Bayesian predictive modeling for gas purification using breakthrough curves.

This study proposes a predictive model for assessing adsorber performance in gas purification processes, specifically targeting the removal of chemical warfare agents (CWAs) using breakthrough curve analysis. Conventional parameter estimation methods, such as Brunauer-Emmett-Teller analysis, encounter challenges due to the limited availability of kinetic and equilibrium data for CWAs. To overcome these challenges, we implement a Bayesian parametric inference method, facilitating direct parameter estimation from breakthrough curves. The model's efficacy is confirmed by applying it to H2S purification in a fixed-bed setup, where predicted breakthrough curves aligned closely with previous experimental and numerical studies. Furthermore, the model is applied to sarin with ASZM-TEDA carbon, estimating key parameters that could not be assessed through conventional experimental techniques. The reconstructed breakthrough curves closely match actual measurements, highlighting the model's accuracy and robustness. This study not only enhances filter performance prediction for CWAs but also offers a streamlined approach for evaluating gas purification technologies under limited experimental data conditions.

Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro.

The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson's disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer's disease-related amyloid-ß (Aß) peptide and has inhibitory activity on the human prion protein PrPSc. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aß aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation.

Dynamic Pore Modulation of Stretchable Electrospun Nanofiber Filter for Adaptive Machine Learned Respiratory Protection.

The recent emergence of highly contagious respiratory disease and the underlying issues of worldwide air pollution jointly heighten the importance of the personal respirator. However, the incongruence between the dynamic environment and nonadaptive respirators imposes physiological and psychological adverse effects, which hinder the public dissemination of respirators. To address this issue, we introduce adaptive respiratory protection based on a dynamic air filter (DAF) driven by machine learning (ML) algorithms. The stretchable elastomer fiber membrane of the DAF affords immediate adjustment of filtration characteristics through active rescaling of the micropores by simple pneumatic control, enabling seamless and constructive transition of filtration characteristics. The resultant DAF-respirator (DAF-R), made possible by ML algorithms, successfully demonstrates real-time predictive adapting maneuvers, enabling personalizable and continuously optimized respiratory protection under changing circumstances.

Binary genetic algorithm for optimal joinpoint detection: Application to cancer trend analysis.

The joinpoint regression model (JRM) is used to describe trend changes in many applications and relies on the detection of joinpoints (changepoints). However, the existing joinpoint detection methods, namely, the grid search (GS)-based methods, are computationally demanding, and hence, the maximum number of computable joinpoints is limited. Herein, we developed a genetic algorithm-based joinpoint (GAJP) model in which an explicitly decoupled computing procedure for optimization and regression is used to embed a binary genetic algorithm into the JRM for optimal joinpoint detection. The combinations of joinpoints were represented as binary chromosomes, and genetic operations were performed to determine the optimum solution by minimizing the fitness function, the Bayesian information criterion (BIC) and BIC3 . The accuracy and computational performance of the GAJP model were evaluated via intensive simulation studies and compared with those of the GS-based methods using BIC, BIC3 , and permutation test. The proposed method showed an outstanding computational efficiency in detecting multiple joinpoints. Finally, the suitability of the GAJP model for the analysis of cancer incidence trends was demonstrated by applying this model to data on the incidence of colorectal cancer in the United States from 1975 to 2016 from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Thus, the GAJP model was concluded to be practically feasible to detect multiple joinpoints up to the number of grids without requirement to preassign the number of joinpoints and be easily extendable to cancer trend analysis utilizing large datasets.

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery.

PURPOSE: In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT). METHODS: Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors. RESULTS: The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145-0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061-4.985). CONCLUSION: Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.

A systematic correlation analysis of carotenoids, chlorophyll, non-pigmented cell mass, and cell number for the blueprint of Dunaliella salina culture in a photobioreactor.

Microalgal carotenoids are attractive health ingredients, but their production should be optimized to improve cost-effectiveness. Understanding cellular physiology centered on carotenoid synthesis is the prerequisite for this work. Therefore, systematic correlation analyses were conducted among chlorophyll, carotenoids, non-pigmented cell mass, and cell number of Dunaliella salina in a specified condition over a relatively long culture time. First, an integrated correlation was performed: a temporal profile of the carotenoids was correlated with those of other factors, including chlorophyll, non-pigmented cell mass, and cell number. Pearson and Spearman correlation analyses were performed to identify linearity and monotonicity of the correlation, respectively, and then cross-correlation was executed to determine if the correlation had a time lag. Second, to understand the cellular potential of metabolism, the procedure was repeated to provide a data set composed of the specific synthesis rates of the factors or growth rate, which additionally provided kinetic correlations among the constituting components of the cell, excluding the effect of cell number. This systematic approach could generate a blueprint model that is composed of only what it needs, which could make it possible to efficiently control and optimize the process.

Promoter methylation of cysteine dioxygenase type 1: gene silencing and tumorigenesis in hepatocellular carcinoma.

