old woman with right facial paralysis was referred to our hospital for treatment because of bilateral middle cerebral artery aneurysms observed using magnetic resonance imaging. She had no headache episodes; however, contrast-enhanced magnetic resonance imaging showed contrast enhancement of the aneurysmal wall only on the left side. Therefore, she was considered to have a ruptured aneurysm and underwent craniotomy and aneurysmal neck clipping. The postoperative course was uneventful; however, she developed aphasia and dysphagia 9 months after the surgery and was readmitted. New cerebral infarction and subarachnoid hemorrhage were observed on the right side, and the patient exhibited marked vasospasm. Because of a headache episode one week earlier, coil embolization was performed after the vasospasm. She was discharged home with a modified Rankin scale score of 2 and planned rehabilitation. Aneurysms that enlarge and rupture in a short time period should be treated with caution. Vessel wall imaging was useful in identifying the ruptured aneurysm in the current case.

Two Patients with Reversible Cerebral Vasoconstriction after Carotid Artery Stenting.

Objective: We herein report two cases of transient cerebral vasoconstriction after carotid artery stenting (CAS). Case Presentation: An 81-year-old man presented with asymptomatic severe stenosis in the right carotid artery accompanied by a slight reduction in cerebrovascular reactivity. CAS was performed, but the patient had a generalized seizure because of transient cerebral ischemia caused by intolerance to carotid artery occlusion with balloon protection. Confusion and left hemiparesis persisted. DSA suggested cerebral ischemia due to vasoconstriction as the cause of these prolonged symptoms. A 66-year-old man presented with asymptomatic severe stenosis in the right carotid artery with slight hypoperfusion. CAS was performed. The patient developed left hemispatial neglect, dysarthria, and left hemiparesis 12 hours after the procedure. DSA revealed cerebral vasoconstriction in the responsible territory. The conditions of both patients improved within several days with medical treatment and they were discharged without neurological deficits. Conclusion: The cases presented herein show that transient ischemic complications caused by cerebral vasoconstriction may develop after CAS.

Carotid Artery Stenting for Patients with Radiation-Induced Carotid Artery Stenosis.

Objective: In radiation-induced carotid artery stenosis (RIS), morphological characteristics, such as bilateral and long lesion distances and in-stent stenosis, have been reported as common after carotid artery stenting (CAS). Here, we present 25 cases at our hospital wherein CAS was performed for RIS and compare the morphological characteristics and the safety of the treatment with cases of atherosclerotic carotid artery stenosis (AS). Methods: Twenty-five lesions from 21 patients underwent CAS for RIS at our hospital between March 2002 and July 2020. The procedure was performed at a mean of 10.0 ± 5.2 years after radiation therapy with 60-72 Gy, with a median follow-up of 45 months. We retrospectively selected consecutive patients with AS with comparable follow-up times from the beginning of the study as controls. We compared the patients' background, stenosis findings including plaque MRI, perioperative period, and postoperative course. Results: All patients in both groups completed the procedure, and the median follow-up time for the RIS and AS groups was 45 and 40 months, respectively (p = 0.1479). Patients in the RIS group had a lower mean age (69.9 ± 6.9 vs. 75.3 ± 7.04, p = 0.0075), a higher stenosis rate (79.1 ± 8.7% vs. 68.6 ± 11.7%, p = 0.0032), and longer stenosis greater than one vertebra (long lesions) (10 vs. 1, p = 0.0046) compared with the patients in the AS group. Although there was no significant difference in outcomes between the two groups, restenosis tended to be more common in the RIS group. Plaque MRI was characterized by a significantly higher T2WI signal (p = 0.0381) in the RIS group, which was attributable to the fact that a necrotic core has been reported commonly in the plaque tissue of RIS. Conclusion: RIS has a high likelihood of restenosis both morphologically and in terms of plaque characteristics. Thus, close follow-up is crucial.

Correlation between Higher Brain Dysfunction and Cerebral Blood Flow after Carotid Artery Stenting.

