Search

Wide-bandgap semiconductors (WBGs) are crucial building blocks of many modern electronic devices. However, there is significant room for improving the crystal quality, available choice of materials/heterostructures, scalability, and cost-effectiveness of WBGs. In this regard, utilizing layered 2D materials in conjunction with WBG is emerging as a promising solution. This review presents recent advancements in the integration of WBGs and 2D materials, including fabrication techniques, mechanisms, devices, and novel functionalities. The properties of various WBGs and 2D materials, their integration techniques including epitaxial and nonepitaxial growth methods as well as transfer techniques, along with their advantages and challenges, are discussed. Additionally, devices and applications based on the WBG/2D heterostructures are introduced. Distinctive advantages of merging 2D materials with WBGs are described in detail, along with perspectives on strategies to overcome current challenges and unlock the unexplored potential of WBG/2D heterostructures., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Purpose: A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects., Methods: A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs., Findings: After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs., Implications: The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties., Clinicaltrials: gov identifier: NCT04324905 (https://classic., Clinicaltrials: gov/ct2/show/NCT04324905)., Competing Interests: Declaration of competing interest Sung Hee Hong and Na Young Kim are full-time employees of Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study focuses on predicting the prognosis of acute ischemic stroke patients with focal neurologic symptoms using a combination of diffusion-weighted magnetic resonance imaging (DWI) and clinical information. The primary outcome is a poor functional outcome defined by a modified Rankin Scale (mRS) score of 3-6 after 3 months of stroke. Employing nnUnet for DWI lesion segmentation, the study utilizes both multi-task and multi-modality methodologies, integrating DWI and clinical data for prognosis prediction. Integrating the two modalities was shown to improve performance by 0.04 compared to using DWI only. The model achieves notable performance metrics, with a dice score of 0.7375 for lesion segmentation and an area under the curve of 0.8080 for mRS prediction. These results surpass existing scoring systems, showing a 0.16 improvement over the Totaled Health Risks in Vascular Events score. The study further employs grad-class activation maps to identify critical brain regions influencing mRS scores. Analysis of the feature map reveals the efficacy of the multi-tasking nnUnet in predicting poor outcomes, providing insights into the interplay between DWI and clinical data. In conclusion, the integrated approach demonstrates significant advancements in prognosis prediction for cerebral infarction patients, offering a superior alternative to current scoring systems., (© 2024. The Author(s).)

Shape memory gels have emerged as crucial elements in soft robotics, actuators, and biomedical devices; however, several problems persist, like the trade-off between shape fixity and shape recovery, and the limited temperature range for their application. This article introduces a new class of shape memory hybrid glycerogels (GGs) designed to address these limitations. The well-modulated internal structure of the GGs, facilitated by the Hofmeister salting-out effect, strategically incorporates a higher crystallite content, abundant crosslinking points, and a high elastic modulus. Unlike reported shape memory gels, the GG exhibits a perfect triple-step shape memory behavior in air with 100% shape fixity in a wide programming temperature range (75-135 °C) and simultaneously achieves 100% shape recoverability. The gel recovers its shape at -40 °C under near-infrared light across a wide programming temperature range (25-135 °C), showing unexpected initiation even at subzero temperatures. Inspired by the mechanics of composite structures, a method is proposed to integrate the GG seamlessly with a shape memory alloy, which further expands the temperature range that yields perfect shape memory properties. Finally, two light-controlled fluttering and crawling soft robot prototypes are engineered to illustrate the versatility and potential applications of the composite gel in soft robotics., (© 2024 Wiley‐VCH GmbH.)

Background Context: Cross-modality image generation from magnetic resonance (MR) to positron emission tomography (PET) using the generative model can be expected to have complementary effects by addressing the limitations and maximizing the advantages inherent in each modality., Purpose: This study aims to generate synthetic PET/MR fusion images from MR images using a combination of generative adversarial networks (GANs) and conditional denoising diffusion probabilistic models (cDDPMs) based on simultaneous 18 F-fluorodeoxyglucose (18F-FDG) PET/MR image data., Study Design: Retrospective study with prospectively collected clinical and radiological data., Patient Sample: This study included 94 patients (60 men and 34 women) with thoraco-lumbar pyogenic spondylodiscitis (PSD) from February 2017 to January 2020 in a single tertiary institution., Outcome Measures: Quantitative and qualitative image similarity were analyzed between the real and synthetic PET/ T2-weighted fat saturation MR (T2FS) fusion images on the test data set., Methods: We used paired spinal sagittal T2FS and PET/T2FS fusion images of simultaneous 18F-FDG PET/MR imaging examination in patients with PSD, which were employed to generate synthetic PET/T2FS fusion images from T2FS images using a combination of Pix2Pix (U-Net generator + Least Squares GANs discriminator) and cDDPMs algorithms. In the analyses of image similarity between the real and synthetic PET/T2FS fusion images, we adopted the values of mean peak signal to noise ratio (PSNR), mean structural similarity measurement (SSIM), mean absolute error (MAE), and mean squared error (MSE) for quantitative analysis, while the discrimination accuracy by three spine surgeons was applied for qualitative analysis., Results: Total of 2,082 pairs of T2FS and PET/T2FS fusion images were obtained from 172 examinations on 94 patients, which were randomly assigned to training, validation, and test data sets in 8:1:1 ratio (1664, 209, and 209 pairs). The quantitative analysis revealed PSNR of 30.634 ± 3.437, SSIM of 0.910 ± 0.067, MAE of 0.017 ± 0.008, and MSE of 0.001 ± 0.001, respectively. The values of PSNR, MAE, and MSE significantly decreased as FDG uptake increased in real PET/T2FS fusion image, with no significant correlation on SSIM. In the qualitative analysis, the overall discrimination accuracy between real and synthetic PET/T2FS fusion images was 47.4%., Conclusions: The combination of Pix2Pix and cDDPMs demonstrated the potential for cross-modal image generation from MR to PET images, with reliable quantitative and qualitative image similarities., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA)., Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study., Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects., Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant., Competing Interests: Kyung Tae Kim is a full-time employee of Addpharma. The other authors report no conflicts of interest associated with this work., (© 2024 Ryu et al.)

This study pioneers a chemical sensor based on surfactant-free aerosol-synthesized single-walled carbon nanotube (SWCNT) films for detecting nitrogen dioxide (NO 2 ). Unlike conventional CNTs, the SWCNTs used in this study exhibit one of the highest surface-to-volume ratios. They show minimal bundling without the need for surfactants and have the lowest number of defects among reported CNTs. Furthermore, the dry-transferrable and facile one-step lamination results in promising industrial viability. When applied to devices, the sensor shows excellent sensitivity (41.6% at 500 ppb), rapid response/recovery time (14.2/120.8 s), a remarkably low limit of detection (below ≈0.161 ppb), minimal noise, repeatability for more than 50 cycles without fluctuation, and long-term stability for longer than 6 months. This is the best performance reported for a pure CNT-based sensor. In addition, the aerosol SWCNTs demonstrate consistent gas-sensing performance even after 5000 bending cycles, indicating their suitability for wearable applications. Based on experimental and theoretical analyses, the proposed aerosol CNTs are expected to overcome the limitations associated with conventional CNT-based sensors, thereby offering a promising avenue for various sensor applications., (© 2024 Wiley‐VCH GmbH.)

