Purpose
To demonstrate robust myelin water fraction (MWF) mapping using an artificial neural network (ANN) with multi‐echo gradient‐echo (GRE) signal.
Methods
Multi‐echo gradient‐echo signals ...simulated with a three‐pool exponential model were used to generate the training data set for the ANN, which was designed to yield the MWF. We investigated the performance of our proposed ANN for various conditions using both numerical simulations and in vivo data. Simulations were conducted with various SNRs to investigate the performance of the ANN. In vivo data with high spatial resolutions were applied in the analyses, and results were compared with MWFs derived by the nonlinear least‐squares algorithm using a complex three‐pool exponential model.
Results
The network results for the simulations show high accuracies against noise compared with nonlinear least‐squares MWFs: RMS‐error value of 5.46 for the nonlinear least‐squares MWF and 3.56 for the ANN MWF at an SNR of 150 (relative gain = 34.80%). These effects were also found in the in vivo data, with reduced SDs in the region‐of‐interest analyses. These effects of the ANN demonstrate the feasibility of acquiring high‐resolution myelin water images.
Conclusion
The simulation results and in vivo data suggest that the ANN facilitates more robust MWF mapping in multi‐echo gradient‐echo sequences compared with the conventional nonlinear least‐squares method.
Metastasis and chemoresistance remain major challenges in the clinical treatment of breast cancer. Recent studies show that dysregulated microRNAs (miRNAs) play an important role in metastasis and ...chemoresistance development in breast cancer. Herein, we identified downregulated expression of miR‐708‐3p in breast cancers. In particular, miR‐708‐3p expression was significantly decreased in specimens from breast cancer patients with metastasis compared to that in specimens from patients with no metastasis. Consistent with clinical data, our in vitro data show that miR‐708‐3p was more significantly decreased in invasive breast cancer cell lines. In addition, our data show that inhibition of miR‐708‐3p significantly stimulated breast cancer cell metastasis and induced chemoresistance both in vitro and in vivo. In contrast, overexpression of miR‐708‐3p dramatically inhibited breast cancer cell metastasis and enhanced the sensitivity of breast cancer cells to chemotherapy both in vitro and in vivo. Furthermore, we identified that miR‐708‐3p inhibits breast cancer cell epithelial‐to‐mesenchymal transition (EMT) by directly targeting EMT activators, including ZEB1, CDH2 and vimentin. Taken together, our findings suggest that miR‐708‐3p acts as a cancer suppressor miRNA and carries out its anticancer function by inhibiting EMT in breast cancer. In addition, our findings suggest that restoration of miR‐708‐3p may be a novel strategy for inhibiting breast cancer metastasis and overcoming the chemoresistance of breast cancer cells.
Decreased expression of miR‐708‐3p was correlated with metastasis in breast cancer. Overexpression of miR‐708‐3p inhibits breast cancer cell metastasis and enhances chemosensitivity of breast cancer cells by inhibiting EMT.
Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a critical threat to human public health. Currently, 78 species, 17 genera, and 4 subfamilies of paramyxoviruses are harbored by ...multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Henipaviruses are critical zoonotic pathogens that cause severe acute respiratory distress and neurological diseases in humans. Using reverse transcription-polymerase chain reaction, 115
species individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was observed in 26 (22.6%) shrews collected at five trapping sites, Republic of Korea. Herein, we report two genetically distinct novel paramyxoviruses (genus:
): Gamak virus (GAKV) and Daeryong virus (DARV) isolated from
and
, respectively. Two GAKVs and one DARV were nearly completely sequenced using next-generation sequencing. GAKV and DARV contain six genes (3'-N-P-M-F-G-L-5') with genome sizes of 18,460 nucleotides and 19,471 nucleotides, respectively. The phylogenetic inference demonstrated that GAKV and DARV form independent genetic lineages of
in
species. GAKV-infected human lung epithelial cells elicited the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. In conclusion, this study contributes further understandings of the molecular prevalence, genetic characteristics and diversity, and zoonotic potential of novel paramyxoviruses in shrews.
The detection of thyroid nodules has become more common with the widespread use of ultrasonography (US). US is the mainstay for detecting and making the differential diagnosis of thyroid nodules as ...well as for providing guidance for a biopsy. The Task Force on Thyroid Nodules of the Korean Society of Thyroid Radiology has developed recommendations for the US diagnosis and US-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature, the results of multicenter studies and from the consensus of experts.
Coronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays.
A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI™ Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA).
With both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15-35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22-35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI™ Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results.
The antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys.
We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor ...thrombosis (PVTT).
A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy.
Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%).
Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.
The development of smart inks that change color and transparency in response to external stimuli is very important for various fields, from modern art to safety and anticounterfeiting technology. A ...uniaxially oriented diacetylene thin film on a macroscopic area is obtained by coating, self‐assembling and topochemical photopolymerizing of imidazolium‐functionalized diacetylenes (M‐DA and T‐DA) and 4,6‐decadiyne ink (70 wt%:20 wt%:10 wt%) exhibiting a lyotropic smectic A liquid‐crystalline phase at room temperature. The color and transparency of letters and symbols written with the DA‐based secret inks change reversibly from blue to red as well as from colorless transparent to black opaque depending on the temperature and polarization axis. A secret code written with thermoresponsive and polarization‐dependent secret inks consisting of imidazolium‐functionalized diacetylenes is successfully deciphered by wearing polaroid glasses and holding a burning torch.
Information is encrypted into a secret code with imidazolium‐functionalized diacetylene secret inks that respond to heat as well as polarization. The secret code can be deciphered by wearing polaroid glasses and holding a burning torch.
We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed ...phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was
and
(54.5%), followed by
(27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia BilIN), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as
,
, and
. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.
Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality ...and morbidity, effective antiviral therapeutics or vaccines for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK).
We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mice harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analyses identified a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence.
Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.
Metformin is associated with good tumor response in preoperative concurrent chemoradiotherapy (CCRT) for rectal cancer. This study aims to demonstrate that the timing of metformin is related to the ...tumor response on preoperative CCRT for rectal cancer. From January 2010 to December 2017, 232 patients who underwent curative resection after preoperative CCRT were reviewed. Patients were divided into groups with or without diabetes or metformin. The timing of metformin administration was divided based on before and from initiation of CCRT. Multivariate logistic regression analysis was used to identify predictors for tumor response. Tumor downstaging (p = 0.02) and good response rates of tumor regression grade (TRG) (p = 0.008) were significantly higher in the group administered metformin before CCRT than other groups. In the multivariate analysis, metformin administration before CCRT was a significant factor in predicting tumor downstaging odds ratio (OR) 10.31, 95% confidence interval (CI) 1.76-102.08, p = 0.02 and good TRG (OR 12.55, 95% CI 2.38-80.24, p = 0.004). In patients with rectal cancer who underwent preoperative CCRT, neoadjuvant therapy of metformin before CCRT was significantly associated with good tumor response.