BACKGROUNDS/AIMS: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the CDO1 methylation status and hepatocellular carcinoma (HCC) tumorigenesis was evaluated. METHODS: Using a HCC cell line (SNU423), an in vitro demethylation study was performed to confirm whether promoter methylation causes CDO1 down-regulation. The SNU423 cells transfected with the CDO1 cell function was compared to that of naïve cells. An in vivo study using immunohistochemical staining of HCC specimens that were collected from patients who underwent curative liver resection was also performed. RESULTS: CDO1 was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after CDO1 transfection (p<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of CDO1 (p=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of CDO1 expression was not an independent prognostic factor in this study's population. CONCLUSIONS: These results suggested that methylation down-regulated CDO1 expression in the HCC cells. CDO1 methylation may be a potentially valuable diagnostic biomarker for HCC.

Comparison of effects of intraoperative nefopam and ketamine infusion on managing postoperative pain after laparoscopic cholecystectomy administered remifentanil.

BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia and reduce the use of postoperative analgesics, it may cause opioid induced hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to determine whether intraoperative nefopam or ketamine, known being related on NMDA receptor, affects postoperative pain and OIH after continuous infusion of intraoperative remifentanil. METHODS: Fifty-four patients undergoing laparoscopic cholecystectomy were randomized into three groups. In the nefopam group (N group), patients received nefopam 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h. In the ketamine group (K group), patients received ketamine 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 3 µg/kg/min. The control group did not received any other agents except for the standard anesthetic regimen. Postoperative pain score, first time and number of demanding rescue analgesia, OIH and degrees of drowsiness/sedation scale were examined. RESULTS: Co-administrated nefopam or ketamine significantly reduced the total amount of intraoperative remifentanil and postoperative supplemental morphine. Nefopam group showed superior property over control and ketamine group in the postoperative VAS score and recovery index (alertness and respiratory drive), respectively. Nefopam group showed lower morphine consumption than ketamine group, but not significant. CONCLUSIONS: Both nefopam and ketamine infusion may be useful in managing in postoperative pain control under concomitant infusion of remifentanil. However, nefopam may be preferred to ketamine in terms of sedation.

Remote Ischemic Preconditioning for the Prevention of Contrast-Induced Acute Kidney Injury in Diabetics Receiving Elective Percutaneous Coronary Intervention.

OBJECTIVE: Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI. METHODS: This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m2 or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning. RESULTS: One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, p = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, p = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, p = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure. CONCLUSIONS: In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329444.

Inverse Problem for Color Doppler Ultrasound-Assisted Intracardiac Blood Flow Imaging.

For the assessment of the left ventricle (LV), echocardiography has been widely used to visualize and quantify geometrical variations of LV. However, echocardiographic image itself is not sufficient to describe a swirling pattern which is a characteristic blood flow pattern inside LV without any treatment on the image. We propose a mathematical framework based on an inverse problem for three-dimensional (3D) LV blood flow reconstruction. The reconstruction model combines the incompressible Navier-Stokes equations with one-direction velocity component of the synthetic flow data (or color Doppler data) from the forward simulation (or measurement). Moreover, time-varying LV boundaries are extracted from the intensity data to determine boundary conditions of the reconstruction model. Forward simulations of intracardiac blood flow are performed using a fluid-structure interaction model in order to obtain synthetic flow data. The proposed model significantly reduces the local and global errors of the reconstructed flow fields. We demonstrate the feasibility and potential usefulness of the proposed reconstruction model in predicting dynamic swirling patterns inside the LV over a cardiac cycle.

Size-Resolved Source Emission Rates of Indoor Ultrafine Particles Considering Coagulation.

Indoor ultrafine particles (UFP, <100 nm) released from combustion and consumer products lead to elevated human exposure to UFP. UFP emitted from the sources undergo aerosol transformation processes such as coagulation and deposition. The coagulation effect can be significant during the source emission due to high concentration and high mobility of nanosize particles. However, few studies have estimated size-resolved UFP source emission strengths while considering coagulation in their theoretical and experimental research work. The primary objective of this study is to characterize UFP source strength by considering coagulation in addition to other indoor processes (i.e., deposition and ventilation) in a realistic setting. A secondary objective is to test a hypothesis that size-resolved UFP source emission rates are unimodal and log-normally distributed for three common indoor UFP sources: an electric stove, a natural gas burner, and a paraffin wax candle. Experimental investigations were performed in a full-scale test building. Size- and time-resolved concentrations of UFP ranging from 2 to 100 nm were monitored using a scanning mobility particle sizer (SMPS). Based on the temporal evolution of the particle size distribution during the source emission period, the size-dependent source emission rate was determined using a material-balance modeling approach. The results indicate that, for a given UFP source, the source strength varies with particle size and source type. The analytical model assuming a log-normally distributed source emission rate could predict the temporal evolution of the particle size distribution with reasonable accuracy for the gas stove and the candle. Including the effect of coagulation was found to increase the estimates of source strengths by up to a factor of 8. This result implies that previous studies on indoor UFP source strengths considering only deposition and ventilation might have largely underestimated the true values of UFP source strengths, especially for combustion due to the natural gas stove and the candle.

Interparticle collision mechanism in turbulence.