Objective: Readmission rates after posterior cervical fusion (PCF) significantly impact patients and healthcare, with complication rates at 15%-25% and up to 12% 90-day readmission rates. In this study, we aim to test whether machine learning (ML) models that capture interfactorial interactions outperform traditional logistic regression (LR) in identifying readmission-associated factors., Methods: The Optum Clinformatics Data Mart database was used to identify patients who underwent PCF between 2004-2017. To determine factors associated with 30-day readmissions, 5 ML models were generated and evaluated, including a multivariate LR (MLR) model. Then, the best-performing model, Gradient Boosting Machine (GBM), was compared to the LACE (Length patient stay in the hospital, Acuity of admission of patient in the hospital, Comorbidity, and Emergency visit) index regarding potential cost savings from algorithm implementation., Results: This study included 4,130 patients, 874 of which were readmitted within 30 days. When analyzed and scaled, we found that patient discharge status, comorbidities, and number of procedure codes were factors that influenced MLR, while patient discharge status, billed admission charge, and length of stay influenced the GBM model. The GBM model significantly outperformed MLR in predicting unplanned readmissions (mean area under the receiver operating characteristic curve, 0.846 vs. 0.829; p < 0.001), while also projecting an average cost savings of 50% more than the LACE index., Conclusion: Five models (GBM, XGBoost [extreme gradient boosting], RF [random forest], LASSO [least absolute shrinkage and selection operator], and MLR) were evaluated, among which, the GBM model exhibited superior predictive performance, robustness, and accuracy. Factors associated with readmissions impact LR and GBM models differently, suggesting that these models can be used complementarily. When analyzing PCF procedures, the GBM model resulted in greater predictive performance and was associated with higher theoretical cost savings for readmissions associated with PCF complications.

Objective: We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs)., Methods: Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively., Results: Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45-0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37-0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95-1.60; p = 0.12; low-certainty of evidence)., Conclusion: In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.

The field of biomimetic electronics that mimic synaptic functions has expanded significantly to overcome the limitations of the von Neumann bottleneck. However, the scaling down of the technology has led to an increasingly intricate manufacturing process. To address the issue, this work presents a one-shot integrable electropolymerization (OSIEP) method with remote controllability for the deposition of synaptic elements on a chip by exploiting bipolar electrochemistry. Condensing synthesis, deposition, and patterning into a single fabrication step is achieved by combining alternating-current voltage superimposed on direct-current voltage-bipolar electropolymerization and a specially designed dual source/drain bipolar electrodes. As a result, uniform 6 × 5 arrays of poly(3,4-ethylenedioxythiophene) channels are successfully fabricated on flexible ultrathin parylene substrates in one-shot process. The channels exhibited highly uniform characteristics and are directly used as electrochemical synaptic transistor with synaptic plasticity over 100 s. The synaptic transistors have demonstrated promising performance in an artificial neural network (NN) simulation, achieving a high recognition accuracy of 95.20%. Additionally, the array of synaptic transistor is easily reconfigured to a multi-gate synaptic circuit to implement the principles of operant conditioning. These results provide a compelling fabrication strategy for realizing cost-effective and disposable NN systems with high integration density., (© 2024 The Author(s). Advanced Materials Technologies published by Wiley‐VCH GmbH.)

Teriparatide and denosumab, anti-osteoporosis medications with different mechanisms, have been widely used in the patients with osteoporotic vertebral fracture (OVF) considered as advanced osteoporosis. Teriparatide has been shown to enhance bone formation and fracture healing in OVF, but there are still no sufficient evidences discussing about the role of denosumab in newly developed OVF. In this study, we found the similar radiological deformation and functional outcomes of conservative treatment with teriparatide and denosumab in thoracolumbar (TL) OVF, and teriparatide showed a more frequent incidence of fracture union with paravertebral bone bridge formation compared to denosumab., Introduction: Teriparatide and denosumab have been widely used to treat advanced osteoporosis and prevent subsequent fractures in patients with OVCF. Unlike teriparatide, which is considered to be effective in fracture healing, there is still no clear role and evidence for the effect of denosumab in acute OVCF. This study compared the radiological and functional outcomes of conservative treatment with teriparatide and denosumab in TL-OVF., Methods: This retrospective study enrolled 78 women with mean age of 74.69 ± 7.66 (60-92) years diagnosed as a TL-OVF with no neurological deficits. All patients were treated conservatively with teriparatide (34 of group T, once-daily 20 μg) or denosumab (44 of group D, once-6 months 60 mg) for 6 months. We evaluated the radiological deformation (kyphotic angle, segmental vertebral kyphotic angle, and compression ratio) and the incidence of fracture union with paravertebral bone bridge formation (FUPB) and functional outcomes using the visual analog scale (VAS) and Oswestry Disability Index (ODI) at 0, 3, and 6 months., Results: In the radiological deformation and functional outcomes, there were no significant differences at 0, 3, and 6 months between the two groups (P > 0.05). However, the incidence of FUPB at 6 months was higher in group T (20/34, 58.8%) compared to group D (11/44, 25.0%) (P = 0.004), and teriparatide was the most statistically significant factor for achieving FUPB (OR 4.486, P = 0.012) in multivariable logistic analysis., Conclusions: Teriparatide and denosumab, despite of their different pharmacological mechanisms, showed similar radiological deformation and functional outcomes in the conservative treatment of TL-OVF. However, teriparatide showed a significantly higher incidence of fracture union with paravertebral bone bridge formation., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Recently, C 60 has emerged as a promising anode material for Li-ion batteries, attracting significant interest due to its excellent lithium storage capacity. The electrochemical performance of C 60 as an anode is largely dependent on its internal crystal structure, which is significantly influenced by the synthesis method and corresponding conditions. However, there have been few reports on how the synthesis process affects the crystal structure and Li + storage capacity of C 60 . This study used the liquid-liquid interface precipitation method and a low-temperature annealing process to fabricate one-dimensional C 60 nanorods (NRs). We thoroughly investigated synthesis conditions, including the growth time, drying temperature, annealing time, and annealing atmosphere. The results demonstrate that these synthesis conditions directly impact the morphology, phase transition, and electrochemical efficiency of pure C 60 NRs. Remarkably, the hexagonal close-packed structural C 60 NRs-6012h, in a metastable form, exhibits a reversible Li + storage capacity as an anode material in Li-ion batteries. Furthermore, the face-centered cubic C 60 NRs-603001h electrode shows significantly enhanced rate performance and long-cycle stability. A discharge-specific capacity of 603 mAh g -1 was maintained after 2000 cycles at a current density of 2 A g -1 . This study elucidates the effect of synthesis conditions on C 60 crystals, offering an effective strategy for preparing high-performance C 60 anode materials.

Background: BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy., Patients and Methods: Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS)., Results: Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses., Conclusion: BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02866006., Competing Interests: Authors from Cellid. Inc. are employees of and/or shareholders of the company, which is developing a BVAC-C vaccine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Choi, Lee, Bae, Kang, Cho, Kim, Kim, Kim, Kim, Kim, Lee, Lim, Oh, Song, Jeon, Park, Kim, Kang and Kim.)

