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BACKGROUND: The extent of perfusion of a deep inferior epigastric artery perforator (DIEP) flap is a primary concern for surgeons. This study aimed to determine whether the flap area or volume can be estimated using perforator and flap characteristics. METHODS: Intraoperative flap perfusion was assessed using indocyanine green angiography in patients who underwent DIEP flap breast reconstruction between November 2018 and February 2023. The area perfused by a single dominant perforator was delineated on the surface of the flap and measured using the ImageJ software. Multiple linear regression analysis was conducted to estimate the 'perfusion ratio,' defined as the perfused area divided by the total flap area. Potential predictor variables included flap size (cm2), flap thickness (mm), perforator diameter (mm), perforator rows (medial/lateral), vertical location of perforator (at or above/below the umbilicus), and perforator eccentricity (vertical distance from upper flap margin to perforator, cm). RESULTS: In total, 101 patients were included in this analysis. The mean 'perfusion ratio' was 67.8% ± 11.5%, predicted by perforator diameter (p = 0.022) and vertical location below umbilicus (p < 0.001) with positive correlations and negatively correlated with flap thickness (p = 0.003) in the multivariable analysis. Both perfusion area and weight were predicted by perforator diameter, vertical location of perforator, flap size, and flap thickness (p < 0.001). The coefficient of determination (adjusted R2) for prediction of perfusion weight was higher than that for the perfusion area (75.5% vs. 69.4%). CONCLUSIONS: Flap volume, rather than area, is determined by a perforator of a given diameter and location.
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Introduction: This study aimed to identify differences in voice characteristics and changes between patients with dysphagia-aspiration and healthy individuals using a deep learning model, with a focus on under-researched areas of pre- and post-swallowing voice changes in patients with dysphagia. We hypothesized that these variations may be due to weakened muscles and blocked airways in patients with dysphagia. Methods: A prospective cohort study was conducted on 198 participants aged >40 years at the Seoul National University Bundang Hospital from October 2021 to February 2023. Pre- and post-swallowing voice data of the participants were converted to a 64-kbps mp3 format, and all voice data were trimmed to a length of 2 s. The data were divided for 10-fold cross-validation and stored in HDF5 format with anonymized IDs and labels for the normal and aspiration groups. During preprocessing, the data were converted to Mel spectrograms, and the EfficientAT model was modified using the final layer of MobileNetV3 to effectively detect voice changes and analyze pre- and post-swallowing voices. This enabled the model to probabilistically categorize new patient voices as normal or aspirated. Results: In a study of the machine-learning model for aspiration detection, area under the receiver operating characteristic curve (AUC) values were analyzed across sexes under different configurations. The average AUC values for males ranged from 0.8117 to 0.8319, with the best performance achieved at a learning rate of 3.00e-5 and a batch size of 16. The average AUC values for females improved from 0.6975 to 0.7331, with the best performance observed at a learning rate of 5.00e-5 and a batch size of 32. As there were fewer female participants, a combined model was developed to maintain the sex balance. In the combined model, the average AUC values ranged from 0.7746 to 0.7997, and optimal performance was achieved at a learning rate of 3.00e-5 and a batch size of 16. Conclusion: This study evaluated a voice analysis-based program to detect pre- and post-swallowing changes in patients with dysphagia, potentially aiding in real-time monitoring. Such a system can provide healthcare professionals with daily insights into the conditions of patients, allowing for personalized interventions. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05149976.
