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Cancer, caused by abnormal and excessive cellular proliferation, can invade and destroy surrounding tissues and organs through the spreading of cancer cells. A general strategy for developing anticancer agents is to identify biomarkers that, if targeted, can produce a robust cytotoxic effect with minimal side effects. Cell-cycle regulators, checkpoint regulatory genes, and apoptosis-related genes are well-known biomarkers that inhibit cancer cell proliferation. Several compounds that target such biomarkers have been patented and more are being developed as novel therapies. Recent additions to this list include anticancer drugs that target signaling pathway proteins, such as 5′ adenosine monophosphate-activated protein kinase (AMPK), which plays a vital role in cancer and normal cell metabolism. Herein, we have reviewed recent patents related to AMPK-targeting anticancer drugs and discussed the mechanisms of action of these drugs. We conclude that these recently published patents include several attractive compounds and methods for targeting AMPK. Further research and clinical trials are required to elucidate the comprehensive role of AMPK in cancer cell metabolism, identify its associated signal transduction systems, and develop novel activators that may find applications in cancer therapy. Clinical Trial Registration number: NCT01904123. [ABSTRACT FROM AUTHOR]

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal–Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia. [ABSTRACT FROM AUTHOR]

Objective: Although blood pressure (BP) variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT.Methods: A total of 211 patients with acute ischemic stroke and successful recanalization (thrombolysis in cerebral infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP. sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale.Results: Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio = 1.71, 95% confidence interval = 1.013-2.886).Interpretation: Time-related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP levels. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT. Ann Neurol 2019;85:574-581. [ABSTRACT FROM AUTHOR]

This study was carried out to develop a prediction model for soluble solid content (SSC) of intact chestnut and to detect internal defects using nuclear magnetic resonance (NMR) relaxometry and magnetic resonance imaging (MRI). Inversion recovery and Carr–Purcell–Meiboom–Gill (CPMG) pulse sequences used to determine the longitudinal (T1) and transverse (T2) relaxation times, respectively. Partial least squares regression (PLSR) was adopted to predict SSCs of chestnuts with NMR data and histograms from MR images. The coefficient of determination (R2), root mean square error of prediction (RMSEP), ratio of prediction to deviation (RPD), and the ratio of error range (RER) of the optimized model to predict SSC were 0.77, 1.41 °Brix, 1.86, and 11.31 with a validation set. Furthermore, an image-processing algorithm has been developed to detect internal defects such as decay, mold, and cavity using MR images. The classification applied with the developed image processing algorithm was over 94% accurate to classify. Based on the results obtained, it was determined that the NMR signal could be applied for grading several levels by SSC, and MRI could be used to evaluate the internal qualities of chestnuts. [ABSTRACT FROM AUTHOR]

In addition, it is difficult to manage the behavior of acute stroke patients with COVID-19 after stroke symptoms occur. We need to note that COVID-19 can appear as a local neurological defect, and the diagnosis and treatment methods for stroke patients caused by COVID-19 need to be re-evaluated. Although the occurrence of stroke due to microvascular thrombosis is becoming more evident, recent studies have shown that a significant number of COVID-19 patients develop large vascular occlusions with severe stroke symptoms [[3]]. [Extracted from the article]

Background/Objective: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. Methods: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. Results: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. Conclusions: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients. [ABSTRACT FROM AUTHOR]

This study provides a newly updated perspective of information on severely screened 21 previous studies of the various measurement methods for improving physical fitness and providing determined cutoff values from our reserved elderly human database. We aimed to provide scientific evidence-based information regarding physical fitness standards for developing useful prognostics, promoting and maintaining health programs for sarcopenic elderly. 21 previous studies emphasizing criterion referenced standards and receiver operator characteristic (ROC) curve analyses for improving physical fitness were screened. For predicting the prevalence of sarcopenia, the t -test, logistic regression, linear regression, ROC curve analyses, and voluntary categorizations such as the twentieth or sixtieth percentile classification were used. Based on these scientific evidences, we determined cutoff values from our reserved DB and realized that 75 years for men and 70 years for women are the transitional period during which there are large declines in muscle and fat mass (p < 0.01), which reflects physical function tests (p < 0.01) in both genders. Using the six factors with ideal cutoff thresholds, an individual exercise program can be designed for alleviating symptoms of frailty caused by sarcopenia for the elderly. [ABSTRACT FROM AUTHOR]

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5–2.4] in children and 21.4 times [2.4–189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs. [ABSTRACT FROM AUTHOR]

Diverse cases regarding the impact, with its related factors, of the COVID-19 pandemic on mental health have been reported in previous studies. In this study, multivariable datasets were collected from 751 college students who could be easily affected by pandemics based on the complex relationships between various mental health factors. We utilized quantum annealing (QA)-based feature selection algorithms that were executed by commercial D-Wave quantum computers to determine the changes in the relative importance of the associated factors before and after the pandemic. Multivariable linear regression (MLR) and XGBoost models were also applied to validate the QA-based algorithms. Based on the experimental results, we confirm that QA-based algorithms have comparable capabilities in factor analysis research to the MLR models that have been widely used in previous studies. Furthermore, the performance of the QA-based algorithms was validated through the important factor results from the algorithms. Pandemic-related factors (e.g., confidence in the social system) and psychological factors (e.g. decision-making in uncertain situations) were more important in post-pandemic conditions. Although the results should be validated using other mental health variables or national datasets, this study will serve as a reference for researchers regarding the use of the quantum annealing approach in factor analysis with validation through real-world survey dataset analysis. [ABSTRACT FROM AUTHOR]

Diverse cases regarding the impact, with its related factors, of the COVID-19 pandemic on mental health have been reported in previous studies. In this study, multivariable datasets were collected from 751 college students who could be easily affected by pandemics based on the complex relationships between various mental health factors. We utilized quantum annealing (QA)-based feature selection algorithms that were executed by commercial D-Wave quantum computers to determine the changes in the relative importance of the associated factors before and after the pandemic. Multivariable linear regression (MLR) and XGBoost models were also applied to validate the QA-based algorithms. Based on the experimental results, we confirm that QA-based algorithms have comparable capabilities in factor analysis research to the MLR models that have been widely used in previous studies. Furthermore, the performance of the QA-based algorithms was validated through the important factor results from the algorithms. Pandemic-related factors (e.g., confidence in the social system) and psychological factors (e.g. decision-making in uncertain situations) were more important in post-pandemic conditions. Although the results should be validated using other mental health variables or national datasets, this study will serve as a reference for researchers regarding the use of the quantum annealing approach in factor analysis with validation through real-world survey dataset analysis. [ABSTRACT FROM AUTHOR]

