CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy.

Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy and have also been reported in families with only a cataract phenotype. Dilated cardiomyopathy (DCM) is a disorder with a highly heterogeneous genetic etiology involving more than 60 causative genes, hindering genetic diagnosis. In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in NM_001289808.2:c.527A>G of CRYAB in one patient. The mutant alpha-B crystallin protein is predicted to have an extended strand with addition of 19 amino acid residues, p.(Ter176TrpextTer19), which may contribute to aggregation and increased hydrophobicity of alpha-B crystallin. The proband, diagnosed with DCM at age 32, had a history of bilateral congenital cataracts but had no evidence of myopathy or associated symptoms. He also has a 10-year-old child diagnosed with bilateral congenital cataracts with the same CRYAB variant. This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Experience of reassessing FBN1 variants of uncertain significance by gene-specific guidelines.

BACKGROUND: Despite the 2015 American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) guideline, many variants of FBN1 gene remain inconclusive. In line with publication of the FBN1-specific variant interpretation guideline by ClinGen in 2022, we reassessed variants of uncertain significance (VUS) in FBN1 gene found in our institution. METHODS: VUS found in the course of FBN1 sequencing between December 2015 and April 2022 were reassessed based on FBN1-specific variant interpretation guideline, review of updated literatures and additional genetic tests including family study and/or RNA study if available. RESULTS: Out of 695 patients who underwent FBN1 sequencing, 61 VUS were found in 69 patients. Among them, 38 VUS in 43 patients (62.3%) were reclassified as pathogenic and likely pathogenic variant ((L)PV), including 20 novel (L)PV. Major causes of reclassification were: (1) gene-specific modification of ACMG/AMP criteria, (2) updated literatures and (3) additional genetic tests. The most important evidence for reclassification was clarification of critical amino acid residues. CONCLUSIONS: After reassessing FBN1 variants according to FBN1-specific guideline and up-to-date database, a significant number of VUS was reclassified. Clinical laboratories are encouraged to perform variant reassessment at regular intervals or when there is a major change in the principle of variant interpretation.

Changes in the Remaining Iliac Artery According to Retrograde Flow after Aorto-Femoral Bypass in Abdominal Aortic Aneurysms.

BACKGROUND: Considering a patient's anatomy and vascular conditions, aorto-femoral bypass is a treatment approach for the open repair of abdominal aortic aneurysms. This study aimed at evaluating changes in the remnant iliac artery and their correlation with the preservation state of retrograde flow from femoral anastomosis. METHODS: Of 221 patients who underwent abdominal aortic aneurysm surgery between 2007 and 2022 in Pusan National University Hospital, 29 patients who underwent aorto-femoral bypass were included in this retrospective cohort study. Of these patients, 21 underwent aortobifemoral bypass and 8 underwent aortoiliac-and-femoral bypass. The change in size of the iliac artery from preoperative to postoperative and whether this difference in size depended on the status of postoperative retrograde flow were investigated. Additionally, factors affecting overall mortality and ischemic complications were identified. RESULTS: The median duration from operation to the last follow-up was 2069.5 days (about 5.7 years). The average age of the patients was 78.1 years, and the proportion of males was 75.9%. In cases of disappearance of postoperative retrograde flow from the femoral anastomosis, the postoperative iliac artery size was significantly reduced compared to its preoperative size (18.4 ± 18.9 mm vs. 13.2 ± 7.9 mm, respectively; P = 0.04). The group with maintained retrograde flow had significantly larger residual common iliac artery size than the group with disappearance of flow. (20.0 ± 28.0 mm vs. 14.6 ± 8.5 mm, respectively; P = 0.02). Disappearance of retrograde flow was a significant factor in the iliac artery size reduction after surgery (odds ratio, 2.5; 95% confidence interval, 1.9-5.3; P = 0.02). Three patients with maintained retrograde flow (18.8%) required intervention owing to an increase in the size of the iliac artery. The factors that significantly influenced overall death as analyzed by Cox proportional hazard regression were chronic obstructive pulmonary disease (hazard ratio, 36.8; 95% confidence interval, 1.6-870.0; P = 0.03), peripheral arterial occlusive disease (hazard ratio, 12.7; 95% confidence interval, 1.4-115.8; P = 0.02), and disappearance of retrograde flow (hazard ratio, 8.7; 95% confidence interval, 1.2-63.9; P = 0.03). CONCLUSIONS: Among the open repair methods for abdominal aortic aneurysms, if retrograde flow was not maintained through femoral anastomosis when aorto-femoral bypass was performed, the size of the remaining iliac artery decreased. However, loss of retrograde flow increased long-term mortality. When aorto-femoral bypass is performed, regular imaging follow-up is necessary at appropriate intervals to check the remnant iliac artery and retrograde flow.

