Identification of molecular subtypes of dementia by using blood-proteins interaction-aware graph propagational network.

Plasma protein biomarkers have been considered promising tools for diagnosing dementia subtypes due to their low variability, cost-effectiveness, and minimal invasiveness in diagnostic procedures. Machine learning (ML) methods have been applied to enhance accuracy of the biomarker discovery. However, previous ML-based studies often overlook interactions between proteins, which are crucial in complex disorders like dementia. While protein-protein interactions (PPIs) have been used in network models, these models often fail to fully capture the diverse properties of PPIs due to their local awareness. This drawback increases the chance of neglecting critical components and magnifying the impact of noisy interactions. In this study, we propose a novel graph-based ML model for dementia subtype diagnosis, the graph propagational network (GPN). By propagating the independent effect of plasma proteins on PPI network, the GPN extracts the globally interactive effects between proteins. Experimental results showed that the interactive effect between proteins yielded to further clarify the differences between dementia subtype groups and contributed to the performance improvement where the GPN outperformed existing methods by 10.4% on average.

Discovering comorbid diseases using an inter-disease interactivity network based on biobank-scale PheWAS data.

MOTIVATION: Understanding comorbidity is essential for disease prevention, treatment and prognosis. In particular, insight into which pairs of diseases are likely or unlikely to co-occur may help elucidate the potential relationships between complex diseases. Here, we introduce the use of an inter-disease interactivity network to discover/prioritize comorbidities. Specifically, we determine disease associations by accounting for the direction of effects of genetic components shared between diseases, and categorize those associations as synergistic or antagonistic. We further develop a comorbidity scoring algorithm to predict whether diseases are more or less likely to co-occur in the presence of a given index disease. This algorithm can handle networks that incorporate relationships with opposite signs. RESULTS: We finally investigate inter-disease associations among 427 phenotypes in UK Biobank PheWAS data and predict the priority of comorbid diseases. The predicted comorbidities were verified using the UK Biobank inpatient electronic health records. Our findings demonstrate that considering the interaction of phenotype associations might be helpful in better predicting comorbidity. AVAILABILITY AND IMPLEMENTATION: The source code and data of this study are available at https://github.com/dokyoonkimlab/DiseaseInteractiveNetwork. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of the Effect of Landmark-Based Midline and Paramedian Approaches on Spinal Anesthesia-Related Complications in Adult Patients: A Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Spinal anesthesia is widely used in various types of surgery. However, several complications can occur afterward. This study aimed to identify differences in the incidence of anesthesia-related complications according to the approach methods (midline versus paramedian) for landmark-based spinal anesthesia. Materials and Methods: We searched electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, for eligible randomized controlled trials. The primary outcome was post-dural puncture headache (PDPH) incidence, and secondary outcomes were low back pain (LBP) incidence and success rate in the first trial of spinal anesthesia. We estimated the odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: In total, 2280 patients from 13 randomized controlled trials were included in the final analysis. The incidence rates of PDPH were 5.9% and 10.4% in the paramedian and midline approach groups, respectively. The pooled effect size revealed that the incidence of PDPH (OR: 0.43, 95% CI [0.22-0.83]; p = 0.01; I2 = 53%) and LBP (OR: 0.27, 95% CI [0.16-0.44]; p < 0.001; I2 = 16%) decreased, and the success rate in the first attempt was higher (OR: 2.30, 95% CI [1.36-3.87]; p = 0.002; I2 = 35%) with the paramedian than with the midline approach. Conclusions: Paramedian spinal anesthesia reduced PDPH and LBP and increased the success rate of the first attempt.