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Autophagy is essential for regulating hair growth. Accordingly, we developed autophagy activator ICP5249 (pentasodium tetracarboxymethyl palmitoyl dipeptide) and investigated its potential role in hair growth. We evaluated its effect on hair growth using in vitro human dermal papilla cells (hDPCs) culture model, human hair follicles (hHFs) organ culture model, and telogenic mouse model. ICP5249 increased hDPCs proliferation and alkaline phosphatase (ALP) expression. It also increased microtubule-associated protein (MAP) light chain 3- II (LC3-II) expression and AMP-activated protein kinase α (AMPKα) and unc-51-like kinase 1 (ULK1) phosphorylation in hDPCs. ICP5249 extended the length of hHFs and increased LC3 II expression. Consistently, ICP5249 also significantly increased hair growth area, dermis thickness, and anagen and telogen ratio in telogenic mice. Furthermore, it upregulated Ki-67 and LC3-II expression and AMPKα phosphorylation on the mice's dorsal skin. To investigate whether AMPK regulates ICP5249-induced hair growth, following treatment with the compound C, AMPK inhibitor, the activity of ICP5249 was evaluated. The effects of ICP5249 on hair growth were assessed following pretreatment with the AMPK inhibitor compound C. The results showed that compound C suppressed ICP5249-mediated proliferation and hair inductivity in hDPCs. Additionally, compound C inhibited ICP5249-mediated hair growth area, dermis thickness, anagen and telogen ration, and LC3-II expression in mice, suggesting that ICP5249 promotes hair growth by modulating autophagy, with AMPKα playing a regulatory role in this process. Taken together, we demonstrate that ICP5249 has the potential as an ingredient for improving hair growth.
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Lipid nanoparticles (LNPs) are gaining recognition as potentially effective carriers for delivery of therapeutic agents, including nucleic acids (DNA and RNA), for the prevention and treatment of various diseases. Much effort has been devoted to the implementation of microfluidic techniques for the production of monodisperse and stable LNPs and the improvement of encapsulation efficiency. Here, we developed three-dimensional (3D)-printed ring micromixers for the production of size-controllable and monodispersed LNPs with a high mRNA delivery efficiency. The effects of flow rate and ring shape asymmetry on the mixing performance were initially examined. Furthermore, the physicochemical properties (such as hydrodynamic diameter, polydispersity, and encapsulation efficiency) of the generated LNPs were quantified as a function of these physical parameters via biochemical analysis and cryo-electron microscopy imaging. With a high production rate of 68 mL/min, our 3D-printed ring micromixers can be used to manufacture LNPs with diameters less than 90 nm, low polydispersity (<0.2), and high mRNA encapsulation efficiency (>91%). Despite the simplicity of the ring-shaped mixer structure, we can produce mRNA-loaded LNPs with exceptional quality and high throughput, outperforming costly commercial micromixers.
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Discrimination is a social determinant of health and health disparities for which the biological mechanisms remain poorly understood. This study investigated the hypothesis that discrimination contributes to poor health outcomes by accelerating biological processes of aging. We analyzed survey and blood DNA methylation data from the Midlife in the United States (MIDUS) study (N = 1967). We used linear regression analysis to test associations of everyday, major, and workplace discrimination with biological aging measured by the DunedinPACE, PhenoAge, and GrimAge2 epigenetic clocks. MIDUS participants who reported more discrimination tended to exhibit a faster pace of aging and older biological age as compared to peers who reported less discrimination. Effect-sizes for associations tended to be larger for the DunedinPACE pace-of-aging clock (effect-size range r = 0.1-0.2) as compared with the PhenoAge and GrimAge2 biological-age clocks (effect-sizes r < 0.1) and for experiences of everyday and major discrimination as compared with workplace discrimination. Smoking status and body-mass index accounted for roughly half of observed association between discrimination and biological aging. Reports of discrimination were more strongly associated with accelerated biological aging among White as compared with Black participants, although Black participants reported more discrimination overall and tended to exhibit older biological age and faster biological aging. Findings support the hypothesis that experiences of interpersonal discrimination contribute to accelerated biological aging and suggest that structural and individual-level interventions to reduce discrimination and promote adaptive coping have potential to support healthy aging and build health equity.
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Output stabilizing control of biological systems is of utmost importance in systems biology since key phenotypes of biological networks are often encoded by a small subset of their phenotypic marker nodes. This study addresses the challenge of output stabilizing control for complex biological systems modeled by Boolean networks (BNs). The objective is to identify a set of constant control inputs capable of driving the BN toward a desirable long-term behavior with respect to specified output nodes. Leveraging the algebraic properties of Boolean logic, we develop a novel control algorithm that reformulates the output stabilizing control problem into a simple graph theoretic problem involving auxiliary BNs, the scale of which significantly decreases compared to the original BN. The proposed method ensures superiority over previous results in terms of both the number of control inputs and computational loads, since it searches for the solution within the reduced BNs while retaining essential structures needed for output stabilization. The efficacy of the proposed control scheme is demonstrated through extensive numerical experiments with complex random BNs and real biological networks. To support the reproducible research initiative, detailed results of numerical experiments are provided in the supplementary material, and all the implementation codes are made accessible at https://github.com/choonlog/OutputStabilization.
