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Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication. [ABSTRACT FROM AUTHOR]

Probiotics are thought to be effective in the treatment of radiation-induced enteropathy (RIE). However, little is known regarding their efficacy in preventing RIE. In this prospective, randomized, double-blinded, placebo-controlled, single-center study, the incidence of grade 2 acute RIE was compared and the safety of probiotics was evaluated. Patients receiving pelvic radiotherapy for a minimum of 40 Gy at the pelvic level were randomized into two groups: (i) a probiotic group receiving Bacillus licheniformis from two weeks before radiotherapy until the end and (ii) a control group receiving a placebo with the same schedule. The toxicities of 234 patients were graded according to the Common Terminology Criteria for Adverse Events v5.0. Grade 1 RIE was observed in 65 (56%) of the probiotics group compared with 75 (64%) of the placebo group. Grade 2 RIE occurred in 30 patients (26%) in the probiotics group compared with 26 (22%) in the placebo group, indicating that probiotics failed in their preventive role compared with placebo (p = 0.493). Medication adherence rates were good, and no difference was observed between the two arms. These findings suggest that B. licheniformis does not significantly prevent RIE. [ABSTRACT FROM AUTHOR]

Background and Objectives: Immune check inhibitor (ICI) colitis is one of most common and adverse side effects of ICI. However, there was no case report of ulcerative colitis (UC)-mimicking colitis after atezolizumab use in hepatocellular carcinoma (HCC) to our knowledge. Materials and Methods: We would like to introduce the case of a patient with Stage IV HCC who complained of abdominal pain, diarrhea and rectal bleeding after two cycles of atezolizumab/bevacizumab chemotherapy and was then diagnosed with UC-mimicking colitis. Results: Endoscopy revealed typical findings of UC, suggesting diagnosis of UC-mimicking colitis. The patient was treated with systemic steroids and oral mesalamine, which significantly improved his symptoms, which were also supported by endoscopic findings. The patient resumed chemotherapy with atezolizumab and bevacizumab without any interruption to the chemotherapy schedule. Conclusions: Early endoscopic evaluation is pivotal to diagnosing UC-mimicking colitis. If diagnosed, UC-based treatments such as steroids and mesalamine should be strongly considered. Given previous reports of inflammatory bowel disease (IBD) flare-ups after immunotherapy, routine lower endoscopy, performed together with upper endoscopy before atezolizumab/bevacizumab therapy, is promising to patients. [ABSTRACT FROM AUTHOR]

Background: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. Methods: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6–9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0–29.9%, 30–49.9%, 50–69.9%, 70–79.9%, 80–89.9%, and 90–100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. Results: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. Conclusion: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ascites, often associated with liver cirrhosis, poses diagnostic challenges, particularly in detecting bacterial infections. Traditional methods have limitations, prompting the exploration of advanced techniques such as 16S rDNA next-generation sequencing (NGS) for improved diagnostics in such low-biomass fluids. The aim of this study was to investigate whether the NGS method enhances detection sensitivity compared to a conventional ascites culture. Additionally, we aimed to explore the presence of a microbiome in the abdominal cavity and determine whether it has a sterile condition. Materials and Methods: Ten patients with clinically suspected spontaneous bacterial peritonitis (SBP) were included in this study. A traditional ascites culture was performed, and all ascites samples were subjected to 16S ribosomal RNA gene amplification and sequencing. 16S rRNA gene sequencing results were interpreted by comparing them to positive and negative controls for each sample. Results: Differential centrifugation was applied to all ascites samples, resulting in very small or no bacterial pellets being harvested. The examination of the 16S amplicon sequencing libraries indicated that the target amplicon products were either minimally visible or exhibited lower intensity than their corresponding negative controls. Contaminants present in the reagents were also identified in the ascites samples. Sequence analysis of the 16S rRNA gene of all samples showed microbial compositions that were akin to those found in the negative controls, without any bacteria isolated that were unique to the samples. Conclusions: The peritoneal cavity and ascites exhibit low bacterial biomass even in the presence of SBP, resulting in a very low positivity rate in 16S rRNA gene sequencing. Hence, the 16S RNA sequencing method does little to enhance the rate of positive samples compared to traditional culture methods, including in SBP cases. [ABSTRACT FROM AUTHOR]