Postoperative Delirium after Dexmedetomidine versus Propofol Sedation in Healthy Older Adults Undergoing Orthopedic Lower Limb Surgery with Spinal Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Delirium is a critical postoperative complication in older patients. Based on the hypothesis that intraoperative dexmedetomidine sedation would lower postoperative delirium than propofol sedation would, the authors compared the incidence of postoperative delirium in older adults, using the mentioned sedatives. METHODS: This double-blinded, randomized controlled study included 748 patients, aged 65 yr or older, who were scheduled for elective lower extremity orthopedic surgery, between June 2017 and October 2021. Patients were randomized equally into two groups in a 1:1 ratio according to the intraoperative sedative used (dexmedetomidine vs. propofol). The postoperative delirium incidence was considered the primary outcome measure; it was determined using the confusion assessment method, on the first three postoperative days. The mean arterial pressure and heart rate were evaluated as secondary outcomes. RESULTS: The authors enrolled 732 patients in the intention-to-treat analyses. The delirium incidence was lower in the dexmedetomidine group than in the propofol group (11 [3.0%] vs. 24 [6.6%]; odds ratio, 0.42; 95% CI, 0.201 to 0.86; P = 0.036). During sedation, the mean arterial pressure (median [interquartile range] mmHg) was higher in the dexmedetomidine group (77 [71 to 84]) than in the propofol group (74 [69 to 79]; P < 0.001); however, it significantly fell lower (74 [68 to 80]) than that of the propofol group (80 [74 to 87]) in the postanesthesia care unit (P < 0.001). Lower heart rates (beats/min) were recorded with the use of dexmedetomidine than with propofol, both during sedation (60 [55 to 66] vs. 63 [58 to 70]) and in the postanesthesia care unit (64 [58 to 72] vs. 68 [62-77]; P < 0.001). CONCLUSIONS: Dexmedetomidine showed a lower incidence of postoperative delirium than propofol in healthy older adults undergoing lower extremity orthopedic surgery.

The Involvement of the Hypothalamus-Pituitary-Adrenal Axis in the Development of Hyperalgesia during the Early Postoperative Period.

INTRODUCTION: Hyperalgesia frequently occurs after surgery and is associated with adverse effects on surgical outcomes. Thus, we aimed to examine whether the hypothalamus-pituitary-adrenal (HPA) axis function after surgery is involved in the development of postoperative hyperalgesia. METHODS: Surgery- and pain-related variables were measured 24 and 48 h after the first and second total knee arthroplasties (TKAs) in postmenopausal patients undergoing 1-week-interval staged bilateral TKA. Two sets of saliva samples were consecutively collected from patients before (pre-T1) and 1 week after (post-T1) the first TKA (n = 69). HPA axis function was analyzed in a subgroup of 20 patients with a typical cortisol awakening response (CAR) in both the sets of saliva samples. RESULTS: Surgery-related variables were comparable between the first and second TKAs. However, pain-related variables (pain ratings and the amount of opioid analgesics consumed) were greater after the second than the first TKA. Cortisol and dehydroepiandrosterone (DHEA) secretion during the post-awakening period (CARauc and Daucawk, respectively) was higher at post-T1 than at pre-T1, but the molar CARauc/Daucawk ratio was comparable between the time points examined. No relationship was observed between the pre-T1 CARauc and pain ratings after the first TKA. However, post-T1 CARauc showed a positive correlation with pain ratings after the second TKA. Postoperative pain ratings were negatively correlated with Daucawk and positively correlated with the molar CARauc/Daucawk ratio at all examined time points. DISCUSSION/CONCLUSION: The results suggest that adrenocortical steroidogenic activity favoring the production of cortisol over DHEA after surgery may contribute to the development of hyperalgesia during the early postoperative period.

