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This work presents a correlation between the behavior of formic acid oxidation (FAO) on various Bi-modified Pt(poly) disk electrodes and their morphologies observed on Bi-modified Pt(111) disk electrodes using electrochemical scanning tunneling microscopy (EC-STM) to understand the effects of Bi on Pt. To distinguish the FAO activities of Bi on Pt and plain Pt around Bi, additional Pt was intentionally deposited using two different routes: direct route and iodine route. In direct route, Pt was directly deposited on Bi islands and plain Pt sites around Bi islands, while in iodine route, Pt was exclusively deposited on Bi islands by protecting plain Pt sites with adsorbed iodine. Thus, a comparison of FAO performances on the two Bi-modified Pt electrodes with additional Pt (deposited in the different ways) disclosed a difference in FAO performances on plain Pt sites and Bi islands. When Bi coverage was ~0.04, the Bi deposits were scattered Bi islands enhancing FAO on Pt(poly). The additional Pt deposits using direct route increased FAO efficiency, while the ones using iodine route slightly decreased FAO current. The EC-STM observations indicated that Pt deposits around Bi islands, not on Bi islands, were responsible for the FAO current increase on Bi-modified Pt(poly). The FAO efficiency on Bi-modified Pt(poly) with a Bi coverage of ~0.25 increased by a factor of 2. However, the additional Pt deposits using the two Pt deposition routes notably decreased the FAO current. The dependency of FAO on Bi coverage was discussed in terms of electronic effect and ensemble effect.

Simply oxygen evolution Ni, Co-doped FeOOH cocatalyst layers were deposited by laser-induced deposition on WO3 photoanodes for enhanced PEC performance.

Background Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME. Methods In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus. Results Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P = 0.569 and P = 1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P = 0.006). Conclusion There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

Understanding the structure-activity relationship at electrochemical interfaces is crucial in improving the performance of practical electrochemical devices, ranging from fuel cells, electrolyzers, and batteries to electrochemical sensors. However, functional electrochemical interfaces are often complex and contain various surface structures, creating heterogeneity in electrochemical activity. In this Perspective, we highlight the role of heterogeneity in electrochemistry, especially in the context of electrocatalysis. Current methods for revealing the heterogeneity at electrochemical interfaces, including nanoelectrochemistry tools and single-entity approaches, are discussed. Lastly, we provide perspectives on what one can learn by studying heterogeneity and how one can use heterogeneity to design more efficient electrochemical devices.

Due to advancements in modern mobile communication technology, massive numbers of devices are now connected to the internet, but the associated information also has to be well protected. Many studies have proposed physical layer security (PLS) approaches utilizing artificial noise (AN), which is a simple approach to protecting information from an illegal receiver. However, this approach requires additional power allocation for AN. This paper proposes an efficient power balancing method for the Alamouti scheme, which provides efficient security capability as well as enhancement of power efficiency. The simulation results investigated in this paper reveal that the proposed scheme requires about 5 dB smaller power to achieve the same performance as that of the conventional AN-aided scheme, and eventually, about 2 dB less power than the conventional scheme without PLS.

The advent of human pluripotent stem cells (hPSCs) presented a new paradigm to employ hPSC-derived cardiomyocytes (hPSC-CMs) in drug screening and disease modeling. However, hPSC-CMs differentiated in conventional two-dimensional systems are structurally and functionally immature. Moreover, these differentiation systems generate predominantly one type of cell. Since the heart includes not only CMs but other cell types, such monolayer cultures have limitations in simulating the native heart. Accordingly, three-dimensional (3D) cardiac tissues have been developed as a better platform by including various cardiac cell types and extracellular matrices. Two advances were made for 3D cardiac tissue generation. One type is engineered heart tissues (EHTs), which are constructed by 3D cell culture of cardiac cells using an engineering technology. This system provides a convenient real-time analysis of cardiac function, as well as a precise control of the input/output flow and mechanical/electrical stimulation. The other type is cardiac organoids, which are formed through self-organization of differentiating cardiac lineage cells from hPSCs. While mature cardiac organoids are more desirable, at present only primitive forms of organoids are available. In this review, we discuss various models of hEHTs and cardiac organoids emulating the human heart, focusing on their unique features, utility, and limitations.