Background and Objectives: Variceal bleeding (VB) is the most concerning condition that is difficult to treat after atezolizumab/bevacizumab in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: We would like to introduce the cases of two patients who underwent bevacizumab reduction or discontinuation when VB occurred after atezolizumab/bevacizumab. Results: VB occurred in two patients who showed good tumor response after atezolizumab/bevacizumab treatment, and all VBs were successfully treated with endoscopic variceal ligations. In the first patient, VB did not occur as the tumor response decreased after a 50% reduction in bevacizumab. In the second patient, VB occurred again after a 50% bevacizumab reduction, so bevacizumab was discontinued and treatment with atezolizumab alone has been successfully maintained. Conclusions: Accordingly, we would like to suggest that considering bevacizumab dose reduction instead of changing to tyrosine kinase inhibitor may be a good clinical choice in atezolizumab/bevacizumab patients who develop VB. [ABSTRACT FROM AUTHOR]

Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based approach, cholera toxin B (CTB) was harnessed as a structural scaffold for the five-fold symmetry of EDIII. Pivoted by an RNA-mediated chaperone for the protein folding and assembly, CTB-EDIII of dengue serotype 1 (DV1) was successfully produced as soluble pentamers in an E. coli host with a high yield of about 28 mg/L. Immunization of mice with CTB-DV1EDIII elicited increased levels of neutralizing antibodies against infectious viruses compared to the control group immunized with DV1EDIII without CTB fusion. IgG isotype switching into a balanced Th1/Th2 response was also observed, probably triggered by the intrinsic adjuvant activity of CTB. Confirming the immune-enhancing potential of CTB in stabilizing the pentamer assembly of EDIII, this study introduces a low-cost bacterial production platform designed to augment the soluble production of subunit vaccine candidates, particularly those targeting flaviviruses. [ABSTRACT FROM AUTHOR]

It is well known that renal dysfunction has a devastating effect on the prognosis of liver cirrhosis. In this study, the aim was to assess whether the incorporation of the kidney dysfunction type into the MELD-Na score enhances its predictive capacity for outcomes in patients awaiting liver transplantation (LT), compared to utilizing the MELD 3.0 score with albumin. In total, 2080 patients awaiting the LT were enrolled at two tertiary care institutions in Korea. Discrimination abilities were analyzed by using Harrell's c-index and iAUC values between MELD-Na-kidney dysfunction type (MELD-Na-KT) and MELD 3.0 with albumin. Clinical endpoints encompassed 3-month survival, 3-month transplant-free survival (TFS), overall survival (OS), and total TFS. Out of the total of 2080 individuals, 669 (32.16%) were male. Regarding the types of renal function impairment, 1614 (77.6%) were in the normal group, 112 (5.38%) in the AKD group, 320 (15.35%) in the CKD group, and 34 (1.63%) were in the AKD on CKD group. MELD 3.0 with albumin showed better discrimination (c-index = 0.714) compared to MELD-Na-KT (c-index = 0.708) in predicting 3-month survival. Similar results were observed for OS, 3-month TFS, and total TFS as well. When divided by sex, MELD 3.0 with albumin showed the comparable prediction of 3-month survival to MELD-Na-KT (c-index 0.675 vs. 0.671, p-value 0.221) in males. However, in the female group, MELD 3.0 with albumin demonstrated better results compared to MELD-Na-KT (c-index 0.733 vs. 0.723, p-value 0.001). The integration of kidney dysfunction types into the MELD-Na did not yield superior prognostic results compared to the MELD 3.0 score with albumin. Rather, in the female group, the MELD 3.0 score with albumin was better able to predict survival. These findings suggest that laboratory values pertaining to liver dysfunction or creatinine levels may be more significant than the type of kidney dysfunction when predicting the short-term prognosis of LT candidates. [ABSTRACT FROM AUTHOR]

