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Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be “fit for purpose” to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

Background Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. Case presentation: Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient’s symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. Conclusion These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Supplementary Table 1 from Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Supplementary Figure Legend from Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

Gene expression profiling indicates that the Sonic Hedgehog (Shh) pathway is active in ∼30% of human medulloblastomas, suggesting that it could provide a useful therapeutic target. Previously, we showed that spontaneous medulloblastomas in Ptc1+/−p53−/− mice could be eradicated by treatment with a small-molecule inhibitor (HhAntag) of Smoothened (Smo). Here, we compared the responses of mouse medulloblastoma cells propagated in flank allografts, either directly or after culture in vitro, to HhAntag. We found that Shh pathway activity was suppressed in medulloblastoma cells cultured in vitro and it was not restored when these cells were transplanted into the flank of nude mice. The growth of these transplanted tumor cells was not inhibited by treatment of mice with doses of HhAntag that completely suppressed Smo activity. Interestingly, tumor cells transplanted directly into the flank maintained Smo activity and were sensitive to treatment with HhAntag. These findings indicate that propagation of tumor cells in culture inhibits Smo activity in a way that cannot be reversed by transplantation in vivo, and they raise concerns about the use of cultured tumor cells to test the efficacy of Shh pathway inhibitors as anticancer therapies. (Cancer Res 2006; 66(8): 4215-22)

Supplementary Figure S1 from Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies

A microfluidic chip is a micro-reactor that precisely manipulates and controls fluids. Zein is a group of prolamines extracted from corn that can form self-assembled nanoparticles in water or a low concentration of ethanol in a microfluidic chip. However, the zein nanoparticles have stability issues, especially in a neutral pH environment due to the proximity of the isoelectric point. This study was designed 1) to evaluate the effect of octenyl succinic anhydride (OSA) modified starch on the stability of zein nanoparticles formed using a microfluidic chip and 2) to apply the zein-OSA starch for encapsulation of nisin and evaluate its anti-microbial activity in a model food matrix. A T-junction configuration of the microfluidic chip was used to fabricate the zein nanoparticles using 1% or 2% zein solution and 0-10% (w/w) of OSA starch solution. The stability of the nanoparticles in various ionic strength environments was assessed. Encapsulation efficiency and anti-microbial activity of nisin in the zein nanoparticles against

This chapter reviews the properties that contribute to the stability of microencapsulated ingredients and their effect on sensory properties. Special focus is given to factors that affect the wall and/or encapsulated core ingredients and how these factors can be measured to assess stability of the microcapsule. Additionally, basic physiology and methodologies in sensory science are reviewed. How these sensory basics are applied to microencapsulation research is shown through a variety of literature.

A gravity inversion technique using Deep Neural Networks (DNN) was developed to construct the 2D basement topography in offshore Abu Dhabi, UAE. Forward model parameters are set based on the geological features in the study area. Hundreds of thousands of synthetic forward models of the basement and their corresponding gravity anomalies are generated in a relatively short time by applying parallel computing. The simulated data are input to our DNN model which conducts the nonlinear inverse mapping of gravity anomalies to basement topography. To assess the model's robustness against noises, DNN models are retrained using datasets with noise-contaminated gravity data whose performances are evaluated by making predictions on unseen synthetic anomalies. Finally, we employed the DNN inversion model to estimate the basement topography using pseudo gravity anomalies over a profile in offshore UAE.

