Longitudinal Change in Brain Functional Connectivity with Herpes Zoster Patients: Neuroimaging Case Series.

The exact mechanism involved in the development of postherpetic neuralgia (PHN) is not yet known. The objective of this study was to evaluate longitudinal functional connectivity (FC) changes in the neuroimaging case series of patients with acute herpes zoster (HZ). Cases: This study included five patients who had symptoms of HZ. Functional magnetic resonance imaging was conducted at enrollment and 3 months to determine FC changes. Of the five patients, three developed PHN. In the PHN subjects, the FC of the left superior frontal gyrus (SFG) and the right inferior frontal gyrus (IFG) were activated. The left SFG is known to contribute to higher cognitive functions and working memory. The right IFG is associated with pain processing and empathy for pain. Conclusions: Although only a few patients were enrolled in this study, the PHN could be affected by pain itself, as well as pain memory and psychological aspects such as empathy for pain.

A method for early diagnosis of lung cancer from tumor originated DNA fragments using plasma cfDNA methylome and fragmentome profiles.

Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients.

Proposed New AV-Type Test-Bed for Accurate and Reliable Fish-Eye Lens Camera Self-Calibration.

The fish-eye lens camera has a wide field of view that makes it effective for various applications and sensor systems. However, it incurs strong geometric distortion in the image due to compressive recording of the outer part of the image. Such distortion must be interpreted accurately through a self-calibration procedure. This paper proposes a new type of test-bed (the AV-type test-bed) that can effect a balanced distribution of image points and a low level of correlation between orientation parameters. The effectiveness of the proposed test-bed in the process of camera self-calibration was verified through the analysis of experimental results from both a simulation and real datasets. In the simulation experiments, the self-calibration procedures were performed using the proposed test-bed, four different projection models, and five different datasets. For all of the cases, the Root Mean Square residuals (RMS-residuals) of the experiments were lower than one-half pixel. The real experiments, meanwhile, were carried out using two different cameras and five different datasets. These results showed high levels of calibration accuracy (i.e., lower than the minimum value of RMS-residuals: 0.39 pixels). Based on the above analyses, we were able to verify the effectiveness of the proposed AV-type test-bed in the process of camera self-calibration.

Analysis of Fish-Eye Lens Camera Self-Calibration.

The fish-eye lens camera offers the advantage of efficient acquisition of image data through a wide field of view. However, unlike the popular perspective projection camera, a strong distortion effect appears as the periphery of the image is compressed. Such characteristics must be precisely analyzed through camera self-calibration. In this study, we carried out a fish-eye lens camera self-calibration while considering different types of test objects and projection models. Self-calibration was performed using the V-, A-, Plane-, and Room-type test objects. In the fish-eye lens camera, the V-type test object was the most advantageous for ensuring the accuracy of the principal point coordinates and focal length, because the correlations between parameters were relatively low. On the other hand, the other test objects were advantageous for ensuring the accuracy of distortion parameters because of the well-distributed image points. Based on the above analysis, we proposed, an accurate fish-eye lens camera self-calibration method that applies the V-type test object. The RMS-residuals of the proposed method were less than 1 pixel.

Effect of Zn on Pore Characteristics in Lotus-Type Porous Cu.

The effect of Zn on pore characteristics in lotus-type porous Cu alloy was investigated. The lotustype porous Cu-Zn alloys were fabricated with Zn content from 0.01 to 0.1 at% by the centrifugal casting method. The results demonstrated that the porosity was rarely affected by Zn content. However, the average pore diameter and pore number density of the lotus type porous Cu-Zn alloys were significantly affected by the Zn content. The average pore diameter decreased as the Zn content increased up to 0.01 at%, and then increased as the Zn content increased up to 0.1 at%. In contrast, the variations in the pore number density of the lotus-type porous Cu-Zn alloys showed the reversed tendency with respect to that of the average pore diameter. The increase in heterogeneous nucleation sites for pores attributed to the decreased average pore diameter and the increased pore number density.

Effects of Heat Treatment on Interfacial Behavior and Bonding Strength of Surface Activated Bonding Ti-Al Laminate.