Background Context: Decompression surgery is a treatment option for patients with degenerative cervical myelopathy (DCM). Surgical decisions primarily depend on clinical symptoms and radiological examinations. The diagnostic and prognostic significance of evoked potential tests for surgical outcomes in patients with DCM has not been thoroughly examined., Purpose: To identify the diagnostic and prognostic significance of preoperative evoked potential tests in patients with DCM who underwent decompression surgery., Study Design: This was a retrospective observational study., Patient Sample: One hundred two consecutive patients who underwent evoked potential tests and surgical treatment between January 2016 and December 2020 in a single spine center and had a minimum follow-up of 6 months., Outcome Measures: Japanese Orthopedic Association (JOA) scores obtained preoperatively and 6 months after surgery., Methods: This study evaluated the preoperative central motor conduction time (CMCT), somatosensory evoked potentials, and Japanese Orthopedic Association (JOA) scores obtained preoperatively and 6 months after surgery., Results: Abnormal CMCT findings were observed in 94 patients (92.2%). Abnormal somatosensory evoked potentials were observed in 77 patients (75.5%). There was a statistically significant correlation between preoperative JOA score and abductor pollicis brevis (APB)-CMCT (r=-0.546, p=.001), tibialis anterior (TA)-CMCT (r=-0.517, p<.001), median nerve (MN)-SSEP (r=-0.353, p=.001), and tibial nerve (TN)-SSEP (r=-0.349, p=.003). There were significant differences in recovery rates associated with diabetes mellitus (DM), preoperative severity of myelopathy, TA-CMCT, MN-SSEP, and TN-SSEP. Stepwise multiple regression analysis showed that the major factors affecting the clinical outcomes were TN-SSEP (β=0.327, p=.004), preoperative JOA score (β=0.278, p=.012), and DM (β=0.241, p=.025)., Conclusions: Evoked potential testing is a functional diagnostic tool that can indicate the severity of myelopathic symptoms in patients with DCM. Additionally, preoperative TN-SSEP may have significant prognostic value in predicting postoperative clinical outcomes. Thus, preoperative evoked potential tests could be helpful for determining suitable surgical treatment candidates and forecasting postoperative prognosis., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Probabilistic graphical modelling (PGM) can be used to predict risk at the individual patient level and show multiple outcomes and exposures in a single model., Objective: To develop PGM for the prediction of clinical outcome in patients with degenerative cervical myelopathy (DCM) after posterior decompression and to use PGM to identify causal predictors of the outcome., Methods: We included data from 59 patients who had undergone cervical posterior decompression for DCM. The candidate predictive parameters were age, sex, body mass index, trauma history, symptom duration, preoperative and last Japanese Orthopaedic Association (JOA) scores, gait impairment, claudication, bladder dysfunction, Nurick grade, American Spinal Injury Association (ASIA) grade, smoking, diabetes mellitus, cardiopulmonary disorders, hypertension, stroke, Parkinson's disease, dementia, psychiatric disorders, arthritis, ossification of the posterior longitudinal ligament, cord signal change, postoperative kyphosis and the cord compression ratio., Results: In regression analyses, preoperative JOA (PreJOA) score, presence of a psychiatric disorder, and ASIA grade were identified as significant factors associated with the last JOS score. Dementia, sex, PreJOA score and gait impairment were causal factors in the PGM. Sex, dementia and PreJOA score were direct causal factors related to the last follow-up JOA (LastJOA) score. Being female, having dementia, and having a low PreJOA score were significantly related to having a low LastJOA score., Conclusions: The causal predictors of surgical outcome for DCM were sex, dementia and PreJOA score. Therefore, PGM may be a useful personalized medicine tool for predicting the outcome of patients with DCM.

Cleaning a fouled membrane using warm water, instead of commonly used fouling control chemicals, is an approach advocated in resource-limited settings, where small-scale membrane filtration is used to provide clean water. Thermoresponsive polymers coated onto membranes undergo a conformational change across their lower critical solution temperature (LCST), enabling foulant removal during such temperature-swing cleaning. However, their intrinsic hydrophobicity above the LCST poses a fundamental material challenge. In this study, we examine how thermoresponsive polymers can be optimally copolymerized with hydrophilic polymers by precisely manipulating monomer arrangement of thermoresponsive N -isopropylacrylamide and hydrophilic 2-[2-(2-methoxyethoxy)ethoxy]ethyl acrylate. We successfully grafted these copolymers with different monomer arrangements onto poly(ether sulfone) ultrafiltration membranes while maintaining other polymer characteristics, such as the degree of polymerization and grafting density, constant. We found that placing hydrophilic polymer blocks at the outermost surface above the thermoresponsive polymer blocks is critical to achieving high surface hydrophilicity while preserving the thermoresponsive functionality. We demonstrate enhanced fouling resistance and efficient temperature-swing cleaning with optimized copolymer design based on their interaction with bovine serum albumin during static adsorption, filtration, and cleaning processes. These findings emphasize the importance of accurately tailoring the polymer architecture to enable more efficient filtration with reduced fouling and the capability to effectively clean the fouled membrane by simply using warm water.

Full comprehension of the pyrolysis of polymer materials is crucial for the design and application of thermal protection systems; however, it involves complex phenomena at different spatial and temporal scales. To bridge the gap between the abundant atomistic simulations and continuum modeling in the literature, we perform a novel mesoscale study of the pyrolysis process using coarse-grained molecular dynamics (CG MD) simulations. Polyethylene (PE) consisting of united atoms including implicit hydrogen is considered a model polymer, and the configurational change of PE in thermal degradation is modeled by applying the bond-breaking phenomenon based on bond energy or bond length criteria. A cook-off simulation is implemented to optimize the heuristic protocol of bond dissociation by comparing the reaction products with a ReaxFF simulation. The aerobic hyperthermal pyrolysis under oxygen bombardment is simulated at a large scale of hundreds of nanometers to observe the intricate phenomena occurring from the surface to the depth inside the material. The intrinsic thermal durability of the model polymer at extreme conditions with and without oxygen environment can be effectively simulated from the proposed mesoscale simulation to predict important thermal degradation properties required for continuum-scale pyrolysis and ablation simulations. This work serves as an initial investigation of polymer pyrolysis at the mesoscale and helps understand the concept at a larger scale.

Although it may appear infeasible and impractical, building artificial intelligence (AI) using a bottom-up approach based on the understanding of neuroscience is straightforward. The lack of a generalized governing principle for biological neural networks (BNNs) forces us to address this problem by converting piecemeal information on the diverse features of neurons, synapses, and neural circuits into AI. In this review, we described recent attempts to build a biologically plausible neural network by following neuroscientifically similar strategies of neural network optimization or by implanting the outcome of the optimization, such as the properties of single computational units and the characteristics of the network architecture. In addition, we proposed a formalism of the relationship between the set of objectives that neural networks attempt to achieve, and neural network classes categorized by how closely their architectural features resemble those of BNN. This formalism is expected to define the potential roles of top-down and bottom-up approaches for building a biologically plausible neural network and offer a map helping the navigation of the gap between neuroscience and AI engineering., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeon and Kim.)