Effect of the Paravertebral Block on Chronic Postsurgical Pain After Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to identify the benefits of thoracic paravertebral block (PVB) by focusing on its role in reducing chronic postsurgical pain (CPSP) after thoracic surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, were searched to identify studies. PARTICIPANTS: Patients undergoing thoracic surgeries. INTERVENTION: Paravertebral block for postoperative analgesia. MEASUREMENT AND MAIN RESULTS: A total of 1,028 adult patients from 10 RCTs were included in the final analysis. The incidence of CPSP at 3 months after surgery was not reduced in the PVB group compared with the no-block (odds ratio [OR] 0.59, 95% CI 0.34-1.04; p = 0.07; I2 = 6.96%) and other-block (OR 1.39, 95% CI 0.30-6.42; p = 0.67; I2 = 77.75%) groups. The PVB did not significantly reduce the incidence of CPSP after 6 months from surgery when compared with no block (OR 0.44, 95% CI 0.08-2.53; p = 0.36; I2 = 87.53%) and other blocks (OR 1.17, 95% CI 0.71-1.95; p = 0.93; I2 = 45.75%). The PVB significantly decreased postoperative pain at 24 and 48 hours at rest compared with the no- block group. The pain score was higher in the PVB group than in the other block groups 48 hours after surgery at rest. CONCLUSIONS: Thoracic PVB does not prevent CPSP after thoracic surgery. Further large RCTs are required to confirm and validate the authors' results.

The effect of intranasal dexmedetomidine administration on emergence agitation or delirium in pediatric patients after general anesthesia: A meta-analysis of randomized controlled trials.

BACKGROUND: Emergence agitation or delirium can occur in pediatric patients after anesthesia. Dexmedetomidine is known to reduce the impairment of postoperative cognitive function. AIMS: This study aimed to identify the role of intranasal administration of dexmedetomidine in lowering the development of emergence agitation or emergence delirium in pediatric patients after general anesthesia. METHODS: Electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, were searched to identify studies. The primary outcome was the proportion of patients who underwent emergence agitation or emergence delirium after the surgery. Secondary outcomes included emergence time and incidence of postoperative nausea and/or vomiting. We estimated the odds ratio and mean difference with 95% confidence intervals for the determination of effect size using a random-effects model. RESULTS: In total, 2103 pediatric patients from 20 randomized controlled trials were included in the final analysis. The incidence of emergence agitation or emergence delirium was 13.6% in the dexmedetomidine group and 33.2% in the control group. The pooled effect size revealed that intranasal dexmedetomidine administration significantly reduced the incidence of postoperative emergence agitation or emergence delirium in pediatric patients undergoing surgery under general anesthesia (odds ratio 0.25, 95% confidence interval 0.18-0.34; p = .0000; I2 = 37.74%). Additionally, significant difference was observed in emergence time between the two groups (mean difference 2.42, 95% confidence interval 0.37-4.46; p = .021; I2 = 98.40%). Children in the dexmedetomidine group had a significantly lower incidence of postoperative nausea and/or vomiting than those in the control group (odds ratio 0.39, 95% confidence interval 0.24-0.64; p = .0002; I2 = 0.00%). CONCLUSIONS: Intranasal dexmedetomidine reduced the incidence of emergence agitation or emergence delirium in pediatric patients after general anesthesia.

Intraoperative 5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older adults undergoing hip fracture surgery: a single-center retrospective study.

PURPOSE: Postoperative delirium (POD) occurs commonly in older adults, resulting in unfavorable outcomes. Several recent clinical studies have suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists can treat and prevent POD. In this retrospective study, the association between 5-HT3 receptor antagonists and POD was investigated in older adults who underwent hip fracture surgery. METHODS: The electronic medical records of older adults aged ≥ 65 years who underwent hip fracture surgery between January 2011 and June 2018 were reviewed retrospectively. Multivariable logistic regression analysis was used to investigate the association between 5-HT3 receptor antagonists and the occurrence of POD. In addition to the incidence of POD, anesthesia-, surgery-, and patient-related factors related to POD were evaluated. RESULTS: Of the 1025 patients included, 813 (79.3%) were administered 5-HT3 receptor antagonists intraoperatively; 471 (45.9%) were administered ramosetron, and 342 (33.4%) were administered palonosetron. POD was identified in 242 patients (23.6%). Ramosetron and palonosetron reduced the POD incidence by 53% (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.32‒0.71; P < 0.001) and 41% (OR 0.59; 95% CI 0.39‒0.89; P = 0.011), respectively. Additionally, age, American Society of Anesthesiologists physical status class 4, and male were confirmed as risk factors for POD. CONCLUSION: Intraoperative 5-HT3 receptor antagonists may be associated with a reduced risk of POD and can be considered one of the preventive strategies for POD in older adults undergoing hip fracture surgery.