Direct imaging of electrochemical processes on electrode surfaces is a central part of understanding spatially heterogeneous electrochemical processes on the surfaces. Herein, we report a strategy for the spatially resolved imaging of local faradaic processes on nanoscale electrochemical interfaces. This strategy is based on fluorescence lifetime imaging microscopy (FLIM) with the use of Amplex Red as a fluorogenic redox probe. After verifying the capability of Amplex Red for fluorescence lifetime imaging, we demonstrated the turn-on FLIM-based imaging of faradaic processes on the electrochemical interfaces of different dimensions. In particular, we achieved spatially resolved visualization of the local electrochemical processes occurring on even nanopore electrode arrays as well as conventional microelectrodes, including disk-shaped ultramicroelectrodes and interdigitated array microelectrodes.

INTRODUCTION The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history. METHODS From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels

This work presents a contrasting behavior of formic acid oxidation (FAO) on the Pt and Bi deposits on different Pt substrates. Using irreversible adsorption method, Bi and Pt were sequentially deposited on Pt electrodes of nanoparticle (Pt NP) and disk (Pt disk). The deposited layers of Bi and Pt on the Pt substrates were characterized with X-ray photoelectron spectroscopy, transmission microscopy and scanning tunneling microscopy. The electrochemical behaviors and FAO enhancements of Pt NP and Pt disk with deposited Bi only (i.e., Bi/Pt NP and Bi/Pt disk), were similar to each other. However, additional deposition of Pt on Bi/Pt NP and Bi/Pt disk (i.e., Pt/Bi/Pt NP and Pt/Bi/Pt disk) changed the electrochemical behavior and FAO activity in different ways depending on the shapes of the Pt substrates. With Pt/Bi/Pt NP, the hydrogen adsorption was suppressed and the surface oxidation of Pt was enhanced; while with Pt/Bi/Pt disk, the opposite behavior was observed. This difference was interpreted as a stronger interaction between the deposited Bi and Pt on Pt NP than that on Pt disk. The FAO performance on Pt/Bi/Pt NP is much better than that on Pt/Bi/Pt disk, most likely due to the difference in the interaction between the deposited Pt and Bi depending on the shapes of Pt substrates. In designing FAO electrochemical catalysts using Pt and Bi, the shape of a Pt substrate was concluded to be critically considered.

Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here, we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types via the microRNA-mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells into the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.

Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC. From 2012 to 2019, treatment-naive CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan–Meier method. In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743). These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

Hye Won Lee,1– 3,* Hyun Woong Lee,4,* Jae Seung Lee,1– 3 Yun Ho Roh,5 Hyein Lee,3 Seung Up Kim,1– 3 Jun Yong Park,1– 3 Do Young Kim,1– 3 Sang Hoon Ahn,1– 3 Beom Kyung Kim1– 3 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea; 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Beom Kyung KimDepartment of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun–Gu, Seoul, 03722, Republic of KoreaTel +82-2-2228-1930Fax +82-2-393-6884Email beomkkim@yuhs.acBackground: Dynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff.Methods: The cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥ 2 years. LS was measured using transient elastography.Results: After ≥ 2 years’ AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p< 0.001). However, unlike cirrhosis on ultrasonography before AVT (p< 0.001), that after ≥ 2 years’ AVT did not discriminate HCC risk (p=0.792). Using the Contal and O’Quigley’s method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p< 0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4– 11.9 and ≥ 12.0 kPa (p=0.920).Conclusion: For HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.Keywords: antiviral treatment, hepatitis B, liver stiffness, hepatocellular carcinoma