Acid or alkali spills destroy the physicochemical properties of soils and cause irreversible damage to their ecological functions. This study examined changes in physicochemical properties ( i.e., organic matter, clay content, and cation exchange capacity (CEC)) as well as pH buffering capacity (indicator of soil ecological function) of 20 field soils in response to the spills. Also, we identified the characteristics of soils vulnerable to the spills. Although the spills did not substantially change the clay content, organic matter decreased by approximately 50%, consequently resulting in a 41% decrease in pH buffering capacity. When we classified soils into three groups based on soil properties and pH buffering capacity, the extent of change in soil properties by spill differed by group. As the organic matter content increased or clay content decreased, the soil tended to be more vulnerable to spills in terms of the degree to which the soil function was changed. Considering that the protonation-deprotonation characteristics of clay sized fraction were not remarkably changed by the spills, this result was mainly attributed to the dissolution of organic matter. Together with the successful prediction of CEC and pH buffering capacity by multiple linear regression models using organic matter and clay content, our findings enable the easy classification of soils based on their vulnerability and site-specific management of areas with a high probability of spills., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Extreme gradient boosting (XGBoost) is an artificial intelligence algorithm capable of high accuracy and low inference time. The current study applies this XGBoost to the production of platinum nano-film coating through atomic layer deposition (ALD). In order to generate a database for model development, platinum is coated on α-Al2O3 using a rotary-type ALD equipment. The process is controlled by four parameters: process temperature, stop valve time, precursor pulse time, and reactant pulse time. A total of 625 samples according to different process conditions are obtained. The ALD coating index is used as the Al/Pt component ratio through ICP-AES analysis during postprocessing. The four process parameters serve as the input data and produces the Al/Pt component ratio as the output data. The postprocessed data set is randomly divided into 500 training samples and 125 test samples. XGBoost demonstrates 99.9% accuracy and a coefficient of determination of 0.99. The inference time is lower than that of random forest regression, in addition to a higher prediction safety than that of the light gradient boosting machine.

Background and Purpose: Pyogenic spinal infection (PSI) has recently been on the rise due to aging and increasing degenerative spinal disease related procedures. PSI requires long-term antibiotic treatment and is followed by sustained functional disability even after successful treatment. This study aimed to analyze the clinical factors associated with medical burden and functional status of PSI., Methods: This retrospective study involved patients with non-postoperative PSI of thoraco-lumbo-sacral area in a single tertiary hospital. The length/cost of hospitalization with an antibiotic therapy and severity of back pain using the short form 36 (SF-36) were defined as the medical burden and functional status, respectively. We analyzed the clinical factors associated with medical burden and functional status., Results: We enrolled 142 patients (91 males and 51 females). The length and cost of hospitalization were 55.56 ± 27.09 (7-172) days and $14,070.17 ± 9289.39 (1611.87-48,722.35), respectively. A recurrence rate of 7.7% (11/142) and significant improvement of SF-36 at six months after completion of antibiotic treatment were noted ( p < 0.05). Procedure-related (OR 2.702), C-reactive protein (CRP; OR 1.062), bacteremia (OR 4.966), additional surgical treatment (OR 6.524), recurrence (OR 12.453), and paraspinal abscess (OR 5.965) for above-average length of hospitalization were observed; female (OR 4.438), CRP (OR 1.071), bacteremia (OR 4.647), additional surgical treatment (OR 6.737), recurrence (OR 22.543), and extent of lesion (OR 1.431) for above-average cost of hospitalization; leg weakness (OR 15.966), white blood cell (WBC; OR 1.116), Charlson's comorbidity index (CCI, OR 1.485), and identification of causative bacteria (OR 2.913) for below-average initial SF-36 were observed; leg weakness (OR 7.975) and WBC (OR 1.094) for below-average 6-month SF-36 were the statistically significant clinical factors in the multivariable logistic regression analysis ( p < 0.05)., Conclusion: Recurrence and leg weakness were identified as the most important clinical factors for medical burden and functional status in PSI, respectively. We think that it is necessary to actively suppress recurrence and manage neurological deficits for decreasing medical burden and achieving favorable functional outcome in the treatment of PSI.

In this study, we report on the electrochemical properties of a solid state lithium ion battery (LIB) using a poly (ethylene glycol) dimethyl ether (PEGDME)-based solid polymer electrolyte (P-SPE). The LIB is prepared using a LiFePO 4 (LFP) cathode and graphite anode material with P-SPE, and the kinetic properties of the lithium ions in the P-SPE are investigated. The synthesized P-SPE is shown to be suitable solid polymer electrolyte candidate for LIB applications. LFP and graphite are selected as electrode materials to validate their effectiveness in different battery cells with respect to their high energy density and inherent safety. The five-layer stacked 5 × 6 cm 2 pouch-type LIB demonstrates a high capacity of 90 mAh (0.6 mAh/cm 2 ) or more in the initial cycle, and it shows cycle stability with a capacity decrease of 20% over 500 cycles. We test the manufactured pouch-type full cells under extreme conditions ( e. g. , cutting, crushing and exposure of the battery cell to the atmosphere). LIBs using the developed P-SPE are promising solid polymer electrolyte candidates for wearable LIB as well as high energy LIB applications., Competing Interests: The authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

Background: Adaptation in proximal muscles for daily motor tasks after sustained use of a prosthetic hand has not been fully understood., Objectives: This study aimed to investigate changes in hand functions and activities of proximal muscles after multiple weeks of using a myoelectric prosthetic hand at home., Study Design: Repeated measures., Methods: Four people with traumatic upper-limb loss used a myoelectric prosthetic hand (bebionic) at home over the 6- to 8-week period. A user survey, Orthotics and Prosthetics User Survey for Upper Extremity Functional Status 2.0, was used to measure upper-limb functions and the degree of using the prosthetic hand each week. Their hand functions, muscle activities, and grip-specific neuromuscular effort were evaluated by the Southampton Hand Assessment Procedure at the preassessment and postassessment sessions (PRE and POST, respectively)., Results: All subjects increased Southampton Hand Assessment Procedure scores at PRE compared with POST with subject-specific changes in muscle activations. In a detail, at POST, subject 1 reduced the shoulder muscle activity compared with PRE, while at POST, subject 2 reduced biceps activity compared with PRE. At POST, greater pectoralis activity and reduced trapezius activity were observed in subject 3, and greater activity in those two muscles was found in subject 4 compared with PRE., Conclusion: After multiple weeks of using the myoelectric prosthetic hands, their hand functions during ADL tasks were improved and changes in the muscle activities were found., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background and Objectives: This study investigated the usefulness of deep neural network (DNN) models based on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and blood inflammatory markers to assess the therapeutic response in pyogenic vertebral osteomyelitis (PVO). Materials and Methods: This was a retrospective study with prospectively collected data. Seventy-four patients diagnosed with PVO underwent clinical assessment for therapeutic responses based on clinical features during antibiotic therapy. The decisions of the clinical assessment were confirmed as 'Cured' or 'Non-cured'. FDG-PETs were conducted concomitantly regardless of the decision at each clinical assessment. We developed DNN models depending on the use of attributes, including C-reactive protein (CRP), erythrocyte sedimentation ratio (ESR), and maximum standardized FDG uptake values of PVO lesions (SUV max ), and we compared their performances to predict PVO remission. Results: The 126 decisions (80 'Cured' and 46 'Non-cured' patients) were randomly assigned with training and test sets (7:3). We trained DNN models using a training set and evaluated their performances for a test set. DNN model 1 had an accuracy of 76.3% and an area under the receiver operating characteristic curve (AUC) of 0.768 [95% confidence interval, 0.625-0.910] using CRP and ESR, and these values were 79% and 0.804 [0.674-0.933] for DNN model 2 using ESR and SUV max , 86.8% and 0.851 [0.726-0.976] for DNN model 3 using CRP and SUV max , and 89.5% and 0.902 [0.804-0.999] for DNN model 4 using ESR, CRP, and SUV max , respectively. Conclusions: The DNN models using SUV max showed better performances when predicting the remission of PVO compared to CRP and ESR. The best performance was obtained in the DNN model using all attributes, including CRP, ESR, and SUV max , which may be helpful for predicting the accurate remission of PVO.