Unsteady flow simulations were conducted to analyze the effects of the freestream on the 3D flow around a piezoelectric fan. Considering computational cost, eight different inlet velocities from 0 to 7 m/s were tested using 2D simulations for the symmetry plane at the plate center, and five velocities of 0, 1, 3, 5 and 7 m/s were then selected for 3D simulations. The counter-rotating vortices from the fan tip are more significantly affected by the freestream than the vortices from the fan side. The axial velocity on the symmetry plane decreases monotonically as the freestream velocity increases, but the axial velocity near the endwall increases at a low freestream velocity. This implies that only a low speed freestream could be helpful to improve the performance of the piezoelectric fan. Based on the vorticity distribution, pressure difference across the fan edge and isosurface of λ 2 , an attempt was made to understand the interaction between the vortices from the fan and the freestream. Finally, two critical values of Strouhal number were found in this study for determining the performance of a vibrating plate within the freestream. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of Poncirus trifoliata aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between depressive symptoms and all‐cause mortality in a population‐based prospective study. Methods: Data from the 2008 baseline and 2011 follow‐up assessments of the Living Profiles of Older People Survey involving 14 976 Korean adults aged ≥60 years (59% women) were used. Depressive symptoms were defined as a score of ≥8 on the self‐administered Korean version of the Geriatric Depression Scale. Results: During the 3‐year follow‐up period, 873 deaths from all causes (372 women) occurred. The Cox proportional regression analyses showed that older men (hazard ratio 2.19, 95% confidence interval 1.83–2.62, P < 0.001) and women (hazard ratio 1.54, 95% confidence interval 1.25–1.89, P < 0.001) with baseline depressive symptoms were at significantly increased risk of all‐cause mortality independent of age, as compared with older men (hazard ratio 1) and women (hazard ratio 1) without baseline depressive symptoms, respectively. When additionally controlled for body mass index, socioeconomic status, health behaviors and health conditions, however, the risk of baseline depressive symptoms for all‐cause mortality still remained significant in men only (hazard ratio 1.40, 95% confidence interval 1.09–1.80, P = 0.008), but not in women only (hazard ratio 1.27, 95% confidence interval 0.98–1.66, P = 0.086). Conclusions: The current findings suggest that the prognostic importance of depressive symptoms for all‐cause mortality might be sex‐specific in Korean older adults. Geriatr Gerontol Int 2018; 18: 950–956 [ABSTRACT FROM AUTHOR]

Extant literature indicates that childhood maltreatment is significantly associated with personality disorders. With the recent call for a more dimensional approach to understanding personality and pathological personality traits, the aim of the present study was to examine whether the experience of childhood maltreatment is associated with pathological personality traits as measured by the Personality Psychopathology Five (PSY-5). We analyzed data from 557 adult psychiatric patients with diverse psychiatric diagnoses, including mood disorders, schizophrenia spectrum disorders, and anxiety disorders. Hierarchical multiple regression analyses were conducted to determine the degree to which childhood maltreatment explained the five trait dimensions after controlling for demographic variables, presence of psychotic symptoms, and degree of depressive symptoms. Childhood maltreatment significantly predicted all of the five trait dimensions of the PSY-5. This suggests that childhood maltreatment may negatively affect the development of an adaptive adjustment system, thereby potentially contributing to the emergence of pathological personality traits. [ABSTRACT FROM AUTHOR]

Flow simulations have been conducted to analyze the three-dimensional flow around a vibrating flat plate confined with two endwalls. A smoothing technique for hexahedral grids was implemented without a local re-meshing technique in order to resolve complex flow in a small gap between the fan side and the endwall. Three-dimensional numerical results showed a good agreement with experimentally measured data and the two-dimensional results in a previous work. In time-averaged flow analysis, the flow generated by the plate tends to move toward the center of it so that the velocity magnitude at the center is much larger than other heights near the endwall. It was found that three-dimensional velocity distribution is closely related to the interaction of two kinds of vortices from the fan tip and the fan side. The tip vortex and the side vortex interfere each other near the plate corner and weaken their intensity. In instantaneous flow analysis, an isosurface of λ 2 is adopted to analyze a complex vortical structure around the oscillating flat plate. Based on the numerical results, an attempt has been made to understand three-dimensional flow generated by a confined oscillating flat plate. [ABSTRACT FROM AUTHOR]

Quantitative Structure-Retention Relationships (QSRR) are used to predict retention times of compounds based only on their chemical structures encoded by molecular descriptors. The main concern in QSRR modelling is to build models with high predictive power, allowing reliable retention prediction for the unknown compounds across the chromatographic space. With the aim of enhancing the prediction power of the models, in this work, our previously proposed QSRR modelling approach called “federation of local models” is extended in ion chromatography to predict retention times of unknown ions, where a local model for each target ion (unknown) is created using only structurally similar ions from the dataset. A Tanimoto similarity (TS) score was utilised as a measure of structural similarity and training sets were developed by including ions that were similar to the target ion, as defined by a threshold value. The prediction of retention parameters ( a - and b -values) in the linear solvent strength (LSS) model in ion chromatography, log k = a – b log[eluent], allows the prediction of retention times under all eluent concentrations. The QSRR models for a - and b -values were developed by a genetic algorithm-partial least squares method using the retention data of inorganic and small organic anions and larger organic cations (molecular mass up to 507) on four Thermo Fisher Scientific columns (AS20, AS19, AS11HC and CS17). The corresponding predicted retention times were calculated by fitting the predicted a - and b -values of the models into the LSS model equation. The predicted retention times were also plotted against the experimental values to evaluate the goodness of fit and the predictive power of the models. The application of a TS threshold of 0.6 was found to successfully produce predictive and reliable QSRR models ( Q ext(F2) 2 > 0.8 and Mean Absolute Error < 0.1), and hence accurate retention time predictions with an average Mean Absolute Error of 0.2 min. [ABSTRACT FROM AUTHOR]