In the present study, the AlCoCrNi high-entropy metallic film was deposited on a Si wafer using a magnetron sputtering system. To capture the effects of the sputtering parameters on the microstructure and mechanical properties of the film, the flow rate of Ar gas injected into the chamber (5, 7, and 8 sccm) was controlled. All films were identified as being of BCC phase with compositions of near equiatomic proportions, regardless of the gas flow rates. Nano-scale clusters were observed on the surfaces of all films, and nano-cracks were found in the film deposited at the Ar gas flow rate of 8 sccm, unlike the films deposited at the gas flow rates of 5 and 7 sccm. Detailed microstructural analysis of film deposition at an Ar gas flow rate of 8 sccm indicated that the void boundaries contribute to the formation of nano-cracks. The nano-indentation results indicated that the Ar gas flow rate 5 sccm specimen, with the smallest cluster size at the topmost surface, showed the highest hardness (12.21 ± 1.05 GPa) and Young's modulus (188.1 ± 11 GPa) values. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic viral hepatitis such as hepatitis B or hepatitis C is frequently related to nephropathies, yet acute hepatitis A virus (HAV) infection is an exception. Materials and Methods: A 43-year-old male presented with jaundice accompanied by nausea and vomiting. The patient was diagnosed with acute HAV infection. Although the liver function improved after conservative treatment, various symptoms such as proteinuria, hypoalbuminemia, generalized edema and pleural effusion persisted. Due to nephrotic syndrome, the patient was referred to the clinic of the nephrology department and a renal biopsy was performed. Results: The result of the renal biopsy was focal segmental glomerulosclerosis (FSGS) based on histology, electron microscopy and immunohistochemistry. Therefore, based on the clinical history and biopsy results, the patient was diagnosed as having FSGS aggravated by acute HAV infection. Proteinuria, hypoalbuminemia and generalized edema were improved after prednisolone treatment. Conclusions: Although less common, acute HAV infection can also present with an extrahepatic manifestation, for example, FSGS. Hence, clinical attention is required if proteinuria or hypoalbuminemia persists in patients with acute HAV infection. [ABSTRACT FROM AUTHOR]

The association of smoking with hepatocellular carcinoma (HCC) or cardiovascular disease (CVD) has been reported, but the study of its relationship with metabolic-associated fatty liver disease (MAFLD) is limited. We aimed to investigate the effect of smoking on the incidence of HCC or CVD in MAFLD patients. Using the Korean nationwide health screening database, we analyzed subjects between 2001 and 2015. A total of 283,088 subjects including 110,863 MAFLD patients and 172,225 controls were analyzed. Smoking status was divided by non-smoker, ex-smoker, or current smoker. In the follow-up period, a total of 2903 (1.0%) subjects developed HCC, and the MAFLD group (1723, 1.6%) had a significantly higher incidence than the control group (1180, 0.7%). In the MAFLD group, current smokers showed significantly higher risk of HCC compared to non-smokers (adjusted HR 1.24, 95% CI 1.08–1.41), whereas the control group did not (adjusted HR 1.07, 95% CI 0.89–1.30). A total of 18,984 (6.7%) patients developed CVD, and the incidence was significantly higher in the MAFLD group (8688, 7.8%) than in the control group (10,296, 6.0%), similar to HCC. The risk of CVD in current smokers increased by 22% compared to non-smokers in the MAFLD group (adjusted HR 1.22, 95% CI 1.15–1.30) and by 21% (adjusted HR 1.21, 95% CI 1.13–1.29) in the control group. Based on sex stratification, men showed increased incidence of both HCC and CVD by smoking, whereas women had only increased risk of CVD. Smoking significantly increases the incidence of HCC and CVD in MAFLD patients; thus, it is highly recommended to quit smoking completely in the population with MAFLD. [ABSTRACT FROM AUTHOR]