Disruption of intestinal integrity and barrier function due to tissue inflammation has negative implications on overall growth and well-being in young pigs. In this study, we investigated the effects of oral gamma-cyclodextrin-encapsulated tributyrin (TBCD) in young pigs experiencing dextran sodium sulfate (DSS)-induced colitis. Pigs (n = 32 boars) were weaned from the sow at postnatal day (PND) 2, allotted to treatment based on the litter of origin and body weight (BW), and reared artificially over a 26-d feeding period. Treatment groups included: 1) nutritionally adequate (control) milk replacer, no DSS (Control n = 8), 2) control milk replacer plus oral DSS (DSS, n = 7), and 3) control diet supplemented with 8.3 g of TBCD per kg of reconstituted milk replacer plus oral DSS (TBCD + DSS, n = 8). Colitis was induced by administering DSS at 1.25 g of DSS/kg BW daily in a reconstituted milk replacer from PND 14-18. Milk replacer and water were provided ad libitum throughout the 26-d study. All the data were analyzed using a one-way ANOVA using the MIXED procedure of SAS. Control and DSS pigs had similar BW throughout the study, while TBCD + DSS pigs exhibited decreased (P0.05) BW starting at approximately PND 15. Additionally, average daily gain (ADG) before and after initiation of DSS dosing, along with over the total study duration, was decreased (P0.05) in pigs receiving TBCD + DSS compared with the Control. Milk disappearance was decreased (P0.05) in TBCD + DSS pigs when compared with Control and DSS groups. Both the concentration and molar ratio of cecal butyrate concentrations were increased (P0.05) in TBCD + DSS pigs compared with the Control group. The DSS and TBCD + DSS treatments also increased (P0.05) butyrate concentrations in the luminal contents with the proximal colon compared with Control. TBCD + DSS and DSS pigs had increased (P0.05) mucosal width in the distal colon compared with Control, thereby indicating heightened intestinal inflammation. Overall, oral supplementation of encapsulated tributyrin increased the concentration of butyrate in the colon, but was unable to mitigate the negative effects of DSS-induced colitis.There are negative implications in young pigs when the integrity and function of the intestine are disrupted due to colonic inflammation. Volatile compounds have been used as dietary supplements to alleviate intestinal inflammation, but little work has been completed on the use of encapsulated tributyrin in newly weaned pigs. In this study, pigs received 1 of 3 treatments: 1) a standard milk replacer without the induction of intestinal inflammation, 2) the same standard milk replacer with the induction of intestinal inflammation, or 3) milk replacer supplemented with encapsulated tributyrin with the induction of intestinal inflammation. Throughout the study period, growth performance was decreased in pigs receiving supplemental tributyrin compared with other treatments. Additionally, experimentally induced colitis increased butyrate concentrations in the cecum, while tributyrin supplementation increased butyrate concentrations in the proximal colon. Pigs undergoing intestinal inflammation had increased thickness of the mucosal layer in the distal colon compared with sham-challenged pigs. Overall, the supplementation of encapsulated tributyrin increased colonic butyrate concentrations, but did not mitigate the negative effects of inflammation in the large intestine.

Successful sugar reduction in food products mimics the sensory and functional properties of the full sugar counterpart. The initial step of sugar reduction is to determine how the absence of sugar affects these properties. Descriptive analysis was conducted on four gel types (gelatin, ι-carrageenan, κ-carrageenan, and konjac glucomannan) and a range of sugar concentrations from 0–20% w/v to create a sensory profile of model confectionary gels for comparison to instrumental texture profile analysis data. The sensory descriptive data were analyzed using analysis of variance and principal component analysis. Correlation analysis, cluster analysis, and partial least squares regression (PLS-R) were used to compare and correlate sensory and instrumental data. Regardless of sugar concentration, sensory analysis primarily clustered samples by gelling agent type, such as in the case of konjac glucomannan consistently being characterized as chewy. Cohesion and gumminess were correlated highly with melt-in-mouth and a jiggly texture, while adhesion and fracturability were negatively correlated. In the PLS-R samples biplot, gelatin and iota carrageenan samples were located near these attributes indicating their aptness as descriptors. In conclusion, descriptive analysis provided a more discriminating method for characterizing model confectionary gels.

This article proposes a framework for service storytelling by analyzing its key elements with Aristotle's Poetics and synthesizing them using the temporal structure of Joseph Campbell's Hero's Journey. Poetics refer to the art of making that is concerned with the general pattern of human experience. We use this framework to study the four causes of storytelling: material cause, efficient cause, formal cause, and end cause. The Hero's Journey is a cyclical model that encompasses both an ordinary and a special world. We utilize this model to synthesize the four causes into a phasic flow, including deficiency, growth, personalization, and transformation.