Retention prediction for unknown compounds based on Quantitative Structure-Retention Relationships (QSRR) can lead to rapid “scoping” method development in chromatography by simplifying the selection of chromatographic parameters. The use of retention factor ratio (or k -ratio) as a chromatographic similarity index can be a potent method to cluster similar compounds into a training set to generate an accurate predictive QSRR model provided that its limitation – that the method is impractical for retention prediction for unknown compounds – is successfully addressed. In this work, we propose a localised QSRR modelling approach with the aim of compensating the critical limitation in the otherwise successful k -ratio filter-based QSRR modelling. The approach is to combine a k -ratio filter with both Tanimoto similarity (TS) and a Δlog P index ( i.e. , log P -Dual filter). QSRR models for two retention parameters ( a and b ) in the linear solvent strength (LSS) model in ion chromatography (IC), log k = a − b log[eluent], were generated for larger organic cations (molecular mass up to 506) on a Thermo Fisher Scientific CS17 column. The application of the developed log P -Dual filter resulted in the production of successful QSRR models for 50 organic cations out of 87 in the dataset. The predicted a - and b -values of the models were then applied to the LSS model to predict the corresponding retention times. External validation showed that QSRR models for a -, b - and t R - values with excellent accuracy and predictability ( Q ext(F2) 2 of 0.96, 0.95, and 0.96, RMSEP of 0.06, 0.02, and 0.38 min) were created successfully, and these models can be employed to speed up the “scoping” phase of method development in IC. [ABSTRACT FROM AUTHOR]

We examined the role of spinally located β-adrenergic receptors in the regulation of the blood glucose level. The intrathecal (i.t.) injections with dobutamine (β1-adrenergic receptor agonist) or terbutaline (β2-adrenergic receptor agonist) caused an elevation of the blood glucose level, whereas metoprolol (β1-adrenergic receptor antagonist) or butoxamine (β2-adrenergic receptor antagonist) did not. In addition, i.t. pretreatment with pertussis toxin (PTX) attenuated the hyperglycemic effect induced by dobutamine or terbutaline. Moreover, plasma insulin level was increased by dobutamine but not by terbutaline, and PTX reduced dobutamine-induced up-regulation of the plasma insulin level. Terbutaline significantly increased plasma corticosterone level, and PTX further enhanced terbutaline-induced corticosterone level. Furthermore, intraperitoneal (i.p.) pretreatment with hexamethonium- (a preganglionic blocker) attenuated dobutamine- and terbutaline-induced hyperglycemic effects. Our results suggest that activation of spinal β1- and β2-adrenergic receptors produces hyperglycemic effects in a different manner. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by terbutaline. Furthermore, dobutamine- or terbutaline-induced hyperglycemia appears to be mediated through the spinal nerves. [ABSTRACT FROM AUTHOR]

Onions are rich in bioactive compounds and have been found to prevent various chronic diseases, including obesity. We performed a systematic review and meta‐analysis to investigate the antiobesity effect of onions. Studies were identified in PubMed/MEDLINE, Embase, Web of Science, and CENTRAL focusing on clinical trials evaluating the antiobesity effects of onion in obese subjects. The risk of bias in the studies was evaluated using Cochrane's Risk of Bias tool. The effect of onions was analyzed using data from the selected studies, and the results were indicated by weighted mean difference with 95% CI. The I2 static test was used to examine heterogeneity between the studies. A total of 38 studies were reviewed, of which five clinical trials meeting the criteria were selected. As investigational products, onion peels were used in four studies and onions were used in one study. Following systematic review, it was determined that the risk of bias was generally low, and body weight, BMI, waist circumference, and triglyceride levels were significantly reduced in the onion groups compared to the placebo. In conclusion, onion intake had an antiobesity effect by reducing body weight and body fat, and this effect was particularly pronounced with onion peel. [ABSTRACT FROM AUTHOR]

Quantitative Structure-Retention Relationships (QSRRs) represent a popular technique to predict the retention times of analytes, based on molecular descriptors encoding the chemical structures of the analytes. The linear solvent strength (LSS) model relating the retention factor, k to the eluent concentration (log k = a − b log [eluent]), is a well-known and accurate retention model in ion chromatography (IC). In this work, QSRRs for inorganic and small organic anions were used to predict the regression parameters a and b in the LSS model (and hence retention times) for these analytes under a wide range of eluent conditions, based solely on their chemical structures. This approach was performed on retention data of inorganic and small organic anions from the “Virtual Column” software (Thermo Fisher Scientific). These retention data were recalibrated via a “porting” methodology on three columns (AS20, AS19, and AS11HC), prior to the QSRR modeling. This provided retention data more applicable on recently produced columns which may exhibit changes of column behavior due to batch-to-batch variability. Molecular descriptors for the analytes were calculated with Dragon software using the geometry-optimized molecular structures, employing the AM1 semi-empirical method. An optimal subset of molecular descriptors was then selected using an evolutionary algorithm (EA). Finally, the QSRR models were generated by multiple linear regression (MLR). As a result, six QSRR models with good predictive performance were successfully derived for a- and b -values on three columns (R 2 > 0.98 and RMSE < 0.11). External validation showed the possibility of using the developed QSRR models as predictive tools in IC (Q ext(F3) 2 > 0.7 and RMSEP < 0.4). Moreover, it was demonstrated that the obtained QSRR models for the a - and b -values can predict the retention times for new analytes with good accuracy and predictability (R 2 of 0.98, RMSE of 0.89 min, Q ext(F3) 2 of 0.96 and RMSEP of 1.18 min). [ABSTRACT FROM AUTHOR]

5,7-Dihydroxytryptamine (5,7-DHT) is a neurotoxin which causes the depletion of serotonin. Moreover, the serotonergic system is the regulator of the blood glucose level. However, the role of centrally located serotonergic system in blood glucose regulation after D-glucose feed and immobilization (IMO) stress was not clearly characterized yet. Thus the present study was designed to examine the effect of 5,7-DHT administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level in D-glucose-fed and immobilization stress models. Mice were pretreated once i.c.v. or i.t. with 5,7-DHT (from 10 to 40 µg) for 3 days and D-glucose (2 g/kg) was fed orally. The blood glucose level was measured at 0, 30, 60 and 120 min after D-glucose feeding and immobilization stress initiation. We found that i.c.v. or i.t. pretreatment with 5,7-DHT attenuated the blood glucose level in both animal models. D-glucose feeding causes an increase in plasma insulin level, whereas the plasma corticosterone level was downregulated in the D-glucose-fed model. The i.c.v. or i.t. pretreatment with 5,7-DHT alone slightly increased the plasma corticosterone level. In addition, the i.c.v. or i.t. pretreatment with 5,7-DHT caused a reversal of the downregulation of plasma corticosterone level induced by D-glucose feeding, whereas immobilization stress causes an increase in plasma corticosterone and insulin levels. The i.c.v or i.t. pretreatment with 5,7-DHT attenuated the immobilization stress-induced plasma corticosterone and plasma insulin levels. Our results suggest that supraspinal and spinal depletion of serotonin appears to be responsible for the downregulation of blood glucose level in both D-glucose-fed and immobilization stress models. [ABSTRACT FROM AUTHOR]