Background: This aim of this study was to develop an objective tool for rating submental fat applied to Koreans. Methods: The study was conducted between April 2019 and October 2019. A total of 92 subjects were enrolled in the study. Clinical photos of the subjects were categorized using validated CR-SMFRS by three plastic surgeons and one dermatologist. The categorized photos were then shown to six different plastic surgeons for evaluation. Results: The Cohen's kappa value for the six raters were 0.830, 0.742, 0.703, 0.907, 0.862, and 0.793 with statistical significance (p < 0.001). ICC value was between 0.860 and 0.966 (p < 0.001). Since the Cohen's value and ICC were above 0.6 for all raters, the ratings performed by all six raters were used in the analysis. The ICC values between raters were between 0.899 and 0.902. Conclusions: We came up with a set of reference photos that can be used for submental fat rating scale applicable to Korean subjects. Level of Evidence: II. [ABSTRACT FROM AUTHOR]

Background and Objectives: Many otologists face a dilemma in the decision-making process of surgical management of patients with cochlear nerve (CN) aplasia. The goal of this study is to provide fresh evidence on cochlear implantation (CI) results in patients with CN aplasia. Materials and Methods: We scrutinized functional outcomes in 37 ears of 21 children with bilateral CN aplasia who underwent unilateral or bilateral CI based on cross-sectional and longitudinal assessments. Results: The Categories of Auditory Performance (CAP) scores gradually improved throughout the 3-year follow-up; however, variable outcomes existed between individuals. Specifically, 90% of recipients with a 1-year postoperative CAP score ≤1 could not achieve a CAP score over 1 even at 3-year postoperative evaluation, while the recipients with a 1-year postoperative CAP score >1 had improved auditory performance, and 72.7% of them were able to achieve a CAP score of 4 or higher. Meanwhile, intraoperative electrically evoked compound action potential was not correlated with postoperative CAP score. Conclusions: Our results further refine previous studies on the clinical feasibility of CI as the first treatment modality to elicit favorable auditory performance in children with CN aplasia. However, special attention should be paid to pediatric patients with an early postoperative CAP score ≤1 for identification of unsuccessful cochlear implants and switching to auditory brainstem implants. [ABSTRACT FROM AUTHOR]

Introduction: The pathogenesis of autoimmune hepatitis (AIH) is little known. Previous case reports suggest that several viral hepatitis, including hepatitis A, can trigger AIH. Patient: A 55-year-old female showed general weakness and jaundice. The patient was diagnosed with acute hepatitis A and discharged after 14 days of hospitalization with improving liver function. However, blood tests performed 6 days after discharge revealed an increase in liver enzymes and high serum titers of an anti-nuclear antibody and immunoglobulin G. She was readmitted for liver biopsy. Diagnosis: Liver biopsy showed acute hepatitis A along with AIH. According to the revised international autoimmune hepatitis group scoring system, her score was 14 and she was diagnosed as AIH induced by acute hepatitis A. Intervention: Conservative treatments with crystalloid (Lactated Ringer's Solution), ursodeoxycholic acid, and silymarin were administered. Outcomes: The patient has been followed up on an outpatient basis and neither symptom recurrence nor an increase in liver enzymes has been reported thus far. Lessons: After the treatment of acute hepatitis A, liver function needs to be carefully monitored over time, and the possibility of autoimmune hepatitis should be considered when liver enzymes increases. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient's serum were cloned into the replication-competent HBV 1.2 mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient. [ABSTRACT FROM AUTHOR]

Background: Patients with non-alcoholic fatty liver disease (NAFLD) have a high prevalence of combined hyperlipidemia. The importance of nutritional education is well-known in NAFLD, but the impact of medical nutrition therapy (MNT) is unclear in patients with NAFLD with hyperlipidemia. The purpose of this study is to investigate the effect of MNT on the improvement of steatohepatitis in patients with NAFLD taking antihyperlipidemic medications. Methods: Nondiabetic patients with dyslipidemia were prospectively randomized (1:1) either to the MNT group or the control group with standard advice for 48 weeks with simultaneous statin/ezetimibe combination pharmacotherapy at three tertiary centers in Korea. Results: Sixty-six patients were enrolled. Among them, 18 patients dropped out and, overall, 48 patients (MNT group 27, control group 21) were prospectively analyzed in the study. The serum ALT level at 48 weeks between the two groups was not significantly different (66.6 ± 37.7 IU/L vs. 57.4 ± 36.7 IU/L, p = 0.40). Serum liver enzymes, controlled attenuation parameter and fibrosis-4 index were significantly improved within the MNT group after 48 weeks compared to baseline. There was no significant difference between the two groups other than the NAFLD fibrosis score (p = 0.017). Conclusions: Although there were no significant differences between the two groups in terms of steatosis, metabolic and fibrosis surrogate indicators after 48 weeks, MNT groups showed significant improvement within patient analysis over time. Future studies with a larger number of subjects and a longer study period regarding the effect of MNT are warranted. [ABSTRACT FROM AUTHOR]

