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Clusterwise inference is a popular approach in neuroimaging to increase sensitivity, but most existing methods are currently restricted to the General Linear Model (GLM) for testing mean parameters. Statistical methods forvariance componentstesting, which are critical in neuroimaging studies that involve estimation of narrow-sense heritability or test-retest reliability, are seriously underdeveloped due to methodological and computational challenges, which would potentially lead to low power. We propose a fast and powerful test for variance components called CLEAN-V (‘CLEAN’ for testing ‘V’ariance components). CLEAN-V models the global spatial dependence structure of imaging data and computes a locally powerful variance component test statistic by data-adaptively pooling neighborhood information. Correction for multiple comparisons is achieved by permutations to control family-wise error rate (FWER). Through analysis of task-fMRI data from the Human Connectome Project across five tasks and comprehensive data-driven simulations, we show that CLEAN-V outperforms existing methods in detecting test-retest reliability and narrow-sense heritability with significantly improved power, with the detected areas aligning with activation maps. The computational efficiency of CLEAN-V also speaks of its practical utility, and it is available as an R package.

Introduction: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness on postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). Methods: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: patient-controlled analgesia (PCA) group (n=132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n=99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin (Hb), length of hospital stay, and total morphine usage after surgery. Results: Postoperative resting VAS at 6 hours and 48 hours was significantly lower in the PNB+PCA group compared with the PCA group (p=0.075, p=0.0318, respectively). However, there was no significant difference in either resting VAS at 24 hours or active VAS. Complications of pneumonia and delirium until one month postoperative were significantly lower in the PNB + PCA group than the PCA group (p=0.0022, p=0.0055, respectively). Conclusion: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

IntroductionBrain age prediction is used to quantify the pathological and cognitive changes associated with brain aging. However, the predicted age derived from certain models can result in biased estimation and the concealment of inherent aged brain function.MethodsWe constructed a brain age prediction model for the East Asian elderly brain using the brain volume and cortical thickness features from cognitively normal (CN) brains. Furthermore, our model was used to estimate different diagnoses and to construct a classification model of mild cognitive impairment (MCI) conversion and Alzheimer’s disease (AD) conversion.ResultsOur model showed a strong association of the brain age difference (BAD) with three diagnosis groups. In addition, the classification models of MCI conversion and AD conversion showed acceptable and robust performances, respectively (area under the curve [AUC] = 0.66, AUC = 0.76).DiscussionWe believe that our model can be used to estimate the predicted status of an East Asian elderly brain. Moreover, the MCI conversion model has the potential to prevent severe cognitive impairment and can be used for the early detection of AD.

Climate-forced, offline ice-sheet model simulations have been used extensively in assessing how much ice-sheets can contribute to future global sea-level rise. Typically, these model projections do not account for the two-way interactions between ice-sheets and climate. To quantify the impact of ice-ocean-atmosphere feedbacks, here we conduct greenhouse warming simulations with a coupled global climate-ice-sheet model of intermediate complexity. Following the Shared Socioeconomic Pathway (SSP) 1-1.9, 2-4.5, 5-8.5 emission scenarios, the model simulations ice-sheet contributions to global sea-level rise by 2150 of 0.2 ± 0.01, 0.5 ± 0.01 and 1.4 ± 0.1 m, respectively. Antarctic ocean-ice-sheet-ice-shelf interactions enhance future subsurface basal melting, while freshwater-induced atmospheric cooling reduces surface melting and iceberg calving. The combined effect is likely to decelerate global sea-level rise contributions from Antarctica relative to the uncoupled climate-forced ice-sheet model configuration. Our results demonstrate that estimates of future sea-level rise fundamentally depend on the complex interactions between ice-sheets, icebergs, ocean and the atmosphere.

