Fully Automated Segmentation Models of Supratentorial Meningiomas Assisted by Inclusion of Normal Brain Images.

To train an automatic brain tumor segmentation model, a large amount of data is required. In this paper, we proposed a strategy to overcome the limited amount of clinically collected magnetic resonance image (MRI) data regarding meningiomas by pre-training a model using a larger public dataset of MRIs of gliomas and augmenting our meningioma training set with normal brain MRIs. Pre-operative MRIs of 91 meningioma patients (171 MRIs) and 10 non-meningioma patients (normal brains) were collected between 2016 and 2019. Three-dimensional (3D) U-Net was used as the base architecture. The model was pre-trained with BraTS 2019 data, then fine-tuned with our datasets consisting of 154 meningioma MRIs and 10 normal brain MRIs. To increase the utility of the normal brain MRIs, a novel balanced Dice loss (BDL) function was used instead of the conventional soft Dice loss function. The model performance was evaluated using the Dice scores across the remaining 17 meningioma MRIs. The segmentation performance of the model was sequentially improved via the pre-training and inclusion of normal brain images. The Dice scores improved from 0.72 to 0.76 when the model was pre-trained. The inclusion of normal brain MRIs to fine-tune the model improved the Dice score; it increased to 0.79. When employing BDL as the loss function, the Dice score reached 0.84. The proposed learning strategy for U-net showed potential for use in segmenting meningioma lesions.

Hepatocyte-specific Prominin-1 protects against liver injury-induced fibrosis by stabilizing SMAD7.

Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (Prom1CreER; R26TdTom) in which cells expressed TdTom under control of the Prom1 promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific Prom1-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific Prom1 deficiency but not by cholangiocyte-specific Prom1 deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific Prom1-deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFß signaling during liver fibrosis.

Role of Serum Pepsinogen II and Helicobacter pylori Status in the Detection of Diffuse-Type Early Gastric Cancer in Young Individuals in South Korea.

Background/Aims: The utility of serum pepsinogen (sPG) I and the sPGI/II ratio as biomarkers for screening individuals with gastric cancer (GC) has not been established in Korea. The aim of this study was to define the role of sPG, especially sPGII, in GC screening. Methods: This study enrolled 2,940 subjects, including patients with GC (n=1,124) or gastric dysplasia (n=353) and controls (n=1,463). Tests to determine sPG levels and Helicobacter pylori (HP) infection status were performed. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for sPG. The usefulness of sPG levels for the detection of GC and gastric dysplasia was validated by multivariate logistic regression. Results: The sPGI/II ratio was associated with the risk of gastric dysplasia and advanced-stage intestinal-type GC (IGC). In contrast, sPGII was associated with the risk of early-stage diffuse-type GC (DGC). Significantly higher risk was indicated by an sPGI/II ratio <3 for gastric dysplasia and advanced-stage IGC and by sPGII levels ≥20 µg/L for early-stage DGC. Positive HP status showed a stronger association with DGC than with IGC. When sPGII level and HP status were combined, the prevalence of DGC was higher in the ≥20 µg/L sPGII and HP-positive group. Age younger than 40 years was strongly related to early-stage DGC, especially in females (odds ratio, 21.00; p=0.006). Conclusions: sPGII ≥20 ng/mL and positive HP status suggest a risk of early-stage DGC, particularly in young adult females in South Korea.

[Development of Koreans Gut Quotient Measurement Scales].

BACKGROUND/AIMS: The aim of this study was to develop 'Koreans Gut Quotient Measurement Scales (GQ)', in which Koreans respond to questionnaires about the subjective feelings and symptoms of their intestinal health status. METHODS: Among 66 items pooled from previous studies and 4 items that were added following a focus group interview, 15 items were chosen using the Delphi survey. The content validity was evaluated using the content validity ratio. Data collected from 1,120 people from the general public in Korea were analyzed to verify the reliability and validity of GQ. RESULTS: The finalized GQ consisted of 17 items (including two exploratory measurement items) that were classified into three independent factors based on exploratory factor analysis (EFA): 'perceived intestine discomfort', 'bowel movement discomfort', and 'bowel movement control discomfort'. The discriminant and convergent validity of GQ were identified using EFA, reliability test, and confirmatory factor analysis. In addition, the criterion-related validity of GQ was identified using correlation and multiple regression analysis. CONCLUSIONS: The GQ, which is a simplified intestinal health index developed based on an easy questionnaire for the public to understand, can be used as a tool for the public to evaluate their own intestinal health and determine when to visit clinics.