Background/Aim: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. Methods: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluate the efficacy and safety of TDO on switching from TDF for 24 weeks in virologically suppressed chronic hepatitis B patients. The primary efficacy endpoint was the maintenance of virologic response. Safety was assessed by evaluating major adverse events, changes in renal function, and occurrence of hepatocellular carcinoma (HCC). Results: TDO treatment was not inferior in terms of virological response when compared with that on TDF treatment, with a noninferiority margin of −10% (risk difference, −3.17%; 95% confidence interval, −7.5–1.15%). The biological response of TDO was also comparable to that of TDF, with no significant difference in the proportion of patients with normalized alanine transaminase levels. After 24 weeks of treatment, hepatitis B core-related antigen (HBcrAg) significantly decreased to a mean titer of 3.91 log U/mL from 4.15 log U/mL at baseline (p = 0.01). There were no cases of grade 3 or higher adverse events and HCC. The mean estimated glomerular filtration rate increased from 91.09 mL/min to 93.34 mL/min (p = 0.056), and the mean serum level of phosphorus increased from 3.33 mg/dL to 3.44 mg/dL (p = 0.045), suggesting improvement in renal function with TDO treatment. Conclusion: In patients with chronic hepatitis B, the efficacy of TDO was noninferior to that of TDF, with a significant decrease in the HBcrAg titer and improved renal function. [ABSTRACT FROM AUTHOR]