During robot-assisted partial nephrectomy (RAPN), renal artery clamping is necessary to optimize the surgical field. However, renal artery clamping can induce renal blood flow reduction and postoperative renal dysfunction. Papaverine is used as a potent vasodilator agent. We determined if periarterial administration of papaverine after renal artery clamping improved intraoperative renal artery blood flow and early postoperative glomerular filtration rate (GFR) compared with placebo in RAPN.In this randomized controlled trial, 96 patients who underwent RAPN were enrolled between November 2019 and December 2020. Patients were administered periarterial normal saline as a placebo (placebo group) or papaverine (papaverine group) just after renal artery declamping. The primary outcome was renal artery blood flow by Doppler ultrasound 2 min after periarterial administration of papaverine or placebo after renal artery declamping. The secondary outcome was GFR estimated by renal scan 3 months after RAPN.Renal artery blood flow and GFR were significantly higher in the papaverine group than in the placebo group (538.0 [376.6-760.0] mL/min versus 338.8 [205.8-603.4] mL/min, P = 0.002 and 93.5 ± 17.1 mL/min/1.73 mPeriarterial papaverine administration increased intraoperative renal artery blood flow and early postoperative GFR in RAPN, suggesting that papaverine administration has beneficial effects on renal perfusion after renal artery clamping and could be a valuable option for improving renal function after RAPN.

In the structural design of a roller-compacted concrete pavement (RCCP), it is crucial to estimate strain and stress developments in the RCCP slab realistically. Since the RCCP mix uses less cement and lower amount of water, shrinkage strain and concrete temperature during the hardening stage are expected to be reduced as compared to those of conventional concrete mixture, resulting in a reduction of the concrete early-age deformation and stress developments in the RCCP slab. In this paper, early-age concrete strain and stress developments in RCCP slab subjected to environmental loads were evaluated. A full-scale test section of RCCP under real climatic conditions was monitored. The early-age total strains, stress-independent strains, shrinkage strains, and coefficient of thermal expansion (CTE) of the RCCP were measured and analyzed. Using the results of measured strains, in-situ CTE and shrinkage strain, and temperature, the early-age concrete stress development is computed by incorporating a viscoelastic property of the early-age concrete. The results revealed that the shrinkage strain of the RCCP is quite low as compared to that of conventional concrete. The early-age stress developments in the RCCP slab are strongly governed by the thermal-induced stresses. Shrinkage-induced stresses were quite small and might be negligible in a preliminary estimation of early-age stress developments in the RCCP slab.

Robotic prostatectomy requires pneumoperitoneum and a steep Trendelenburg position; however, this condition may compromise cerebral blood flow. Here, we evaluated the effect of pneumoperitoneum and the steep Trendelenburg position on internal carotid artery (ICA) blood flow measured by Doppler ultrasound during robotic prostatectomy.Patients who underwent robotic prostatectomy were prospectively recruited. The ICA blood flow was measured at the following five time-points: with the patient awake and in the supine position (Ta), 10 min after anaesthetic induction in the supine position (T1), 10 (T2) and 30 (T3) min after pneumoperitoneum in the steep Trendelenburg position, and at the end of surgery in the supine position after desufflation of the pneumoperitoneum (T4). Hemodynamic and cerebrovascular variables were measured at each time-point.A total of 28 patients were evaluated. The ICA blood flows were significantly lower at T2 and T3 than at T1 (162.3 ± 44.7 [T2] vs. 188.0 ± 49.6 ml/min [T1]; p = .002, 163.1 ± 39.9 [T3] vs. 188.0 ± 49.6 ml/min [T1]; p = .009). The ICA blood flow also differed significantly between Ta and T1 (236.8 ± 58.3 vs. 188.0 ± 49.6 ml/min; p .001). Heart rates, cardiac indexes, peak systolic velocity, and end-diastolic velocity were significantly lower at T2 and T3 than at T1. However, ICA diameter, mean blood pressure, and end-tidal carbon dioxide partial pressure did not differ significantly at all time-points.Pneumoperitoneum and the steep Trendelenburg position caused decreased ICA blood flow, suggesting that they should be carefully performed during robotic prostatectomy, especially in patients at risk of postoperative cerebrovascular accident.