Since there is no single cybersecurity law in Korea, cybersecurity regulations are embedded in several different laws. Penalty provisions applicable to cybercriminals are included in the Network Act, the Electronic Financial Transactions Act, and the Special Act on Financial Fraud. Separately, if personal information is compromised due to cybercrime, the person and/or entity responsible for processing the personal information may be subject to administrative/criminal penalties under the Personal Information Protection Act (PIPA) and Credit Information Use and Protection Act. When determining whether a data handler is responsible for a personal information leak under the PIPA, an important considerations is whether they implemented all the required technical and managerial security measures to safeguard the personal information. Also, even without a place of business in Korea, a foreign company is still highly likely to be subject to Korean law if it targets the Korean market. Furthermore, in some cases, the foreign company will be required to appoint a local privacy agent in Korea. In the case of a leak of personal information, the PIPC conducts an investigation into the data breach. A data handler’s failure to respond to a PIPC investigation may result in an administrative fine, thus most companies cooperate. The potential penalties imposable on companies suffering a personal information leak differ depending on whether the company is an information and communications service provider (ICSP) or a data handler. For ICSPs, a penalty surcharge of up to 3% of the relevant sales, an administrative fine, and a corrective order may be imposed, among others. Under certain circumstances, criminal proceedings may also be initiated against the ICSP.

We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC). Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates. The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group. The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.

Genomic analysis indicated that the genome of

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 30 million people worldwide. Despite growing knowledge of AD pathophysiology, a complete understanding of the pathogenic mechanisms underpinning AD is lacking, and there is currently no cure for AD. Extant literature suggests that AD is a polygenic and multifactorial disease underscored by complex and dynamic pathogenic mechanisms. Despite extensive research and clinical trials, there has been a dearth of novel drugs for AD treatment on the market since memantine in 2003. This lack of therapeutic success has directed the entire research community to approach the disease from a different angle. In this review, we discuss growing evidence for the close link between altered glucose metabolism and AD pathogenesis by exploring how genetic risk factors for AD are associated with dysfunctional glucose metabolism. We also discuss modification of genes responsible for metabolic pathways implicated in AD pathology.

The application of plant factory with artificial lighting (PFAL) for producing strawberry transplants (S-PFAL) was recently introduced due to the capacity for high quality and year-round transplant production. To achieve greater efficiency with this system, it is essential to select lighting sources that have a suitable spectrum for runner plant propagation. This study was conducted to investigate the effects of the light spectrum of white light-emitting diodes (LEDs), which have a different correlated color temperature compared with that of white fluorescent lamps, on the growth of strawberry (Fragaria × ananassa Duch. cv. Maehyang) propagules and runner plants in a PFAL. Uniform propagules with one fixed runner each were placed into a PFAL for transplant production and were grown under either warm-white LEDs (WWL), mint-white LEDs (MWL), or cool-white fluorescent lamps (CWF) for 21 days. The propagules in the MWL treatment group had the greatest number of leaves, leaf area, top/root dry weight ratio and number of newly formed runners per propagule among the treatments. The dry weight of the newly formed runners of each propagule was also greatest after MWL treatment, whereas it was lowest after CWF treatment. However, there was no significant difference in the growth parameters of the runner plants among the three treatments. The photosynthetic photon efficacy of WWL and MWL was 5.40 µmol s− 1 W− 1, which was 62.6% higher than that of CWF (3.38 µmol s− 1 W− 1). The dry weight efficacies of the MWL, WWL, and CWF treatments were 23.5, 22.1, and 10.0 g kWh− 1, respectively. These results indicate that MWL with high photosynthetic photon efficacy can have positive effects on the runner formation and growth of strawberry propagules and can replace cool-white fluorescent lamps in an S-PFAL.

Fully depleted silicon on insulator (FDSOI) is attractive for its low cost and low power; the mixed-Vt and body-bias levers that it affords expand the performance-power solution space. However, in FDSOI, different-Vt (i.e., low Vt and regular Vt) devices must be isolated from each other, which makes realization of fine-grained mixed-Vt/body-biasing in layout extremely challenging. In this article, we study heuristic methods aimed at exploitation of fine-grained mixed-Vt in FDSOI implementation. We propose a novel speed domain partitioning (SDP) problem formulation that comprehends the spatial contiguity restrictions arising from flip-well structure of low Vt regions in popular 28-nm commercial FDSOI offerings. We explore a wide space of implementation flows that include an integer linear programming (ILP)-based approach, and a heuristic (sensitivity-based) optimization. Our experimental studies have been performed across multiple commercial enablements. We observe that outcomes are library- and design-dependent. For implementations using generic library options, up to 20% speed improvement with 54% low Vt region is seen for one out of four testcases studied. For implementations using “rich” library options, up to 7% speed improvement with 26% low Vt region is achieved. We provide a discussion that summarizes root-cause, intrinsic difficulties of fine-grained exploitation of mixed-Vt. Finally, we suggest a “decision tree” to help assess a design’s amenability to fine-grained mixed-Vt implementation, and to help guide design flow selection for better design QoR.

