Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC).

(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfDHCC), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfDHCC score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients' survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC.

Multiple Cycle Slip Detection Algorithm for a Single Frequency Receiver.

A satellite navigation system makes it simple to find and navigate to a specific position. Although a carrier measurement is required to establish a precise position due to the characteristics of the carrier observation, it is difficult to determine a robust position in a poor signal reception environment such as urban areas. Various studies are being carried out to overcome this problem, with cycle slips being the most important factor. With only a single frequency, it is very challenging to detect cycle slips in multiple satellite channels at the same time. A geometry-based technique is proposed in this study as a technical solution for detecting simultaneous cycle slips for multiple channels utilizing only a single-frequency receiver. The method could detect a half-wavelength size of cycle slip for each channel through the geometry information.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

Butylparaben Induces the Neuronal Death Through the ER Stress-Mediated Apoptosis of Primary Cortical Neurons.

Butylparaben is an organic compound that is used as an antimicrobial preservative in cosmetics and can cause neurotoxicity. However, whether butylparaben induces neuronal death is unclear. In this study, we report that butylparaben exposure induced neuronal apoptosis mediated by ER stress in primary cortical neurons. We found that butylparaben significantly inhibited the viability of primary cortical neurons and led to lactate dehydrogenase (LDH) release from primary cortical neurons. Upon exposure to butylparaben, primary cortical neurons exhibited increased levels of apoptosis-related proteins such as Cleaved-caspase3 and Bax. Interestingly, butylparaben-induced activation of apoptosis involved the upstream activation of ER stress proteins such as GRP78, CHOP, and ATF4. However, pharmacological inhibition of ER stress prevented the butylparaben-induced induction of apoptosis. Taken together, our findings suggest that butylparaben exposure activates the ER stress-mediated apoptosis of primary cortical neurons, which is closely linked with neurodegeneration in the brain. Therefore, targeting ER stress may be considered a strategy for the treatment of butylparaben-induced neurodegeneration.

Suppressed Formation of Conductive Phases in One-Pot Electrodeposited CuInSe2 by Tuning Se Concentration in Aqueous Electrolyte.

The single-bath electrochemical deposition of CuInSe2 often leads to short-circuit behavior of the resulting solar cells due to the high shunt conductance. In this study, in an attempt to resolve this problem, the influence of the Se precursor concentration (CSe) on electrodeposited CuInSe2 films and solar cell devices is examined in the CSe range of 4.8 to 12.0 mM in selenite-based aqueous solutions containing Cu and In chlorides along with sulfamic acid (H3NSO3) and potassium hydrogen phthalate (C8H5KO4) additives. As CSe increases, the CuInSe2 layers become porous, and the grain growth of the CuInSe2 phase is restricted, while the parasitic shunting problem was markedly alleviated, as unambiguously demonstrated by measurements of the local current distribution. Due to these ambivalent influences, an optimal value of CSe that achieves the best quality of the films for high-efficiency solar cells is identified. Thus, the device prepared with 5.2 mM Se exhibits a power-conversion efficiency exceeding 10% with greatly improved device parameters, such as the shunt conductance and the reverse saturation current. The rationale of the present approach along with the physicochemical origin of its conspicuous impact on the resulting devices is discussed in conjunction with the electro-crystallization mechanism of the CuInSe2 compound.

Prevalence of metabolic syndrome is higher among non-obese PCOS women with hyperandrogenism and menstrual irregularity in Korea.

BACKGROUND: Hyperandrogenism (HA) has been linked with several components of metabolic syndrome (MetS). Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS. MATERIALS AND METHODS: This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15-40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International Diabetes Federation (IDF) criteria. RESULTS: MetS was more prevalent in the PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893-9.474) and 4.612 (95% CI, 1.978-10.750), respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects. CONCLUSIONS: Our results indicate that HA and its associated parameters (FAI and SHBG) are significantly associated with MetS in non-obese PCOS subjects, whereas this association was not observed in obese subjects.

Study on thermal evolution of the CuSe phase in nanoparticle-based absorber layers for solution-processed chalcopyrite photovoltaic devices.

Nanoparticle-based, solution-processed chalcopyrite photovoltaic devices have drawn tremendous attraction for the realization of low-cost, large-area solar cell applications. In particular, it has been recently demonstrated that the CuSe phase plays a critical role in allowing the formation of device-quality, nanoparticle-based chalcopyrite absorber layers. For further in-depth study, with the aim of understanding the thermal behavior of the CuSe phase that triggers the vigorous densification reaction, a requisite for high-performance chalcopyrite absorber layers, both multiphase (CuSe-phase including) and single-phase (CuSe-phase free) CISe nanoparticles are investigated from the viewpoint of compositional variation and crystalline structural evolution. In addition, with CuSe-phase including CISe particulate layers, the basic restrictions in thermal treatment necessary for activating effectively the CuSe-phase induced densification reaction are suggested, in conjunction with consideration on the thermal decomposition of organic additives that are inevitably incorporated in nanoparticle-based absorber layers.

Intrahepatic portosystemic venous shunt: successful embolization using the Amplatzer Vascular Plug II.