Depression is more common among diabetes people than in the general population. In the present study, blood glucose change in depression animal model was characterized by various types of hyperglycemia models such as d -glucose-fed-, immobilization stress-, and drug-induced hyperglycemia models. First, the ICR mice were enforced into chronic restraint stress for 2 h daily for 2 weeks to produce depression animal model. The animals were fed with d -glucose (2 g/kg), forced into restraint stress for 30 min, or administered with clonidine (5 μg/5 μl) supraspinally or spinally to produce hyperglycemia. The blood glucose level in depression group was down-regulated compared to that observed in the normal group in d -glucose-fed-, restraint stress-, and clonidine-induced hyperglycemia models. The up-regulated corticosterone level induced by d -glucose feeding or restraint stress was reduced in the depression group while the up-regulation of plasma corticosterone level is further elevated after i.t. or i.c.v. clonidine administration in the depression group. The up-regulated insulin level induced by d -glucose feeding or restraint stress was reduced in the depression group. On the other hand, blood corticosterone level in depression group was up-regulated compared to the normal group after i.t. or i.c.v. clonidine administration. Whereas the insulin level in depression group was not altered when mice were administered clonidine i.t. or i.c.v. Our results suggest that the blood glucose level in depression group is down-regulated compared to the normal group during d -glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. The down-regulation of the blood glucose level might be one of the important pathophysiologic changes in depression. [ABSTRACT FROM AUTHOR]

DSP-4[ N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d -glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10–40 μg) for 3 days, and d -glucose (2 g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120 min after d -glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d -glucose-fed model. Plasma corticosterone level was downregulated in the d -glucose-fed model, whereas plasma insulin level increased in the d -glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d -glucose. In addition, the d -glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d -glucose-fed and restraint stress models. [ABSTRACT FROM AUTHOR]

Porting is a powerful methodology to recalibrate an existing database of ion chromatography (IC) retention times by reflecting the changes of column behavior resulting from either batch-to-batch variability in the production of the column or the manufacture of new versions of a column. This approach has been employed to update extensive databases of retention data of inorganic and organic anions forming part of the “Virtual Column” software marketed by Thermo Fisher Scientific, which is the only available commercial optimization tool for IC separation. The current porting process is accomplished by performing three isocratic separations with two representative analyte ions in order to derive a porting equation which expresses the relationship between old and new data. Although the accuracy of retention prediction is generally enhanced on new columns, errors were observed on some columns. In this work, the porting methodology was modified in order to address this issue, where the porting equation is now derived by using six representative analyte ions (chloride, bromide, iodide, perchlorate, sulfate, and thiosulfate). Additionally, the updated porting methodology has been applied on three Thermo Fisher Scientific columns (AS20, AS19, and AS11HC). The proposed approach showed that the new porting methodology can provide more accurate and robust retention prediction on a wide range of columns, where average errors in retention times for ten test anions under three eluent conditions were less than 1.5%. Moreover, the retention prediction using this new approach provided an acceptable level of accuracy on a used column exhibiting changes in ion-exchange capacity. [ABSTRACT FROM AUTHOR]

Glaucoma is a vision-threatening disorder characterized by progressive death of retinal ganglion cells (RGCs), although little is known about therapeutic milestones. Due to its complex and multifactorial pathogenesis, multipronged therapeutic approach is needed. Angiogenin (ANG), now called ribonuclease (RNase) 5, has been previously known as angiogenic factor and more recently its biologic activity is extended to promoting cell survival via its ribonucleolytic activity. Here, we revealed the defect of ANG in human glaucomatous trabecular meshwork (TM) cells and identified novel multiple functions of ANG as an anti-glaucomatous strategy. ANG was highly expressed in normal eyes and normal TM cells compared to glaucomatous TM cells. ANG induced intraocular pressure (IOP) lowering in rat models of both normal and elevated IOP, and as a possible mechanism, activated Akt-mediated signals for nitric oxide (NO) production, an important regulator of IOP in glaucomatous TM cell. Moreover, we demonstrated ANG-induced production of matrix metalloproteinase (MMP)-1 and -3 and rho-kinase inhibition for TM remodeling. For anti-glaucomatous defense optimization, ANG not only elicited immune-modulative pathways via indolamine 2,3-dioxygenase (IDO) activation in TM cells and suppression of Jurkat T cells, but also rescued neural stem cells (NSCs) from apoptosis induced by glaucomatous stress. These results demonstrate that novel multi-functional effects of ANG may have benefits against glaucoma in ocular tissues. [ABSTRACT FROM AUTHOR]

Activation of fibroblasts is a vital process during wound healing. However, if prolonged and exaggerated, profibrotic pathways lead to tissue fibrosis or scarring and further organ malfunction. Although the pathogenesis of pterygium is known to be multi-factorial, additional studies are needed to better understand the pathways initiated by fibroblast activation for the purpose of therapeutic translation. Regarding pterygium as a possible systemic disorder, we discuss the different cell types that pterygium fibroblasts originate from. These may include bone marrow-derived progenitor cells, cells undergoing epithelial–mesenchymal transition (EMT), and local resident stromal cells. We also describe how pterygium fibroblasts can be activated and perpetuate profibrotic signaling elicited by various proliferative drivers, immune-inflammation, and novel factors such as stromal cell-derived factor-1 (SDF-1) as well as a known key fibrotic factor, transforming growth factor-beta (TGF-β). Finally, epigenetic modification is discussed to explain inherited susceptibility to pterygium. [ABSTRACT FROM AUTHOR]

This study reports simulation and optimization of ion chromatography separations using multi-segment gradient elution. First, an analytical expression for the gradient retention factor under these complex elution profiles was derived. This allows a rapid retention time prediction calculations under different gradient conditions, during computer-assisted method development. Next, these analytical expressions were implemented in an in-house written Matlab ® routine that searches for the optimal (multi-segment) gradient conditions, either via a four-segment grid search or via the recently proposed one-segment-per-component search, in which the slope is adjusted after the elution of each individual component. Evaluation of the retention time simulation and optimization approaches was performed on a mixture of 18 inorganic anions and different subsets with varying number of compounds. The two considered multi-segment gradient optimization searches resulted in similar proposed gradient profiles, and corresponding chromatograms. Moreover, the resultant chromatograms were clearly superior to the chromatograms obtained from the best simple linear gradient profiles, found via a fine grid search . The proposed approach is useful for automated method development in ion chromatography in which complex elution profiles are often used to increase the separation power. [ABSTRACT FROM AUTHOR]