The skin is the largest organ in the human body, providing a barrier to the external environment. It is composed of three layers: epidermis, dermis and hypodermis. The most external epidermis is exposed to stress factors that may lead to skin conditions such as photo-aging and skin cancer. Some treatments for skin disease utilize the incorporation of drugs or bioactive compounds into nanocarriers known as liposomes. Liposomes are membranes whose sizes range from nano to micrometers and are composed mostly of phospholipids and cholesterol, forming similar structures to cell membranes. Thus, skin treatments with liposomes have lower toxicity in comparison to traditional treatment routes such as parenteral and oral. Furthermore, addition of edge activators to the liposomes decreases the rigidity of the bilayer structure making it deformable, thereby improving skin permeability. Liposomes are composed of an aqueous core and a lipidic bilayer, which confers their amphiphilic property. Thus, they can carry hydrophobic and hydrophilic compounds, even simultaneously. Current applications of these nanocarriers are mainly in the cosmetic and pharmaceutic industries. Nevertheless, new research has revealed promising results regarding the effectiveness of liposomes for transporting bioactive compounds through the skin. Liposomes have been well studied; however, additional research is needed on the efficacy of liposomes loaded with bioactive peptides for skin delivery. The objective of this review is to provide an up-to-date description of existing techniques for the development of liposomes and their use as transporters of bioactive compounds in skin conditions such as melanoma and skin inflammation. Furthermore, to gain an understanding of the behavior of liposomes during the process of skin delivery of bioactive compounds into skin cells.

Butyrate is a short-chain fatty acid (SCFA) known for support in gastrointestinal (GI) health. Tributyrin (TB) could be used as an alternate source of butyrate. The objectives of this study were to encapsulate TB using gamma-cyclodextrin (CD) by spray-drying and to investigate the physicochemical and the fermentation properties of TB/CD complex. The TB/CD complex precipitated in water with an average stoichiometry of 1:1.3 of TB:CD. At a 1:2 molar ratio of TB:CD, TB was fully retained in the spray-dried TB/CD complex. The spray-dried TB/CD complex showed crystalline structure, supported by both X-ray diffraction spectra and scanning electron microscopy images. The TB/CD complex at 1:2 molar ratio was fermented and several SCFAs, including butyrate, were produced in an in vitro test using piglets' ileal and colonic contents. A dose-dependent increase in the butyrate concentration in both ileum and ascending colon was observed. Approximately, 426 and 1189 μmole butyrate was produced per gram of TB/CD powder at 9 mM treatment in ileum and ascending colon, respectively. Thus, the production of the TB/CD complex using spray drying is feasible and the complex has the potential for food applications to improve intestinal health. PRACTICAL APPLICATION: The findings in this study can be applied to produce encapsulated tributyrin with gamma-cyclodextrin efficiently using spray-drying. The TB/CD complex was highly fermentable and caused an increase in the butyrate concentration in both ileum and ascending colon, which can be incorporated in foods to enhance butyrate delivery to the GI tract to assist gut health.

Genomic instability resulting from defective DNA damage responses or repair causes several abnormalities, including progressive cerebellar ataxia, for which the molecular mechanisms are not well understood. Here, we report a new murine model of cerebellar ataxia resulting from concomitant inactivation of POLB and ATM. POLB is one of key enzymes for the repair of damaged or chemically modified bases, including methylated cytosine, but selective inactivation of Polb during neurogenesis affects only a subpopulation of cortical interneurons despite the accumulation of DNA damage throughout the brain. However, dual inactivation of Polb and Atm resulted in ataxia without significant neuropathological defects in the cerebellum. ATM is a protein kinase that responds to DNA strand breaks, and mutations in ATM are responsible for Ataxia Telangiectasia, which is characterized by progressive cerebellar ataxia. In the cerebella of mice deficient for both Polb and Atm, the most downregulated gene was Itpr1, likely because of misregulated DNA methylation cycle. ITPR1 is known to mediate calcium homeostasis, and ITPR1 mutations result in genetic diseases with cerebellar ataxia. Our data suggest that dysregulation of ITPR1 in the cerebellum could be one of contributing factors to progressive ataxia observed in human genomic instability syndromes.

In response to health concerns generated by increased sodium intake, many new approaches have been studied to reduce the sodium content in processed food. It has been suggested that reducing sodium in the food supply may be the most appropriate solution. The aim of this scoping review was to establish what sodium reduction strategies are effective in maintaining acceptable sensory qualities for various food industry applications. Studies that evaluate and report on the effectiveness of a sodium reduction strategy relevant to food and included outcomes detailing how the strategies were received by human subjects using sensory data are included, as well as book chapters, literature reviews, and patents focusing on sodium reduction strategies. Only those published in English and since 1970 were included. Literature was obtained through Scopus, PubMed, EBSCOhost, and ScienceDirect databases, whereas patents were obtained through US Patent Trademark Office, Google Patents, and PATENTSCOPE databases. Two-hundred and seventy-seven primary studies, 27 literature reviews, 10 book chapters, and 143 patents were selected for inclusion. Data extracted included details such as analytical methods, broad and specific treatment categories, significant outcomes, and limitations among other material. Sodium reduction methods were categorized as either salt removal, salt replacement, flavor modification, functional modification, or physical modification. Although salt removal and salt replacement were the majority of included studies, future research would benefit from combining methods from other categories while investigating the impact on sensory characteristics, technological aspects, and consumer perception of the strategy.