The surface activated bonding (SAB) method generally has the advantage of high bonding strength, low contact resistance, and high microstructural stability at room temperature. In this study, Ti-Al laminates were produced by surface activated bonding with aluminum and titanium foils. Heat treatment was conducted at the temperature range from 200 to 550 °C in vacuum. The bonding strength Ti-Al laminates was measured by a peel test, and the interfacial characteristics were investigated microstructural observation. The results showed that the bonding strength was the highest with heat treatment at 400 °C, microstructure observation revealed that the bonding strength of the Ti-Al laminate was influenced by the interfacial characteristics.

Segmentation of Planar Surfaces from Laser Scanning Data Using the Magnitude of Normal Position Vector for Adaptive Neighborhoods.

Diverse approaches to laser point segmentation have been proposed since the emergence of the laser scanning system. Most of these segmentation techniques, however, suffer from limitations such as sensitivity to the choice of seed points, lack of consideration of the spatial relationships among points, and inefficient performance. In an effort to overcome these drawbacks, this paper proposes a segmentation methodology that: (1) reduces the dimensions of the attribute space; (2) considers the attribute similarity and the proximity of the laser point simultaneously; and (3) works well with both airborne and terrestrial laser scanning data. A neighborhood definition based on the shape of the surface increases the homogeneity of the laser point attributes. The magnitude of the normal position vector is used as an attribute for reducing the dimension of the accumulator array. The experimental results demonstrate, through both qualitative and quantitative evaluations, the outcomes' high level of reliability. The proposed segmentation algorithm provided 96.89% overall correctness, 95.84% completeness, a 0.25 m overall mean value of centroid difference, and less than 1° of angle difference. The performance of the proposed approach was also verified with a large dataset and compared with other approaches. Additionally, the evaluation of the sensitivity of the thresholds was carried out. In summary, this paper proposes a robust and efficient segmentation methodology for abstraction of an enormous number of laser points into plane information.

Bore-Sight Calibration of Multiple Laser Range Finders for Kinematic 3D Laser Scanning Systems.

The Simultaneous Localization and Mapping (SLAM) technique has been used for autonomous navigation of mobile systems; now, its applications have been extended to 3D data acquisition of indoor environments. In order to reconstruct 3D scenes of indoor space, the kinematic 3D laser scanning system, developed herein, carries three laser range finders (LRFs): one is mounted horizontally for system-position correction and the other two are mounted vertically to collect 3D point-cloud data of the surrounding environment along the system's trajectory. However, the kinematic laser scanning results can be impaired by errors resulting from sensor misalignment. In the present study, the bore-sight calibration of multiple LRF sensors was performed using a specially designed double-deck calibration facility, which is composed of two half-circle-shaped aluminum frames. Moreover, in order to automatically achieve point-to-point correspondences between a scan point and the target center, a V-shaped target was designed as well. The bore-sight calibration parameters were estimated by a constrained least squares method, which iteratively minimizes the weighted sum of squares of residuals while constraining some highly-correlated parameters. The calibration performance was analyzed by means of a correlation matrix. After calibration, the visual inspection of mapped data and residual calculation confirmed the effectiveness of the proposed calibration approach.

Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer.

BACKGROUND: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups.

BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.

The Effects of an Order-Assist Mobile Application on Pediatric Anesthesia Safety: An Observational Study.

Pediatric anesthesia requires the rapid creation, communication, and execution of anesthesia orders, and there is a risk of human error. The authors developed an order-assisted mobile application (app) to reduce human error during pediatric anesthesia preparation. The authors conducted an observational study that compared the effects of the application by comparing anesthesiologists' errors, nurses' errors, nurses leaving the operating room, and delays in surgery, between the Conventional group (n = 101) and the App group (n = 101). The app was associated with reduced human error by anesthesiologists and nurses, and it lowered the frequency and duration of nurses leaving the operating room during anesthesia. In addition, the authors surveyed anesthesia nurses regarding the effectiveness of the app. The nurses confirmed that the app was convenient and reduced human error. This study revealed that the order-assisted mobile app developed by a pediatric anesthesiologist could reduce human errors by anesthesiologists and nurses during pediatric anesthesia preparation.

Conservation implications of elucidating the Korean wolf taxonomic ambiguity through whole-genome sequencing.