The prevalence of histologic atrophy and intestinal metaplasia in the corpus has decreased over 15 years in females in the Korean population.

BACKGROUND: The aim of this study was to investigate the trends of atrophy and intestinal metaplasia (IM) in 2002 subjects without significant gastroduodenal diseases. MATERIALS AND METHODS: A total of 2002 subjects were prospectively enrolled and divided into three periods (2003-2007, 2008-2012, and 2013-2018). Trends of H pylori and atrophy/IM scored by Updated Sydney System were analyzed according to sex, and multivariate logistic analysis was performed for the risk factors for atrophy/IM. RESULTS: H pylori-negative and H pylori-positive subjects were 1220 (61.0%) and 782 (38.0%), respectively. H pylori positivity decreased from 149/303 (49.2%), 207/515 (40.2%) and 426/1184 (36.0%), in the three periods, respectively (P < 0.001). The prevalence of atrophy (P < 0.001) and IM in the corpus (P < 0.001) significantly decreased over 15 years in females, but not in males. The mean grade of atrophy and IM was higher in males (0.36 and 0.51) than in females (0.28 and 0.41) in the corpus (P = 0.027) and in the antrum (P = 0.006), respectively. Similarly, the mean grade of IM in males (0.34) was higher in females (0.19; P < 0.001) in the corpus. Multivariate analysis showed that old age, study period, and H pylori were statistically significant in atrophy of antrum and corpus, and IM in the corpus. In cases of IM of antrum, old age, H pylori, and smoking were statistically significant. CONCLUSION: A significant decrease in atrophy and IM in the corpus in females over 15 years suggests sex- or gender-specific characteristics.

Dispersion in Ferroelectric Switching Performance of Polycrystalline Hf0.5Zr0.5O2 Thin Films.

Interests in nanoscale integrated ferroelectric devices using doped HfO2-based thin films are actively reviving in academia and industry. The main driving force for the formation of the metastable non-centrosymmetric ferroelectric phase is considered to be the interface/grain boundary energy effect of the small grains in polycrystalline configuration. These small grains, however, can invoke unfavorable material properties, such as nonuniform switching performance. This study provides an in-depth understanding of such aspects of this material through careful measurement and modeling of the ferroelectric switching kinetics. Various previous switching models developed for conventional ferroelectric thin-film capacitors cannot fully account for the observed time- and voltage-dependent switching current evolution. The accurate fitting of the experimental results required careful consideration of the inhomogeneous field distribution across the electrode area, which could be acquired by an appropriate mathematical formulation of polarization as a function of electric field and time. Compared with the conventional polycrystalline Pb(Zr,Ti)O3 film, the statistical distribution of the local field was found to be three times wider. The activation field and characteristic time for domain switching were larger by more than 1 order of magnitude. It indicates that doped HfO2 is inhomogeneous and "hard" ferroelectric material compared with conventional perovskite-based ferroelectrics.

Atomic layer deposition of GeSe films using HGeCl3 and [(CH3)3Si]2Se with the discrete feeding method for the ovonic threshold switch.

The ovonic threshold switch (OTS) based on the voltage snapback of amorphous chalcogenides possesses several desirable characteristics: bidirectional switching, a controllable threshold voltage (V th) and processability for three-dimensional stackable devices. Among the materials that can be used as OTS, GeSe has a strong glass-forming ability (∼350 °C crystallization temperature), with a simple binary composition. Described herein is a new method of depositing GeSe films through atomic layer deposition (ALD), using HGeCl3 and [(CH3)3Si]2Se as Ge and Se precursors, respectively. The stoichiometric GeSe thin films were formed through a ligand exchange reaction between the two precursor molecules, without the adoption of an additional reaction gas, at low substrate temperatures ranging from 70 °C-150 °C. The pseudo-saturation behavior required a long time of Ge precursor injection to achieve the saturation growth rate. This was due to the adverse influence of the physisorbed precursor and byproduct molecules on the efficient chemical adsorption reaction between the precursors and reaction sites. To overcome the slow saturation and excessive use of the Ge precursor, the discrete feeding method (DFM), where HGeCl3 is supplied multiple times consecutively with subdivided pulse times, was adopted. DFM led to the saturation of the GeSe growth rate at a much shorter total injection time of the Ge precursor, and improved the film density and oxidation resistance properties. The GeSe film grown via DFM exhibited a short OTS time of ∼40 ns, a ∼107 ON/OFF current ratio, and ∼104 selectivity. The OTS behavior was consistent with the modified Poole-Frenkel mechanism in the OFF state. In contrast, the similar GeSe film grown through the conventional ALD showed a low density and high vulnerability to oxidation, which prevented the OTS performance. The ALD method of GeSe films introduced here will contribute to the fabrication of a three-dimensionally integrated memory as a selector device for preventing sneak current.