Background and Aims: Currently, it is difficult to predict the reversibility of renal function and to discriminate renal parenchymal injury in cirrhotic patients with acute kidney injury (AKI). The aim of this study is to evaluate whether urine N-acetyl-β-d-Glucosaminidase (NAG) can predict the survival and response to terlipressin in cirrhotic patients with AKI. Methods: Two hundred sixty-two cirrhotic consecutive patients who developed AKI were prospectively enrolled from 11 tertiary medical centers in Korea between 2016 to 2019. AKI was defined as an increase in serum Cr (SCr) of 0.3 mg/dL or a 50% increase in baseline SCr. Patients diagnosed with hepatorenal syndrome (HRS-AKI) were treated with terlipressin plus albumin. Results: The patients were 58.8 ± 12.9 years old on average and were predominantly male (72.5%). The mean MELD score was 25.3 ± 9.1. When classified according to the AKI phenotype, there were 119 pre-renal, 52 acute tubular necrosis, 18 miscellaneous, and 73 HRS-AKI patients. However, the urine NAG was not effective at discriminating AKI phenotypes, except for HRS-AKI. The baseline urine NAG increased as the baseline AKI stage increased (p < 0.001). In addition, within the same AKI stage, the urine NAG values were significantly lower in the AKI-resolved group than in the unresolved group. The urine NAG level was significantly lower in living patients compared with those who died or who underwent a liver transplant within 3 months (p = 0.005). In the multivariate analysis, the increased urine NAG was a significant risk factor for the 3-month transplant-free survival (TFS) rate, especially in patients with Child–Pugh class ≤ B or MELD < 24. The urine NAG did not predict the response to terlipressin treatment in patients with HRS. Conclusions: Urine NAG is strongly associated with the severity of AKI in patients with liver cirrhosis and is useful for predicting the 3-month TFS. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the usefulness of two different types of 2-dimensional shear wave elastography (2D-SWE) for predicting liver fibrosis stages in comparison to transient elastography (TE), using a histologic METAVIR scoring system as the reference method. Methods: A total of 203 patients with chronic liver disease were prospectively enrolled in the study. Two different 2D-SWEs (LOGIQ S8 and E9 systems, GE Healthcare, Chalfont St Giles, UK) were assessed for liver stiffness in patients with chronic liver diseases. Patients received 2D-SWE examinations with the S8 and E9 systems, and also underwent TE (FibroScan®, Echosens, France) tests and liver biopsies on the same day. Results: The most common etiology of chronic liver disease was non-alcoholic fatty liver disease (28.7%), followed by chronic hepatitis B (25.1%). Liver fibrosis stages consisted of F0 (22.6%), F1 (29.7%), F2 (16.9%), F3 (12.8%) and F4 (17.9%). Overall, S8 and E9 were well correlated with the histologic fibrosis stages. The optimal cut-off values for S8 and E9 to differentiate significant fibrosis (≥F2) were 6.70 kPa and 6.42 kPa, respectively, while the cut-off values for S8 and E9 in distinguishing liver cirrhosis were 9.15 kPa and 8.88 kPa, respectively. Among the 195 patients who had successful measurements in both S8 and E9, liver stiffness showed good inter-equipment correlation (ICC: 0.900, p < 0.001). Regarding diagnostic ability, upon comparison (FibroScan®), there were no significant differences between 2D-SWEs and TE for detecting every stage of liver fibrosis. Conclusion: In comparison to TE, 2D-SWE with LOGIQ S8 and E9 (GE Healthcare) are useful non-invasive tools for predicting significant fibrosis and liver cirrhosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Pelvic nodal involvement is frequently present in early-stage cervical cancer patients on pretreatment imaging studies. However, it is unclear whether radical chemoradiotherapy (CRT) or radical hysterectomy RH followed by tailored adjuvant radiotherapy is more appropriate in these patients. We compared oncological outcomes of up-front surgery followed by tailored adjuvant radiotherapy and definitive CRT in these patients. We found no differences in outcomes existed between definitive CRT and hysterectomy with tailored adjuvant radiotherapy. However, after surgery, 88.7% of patients required adjuvant radiotherapy. These findings suggest that definitive CRT can avoid unplanned tri-modality therapy without compromising oncologic outcomes. To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified; among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer to identify the optimal EBRT strategy for each risk-stratified patient subgroup for clinical practice implementation. In 1573 patients from 17 institutions, EBRT treated prostate cancer effectively. Also, among various risk classification tools, NCCN classification revealed the highest predictive power. The modern RT techniques and dose escalation (≥179 Gy1.5) enhanced therapeutic effects of RT significantly, especially in the high-risk group. On the other hand, modest doses (≥170 Gy1.5) was a significant factor in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. IMRT+ ≥179 Gy1.5+ hypofractionation resulted in higher biochemical failure-free survival in all risk groups, and it translated into survival benefits in the high-risk group. Therefore, risk-adapted RT (more intense RT, high-risk patients; moderate-dose RT, low-risk patients) can be considered, although further prospective studies are warranted. Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588; p < 0.001). Gleason score, iPSA < 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p < 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited. [ABSTRACT FROM AUTHOR]

Thermally conductive films play a crucial role in expanding the lifetime of electronics by dissipating concentrated heat to heatsinks. In this work, a thermally conductive film (g-TC film) was manufactured using a perforated graphite sheet (p-GS) and a UV-curable pressure-sensitive adhesive (PSA) by lamination. A novel UV-curable PSA was prepared by incorporating a UV-curable abietic acid ester into a PSA composition. The UV-curable PSA became a tack-free film upon UV irradiation; thus, a flexible g-TC film with a 52-μm thickness was obtained. The defects in the g-TC film caused by air bubbles were removed by treating the p-GS with oxygen plasma. As the UV-cured PSA made a joint through the holes in the p-GS, cleavage of the graphite was not observed after 10,000 U-folding test cycles with a folding radius of 1 mm. The calculated in-plane thermal conductivity of the fabricated g-TC film was 179 W∙m−1K−1, which was stable after the U-folding tests. [ABSTRACT FROM AUTHOR]