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We aimed to determine the risk factors for non-responsiveness to intravenous immunoglobulin (IVIG) and coronary ectasia in Korean children with Kawasaki disease (KD) and compare the efficacy of previously published Japanese and Chinese risk scoring systems in the same cohort. We retrospectively reviewed 459 KD cases diagnosed from January 1, 2013, to December 31, 2022. Age (odds ratio [OR]: 0.983; 95% confidence interval [CI]: 0.968-0.999), change in extremities (OR: 3.308; 95% CI: 1.530-7.151), neutrophils (OR: 1.078; 95% CI: 1.049-1.108), and alanine aminotransferase (OR: 1.002; 95% CI: 1.000-1.004) were identified as independent risk factors for IVIG non-responsiveness, and age (OR: 0.945; 95% CI: 0.902-0.989), C-reactive protein (OR: 1.092; 95% CI: 1.004-1.188), and creatinine kinase (OR: 1.004; 95% CI: 1.001-1.006) were identified as independent risk factors for coronary ectasia. Among previously published risk scoring systems, the Egami (area under the receiver operating characteristics curve [AUC]: 0.695; 95% CI: 0.651-0.737) for IVIG non-responsiveness and the Tang score (AUC: 0.726; 95% CI: 0.578-0.874) for coronary ectasia showed the highest predictive value for our study cohort.
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BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.
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Acute coronary syndromes (ACS) often result from the rupture or erosion of high-risk coronary atherosclerotic plaques (ie, vulnerable plaques). Advances in intracoronary imaging such as intravascular ultrasound, optical coherence tomography, or near-infrared spectroscopy have improved the identification of vulnerable plaques, characterized by large plaque burden, small minimal luminal area, thin fibrous cap, and large lipid content. Although pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques and secondary prevention, recurrent events tend to accrue despite intensive pharmacotherapy. Therefore, it has been hypothesized that local preventive percutaneous coronary intervention may passivate these vulnerable plaques, preventing the occurrence of plaque-related ACS. However, solid evidence is lacking on its use for treatment of non-flow-limiting vulnerable plaques. As such, the optimal management of vulnerable plaques has not been established. Herein, we have reviewed the diagnosis and management of vulnerable plaques, focusing on systematic pharmacology and focal treatments.
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Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/ß-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/ß-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/ß-catenin pathway and highlight its therapeutic potential in hair loss treatment.
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Fibronectinas , Glicogênio Sintase Quinase 3 beta , Folículo Piloso , Cabelo , Camundongos Endogâmicos C57BL , Via de Sinalização Wnt , beta Catenina , Animais , Humanos , Fibronectinas/metabolismo , Camundongos , Glicogênio Sintase Quinase 3 beta/metabolismo , Cabelo/crescimento & desenvolvimento , beta Catenina/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Proliferação de Células , Proteína Wnt-5a/metabolismo , Proteínas Wnt/metabolismo , Masculino , Feminino , Proteínas Proto-OncogênicasRESUMO
INTRODUCTION: To seek an optimal measurement method with high reliability and high validity for evaluation of the anterior knee laxity on stress radiographs and comparing the translation values to those of KT-2000 arthrometer. METHODS: Anterior knee laxity in 77 patients was measured preoperatively using the TelosTM and the KT-2000 arthrometer. Side-to-side difference measurements were taken using three conventional measuring methods and one proposed method (Modified Lateral). The knee position on the stress radiograph was evaluated and scored based on the stress radiograph qualifying criteria depending on stress film correctiveness. Intraclass correlation coefficients were analyzed to evaluate the reliability of the measurement methods and were compared between high (Group H) and low (Group L) radiograph quality score groups for each method. Validity was assessed by comparing the KT-2000 and the TelosTM using Pearson correlation (r value). RESULTS: The Modified Lateral method showed the best Intraclass Correlation Coefficients (ICCs), followed by Center to Center, and Medial to Medial and Lateral to Lateral methods without considering the quality of Telos. In the comparison between groups based on Telos quality for intra-rater reliability, the Medial to Medial (MM) method demonstrated the best reliability in both groups (MM: ICCs, Group H = 0.942, Group L = 0.917, P = 0.693). As for inter-rater reliability, the Modified Lateral (ML) method exhibited the best reliability in both groups (ML: ICCs, Group H = 0.923, Group L = 0.882, P = 0.547). The value measured using the ML method in Telos showed the highest correlation coefficient with the KT-2000 measured value in both groups H and L. There were no statistically significant differences among the correlation coefficient values. CONCLUSION: The Modified Lateral method is recommended for its high reliability, taking into account the differences in bilateral knee positions and anatomical discriminability on stress radiographs when evaluating anterior knee translation with Telos. It also best reflected the KT-2000 arthrometer. LEVEL OF EVIDENCE: Case Series, Level IV.