Rejoining Veins for Forced Maturation of Small-Caliber Arteriovenous Fistula.

BACKGROUND: To evaluate the efficacy of rejoining mainstream and accessory veins for forced maturation of autogenous arteriovenous fistula (AVF). METHODS: Twenty-three patients who underwent forced maturation through vein rejoining between January 2018 and September 2022 were included. In cases where AVF maturation failure due to the presence of accessory veins, rejoining was primarily considered when distinguishing the main branch becomes challenging. This difficulty typically occurs when the sizes of the 2 vessels are nearly equal and the combined diameters of these veins exceed 6 mm. RESULTS: The mean age and follow-up duration were 57.39 ± 16.22 years and 965.65 ± 573.42 days, respectively. Rejoining of both arterial and venous cannulation sites was performed in 11 patients (47.8%), and rejoining of only the venous cannulation site or only the arterial cannulation site was performed in 11 patients (47.8%) and 1 patient (4.3%), respectively. The mean vein size was 0.35 ± 0.06 cm before rejoining and 0.69 ± 0.07 cm after surgery, indicating a significant increase in size (P < 0.01), whereas the flow did not change significantly following rejoining surgery. Maturation and cannulation success was 100%. The 1-year primary patency rate after surgery was 82.0%. During the follow-up period, 34.8% of the patients required additional percutaneous transluminal angioplasty to maintain patency, and 2 patients (11.8%) had stenosis in the rejoined section. CONCLUSIONS: Rejoining surgery is an effective method for achieving AVF maturation in patients with accessory veins when identification of the mainstream vein is difficult, and this method may be considered when achieving maturation by sacrificing 1 vein is expected to be challenging.

Overcoming challenges associated with identifying FBN1 deep intronic variants through whole-genome sequencing.

BACKGROUND: Marfan syndrome (MFS), caused by pathogenic variants of FBN1 (fibrillin-1), is a systemic connective tissue disorder with variable phenotypes and treatment responsiveness depending on the variant. However, a significant number of individuals with MFS remain genetically unexplained. In this study, we report novel pathogenic intronic variants in FBN1 in two unrelated families with MFS. METHODS: We evaluated subjects with suspected MFS from two unrelated families using Sanger sequencing or multiplex ligation-dependent probe amplification of FBN1 and/or panel-based next-generation sequencing. As no pathogenic variants were identified, whole-genome sequencing was performed. Identified variants were analyzed by reverse transcription-PCR and targeted sequencing of FBN1 mRNA harvested from peripheral blood or skin fibroblasts obtained from affected probands. RESULTS: We found causative deep intronic variants, c.6163+1484A>T and c.5788+36C>A, in FBN1. The splicing analysis revealed an insertion of in-frame or out-of-frame intronic sequences of the FBN1 transcript predicted to alter function of calcium-binding epidermal growth factor protein domain. Family members carrying c.6163+1484A>T had high systemic scores including prominent skeletal features and aortic dissection with lesser aortic dilatation. Family members carrying c.5788+36C>A had more severe aortic root dilatation without aortic dissection. Both families had ectopia lentis. CONCLUSION: Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies. This study expands the mutation spectrum of FBN1 and points out the importance of intronic sequence analysis and the need for integrative functional studies in MFS diagnosis.

The optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: a multicenter cohort study.

BACKGROUND/AIMS: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia. METHODS: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated. RESULTS: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008). CONCLUSIONS: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.

The Performance Analysis of PSO-ResNet for the Fault Diagnosis of Vibration Signals Based on the Pipeline Robot.