As the degradation of polymer electrolyte membranes (PEMs) shows catastrophic failures with pinholes and cracks, studies on PEM degradation are essential to improve the reliability and lifetime of polymer electrolyte membrane fuel cell (PEMFC) membrane electrode assemblies (MEAs). However, the investigation of the degradation patterns and understanding of the degradation mechanisms of PEMs are still very limited at the PEMFC MEA level. Herein, open-circuit voltage (OCV) hold (chemical degradation) and humidity cycle test (mechanical degradation) protocols are applied to assess the durability of membrane components of PEMFC MEAs. OCV hold test is conducted at low relative humidity (30%) and OCV condition for 540 h. Humidity cycle test (5000 cycles) is carried out under repeating low (0%) and high (150%) relative humidities. We investigate degradation patterns and mechanisms of PEMs for MEAs after OCV hold and humidity cycle tests using various electrochemical and physicochemical analyses tools. The present study, by providing fundamental understanding of major degradation mechanisms, generates scientific information regarding design tools for the fabrication of highly durable PEMs. Additionally, this study, through accelerated degradation tests, can provide baseline information regarding the durability and lifetime of PEMs by statistically analyzing the deterioration pattern of MEAs.

Cu–Mn foam provides reliable high-temperature electronic conduction paths via in situ phase transformation for large-scale solid oxide fuel cell stacks.

Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.

Recently, noncontact vital sign monitors have attracted attention because of issues related to the transmission of contagious diseases. We developed a real-time vital sign monitor using impulse-radio ultrawideband (IR-UWB) radar with embedded processors and software; we then evaluated its accuracy in measuring heart rate (HR) and respiratory rate (RR) and investigated the factors affecting the accuracy of the radar-based measurements. In 50 patients visiting a cardiology clinic, HR and RR were measured using IR-UWB radar simultaneously with electrocardiography and capnometry. All patients underwent HR and RR measurements in 2 postures—supine and sitting—for 2 min each. There was a high agreement between the RR measured using radar and capnometry (concordance correlation coefficient [CCC] 0.925 [0.919–0.926]; upper and lower limits of agreement [LOA], − 2.21 and 3.90 breaths/min). The HR measured using radar was also in close agreement with the value measured using electrocardiography (CCC 0.749 [0.738–0.760]; upper and lower LOA, − 12.78 and 15.04 beats/min). Linear mixed effect models showed that the sitting position and an HR

Purpose To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan. Design Retrospective case series. Participants We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote. Methods Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes. Main Outcome Measures Best-corrected visual acuity, visual field (VF), and their changes during follow-up. Results The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy. Conclusions Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with Dabie bandavirus [formerly SFTS virus (SFTSV)] and is an emerging zoonotic disease. Dogs can be infected with SFTSV, but its pathogenicity and transmissibility have not been fully elucidated. In experiment 1, immunocompetent dogs were intramuscularly inoculated with SFTSV. In experiment 2, immunosuppressed dogs (immunosuppressed group; oral azathioprine 5 mg/kg/day for 30 days) were intramuscularly inoculated with SFTSV. Both immunosuppressed and immunocompetent contact dogs were co-housed with the SFTSV-inoculated dogs that had been immunosuppressed. Immunocompetent SFTSV-infected dogs did not show any clinical symptom. However, immunosuppressed SFTSV-infected dogs showed high fever and weight loss without lethality. In all SFTSV-infected dogs, viral RNA could be measured in the serum only after 3 days post infection (DPI) and neutralizing antibodies were detected in the serum beginning 9 DPI. SFTSV shedding in the urine and faeces of some infected dogs occurred between 4 and 6 DPI. The immunocompromised SFTSV-infected dogs showed thrombocytopenia beginning 3 DPI to the end of the experiment (24 DPI). We confirmed SFTSV transmission to one of three immunocompetent co-housed dogs. This dog showed a high fever, weight loss, and shed viral RNA by urine. Viral RNA and neutralizing antibodies were also detected in the serum. These results demonstrated that intramuscular inoculation with SFTSV induced minor clinical symptoms in dogs, and intraspecies SFTSV transmission in dogs can occur by contact.