Balancing the Source and Sink of Oxygen Vacancies for the Resistive Switching Memory.

The high nonuniformity and low endurance of the resistive switching random access memory (RRAM) are the two major remaining hurdles at the device level for mass production. Incremental step pulse programming (ISPP) can be a viable solution to the former problem, but the latter problem requires material level innovation. In valence change RRAM, electrodes have usually been regarded as inert (e.g., Pt or TiN) or oxygen vacancy (VO) sources (e.g., Ta), but different electrode materials can serve as a sink of VO. In this work, an RRAM using a 1.5 nm-thick Ta2O5 switching layer is presented, where one of the electrodes was VO-supplying Ta and the other was either inert TiN or VO-sinking RuO2. Whereas TiN could not remove the excessive VO in the memory cell, RuO2 absorbed the unnecessary VO. By carefully tuning (balancing) the capabilities of VO-supplying Ta and VO-sinking RuO2 electrodes, an almost invariant ISPP voltage and a greatly enhanced endurance performance can be achieved.

Dog and Cat Allergies and Allergen Avoidance Measures in Korean Adult Pet Owners Who Participated in a Pet Exhibition.

PURPOSE: This study evaluated dog and cat allergies and their association with allergen avoidance measures in Korean adults. METHODS: The study population consisted of 537 adults who currently kept dogs or cats and participated in a pet exhibition in Korea. The subjects were asked to complete questionnaires regarding pet ownership, allergen avoidance, and allergy symptoms, and underwent skin prick tests. They were considered to have a dog or cat allergy if they suffered from one or more of allergy symptoms during contact with their pets. RESULTS: In total, 103 of 407 dog owners (25.3%) and 45 of 130 cat owners (34.6%) had a dog or cat allergy, respectively. Dog owners kept 1.3±1.5 dogs; this number did not differ according to the presence of dog allergy. Dog owners with a dog allergy had owned their dogs longer than those without (88.0±72.0 vs 67.5±72.7 months, P<0.05). Cat owners kept 2.1±3.6 cats; this number did not differ according to the presence of cat allergy, nor did the duration of cat ownership. Cat owners with a cat allergy had facial contact and slept with their cats less frequently (8.6±11.9 vs 18.3±27.0 times/day, P<0.01; 71.1% vs 81.2%, P<0.05); however, they had their cats shaved and beds cleaned less frequently than those without (1.8±3.3 vs 3.2±4.4 times/year, P<0.05; 1.5±1.5 vs 3.9±6.0 times/month, P<0.01). CONCLUSIONS: Cat owners with a cat allergy tried to minimize contact with their cats, but efforts to avoid indoor cat allergens were lower than those without. In comparison, dog owners with a dog allergy had kept their dogs for longer time than those without; however, current contact with their dogs and allergen avoidance measures did not differ between the 2 groups.

Nociceptive Memristor.

The biomimetic characteristics of the memristor as an electronic synapse and neuron have inspired the advent of new information technology in the neuromorphic computing. The application of the memristors can be extended to the artificial nerves on condition of the presence of electronic receptors which can transfer the external stimuli to the internal nerve system. In this work, nociceptor behaviors are demonstrated from the Pt/HfO2 /TiN memristor for the electronic receptors. The device shows four specific nociceptive behaviors; threshold, relaxation, allodynia, and hyperalgesia, according to the strength, duration, and repetition rate of the external stimuli. Such nociceptive behaviors are attributed to the electron trapping/detrapping to/from the traps in the HfO2 layer, where the depth of trap energy level is ≈0.7 eV. Also, the built-in potential by the work function mismatch between the Pt and TiN electrodes induces time-dependent relaxation of trapped electrons, providing the appropriate relaxation behavior. The relaxation time can take from several milliseconds to tens of seconds, which corresponds to the time span of the decay of biosignal. The material-wise evaluation of the electronic nociceptor in comparison with other material, which did not show the desired functionality, Pt/Ti/HfO2 /TiN, reveals the importance of careful material design and fabrication.

The current limit and self-rectification functionalities in the TiO2/HfO2 resistive switching material system.

