Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Purpose: Lower-grade gliomas of histologic grades 2 and 3 follow heterogenous clinical outcomes, which necessitates risk stratification. This study aimed to evaluate whether diffusion-weighted and perfusion-weighted MRI radiomics allow overall survival (OS) prediction in patients with lower-grade gliomas and investigate its prognostic value. Materials and Methods: In this retrospective study, radiomic features were extracted from apparent diffusion coefficient, relative cerebral blood volume map, and Ktrans map in patients with pathologically confirmed lower-grade gliomas (January 2012–February 2019). The radiomics risk score (RRS) calculated from selected features constituted a radiomics model. Multivariable Cox regression analysis, including clinical features and RRS, was performed. The models’ integrated area under the receiver operating characteristic curves (iAUCs) were compared. The radiomics model combined with clinical features was presented as a nomogram. Results: The study included 129 patients (median age, 44 years; interquartile range, 37–57 years; 63 female): 90 patients for training set and 39 patients for test set. The RRS was an independent risk factor for OS with a hazard ratio of 6.01. The combined clinical and radiomics model achieved superior performance for OS prediction compared to the clinical model in both training (iAUC, 0.82 vs.0.72, p=0.002) and test sets (0.88 vs. 0.76, p=0.04). The radiomics nomogram combined with clinical features exhibited good agreement between the actual and predicted OS with C-index of 0.83 and 0.87 in the training and test sets, respectively. Conclusion Adding diffusion- and perfusion-weighted MRI radiomics to clinical features improved survival prediction in lowergrade glioma.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Objective: Our study aimed to evaluate the quality of radiomics studies on brain metastases based on the radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guidelines. Materials and Methods: PubMed MEDLINE, and EMBASE were searched for articles on radiomics for evaluating brain metastases, published until February 2021. Of the 572 articles, 29 relevant original research articles were included and evaluated according to the RQS, TRIPOD checklist, and IBSI guidelines. Results: External validation was performed in only three studies (10.3%). The median RQS was 3.0 (range, -6 to 12), with a low basic adherence rate of 50.0%. The adherence rate was low in comparison to the “gold standard” (10.3%), stating the potential clinical utility (10.3%), performing the cut-off analysis (3.4%), reporting calibration statistics (6.9%), and providing open science and data (3.4%). None of the studies involved test-retest or phantom studies, prospective studies, or cost-effectiveness analyses. The overall rate of adherence to the TRIPOD checklist was 60.3% and low for reporting title (3.4%), blind assessment of outcome (0%), description of the handling of missing data (0%), and presentation of the full prediction model (0%). The majority of studies lacked pre-processing steps, with bias-field correction, isovoxel resampling, skull stripping, and gray-level discretization performed in only six (20.7%), nine (31.0%), four (3.8%), and four (13.8%) studies, respectively. Conclusion The overall scientific and reporting quality of radiomics studies on brain metastases published during the study period was insufficient. Radiomics studies should adhere to the RQS, TRIPOD, and IBSI guidelines to facilitate the translation of radiomics into the clinical field.

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immunooncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb.Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l’Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 Aspergillus (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed “no identification” or “multiple species identification” results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for Aspergillus, dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed “no identification” and “misidentification” results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification

Background: Hepatocellular carcinoma (HCC) is the second-most-common cause of cancer-related deaths worldwide, and an accurate and non-invasive biomarker for the early detection and monitoring of HCC is required. We assessed pathogenic variants of HCC driver genes in cell-free DNA (cfDNA) from HCC patients who had not undergone systemic therapy. Methods: Plasma cfDNA was collected from 20 HCC patients, and deep sequencing was performed using a customized cfDNA next-generation sequencing panel, targeting the major HCC driver genes (TP53, CTNNB1, TERT) that incorporates molecular barcoding. Results: In 13/20 (65%) patients, we identified at least one pathogenic variant of two major HCC driver genes (TP53 and CTNNB1), including 16 variants of TP53 and nine variants of CTNNB1. The TP53 and CTNNB1 variants showed low allele frequencies, with median values of 0.17% (range: 0.06%–6.99%) and 0.07% (range: 0.05%–0.96%), respectively. However, the molecular coverage of variants was sufficient, with median values of 5,543 (range: 2,317–9,088) and 7,568 (range: 2,400–9,633) for TP53 and CTNNB1 variants, respectively. Conclusions Our targeted DNA sequencing successfully identified low-frequency pathogenic variants in the cfDNA from HCC patients by achieving high coverage of unique molecular families. Our results support the utility of cfDNA analysis to identify somatic gene variants in HCC patients.