Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Objective: A deep learning-based classification system (DLCS) which uses structural brain magnetic resonance imaging (MRI) to diagnose Alzheimer’s disease (AD) was developed in a previous recent study. Here, we evaluate its performance by conducting a single-center, case-control clinical trial. Methods: We retrospectively collected T1-weighted brain MRI scans of subjects who had an accompanying measure of amyloid-beta (Aβ) positivity based on a 18F-florbetaben positron emission tomography scan. The dataset included 188 Aβ-positive patients with mild cognitive impairment or dementia due to AD, and 162 Aβ-negative controls with normal cognition. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) of the DLCS in the classification of Aβ-positive AD patients from Aβ-negative controls. Results: The DLCS showed excellent performance, with sensitivity, specificity, positive predictive value, negative predictive value, and AUC of 85.6% (95% confidence interval [CI], 79.8–90.0), 90.1% (95% CI, 84.5–94.2), 91.0% (95% CI, 86.3–94.1), 84.4% (95% CI, 79.2–88.5), and 0.937 (95% CI, 0.911–0.963), respectively. Conclusion The DLCS shows promise in clinical settings where it could be routinely applied to MRI scans regardless of original scan purpose to improve the early detection of AD.

As a technique mainly hiring in forensic investigation field to identify the descents, craniofacial reconstruction (CFR) is also used in archaeology to create the faces from ancient or medieval human remains, when there is little information about his/her appearance. Eung-Cheok Ko (1531–1605) was a writer and scholar in the mid Joseon period. In January of 2019, His mummified body was found at Gumi, Kyeonsangbuk-do, Korea. The remains were anthropologically examined, and archaeological CFR was also requested for this case. This report reveals the case’s facial reconstruction process and his portrait that is drawn based on the 3-dimensional CFR result.

A three-dimensional (3D) segmentation and model reconstruction is a specialized tool to reveal spatial interrelationship between multiple internal organs by generating images without overlapping structures. This technique can also be applicable to mummy studies, but related reports have so far been very rare. In this study, we applied 3D segmentation and model reconstruction to computed tomography images of a Korean mummy with congenital diaphragmatic hernia. As originally revealed by the autopsy in 2013, the current 3D reconstruction reveals that the mummy’s heart is shifted to the left due to the liver pushing up to thoracic cavity thorough diaphragmatic hernial defect. We can generate 3D images by calling up the data exclusively from mummy’s target organs, thus minimizing the confusion of diagnosis that could be caused by overlapping organs.

Arachnoid cysts are benign lesions that are formed between the inner and outer layers of the arachnoid, accounting for 1% of all intracranial space occupying lesions. Usually, arachnoid cysts are asymptomatic. It can be symptomatic in case of complication such as intracystic hemorrhage or acute cyst expansion. We present a case of incidentally prediagnosed arachnoid cyst which undergone intracystic hemorrhage combined with ipsilateral SDH in a young male.

Arachnoid cysts are benign lesions that are formed between the inner and outer layers of the arachnoid, accounting for 1% of all intracranial space occupying lesions. Usually, arachnoid cysts are asymptomatic. It can be symptomatic in case of complication such as intracystic hemorrhage or acute cyst expansion. We present a case of incidentally prediagnosed arachnoid cyst which undergone intracystic hemorrhage combined with ipsilateral SDH in a young male.

Purpose: High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detectionas a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer(HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18,and 58 are useful biomarkers for HSIL+. Materials and Methods: Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16–,18–, and 58–infected women, respectively, were determined using real-time polymerasechain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integratedviral loads and physical state were compared between HSIL+ and controls, and diagnosticvalue was determined using receiver operating characteristic analysis. Results: Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologicgrade. High type-specific total viral loads were significantly associated with HSIL+ (oddsratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integratedviral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated statewas associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral loadwas significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 forHPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. Conclusion Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16–,18–, and 58–infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, thismethod can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.