Presented in this work is an investigation of co-deposits of Pt and Bi on Au disk (Pt-Bi/Au) toward formic acid oxidation (FAO) using voltammetry and X-ray photoelectron spectroscopy (XPS). The co-deposits of Pt and Bi on Au were prepared using an irreversible method in a mixed solution of Pt ion (1 mM) and Bi ion (5 mM), and the amount of co-deposits was controllable by the number of deposition cycles. The voltammetric studies revealed that the Pt-Bi/Au surfaces presented the characteristics of Pt, Bi, and Au depending on the number of deposition cycles. A detailed analysis of semi-quantitative results of XPS combined with hydrogen coverage on Pt and covered fraction of Au surface suggested two aspects of Pt-Bi co-deposits. One is that during co-adsorption, Bi adsorbing with a low efficiency enhanced irreversible adsorption of Pt. The other is that the Pt-Bi co-deposits would be an alloy of Pt-Bi when the Pt amount was low or Pt deposits enriched with Bi in surface regions when the Pt amount was high. The best FAO catalytic efficiency among the investigated Pt-Bi/Au surfaces was ~ 14 mA/cm2, which was higher than that of plain Pt deposits on Au (~ 6 mA/cm2) and comparable to that of sequentially prepared Bi-modified Pt deposits on Au (Bi/Pt/Au, ~ 20 mA/cm2). Because of a similarity in compositions and catalytic performances of the best Pt-Bi/Au and Bi/Pt/Au, the preparation procedure was concluded not to be critical so that the co-deposition method was more beneficial in terms of the number of deposition cycles in manufacturing electrocatalysts toward FAO.

Objectives; The accumulation and usefulness of clinical data have increased with IT development. While using clinical data that needs to be identifiable to obtain meaningful information, it is essential to ensure that data is de-identified and unnecessary clinical information is minimized to protect personal information. This process requires criteria and an appropriate method as there are clear identifiers as well as quasi-identifiers that are not readily identifiable. Methods; To formulate such a method, first, primary quasi-identifiers were selected by classifying information in 20 clinical personal information database tables into Direct-Identifier (DID), Quasi-Identifier (QI), Sensitive Attribute (SA), and Non-Sensitive Attribute (NSA) according to its type. Secondary QIs were then selected by assessing the risk for outliers by measuring uniqueness values of the selected data and scoring re-identification by calculating equivalence class of the influence on other data on QI removal. Third, the risk of re-identification of data users was numeralized and classified. Lastly, the final QI according to user class was determined by comparing the calculated re-identification scores to the threshold values of user classes. Results; Eventually, final QIs ranging from a minimum of 18 to a maximum of 28 were selected by making an assumption about user classes and using it as criteria. Conclusions; The QI selection method presented by the current investigators can be used by researchers at the final checkup stage before they de-identify the selected QIs. Therefore, clinical data users can securely and efficiently use clinical data containing personal information by objectively selecting QIs using the method proposed in the present study.