In the context of pipeline robots, the timely detection of faults is crucial in preventing safety incidents. In order to ensure the reliability and safety of the entire application process, robots' fault diagnosis techniques play a vital role. However, traditional diagnostic methods for motor drive end-bearing faults in pipeline robots are often ineffective when the operating conditions are variable. An efficient solution for fault diagnosis is the application of deep learning algorithms. This paper proposes a rolling bearing fault diagnosis method (PSO-ResNet) that combines a Particle Swarm Optimization algorithm (PSO) with a residual network. A number of vibration signal sensors are placed at different locations in the pipeline robot to obtain vibration signals from different parts. The input to the PSO-ResNet algorithm is a two-bit image obtained by continuous wavelet transform of the vibration signal. The accuracy of this fault diagnosis method is compared with different types of fault diagnosis algorithms, and the experimental analysis shows that PSO-ResNet has higher accuracy. The algorithm was also deployed on an Nvidia Jetson Nano and a Raspberry Pi 4B. Through comparative experimental analysis, the proposed fault diagnosis algorithm was chosen to be deployed on the Nvidia Jetson Nano and used as the core fault diagnosis control unit of the pipeline robot for practical scenarios. However, the PSO-ResNet model needs further improvement in terms of accuracy, which is the focus of future research work.

Variation spectrum of MECP2 in Korean patients with Rett and Rett-like syndrome: a literature review and reevaluation of variants based on the ClinGen guideline.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by variants in MECP2. Emerging evidence of ethnic specificity of genetic variations has allowed precise diagnostic approaches with tailored therapies. In this study, we reviewed the variation spectrum of MECP2 in Korean RTT(-like) patients and compared it with previous reports in multiple ethnic groups. We reevaluated variants found in Korean RTT patients according to the new Clinical Genome Resource guideline to reinterpret and reclassify variants of uncertain significance in MECP2. Among 377 cases, 56 (14.9%) showed pathogenic variants, and three novel variants, p.(Ala277Argfs*7), p.(Ala378Glyfs*8), and p.(Arg270_Ser332del), were identified. Comprehensive data from Korea revealed an overall consistent variation spectrum with those from other ethnicities. Through the reevaluation of variants, nine that previously had insufficient evidence for pathogenicity were reclassified into pathogenic variants. Our study provided insight on the genetic contribution of MECP2 in RTT and a useful background for genetic counseling in the Korean population.

A Fault Diagnosis System for a Pipeline Robot Based on Sound Signal Recognition.

Timely and accurate identification of fault types at the early stage of minor faults is significant for cutting off fault evolution. In order to have a clear understanding of the pipeline robot's own situation in the pipeline, this paper proposes a fault diagnosis system for pipeline robots based on sound signal recognition. This can effectively reduce the probability of serious faults such as shutdown and loss of control in the pipeline without affecting the safe operation of the pipeline robot, which is a key issue to improve the reliability of the pipeline robot. The system consists of a combination of three parts: hardware, software, and algorithm. On the one hand, Raspberry Pi is the core module, while on the other hand, it is also responsible for the data transmission between the various modules, including storing the original sound signals collected by the sensors and transmitting the diagnosis results to the upper computer software interface. The proposed system is validated on the dataset collected by the data experimentation platform. The experimental results show that the proposed fault prediction method obtains advanced results on this dataset, verifying the effectiveness and stability of the proposed fault diagnosis system for pipeline robots based on sound signal recognition.

Predictive Values of Procalcitonin and Presepsin for Acute Kidney Injury and 30-Day Hospital Mortality in Patients with COVID-19.

Background and Objectives: Acute kidney injury (AKI) is a common complication in patients with coronavirus disease 2019 (COVID-19). We investigated the values of procalcitonin (PCT) and presepsin (PSS) for predicting AKI and 30-day hospital mortality in patients with COVID-19. Materials and Methods: We retrospectively evaluated 151 patients with COVID-19 who were admitted to the hospital via the emergency department. The diagnosis of AKI was based on the Kidney Disease: Improving Global Outcomes clinical practice guidelines. Results: The median patient age was 77 years, and 86 patients (57%) were male. Fifty-six patients (37.1%) developed AKI, and 19 patients (12.6%) died within 30 days of hospital admission. PCT and PSS levels were significantly higher in patients with AKI and non-survivors. The cutoff values of PCT levels for predicting AKI and mortality were 2.26 ng/mL (sensitivity, 64.3%; specificity, 89.5%) and 2.67 ng/mL (sensitivity, 68.4%; specificity, 77.3%), respectively. The cutoff values of PSS levels for predicting AKI and mortality were 572 pg/mL (sensitivity, 66.0%; specificity, 69.1%) and 865 pg/mL (sensitivity, 84.6%; specificity, 76.0%), respectively. Conclusion: PCT and PSS are valuable biomarkers for predicting AKI and 30-day hospital mortality in patients with COVID-19.