The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level. [ABSTRACT FROM AUTHOR]

Topology optimization problem requires repeated evaluations of the objective function and design sensitivity in the design domain with various density distributions. A repeated computations in the optimization process, requires a large amount of computing time and resources. These issues have inspired the development of optimization techniques combined with a system reduction. In order to reduce the system, this study employs a system dynamic condensation method based on selected primary degrees of freedom. Based on a system reduction, this study performs a topology optimization to maximize the eigenvalue and linear summation of each eigenvalue. In the optimization procedure, mode tracking method, called MAC, is used to pursue target modes, and the design sensitivity is calculated by a method of the rigid body mode separation assuring the reliability of sensitivity regardless of the design variable perturbation size. Each result of the numerical examples based on the reduction system is compared to that of the full system. Through a few numerical examples, it is demonstrated that the proposed method can provide efficient and reliable results in topology optimization. [ABSTRACT FROM AUTHOR]

The roles of α 2 -adrenergic receptors located in the spinal cord in the regulation of blood glucose levels were studied in imprinting control region (ICR) mice. Mice were treated intrathecally (i.t.) with clonidine or yohimbine, and the blood glucose levels were measured at 0, 30, 60 and 120 min after i.t. administration. The i.t. injection with clonidine caused a pronounced elevation of the blood glucose levels in a dose-dependent manner. Clonidine-induced hyperglycemic effect was dose-dependently attenuated by i.t. pretreatment with yohimbine. Furthermore, plasma insulin level was attenuated by clonidine, and yohimbine pretreatment reversed partially, but significantly, clonidine-induced down-regulation of the plasma insulin level. I.t. pretreatment with pertussis toxin (PTX) almost abolished the hyperglycemic effect induced by clonidine. PTX pretreatment reversed the induced down-regulation of the insulin level. In addition, i.t. pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or intraperitoneal (i.p.) pretreatment with mifepristone, hexamethonium and 6-hydroxydopamine (6-OHDA) attenuated the hyperglycemic effect induced by clonidine. I.t. injected clonidine significantly increased plasma corticosterone level. The elevated blood glucose level induced by clonidine was significantly decreased in adrenalectomized (ADX) mice. Our results suggest that the α 2 -adrenergic receptors located in the spinal cord play important roles for the elevation of the blood glucose level. The hyperglycemic effect induced by clonidine appears to be mediated by a reduction of the plasma insulin level. In addition, glucocortioid system appears to be involved in clonidine-induced hyperglycemic effect. Furthermore, the clonidine-induced hyperglycemia appears to be mediated via activating the spinal nerves or peripheral sympathetic nervous system. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone (CRH) is known to be involved in both antinociceptive and nociceptive processing. In the present study, we examined the role of the CRH receptor 1 in the regulation of nociception in mice. First, we found that CRH mRNA level was elevated in the hypothalamus or hippocampus by intraperitoneal (i.p.) injection with 1% acetic acid, intraplantar injection of 5% formalin, or intrathecal (i.t.) injection of substance P (0.7 μg/5 μl). Nociceptive behavior induced by acetic acid, formalin, or substance P were reduced in CRHR1 heterozygous (CRHR1+/−) mice compared to that in C57BL6 (wild type, CRHR1+/+) mice group. Furthermore, administration with CRHR1 antagonists such as CP 154526 (10 mg/kg, i.p.) orα-helical CRF 9-41 (10 μg/5 μl, intracerebroventricular [i.c.v.]) attenuated nociceptive behaviors observed in the substance P and writhing pain models. Our results suggest that CRHR1 might play an important role in the regulation of nociception, especially, toward nociceptive activation rather than producing the antinociception. [ABSTRACT FROM PUBLISHER]

Background/Aims: To show whether intrathecal (i.t.) treatment with pertussis toxin (PTX) produces a hypoglycemic effect in ICR, db/db and streptozotocin-treated mice. Methods: The blood glucose level (BGL) was measured after i.t. treatment with PTX, AB5 toxins and PTX subunits. Insulin or leptin levels were measured after PTX injection. The effect of PTX on the BGL was examined in adrenalectomized (ADX) mice. Glucose transporter (GLUT) levels were determined by Western blotting. Results: PTX attenuated the elevated BGL in the D-glucose-fed model in a long-term manner. Heat-labile toxin (HLT), HLT subunit B or Shiga toxin, which belong to the AB5 toxins, administered i.t. did not affect the BGL. PTX A protomer (PTX-A) or PTX B oligomers (PTX-B) injected i.t. did not have an effect on the BGL as well. However, combined treatment with PTX-A and PTX-B subunits caused a hypoglycemic effect. The leptin level was gradually reduced by PTX for up to 6 days, without affecting the insulin level. PTX administered i.t. significantly decreased the BGL further in ADX mice. Moreover, GLUT-2 (hypothalamus and pituitary gland), GLUT-4 (muscle) and GLUT-3 (adrenal gland) expression levels were increased, whereas GLUT-1 (brain cortex, liver, muscle and spinal cord), GLUT-2 (liver) and GLUT-3 (brain cortex and pituitary gland) expression levels were decreased. Discussion: Our data suggest that PTX administered spinally produces a hypoglycemic effect in a long-term manner, and PTX-induced hypoglycemia appears to be mediated by the reduction in activity of the glucocorticoid system. Furthermore, PTX may modulate the insulin level during hypoglycemia. Among GLUTs, GLUT-4 in muscle, GLUT-2 in the liver, hypothalamus and pituitary gland as well as GLUT-1 in the adrenal gland may be responsible for PTX-induced hypoglycemia. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Micronutrient (MN) supplementation has a positive impact on clinical outcomes. However, the evidence for the impact of MN supplementation remains controversial. Therefore, our study aims to assess the impact on nutritional outcomes according to exploring the implementation of MN support with multidisciplinary collaboration. Methods: This retrospective cohort study was conducted at a university hospital in Incheon, Korea. All patients referred to a nutrition support team (NST) between July and November 2022 were included. The NST reviews the MN protocol, which includes multivitamins and trace elements, based on international nutrient guidelines. All patients who were on nothing per oral and did not meet ≥70% of their nutritional requirements within 1 week were recommended MN supplements. Compliance with the MN protocol was evaluated, alterations in nutritional status based on the Nutrition Risk Screening 2002 (NRS 2002) scoring system and clinical outcomes were assessed after 7 day and at discharge. Multiple logistic regression analysis was used to identify factors associated with high nutritional risk in discharged patients. In addition, a sub-analysis was performed on changes in the nutritional of patients on the ward and in the ICU. Results: A total of 255 patients were eligible for analysis, with many patients requiring an MN supply of nothing per oral. The rate of implementation of MN supplementation was 50.2%. The findings indicate a significant decrease in the NRS 2002 score in the good compliance group with MN supplementation. No significant differences in protocol compliance were observed in terms of mortality, hospital stay, or length of stay in the intensive care unit. However, bad compliance with MN supplementation was correlated with risk factors for malnutrition at discharge. In subgroup analysis, nutritional status in the ICU and wards improved, with a significant difference between the two groups. Conclusions: The implementation of a MN supplementation protocol by a multidisciplinary NST is a feasible approach for improving the nutritional status of inpatients. Ensuring high compliance with this protocol is crucial, as poor compliance has been identified as a risk factor for malnutrition at discharge. Active intervention by the NST is essential to achieve optimal nutritional outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. Methods: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. Results: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. Conclusion: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin. [ABSTRACT FROM AUTHOR]