Polypharmacy side-effect prediction with enhanced interpretability based on graph feature attention network.

MOTIVATION: Polypharmacy side effects should be carefully considered for new drug development. However, considering all the complex drug-drug interactions that cause polypharmacy side effects is challenging. Recently, graph neural network (GNN) models have handled these complex interactions successfully and shown great predictive performance. Nevertheless, the GNN models have difficulty providing intelligible factors of the prediction for biomedical and pharmaceutical domain experts. METHOD: A novel approach, graph feature attention network (GFAN), is presented for interpretable prediction of polypharmacy side effects by emphasizing target genes differently. To artificially simulate polypharmacy situations, where two different drugs are taken together, we formulated a node classification problem by using the concept of line graph in graph theory. RESULTS: Experiments with benchmark datasets validated interpretability of the GFAN and demonstrated competitive performance with the graph attention network in a previous work. And the specific cases in the polypharmacy side-effect prediction experiments showed that the GFAN model is capable of very sensitively extracting the target genes for each side-effect prediction. AVAILABILITY AND IMPLEMENTATION: https://github.com/SunjooBang/Polypharmacy-side-effect-prediction.

High-Efficiency Perovskite Solar Cells.

With rapid progress in a power conversion efficiency (PCE) to reach 25%, metal halide perovskite-based solar cells became a game-changer in a photovoltaic performance race. Triggered by the development of the solid-state perovskite solar cell in 2012, intense follow-up research works on structure design, materials chemistry, process engineering, and device physics have contributed to the revolutionary evolution of the solid-state perovskite solar cell to be a strong candidate for a next-generation solar energy harvester. The high efficiency in combination with the low cost of materials and processes are the selling points of this cell over commercial silicon or other organic and inorganic solar cells. The characteristic features of perovskite materials may enable further advancement of the PCE beyond those afforded by the silicon solar cells, toward the Shockley-Queisser limit. This review summarizes the fundamentals behind the optoelectronic properties of perovskite materials, as well as the important approaches to fabricating high-efficiency perovskite solar cells. Furthermore, possible next-generation strategies for enhancing the PCE over the Shockley-Queisser limit are discussed.

Ultrasound assessment of gastric volume in older adults after drinking carbohydrate-containing fluids: a prospective, nonrandomized, and noninferiority comparative study.

PURPOSE: The aim of this study was to evaluate the safety of drinking carbohydrate-containing fluids two hours prior to surgery in older adults using ultrasonography. METHODS: We conducted a nonrandomized and noninferiority comparative study in 60 patients aged over 65 yr who were scheduled for total knee arthroplasty. Patients who were fasted from midnight (fasting group) or who drank 400 mL of a carbohydrate-containing fluid (carbohydrate ingestion group) two hours prior to surgery were matched for age, sex, and body mass index. We measured the cross-sectional area (CSA) of gastric antrum using ultrasound and estimated the gastric fluid volume as the study's primary outcome measure. The noninferiority margin (δ) for the mean difference was predefined as 50 mL. The secondary outcome measures included CSA of the antrum and qualitative gastric volume. RESULTS: The mean (standard deviation) gastric volume was not significantly different between the fasting group and the carbohydrate ingestion group (30.2 [25.4] mL vs 28.4 [35.8] mL; each group, n = 30; P = 0.81). The mean difference in gastric volume was -1.9 mL (95% confidence interval [CI], -17.9 to 14.2), and the upper limit of the 95% CI was lower than the prespecified noninferiority limit (δ = 50 mL). Secondary outcomes were not significantly different between the two groups. CONCLUSION: Drinking of carbohydrate-containing fluid two hours prior to surgery was noninferior to overnight fasting with respect to residual gastric volume at induction of anesthesia in healthy older adults who undergoing total knee arthroplasty. STUDY REGISTRATION: ClinicalTrials.gov (NCT04514380); registered 14 August 2020.