Macrophage-Inducible C-Type Lectin Signaling Exacerbates Acetaminophen-Induced Liver Injury by Promoting Kupffer Cell Activation in Mice.

Overdose of acetaminophen (APAP) has become one of the most frequent causes of acute liver failure. Macrophage-inducible C-type lectin (Mincle) acts as a key moderator in immune responses by recognizing spliceosome-associated protein 130 (SAP130), which is an endogenous ligand released by necrotic cells. This study aims to explore the function of Mincle in APAP-induced hepatotoxicity. Wild-type (WT) and Mincle knockout (KO) mice were used to induce acute liver injury by injection of APAP. The hepatic expressions of Mincle, SAP130, and Mincle signaling intermediate (Syk) were markedly upregulated after the APAP challenge. Mincle KO mice showed attenuated injury in the liver, as shown by reduced pathologic lesions, decreased alanine aminotransferase and aspartate aminotransferase levels, downregulated levels of inflammatory cytokines, and decreased neutrophil infiltration. Consistently, inhibition of Syk signaling by GS9973 alleviated APAP hepatotoxicity. Most importantly, Kupffer cells (KCs) were found as the major cellular source of Mincle. The depletion of KCs abolished the detrimental role of Mincle, and the adoptive transfer of WT KC to Mincle KO mice partially reversed the hyporesponsiveness to hepatotoxicity induced by APAP. Furthermore, the expression levels of interleukin (IL)-1ß and neutrophil-attractant CXC chemokines were substantially lower in KCs isolated from APAP-treated Mincle KO mice compared with those from WT mice. Similar results were found in primary Mincle KO KCs treated with a ligand of Mincle (trehalose-6,6-dibehenate) or in conditioned media obtained from APAP-treated hepatocytes. Collectively, Mincle can regulate the inflammatory response of KCs, which is necessary for the complete progression of hepatotoxicity induced by APAP. SIGNIFICANCE STATEMENT: Acetaminophen (APAP) overdose is becoming a main cause of drug-induced acute liver damage in the developed world. This study showed that macrophage-inducible C-type lectin (Mincle) deletion or inhibition of Mincle downstream signaling attenuates APAP hepatotoxicity. Furthermore, Mincle as a modulator of Kupffer cell activation contributes to the full process of hepatotoxicity induced by APAP. This mechanism will offer valuable insights to overcome the limitation of APAP hepatotoxicity treatment.

Prevalence and clinical characterization of BRCA1 and BRCA2 mutations in Korean patients with epithelial ovarian cancer.

This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two-hundred and ninety-eight Korean women diagnosed with high-grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P < .001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first-line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients.

Ferroptosis Affects the Progression of Nonalcoholic Steatohepatitis via the Modulation of Lipid Peroxidation-Mediated Cell Death in Mice.

Oxidative stress and its associated lipid peroxidation play a key role in nonalcoholic steatohepatitis (NASH). Ferroptosis is a recently recognized type of cell death characterized by an iron-dependent and lipid peroxidation-mediated nonapoptotic cell death. We demonstrate the impact of ferroptosis on the progression of NASH induced by methionine/choline-deficient diet (MCD) feeding for 10 days. RSL-3 (a ferroptosis inducer) treatment showed decreased hepatic expression of glutathione peroxidase 4 (GPX4) and conversely increased 12/15-lipoxygenase, and apoptosis-inducing factor, indicating that ferroptosis plays a key role in NASH-related lipid peroxidation and its associated cell death. Consistently, levels of serum biochemical, hepatic steatosis, inflammation, and apoptosis in MCD-fed mice were exacerbated with RSL-3 treatment. However, MCD-fed mice treated with sodium selenite (a GPX4 activator) showed increase of hepatic GPX4, accompanied by reduced NASH severity. To chelate iron, deferoxamine mesylate salt was used. Administration of deferoxamine mesylate salt significantly reduced NASH severity and abolished the harmful effects of RSL-3 in MCD-fed mice. Finally, treatment with liproxstatin-1 (a ferroptosis inhibitor) repressed hepatic lipid peroxidation and its associated cell death, resulting in decreased NASH severity. Consistent with the in vivo findings, modulation of ferroptosis/GPX4 affected hepatocellular death in palmitic acid-induced in vitro NASH milieu. We conclude that GPX4 and its related ferroptosis might play a major role in the development of NASH.