Direct numerical simulations of particle-laden homogeneous isotropic turbulence are performed to investigate interparticle collisions in a wide range of Stokes numbers. Dynamics of the particles are described by Stokes drag including particle-particle interactions via hard-sphere collisions, while fluid turbulence is solved using a pseudospectral method. Particular emphasis is placed on interparticle-collision-based conditional statistics of rotation and dissipation rates of the fluid experienced by heavy particles, which provide essential information on the collision process. We also investigate the collision statistics of collision time interval and angle. Based on a Lamb vortex model for a vortex structure, we claim that collision events occur in the edge region for vortical structures in the intermediate-Stokes-number regime, suggesting that the sling effect enhances collision as well as clustering.

A Comparative Efficacy of Propacetamol and Ketorolac in Postoperative Patient Controlled Analgesia.

BACKGROUND: Ketorolac has been used as a postoperative analgesia in combination with opioids. However, the use of ketorolac may produce serious side effects in vulnerable patients. Propacetamol is known to induce fewer side effects than ketorolac because it mainly affects the central nervous system. We compared the analgesic effects and patient satisfaction levels of each drug when combined with fentanyl patient-controlled analgesia (PCA). METHODS: The patients were divided into two groups, each with n = 46. The patients in each group were given 60 mg of ketorolac or 2 g of propacetamol (mixed with fentanyl) for 10 minutes. The patients were then given 180 mg of ketorolac or 8 g of propacetamol (mixed with fentanyl and ramosetron) through PCA. We assessed the visual analogue pain scale (VAS) at the time point immediately before administration (baseline) and at 15, 30, and 60 minutes, and 24 hours after administration. Also, the side effects of each regimen and each patient's degree of satisfaction were assessed. RESULTS: There was a significant decline in the VAS score in both groups (P < 0.05). However, there were no significant differences in the VAS scores between the groups at each time point. Satisfaction scores between the groups showed no significant difference. CONCLUSIONS: The efficacy of propacetamol is comparable to that of ketorolac in postoperative PCA with fentanyl.

A Reconstruction Method of Blood Flow Velocity in Left Ventricle Using Color Flow Ultrasound.

Vortex flow imaging is a relatively new medical imaging method for the dynamic visualization of intracardiac blood flow, a potentially useful index of cardiac dysfunction. A reconstruction method is proposed here to quantify the distribution of blood flow velocity fields inside the left ventricle from color flow images compiled from ultrasound measurements. In this paper, a 2D incompressible Navier-Stokes equation with a mass source term is proposed to utilize the measurable color flow ultrasound data in a plane along with the moving boundary condition. The proposed model reflects out-of-plane blood flows on the imaging plane through the mass source term. The boundary conditions to solve the system of equations are derived from the dimensions of the ventricle extracted from 2D echocardiography data. The performance of the proposed method is evaluated numerically using synthetic flow data acquired from simulating left ventricle flows. The numerical simulations show the feasibility and potential usefulness of the proposed method of reconstructing the intracardiac flow fields. Of particular note is the finding that the mass source term in the proposed model improves the reconstruction performance.

Osteopontin levels in patients with papillary thyroid cancer according to the presence of Hashimoto's thyroiditis.

BACKGROUND: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. MATERIALS AND METHODS: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. CONCLUSIONS: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid Carcinoma Cells.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. METHODS: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-κB levels were assayed by Western blotting. RESULTS: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. CONCLUSION: We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-κB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.

Effects of rosiglitazone on inflammation in Otsuka long-evans Tokushima Fatty rats.

BACKGROUND: Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes. METHODS: We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-alpha, interleukin [IL]-1beta and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age). RESULTS: Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-kappaB expression in the skeletal muscle of OLETF rats. CONCLUSION: These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

Mathematical analysis of particle deposition in human lungs: an improved single path transport model.

A dynamic single-path mathematical model was developed that is capable of analyzing detailed deposition patterns of inhaled particles in human lungs. Weibel's symmetric lung morphology was adopted as the basic lung structure, and detailed transport processes were evaluated numerically using the fully implicit procedure. Deposition efficiencies by specific mechanisms were individually examined for accuracy and new empirical formulas were incorporated whenever appropriate. Deposition in the alveolar region was divided into deposition fractions in the alveolar duct and alveoli, considering active transport processes between the two regions. The deposition fractions were obtained for each airway generation, serial lung volumetric compartments, and conventional three-compartment anatomic lung regions. In addition, the surface dose and cumulative deposition with time were analyzed. The results showed excellent agreement with available experimental data. The present model provides an improvement from the previously reported models and can be used as a tool in assessing internal dose of inhaled particles under various inhalation conditions.

Intermittent nature of acceleration in near wall turbulence.

Using direct numerical simulation of a fully developed turbulent channel flow, we investigate the behavior of acceleration near a solid wall. We find that acceleration near the wall is highly intermittent and the intermittency is in large part associated with the near wall organized coherent turbulence structures. We also find that acceleration of large magnitude is mostly directed towards the rotation axis of the coherent vortical structures, indicating that the source of the intermittent acceleration is the rotational motion associated with the vortices that causes centripetal acceleration.