Objective: This study investigated the changes in higher brain function and cerebral blood flow (CBF) after carotid artery stenting (CAS), the relationship with CBF, and the impact of high intensities in diffusion-weighted imaging (DWI) after CAS. Methods: We performed CAS between September 2017 and September 2019 in our department in 88 patients. Patients who did not undergo higher brain function tests according to our protocol or those who did not consent to participate in our study were excluded. This study targeted the 26 patients who were able to undergo the tests, including the Kana Pick-out Test (KPOT) II, three times: before, 1 week after, and 1-3 months after CAS. We investigated the chronological changes in higher brain function and their relationship with high intensity on DWI. Results: The results of Symbol Digit Modalities Tests (SDMT) and KPOT I and II improved significantly. There was a significant correlation between the improvement of higher brain function and CBF in patients with stenosis exceeding 60%, a score of the Mini-Mental State Examination (MMSE) of 26 or less, and without other cause of higher brain dysfunction, including known dementia. High-intensity spots on DWI after CAS had no significant impact on higher brain function. Conclusion: Higher brain function associated with attention and working memory improved significantly after CAS. There was a correlation between the improvement of higher brain function and CBF in patients with severe stenosis, mild cognitive impairment, and no known dementia. The prevention of subsequent ischemic attack and higher brain function should both be taken into account when performing CAS.

Mechanical Thrombectomy for Acute Ischemic Stroke Complicated by Bacterial Meningitis and Infective Endocarditis.

Objective: We report a case of cerebral embolism from a bacterial embolus due to infective endocarditis (IE) during treatment of bacterial meningitis. Case Presentation: During treatment of bacterial meningitis, an 82-year-old woman developed left middle cerebral artery embolism. Mechanical thrombectomy was performed, and the yellowish-white emboli were retrieved. From the culture and pathological findings of the embolus, the same bacteria as the meningitis, Streptococcus gordonii, was identified and was considered to originate from IE. She was treated by postoperative antibiotics, but was transferred to the rehabilitation hospital on the 37th postoperative day due to slight right hemiparesis. Conclusion: We should always consider bacterial embolism in acute ischemic stroke combined with bacterial meningitis.

A prehospital diagnostic algorithm for strokes using machine learning: a prospective observational study.

High precision is optimal in prehospital diagnostic algorithms for strokes and large vessel occlusions. We hypothesized that prehospital diagnostic algorithms for strokes and their subcategories using machine learning could have high predictive value. Consecutive adult patients with suspected stroke as per emergency medical service personnel were enrolled in a prospective multicenter observational study in 12 hospitals in Japan. Five diagnostic algorithms using machine learning, including logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting, were evaluated for stroke and subcategories including acute ischemic stroke with/without large vessel occlusions, intracranial hemorrhage, and subarachnoid hemorrhage. Of the 1446 patients in the analysis, 1156 (80%) were randomly included in the training (derivation) cohort and cohorts, and 290 (20%) were included in the test (validation) cohort. In the diagnostic algorithms for strokes using eXtreme Gradient Boosting had the highest diagnostic value (test data, area under the receiver operating curve 0.980). In the diagnostic algorithms for the subcategories using eXtreme Gradient Boosting had a high predictive value (test data, area under the receiver operating curve, acute ischemic stroke with/without large vessel occlusions 0.898/0.882, intracranial hemorrhage 0.866, subarachnoid hemorrhage 0.926). Prehospital diagnostic algorithms using machine learning had high predictive value for strokes and their subcategories.

Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction.

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Circulating Anti-Sorting Nexins 16 Antibodies as an Emerging Biomarker of Coronary Artery Disease in Patients with Obstructive Sleep Apnea.

Biomarkers are not available for monitoring the onset and progression of coronary artery disease (CAD) in patients with obstructive sleep apnea (OSA), a major risk factor for arteriosclerotic cardiovascular diseases. This study aimed to test for correlation between circulating anti-Sorting Nexins 16 antibody (SNX16-Ab) levels, CAD history and clinical parameters of patients with OSA. Sixty-four healthy donors, 82 adults with OSA, and 96 with acute coronary syndrome (ACS) were studied. Serum samples were collected at diagnostic polysomnography in the OSA group or at the disease onset in the ACS group. Serum SNX16-Ab levels were measured by amplified luminescence proximity homogeneous assay (AlphaLISA), and correlation between SNX16-Ab levels and clinical parameters was analyzed. SNX16-Ab levels and apnea-hypopnea index (AHI) were weakly correlated. Additionally, logistic regression analyses of OSA group identified that elevated SNX16-Ab level associated with the history of CAD. Circulating SNX16-Ab could increase during CAD pathogenesis in patients with OSA. Further prospective studies are required to prove the predictive potential of SNX16-Ab level in CAD onset of patients with OSA.