We demonstrated that a well-designed nanopatterned cover improves photovoltaic efficiency across a wide range of incident angles (θ). A nanopatterned cover was created using an integrated ray-wave optics simulation to maximize the light absorption of the surface-textured Si photovoltaic device. A hexagonally arranged nanocone array with a 300 nm pitch was formed into a polymer using nanoimprinting, and the nanostructured polymer was then attached to a glass cover with an index-matching adhesive. Angle-resolved current density-voltage measurements on Si photovoltaic devices showed that the nanopatterned glass cover yielded a 2-13% enhancement in power conversion efficiency at θ = 0-60°, which accounted for its broadband antireflective feature. We performed all-season-perspective simulations based on the results of the integrated ray-wave optics simulations and solar altitude database of South Korea, which validated the sustainability of the developed nanopatterned cover during significant seasonal fluctuations.

The development of advanced hierarchical anode materials has recently become essential to achieving high-performance sodium-ion batteries. Herein, we developed a facile and cost-effective scheme for synthesizing graphene-wrapped, nitrogen-rich carbon-coated iron sulfide nanofibers (FeS@NCG) as an anode for SIBs. The designed FeS@NCG can provide a significant reversible capacity of 748.5 mAh g -1 at 0.3 A g -1 for 50 cycles and approximately 3.9-fold higher electrochemical performance than its oxide analog (Fe 2 O 3 @NCG, 192.7 mAh g -1 at 0.3 A g -1 for 50 cycles). The sulfur- and nitrogen-rich multilayer package structure facilitates efficient suppression of the porous FeS volume expansion during the sodiation process, enabling a long cycle life. The intimate contact between graphene and porous carbon-coated FeS nanofibers offers strong structural barriers associated with charge-transfer pathways during sodium insertion/extraction. It also reduces the dissolution of polysulfides, enabling efficient sodium storage with superior stable kinetics. Furthermore, outstanding capacity retention of 535 mAh g -1 at 5 A g -1 is achieved over 1010 cycles. The FeS@NCG also exhibited a specific capacity of 640 mAh g -1 with a Coulombic efficiency of above 99.8% at 5 A g -1 at 80 °C, indicating its development prospects in high-performance SIB applications.

Li@PCBM, the first neutral Li@C 60 derivative, was synthesized. The Li@PCBM exists in a monomer-dimer equilibrium in solution but as a monomer in the PCBM matrix. The fully dispersed Li@PCBM n-doped the surrounding empty PCBM, raising the Fermi level by 0.13 eV compared with the undoped PCBM film. The hybrid films were utilized as an ETL for PSCs, promoting the efficiency of the device.

Optical nanoantennas provide control of light at the nanoscale, which makes them important for diverse areas ranging from photocatalysis and flat metaoptics to sensors and biomolecular tweezing. They have traditionally been limited to metallic and dielectric nanostructures that sustain plasmonic and Mie resonances, respectively. More recently, nanostructures of organic J-aggregate excitonic materials have been proposed capable of also supporting nanooptical resonances, although their advance has been hampered from difficulty in nanostructuring. Here, the authors present the realization of organic J-aggregate excitonic nanostructures, using nanocylinder arrays as model system. Extinction spectra show that they can sustain both plasmon-like resonances and dielectric resonances, owing to the material providing negative and large positive permittivity regions at the different sides of its exciton resonance. Furthermore, it is found that the material is highly anisotropic, leading to hyperbolic and elliptic permittivity regions. Nearfield analysis using optical simulation reveals that the nanostructures therefore support hyperbolic localized surface exciton resonances and elliptic Mie resonances, neither of which has been previously demonstrated for this type of material. The anisotropic nanostructures form a new type of optical nanoantennas, which combined with the presented fabrication process opens up for applications such as fully organic excitonic metasurfaces., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Five-fluorouracil (5-FU) is a chemotherapeutic agent that is mainly metabolized by the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5-FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into two groups based on DHU/U ratio. The calculated DHU/U ratios ranged from 0.52 to 7.12, and the two groups were classified into the 10th percentile and 90th percentile for untargeted metabolomics analysis using liquid chromatography-quantitative time-of-flight-mass spectrometry. A total of 4440 compounds were detected and filtered out based on a coefficient of variation below 30%. Our results revealed that six metabolites differed significantly between the high activity group and low activity group (false discovery rate q-value < 0.05). Uridine was significantly higher in the low DPD activity group and is a precursor of U involved in pyrimidine metabolism; therefore, we speculated that DPD deficiency can influence uridine levels in plasma. Furthermore, the cutoff values for detecting DPD deficient patients from previous studies were unsuitable for Koreans. Our metabolomics approach is the first study that reported the DHU/U ratio distribution in healthy Korean subjects and identified a new biomarker of DPD deficiency., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: Adjacent segment disease (ASD) requiring revision surgery is the most serious complication that can occur in patients undergoing posterior lumbar interbody fusion (PLIF) surgery. This study aimed to determine the risk factors for surgical ASD requiring revision surgery after PLIF with screw fixation surgery. We especially focused on paraspinal muscle, facet joint, and disc degeneration., Methods: Among the patients who underwent PLIF with screw fixation due to degenerative spinal disease from January 2010 to December 2019, patients who underwent revision surgery for the development of ASD were enrolled. To evaluate the risk factors for surgical ASD, we selected a control group. Each patient in the control group was matched by age, sex, fusion level, number of fused segments, secondary MRI follow-up interval, and follow-up duration with a patient in the surgical ASD group. The radiographic and demographic data were compared between the surgical ASD and control groups., Results: There were statistically significant differences between the two groups in radiological parameters of preoperative facet degeneration, facet effusion, facet angle, and fatty degeneration of the multifidus muscle. Multivariable logistic regression analysis revealed that preoperative facet effusion (odds ratio [OR] 6.48), preoperative facet angle (OR 1.24), and progression of fatty degeneration in the multifidus muscle (OR 1.07) were significant risk factors for surgical ASD., Conclusions: Preexisting high-grade adjacent facet effusion, sagittally oriented facet joint angle, and progressive fatty degeneration of the multifidus muscle are associated with the development of surgical ASD after PLIF surgery., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background Context: Most osteoporotic vertebral compression fractures (OVCFs) are treated conservatively; however, in some patients, progressive vertebral body collapse leads to spinal deformity and cord compression. These complications are strongly associated with impaired performance activities of daily living and a poor quality of life., Purpose: To identify the role of the paraspinal muscle as a risk factor for progressive vertebral body collapse in patients with OVCF., Study Design: This was a retrospective observational study., Patient Sample: Fifty-five consecutive patients with OVCF who were treated conservatively from January 2018 to June 2020 in a single spine center and had a minimum follow-up of 6 months., Outcome Measures: A lateral plain radiograph in a neutral posture was taken when the patient was first diagnosed and at 1, 3, and 6 months after the first diagnosis. Vertebral height was measured at the point of maximal collapse of the affected vertebral body; vertebral collapse (%) was also measured. The cross-sectional area (CSA) and fatty degeneration of the paraspinal muscle were measured using the open-source software Image J. The visual analogue scale (VAS) scores were collected at the time of initial fracture diagnosis and at 1, 3, and 6 months., Methods: The clinical and radiological data were analyzed. In the L4-5 intervertebral disc level, axial T2-weighted magnetic resonance imaging was used to measure the CSA and fatty degeneration of the paraspinal muscles. Correlation and multiple regression analyses were performed to analyze the risk factors associated with progressive vertebral body collapse., Results: The vertebral collapse difference was strongly associated with paraspinal muscle fatty degeneration (r=0.684, p=.000) and body mass index (r=0.300, p=.026). Multiple linear regression analysis demonstrated that the risk factor for progression of vertebral collapse was paraspinal muscle fatty degeneration (β=0.724, p=.000). There was a statistically significant correlation between the progression in vertebral collapse and VAS score at 3 (r=0.402, p=.002) and 6 months (r=0.604, p=.000)., Conclusions: In patients with OVCF, fatty degeneration of the paraspinal muscle was a predictive factor for progressive vertebral body collapse. This study suggests that more attention should be paid to patients with paraspinal sarcopenia among those with OVCFs., Competing Interests: Declarations of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The ability to generate lower-noise microwaves has greatly advanced high-speed, high-precision scientific and engineering fields. Microcombs have high potential for generating such low-noise microwaves from chip-scale devices. To realize an ultralow-noise performance over a wider Fourier frequency range and longer time scale, which is required for many high-precision applications, free-running microcombs must be locked to more stable reference sources. However, ultrastable reference sources, particularly optical cavity-based methods, are generally bulky, alignment-sensitive and expensive, and therefore forfeit the benefits of using chip-scale microcombs. Here, we realize compact and low-phase-noise microwave and soliton pulse generation by combining a silica-microcomb (with few-mm diameter) with a fibre-photonic-based timing reference (with few-cm diameter). An ultrastable 22-GHz microwave is generated with -110 dBc/Hz (-88 dBc/Hz) phase noise at 1-kHz (100-Hz) Fourier frequency and 10 -13 -level frequency instability within 1-s. This work shows the potential of fully packaged, palm-sized or smaller systems for generating both ultrastable soliton pulse trains and microwaves, thereby facilitating a wide range of field applications involving ultrahigh-stability microcombs., (© 2022. The Author(s).)