This paper presents an energy-optimized electronic performance tracking system (EPTS) device for analyzing the athletic movements of football players. We first develop a tiny battery-operated wearable device that can be attached to the backside of field players. In order to analyze the strategic performance, the proposed wearable EPTS device utilizes the GNSS-based positioning solution, the IMU-based movement sensing system, and the real-time data acquisition protocol. As the life-time of the EPTS device is in general limited due to the energy-hungry GNSS sensing operations, for the energy-efficient solution extending the operating time, in this work, we newly develop the advanced optimization methods that can reduce the number of GNSS accesses without degrading the data quality. The proposed method basically identifies football activities during the match time, and the sampling rate of the GNSS module is dynamically relaxed when the player performs static movements. A novel deep convolution neural network (DCNN) is newly developed to provide the accurate classification of human activities, and various compression techniques are applied to reduce the model size of the DCNN algorithm, allowing the on-device DCNN processing even at the memory-limited EPTS device. Experimental results show that the proposed DCNN-assisted sensing control can reduce the active power by 28%, consequently extending the life-time of the EPTS device more than 1.3 times. [ABSTRACT FROM AUTHOR]

Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low. Methods: This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts. Results: The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. Conclusion: This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low. [ABSTRACT FROM AUTHOR]

Numerous wearable sensors have been developed for a variety of needs in medical/healthcare/wellness/sports applications, but there are still doubts about their usefulness due to uncomfortable fit or frequent battery charging. Because the size or capacity of battery is the major factor affecting the convenience of wearable sensors, power consumption must be reduced. We developed a method that can significantly reduce the power consumption by introducing a signal repeater and a special switch that provides power only when needed. Antenna radiation characteristics are an important factor in wireless wearable sensors, but soft material encapsulation for comfortable fit results in poor wireless performance. We improved the antenna radiation characteristics by a local encapsulation patterning. In particular, ultra-low power operation enables the use of paper battery to achieve a very thin and flexible form factor. Also, we verified the human body safety through specific absorption rate simulations. With these methods, we demonstrated a wearable infant sleep position sensor. Infants are unable to call for help in unsafe situations, and it is not easy for caregivers to observe them all the time. Our wearable sensor detects infants' sleep positions in real time and automatically alerts the caregivers when needed. [ABSTRACT FROM AUTHOR]

In this study, Mo–Si–N coatings were deposited on Si wafers and tungsten carbide substrates using a reactive direct current magnetron sputtering system with a MoSi powder target. The influence of sputtering parameters, such as the N2 gas flow ratio and working pressure, on the microstructure and mechanical properties (hardness (H), elastic modulus (E), and H/E ratio) of the Mo–Si–N coatings was systematically investigated using X-ray diffractometry (XRD), scanning electron microscopy (SEM), nanoindentation, and transmission electron microscopy (TEM). The gas flow rate was a significant parameter for determining the crystallinity and microstructure of the coatings. A Mo2N crystalline coating could be obtained by a high N2 gas flow ratio of more than 35% in the gas mixture, whereas an amorphous coating could be formed by a low N2 gas flow ratio of less than 25%. Furthermore, the working pressure played an important role in controlling the smooth surface and densified structure of the Mo–Si–N coating. For the amorphous Mo–Si–N coating deposited with the lowest working pressure (1 mTorr), the hardness, elastic modulus, and H/E ratio reached from 9.9 GPa, 158.8 GPa, and 0.062 up to 17.9 GPa, 216.1 GPa, and 0.083, respectively. [ABSTRACT FROM AUTHOR]

In the present study, novel AlCoCrNi high entropy nitride (HEN) films were deposited on Si substrate by a reactive direct current magnetron sputtering system. In order to investigate the influence of sputtering parameters on the microstructure and mechanical properties of the film, nitrogen flow ratio (RN: 25–100%) and process pressure (1.33 × 10−1–1.33 Pa) were controlled, respectively. All the films were identified as an amorphous phase with composition of near equiatomic ratios, regardless of the conditions of nitrogen flow ratios and process pressures. However, the limited mechanical properties were found for the films deposited under different nitrogen flow ratios with retaining the process pressure of 1.33 Pa. To enhance the mechanical properties of the AlCoCrNi HEN film, process pressure was adjusted. From the transmission electron microscopy (TEM) observation, the structure of the film deposited at the process pressure of 1.33 Pa is identified as a porous and open structure with a number of density-deficient boundary and nano-scale voids. On the other hand, densified morphology of the film was observed at pressure of 1.33 × 10−1 Pa. As a result, the hardness, elastic modulus, and H/E were improved up to 16.8, 243 GPa, and 0.0692, respectively. [ABSTRACT FROM AUTHOR]