To replace the present NAND flash memory, resistance switching random access memory (ReRAM), which has both memory and selection functionalities with a simple metal-insulator-metal structure should be implemented. To accomplish this goal, ReRAM must be self-rectifying, low-power-consuming, and highly uniform, and it must have reliable states. In this work, the Pt/TiO2/HfO2-x/TiN resistive switching memory structure showed self-rectifying resistive switching behavior with unprecedented unique I-V curves. This is named "self-current saturation," which can give an extremely uniform variation of the low resistance state. The plausible reasons for the whole switching behavior, including the unique I-V curves, in this material system are presented herein. The diffusion of Ti along the grain boundaries of HfO2 down to the bottom electrode TiN and the defect formation within the HfO2 layer near the TiO2/HfO2 interface made the resistance switching device have the characteristics of both the unidirectional diode and electronic bipolar switching devices.

A study of the transition between the non-polar and bipolar resistance switching mechanisms in the TiN/TiO2/Al memory.

Thermochemical and electronic trapping/detrapping mechanism-based resistance switching in TiO2 is one of the most extensively researched topics in the field of resistance-switching random access memory (ReRAM). In this study, the subtle correlation between the formation and rupture of the Magnéli-based conducting filament (CF), which is the mechanism of non-polar thermochemical-reaction-based switching, and the electron trapping/detrapping at the defect centers, which is the mechanism of bipolar electronic switching, is examined in detail. The chemical interaction between the TiN top electrode and the TiO2 layer generates a stable and immobile electron trapping layer, which is called a "switching layer", whereas the thin region between the just-mentioned switching layer and the remaining Magnéli CF after the thermochemical reset comprises a non-switching layer. The seemingly very complicated switching behavior with respect to the bias polarity, compliance current, and detailed biasing sequence could be reasonably explained by the phenomenological model based on the combined motions of the CF, switching layer, and non-switching layer. Light-induced detrapping experiments further supplement the suggested switching model.

Uniform Self-rectifying Resistive Switching Behavior via Preformed Conducting Paths in a Vertical-type Ta2O5/HfO2-x Structure with a Sub-µm(2) Cell Area.

To replace or succeed the present NAND flash memory, resistive switching random access memory (ReRAM) should be implemented in the vertical-type crossbar array configuration. The ReRAM cell must have a highly reproducible resistive switching (RS) performance and an electroforming-free, self-rectifying, low-power-consumption, multilevel-switching, and easy fabrication process with a deep sub-µm(2) cell area. In this work, a Pt/Ta2O5/HfO2-x/TiN RS memory cell fabricated in the form of a vertical-type structure was presented as a feasible contender to meet the above requirements. While the fundamental RS characteristics of this material based on the electron trapping/detrapping mechanisms have been reported elsewhere, the influence of the cell scaling size to 0.34 µm(2) on the RS performance by adopting the vertical integration scheme was carefully examined in this work. The smaller cell area provided much better switching uniformity while all the other benefits of this specific material system were preserved. Using the overstressing technique, the nature of RS through the localized conducting path was further examined, which elucidated the fundamental difference between the present material system and the general ionic-motion-related bipolar RS mechanism.

Time-Dependent Negative Capacitance Effects in Al2O3/BaTiO3 Bilayers.

The negative capacitance (NC) effects in ferroelectric materials have emerged as the possible solution to low-power transistor devices and high-charge-density capacitors. Although the steep switching characteristic (subthreshold swing < sub-60 mV/dec) has been demonstrated in various devices combining the conventional transistors with ferroelectric gates, the actual applications of the NC effects are still some way off owing to the inherent hysteresis problem. This work reinterpreted the hysteretic properties of the NC effects within the time domain and demonstrated that capacitance (charge) boosting could be achieved without the hysteresis from the Al2O3/BaTiO3 bilayer capacitors through short-pulse charging. This work revealed that the hysteresis phenomenon in NC devices originated from the dielectric leakage of the dielectric layer. The suppression of charge injection via the dielectric leakage, which usually takes time, inhibits complete ferroelectric polarization switching during a short pulse time. It was demonstrated that a nonhysteretic NC effect can be achieved only within certain limited time and voltage ranges, but that these are sufficient for critical device applications.

Pt/Ta2 O5 /HfO2- x /Ti resistive switching memory competing with multilevel NAND flash.

Pt/Ta2 O5 /HfO2- x /Ti resistive switching memory with a new circuit design is presented as a feasible candidate to succeed multilevel-cell (MLC) NAND flash memory. This device has the following characteristics: 3 bit MLC, electroforming-free, self-rectifying, much higher cell resistance than interconnection wire resistance, low voltage operation, low power consumption, long-term reliability, and only an electronic switching mechanism, without an ionic-motion-related mechanism.