Neuropathic pain is described as the "most terrible of all tortures that a nerve wound may inflict." The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwi water extract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid-induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve injury (SNI) models and tail-flick test with a vincristine-induced pain model. An Ames test was also conducted. 5-hydroxymethylfurfural (5-HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5-HMF was identified as an effective compound. Because 5-HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5-succinoxymethylfurfural (5-SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5-SMF, possess effective antinociceptive activity against neuropathic pain. [ABSTRACT FROM AUTHOR]

How the brain fluidly orchestrates visual behavior is a central question in cognitive neuroscience. Researchers studying neural responses in humans and nonhuman primates have mapped out visual response profiles and cognitive modulation in a large number of brain areas, most often using pared down stimuli and highly controlled behavioral paradigms. The historical emphasis on reductionism has placed most studies at one pole of an inherent trade-off between strictly controlled experimental variables and open designs that monitor the brain during its natural modes of operation. This bias toward simplified experiments has strongly shaped the field of visual neuroscience, with little guarantee that the principles and concepts established within that framework will apply more generally. In recent years, a growing number of studies have begun to relax strict experimental control with the aim of understanding how the brain responds under more naturalistic conditions. In this article, we survey research that has explicitly embraced the complexity and rhythm of natural vision. We focus on those studies most pertinent to understanding high-level visual specializations in brains of humans and nonhuman primates. We conclude that representationalist concepts borne from conventional visual experiments fall short in their ability to capture the real-life visual operations undertaken by the brain. More naturalistic approaches, though fraught with experimental and analytic challenges, provide fertile ground for neuroscientists seeking new inroads to investigate how the brain supports core aspects of our daily visual experience. • Current concepts in primate visual neuroscience stem from a tradition of strict experimental reductionism. • Some vision researchers have begun to investigate brain activity during naturalistic stimulation and behavior. • These experiments are challenging but have begun to shed light on aspects of brain function that were previously hidden. • This work and its imminent extension to freely moving subjects will gradually impact core concepts in visual neuroscience. [ABSTRACT FROM AUTHOR]

• QSRR models predicting η ′ values in the hydrophobic subtraction model in reversed-phase liquid chromatography are generated. • Dual clustering-based localised QSRR modelling, combining a P -ratio clustering with the second dominant interaction-based clustering, is employed. • Predicted η ′ values, combined with H values embedded in the USP website, provide an acceptable level of retention time predictions of unknown compounds for column scoping purposes. • The most promising column for the separation of analytes is proposed, comparing predicted resolution values for a set of possible critical pairs. Quantitative structure–retention relationships (QSRR) predicting the values of solute "hydrophobicity" coefficient η ′ in the approximate hydrophobic subtraction model (HSM) can be used to predict retention times of compounds on numerous reversed-phase (RP) columns, provided that column parameters on the corresponding stationary phases are available. In the present study, we propose a new dual clustering-based localised QSRR approach, combining P -ratio clustering (where P is the octanol–water partition coefficient) with second dominant interaction (SDI)-based clustering, to produce predictive models with an acceptable level of prediction accuracy for in silico column scoping in RP method development. QSRR models for η ′ values were derived for 49 compounds out of 63 in a dataset extracted from the literature, where retention data were measured under one isocratic mobile phase condition (i.e. , acetonitrile-water, 50:50 [v/v]). These models gave a predictive squared correlation coefficient Q ext(F2) 2 of 0.83 and a root mean square error of prediction (RMSEP) of 0.14. For the modelling, a genetic algorithm-partial least square regression (GA-PLS) approach was performed using the η ′ values and their relevant molecular descriptors. The corresponding retention times were predicted by applying the predicted η ′ values of the models and the stationary phase "hydrophobicity" parameter H values for the corresponding columns to the approximate HSM, resulting in excellent accuracy and predictability (Q ext(F2) 2 of 0.90 and RMSEP of 0.72 min). The established QSRR approach was experimentally verified for six Thermo Scientific columns (Acclaim™ 120 C18, Acclaim Polar Advantage, Acclaim Polar Advantage II, Accucore™ aQ, Accucore Phenyl-X, and Hypersil Gold C18 columns) using two types of datasets. The first dataset consisted of eight model compounds extracted from the original dataset and retention time predictions for those compounds were then evaluated on the above columns. The result showed good agreement between predicted and observed retention times with an acceptable error in retention time predictions (slope of 0.97, Q ext(F2) 2 of 0.95, a mean absolute error (MAE) of 0.43 min and RMSEP of 0.61 min). The second dataset included eight test compounds not included in the original dataset, which were all classified into the η ′ cluster by applying a Tanimoto similarity (TS) threshold of 0.7. Similarly, predicted retention times of the test compounds were compared with their corresponding observed retention times, resulting in acceptable retention time predictions with the slope of 0.99, Q ext(F2) 2 of 0.93 and RMSEP of 0.52 min. Comparisons of resolution values between columns were utilised to select the most suitable columns for separations of the compounds in the respective test sets. Actual chromatograms obtained on the chosen columns showed the feasibility for effective column scoping without experimentation on numerous RP stationary phases available in the USP website, based on the predicted resolution values. [ABSTRACT FROM AUTHOR]

