Recent Advances in Lateral Flow Assays for Viral Protein Detection with Nanomaterial-Based Optical Sensors.

Controlling the progression of contagious diseases is crucial for public health management, emphasizing the importance of early viral infection diagnosis. In response, lateral flow assays (LFAs) have been successfully utilized in point-of-care (POC) testing, emerging as a viable alternative to more traditional diagnostic methods. Recent advancements in virus detection have primarily leveraged methods such as reverse transcription-polymerase chain reaction (RT-PCR), reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and the enzyme-linked immunosorbent assay (ELISA). Despite their proven effectiveness, these conventional techniques are often expensive, require specialized expertise, and consume a significant amount of time. In contrast, LFAs utilize nanomaterial-based optical sensing technologies, including colorimetric, fluorescence, and surface-enhanced Raman scattering (SERS), offering quick, straightforward analyses with minimal training and infrastructure requirements for detecting viral proteins in biological samples. This review describes the composition and mechanism of and recent advancements in LFAs for viral protein detection, categorizing them into colorimetric, fluorescent, and SERS-based techniques. Despite significant progress, developing a simple, stable, highly sensitive, and selective LFA system remains a formidable challenge. Nevertheless, an advanced LFA system promises not only to enhance clinical diagnostics but also to extend its utility to environmental monitoring and beyond, demonstrating its potential to revolutionize both healthcare and environmental safety.

One-Pot CRISPR-Cas12a-Based Viral DNA Detection via HRP-Enriched Extended ssDNA-Modified Au@Fe3O4 Nanoparticles.

In the context of virus outbreaks, the need for early and accurate diagnosis has become increasingly urgent. In addition to being crucial for effective disease control, timely and precise detection of viral infections is also necessary for the implementation of essential public health measures, especially during pandemics. Among these measures, point-of-care testing (POCT) stands out as a powerful approach with the potential to revolutionize the landscape of viral diagnosis. In this study, we developed a one-pot clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a-based viral DNA detection system tailored for POCT; this method utilizes multi-enzyme-modified Au@Fe3O4 nanoparticles. As an alternative to nucleic acid amplification, our method uses single-stranded DNA elongation to facilitate multi-enzyme modification; this guarantees heightened sensitivity and expedites the diagnostic process. We achieved a satisfactory limit of detection of 0.25 nM, demonstrating the remarkable sensitivity of the method without the need for sophisticated equipment. The incorporation of Au@Fe3O4 magnetic nanoparticles facilitates sample separation, further streamlining the workflow and reinforcing the simplicity of our method. This integrated approach offers a practical solution for sensitive viral DNA detection in POCT scenarios, advancing the field of rapid and accurate diagnostics.

Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis.

BACKGROUND: This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA. METHODS: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging. RESULTS: In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group. CONCLUSION: Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.

Caffeic acid phenethyl ester: Unveiling its potential as a potent apoptosis inducer for combating hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare form of head and neck cancer that is notorious for its poor prognosis and low overall survival rate. This highlights the need for new therapeutic options for this malignancy. The objective of the present study was to examine the ability of caffeic acid phenethyl ester (CAPE), which is an active compound found in propolis, to combat HSCC tumor growth. CAPE exerted its tumor­suppressive activity in HSCC cell lines through the induction of apoptosis. Mechanistically, the CAPE­mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase­9. CAPE also modulated survivin and X­linked inhibitor of apoptosis, which are potent members of the inhibitors of apoptosis protein family, either through transcriptional or post­translational regulation, leading to HSCC cell line death. Therefore, the findings of the present study suggested that CAPE is an effective treatment alternative for HSCC via the stimulation of mitochondria­dependent apoptosis.