There have been attempts to provide new cinematic experiences by connecting TV or movie content to suitable locations through augmented reality (AR). However, few studies have suggested a method to manage breakdowns in continuity due to spatial transitions. Thus, we propose a method to manage the spatial transition that occurs when we create a TV show trajectory by mapping TV show scenes with spatiotemporal information to the real world. Our approach involved two steps. The first step is to reduce the spatial transition considering the sequence, location, and importance of TV show scenes when creating the TV show trajectory in the authoring tool. The second is to fill the spatial transition with additional TV show scenes considering sequence, importance, and user interest when providing the TV show trajectory in the mobile application. The user study results showed that reducing spatial transition increases narrative engagement by allowing participants to see important content within the trajectory. The additional content in spatial transition decreased the physical demand and effort in terms of the perceived workload, although it increased the task completion time. Integrated spatial transition management improved the overall cinematic augmented reality (CAR) experience of the TV show. Furthermore, we suggest design implications for realizing the CAR of TV shows based on our findings., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2022.)

Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination., (© 2021, The American College of Clinical Pharmacology.)

Omeprazole blocks the gastric H + /K +  adenosine triphosphatase, thus inhibiting gastric acid secretion, and is metabolized by cytochrome P450 (CYP) 2C19. Due to the physiological changes in the elderly, there are different pharmacokinetic consequences compared to young people. The aim of this study was to evaluate the pharmacokinetic profiles of omeprazole in 15 elderly participants according to the CYP2C19 genotype. The concentration-time profiles of omeprazole and its metabolites, 5-hydroxy (5-OH) omeprazole and omeprazole sulfone, were similar between the CYP2C19 extensive metabolizer (EM) and intermediate metabolizer groups. In contrast, when comparing the EM group and CYP2C19 poor metabolizer (PM) group, the EM/PM geometric mean ratio (95% confidence interval) of area under the plasma concentration-time curve from time of dosing to the last measurable concentration was 0.52 (0.27-1.01) and that of the IM group was 0.71 (0.32-1.59), indicating that the exposure of omeprazole in the PM group was increased. The exposure of 5-OH omeprazole was significantly decreased in the PM group when compared to the EM group, with an EM/PM geometric mean ratio (95% confidence interval) of 2.20 (1.50-3.22). In conclusion, the tendency of drug exposure according to the CYP2C19 genotype in the elderly and young adults was similar in that the exposure level was highest in the PM group. However, when compared to young adults, the difference between the genotype groups was smaller in the elderly., (© 2021, The American College of Clinical Pharmacology.)

Various studies have highlighted the importance of ethnic differences. The consideration of ethnic differences in the field of individualized pharmacotherapy is imperative. Therefore, various organizations and networks across countries should aim to conduct multicountry and multiregional clinical trials (MRCTs). If there is solid evidence available to evaluate the existence of ethnic differences between the same regional areas, it will lead to an increase in the efficiency of drug development. The purpose of this paper was to compare the approval dosing regimen among four Asian countries (Korea, Japan, China, and Taiwan) and elucidate the readiness and current status of the implementation of the International Conference on Harmonization (ICH) E17 guidelines on MRCTs. Reducing unnecessary clinical trials via multinational clinical trials in East Asian countries is also suggested. The approved dosing regimens for some drugs in the four Asian countries were similar; however, some differences might be caused by differences in legislation, even though there were no ethnic differences. This indicates that there are several roles to be expected of the Asia Clinical Pharmacology study network for exploratory MRCTs, which would lead to the accumulation of evidence for MRCTs, ultimately accelerating the efficiency of drug development in East Asian countries. The exposure of the new treatment to the necessary patients through collaborative research coordination and simultaneous multinational subject recruitment would serve its role in providing East Asia with specific personalized medicine with a high treatment success rate., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Understanding the rationale of combining immunotherapy and other anticancer treatment modalities is of great interest because of interpatient variability in single-agent immunotherapy. Here, we demonstrated that topoisomerase I inhibitors, a class of chemotherapeutic drugs, can alter the tumor immune landscape, corroborating their antitumor effects combined with immunotherapy. We observed that topotecan-conditioned TC-1 tumors were occupied by a vast number of monocytic cells that highly express CD11c, CD64, and costimulatory molecules responsible for the favorable changes in the tumor microenvironment. Ly6C + MHC-II + CD11c hi CD64 hi cells, referred to as topotecan-induced monocyte-derived dendritic cells (moDCs), proliferate and activate antigen-specific CD8 + T cells to levels equivalent to those of conventional DCs. Phenotypic changes in Ly6C + cells towards moDCs were similarly induced by exposure to topotecan in vitro, which was more profoundly facilitated in the presence of tumor cells. Notably, anti-M-CSFR reversed the acquisition of DC-like properties of topotecan-induced moDCs, leading to the abolition of the antitumor effect of topotecan combined with a cancer vaccine. In short, topoisomerase I inhibitors generate monocyte-derived antigen-presenting cells in tumors, which could be mediated by M-CSF-M-CSFR signaling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Li + intercalates into a pure face-centered-cubic (fcc) C 60 structure instead of being adsorbed on a single C 60 molecule. This hinders the excess storage of Li ions in Li-ion batteries, thereby limiting their applications. However, the associated electrochemical processes and mechanisms have not been investigated owing to the low electrochemical reactivity and poor crystallinity of the C 60 powder. Herein, a facile method for synthesizing pure fcc C 60 nanoparticles with uniform morphology and superior electrochemical performance in both half- and full-cells is demonstrated using a 1 m LiPF 6 solution in ethylene carbonate/diethyl carbonate (1:1 vol%) with 10% fluoroethylene carbonate. The specific capacity of the C 60 nanoparticles during the second discharge reaches ≈750 mAh g -1 at 0.1 A g -1 , approximately twice that of graphite. Moreover, by applying in situ X-ray diffraction, high-resolution transmission electron microscopy, and first-principles calculations, an abnormally high Li storage in a crystalline C 60 structure is proposed based on the vacant sites among the C 60 molecules, Li clusters at different sites, and structural changes during the discharge/charge process. The fcc of C 60 transforms tetragonal via orthorhombic Li x C 60 and back to the cubic phase during discharge. The presented results will facilitate the development of novel fullerene-based anode materials for Li-ion batteries., (© 2021 Wiley-VCH GmbH.)