In greenhouses, plant growth is directly influenced by internal environmental conditions, and therefore requires continuous management and proper environmental control. Inadequate environmental conditions make plants vulnerable to pests and diseases, lower yields, and cause impaired growth and development. Previous studies have explored the combination of greenhouse actuator control history with internal and external environmental data to enhance prediction accuracy, using deep learning-based models such as RNNs and LSTMs. In recent years, transformer-based models and RNN-based models have shown good performance in various domains. However, their applications for time-series forecasting in a greenhouse environment remain unexplored. Therefore, the objective of this study was to evaluate the prediction performance of temperature, relative humidity (RH), and CO2 concentration in a greenhouse after 1 and 3 h, using a transformer-based model (Autoformer), variants of two RNN models (LSTM and SegRNN), and a simple linear model (DLinear). The performance of these four models was compared to assess whether the latest state-of-the-art (SOTA) models, Autoformer and SegRNN, are as effective as DLinear and LSTM in predicting greenhouse environments. The analysis was based on four external climate data samples, three internal data samples, and six actuator data samples. Overall, DLinear and SegRNN consistently outperformed Autoformer and LSTM. Both DLinear and SegRNN performed well in general, but were not as strong in predicting CO2 concentration. SegRNN outperformed DLinear in CO2 predictions, while showing similar performance in temperature and RH prediction. The results of this study do not provide a definitive conclusion that transformer-based models, such as Autoformer, are inferior to linear-based models like DLinear or certain RNN-based models like SegRNN in predicting time series for greenhouse environments. [ABSTRACT FROM AUTHOR]

Inadequate cerebral perfusion is a risk factor for cerebral ischemia in patients with large artery steno-occlusion. We investigated whether prefrontal oxyhemoglobin oscillation (ΔHbO2, 0.6–2 Hz) was associated with decreased vascular reserve in patients with steno-occlusion in the large anterior circulation arteries. Thirty-six patients with steno-occlusion in the anterior circulation arteries (anterior cerebral artery, middle cerebral artery, and internal carotid artery) were included and compared to thirty-six control subjects. Patients were categorized into two groups (deteriorated vascular reserve vs. preserved vascular reserve) based on the results of Diamox single- photon emission computed tomography imaging. HbO2 data were collected using functional near-infrared spectroscopy. The slope of ΔHbO2 and the ipsilateral/contralateral slope ratio of ΔHbO2 were analyzed. Among the included patients (n = 36), 25 (69.4%) had deteriorated vascular reserve. Patients with deteriorated vascular reserve had a significantly higher average slope of ΔHbO2 on the ipsilateral side (5.01 ± 2.14) and a higher ipsilateral/contralateral ratio (1.44 ± 0.62) compared to those with preserved vascular reserve (3.17 ± 1.36, P = 0.014; 0.93 ± 0.33, P = 0.016, respectively) or the controls (3.82 ± 1.69, P = 0.019; 0.94 ± 0.29, P = 0.001). The ipsilateral/contralateral ΔHbO2 ratio could be used as a surrogate for vascular reserve in patients with severe steno-occlusion in the anterior circulation arteries. [ABSTRACT FROM AUTHOR]

Diabetes is characterized by persistently high blood glucose levels and severe complications and affects millions of people worldwide. In this study, we explored the epigenetic landscape of diabetes using data from the Korean Genome and Epidemiology Study (KoGES), specifically the Ansung–Ansan (AS–AS) cohort. Using epigenome-wide association studies, we investigated DNA methylation patterns in patients with type 2 diabetes mellitus (T2DM) and those with normal glucose regulation. Differential methylation analysis revealed 106 differentially methylated probes (DMPs), with the 10 top DMPs prominently associated with TXNIP, PDK4, NBPF20, ARRDC4, UFM1, PFKFB2, C7orf50, and ABCG1, indicating significant changes in methylation. Correlation analysis highlighted the association between the leading DMPs (e.g., cg19693031 and cg26974062 for TXNIP and cg26823705 for NBPF20) and key glycemic markers (fasting plasma glucose and hemoglobin A1c), confirming their relevance in T2DM. Moreover, we identified 62 significantly differentially methylated regions (DMRs) spanning 61 genes. A DMR associated with PDE1C showed hypermethylation, whereas DMRs associated with DIP2C, FLJ90757, PRSS50, and TDRD9 showed hypomethylation. PDE1C and TDRD9 showed a strong positive correlation between the CpG sites included in each DMR, which have previously been implicated in T2DM-related processes. This study contributes to the understanding of epigenetic modifications in T2DM. These valuable insights can be utilized in identifying potential biomarkers and therapeutic targets for effective management and prevention of diabetes. [ABSTRACT FROM AUTHOR]

Summary Neurons within fMRI-defined face patches of the macaque brain exhibit shared categorical responses to flashed images but diverge in their responses under more natural viewing conditions. Here we investigate functional diversity among neurons in the anterior fundus (AF) face patch, combining whole-brain fMRI with longitudinal single-unit recordings in a local population (<1 mm 3 ). For each cell, we computed a whole-brain correlation map based on its shared time course with voxels throughout the brain during naturalistic movie viewing. Based on this mapping, neighboring neurons showed markedly different affiliation with distant visually responsive areas and fell coarsely into subpopulations. Of these, only one subpopulation (∼16% of neurons) yielded similar correlation maps to the local fMRI signal. The results employ the readout of large-scale fMRI networks and, by indicating multiple functional domains within a single voxel, present a new view of functional diversity within a local neural population. [ABSTRACT FROM AUTHOR]

The breeding of new stenospermocarpic seedless grape cultivars is of particular importance to the growing table grape market and grape processing industry. However, the developmental and genetic architectures of soft‐seed and seedlessness traits are unclear. In this study, we performed anatomical, histochemical and gene expression analyses to characterize the morphological and genetic basis of the seed hardness of 'Hongju', a stenospermocarpic soft‐seed grape cultivar developed by crossbreeding maternal 'Italia' and paternal 'Perlon' cultivars. We found intensively lignified medium integument layers in the seeds of hard‐seed cultivars, but these layers were degraded in the stenospermocarpic seedless cultivars beginning 35 days after flowering. The expression of genes related to the lignin and cellulose biosynthesis pathways was downregulated, whereas that of several cell‐wall loosening‐related genes was upregulated in 'Hongju' compared with 'Italia' beginning at 21 days after flowering. These results suggest that transcriptional suppression of the lignin and cellulose biosynthesis pathways coupled with reduced formation of medium integument plays an important role in the development of soft seeds in stenospermocarpic seedless grape cultivars. [ABSTRACT FROM AUTHOR]