Established genetic risk factors for Alzheimer’s disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal cortical thickness in 2643 Koreans meeting the clinical criteria for AD (n = 209), mild cognitive impairment (n = 1449) or normal cognition (n = 985). A missense variant, rs77359862 (R274W), in the SHANK-associated RH Domain Interactor (SHARPIN) gene was associated with entorhinal cortical thickness (p = 5.0 × 10−9) and hippocampal volume (p = 5.1 × 10−12). It revealed an increased risk of developing AD in the mediation analyses. This variant was also associated with amyloid-β accumulation (p = 0.03) and measures of memory (p = 1.0 × 10−4) and executive function (p = 0.04). We also found significant association of other SHARPIN variants with hippocampal volume in the Alzheimer’s Disease Neuroimaging Initiative (rs3417062, p = 4.1 × 10−6) and AddNeuroMed (rs138412600, p = 5.9 × 10−5) cohorts. Further, molecular dynamics simulations and co-immunoprecipitation indicated that the variant significantly reduced the binding of linear ubiquitination assembly complex proteins, SHPARIN and HOIL-1 Interacting Protein (HOIP), altering the downstream NF-κB signaling pathway. These findings suggest that SHARPIN plays an important role in the pathogenesis of AD.

We analyzed the degradation features by measuring the capacitance–voltage characteristics after electrically aging blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs). The measurement was investigated in terms of the hole transfer layer (HTL) and electron transfer layer (ETL) structures. For the HTL, three different materials—N,N′–bis(naphthalen–1–yl)–N,N′–bis(phenyl)–benzidine (NPB), 4,4′,4″-tris(carbazol–9–yl)triphenylamine (TCTA), and 1,3–bis(carbazol–9–yl)benzene (mCP)—were used at the HTL/emission layer (EML) interface; the TCTA/EML interface had the highest stability among the interfaces. For the ETL, bis [2–(diphenylphosphino)phenyl] ether oxide (DPEPO) without further dopants was used as an exciton blocking layer (ExBL) to effectively confine the excitons at the EML. However, DPEPO has low stability and carrier mobility. Therefore, 0, 10, and 40 nm-thick ExBL devices were investigated; it was found that the 0 nm-thick ExBL device was the most stable. However, the 10 nm-thick ExBL is essential to confine the excitons at the EML, which ensures a high EL performance.

Hyperstoichiometric (p-type) misfit-layered calcium cobaltites have been studied as components in various high-temperature electrochemical devices. Multiple studies have reported their applications or physical properties, but systematic studies on their defect structures and thermodynamic quantities are still insufficient. In this study, the oxygen nonstoichiometry and the electrical conductivity of Gd-Cu co-doped misfit cobalt oxide were measured as functions of temperature and oxygen partial pressure, along with thermodynamic quantities. The behavior of oxygen nonstoichiometry could not be explained by a defect structure assuming the ideal solution, as it showed a positive deviation in Raoult's law. The redesigned nonideal proposed defect structure, considering that the deviation originated from the high concentration of degenerate holes, could describe the oxygen nonstoichiometry precisely; and in this process, the values of ,

Protonic ceramic fuel cells have become extremely interesting due to their high power output at the intermediate temperature range (400–700 °C). Significant progress has been made to develop electrolyte materials, doped barium cerates-zirconate, which gets the leading role due to its high chemical stability and high ionic conductivity. Here, we present a new composition BaCe0.5Zr0.3Y0.1Yb0.05Zn0.05O3-δ (BCZYYbZn05), where addition of 5 mol% Zn with Ce, Zr, Y, and Yb at the B-site of the perovskite material shows high stability with high conductivity. The material was synthesized by solid-state reaction route at 1400 °C which showed 98% relative density. Rietveld analysis of neutron powder diffraction data reveal an orthorhombic structure with Pbnm space group. Thermogravimetric analysis shows about 1.06% weight loss from 200 to 1000 °C which is mainly related to the formation of the oxygen vacancies. In wet hydrogen atmosphere, this material shows higher conductivity and lower activation energy than dry hydrogen atmosphere indicates the conduction type as protonic conduction. The anode-supported single test cell based on this electrolyte material demonstrates peak power densities 649 mW cm−2 at 700 °C using conventional BSCF cathode, representing an important step toward commercially viable SOFC technology.