To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration-time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem., (© 2021. The Author(s).)

Lead-free perovskite solar cells (PSCs) have attracted interest among scientists searching for eco-friendly energy harvesting devices. Herein, the effects of ozone exposure on poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) in lead-free tin halide PSCs as a facile and low-cost process for improving device performance are analyzed. Two types of tin-based PSCs and one typical lead-based PSC were fabricated. The ozone exposure on PEDOT:PSS increases the short-circuit current density ( J SC ) and the fill factor (FF) of PSCs in all cases with perovskite grain enlargement and hole-mobility enhancement of the devices, respectively. For open-circuit voltage ( V OC ), the outcome depends on the band gap and the energy levels of the perovskite films. While ozone exposure treatment is favorable for PEA 0.15 FA 0.85 SnI 3 -based tin PSCs, V OC decreases with ozone exposure in the case of Ge:EDA 0.01 FA 0.98 SnI 3 -based tin PSCs because of a misalignment of the energy levels. Regardless, the efficiency of PEA 0.15 FA 0.85 SnI 3 -based tin PSCs increases from 8.7 to 10.1% when measured inside a glovebox upon ozone exposure of PEDOT:PSS. The efficiency of Ge:EDA 0.01 FA 0.98 SnI 3 -based tin PSCs increases from 6.8 to 8.1%, and the devices retain an efficiency of 5.0% even after 50 days in air.

Perovskite solar cells (PSCs) are regarded as the next-generation thin-film energy harvester, owing to their high performance. However, there is a lack of studies on their encapsulation technology, which is critical for resolving their shortcomings, such as their degradation by oxygen and moisture. It is determined that the moisture intrusion and the heat trapped within the encapsulating cover glass of PSCs influenced the operating stability of the devices. Therefore, we improved the moisture and oxygen barrier ability and heat releasing capability in the passivation of PSCs by adding multi-walled carbon nanotubes to the epoxy resin used for encapsulation. The 0.5 wt% of carbon nanotube-added resin-based encapsulated PSCs exhibited a more stable operation with a ca. 30% efficiency decrease compared to the ca. 63% decrease in the reference devices over one week under continuous operation. Specifically, the short-circuit current density and the fill factor, which are affected by moisture and oxygen-driven degradation, as well as the open-circuit voltage, which is affected by thermal damage, were higher for the multi-walled carbon nanotube-added encapsulated devices than the control devices, after the stability test.

Next-generation renewable energy sources and perovskite solar cells have revolutionised photovoltaics research and the photovoltaic industry. However, the presence of toxic lead in perovskite solar cells hampers their commercialisation. Lead-free tin-based perovskite solar cells are a potential alternative solution to this problem; however, numerous technological issues must be addressed before the efficiency and stability of tin-based perovskite solar cells can match those of lead-based perovskite solar cells. This report summarizes the development of lead-free tin-based perovskite solar cells from their conception to the most recent improvements. Further, the methods by which the issue of the oxidation of tin perovskites has been resolved, thereby enhancing the device performance and stability, are discussed in chronological order. In addition, the potential of lead-free tin-based perovskite solar cells in energy storage systems, that is, when they are integrated with batteries, is examined. Finally, we propose a research direction for tin-based perovskite solar cells in the context of battery applications.

Background and objectives: The clinical assessment of therapeutic response in pyogenic vertebral osteomyelitis (PVO) has been usually performed based on the changes of clinical symptoms and blood inflammatory markers. Recently, 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) has emerged as an alternative independent method. We analyzed the validity of the clinical assessment for detecting residual PVO based on 18 F-FDG-PET. Materials and Methods: This study was conducted with 53 patients confirmed as lumbar PVO under retrospective design. All patients underwent clinical assessment using clinical symptoms and C-reactive protein (CRP) for therapeutic response after parenteral antibiotic therapy, which led to the decision of placement in the uncontrolled (group UC) or controlled (group C) group. The validity of clinical assessment was analyzed based on the cut-off values of FDG uptake for detecting residual PVO as references, which are already established in the previous literature. Results : The mean duration of parenteral antibiotic therapy and recurrence rate were 42.19 ± 15.84 (21-89) days and 9.4% (5/53), respectively. 18 F-FDG-PETs were performed at 80 rounds of clinical assessment on 37.40 ± 13.15 (21-83) days of parenteral antibiotic therapy and divided: 31 into group UC and 49 into group C, according to the decisions of clinical assessment. Based on the cut-off values of FDG uptake, clinical assessment showed 48.4-58.1% of false positive for residual PVO in group UC. However, 18 F-FDG-PET showed 8.2% (4/49) of false negative for residual PVO in group C, which led to recurrences. Conclusions: Clinical assessment using clinical symptoms and CRP for evaluating therapeutic response in PVO is still a useful method in terms of similar recurrence rate compared to 18 F-FDG-PET. However, the high rate of false positive for residual PVO can prolong the use of unnecessary antibiotics and overall treatment period.