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23–0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19–0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31–21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of frailty in patients with symptomatic lumbar spinal stenosis (LSS) and a propensity score-matched control group, and to analyze the association between symptomatic LSS and frailty.Methods: This study included 2 groups: 1 consisting of patients with symptomatic LSS (LSS group) and the other including healthy elderly subjects without degenerative spinal disease (control group). Baseline sociodemographic data, variables regarding frailty assessment, and clinical outcomes were collected. The frailty was assessed with Fried criteria. Between the LSS and control groups, the prevalence of frailty was compared. Among all participants, risk factors for frailty were identified using multivariate logistic regression.Results: Totally, 843 subjects participated (142 in LSS group and 701 in control group) in this study. After the propensity score matching (142 in each group), the LSS group had significantly higher prevalence of frail than the control group (P < 0.001): 59 (41.5%) participants in the LSS group were frail, whereas 10 (7.0%) participants in the control group were frail. Within LSS group analysis showed that participants with frailty had significantly higher disability and lower quality of life compared to those in a robust state. Among all participants, LSS and age were found to be significant risk factors for frail in multivariate logistic regression model.Conclusions: The present study highlights a strong association between symptomatic LSS and frailty. Furthermore, symptom severity and disability caused by LSS are significantly related to frailty. Therefore, early detection and appropriate treatment for frailty in patients with LSS is important.Graphical abstract: These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Introduction: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. Methods: We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. Results: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. Conclusion: Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated. [ABSTRACT FROM AUTHOR]

Background. Little is known regarding the effects of socioeconomic status (SES) and frailty on mortality in Korea. Objective. This study investigated the combined impact of low SES and frailty on all-cause mortality in Korean older adults. Methods. Study sample at baseline comprised 7,960 community-dwelling adults (56.8% women) aged 65 years and older. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of low SES and frailty for all-cause mortality. Results. Overall, low SES plus frailty resulted in an increased risk of all-cause mortality (HR = 1.56, 95% CI = 1.09–2.23, P=0.015) even after adjustments for all the measured covariates, as compared with high SES plus nonfrailty (HR = 1). Among older adults aged 65–75 years, the increased mortality risk of either low SES plus nonfrailty (HR = 1.37, 95% CI = 1.02–1.84, P=0.038) or high SES plus frailty (HR = 2.09, 95% CI = 1.12–3.91, P=0.021) remained significant even after adjustments for all the covariates, as compared with high SES plus nonfrailty (HR = 1). Conclusion. The current findings suggest that either low SES or frailty is significantly associated with increased all-cause mortality in Korean older adults. [ABSTRACT FROM AUTHOR]

Purpose: Firstly, to investigate the prevalence of frailty and impact on health-related quality of life (HRQOL) in a Korean community-dwelling elderly population using the Fried frailty criteria; secondly, to investigate the associations among frailty, socioeconomic status (SES), and HRQOL of the Korean community-based population; and thirdly, to analyze the relationship between education, income, and frailty.Methods: Nine hundred and sixty-four apparently heathy subjects from the Korean community-based population were enrolled in this prospective cross-sectional study. Using self-reported questionnaires, demographic data, SES, and HRQOL were evaluated. Frailty status was determined according to the Fried frailty criteria. After adjustment of covariates including age, sex, and BMI, multivariate linear regression analyses were conducted to assess each component of the proposed mediation models, and mediation was also verified by the bootstrapping technique.Results: Among the 964 participants, 530 (55.0%), 399 (41.4%), and 35 (3.6%) participants were classified into the robust, pre-frailty, and frailty group, respectively. The frail group demonstrated significantly lower HRQOL. Participants with lower income or education level had significantly higher chances of being frail. Frailty acted as a mediator in this association between low SES (education and income) and low HRQOL. Furthermore, income contributed most to the explanation of educational differences in frailty, suggesting full mediation.Conclusion: Frailty has a significant negative influence on HRQOL in the community-based elderly population, and acts as a mediator between SES and HRQOL. As a mediator, income can explain educational difference related with the frailty. [ABSTRACT FROM AUTHOR]

The greenhouse industry achieves stable agricultural production worldwide. Various information and communication technology techniques to model and control the environment have been applied as data from environmental sensors and actuators in greenhouses are monitored in real time. The current study designed data-based, deep learning models for evapotranspiration (ET) and humidity in tomato greenhouses. Using time-series data and applying long short-term memory (LSTM) modeling, an ET prediction model was developed and validated in comparison with the Stanghellini model. Training with 20-day and testing with 3-day data resulted in RMSEs of 0.00317 and 0.00356 kgm−2 s−1, respectively. The standard error of prediction indicated errors of 5.76 and 6.45% in training and testing, respectively. Variables were used to produce a feature map using a two-dimensional convolution layer which was transferred to a subsequent layer and finally connected with the LSTM structure for modeling. The RMSE in humidity prediction using the test dataset was 2.87, indicating a performance better than conventional RNN-LSTM models. Irrigation plans and humidity control may be more accurately conducted in greenhouse cultivation using this model. [ABSTRACT FROM AUTHOR]

Effects of histamine receptors agonists or antagonists administered centrally (supraspinally or spinally) on immobilization stress-induced blood glucose levels were studied in Institute for Cancer Research mice. Mice were pretreated intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with histamine (H1, H2, H3 and H4) receptor agonists or antagonists 10 min prior to immobilization stress (IMO) stimulation for 30 min. We found that the increased blood glucose level induced by IMO was attenuated by the i.c.v. pretreatment withα-methylhistamine (H3 agonist). However, H3 antagonist, H1, H2 and H4 receptor agonists and antagonists did not affect the blood glucose level. Also, i.t. pretreatment withα-methylhistamine or VUF 8430 attenuated the increased blood glucose level induced by IMO. In addition, cetirizine and carcinine enhanced the increased blood glucose level induced by IMO. However, the blood glucose level was not affected by H1 and H2 receptor agonists, H2 and H4 receptor antagonists. Corticosterone and insulin levels were also measured inα-methylhistamine (i.c.v or i.t) and with VUF 8430, carcinine and cetirizine (i.t.) treated group. We found that the corticosterone level was increased only by i.t treatment withα-methylhistamine, whereas the insulin level was attenuated by i.c.v or i.t. treatment withα-methylhistamine and i.t treatment with VUF 8430, carcinine and cetirizine. Our results suggest the active involvement of histamine receptor in blood glucose regulation in IMO. [ABSTRACT FROM AUTHOR]