A critical issue to tackle before successful commercialization of solid oxide fuel cells (SOFCs) can be achieved is the long-term thermal stability required for SOFCs to operate reliably without significant performance degradation despite enduring thermal cycling. In this work, the impact of thermal cycling on the durability of NiO-yttria-stabilized zirconia-based anode-supported cells is studied using three different heating/cooling rates (1, 2, and 5 °C min-1) as the temperature fluctuated between 400 and 700 °C. Our experiments simulate time periods when power from SOFCs is not required (e.g., as might occur at night or during an emergency shutdown). The decay ratios of the cell voltages are 8.8% (82 μV h-1) and 19.1% (187 μV h-1) after thermal cycling testing at heating/cooling rates of 1 and 5 °C min-1, respectively, over a period of 1000 h. The results indicate SOFCs that undergo rapid thermal cycling experience much greater performance degradation than cells that experience slow heating/cooling rates. The changes in total resistance for thermally cycled cells are determined by measuring the Rpol of the electrodes (whereas the ohmic resistances of the cells remain unchanged from their initial value), signifying that electrode deterioration is the main degradation mechanism for SOFCs under thermal cycling. In particular, fast thermal cycling leads to severe degradation in the anode part of SOFCs with substantial agglomeration and depletion of Ni particles seen in our characterizations with field emission-scanning electron microscopy and electron probe microanalysis. In addition, the mean particle size in the cathode after thermal cycling testing increases from 0.104 to 0.201 μm for the 5 °C min-1 cell. Further, the presence of Sr-enriched regions is more significant in the La0.6Sr0.4Co0.2Fe0.8O3-δ cathode after fast thermally cycled SOFCs.

Purpose Despite improvements of strategy in radical retropubic prostatectomy, blood loss is still a major concern. The lymphocyte/monocyte (LM) ratio is a prognostic indicator for various diseases. We identified the risk factors, including the LM ratio, for red blood cell (RBC) transfusion during radical retropubic prostatectomy. Methods This retrospective study assessed patients who underwent radical retropubic prostatectomy between March 2009 and December 2020. To determine the risk factors for RBC transfusion, a multivariate logistic regression analysis was conducted. A receiver operating characteristic (ROC) curve analysis was also performed. Postoperative outcomes, including acute kidney injury (AKI), hospitalization duration, and intensive care unit (ICU) admission, were also evaluated. Results Among 1302 patients, 158 patients (12.1%) received an intraoperative RBC transfusion. Multivariate logistic regression analysis demonstrated that the risk factors for RBC transfusion were the LM ratio, hemoglobin, 6% hydroxyethyl starch amount, and positive surgical margin. The area under the ROC curve of LM ratio was 0.706 (cut-off = 4.3). The LM ratio at ≤ 4.3 was significantly related to transfusion in multivariate-adjusted analysis (odds ratio = 4.598, P

An ensemble model of convolutional neural network (CNN) and multilayer perceptron (MLP) models was developed to detect sweet pepper (Capsicum annuum var. annuum) fruits in images and predict their development stages. The plants were grown in four rows in a greenhouse, and images were collected from each row. Plant environment and growth data were collected every minute and month, respectively. The fruit development stage was classified into immature, breaking, and mature stages with a CNN using images. The immature stage was internally divided into four stages with an MLP, so a total of six stages were classified using the CNN–MLP ensemble model. The plant growth and environmental data and the information from the CNN output were used for the MLP input. The average accuracy of the six stages was F1 score = 0.77 and IoU = 0.86. The ensemble model showed acceptable performance in predicting fruit development stages. The CNN-only model could classify the mature and breaking stages well, but the immature stages were not distinguished, while the MLP-only model could hardly classify the fruit stage except the immature stages. The most influential factors in classification were the data obtained from CNN and the plant growth and environment data. The ensemble models could help in appropriate labour allocation and strategic management by detecting individual fruits in images and predicting precise fruit development stages.

In this study, we investigated the long-term stability of anion exchange membrane water electrolyzers (AEMWEs) under various bias conditions. The cell performance was relatively stable under conditions of voltage cycling in a narrow range, constant voltage and constant current. On the other hand, a relatively dynamic condition, voltage cycling, in a wide range detrimentally affected the cell stability. Abnormally high negative and positive currents were observed when the cell voltage was switched between 2.1 and 0 V. Impedance results and post-material analyses indicated that the performance degradation was mainly due to anode catalyst detachments, which increased non-ohmic resistance in the wide range voltage cycling. An increase in ohmic resistance was also observed, which was due to the membrane dehydration that occurred in the frequent rest times. Thus, it can be said that the voltage cycling range as well as the frequency of rest times are critical operational parameters in determining the long-term stability of AEMWEs.