The induction of leaf injuries, including leaf chlorosis and epinasty, by continuous light in tomato plants is one of the most interesting and mysterious phenomena regarding plant interactions with light, the mechanism of which has not yet been revealed. To gain further insights into this particular response of tomato plants, we cultivated tomato seedlings (Solanum lycopersicum cv. Momotaro) for 14 days under continuous light with different ratios of red and blue light and compared their performance to those grown under continuous or 14/10-h photoperiodic white light using novel methods to quantitatively evaluate the level of leaf chlorosis and epinasty. Continuous monochromatic blue light induced severe chlorosis but almost completely alleviated epinasty in tomato leaf. In contrast, continuous monochromatic red light caused a lower level of leaf chlorosis but very severe epinasty. The combination of red and blue light at different ratios significantly reduced both leaf chlorosis and epinasty under continuous light condition. Carbohydrate contents showed no correlation with leaf chlorosis, while glucose and fructose contents showed correlations with the petiole and leaflet curvatures. Histochemical staining with 3,3'-diaminobenzidine and nitro blue tetrazodium chloride also did not reveal any significant buildup of hydrogen peroxide and superoxide anion in monochromatic blue light treatment. Taken together, these results suggest that chlorosis and epinasty are two distinctive leaf injuries caused by continuous light that may follow very different mechanisms, and an overaccumulation of carbohydrates in the leaf may not be the main cause of continuous light-induced leaf chlorosis in tomato.

This work presents the formic acid oxidation (FAO) behavior on three model Pt deposit catalysts on Au. The investigated model Pt catalysts were single-layered Pt deposits, plateau-type Pt deposits and tall conical Pt deposits, produced via irreversible adsorption of Pt ions according to the protocols of conventional route, CO route and iodine route, respectively. The shapes and populations of the model Pt deposits were controlled by the deposition protocols and number of deposition cycles. The most effective Pt deposit catalyst in FAO was verified to be single-layered one with a population of ∼50% which inhibited dehydration (poison formation) and promoted dehydrogenation. As the population of Pt deposits became higher than 50%, the dehydration process activated to decrease the FAO catalytic efficiency. Furthermore, multiple layered Pt deposits such as conical ones were not so efficient due to activation of dehydration even at a population below 50%. More detailed analysis of the observed voltammograms in the negative-going scan suggested that dehydrogenation took place at two different potentials depending on the shapes and populations of Pt deposits. One was low potential dehydrogenation occurring on separated single-layered Pt deposits at 0.14 V; the other was high potential dehydrogenation taking place on continuous Pt surface at 0.34 V. This particular suggestion was successfully applicable to explaining the FAO voltammograms of Pt electrodes of disk and nanoparticle.

Partial least squares regression (PLSR) prediction models were developed using hyperspectral imaging for noninvasive detection of the five most representative functional components in Brassica juncea leaves: chlorophyll, carotenoid, phenolic, glucosinolate, and anthocyanin contents. The region of interest for functional component analysis was chosen by polygon selection and the extracted average spectra were used for model development. For pre-processing, 10 combinations of Savitzky–Golay filter (S. G. filter), standard normal variate (SNV), multiplicative scatter correction (MSC), 1st-order derivative (1st-Der), 2nd-order derivative (2nd-Der), and normalization were applied. Root mean square errors of calibration (RMSEP) was used to assess the performance accuracy of the constructed prediction models. The prediction model for total anthocyanins exhibited the highest prediction level (RV2 = 0.8273; RMSEP = 2.4277). Pre-processing combination of SNV and 1st-Der with spectral data resulted in high-performance prediction models for total chlorophyll, carotenoid, and glucosinolate contents. Pre-processing combination of S. G. filter and SNV gave the highest prediction rate for total phenolics. SNV inclusion in the pre-processing conditions was essential for developing high-performance accurate prediction models for functional components. By enabling visualization of the distribution of functional components on the hyperspectral images, PLSR prediction models will prove valuable in determining the harvest time.

It is unclear whether tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) is more effective for preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). In this study, we compared the effectiveness of these two antiviral agents for preventing HCC. We included treatment-naive CHB patients undergoing antiviral therapy with TDF only (TDF group) or a TAF-based regimen (TAF group) at three academic teaching hospitals from 2012 to 2019. The TAF group included patients receiving TAF as first-line treatment and patients switching from TDF to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded. Cumulative probabilities of HCC were assessed using Kaplan-Meier methodology. In total, 2,117 patients were included: 1,832 in the TDF group and 285 in the TAF group. The annual HCC incidence was not significantly different between TDF and TAF groups: 1.66 vs. 1.19 per 100 person-years [PY], respectively (multivariate analysis: adjusted hazard ratio [HR] 0.774 [reference: TDF group]; p = .438). Male, liver cirrhosis, hepatitis B e antigen negativity, Fibrosis-4 index>3.25 and low albumin were independently associated with a higher risk of HCC. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results: 1.56 vs. 1.19 per 100 PY, respectively (HR 1.175; p = .708) and 1.66 vs. 1.29 per 100 PY, respectively (HR 0.888; p = .446). The risk of HCC development was not significantly different between TDF and TAF groups of CHB patients. Further studies with a larger sample size and longer follow-up are required to validate our results.