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BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.
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Despite the importance of the stability of the 2D catalysts in harsh electrolyte solutions, most studies have focused on improving the catalytic performance of molybdenum disulfide (MoS2) catalysts rather than the sustainability of hydrogen evolution. In previous studies, the vulnerability of MoS2 crystals is reported that the moisture and oxygen molecules can cause the oxidation of MoS2 crystals, accelerating the degradation of crystal structure. Therefore, optimization of catalytic stability is crucial for approaching practical applications in 2D catalysts. Here, it is proposed that monolayered MoS2 catalysts passivated with an atomically thin hexagonal boron nitride (h-BN) layer can effectively sustain hydrogen evolution reaction (HER) and demonstrate the ultra-high current density (500 mA cmâ»2 over 11 h) and super stable (64 h at 150 mA cmâ»2) catalytic performance. It is further confirmed with density functional theory (DFT) calculations that the atomically thin h-BN layer effectively prevents direct adsorption of water/acid molecules while allowing the protons to be adsorbed/penetrated. The selective penetration of protons and prevention of crystal structure degradation lead to maintained catalytic activity and maximized catalytic stability in the h-BN covered MoS2 catalysts. These findings propose a promising opportunity for approaching the practical application of 2D MoS2 catalysts having long-term stability at high-current operation.
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Duck meat is recognized as a healthier poultry product that contains higher amounts of unsaturated and essential fatty acids, iron, and excellent amounts of protein. It has been found to possess the ability to reduce low-density lipoprotein cholesterol and subsequently, blood pressure in the human body; and improve the immunity system. The current study investigated the appropriate bedding depths of rice hulls as a preferred bedding material by evaluating the growth performance and carcass traits of White Pekin ducks raised for 42 days. A total of 288 one-day-old White Pekin ducklings were randomly allotted to floor cages with one of four bedding depths at 4 cm, 8 cm, 12 cm, and 16 cm. Ducklings were fed standard duck starter (days 1-21) and finisher (days 22-42) diets. The birds were stocked at a rate of 6 birds/m2 with 6 replicates per treatment. Growth performance evaluation for the body weight, average daily gain, and average daily feed intake were measured to calculate the weekly feed conversion ratio. Breast, leg, and carcass yield were assessed as carcass traits. The muscle color and proximate composition were also analyzed for meat quality. Footpad dermatitis was also evaluated on day 42. Ducks reared on 16 cm bedding depth over the 42 days recorded higher (p < 0.05) body weight, average daily, average daily feed intake, and improved feed conversion ratios compared to other groups. The crude fat in breast meat also lowered (p < 0.05) in ducks reared at 16 cm (1.02%) when compared to ducks raised at 4 cm bedding depth (2.11%). Our results showed improved redness (p < 0.05) when the depth of bedding materials was elevated. Except for the breast meat fat, the dissimilar bedding depths did not affect (p < 0.05) the breast and leg meat composition, footpad dermatitis, and mortality for the current study. In conclusion, this study indicated that the bedding depths would directly or indirectly affect the growth performance and meat color of White Pekin ducks; and the bedding depth of rice hulls at 16 cm improved the growth performance of White Pekin ducks for 42 days.