RéSUMé: OBJECTIF: L'objectif de cette étude était d'évaluer l'innocuité de la consommation d'une préparation glucidique deux heures avant une chirurgie chez les personnes âgées à l'aide de l'échographie. MéTHODE: Nous avons mené une étude comparative non randomisée et de non-infériorité chez 60 patients âgés de plus de 65 ans qui devaient bénéficier d'une arthroplastie totale du genou. Les patients étaient à jeun depuis minuit (groupe à jeun) ou avaient bu 400 mL d'une préparation glucidique (groupe d'ingestion de glucides) deux heures avant la chirurgie et ont été appariés pour l'âge, le sexe et l'indice de masse corporelle. Nous avons mesuré la section transversale de l'antre gastrique à l'aide de l'échographie et estimé le volume de liquide gastrique en tant que mesure du critère d'évaluation principal de l'étude. La marge de non-infériorité (δ) pour la différence moyenne a été prédéfinie à 50 mL. Les mesures de critères d'évaluation secondaires comprenaient la section transversale de l'antre et le volume gastrique qualitatif. RéSULTATS: Le volume gastrique moyen (écart type) n'était pas significativement différent entre le groupe à jeun et le groupe d'ingestion de glucides (30,2 [25,4] mL vs 28,4 [35,8] mL; chaque groupe, n = 30; P = 0,81). La différence moyenne de volume gastrique était de -1,9 mL (intervalle de confiance [IC] à 95 %, -17,9 à 14,2), et la limite supérieure de l'IC 95 % était inférieure à la limite de non-infériorité prédéfinie (δ = 50 mL). Aucune différence intergroupe significative n'a été observée dans les critères d'évaluation secondaires. CONCLUSION: La consommation d'une préparation glucidique deux heures avant la chirurgie n'était pas inférieure au jeûne nocturne en ce qui concerne le volume gastrique résiduel à l'induction de l'anesthésie chez les personnes âgées en bonne santé qui bénéficient d'une arthroplastie totale du genou. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04514380); enregistrée le 14 août 2020.

Efficacy of Erector Spinae Plane Block for Analgesia in Thoracic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study was to determine whether erector spinae plane block (ESPB) can provide an effective analgesia for managing pain after thoracic surgery and compare the efficacy of ESPB with that of other regional analgesic techniques. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science were searched. PARTICIPANTS: Patients undergoing thoracic surgeries. INTERVENTION: Erector spinae plane block with local anesthetics for postoperative analgesia. MEASUREMENT AND MAIN RESULTS: Seventeen studies, including 1,092 patients, were included in the final analysis. Erector spinae plane block reduced 24-hour postoperative opioid consumption (mean difference [MD] -17.49, 95% CI -26.87 to -8.12), pain score at rest (MD -0.82, 95% CI -1.31 to -0.33), and pain score at movement (MD -0.77, 95% CI -1.20 to -0.3) compared to no block. Compared with other regional blocks, various results have been observed. Although statistical results showed that ESPB is inferior to thoracic paravertebral block and intercostal nerve block and superior to serratus anterior plan block in postoperative analgesia, clinical differences remain unclear. The incidence of hematoma was lower in the ESPB group than in the other groups (odds ratio 0.19, 95% CI 0.05-0.73). CONCLUSION: Erector spinae plane block may provide effective analgesia after thoracic surgery. Compared with other techniques, it is a safer method, without clinically important differences, for postoperative pain control. Therefore, ESPB may be considered as a valuable option for postoperative pain management after thoracic surgery.