The taxonomic status of the now likely extirpated Korean Peninsula wolf has been extensively debated, with some arguing it represents an independent wolf lineage, Canis coreanus. To investigate the Korean wolf's genetic affiliations and taxonomic status, we sequenced and analysed the genomes of a Korean wolf dated to the beginning of the 20th century, and a captive wolf originally from the Pyongyang Central Zoo. Our results indicated that the Korean wolf bears similar genetic ancestry to other regional East Asian populations, therefore suggesting it is not a distinct taxonomic lineage. We identified regional patterns of wolf population structure and admixture in East Asia with potential conservation consequences in the Korean Peninsula and on a regional scale. We find that the Korean wolf has similar genomic diversity and inbreeding to other East Asian wolves. Finally, we show that, in contrast to the historical sample, the captive wolf is genetically more similar to wolves from the Tibetan Plateau; hence, Korean wolf conservation programmes might not benefit from the inclusion of this specimen.

KOREF_S1: phased, parental trio-binned Korean reference genome using long reads and Hi-C sequencing methods.

BACKGROUND: KOREF is the Korean reference genome, which was constructed with various sequencing technologies including long reads, short reads, and optical mapping methods. It is also the first East Asian multiomic reference genome accompanied by extensive clinical information, time-series and multiomic data, and parental sequencing data. However, it was still not a chromosome-scale reference. Here, we updated the previous KOREF assembly to a new chromosome-level haploid assembly of KOREF, KOREF_S1v2.1. Oxford Nanopore Technologies (ONT) PromethION, Pacific Biosciences HiFi-CCS, and Hi-C technology were used to build the most accurate East Asian reference assembled so far. RESULTS: We produced 705 Gb ONT reads and 114 Gb Pacific Biosciences HiFi reads, and corrected ONT reads by Pacific Biosciences reads. The corrected ultra-long reads reached higher accuracy of 1.4% base errors than the previous KOREF_S1v1.0, which was mainly built with short reads. KOREF has parental genome information, and we successfully phased it using a trio-binning method, acquiring a near-complete haploid-assembly. The final assembly resulted in total length of 2.9 Gb with an N50 of 150 Mb, and the longest scaffold covered 97.3% of GRCh38's chromosome 2. In addition, the final assembly showed high base accuracy, with <0.01% base errors. CONCLUSIONS: KOREF_S1v2.1 is the first chromosome-scale haploid assembly of the Korean reference genome with high contiguity and accuracy. Our study provides useful resources of the Korean reference genome and demonstrates a new strategy of hybrid assembly that combines ONT's PromethION and PacBio's HiFi-CCS.

LT1, an ONT long-read-based assembly scaffolded with Hi-C data and polished with short reads.

We present LT1, the first high-quality human reference genome from the Baltic States. LT1 is a female de novo human reference genome assembly, constructed using 57× nanopore long reads and polished using 47× short paired-end reads. We utilized 72 GB of Hi-C chromosomal mapping data for scaffolding, to maximize assembly contiguity and accuracy. The contig assembly of LT1 was 2.73 Gbp in length, comprising 4490 contigs with an NG50 value of 12.0 Mbp. After scaffolding with Hi-C data and manual curation, the final assembly has an NG50 value of 137 Mbp and 4699 scaffolds. Assessment of gene prediction quality using Benchmarking Universal Single-Copy Orthologs (BUSCO) identified 89.3% of the single-copy orthologous genes included in the benchmark. Detailed characterization of LT1 suggests it has 73,744 predicted transcripts, 4.2 million autosomal SNPs, 974,616 short indels, and 12,079 large structural variants. These data may be used as a benchmark for further in-depth genomic analyses of Baltic populations.

Polygenic risk score validation using Korean genomes of 265 early-onset acute myocardial infarction patients and 636 healthy controls.

BACKGROUND: The polygenic risk score (PRS) developed for coronary artery disease (CAD) is known to be effective for classifying patients with CAD and predicting subsequent events. However, the PRS was developed mainly based on the analysis of Caucasian genomes and has not been validated for East Asians. We aimed to evaluate the PRS in the genomes of Korean early-onset AMI patients (n = 265, age ≤50 years) following PCI and controls (n = 636) to examine whether the PRS improves risk prediction beyond conventional risk factors. RESULTS: The odds ratio of the PRS was 1.83 (95% confidence interval [CI]: 1.69-1.99) for early-onset AMI patients compared with the controls. For the classification of patients, the area under the curve (AUC) for the combined model with the six conventional risk factors (diabetes mellitus, family history of CAD, hypertension, body mass index, hypercholesterolemia, and current smoking) and PRS was 0.92 (95% CI: 0.90-0.94) while that for the six conventional risk factors was 0.91 (95% CI: 0.85-0.93). Although the AUC for PRS alone was 0.65 (95% CI: 0.61-0.69), adding the PRS to the six conventional risk factors significantly improved the accuracy of the prediction model (P = 0.015). Patients with the upper 50% of PRS showed a higher frequency of repeat revascularization (hazard ratio = 2.19, 95% CI: 1.47-3.26) than the others. CONCLUSIONS: The PRS using 265 early-onset AMI genomes showed improvement in the identification of patients in the Korean population and showed potential for genomic screening in early life to complement conventional risk prediction.