Toll-Like Receptor 5 Signaling Ameliorates Liver Fibrosis by Inducing Interferon ß-Modulated IL-1 Receptor Antagonist in Mice.

Bacterial flagellin, recognized by cell surface of Toll-like receptor (TLR) 5, is a potent activator of many types of cells, leading to the activation of innate or adaptive immunity, which are pivotal in regulating fibrotic process. However, the exact role of TLR5 signaling in hepatic fibrogenesis remains unclear, and this study aims to elucidate its underlying mechanisms. Flagellin was injected to hepatotoxin- and cholestasis-induced liver fibrosis murine models. Flagellin-induced TLR5 activation significantly decreased the severity of liver fibrosis. Interestingly, the expression levels of IL-1 receptor antagonist (IL1RN) and interferon (IFN)ß markedly increased in fibrotic livers on flagellin treatment. Consistently, in vivo activation of TLR5 signaling markedly increased IFNß and IL1RN expression in the livers. Notably, flagellin injection significantly exacerbated the severity of liver fibrosis in IFN-α/ß receptor 1 (IFNAR1) knockout mice. Furthermore, hepatic expression of IL1RN in the fibrotic livers of IFNAR1 knockout mice was significantly lower than those of wild-type mice. In support of these findings, flagellin-mediated IL1RN production is not sufficient to alleviate the severity of hepatic fibroinflammatory responses in IFNAR1-deficient milieu. Finally, hepatic stellate cells treated with IL1RN had significantly decreased cellular activation and its associated fibrogenic responses. Collectively, manipulation of TLR5 signaling may be a promising therapeutic strategy for the treatment of liver fibrosis.

RGDiNet: Efficient Onboard Object Detection with Faster R-CNN for Air-to-Ground Surveillance.

An essential component for the autonomous flight or air-to-ground surveillance of a UAV is an object detection device. It must possess a high detection accuracy and requires real-time data processing to be employed for various tasks such as search and rescue, object tracking and disaster analysis. With the recent advancements in multimodal data-based object detection architectures, autonomous driving technology has significantly improved, and the latest algorithm has achieved an average precision of up to 96%. However, these remarkable advances may be unsuitable for the image processing of UAV aerial data directly onboard for object detection because of the following major problems: (1) Objects in aerial views generally have a smaller size than in an image and they are uneven and sparsely distributed throughout an image; (2) Objects are exposed to various environmental changes, such as occlusion and background interference; and (3) The payload weight of a UAV is limited. Thus, we propose employing a new real-time onboard object detection architecture, an RGB aerial image and a point cloud data (PCD) depth map image network (RGDiNet). A faster region-based convolutional neural network was used as the baseline detection network and an RGD, an integration of the RGB aerial image and the depth map reconstructed by the light detection and ranging PCD, was utilized as an input for computational efficiency. Performance tests and evaluation of the proposed RGDiNet were conducted under various operating conditions using hand-labeled aerial datasets. Consequently, it was shown that the proposed method has a superior performance for the detection of vehicles and pedestrians than conventional vision-based methods.

DBSCAN-Based Tracklet Association Annealer for Advanced Multi-Object Tracking.

Recently, as the demand for technological advancement in the field of autonomous driving and smart video surveillance is gradually increasing, considerable progress in multi-object tracking using deep neural networks has been achieved, and its application field is also expanding. However, various problems have not been fully addressed owing to the inherent limitations in video cameras, such as the tracking of objects in an occluded environment. Therefore, in this study, we propose a density-based object tracking technique redesigned based on DBSCAN, which has high robustness against noise and is excellent for nonlinear clustering. Moreover, it improves the noise vulnerability inherent to multi-object tracking, reduces the difficulty of trajectory separation, and facilitates real-time processing through simple structural expansion. Through performance test evaluation, it was confirmed that by using the proposed technique, several performance indices were improved compared to the existing tracking technique. In particular, when added as a post processor to the existing tracker, the tracking performance owing to noise suppression was considerably improved by more than 10%. Thus, the proposed method can be applied in industrial environments, such as real pedestrian analysis and surveillance security systems.

Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging.

Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget's disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Here, we report the synthesis of bone-targeting ferritin nanoparticles for bone imaging. Ferritin, which is a globular protein composed of 24 subunits, was employed as a carrier molecule. Bone-targeting peptides that have been reported to specifically bind to osteoblast and hydroxyapatite were genetically fused to the N-terminus of the heavy subunit of human ferritin in such a way that the peptides faced outwards. Ferritin nanoparticles with fused bone-targeting peptides were also conjugated with fluorescent dyes to assess their binding ability using osteoblast imaging and a hydroxyapatite binding assay; the results showed their specific binding with osteoblasts and hydroxyapatite. Using in vivo analysis, a specific fluorescent signal from the lower limb was observed, demonstrating a highly selective affinity of the modified nanoparticles for the bone tissue. These promising results indicate a specific binding ability of the nanoscale targeting system to the bone tissue, which might potentially be used for bone disease therapy in future clinical applications.

Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin-induced liver fibrosis and biliary fibrosis in mice.

Although numerous studies have suggested that canonical IκB kinases (IKK) play a key role in the progression of liver fibrosis, the role of non-canonical IKKε and TANK-binding kinase 1 (TBK1) on the development and progression of liver fibrosis remains unclear. To demonstrate such issue, repeated injection of CCl4 was used to induce hepatotoxin-mediated chronic liver injury and biliary fibrosis was induced by 0.1% diethoxycarbonyl-1, 4-dihydrocollidine diet feeding for 4 weeks. Mice were orally administered with amlexanox (25, 50, and 100 mg/kg) during experimental period. Significantly increased levels of TBK1 and IKKε were observed in fibrotic livers or hepatic stellate cells (HSCs) isolated from fibrotic livers. Interestingly, amlexanox treatment significantly inhibited the phosphorylation of TBK1 and IKKε accompanied by reduced liver injury as confirmed by histopathologic analysis, decreased serum biochemical levels and fibro-inflammatory responses. Additionally, treatment of amlexanox promoted the fibrosis resolution. In accordance with these findings, amlexanox treatment suppressed HSC activation and its related fibrogenic responses by partially inhibiting signal transducer and activator of transcription 3. Furthermore, amlexanox decreased the activation and inflammatory responses in Kupffer cells. Collectively, we found that inhibition of the TBK1 and IKKε by amlexanox is a promising therapeutic strategy to cure liver fibrosis.

Quantitative and Qualitative QC of Next-Generation Sequencing for Detecting Somatic Variants: An Example of Detecting Clonal Hematopoiesis of Indeterminate Potential.

BACKGROUND: Because next-generation sequencing (NGS) for detecting somatic mutations has been adopted in clinical fields, both qualitative and quantitative QC of the somatic variants through whole coding regions detected by NGS is crucial. However, specific applications or guidelines, especially for quantitative QC, are currently insufficient. Our goal was to devise a practical approach for both quantitative and qualitative QC using an example of detecting clonal hematopoiesis of indeterminate potential (CHIP). METHODS: We applied the QC scheme using commercial reference materials and in-house QC materials (IQCM) composed of haplotype map and cancer cell lines for monitoring CHIP. RESULTS: This approach efficiently validated a customized CHIP NGS assay. Accuracy, analytical sensitivity, analytical specificity, qualitative precision (concordance), and limit of detection achieved were 99.87%, 98.53%, 100.00%, 100.00%, and 1.00%, respectively. The quantitative precision analysis also had a higher CV percentage at a lower alternative read depth (R2 = 0.749∼0.858). Use of IQCM ensured more than 100-fold reduction in the cost per run compared with that achieved using commercial reference materials. CONCLUSION: Our approach determined the general analytical performance of NGS for detecting CHIP and recognized limitations such as lower precision at a lower level of variant burden. This approach could also be theoretically expanded to a general NGS assay for detecting somatic variants. Considering the reliable NGS results and cost-effectiveness, we propose the use of IQCM for QC of NGS assays at clinical laboratories.