Background: Transient elastography is now an indispensable tool for estimating liver fibrosis. Although many clinical factors other than fibrosis itself are known to affect liver stiffness (LS) values, it is still not yet clear what factors are related to improving LS values. The aim of this study was to find out how baseline histologic inflammation influences LS values and how much this inflammation affects improvement in LS values over time, regardless of actual fibrosis content. Methods: This retrospective study included 678 consecutive patients who underwent liver biopsy and sequential LS assessment from 2006 to 2015 at six tertiary hospitals in Korea. Linear regression analysis was used to evaluate how improvement of LS value can be associated with other factors besides fibrosis content. Results: Basal LS values increased with increasing inflammation in the same fibrosis stage. Degree of inflammation influenced the baseline LS value in a proportional manner (beta coefficient (BE), 6.476; 95% confidence interval (CI), 2.24–10.72; p = 0.003). Moreover, histologic inflammation affected the change in LS value significantly. Higher inflammation grade at baseline was a significant predictor for an improvement in LS value, regardless of the fibrosis stage (BE, −8.581; 95% CI, −15.715–−1.447; p = 0.019). In a subgroup analysis of patients who received repeated liver biopsies, the results showed a similar tendency. Conclusions: The LS value is affected by the degree of inflammation even at a low ALT level. Furthermore, baseline histologic inflammation has a significant impact on the improvement of LS values over time. Therefore, baseline inflammation should be taken into consideration when interpreting an improvement in LS value. [ABSTRACT FROM AUTHOR]

Numerous wearable sensors have been developed for a variety of needs in medical/healthcare/wellness/sports applications, but there are still doubts about their usefulness due to uncomfortable fit or frequent battery charging. Because the size or capacity of battery is the major factor affecting the convenience of wearable sensors, power consumption must be reduced. We developed a method that can significantly reduce the power consumption by introducing a signal repeater and a special switch that provides power only when needed. Antenna radiation characteristics are an important factor in wireless wearable sensors, but soft material encapsulation for comfortable fit results in poor wireless performance. We improved the antenna radiation characteristics by a local encapsulation patterning. In particular, ultra-low power operation enables the use of paper battery to achieve a very thin and flexible form factor. Also, we verified the human body safety through specific absorption rate simulations. With these methods, we demonstrated a wearable infant sleep position sensor. Infants are unable to call for help in unsafe situations, and it is not easy for caregivers to observe them all the time. Our wearable sensor detects infants' sleep positions in real time and automatically alerts the caregivers when needed.

The functional inactivation of TP53 and Rb tumor suppressor proteins by the HPV-derived E6 and E7 oncoproteins is likely an important step in cervical carcinogenesis. We have previously shown siRNA technology to selectively silence both E6/E7 oncogenes and demonstrated that the synthetic siRNAs could specifically block its expression in HPV-positive cervical cancer cells. Herein, we investigated the potentiality of E6/E7 siRNA candidates as radiosensitizers of radiotherapy for the human cervical carcinomas. HeLa and SiHa cells were transfected with HPV E6/E7 siRNA; the combined cytotoxic effect of E6/E7 siRNA and radiation was assessed by using the cell viability assay, flow cytometric analysis and the senescence-associated β-galactosidase (SA-β-Gal) assay. In addition, we also investigated the effect of combined therapy with irradiation and E6/E7 siRNA intravenous injection in an in vivo xenograft model. Combination therapy with siRNA and irradiation efficiently retarded tumor growth in established tumors of human cervical cancer cell xenografted mice. In addition, the chemically-modified HPV16 and 18 E6/E7 pooled siRNA in combination with irradiation strongly inhibited the growth of cervical cancer cells. Our results indicated that simultaneous inhibition of HPV E6/E7 oncogene expression with radiotherapy can promote potent antitumor activity and radiosensitizing activity in human cervical carcinomas.