Real-world evidence on the effectiveness of maintenance and reliever therapy (MART) using inhaled corticosteroids plus long-acting beta-2 agonist (ICS-LABA) is sparse.This study aimed to evaluate the clinical effectiveness of MART (ICS-formoterol) by comparing its effectiveness with that of ICS-LABA plus as-needed short-acting beta-2 agonist (SABA) in adult asthmatics.We retrospectively retrieved data from the medical records of the Ajou University Medical Center, Korea, to compare clinical outcomes between patients treated with MART (the MART group) and those treated with ICS-LABA plus SABA (the non-MART group). Propensity score matching was performed and hazard ratios (HRs) with 95% confidence intervals were calculated using the Cox proportional hazards model. Severe asthma exacerbation (SAEx) was the primary end point, and asthma exacerbation (AEx), hospitalization, and pneumonia were secondary end points. Corticosteroid requirement was also analyzed.After propensity score matching, the MART and the non-MART groups included 231 and 512 adult asthmatics, respectively. The risk of SAEx and AEx was significantly lower in the MART group than in the non-MART group (HR [95% CI] 0.39 [0.18-0.77] and 0.61 [0.37-0.99], respectively). There was no significant difference in hospitalization and pneumonia risk between the 2 groups (HR [95% CI] 0.88 [0.55-1.37] and 0.63 [0.03-4.51], respectively). Corticosteroid requirements were lower in the MART group than in the non-MART group (median [interquartile range], 190.0 [97.9-420.0] and 411.0 [143.0-833.0] mg/person-year, respectively; P.01).The MART strategy of ICS-formoterol was associated with lower risk of AEx and reduced corticosteroid requirement.

Background Evaluation of interstitial lung disease (ILD) at CT is a challenging task that requires experience and is subject to substantial interreader variability. Purpose To investigate whether a proposed content-based image retrieval (CBIR) of similar chest CT images by using deep learning can aid in the diagnosis of ILD by readers with different levels of experience. Materials and Methods This retrospective study included patients with confirmed ILD after multidisciplinary discussion and available CT images identified between January 2000 and December 2015. Database was composed of four disease classes: usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia, and chronic hypersensitivity pneumonitis. Eighty patients were selected as queries from the database. The proposed CBIR retrieved the top three similar CT images with diagnosis from the database by comparing the extent and distribution of different regional disease patterns quantified by a deep learning algorithm. Eight readers with varying experience interpreted the query CT images and provided their most probable diagnosis in two reading sessions 2 weeks apart, before and after applying CBIR. Diagnostic accuracy was analyzed by using McNemar test and generalized estimating equation, and interreader agreement was analyzed by using Fleiss κ. Results A total of 288 patients were included (mean age, 58 years ± 11 [standard deviation]; 145 women). After applying CBIR, the overall diagnostic accuracy improved in all readers (before CBIR, 46.1% [95% CI: 37.1, 55.3]; after CBIR, 60.9% [95% CI: 51.8, 69.3]

Receptor-interacting protein kinase 3 (RIPK3) is the primary regulator of necroptotic cell death. RIPK3 expression is often silenced in various cancer cells, which suggests that it may have tumor suppressor properties. However, the exact mechanism by which RIPK3 negatively regulates cancer development and progression remains unclear. This report indicates that RIPK3 acts as a potent regulator of the homeostatic proliferation of CD4

Crossfield is located in the province of Alberta in Canada and is one of the most well-known reservoirs of hydrocarbons. Since the 1950s, there has been continuous exploitation of more than 10 formations such as Cardium, Viking, Ellerslie, Elkton, Shunda, and Wabamun. Because of its location near the Foothills, the southwestern part of the Western Canada Sedimentary Basin, the Crossfield area has a complex geology and relatively deeper reservoirs, therefore requiring an in-depth examination of each formation. In this study, geological, technical, and economic analyses were performed on each formation within the 10 sections of the study lands in the Crossfield area. As the result of the study, there was potential for drilling 48 horizontal wells in the Cardium A zone and the Viking formation. In addition, it turned out to be economically feasible even at the WTI price of 60 dollars per barrel considering Alberta’s Royalty Framework, which is determined by the production rate and the price of oil, and the Horizontal Oil New Well Royalty Rate feature. A further study is required to investigate the exploitation potential of the Cardium B zone, the Ellerslie, and the Elkton formations in this area.