Angiotensin receptor blockers, but not angiotensin-converting enzyme inhibitors, inhibit abnormal bone changes in spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disease that results in bone ankylosis. The tissue renin-angiotensin system (RAS) is an emerging pathway potentially implicated in SpA-associated bone changes. The aim of the present study was to determine the mechanisms underlying this relationship. Sakaguchi (SKG) mice injected with curdlan (SKGc), animal models for SpA, were treated with RAS modulators, angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis). Disease activity was assessed using clinical scores and computed tomography scans. Mouse primary bone marrow monocytes (BMMs), osteoblast (OB) progenitor cells, peripheral blood monocytes (PBMCs), and bone-derived cells (BdCs) from patients with radiographic axial SpA (r-axSpA) were used to investigate the role of RAS in SpA pathogenesis. The expression of RAS components was significantly increased in SKGc mouse joints, and ARBs significantly reduced erosion and systemic bone loss, whereas ACEis did not. Osteoclast (OC) differentiation from primary BMMs, mediated by TRAF6, was inhibited by ARBs but promoted by ACEis; the modulators also exerted opposite effects on OB differentiation. Expression of RAS molecules was higher in PBMCs and BdCs of patients with r-axSpA than in control participants. ARBs inhibited OB differentiation in the BdCs of patients with r-axSpA, whereas ACEis did not. Neither ARBs nor ACEis affected OB differentiation in the control participants. In SpA, a condition characterized by RAS overexpression, ARBs, but not ACEis, inhibited OC and OB differentiation and bone progression. The findings should be taken into account when treating patients with SpA using RAS modulators.

Neuropilin-2 acts a critical determinant for epithelial-to-mesenchymal transition and aggressive behaviors of human head and neck cancer.

PURPOSE: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. METHODS: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. RESULTS: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. CONCLUSIONS: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.

A Whole-Genome Analysis of the African Swine Fever Virus That Circulated during the First Outbreak in Vietnam in 2019 and Subsequently in 2022.

Since its initial report in Vietnam in early 2019, the African swine fever (ASF), a highly lethal and severe viral swine disease worldwide, continues to cause outbreaks in other Southeast Asian countries. This study analyzed and compared the genomic sequences of ASF viruses (ASFVs) during the first outbreak in Hung Yen (VN/HY/2019-ASFV1) and Quynh Phu provinces (VN/QP/2019-ASFV1) in Vietnam in 2019, and the subsequent outbreak in Hung Yen (VN/HY/2022-ASFV2) in 2022, to those of other ASFV strains. VN/HY/2019-ASFV1, VN/QP/2019-ASFV1, and VN/HY/2022-ASFV2 genomes were 189,113, 189,081, and 189,607 bp in length, encoding 196, 196, and 203 open reading frames (ORFs), respectively. VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 shared a 99.91-99.99% average nucleotide identity with genotype II strains. Variations were identified in 28 ORFs in VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 compared to 20 ASFV strains, and 16 ORFs in VN/HY/2022-ASFV2 compared to VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1. Vietnamese ASFV genomes were classified as IGR II variants between the I73R and I329L genes, with two copy tandem repeats between the A179L and A137R genes. A phylogenetic analysis based on the whole genomes of 27 ASFV strains indicated that the Vietnamese ASFV strains are genetically related to Estonia 2014, ASFV-SY18, and Russia/Odintsovo_02/14. These results reveal the complete genome sequences of ASFV circulating during the first outbreak in 2019, providing important insights into understanding the evolution, transmission, and genetic variation of ASFV in Vietnam.

Effective Chemical Lift-Off for Air-Tunnel GaN on a Trapezoid-Patterned Sapphire Substrate.

We fabricated an air-tunnel structure between a gallium nitride (GaN) layer and trapezoid-patterned sapphire substrate (TPSS) through the in situ carbonization of a photoresist layer to enable rapid chemical lift-off (CLO). A trapezoid-shaped PSS was used, which is advantageous for epitaxial growth on the upper c-plane when forming an air tunnel between the substrate and GaN layer. The upper c-plane of the TPSS was exposed during carbonization. This was followed by selective GaN epitaxial lateral overgrowth using a homemade metal organic chemical vapor deposition system. The air tunnel maintained its structure under the GaN layer, whereas the photoresist layer between the GaN layer and TPSS disappeared. The crystalline structures of GaN (0002) and (0004) were investigated using X-ray diffraction. The photoluminescence spectra of the GaN templates with and without the air tunnel showed an intense peak at 364 nm. The Raman spectroscopy results for the GaN templates with and without the air tunnel were redshifted relative to the results for free-standing GaN. The CLO process using potassium hydroxide solution neatly separated the GaN template with the air tunnel from the TPSS.

