IMPORTANCE There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).OBJECTIVE To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. DESIGN, SETTING, AND PARTICIPANTSA retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea.MAIN OUTCOMES AND MEASURES Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients' symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription-polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients. RESULTSOf the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (β = −0.065 [SE, 0.023]; P = .005). CONCLUSIONS AND RELEVANCEIn this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread o...

Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CMs), 3 melanomas arising in congenital nevi (CNMs), and 5 spitzoid melanomas (SMs), using various platforms, including whole genome or exome sequencing, the molecular inversion probe assay, and/or targeted sequencing. CMs demonstrated a high burden of somatic single-nucleotide variations (SNVs), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and >80% of the identified SNVs consistent with UV damage. In contrast, the three CNMs contained an activating NRAS Q61 mutation and no TERT-p mutations. SMs were characterized by chromosomal rearrangements resulting in activated kinase signaling in 40%, and an absence of TERT-p mutations, except for the one SM that succumbed to hematogenous metastasis. We conclude that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients. In contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.

Spitzoid neoplasms constitute a morphologically distinct category of melanocytic tumors, encompassing Spitz nevus (benign), atypical Spitz tumor (intermediate malignant potential), and spitzoid melanoma (fully malignant). Currently, no reliable histopathological criteria or molecular marker is known to distinguish borderline from overtly malignant neoplasms. Because TERT promoter (TERT-p) mutations are common in inherently aggressive cutaneous conventional melanoma, we sought to evaluate their prognostic significance in spitzoid neoplasms. We analyzed tumors labeled as atypical Spitz tumor or spitzoid melanoma from 56 patients with available follow-up data for the association of TERT-p mutations, biallelic CDKN2A deletion, biallelic PTEN deletion, kinase fusions, BRAF/NRAS mutations, nodal status, and histopathological parameters with risk of hematogenous metastasis. Four patients died of disseminated disease and 52 patients were alive and disease free without extranodal metastasis (median follow-up, 32.5 months). We found TERT-p mutations in samples from the 4 patients who developed hematogenous metastasis but in none of tumors from patients who had favorable outcomes. Presence of TERT-p mutations was the most significant predictor of haematogenous dissemination (P < 0.0001) among variables analyzed. We conclude that TERT-p mutations identify a clinically high-risk subset of patients with spitzoid tumors. Application of TERT-p mutational assays for risk stratification in the clinic requires large-scale validation.

Hierarchical and gradient structures in biological systems with special mechanical properties have inspired innovations in materials design for construction and mechanical applications. Analogous to the control of stress transfer in gradient mechanical structures, the control of electron transfer in gradient electrical structures should enable the development of high-performance electronics. This paper demonstrates a high performance electronic skin (e-skin) via the simultaneous control of tactile stress transfer to an active sensing area and the corresponding electrical current through the gradient structures. The flexible e-skin sensor has extraordinarily high piezoresistive sensitivity at low power and linearity over a broad pressure range based on the conductivity-gradient multilayer on the stiffness-gradient interlocked microdome geometry. While stiffness-gradient interlocked microdome structures allow the efficient transfer and localization of applied stress to the sensing area, the multilayered structure with gradient conductivity enables the efficient regulation of piezoresistance in response to applied pressure by gradual activation of current pathways from outer to inner layers, resulting in a pressure sensitivity of 3.8 × 10 5 kPa −1 with linear response over a wide range of up to 100 kPa. In addition, the sensor indicated a rapid response time of 0.016 ms, a low minimum detectable pressure level of 0.025 Pa, a low operating voltage (100 μV), and high durability during 8000 repetitive cycles of pressure application (80 kPa). The high performance of the e-skin sensor enables acoustic wave detection, differentiation of gas characterized by different densities, subtle tactile manipulation of objects, and real-time monitoring of pulse pressure waveform.

In this paper, an effective fault location algorithm and intelligent fault diagnosis scheme are proposed. The proposed scheme first identifies fault locations using an iterative estimation of load and fault current at each line section. Then an actual location is identified, applying the current pattern matching rules. If necessary, comparison of the interrupted load with the actual load follows and generates the final diagnosis decision. Effect of load uncertainty and fault resistance has been carefully investigated through simulation results that turns out to be very satisfactory.