Disruption of intestinal integrity and function due to inflammatory mediators in young pigs has economic implications for swine producers. In this study, we investigated the effects of oral gamma-cyclodextrin-encapsulated tributyrin (TBCD) in young pigs experiencing dextran sodium sulfate (DSS)-induced colitis. Pigs (n = 32 boars) were weaned at postnatal day (PND) 2, allotted to treatment based on litter of origin and body weight (BW), and reared artificially over a 28-d period. Treatment groups included: 1) control (nutritionally adequate milk replacer, no DSS), 2) DSS (control diet plus oral DSS), and 3) DSS+TBCD (control diet supplemented with 8.3g of TBCD per kg reconstituted milk replacer plus oral DSS). Colitis was induced by orally administering DSS at 1.25 g/kg BW/d from PND 14-18. Milk replacer and water were provided ad libitum throughout the study. At study conclusion, pigs were euthanized for collection of samples to measure intestinal morphology and volatile fatty acids. All data were analyzed by ANOVA using the MIXED procedures of SAS. Control and DSS pigs had similar BW throughout the study, while DSS+TBCD pigs exhibited decreased (P < 0.05) BW starting around PND 15. Additionally, BW gain was decreased (P < 0.05) in DSS+TBCD compared with control, and milk disappearance was decreased (P < 0.05) in DSS+TBCD when compared with control and DSS. Relative cecal butyrate was increased (P < 0.05) in DSS+TBCD pigs, compared with the control. DSS and DSS+TBCD treatments had increased (P < 0.05) absolute butyrate in the ascending colon compared with the control. Mucosal width and total lesion scores were responsive to treatment, with DSS+TBCD pigs exhibiting increased (P < 0.05) values in the ascending and descending colon compared with control. Overall, the negative effects of DSS-induced colitis were not mitigated by dietary encapsulated tributyrin in young pigs.

In this paper, we propose a new load balancing algorithm for function-as-a-service (FaaS) platforms. We argue that the load balancing algorithm greatly affects the performance of FaaS platforms because heavy operations, such as virtualization and initialization, can be reduced using caching techniques. We demonstrate that a load balancing algorithm that provides higher locality could accelerate the FaaS platforms by increasing the cache-hit ratio, and propose a greedy load balancing algorithm optimized for FaaS. To generalize the experimental results, we conducted the experiment under three different caching policies that could be adopted in various FaaS platforms. Our evaluation reveals that load balancing algorithms with higher locality and a uniform load balance exhibit better results in all three caching policies, and our proposed algorithm achieves better performance compared to the state-of-the-art algorithms.

This study presents the correlation analysis between pore size distribution and diffusion coefficient based on the experimental results to evaluate the effect of pore size distribution on the acid-rock reaction in carbonate acidizing. The mercury injection capillary pressure (MICP) was used to analyze the pore size distribution of four limestone samples. Also, the acid-rock reaction experiments were conducted to measure diffusion coefficients using rotating disk apparatus (RDA). In the experimental results, micropore dominated rock samples have lower dissolution rate and diffusion coefficient than macropore dominated rock samples. It is obviously revealed that the dissolution rate and diffusion coefficient for limestone samples with similar mineral compositions are quite different due to various pore size distribution. In the result of correlation analysis, it is revealed that neither porosity nor permeability exhibits a strong correlation with diffusion coefficient compared with pore size distribution. Therefore, it can imply that the petro-physical properties such as porosity and permeability have a lower relevance to the acid-rock reaction kinetics than pore size distribution. To investigate the effect of pore size distribution on matrix acidizing, optimum injection rates were derived by the experimental results. As a result, the optimum injection rates increase with the mean and median pore size, and the micropore dominated rock samples show lower optimum injection rate than the macropore dominated rock samples. Although the pore size distribution shows a strong correlations with matrix acidizing, the optimum injection rate has been estimated without ample considerations of pore size distribution. Therefore, the effect of pore size distribution on diffusion coefficient should be considered to design the optimum injection conditions in carbonate acidizing job.