Neuromyelitis optica (NMO) is an autoimmune disease that primarily targets astrocytes. Autoantibodies (NMO-IgG) against the water channel protein, aquaporin 4 (AQP4), are a serologic marker in NMO patients, and they are known to be responsible for the pathophysiology of the disease. In the brain, AQP4 is mainly expressed in astrocytes, especially at the end-feet, where they form the blood-brain barrier. Following the interaction between NMO-IgG and AQP4 in astrocytes, rapid AQP4 endocytosis initiates pathogenesis. However, the cellular and molecular mechanisms of astrocyte destruction by autoantibodies remain largely elusive. We established an in vitro human astrocyte model system using induced pluripotent stem cells (iPSCs) technology in combination with NMO patient-derived serum and IgG to elucidate the cellular and functional changes caused by NMO-IgG. Herein, we observed that NMO-IgG induces structural alterations in mitochondria and their association with the endoplasmic reticulum (ER) and lysosomes at the ultrastructural level, which potentially leads to impaired mitochondrial functions and dynamics. Indeed, human astrocytes display impaired mitochondrial bioenergetics and autophagy activity in the presence of NMO-IgG. We further demonstrated NMO-IgG-driven ER membrane deformation into a multilamellar structure in human astrocytes. Together, we show that NMO-IgG rearranges cellular organelles and alter their functions and that our in vitro system using human iPSCs offers previously unavailable experimental opportunities to study the pathophysiological mechanisms of NMO in human astrocytes or conduct large-scale screening for potential therapeutic compounds targeting astrocytic abnormalities in patients with NMO.

Background & aims: Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC.Methods: From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan-Meier method.Results: In total, 1,810 patients (1,525 and 286 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p=0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR=0.973; p=0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR=0.949; p=0.743).Conclusions: These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

Summary The ε4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer’s disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aβ secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aβ production through an oversupply of cholesterol., Graphical abstract, Highlights • ApoE4 ACM induces neuronal lipid raft expansion and Aβ42 overproduction • Co-localization of lipid rafts and APP increases in neurons by ApoE4 ACM • Increasing cholesterol in media recapitulates the effects of ApoE4 ACM on neurons • Cholesterol depletion in ApoE4 ACM abolishes its effects on neurons, In this report, Seo and colleagues use human iPSCs to generate isogenic neurons and astrocytes carrying either APOE ε3 or APOE ε4 allele and demonstrate that ApoE4 astrocytes secrete more cholesterol to the extracellular space, which is sufficient and necessary to induce lipid raft expansion and Aβ42 overproduction in neurons.

Here, we present the controllable synthesis of dendrimer-encapsulated Pt nanoparticles (Pt DENs) utilizing repetitively coupled chemical reduction and galvanic exchange reactions. This facile method allowed controllable synthesis of the Pt DENs with fair homogeneity in size and composition. In particular, in contrast to the conventional dendrimer-templating methods, the proposed synthesis method allowed substantial increase in the applicable number of Pt atoms up to 1320 in Pt DENs without being limited by the fixed number of complexation sites for the Pt2+ precursor ions in dendrimers. We also present a detailed investigation on the oxidase-mimetic activity of the Pt DENs for catalytic oxidation of Amplex Red to resorufin with O2. Importantly, after clarifying intrinsic oxidase-mimetic activity of the Pt DENs, we disclosed that the Pt DENs’ oxidase-mimetic activity was tailorable for the oxidation of Amplex Red to resorufin especially with fine-tuning of the Pt2+/dendrimer ratios by using the proposed synthesis method.

