Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

INTRODUCTION: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. RESULTS: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. CONCLUSION: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals.

BACKGRUOUND: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. METHODS: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. RESULTS: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. CONCLUSION: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.

Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

Performance Evaluation of Two Kinds of Rapid Antigen Test Kits for Detection of COVID-19 Infection.

BACKGROUND: The diagnostic standard for COVID-19 infection is real-time reverse transcription-polymerase chain reaction (rRT-PCR) of nasopharyngeal swab and oropharyngeal swab specimens. Rapid antigen tests are cheaper and easier to use than the rRT-PCR method. Although the COVID-19 pandemic is settling down, seasonal epi¬demic is expected. In this study, the performance of two rapid antigen test kits was evaluated based on rRT-PCR test results. METHODS: A total of 346 residual samples was tested by the PowerChek SARS-CoV-2 Real-time PCR Kit or STAN-DARD M nCoV Real-Time-Detection kit, STANDARD Q COVID-19 Ag test kit (SQ RAT), and ND COVID-19 Ag test kit (ND RAT). RESULTS: Compared to rRT-PCR as the standard method, the SQ RAT test kit yielded 77.1% sensitivity (101/131) and 100% specificity (215/215), and the ND RAT yielded 89.3% sensitivity (117/131) and 100% specificity (215/ 215). Both RATs showed sensitivity greater than 85% in samples with RdRp gene Ct value less than 25. There was a false-negative case suspected of prozone phenomenon. CONCLUSIONS: Both RATs showed significant performance, but users should beware of the prozone phenomenon.

In vitro and in vivo phototoxicity on gastric mucosa induced by methylene blue.

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.

Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Causing Invasive Pneumococcal Disease in Korea Between 2017 and 2019 After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine.

Background: Streptococcus pneumoniae is a serious pathogen causing various infections in humans. We evaluated the serotype distribution and antimicrobial resistance of S. pneumoniae causing invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine (PCV)13 in Korea and investigated the epidemiological characteristics of multidrug-resistant (MDR) isolates. Methods: S. pneumoniae isolates causing IPD were collected from 16 hospitals in Korea between 2017 and 2019. Serotyping was performed using modified sequential multiplex PCR and the Quellung reaction. Antimicrobial susceptibility tests were performed using the broth microdilution method. Multilocus sequence typing was performed on MDR isolates for epidemiological investigations. Results: Among the 411 S. pneumoniae isolates analyzed, the most prevalent serotype was 3 (12.2%), followed by 10A (9.5%), 34 (7.3%), 19A (6.8%), 23A (6.3%), 22F (6.1%), 35B (5.8%), 11A (5.1%), and others (40.9%). The coverage rates of PCV7, PCV10, PCV13, and pneumococcal polysaccharide vaccine (PPSV)23 were 7.8%, 7.8%, 28.7%, and 59.4%, respectively. Resistance rates to penicillin, ceftriaxone, erythromycin, and levofloxacin were 13.1%, 9.2%, 80.3%, and 4.1%, respectively. MDR isolates accounted for 23.4% of all isolates. Serotypes 23A, 11A, 19A, and 15B accounted for the highest proportions of total isolates at 18.8%, 16.7%, 14.6%, and 8.3%, respectively. Sequence type (ST)166 (43.8%) and ST320 (12.5%) were common among MDR isolates. Conclusions: Non-PCV13 serotypes are increasing among invasive S. pneumoniae strains causing IPD. Differences in antimicrobial resistance were found according to the specific serotype. Continuous monitoring of serotypes and antimicrobial resistance is necessary for the appropriate management of S. pneumoniae infections.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BACKGROUND: Cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high-sensitivity cTn (hs-cTn) assays (Beckman Coulter Access hs-cTnI, Abbott STAT hs-cTnI, and Roche Elecsys hs-cTnT) using a healthy population in Korea. METHODS: Each cTn value was measured by three assays and analyzed by dividing by gender and age. RESULTS: The frequency histograms of log-transformed cTn values for Beckman and Abbott assays exhibited a bell-shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively. CONCLUSION: Among the three assays, bell-shaped distributions were observed in a frequency histogram of log-transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

Comparison of ACCEL ELISA COVID-19 with Elecsys Anti-SARS-CoV-2 for Screening of COVID-19.

OBJECTIVE: Although real-time reverse transcription-PCR (RT-PCR) is the gold standard for diagnosing coronavirus disease 2019 (COVID-19), simpler and faster antibody detection tests can be complementary for diagnosis of COVID-19. To manage the COVID-19 pandemic, the need for serologic testing has increased. In this report, the newly developed antibody detection assays ACCEL ELISA COVID-19 (ACCEL) and Elecsys anti-SARS-CoV-2 (Elecsys) were evaluated. METHODS: Serum samples submitted for routine laboratory testing were analyzed (66 and 161 PCR-positive and PCR-negative samples). After the samples were aliquoted, antibody detection tests were performed using ACCEL and Elecsys assays. RESULTS: When detection of viral RNA using RT-PCR was set as the reference method for diagnosis of COVID-19, the sensitivity was 83.3% and 75.8, and the specificity was 96.9 and 99.4% in ACCEL and Elecsys, respectively. The true positivity rates of ACCEL and Elecsys assays were 57.1%/42.9%, 57.1%/28.6%, 77.8%/66.7%, and 97.1%/97.1% among the specimens collected ≤3, 4-7, 8-14, and >14 days after symptom onset, respectively. CONCLUSIONS: The ACCEL assay showed high sensitivity in samples collected within 7 days after symptom onset. Because many patients are asymptomatic in the early stage of SARS-CoV-2 infection, the ACCEL assay could be a good screening tool due to high sensitivity in the early stage of SARS-CoV-2 infection.