Histone Deacetylase Inhibitor, Sodium Butyrate-Induced Metabolic Modulation in Platycodon grandiflorus Roots Enhances Anti-Melanogenic Properties.

While the status of histone acetylation is a critical regulator of chromatin's structure with a significant impact on plant physiology, our understanding of epigenetic regulation in the biosynthesis of active compounds in plants is limited. In this study, Platycodon grandiflorus was treated with sodium butyrate (NaB), a histone deacetylase inhibitor, to investigate the influence of histone acetylation on secondary metabolism. Its treatment with NaB increased the acetylation of histone H3 at lysine 9, 14, and 27 and enhanced the anti-melanogenic properties of P. grandiflorus roots. Through transcriptome and differentially expressed gene analyses, we found that NaB influenced the expression of genes that were involved in both primary and secondary metabolic pathways. In addition, NaB treatment caused the accumulation of polyphenolic compounds, including dihydroquercetin, gallic acid, and 2,4-dihydroxybenzoic acid. The NaB-induced transcriptional activation of genes in the phenylpropanoid biosynthetic pathway influenced the anti-melanogenic properties of P. grandiflorus roots. Overall, these findings suggest the potential of an epigenomic approach to enhance the medicinal qualities of medicinal plants.

CoAt-Mixer: Self-attention deep learning framework for left ventricular hypertrophy using electrocardiography.

Left ventricular hypertrophy is a significant independent risk factor for all-cause mortality and morbidity, and an accurate diagnosis at an early stage of heart change is clinically significant. Electrocardiography is the most convenient, economical, and non-invasive method for screening in primary care. However, the coincidence rate of the actual left ventricular hypertrophy and diagnostic findings was low, consequently increasing the interest in algorithms using big data and deep learning. We attempted to diagnose left ventricular hypertrophy using big data and deep learning algorithms, and aimed to confirm its diagnostic power according to the differences between males and females. This retrospective study used electrocardiographs obtained at Yonsei University Wonju Severance Christian Hospital, Wonju, Korea, from October 2010 to February 2020. Binary classification was performed for primary screening for left ventricular hypertrophy. Three datasets were used for the experiment: the male, female, and entire dataset. A cutoff for binary classification was defined as the meaningful as a screening test (<132 g/m2 vs. ≥132 g/m2, <109 g/m2 vs. ≥109 g/m2). Six types of input were used for the classification tasks. We attempted to determine whether electrocardiography had predictive power for left ventricular hypertrophy diagnosis. For the entire dataset, the model achieved an area under the receiver operating characteristic (AUROC) curve of 0.836 (95% CI, 0.833-838) with a sensitivity of 78.37% (95% CI, 76.79-79.95). For the male dataset, the AUROC was 0.826 (95% CI, 0.822-830) with a sensitivity of 76.73% (95% CI, 75.14-78.33). For the female dataset, the AUROC was 0.772 (95% CI, 0.769-775) with a sensitivity of 72.90% (95% CI, 70.33-75.46). Our model confirmed that left ventricular hypertrophy can be classified to some extent using electrocardiography, demographics, and electrocardiography features. In particular, a learning environment that considered gender differences was constructed. Consequently, the difference in diagnostic power between men and women was confirmed. Our model will help patients with suspected left ventricular hypertrophy to undergo screening tests at a low cost. In addition, our research and attempts will show the expected effect that gender-consideration approaches can help with various currently proposed diagnostic methods.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

Selective-Area Growth Mechanism of GaN Microrods on a Plateau Patterned Substrate.

