Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

Vaccination is an important strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. We conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers (HCWs). Among the 1,676 vaccinated HCWs, 59.5% (998/1,676) responded to the survey. In total, 809 (81.1%) respondents reported experiencing AEs. There were no serious AEs, such as anaphylaxis. The most common AE was pain at the injection site (76.2%), followed by fatigue (75.9%), myalgia (74.9%), and fever (58.4%). HCWs in the younger age group experienced significantly more AEs than in the older age group.

Vaccination is an important strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. We conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers (HCWs). Among the 1,676 vaccinated HCWs, 59.5% (998/1,676) responded to the survey. In total, 809 (81.1%) respondents reported experiencing AEs. There were no serious AEs, such as anaphylaxis. The most common AE was pain at the injection site (76.2%), followed by fatigue (75.9%), myalgia (74.9%), and fever (58.4%). HCWs in the younger age group experienced significantly more AEs than in the older age group.

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. METHODS: To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. RESULTS: Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 microIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. CONCLUSION: The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.
Autoantibodies ; Autoimmune Diseases ; Blood Glucose ; Diagnosis ; Humans ; Hyperinsulinism ; Hypoglycemia* ; Insulin ; Insulin Antibodies ; Insulinoma ; Korea ; Nesidioblastosis ; Pancreatectomy ; Plasma ; Prevalence ; Retrospective Studies

OBJECTIVES: The aim of this study was to investigate brain activation during a Korean language-based 'theory of mind (TOM)' task and fMRI in Korean schizophrenic patients. METHODS: Fourteen Korean schizophrenic patients and 15 normal controls participated in this study. For all participants, several clinical states and psychosocial functions were evaluated. The subjects were then scanned while performing Korean language-based fMRI tasks. The tasks were comprised of conditions-first order false belief (TOM task), physical causality, and unrelated situations. Imaging data were analyzed using SPM2 software (uncorrected p<0.005, extent threshold kappa=10). RESULTS: 1) Compared with the control group, the patient group showed significantly poorer performance on the TOM task, and no significant correlation between TOM and empathic abilitiesy. 2) In the patient group, there were no significantly activated brain regions associated with the TOM task as compared to the physical causality task. With respect to between-group differences, the patient group showed significantly less activation of the left medial frontal region (primarily BA 8) and signifcantly different activation of the left precuneus (BA 7) associated with the TOM task. CONCLUSION: These results suggest that Korean schizophreniac patients show different brain activity associated with TOM functions, especially with respect to the Korean language-based first order false belief tasks.
Brain ; Humans ; Magnetic Resonance Imaging ; Schizophrenia ; Theory of Mind

PURPOSE: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. RESULTS: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli. CONCLUSION: These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.
Albuminuria ; Animals ; Blotting, Western ; Cadherins ; Diabetic Nephropathies ; Enzyme-Linked Immunosorbent Assay ; Membrane Proteins ; p38 Mitogen-Activated Protein Kinases ; Protein Kinases ; Proteins ; Pyrazoles ; Pyridines ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Streptozocin

The optimal dark adaptation time of electroretinograms (ERG's) performed on conscious dogs were determined using a commercially available ERG unit with a contact lens electrode and a built-in light source (LED-electrode). The ERG recordings were performed on nine healthy Miniature Schnauzer dogs. The bilateral ERG's at seven different dark adaptation times at an intensity of 2.5 cd.s/m2 was performed. Signal averaging (4 flashes of light stimuli) was adopted to reduce electrophysiologic noise. As the dark adaptation time increased, a significant increase in the mean a-wave amplitudes was observed in comparison to base-line levels up to 10 min (p > 0.05). Thereafter, no significant differences in amplitude occured over the dark adaptation time. Moreover, at this time the mean amplitude was 60.30 +/- 18.47 microV. However, no significant changes were observed for the implicit times of the a-wave. The implicit times and amplitude of the b-wave increased significantly up to 20 min of dark adaptation (p > 0.05). Beyond this time, the mean b-wave amplitudes was 132.92 +/- 17.79 microV. The results of the present study demonstrate that, the optimal dark adaptation time when performing ERG's, should be at least 20 min in conscious Miniature Schnauzer dogs.
Animals ; Dark Adaptation/*physiology ; Dogs/*physiology ; Electroretinography/*veterinary ; Male ; Retina/*physiology ; Time Factors

This study evaluated the surgical outcome and complications of phacoemulsification and the implantation of an acryl foldable intraocular lens (IOL) with a squared edge in dogs with cataracts. Thirty-two eyes from 26 dogs were examined. The mean follow up period was 75.9 days ranging from 23 to 226 days. The complications after phacoemulsification were posterior capsular opacity (PCO) around the IOL (n = 11), ocular hypertension (n = 4), focal posterior synechia (n = 4), hyphema (n = 3) and corneal ulcer (n = 2). The complications associated with the IOL were decenteration of the optic (n = 2) and ventral haptic displacement (n = 1). Most cases of PCO were found only around the margin of the IOL, and all eyes had vision during the observation period. In conclusion, the implantation of an acryl-foldable lens with a squared edge at the time of phacoemulsification is an effective method for preserving the central visual field of dogs with cataract.
Animals ; Cataract/*veterinary ; Dog Diseases/*surgery ; Dogs/*surgery ; Female ; Lens Implantation, Intraocular/adverse effects/*veterinary ; Male ; Phacoemulsification/adverse effects/*veterinary ; Retrospective Studies

OBJECTIVES: There are a number of preceding epidemiological studies reporting gender differences in the genetic etiology of alcohol dependence. The author investigated gender difference in the frequencies of ADH2 and ALDH2 genoypes between the patients with alcohol dependence and normal control. METHODS: The subjects were 141 alcohol dependent patients (104 males, 37 females) and 138 normal control (79 males, 59 females). The frequencies of 1/1 and 1/2+2/2 (2+ afterward) genotypes for ADH2 and ALDH2 were investigated in male and female between alcohol dependence and normal control group. DNA was extracted from WBC in peripheral venous blood and PCR-RFLP method was used out for genotyping. RESULTS: First, the frequency of ADH2 1/1 genotype was significantly higher in alcohol dependent patients than normal control in both genders. Second, while there was no gender difference in the frequency of ADH2 1/1 genotype in normal controls, in the patient group however, the frequency was significantly higher in females than males. Third, in male subjects with alcohol dependence, the frequency of ALDH2 1/1 genotype was significantly higher than in male normal control subjects. On the other hand, in female subjects with alcohol dependence, the frequency of ALDH2 2+ genotype was significantly higher than in female normal control subjects. CONCLUSION: These results suggest that while the risk of alcohol dependence is predominantly affected by ALDH2 1/1 genotype in male, the female ADH2 1/1 genotype is mainly associated with the risk of alcohol dependence. This means that there are gender differences in the genetic etiology of alcohol dependence.
Alcoholism* ; DNA ; Epidemiologic Studies ; Female ; Genotype* ; Hand ; Humans ; Male