Korean Genome Project: 1094 Korean personal genomes with clinical information.

We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.

Object-Based Integration of Photogrammetric and LiDAR Data for Automated Generation of Complex Polyhedral Building Models.

This research is concerned with a methodology for automated generation of polyhedral building models for complex structures, whose rooftops are bounded by straight lines. The process starts by utilizing LiDAR data for building hypothesis generation and derivation of individual planar patches constituting building rooftops. Initial boundaries of these patches are then refined through the integration of LiDAR and photogrammetric data and hierarchical processing of the planar patches. Building models for complex structures are finally produced using the refined boundaries. The performance of the developed methodology is evaluated through qualitative and quantitative analysis of the generated building models from real data.

Chromosome-scale assembly comparison of the Korean Reference Genome KOREF from PromethION and PacBio with Hi-C mapping information.

BACKGROUND: Long DNA reads produced by single-molecule and pore-based sequencers are more suitable for assembly and structural variation discovery than short-read DNA fragments. For de novo assembly, Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are the favorite options. However, PacBio's SMRT sequencing is expensive for a full human genome assembly and costs more than $40,000 US for 30× coverage as of 2019. ONT PromethION sequencing, on the other hand, is 1/12 the price of PacBio for the same coverage. This study aimed to compare the cost-effectiveness of ONT PromethION and PacBio's SMRT sequencing in relation to the quality. FINDINGS: We performed whole-genome de novo assemblies and comparison to construct an improved version of KOREF, the Korean reference genome, using sequencing data produced by PromethION and PacBio. With PromethION, an assembly using sequenced reads with 64× coverage (193 Gb, 3 flowcell sequencing) resulted in 3,725 contigs with N50s of 16.7 Mb and a total genome length of 2.8 Gb. It was comparable to a KOREF assembly constructed using PacBio at 62× coverage (188 Gb, 2,695 contigs, and N50s of 17.9 Mb). When we applied Hi-C-derived long-range mapping data, an even higher quality assembly for the 64× coverage was achieved, resulting in 3,179 scaffolds with an N50 of 56.4 Mb. CONCLUSION: The pore-based PromethION approach provided a high-quality chromosome-scale human genome assembly at a low cost with long maximum contig and scaffold lengths and was more cost-effective than PacBio at comparable quality measurements.

Zolpidem-Induced Arousal by Paradoxical GABAergic Stimulation: A Case Report With F-18 Flumazenil Positron Emission Tomography and Single Photon Emission Computed Tomography Study.

Zolpidem is a non-benzodiazepine drug that has selectivity for the gamma-aminobutyric acid (GABA) receptors. We experienced paradoxical effect of zolpidem in a 48-year-old male patient with hypoxic-ischemic brain injury after cardiac arrest. The patient was in stupor and could not communicate. His Glasgow Coma Scale (GCS) was E2M4V2 and Rancho Los Amigos (RLA) was grade III to IV. Zolpidem was prescribed to induce sedation but paradoxically, he became alert (GCS 15, RLA VII) and was able to communicate. The arousal lasted for 2 hours repeatedly following each administration of the medication. While he was alert, electroencephalogram showed the reversal of slow wave into beta range fast activity and F-18 flumazenil positron emission tomography (PET) showed increased GABAergic receptor activity in both frontoparietotemporal cortices. Single photon emission computed tomography (SPECT) also showed increased cerebral perfusion and reversal of cerebellar diaschisis.

Overexpression of S100A4 is closely associated with progression of colorectal cancer.

AIM: To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS: A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS: Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes' stage and lymph node metastasis. Nuclear staining was also observed in 24 (19.4%) of 124 samples and closely associated with Dukes' stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.