A 67-year-old woman presented with memory impairment and behavioral changes. Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the aneurysmal sac that communicated directly with the right hepatic vein. The large tract was successfully occluded by embolization using the newly available AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The patient's symptoms disappeared after shunt closure and she remained free of recurrence at the 3-month follow-up evaluation.

Clinical effects of the levonorgestrel-releasing intrauterine device in patients with adenomyosis.

OBJECTIVE: The aim of this study was to evaluate the long-term clinical effects of a levonorgestrel-releasing intrauterine device (LNG-IUD) on adenomyosis. STUDY DESIGN: A LNG-IUD was inserted into 47 patients who were diagnosed with adenomyosis. Uterine volume, uterine artery blood flow, pictorial blood loss assessment chart (PBAC) scores, and the degree of dysmenorrhea were evaluated before and 36 months after insertion of the LNG-IUD. RESULTS: Pain scores and PBAC scores dropped dramatically in 6 months and showed significant decrease after 36 months. A significant decrease in mean uterine volume was noted 12 months (156.85 +/- 49.79 mL to 118.64 +/- 41.36 mL; P < .001) and 24 months (128.84 +/- 48.70 mL; P < .001) after LNG-IUD insertion, but no significant differences were noted at 36 months. The mean pulsatility indices of both uterine arteries increased significantly 12 months after insertion (P = .002 for right; P = .011 for left) and decreased after 24 months without significance. Uterine volume and uterine blood flow were negatively correlated (Pearson's correlation, P < .05). Significant increase of uterine volume, pain scores, and PBAC scores were noted at 36 months compared with 12 months after insertion (P = .034, .021, and .001, respectively). CONCLUSION: For patients with clinical diagnosis of adenomyosis, the LNG-IUD is effective for the reduction of uterine volume with improvement of vascularity and relief of symptoms. However, the efficacy of LNG-IUD on uterine volume may begin to decrease 2 years after insertion.

Predictors of leiomyoma recurrence after laparoscopic myomectomy.

STUDY OBJECTIVE: To evaluate recurrence and reoperation rate after laparoscopic myomectomy in relation to risk factors and identify suitable candidates for laparoscopic myomectomy to decrease recurrence. DESIGN: Multicenter retrospective cohort study (Canadian Task Force classification II-2). SETTING: Five university hospitals and a university-affiliated teaching hospital. PATIENTS: Five hundred and twelve women who underwent laparoscopic myomectomy between 1995 and 2004. All patients had a follow-up with clinical examination and transvaginal sonography for a median 13 months after surgery. INTERVENTION: Laparoscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: Recurrence was defined as the appearance of a leiomyoma on ultrasound examination or identification of leiomyoma during subsequent surgery after the initial surgery. Cox regression (full model) analysis of the possible risk factors for recurrence followed by a stepwise variable selection was performed to eliminate confounding factors. The cumulative probability of leiomyoma recurrence increased steadily during the follow-up period, 11.7% after 1 year, 36.1% after 3 years, 52.9% at 5 years, and reached 84.4% at 8 years. The cumulative probability of reoperation for recurrent leiomyoma was much lower: 6.7% at 5 years and 16% at 8 years. Significant risk factors that were independently associated with cumulative recurrence were age, preoperative number of myoma, preoperative uterine size by pelvic examination, presence of associated pelvic disease, and delivery after laparoscopic myomectomy. The operative time and change of hematocrit were associated with the reoperation. Those who had fewer than 2 myomas before surgery, uterus size less than 13 gestational weeks measured by pelvic examination, no childbirth after laparoscopic myomectomy, and age at index surgery less than 35.5 years showed the lowest recurrence after laparoscopic myomectomy from Classification and Regression trees analysis. CONCLUSION: The risk of recurrence of leiomyoma after laparoscopic myomectomy is linked with the age, preoperative number of leiomyoma, preoperative uterine size, presence of associated pelvic disease, and childbirth after surgery.

Treatment outcomes of uterine artery embolization and laparoscopic uterine artery ligation for uterine myoma.

In treating women with leiomyoma and who wish to preserve their uterus, laparoscopic uterine artery ligation or uterine artery embolization should be considered as possible options. This study was performed to evaluate the efficacy of laparoscopic uterine artery ligation and uterine artery embolization in treating uterine myoma. The treatment outcomes of 23 patients who underwent uterine artery embolization and 17 laparoscopic uterine artery ligation were evaluated. The uterine volume reduced 3 months after uterine artery embolization, but thereafter no significant changes were observed. On the other hand, the uterine volumes were only slightly reduced 3 months after laparoscopic uterine artery ligation, and slightly more reduced 6 months later. The average reduction in the case of laparoscopic uterine artery ligation was about 58.5%. After laparoscopic uterine artery ligation, 20% of the patients complained of vaginal spotting. Furthermore, the mechanism of volume reduction was evaluated using specimens obtained from a biopsy taken after each procedure. The results suggested that laparoscopic uterine artery ligation results mainly in physiologic cell death, that is apoptosis, whereas, the corresponding result is cell necrosis for uterine artery embolization. Uterine artery embolization and laparoscopic uterine artery ligation are both effective in relieving the symptoms caused by uterine myoma, and therefore both procedures can be used in place of hysterectomy or myomectomy.