Comparison of Six Antifungal Susceptibilities of 11 Candida Species Using the VITEK2 AST-YS08 Card and Broth Microdilution Method.

We used a Vitek 2 AST-YS08 (YS08) system and the broth microdilution method (BMD) adopted by the Clinical and Laboratory Standards Institute (CLSI) to compare the susceptibility of 184 isolates of 11 Candida species to fluconazole, voriconazole, micafungin, caspofungin, amphotericin B, and flucytosine. In Candida albicans, the categorical agreement (CA) was 79.2%, 91.7%, 95.8%, and 95.8% for fluconazole, voriconazole, micafungin, and caspofungin, respectively. About 12.5% and 4.2% of very major errors were detected for fluconazole and voriconazole, respectively. C. glabrata showed excellent essential agreements (EAs) (>90%) for azoles but different MIC distributions for fluconazole and caspofungin. The CA between BMD fluconazole MICs and YS08 voriconazole MICs by the method-specific clinical breakpoint (CBP) was 90% in C. glabrata. Over 80% of C. glabrata and C. krusei isolates identified as micafungin-susceptible were labeled intermediate or resistant to caspofungin in YS08. In C. parapsilosis, 5.3% of very major errors and 10.5% of minor errors were found, whereas 33.3% of minor errors were observed in C. tropicalis for fluconazole. For C. tropicalis, 13 (61.9%) non-wild type (WT) isolates of fluconazole and 7 (33.3%) non-WTs of voriconazole were classified in YS08 as WT. For C. auris, the EAs were 93.3%, 100%, 82.2%, 97.8%, and 97.8% for fluconazole, voriconazole, micafungin, caspofungin, and amphotericin B, respectively. YS08 showed comparable results to the BMD. However, considering the lower YS08 fluconazole MIC results compared with BMD in Candida species and YS08 caspofungin results in C. glabrata and C. krusei, improvements are needed. IMPORTANCE The new Vitek 2 AST-YS08 (YS08) card has been updated to reflect the recently revised Clinical and Laboratory Standards Institute (CLSI) guideline. In this study, antifungal drug susceptibility tests were performed using the YS08 card and compared with the CLSI broth microdilution (BMD) method. In conclusion, YS08 showed similar results to BMD, including with C. auris. However, about 12.5% and 4.2% of major errors were detected for fluconazole and voriconazole, respectively, in C. albicans. More than 80% of C. glabrata and C. krusei isolates identified as susceptible to micafungin were labeled moderate or resistant to caspofungin in YS08. The categorical agreement between BMD fluconazole MICs and YS08 voriconazole MICs was 90% by the method-specific CBP of voriconazole, 80% by the current epidemiological cutoff value (ECV) (0.25 µg/mL) of voriconazole, and 85% by the previous ECV (0.5 µg/mL) of voriconazole. Further improvements in YS08 for the detection of fluconazole and echinocandin resistance are thus needed.

Serotype Distribution and Antimicrobial Resistance of Salmonella Isolates in Korea between 2016 and 2017.

Salmonella is one of the major causes of food-borne infections. We investigated the serotype distribution and antimicrobial resistance of Salmonella isolates collected in Korea between January 2016 and December 2017. In total, 669 Salmonella isolates were collected from clinical specimens at 19 university hospitals. Serotyping was performed according to the Kauffmann-White scheme, and antimicrobial susceptibility was tested using Sensititre EUVSEC plates or disk diffusion. Among the strains, C (39.8%) and B (36.6%) were the most prevalent serogroups. In total, 51 serotypes were identified, and common serotypes were S. enterica serovar I 4,[5],12:i:- (16.7%), S. Enteritidis (16.1%), S. Bareilly (14.6%), S. Typhimurium (9.9%), and S. Infantis (6.9%). The resistance rates to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were 32.6%, 12.1%, and 8.4%, respectively. The resistance rates to cefotaxime and ciprofloxacin were 8.1% and 3.0%, respectively, while 5.4% were multidrug-resistant. S. enterica serovar I 4,[5],12:i:- and S. Enteritidis were highly prevalent, and there was an increase in rare serotypes. Multidrug resistance and ciprofloxacin resistance were highly prevalent. Periodic investigations of Salmonella serotypes and antimicrobial resistance are needed.

Correction: The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells.

[This corrects the article DOI: 10.18632/oncotarget.15991.].

Effect of an Endoplasmic Reticulum Retention Signal Tagged to Human Anti-Rabies mAb SO57 on Its Expression in Arabidopsis and Plant Growth.