CAGE-B and SAGE-B scores, consisting of age and fibrotic burden as cirrhosis and/or liver stiffness, were recently proposed to predict hepatocellular carcinoma (HCC) risk among Caucasian chronic hepatitis B (CHB) patients undergoing long-term antiviral therapy. We externally validated their predictive performances among an independent cohort from Asia, compared to other conventional prediction models. We consecutively recruited CHB patients with well-controlled viremia (serum HBV DNA

Background: The onset of Alzheimer’s disease (AD) typically occurs later in life. Recent genetic analysis of patients and unaffected individuals revealed multiple genetic variants associated with late-onset AD. One of the strongest genetic risk factors for AD is 𝜀4 allele of APOE encoding apolipoprotein (ApoE), which is predominantly expressed in astrocytes. The role and mechanism of ApoE in initiating AD-associated pathologies, including amyloid-β (Aβ) accumulation and neurodegeneration in neurons, remains to be elucidated.Methods: Human induced pluripotent stem cells (hiPSCs) from healthy individuals and isogenic cells in which the ApoE 𝜀3 allele was replaced with an 𝜀4 allele were selected to generate human neurons and astrocytes. To investigate the effect of astrocytic ApoE4 on neuronal Aβ production, iPSC-derived neurons carrying the ApoE 𝜀3 allele were cultured in conditioned media from healthy iPSC-derived astrocytes (ApoE3/E4 heterozygote) for five weeks. Then, the media were replaced with either ApoE3 or ApoE4 astrocyte conditioned media (ACM), cultured for four days, and neuronal amyloid precursor protein (APP) expression and Aβ production were measured. To determine potential mechanisms for upregulation of APP in neurons by ApoE4 ACM, changes in plasma membrane lipid rafts were investigated by staining for cholera toxin B. Methyl-b-cyclodextrin (MβCD) was applied to deplete cholesterol in ApoE4 ACM.Results: Secretory factors in conditioned media from hiPSC-derived astrocytes carrying APOE4 significantly increased the levels of APP and Aβ secretion in hiPSC-derived neurons. Increasing cholesterol levels in culture media mimicked the effects of ApoE4 ACM by inducing the formation of lipid rafts that potentially provide a physical platform for APP localization on the membrane. We further found that reducing cholesterol levels in ApoE4 ACM with MβCD abolished its effects on neuronal lipid raft expansion and Aβ generation.Conclusions: Our study suggests that ApoE4 astrocytes contribute to amyloidosis by the expansion of lipid rafts and facilitate neuronal Ab production through oversupply of cholesterol.

We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC).Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates.The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group.The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.

Personal protective equipment, particularly face masks, have become increasingly common with the rise of global health issues, such as fine-dust storms and pandemics. Face masks, however, also degrade speech intelligibility by effectively occluding visual cues, such as lip motions and facial expressions. In this paper, we propose MAScreen, a wearable LED display in the shape of a mask, which is capable of sensing lip motion and speech and provides real-time visual feedback of the mouth behind the mask.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 30 million people worldwide. Despite growing knowledge of AD pathophysiology, a complete understanding of the pathogenic mechanisms underpinning AD is lacking, and there is currently no cure for AD. Extant literature suggests that AD is a polygenic and multifactorial disease underscored by complex and dynamic pathogenic mechanisms. Despite extensive research and clinical trials, there has been a dearth of novel drugs for AD treatment on the market since memantine in 2003. This lack of therapeutic success has directed the entire research community to approach the disease from a different angle. In this review, we discuss growing evidence for the close link between altered glucose metabolism and AD pathogenesis by exploring how genetic risk factors for AD are associated with dysfunctional glucose metabolism. We also discuss modification of genes responsible for metabolic pathways implicated in AD pathology.