Background: Pyogenic vertebral osteomyelitis (PVO) is a bacterial infection involving the intervertebral disc, vertebral body, and paravertebral soft tissues. Damaged intervertebral structure is a major cause of persistent back pain even after successful antibiotic therapy, which can be improved by achieving autofusion or via additional surgical fixation. In this study, we analyzed the clinical and radiological features predicting intervertebral autofusion after successful antibiotic therapy in lumbar PVO., Methods: This study was retrospectively conducted with 32 patients (20 men and 12 women) diagnosed with lumbar PVO that was completely cured with no recurrences after antibiotic therapy. They were divided into two groups with (group A, n = 18) and without (group B, n = 14) intervertebral autofusion at six-month follow-up. Differences in back pain, blood inflammatory markers, and radiological features of PVO on simultaneous 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ( 18 F-FDG-PET/MRI) of the intervertebral structure between the two groups were analyzed., Results: The mean duration of antibiotic therapy was 41.44 ± 14.21 (21-89) days. Group A showed a statistically higher erythrocyte sedimentation ratio (ESR; 59.28 ± 32.33 vs. 33.93 ± 18.76 mm/h, p = 0.014; normal range of ESR < 25), maximum standardized 18 F-FDG uptake (SUV max ; 5.56 ± 1.86 vs. 3.98 ± 1.40, p = 0.013), and sustained extensive edematous changes on T2-weighted fat saturation (T2FS) MRI ( p = 0.015) immediately after successful antibiotic therapy. However, no significant differences were observed in back pain, C-reactive protein, or the distribution of 18 F-FDG uptake/contrast enhancement on 18 F-FDG-PET/MRI ( p > 0.05)., Conclusions: Higher ESR and SUV max of the intervertebral structure and sustained extensive edematous change on T2FS MRI immediately after successful antibiotic therapy are related with subsequent intervertebral autofusion, which should be carefully considered when assessing therapeutic response in PVO.

Carbon nanotube face mask filters have strong and uniform hydrophobicity, high durability, and high thermal conductivity and exhibit excellent barrier and antiviral effects against SARS-CoV-2. The nanocarbon filter functions as a superior barrier compared to those in conventional masks owing to the stronger, more uniform, and more durable hydrophobic nature of the carbon nanotubes. A tightly knit carbon nanotube network has a pore size smaller than that of the average coronavirus; nevertheless, the breathability is equal to that of the conventional polypropylene filter. The exceptional thermal conductivity of carbon nanotubes transpires hyperthermic antiviral effects, which offers stronger protection against the virus, as well as reusability. The facile processability, low cost, and light weight of the aerosol-synthesized carbon nanotube filter warrants its viability, reinforcing the fight against the COVID-19 pandemic., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Seed oils are used as edible oils and increasingly also for industrial applications. Although high-oleic seed oil is preferred for industrial use, most seed oil is high in polyunsaturated fatty acids (PUFAs) and low in monounsaturated fatty acids (MUFAs) such as oleic acid. Oil from Camelina, an emerging oilseed crop with a high seed oil content and resistance to environmental stress, contains 60% PUFAs and 30% MUFAs. Hexaploid Camelina carries three homoeologs of FAD2 , encoding fatty acid desaturase 2 (FAD2), which is responsible for the synthesis of linoleic acid from oleic acid. In this study, to increase the MUFA contents of Camelina seed oil, we generated CsFAD2 knockout plants via CRISPR-Cas9-mediated gene editing using the pRedU6fad2EcCas9 vector containing DsRed as a selection marker, the U6 promoter to drive a single guide RNA (sgRNA) covering the common region of the three CsFAD2 homoeologs, and an egg-cell-specific promoter to drive Cas9 expression. We analyzed CsFAD2 homoeolog-specific sequences by PCR using genomic DNA from transformed Camelina leaves. Knockout of all three pairs of FAD2 homoeologs led to a stunted bushy phenotype, but greatly enhanced MUFA levels (by 80%) in seeds. However, transformants with two pairs of CsFAD2 homoeologs knocked out but the other pair wild-type heterozygous showed normal growth and a seed MUFAs production increased up to 60%. These results provide a basis for the metabolic engineering of genes that affect growth in polyploid crops through genome editing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Jeon, Yu, Kim, Kim, Ahn, Lee, Lee and Kim.)

Double-walled carbon nanotubes (DWNTs) have shown potential as promising alternatives to conventional transparent electrodes owing to their solution processability as well as high conductivity and transparency. However, their DC to optical conductivity ratio is limited by the surrounding surfactants that prevent the p-doping of the DWNTs. To maximize the doping effectiveness, the surfactants are removed from the DWNTs, with negligible damage to the nanotubes, by calcination in an Ar atmosphere. The effective removal of the surfactants is characterized by various analyses, and the results show that the optimal calcination temperature is 400 °C. The conductivity of the DWNTs films improves when doped by triflic acid. While the conductivity increase of the surfactants-wrapped DWNT films is 31.9%, the conductivity increase of the surfactants-removed DWNT is found to be 59.7%. Using the surfactants-removed, p-doped, solution-processed transparent electrodes, inverted-type perovskite solar cells are fabricated, resulting in a power conversion efficiency of 17.7% without hysteresis. This work advances the application of DWNTs in transparent conductors, as the efficiency obtained is the highest value achieved to date for carbon nanotube electrode-based perovskite solar cells and solution-processable transparent electrode-based solar cells., (© 2021 Wiley-VCH GmbH.)

Ketones are widely applied moieties in designing functional materials and are commonly obtained by oxidation of alcohols. However, when alcohols are protected/functionalized, the direct oxidation strategies are substantially curbed. Here we show a highly efficient copper bromide promoted one-step direct oxidation of benzylic ethers to ketones with the aid of a fullerene pendant. Mechanistic studies unveil that fullerene can serve as an electron pool proceeding the one-step oxidation of alkoxy group to ketone. In the absence of the fullerene pendant, the unreachable activation energy threshold hampers the direct oxidation of the alkoxy group. In the presence of the fullerene pendant, generated fullerene radical cation can activate the neighbour C-H bond of the alkoxy moiety, allowing a favourable energy barrier for initiating the direct oxidation. The produced fullerene-fused ketone possesses high thermal stability, affording the pin-hole free and amorphous electron-transport layer with a high electron-transport mobility., (© 2021. The Author(s).)

Background: Primary decompressive craniectomy (DC) is considered for traumatic brain injury (TBI) patients with clinical deterioration, presenting large amounts of high-density lesions on computed tomography (CT). Postoperative CT findings may be suitable for prognostic evaluation. This study evaluated the radiographic predictors of clinical outcome and survival using pre- and postoperative CT scans of such patients., Methods: We enrolled 150 patients with moderate to severe TBI who underwent primary DC. They were divided into two groups based on the 6-month postoperative Glasgow Outcome Scale Extended scores (1-4, unfavorable; 5-8, favorable). Radiographic parameters, including hemorrhage type, location, presence of skull fracture, midline shifting, hemispheric diameter, effacement of cisterns, parenchymal hypodensity, and craniectomy size, were reviewed. Stepwise logistic regression analysis was used to identify the prognostic factors of clinical outcome and 6-month mortality., Results: Multivariable logistic regression analysis revealed that age (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.032-1.151; p = 0.002), postoperative low density (OR = 12.58; 95% CI 1.247-126.829; p = 0.032), and postoperative effacement of the ambient cistern (OR = 14.52; 95% CI 2.234-94.351; p = 0.005) and the crural cistern (OR = 4.90; 95% CI 1.359-17.678; p = 0.015) were associated with unfavorable outcomes. Postoperative effacement of the crural cistern was the strongest predictor of 6-month mortality (OR = 8.93; 95% CI 2.747-29.054; p = 0.000)., Conclusions: Hemispheric hypodensity and effacement of the crural and ambient cisterns on postoperative CT after primary DC seems to associate with poor outcome in patients with TBI.