Transgenic Arabidopsis thaliana expressing an anti-rabies monoclonal antibody (mAb), SO57, was obtained using Agrobacterium-mediated floral dip transformation. The endoplasmic reticulum (ER) retention signal Lys-Asp-Glu-Leu (KDEL) was tagged to the C-terminus of the anti-rabies mAb heavy chain to localize the mAb to the ER and enhance its accumulation. When the inaccurately folded proteins accumulated in the ER exceed its storage capacity, it results in stress that can affect plant development and growth. We generated T1 transformants and obtained homozygous T3 seeds from transgenic Arabidopsis to investigate the effect of KDEL on plant growth. The germination rate did not significantly differ between plants expressing mAb SO57 without KDEL (SO plant) and mAb SO57 with KDEL (SOK plant). The primary roots of SOK agar media grown plants were slightly shorter than those of SO plants. Transcriptomic analysis showed that expression of all 11 ER stress-related genes were not significantly changed in SOK plants relative to SO plants. SOK plants showed approximately three-fold higher mAb expression levels than those of SO plants. Consequently, the purified mAb amount per unit of SOK plant biomass was approximately three times higher than that of SO plants. A neutralization assay revealed that both plants exhibited efficient rapid fluorescent focus inhibition test values against the rabies virus relative to commercially available human rabies immunoglobulins. KDEL did not upregulate ER stress-related genes; therefore, the enhanced production of the mAb did not affect plant growth. Thus, KDEL fusion is recommended for enhancing mAb production in plant systems.

Application of Thromboelastographic Markers to Predict the Survival in Acute Trauma Patients.

BACKGROUND: The aim of the study is to investigate the coagulation status in trauma patients using thromboelastography and their association with survival and blood transfusion. METHODS: We included 452 trauma patients who visited the trauma center of Uijeongbu St. Mary's Hospital. The thromboelastography (TEG) clotting variables and routine coagulation tests were evaluated. Also, we investigated the transfusion requirement and mortality during hospitalization period. RESULTS: The mean age was 52.3 years and the mortality rate was 39/452 (8.6%). Lower GCS, longer TEG K-time, and lower TEG MA were independent factors associated with mortality. The lower MA group demonstrated the highest probability of survival (odds ratio 0.207), followed by prolonged R-time (odds ratio 0.220). The patient numbers in fibrinolysis shutdown (SD), physiologic fibrinolysis, and hyperfibrinolysis groups were 219 (52.3%), 131 (31.4%), and 68 (16.3%), respectively. The mortality rates of fibrinolysis SD group (11.9%) and hyperfibrinolysis (8.8%) were higher than the physiologic fibrinolysis groups (3.8%). The cutoff obtained from ROC analysis was found to be suitable for predicting survival. The transfusion requirements were significantly higher in the fibrinolysis SD group than in the other two groups. CONCLUSIONS: TEG based markers were shown to be more useful to make a diagnosis of coagulopathies including dysfibrinolysis and predict the survival than routine coagulation tests. Dysfunctional fibrinolysis showed higher mortality than physiologic group. If multiple integrations of each TEG markers are used, it would be helpful for prompt diagnosis and management of coagulopathies and to decrease preventable deaths in trauma.

Epidemiologic Linkage of COVID-19 Outbreaks at Two University-affiliated Hospitals in the Seoul Metropolitan Area in March 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks emerged at two university-affiliated hospitals in Seoul (hospital A) and Uijeongbu City (hospital S) in the metropolitan Seoul area in March 2020. The aim of this study was to investigate epidemiological links between the outbreaks using whole genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Fifteen patients were enrolled in the study, including four non-outbreak (A1-A4) and three outbreak cases (A5-A7) in hospital A and eight cases (S1-S8) in hospital S. Patients' hospital stays, COVID-19 symptoms, and transfer history were reviewed. RNA samples were submitted for WGS and genome-wide single nucleotide variants and phylogenetic relationships were analyzed. RESULTS: The index patient (A5) in hospital A was transferred from hospital S on 26 March. Patients A6 and A7 were the family caregiver and sister, respectively, of the patient who shared a room with A5 for 4 days. Prior to transfer, A5 was at the next bed to S8 in the emergency room on 25 March. Patient S6, a professional caregiver, took care of the patient in the room next to S8's room for 5 days until 22 March and then S5 for another 3 days. WGS revealed that SARS-CoV-2 in A2, A3, and A4 belong to clades V/B.2, S/A, and G/B.1, respectively, whereas that of A5-A7 and S1-S5 are of the V/B.2.1 clade and closely clustered. In particular, SARS-CoV-2 in patients A5 and S5 showed perfect identity. CONCLUSION: WGS is a useful tool to understand epidemiology of SARS-CoV-2. It is the first study to elucidate the role of patient transfer and caregivers as links of nosocomial outbreaks of COVID-19 in multiple hospitals.

Multilaboratory Evaluation of the MALDI-TOF Mass Spectrometry System, MicroIDSys Elite, for the Identification of Medically Important Filamentous Fungi.

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.