This study provides experimental evidence regarding the mechanism of gallium nitride (GaN) selective-area growth (SAG) on a polished plateau-patterned sapphire substrate (PP-PSS), on which aluminum nitride (AlN) buffer layers are deposited under the same deposition conditions. The SAG of GaN was only observed on the plateau region of the PP-PSS, irrespective of the number of growth cycles. Indirect samples deposited on the bare c-plane substrate were prepared to determine the difference between the AlN buffer layers in the plateau region and silicon oxide (SiO2). The AlN buffer layer in the plateau region exhibited a higher surface energy, and its crystal orientation is indicated by AlN [001]. In contrast, regions other than the plateau region did not exhibit crystallinity and presented lower surface energies. The direct analysis results of PP-PSS using transmission electron microscopy (TEM) and electron backscattered diffraction (EBSD) are similar to the results of the indirect samples. Therefore, under the same conditions, the GaN SAG of the deposited layer is related to crystallinity, crystal orientation, and surface energy.

Proximal peroneal perforator flap, cadaveric study, and clinical applications for shallow defect reconstructions.

PURPOSE: Peroneal artery perforator offers a versatile range of microvascular tissue transfer methods from local flaps to vascularized osteocutaneous fibula flaps. It is one of the few flaps that can cover shallow defects that require thin and pliable skin paddles, such as in hands and feet (Han et al., 2018). The proximal region of the lower leg offers such flexible and thin flap compared to the middle and distal lower leg (Winters & de Jongh, 1999). However, the anatomy of the proximal peroneal artery perforator is relatively unknown in literature and its proximity to the common peroneal nerve (CPN) has not yet been studied. This study conducted a cadaveric study and put it in application into clinical settings. METHODS: Twenty lower leg specimens were dissected according to the methods of clinical proximal peroneal artery perforator flap harvest. Perforators arising in the proximal lower leg area of between 20 and 40 percentile of fibular length were inspected. Perforator length, location from fibular head, course, and location of CPN were recorded. Clinical reconstruction cases using the proximal lateral lower leg were analyzed. Six patients between the ages of thirty and seventy were included. Five cases were due to trauma, and one from mass excision, but all required thin and pliable flaps for reconstructions in hands or feet. Flaps were designed concentrical oval shapes, and harvest was done similarly to cadaveric perforator dissection, but perforator dissection was done only up to the required pedicle length. Perforator length, flap size, thickness, and long-term complications were recorded. RESULTS: Among 20 specimens, a total of 20 perforators were found in 18 cadavers (90%). Two specimens showed no perforators while two specimens showed multiple perforators. The perforators were located at an average of 101 mm from fibular head, with an average length of 55 mm ranging from 20 to 153 mm. The average size of perforator at origin was 2.0 mm, ranging from 1.0 to 3.6 mm. 45% showed septocutaneous course and 55% intramuscular course. Two out of 20 perforators were shown to arise from source vessels other than the peroneal artery. All clinical cases were successful without complications or debulking for contour shaping. Flap sizes ranged from 15 to 40 cm2 . Largest flap width was 5 cm, and all donor sites were primarily closed without complications. One year of follow-up showed no complications. CONCLUSION: Proximal peroneal artery perforator flap provides a reliable pedicle for a versatile tissue transfer. This study shows that the perforators of the proximal lateral lower leg often arise from vessels other than the peroneal artery, such as the anterior tibial artery or popliteal artery, as had been previously reported (Winters & de Jongh, 1999). Although the source vessel varies, perforator anatomy is at a safe distance from CPN. This variation of source vessels suggests a change in nomenclature to "proximal peroneal perforator flap." The clinical applications of this flap showed that it can be effectively used for reconstructions of shallow defects, such as in the hands and feet without secondary procedures for debulking.

ANGPTL4 stabilizes atherosclerotic plaques and modulates the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation.