OBJECTIVES: Body mass index (BMI) is commonly used in epidemiological study or clinical center. However, it is not exactly correlated with body fat composition and does not reflect sex, age, or race. The aim of this article is to evaluate the validity of BMI standards relative to total body fat (TBF) and to estimate new BMI criteria that correspond to TBF for obesity, especially for Asian postmenopausal women. METHODS: A total 3,936 patients were included in this cross-sectional study, including 1,565 premenopausal and 2,371 postmenopausal women. At the time of visit, demographic data were collected. We demonstrated the validity of BMI cut-point of 25 kg/m2 by using area under the curve (AUC), and presented the empirical optimal BMI cut-point by using Youden's index and overall accuracy in both premenopausal and postmenopausal women. RESULTS: BMI-defined obesity (≥ 25 kg/m2) represents high AUC values (> 0.9) for each TBF. In premenopausal women, TBF ≥ 38% and corresponding BMI value was 29.45 kg/m2 indicated the highest both Youden's index and overall accuracy. In comparison, postmenopausal women who were TBF ≥ 38% showed the highest Youden's index and overall accuracy, and corresponding BMI value was 26.45 kg/m2. CONCLUSIONS: We proposed new BMI criteria for obesity by using TBF reference. With application of bioelectrical impedance analysis, the diagnosis of obesity using BMI criteria may differ between premenopausal and postmenopausal women.
Adipose Tissue ; Area Under Curve ; Asian Continental Ancestry Group ; Body Mass Index ; Continental Population Groups ; Cross-Sectional Studies ; Diagnosis ; Electric Impedance ; Epidemiologic Studies ; Female ; Humans ; Menopause ; Obesity

Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4′,6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo. Co-treatment with TMF and glycitin synergistically promotes the proliferation and migration of both keratinocytes and dermal fibroblasts, with a 1:1 ratio of these compounds showing the greatest efficacy in our co-culture system. This keratinocyte-fibroblast interaction occurred via the secretion of TGF-β, and the induction of differentiation and proliferation was confirmed in both indirect and direct co-culture assays. In an excisional and burn wound animal model, mice treated with a 1:1 ratio of TMF and glycitin showed faster wound closure, regeneration and scar reduction than even the positive control drug. These data indicate that two isoflavones, TMF and glycitin, act synergistically to promote wound healing and anti-scarring and could potentially be developed together as a bioactive therapeutic for wound treatment.
Animals ; Burns ; Cicatrix ; Coculture Techniques ; Fibroblasts* ; In Vitro Techniques ; Isoflavones ; Keratinocytes* ; Mice ; Models, Animal ; Regeneration ; Skin ; Wound Healing* ; Wounds and Injuries*

OBJECTIVETo investigate the potential alleviating effects of acupuncture on maternal separation (MS)-induced changes in plasma pro-inflammatory cytokine levels of rat pups.

METHODSOn postnatal day 15, rat pups were randomly assigned to 4 groups (n=6 per group) using a random number table: normal, MS, MS with acupuncture stimulation at Shenmen (HT 7) acupoint (MS+HT 7), and MS with acupuncture stimulation at Chengshan (BL 57) acupoint (MS+BL 57) groups. Rat pups in the normal group were housed with their mothers under standard conditions; those in the MS, MS+HT 7 and MS+BL 57 groups were maternally separated and individually maintained. Acupuncture stimulation was performed at HT 7 or BL 57 acupoints once a day for 7 consecutive days. A tail suspension test was performed to measure immobility time of rats and the plasma was collected on postnatal day 21, then levels of corticosterone (CORT), interleukin (IL)-1β, IL-6 and glial cell-derived neurotrophic factor (GDNF) in plasma were measured.

RESULTSCompared with the normal group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF in the MS group were significantly increased (P<0.05 or P<0.01). Compared with the MS group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF were significantly reduced in the MS+HT 7 group (P<0.05 or P<0.01). Moreover, the immobility time and plasma levels of IL-1β and IL-6 in the MS+HT 7 group were significantly lower than those in the MS+BL 57 group (P<0.05).

CONCLUSIONAcupuncture stimulation at HT 7 can alleviate the behavioral impairment and changes of the cytokines by MS, indicating that acupuncture can help to relieve MS-induced depression.