The effects of intraoperative magnesium sulfate administration on emergence agitation and delirium in pediatric patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of intraoperative magnesium for the prevention of emergence agitation or delirium is unclear as there have been conflicting results reported by several randomized controlled trials. AIMS: The aim of this study was to investigate the effect of magnesium sulfate on emergence agitation or emergence delirium in pediatric patients. METHODS: Electronic databases, including PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science, were searched to identify studies which evaluated the effects of magnesium on postoperative emergence agitation or emergence delirium. The primary outcome was the incidence of emergence agitation or emergence delirium during the post-anesthesia stay. The secondary outcome was the agitation or delirium score upon admission to the post-anesthesia care unit. We estimated the odds ratio and standardized mean difference using a random-effect model. RESULTS: A total of 712 pediatric patients from 10 randomized controlled trials were included in the final analysis. The incidence of emergence agitation or emergence delirium was 29.7% in the magnesium group and 50.5% in the control group. The pooled effect size revealed that the administration of magnesium sulfate significantly reduced the incidence of postoperative emergence agitation or emergence delirium in pediatric patients undergoing surgery with general anesthesia (Odds ratio, 0.31; 95% confidence interval, 0.15 to 0.64; p = .002). Additionally, children in the magnesium group reported significantly lower agitation or delirium scores than those in the control group (standardized mean difference, -0.70; 95% confidence interval, -1.15 to -0.24; p = .003). CONCLUSION: The administration of magnesium sulfate reduced the incidence and severity of emergence agitation or emergence delirium in pediatric patients after the use of general anesthesia during surgery.

Dementia key gene identification with multi-layered SNP-gene-disease network.

MOTIVATION: Recently, various approaches for diagnosing and treating dementia have received significant attention, especially in identifying key genes that are crucial for dementia. If the mutations of such key genes could be tracked, it would be possible to predict the time of onset of dementia and significantly aid in developing drugs to treat dementia. However, gene finding involves tremendous cost, time and effort. To alleviate these problems, research on utilizing computational biology to decrease the search space of candidate genes is actively conducted.In this study, we propose a framework in which diseases, genes and single-nucleotide polymorphisms are represented by a layered network, and key genes are predicted by a machine learning algorithm. The algorithm utilizes a network-based semi-supervised learning model that can be applied to layered data structures. RESULTS: The proposed method was applied to a dataset extracted from public databases related to diseases and genes with data collected from 186 patients. A portion of key genes obtained using the proposed method was verified in silico through PubMed literature, and the remaining genes were left as possible candidate genes. AVAILABILITY AND IMPLEMENTATION: The code for the framework will be available at http://www.alphaminers.net/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Role of Electrostatics in the Heterogeneous Interaction of Two-Dimensional Engineered MoS2 Nanosheets and Natural Clay Colloids: Influence of pH and Natural Organic Matter.

Few-layered molybdenum disulfide (MoS2) nanosheets are poised to be at the core of low-voltage electronic device development. Upon environmental release, these two-dimensional (2D) structures can interact with abundant natural geocolloids. This study probes the role of dimensionality in modulating the aggregation behavior of 2D MoS2 nanosheets with plate-like geocolloids (i.e., homoionized kaolinite and montmorillonite clays). MoS2 nanosheets were exfoliated using an ethanol/water mixture, and aggregation kinetics were investigated with time-resolved dynamic light scattering at low monovalent salt concentrations and at three pH levels, in the presence and absence of Suwannee River humic acid (SRHA). Results indicate that pH and particle ratios are key to modulating the stability of MoS2/clay systems. At pH 4, aggregation of MoS2 increased with increasing MoS2/clay ratios and approached maximum values of 0.09 and 0.06 nm/s in the binary systems with montmorillonite and kaolinite, respectively. Electrostatic attraction facilitates heteroaggregation at pH values of 4 and 6; differences in the clay structures (i.e., face-face or face-edge aggregates) might explain the resulting MoS2/clay aggregate configurations, which were probed via the evolution of particle size distribution. The presence of only 0.1 mg/L SRHA drastically suppresses the heteroaggregation propensity of MoS2 nanosheets with geocolloids (to less than 0.01 nm/s at all pH values tested). The high stability of these heterogeneous systems under environmentally relevant conditions can increase the likelihood for cellular uptake and long-distance transport of MoS2.

Role of Unfolded Protein Response and Endoplasmic Reticulum-Associated Degradation by Repeated Exposure to Inhalation Anesthetics in Caenorhabditis elegans.