Atherosclerosis, the leading cause of death, is a vascular disease of chronic inflammation. We recently showed that angiopoietin-like 4 (ANGPTL4) promotes cardiac repair by suppressing pathological inflammation. Given the fundamental contribution of inflammation to atherosclerosis, we assessed the role of ANGPTL4 in the development of atherosclerosis and determined whether ANGPTL4 regulates atherosclerotic plaque stability. We injected ANGPTL4 protein twice a week into atherosclerotic Apoe-/- mice and analyzed the atherosclerotic lesion size, inflammation, and plaque stability. In atherosclerotic mice, ANGPTL4 reduced atherosclerotic plaque size and vascular inflammation. In the atherosclerotic lesions and fibrous caps, the number of α-SMA(+), SM22α(+), and SM-MHC(+) cells was higher, while the number of CD68(+) and Mac2(+) cells was lower in the ANGPTL4 group. Most importantly, the fibrous cap was significantly thicker in the ANGPTL4 group than in the control group. Smooth muscle cells (SMCs) isolated from atherosclerotic aortas showed significantly increased expression of CD68 and Krüppel-like factor 4 (KLF4), a modulator of the vascular SMC phenotype, along with downregulation of α-SMA, and these changes were attenuated by ANGPTL4 treatment. Furthermore, ANGPTL4 reduced TNFα-induced NADPH oxidase 1 (NOX1), a major source of reactive oxygen species, resulting in the attenuation of KLF4-mediated SMC phenotypic changes. We showed that acute myocardial infarction (AMI) patients with higher levels of ANGPTL4 had fewer vascular events than AMI patients with lower levels of ANGPTL4 (p < 0.05). Our results reveal that ANGPTL4 treatment inhibits atherogenesis and suggest that targeting vascular stability and inflammation may serve as a novel therapeutic strategy to prevent and treat atherosclerosis. Even more importantly, ANGPTL4 treatment inhibited the phenotypic changes of SMCs into macrophage-like cells by downregulating NOX1 activation of KLF4, leading to the formation of more stable plaques.

Impact of the ultra-long 48 mm drug-eluting stent on procedural and clinical outcomes in patients with diffuse long coronary artery disease.

BACKGROUND: Diffuse coronary artery disease (CAD) is a prognostic factor after percutaneous coronary intervention (PCI) and requires multiple overlapping stent implantations. HYPOTHESIS: We investigated the impact of ultra-long 48 mm drug-eluting stent (DES) on procedural and clinical outcomes in real-world practice. METHODS: Patients who underwent DES implantation for a lesion length of >40 mm were selected from a prospective registry between 2019 and 2021. Patients treated with one or more ultra-long 48 mm DES were in the ultra-long DES group (n = 221). The others comprised the conventional DES group (n = 428). Procedural and clinical outcomes were compared after propensity score matching (PSM). The primary endpoint was a device-oriented composite outcome (DOCO) consisting of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 1-year follow-up. RESULTS: After PSM, 158 matched pairs of patients showed no differences in the baseline clinical and angiographic characteristics. The stent delivery failure rate, the use of guide-extension catheter or anchor balloon technique, and the procedural success rate were similar for both groups. Approximately two-thirds of lesions could be treated with one DES in the ultra-long DES group. At 1-year follow-up, the DOCO was similar for both groups (2.5% vs. 0.6%, p = .168). CONCLUSIONS: In daily clinical practice, ultra-long DES implantation is as safe and effective as multiple overlapping conventional DES implants in treating diffuse long CAD. However, ultra-long DES can reduce the number of stents. (Trial Registration: ClinicalTrials.gov Identifier: NCT02038127).

Evaluation of a biotin-based surrogate virus neutralization test for detecting postvaccination antibodies against SARS-CoV-2 variants in sera.

A severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) surrogate virus neutralization test (sVNT) was used to determine the degree of inhibition of binding between human angiotensin converting enzyme 2 (hACE2) and the receptor binding domain (RBD) of spike protein by neutralizing antibodies in a biosafety level 2 facility. Here, to improve the sensitivity and specificity of the commercial sVNT, we developed a new biotin based sVNT using biotinylated RBD and HRP conjugated streptavidin instead of HRP conjugated RBD for direct detection in an ELISA assay that strongly correlated to the FDA approved cPass sVNT commercial kit (R2 = 0.8521) and pseudo virus neutralization test (R2 = 0.9006) (pVNT). The biotin based sVNT was evaluated in 535 postvaccination serum samples corresponding to second and third boosts of AZD1222 and BNT162b2 vaccines of the wild type strain. We confirmed that the neutralizing antibodies against SARS-CoV-2 variants in second vaccination sera decreased after a median of 141.5 days. Furthermore, vaccination sera from BNT162b2-BNT162b2 vaccines maintained neutralizing antibodies for longer than those of AZD1222 only vaccination. In addition, both vaccines maintained high neutralizing antibodies in third vaccination sera against Omicron BA.2 after a median of 27 days, but neutralizing antibodies significantly decreased after a median of 141.5 days. Along with the cPass sVNT commercial kit, biotin based sVNTs may also be suitable for specifically detecting neutralizing antibodies against multiple SARS-CoV-2 variants; however, to initially monitor the neutralizing antibodies in vaccinated sera using high throughput screening, conventional PRNT could be replaced by sVNT to circumvent the inconvenience of a long test time.

Neurobiological Signatures of Auditory False Perception and Phantom Perception as a Consequence of Sensory Prediction Errors.

In this study, we hypothesized that top-down sensory prediction error due to peripheral hearing loss might influence sensorimotor integration using the efference copy (EC) signals as functional connections between auditory and motor brain areas. Using neurophysiological methods, we demonstrated that the auditory responses to self-generated sound were not suppressed in a group of patients with tinnitus accompanied by significant hearing impairment and in a schizophrenia group. However, the response was attenuated in a group with tinnitus accompanied by mild hearing impairment, similar to a healthy control group. The bias of attentional networks to self-generated sound was also observed in the subjects with tinnitus with significant hearing impairment compared to those with mild hearing impairment and healthy subjects, but it did not reach the notable disintegration found in those in the schizophrenia group. Even though the present study had significant constraints in that we did not include hearing loss subjects without tinnitus, these results might suggest that auditory deafferentation (hearing loss) may influence sensorimotor integration process using EC signals. However, the impaired sensorimotor integration in subjects with tinnitus with significant hearing impairment may have resulted from aberrant auditory signals due to sensory loss, not fundamental deficits in the reafference system, as the auditory attention network to self-generated sound is relatively well preserved in these subjects.

Neurodynamic correlates for the cross-frequency coupled transcranial alternating current stimulation during working memory performance.

Transcranial current stimulation is a neuromodulation technique used to modulate brain oscillations and, in turn, to enhance human cognitive function in a non-invasive manner. This study investigated whether cross-frequency coupled transcranial alternating current stimulation (CFC-tACS) improved working memory performance. Participants in both the tACS-treated and sham groups were instructed to perform a modified Sternberg task, where a combination of letters and digits was presented. Theta-phase/high-gamma-amplitude CFC-tACS was administered over electrode F3 and its four surrounding return electrodes (Fp1, Fz, F7, and C3) for 20 min. To identify neurophysiological correlates for the tACS-mediated enhancement of working memory performance, we analyzed EEG alpha and theta power, cross-frequency coupling, functional connectivity, and nodal efficiency during the retention period of the working memory task. We observed significantly reduced reaction times in the tACS-treated group, with suppressed treatment-mediated differences in frontal alpha power and unidirectional Fz-delta-phase to Oz-high-gamma-amplitude modulation during the second half of the retention period when network analyses revealed tACS-mediated fronto-occipital dissociative neurodynamics between alpha suppression and delta/theta enhancement. These findings indicate that tACS modulated top-down control and functional connectivity across the fronto-occipital regions, resulting in improved working memory performance. Our observations are indicative of the feasibility of enhancing cognitive performance by the CFC-formed tACS.

Validation of Biomarker-Based ABCD Score in Atrial Fibrillation Patients with a Non-Gender CHA2DS2-VASc Score 0-1: A Korean Multi-Center Cohort.

PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0-1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0-1.