The authors AA and NR would like to thank Universiti Brunei Darussalam for providing a UGS scholarship to perform this research. This work was supported by the UBD CRG project: UBD/OVACRI/CRGWG(006)/161201. Protonic ceramic fuel cells (PCFCs) have become the most efficient, clean and cost-effective electrochemical energy conversion devices in recent years. While significant progress has been made in developing proton conducting electrolyte materials, mechanical strength and durability still need to be improved for efficient applications. We report that adding 5 mol% Zn to the Y-doped barium cerate-zirconate perovskite electrolyte material can significantly improve the sintering properties, mechanical strength, durability and performance. Using same proton conducting material in anodes, electrolytes and cathodes to make a strong structural backbone shows clear advantages in mechanical strength over other arrangements with different materials. Rietveld analysis of the X-ray and neutron diffraction data of BaCe0.7Zr0.1Y0.15Zn0.05O3−δ (BCZYZn05) revealed a pure orthorhombic structure belonging to the Pbnm space group. Structural and electrochemical analyses indicate highly dense and high proton conductivity at intermediate temperature (400–700 °C). The anode-supported single cell, NiO-BCZYZn05|BCZYZn05|BSCF-BCZYZn05, demonstrates a peak power density of 872 mW cm−2 at 700 °C which is one of the highest power density in an all-protonic solid oxide fuel cell. This observation represents an important step towards commercially viable SOFC technology. Publisher PDF

Neuroendocrine neoplasms (NENs) such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have characteristic histologies, but immunohistochemistry using neuroendocrine markers is still desirable to confirm diagnosis. CD56 is the most sensitive marker, but also stains various normal tissues and other tumors. Recently, we reported that nucleolar protein 4 (NOL4) is present in the blood of SCLC patients and found it was stained in the SCLC nuclei. In this study, we compared expressions of NOL4 and CD56, using 64 cases of SCLC, 18 cases of LCNEC, 6 cases of atypical carcinoid tumor, 7 cases of typical carcinoid tumor, 68 cases of lung adenocarcinoma, and 62 cases of lung squamous cell carcinoma. For primary lung NENs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of NOL4 were 77.5%, 95.8%, 93.2%, and 85.1%, respectively, while those of CD56 were 92.1%, 93.3%, 91.1%, and 94.1%. The specificity and PPV of NOL4 were higher than those of CD56, although the differences were not statistically significant. However, NOL4 retains its nuclear immunoreactivity in areas of crush artifact or necrosis. Furthermore, NOL4 was not expressed in adjacent normal tissues including bronchial cells and pneumocytes. Therefore, a combination of NOL4 staining with other cytoplasmic or membranous neuroendocrine markers might enhance diagnostic utility for SCLC and other NENs.

We sought to determine whether multiple drilling (MD) combined with the injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) and β-tricalcium phosphate (β-TCP) could improve survival of the femoral head in pre-collapse lesions of non-traumatic osteonecrosis of the femoral head (ONFH) as compared with MD alone. We conducted a single-site, off-label, comparative and prospective cohort study between November 2017 and May 2019. We enrolled 25 hips (25 patients) with non-traumatic ONFH (Ficat–Arlet stage 2A or less). We performed a survival analysis, and the primary outcome was the occurrence of femoral head collapse on follow-up radiograph. Our cohort consisted of 11 men and 9 women of age 52.5 ± 8.8 years and a body mass index of 24.3 ± 3.0 kg/m2. The femoral heads were preserved in 9 hips (45.0%) and collapsed in 11 hips (55.0%) at the final follow-up; mean survival to collapse was 6.9 (range 2.8–13.5) months. There were no significant differences in the survival of the femoral head between the MD alone group and the MD with rhBMP-2 and β-TCP group (five hips survived, 50% vs. four hips survived, 40%, respectively; p = 0.83). MD combined with the injection of rhBMP-2 and β-TCP did not improve femoral head survival compared to MD alone in the pre-collapse non-traumatic ONFH lesion.