Background: When an imbalance occurs between the demand and capacity for protein folding, unfolded proteins accumulate in the endoplasmic reticulum (ER) lumen and activate the unfolded protein response (UPR). In addition, unfolded proteins are cleared from the ER lumen for ubiquitination and subsequent cytosolic proteasomal degradation, which is termed as the ER-associated degradation (ERAD) pathway. This study focused on changes in the UPR and ERAD pathways induced by the repeated inhalation anesthetic exposure in Caenorhabditis elegans. Methods: Depending on repeated isoflurane exposure, C. elegans was classified into the control or isoflurane group. To evaluate the expression of a specific gene, RNA was extracted from adult worms in each group and real-time polymerase chain reaction was performed. Ubiquitinated protein levels were measured using western blotting, and behavioral changes were evaluated by chemotaxis assay using various mutant strains. Results: Isoflurane upregulated the expression of ire-1 and pek-1 whereas the expression of atf-6 was unaffected. The expression of both sel-1 and sel-11 was decreased by isoflurane exposure, possibly indicating the inhibition of retro-translocation. The expression of cdc-48.1 and cdc-48.2 was decreased and higher ubiquitinated protein levels were observed in the isoflurane group than in the control, suggesting that deubiquitination and degradation of misfolded proteins were interrupted. The chemotaxis indices of ire-1, pek-1, sel-1, and sel-11 mutants decreased significantly compared to N2, and they were not suppressed further even after the repeated isoflurane exposure. Conclusion: Repeated isoflurane exposure caused significant ER stress in C. elegans. Following the increase in UPR, the ERAD pathway was disrupted by repeated isoflurane exposure and ubiquitinated proteins was accumulated subsequently. UPR and ERAD pathways are potential modifiable neuroprotection targets against anesthesia-induced neurotoxicity.

Effects of dexmedetomidine on blood coagulation: an in vitro study using rotational thromboelastometry.

PURPOSE: To assess the effects of various concentrations of dexmedetomidine on the human blood coagulation profile using rotational thromboelastometry (ROTEM). METHODS: Venous blood samples were collected from 11 healthy volunteers and divided into four specimen bottles; dexmedetomidine was added to attain final sample concentrations of 0, 0.5, 1.0, and 1.5 ng/mL. ROTEM was performed on each study sample. RESULTS: The concentration of dexmedetomidine increased, and the ROTEM values showed a hypercoagulable state. The change in clotting time (CT) for INTEM was larger in samples with a dexmedetomidine concentration of 1.5 ng/mL (- 34%) than in the 0.5 ng/mL samples (- 16%) (P = 0.010). The change in clot formation time (CFT) for INTEM was greater in 1.5 ng/mL samples (- 16%) than in 0.5 ng/mL samples (- 4%) (P = 0.004). A greater decrease in CT for EXTEM was identified in the 1.0 ng/mL and 1.5 ng/mL samples (- 36% and - 37%, respectively) than in the 0.5 ng/mL samples (- 12%) (P = 0.003 for both categories). The change in CFT for EXTEM was greater in the 1.0 ng/mL and 1.5 ng/mL samples (- 11% and - 13%, respectively) than in the 0.5 ng/mL samples (- 4%) (P = 0.006 and P = 0.001, respectively). A bigger change in maximum clot firmness (MCF) for EXTEM was observed in the 1.5 ng/mL samples (4%) than in the 0.5 ng/mL samples (0%) (P = 0.002). The change in MCF for FIBTEM was greater in the 1.5 ng/mL samples (19%) than in the 0.5 ng/mL samples (5%) (P = 0.001). CONCLUSIONS: All coagulation pathways showed a hypercoagulable state as the concentration of dexmedetomidine increased. Nevertheless, most of the values of ROTEM were maintained within the reference ranges. Clinical Trial NCT04269278.

Disease gene identification based on generic and disease-specific genome networks.