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Truffles, belonging to the genus Tuber, are ectomycorrhizal (ECM) fungi that form underground ascocarps and primarily establish symbiosis with oaks and hazels. The cultivation of Tuber spp. involves transplanting inoculated seedlings that have formed ectomycorrhiza with Tuber species, with mulching being effective for truffle cultivation. In this study, we investigated the effects of mulching on the mycelial growth of four Tuber species (T. himalayense, T. koreanum, T. melanosporum, and T. borchii) in the Korean natural environment, highlighting the potential for Korea as a truffle cultivation site. We developed and tested species-specific primers for quantifying the soil mycelial biomass of Tuber spp. by qRT-PCR, determined the superior mulch color for mycelial growth, and identified the Tuber species exhibiting the highest growth rate in the Korean field environment. Our results demonstrated that white mulch significantly enhanced mycelial growth in Tuber species than black mulch, likely owing to its ability to maintain low soil temperatures, control weeds, and improve host plant growth. Among the Tuber species, T. himalayense showed the greatest growth potential in the Korean natural environment. Additionally, a significant and positive correlation was observed between the mycelial biomass of Tuber species and the growth of inoculated seedlings, as measured by the total stem length and the number of leaves, thereby indicating the importance of symbiosis between ECM fungi and host plants. This study provides valuable insights into truffle cultivation in Korea and highlights the potential of using white mulch to promote mycelial growth, thereby contributing essential data for understanding the appropriate environmental conditions for Tuber spp. cultivation in Korea. Further study is needed to assess the long-term impact of mulching and to explore the effectiveness of other mulching materials.
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Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.
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Photocatalytic hydrogen production offers an alternative pathway to establish a sustainable energy economy. While numerous photoactive materials exhibit potential for generating hydrogen from water, the synergy achieved by combining two different materials with complementary properties in the form of heterojunctions can significantly their photocatalytic activity. Our study describes the design and generation of the metal-organic framework-derived (MOF) metal oxide heterojunction composed of RuO2/N,S-TiO2. The RuO2/N,S-TiO2 is generated through the pyrolysis of MOFs, Ru- HKUST-1, and the amino-functionalized MIL-125-NH2. Among the various RuO2/N,S- TiO2 materials tested, the material characterized by the lowest RuO2 content, exhibited the highest hydrogen evolution rate, producing 10,761 µmol·hr-1·g-1 of hydrogen with an apparent quantum-yield of 10.0% in pure water. In addition to RuO2/N,S-TiO2, we generated two other MOF-derived metal-oxide heterojunctions, ZnO/N,S-TiO2 and In2O3/N,S-TiO2, leading to apparent quantum yields of 0.7% and 0.3%, respectively. The remarkable photocatalytic activity observed in RuO2/N,S-TiO2 is thought to be attributed to the synergistic effects arising from the combination of metallic properties inherent in the metal oxides, their band alignment, porosity, and surface properties inherited from the parent MOFs. The photocatalytic efficiency of RuO2/N,S-TiO2 was further demonstrated in actual water samples, producing hydrogen with a rate of 8,190 µmol·hr-1·g-1 in tap water.
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OBJECTIVE: Recent years have seen an increase in machine learning (ML)-based blood glucose (BG) forecasting models, with a growing emphasis on potential application to hybrid or closed-loop predictive glucose controllers. However, current approaches focus on evaluating the accuracy of these models using benchmark data generated under the behavior policy, which may differ significantly from the data the model may encounter in a control setting. This study challenges the efficacy of such evaluation approaches, demonstrating that they can fail to accurately capture an ML-based model's true performance in closed-loop control settings. METHODS: Forecast error measured using current evaluation approaches was compared to the control performance of two forecasters-a machine learning-based model (LSTM) and a rule-based model (Loop)-in silico when the forecasters were utilized with a model-based controller in a hybrid closed-loop setting. RESULTS: Under current evaluation standards, LSTM achieves a significantly lower (better) forecast error than Loop with a root mean squared error (RMSE) of 11.57 ±0.05 mg/dL vs. 18.46 ±0.07 mg/dL at the 30-minute prediction horizon. Yet in a control setting, LSTM led to significantly worse control performance with only 77.14% (IQR 66.57-84.03) time-in-range compared to 86.20% (IQR 78.28-91.21) for Loop. CONCLUSION: Prevailing evaluation methods can fail to accurately capture the forecaster's performance when utilized in closed-loop settings. SIGNIFICANCE: Our findings underscore the limitations of current evaluation standards and the need for alternative evaluation metrics and training strategies when developing BG forecasters for closed-loop control systems.