Background: The Rey Complex Figure Test (RCFT) has been widely used to evaluate neurocognitive functions in various clinical groups with a broad range of ages. However, despite its usefulness, the scoring method is as complex as the figure. Such a complicated scoring system can lead to the risk of reducing the extent of agreement among raters. Although several attempts have been made to use RCFT in clinical settings in a digitalized format, little attention has been given to develop direct automatic scoring that is comparable to experienced psychologists. Therefore, we aimed to develop an artificial intelligence (AI) scoring system for RCFT using a deep learning (DL) algorithm and confirmed its validity.Methods:A total of 6,680 subjects were enrolled in the Gwangju Alzheimer’s and Related Dementia cohort registry, Korea from January 2015 to June 2021. We obtained 20,040 scanned images using three images per subject (copy, immediate recall, and delayed recall) and scores rated by 32 experienced psychologists. We trained the automated scoring system using the DenseNet architecture. To increase the model performance, we improved the quality of training data by re-examining some images with poor results (mean absolute error (MAE) 5 [points]) and re-trained our model. Finally, we conducted an external validation with 150 images scored by five experienced psychologists.Results: For five-fold cross-validation, our first model obtained MAE = 1.24 [points] and R-squared ( ) = 0.977. However, after evaluating and updating the model, the performance of the final model was improved (MAE = 0.95 [points], = 0.986). Predicted scores among cognitively normal, mild cognitive impairment, and dementia were significantly differed. For the 150 independent test sets, the MAE and between AI and average scores by five human experts was 0.64 [points] and 0.994, respectively.Conclusion: We concluded that there was no fundamental difference between the rating scores of experienced psychologists and those of our AI scoring system. We expect that our AI psychologist will be able to contribute to screen the early stages of Alzheimer’s disease pathology in medical checkup centers or large-scale community-based research institutes in a faster and cost-effective way.

In this study, we tried to develop a FimH inhibitor that inhibits adhesion of enterohemorrhagic

Combining data collected from multiple study sites is becoming common and is advantageous to researchers to increase the generalizability and replicability of scientific discoveries. However, at the same time, unwantedinter-scanner biasesare commonly observed across neuroimaging data collected from multiple study sites or scanners, rendering difficulties in integrating such data to obtain reliable findings. While several methods for handling such unwanted variations have been proposed, most of them use univariate approaches that could be too simple to capture all sources of scanner-specific variations. To address these challenges, we propose a novel multivariate harmonization method, called RELIEF (REmoval ofLatentInter-scannerEffects throughFactorization) for estimating and removing both explicit and latent scanner effects. Our method is the first approach to introduce the simultaneous dimension reduction and factorization of interlinked matrices to a data harmonization context, which provides a new direction in methodological research for correcting inter-scanner biases. Analyzing diffusion tensor imaging (DTI) data from the Social Processes Initiative in Neurobiology of the Schizophrenia (SPINS) study and conducting extensive simulation studies, we show that RELIEF outperforms existing harmonization methods in mitigating inter-scanner biases and retaining biological associations of interest to increase statistical power. RELIEF is publicly available as an R package.

Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition.

Freezing is a common method for improving enzyme storage stability. During the freezing process, the freezing rate is an important parameter that can affect protein stability. However, there is limited information on the denaturation mechanisms and protein conformational changes associated with the freezing rate. In this study, the effects of freezing rate on activity loss and conformational changes in a model enzyme, l-lactate dehydrogenase, were evaluated. Enzyme solutions were frozen at various rates, from 0.2 to 70.6 °C/min, and ice seeding was conducted to reduce supercooling. The results demonstrated that fast freezing results in activity loss, structural changes, and aggregation. The residual activities at freezing rates of 0.2, 12.8, and 70.6 °C/min were 77.6 ± 0.9%, 64.1 ± 0.4%, and 44.8 ± 2.0%, respectively. As the freezing rate increased, the degree of dissociation and unfolding increased significantly, as determined using blue native-polyacrylamide gel electrophoresis and fluorescence spectroscopy. Moreover, a large number of amyloid aggregates were detected in samples frozen at a fast freezing rate (70.6 °C/min). The enzyme inactivation mechanism induced by fast freezing was proposed in terms of increased dehydration at the enzyme surface and an ice/unfroze solution interface, which could be helpful to establish a common understanding of enzyme inactivation during the freezing process.