SUMMARY: Immune diseases have a strong genetic component with Mendelian patterns of inheritance. While the tight association has been a major understanding in the underlying pathophysiology for the category of immune diseases, the common features of these diseases remain unclear. Based on the potential commonality among immune genes, we design Gene Ranker for key gene identification. Gene Ranker is a network-based gene scoring algorithm that initially constructs a backbone network based on protein interactions. Patient gene expression networks are added into the network. An add-on process screens the networks of weighted gene co-expression network analysis (WGCNA) on the samples of immune patients. Gene Ranker is disease-specific; however, any WGCNA network that passes the screening procedure can be added on. With the constructed network, it employs the semi-supervised learning for gene scoring. RESULTS: The proposed method was applied to immune diseases. Based on the resulting scores, Gene Ranker identified potential key genes in immune diseases. In scoring validation, an average area under the receiver operating characteristic curve of 0.82 was achieved, which is a significant increase from the reference average of 0.76. Highly ranked genes were verified through retrieval and review of 27 million PubMed literatures. As a typical case, 20 potential key genes in rheumatoid arthritis were identified: 10 were de facto genes and the remaining were novel. AVAILABILITY AND IMPLEMENTATION: Gene Ranker is available at http://www.alphaminers.net/GeneRanker/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Effect of Perioperative Intravenous Iron on Hemoglobin in Surgical Patients: A Meta-Analysis.

BACKGROUND: Patient blood management aims to maintain hemoglobin level, minimize blood loss, and avoid unnecessary blood transfusion. Ferric carboxymaltose, an intravenous iron agent, was included as a part of surgical patient blood management strategy. However, it is still controversial that ferric carboxymaltose can reduce transfusion requirements. The purpose of this systematic review and meta-analysis is to evaluate the benefits of perioperative ferric carboxymaltose on the postoperative hematological parameters and transfusion requirements. METHODS: Randomized controlled trials evaluating the effects of ferric carboxymaltose were searched through databases: MEDLINE, EMBASE, CENTRAL, CINAHL, Scopus, Web of Science, and KoreaMed. Meta-analysis was performed using random effect models. RESULTS: A total of 8 studies (n = 471) were included in the final analysis. Postoperative hemoglobin was higher in the ferric carboxymaltose group than in the control group (mean difference [MD], 0.58 g/dL; 95% confidence interval [CI], 0.36 to 0.80; P < 0.00001). Postoperative serum ferritin and transferrin saturation were also higher in the ferric carboxymaltose group (MD, 373.85 µg/L; 95% CI, 298.13 to 449.56; P < 0.00001; MD, 10.35%; 95% CI, 4.59 to 16.10; P < 0.00001, respectively). However, there were no significant differences in the number of transfused patients, length of hospital stay, and adverse events between groups. Subgroup analysis revealed that adverse events were lower in the ferric carboxymaltose group than the oral iron group. CONCLUSIONS: This study supports that ferric carboxymaltose may increase the postoperative hemoglobin level in surgical patients. However, transfusion requirements could not be reduced by ferric carboxymaltose. Optimal dose and time should be further analyzed.

Grain Boundary Healing of Organic-Inorganic Halide Perovskites for Moisture Stability.

Although organic-inorganic halide perovskite (OIHP)-based photovoltaics have high photoconversion efficiency (PCE), their poor humidity stability prevents commercialization. To overcome this critical hurdle, focusing on the grain boundary (GB) of OIHPs, which is the main humidity penetration channel, is crucial. Herein, pressure-induced crystallization of OIHP films prepared with controlled mold geometries is demonstrated as a GB-healing technique to obtain high moisture stability. When exposed to 85% RH at 30 °C, OIHP films fabricated by pressure-induced crystallization have enhanced moisture stability due to the enlarged OIHP grain size and low-angle GBs. The crystallographic and optical properties indicate the effect of applying pressure onto OIHP films in terms of moisture stability. The photovoltaic devices with pressure-induced crystallization exhibited dramatically stabilized performance and sustained over 0.95 normalized PCE after 200 h at 40% RH and 30 °C.