This work presents an improvement in the activity and catalytic lifetime of Pt deposits on Bi-modified Pt nanoparticles (Bi/Pt NP) toward formic acid oxidation (FAO). Using an irreversible adsorption method, Bi was deposited on Pt NP to form Bi/Pt NP and sequentially Pt was deposited on Bi/Pt NP to form Pt/Bi/Pt NP. Voltammetric studies of Pt NP, Bi/Pt NP, and Pt/Bi/Pt NPs supported that Pt deposits of Pt/Bi/Pt NPs provided quite a unique behavior: simultaneous surface oxidation of deposited Pt and Bi and significant resistance to the oxidative removal of Bi. Furthermore, combined spectroscopic investigations revealed that the concentration of the employed Pt precursor ion solution determined the amount of deposited Pt from ∼0.2 to ∼0.4 in coverage. The best Pt/Bi/Pt NP catalyst with a Pt coverage of ∼0.25 enhanced the dehydrogenation processes below ∼0.4 V by a factor of more than 2 and increased the FAO current at ∼0.8 V roughly by 15 times, referring to those of Bi/Pt NP. The lifetime measurement works revealed that after the 1000th voltammetric cycle to 0.4 V, the FAO currents of Pt/Bi/Pt NPs were 2 and 4 times higher than those of Bi/Pt NP and Pt NP, respectively. The Pt deposits on Bi/Pt NP were concluded to play two roles in FAO: the promotion of FAO processes to increase the activity and the retardation of Bi oxidative removal to maintain the activity much longer.

Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase(HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

In advanced technology nodes, correctly choosing among available back-end-of-line (BEOL) stack options is important to meet stringent design quality of results requirements. However, it is nontrivial to evaluate BEOL stack options since the routing outcomes highly depend on the input design (e.g., netlist, placement, etc.). In this paper, we propose a systematic framework to measure routing capacity of a BEOL stack as well as inherent capability of routers. Based on our experimental results, we observe consistent results across mesh-like placement and placements from various placers. Also, our proposed framework enables new insights into important questions regarding BEOL stack options. Using our framework, we further study the relation between the routing hotspot size and routing failure empirically. Lastly, we present an analytical study based on exponentiation of a Markov transition matrix about the impact of design size on routing failure.

This paper presents the design of an optical torque sensor that can structurally decouple the effect of axial-interference for use in various robotics applications. Torque sensors are widely used in the joints of intelligent service or wearable robots to realize safe human-robot interaction. Whole robot body sensing using torque sensors is essential for safe interaction. However, most torque sensors are bulky, heavy and expensive. Therefore, many optical-based torque sensors have been proposed to deal with such problems, but the issue of axial-interference still remains. We resolved the axial-interference problem via the geometrical structure of the sensor body and differential signaling using two reflective optical sensors. The moment interference error was successfully decreased from 4.49% (with one optical sensor) to 0.11% (with two optical sensors) using the proposed sensor structure while maintaining a compact size, lightweight, and low cost. Static tests and dynamic tests were carried out and analyzed for accuracy error, hysteresis, and repeatability. We then compared the performance of an impedance controller that is widely used in service and wearable robots using the proposed sensor and a commercial torque sensor with respect to various control loop rates. The control performance of the proposed sensor was comparable to that of commercial sensors.

Self-aligned multiple patterning, due to its low overlay error, has emerged as the leading option for 1-D gridded back-end-of-line (BEOL) in sub-14-nm nodes. To form actual routing patterns from a uniform “sea of wires,” cut masks are needed for line-end cutting or realization of space between routing segments. The line-end cutting results in nonfunctional (i.e., dummy fill) patterns that change wire capacitance, and hence design timing and power. Therefore, to remove such dummy fill patterns, extra 2-D block masks are used. However, 2-D block masks cannot remove arbitrary dummy fill patterns, due to design rule constraints on the block mask shapes. In this paper, we address the timing-aware optimization of 2-D block mask layouts under various sets of mask rules that are derived from mask patterning technology options (e.g., 193i and 193d) for foundry 7-/5-nm (N7/N5) BEOL. Our central contribution is a mixed integer linear programming (MILP) optimization that minimizes timing impact due to dummy metal segments while satisfying block mask rules and metal density constraints. We also propose a distributed optimization flow to improve the scalability. With our optimizer, we recover up to 84% of the worst negative slack impact from dummy segments, with up to 64% dummy removal rate. We further extend our MILP to a co-optimization of cut and block masks. This paper gives new insights into fundamental limits of benefit from emerging cut and block mask technology options.