Nisin-loaded zein microcapsules were prepared in a microfluidic chip using an internal phase separation method. The release profiles of nisin from the microcapsules were modified by varying nisin loading and flow rate during the microfluidic process. Rapid release of nisin was achieved with low flow rate in dispersed phase (0.2 ml/h) and high loading (9.67–12.64 μg/mg) of nisin in the microcapsule, while slow release of nisin was achieved with high flow rate in dispersed phase (0.3 ml/h) and low loading of nisin (5.94 μg/mg) in the microcapsule. When tested in fresh cheese, all treatments with the nisin loaded zein microcapsules achieved overall lower viable Listeria cell counts relative to the treatment with free nisin, notably at early cheese storage. After 3 days of cold storage, the microcapsules with high flow rate and low nisin load reduced the initial viable population of L. monocytogenes by approximately 1 Log CFU/g, and the high nisin load capsules exhibited a reduction of approximately 0.5 Log CFU/g of the pathogen. Although subsequent regrowth of L. monocytogenes was observed after 7 days of cold storage for all the encapsulated nisin treatments, the high flow rate and low load microcapsules maintained the greatest difference in L. monocytogenes counts, approximately 2 Log CFU/g, compared to the untreated cheese. The cheese with the high flow rate and high load microcapsules was least effective on controlling L. monocytogenes. Nano-FTIR spectrum suggested that the distribution of nisin in the zein microcapsule was homogeneous, which indicates that a co-assembly of zein and nisin occurred during the internal phase separation process.

Background Microfluidic process is an emerging technique that can be applied to fabricate functional delivery systems with a precise control. Assembling food-grade delivery systems using microfluidic platforms is gaining more and more interest. Synthetic polymers have been extensively studied for microfluidic assembly as wall materials, while very few of them are food-grade materials. In the past decade, several food-grade biopolymers were found as feasible materials for microfluidic assembly. This review will summarize the recent advances in microfluidic process in which food-grade materials were successfully utilized to fabricate various delivery systems. Scope and approach In this review, the significance of controlled delivery in food-related applications is addressed. Using a microfluidic device, controlled delivery can be achieved by the accurate structural design and the precise production of the delivery systems. An introduction of microfluidic devices is presented, including mechanisms, basic principles in physics, and chip designs. Previous studies that used food-grade materials to fabricate delivery systems in microfluidic devices are summarized, categorized and discussed. Current hurdles and future directions are implied. Key findings and conclusions The principles of microfluidic systems and categorized five common delivery matrices with food-grade or nonfood-grade materials are discussed. Various food-grade materials showing great potential in microfluidic process, such as lipids and carbohydrates, are introduced. Scalability and reliability have always been issues toward the mass production using microfluidics and a few solutions are discussed. Additional studies focusing on prevention of clogging during a microfluidic production are needed, especially when biomaterials are used.

PURPOSE OF REVIEW The aim of this review is to emphasize the role of neutrophils in patients with occupational asthma. This review facilitates a better understanding, accurate diagnosis, and proper management of asthmatic reactions provoked at the workplace. RECENT FINDINGS Increased recruitment and infiltration of neutrophils are found in patients with occupational asthma. Activated neutrophils release several mediators including pro-inflammatory cytokines and extracellular traps, leading to stimulation of airway epithelium and other inflammatory cells. SUMMARY New insights into neutrophils in the pathogenesis of occupational asthma may provide a novel approach to the individual patient with occupational asthma.

Wrinkled microcapsules have attracted great interest due to their distinguished features, including enhanced adhesion propensity and release profiles. These features could be beneficial for food-related applications and improve the bioavailability of encapsulated compounds by promoting their attachment to epithelium. However, the fabrication of such microcapsules with food-grade materials has been met with limited success. In this study, a facile approach to produce wrinkled microcapsules using a food-grade protein, zein, is proposed. Internal phase separation was used to form zein microcapsules and three acids (phytic acid, citric acid, and succinic acid) were incorporated at two concentration levels (10 mM and 20 mM) to modify the secondary structure of zein in the microcapsules. The results showed that the mechanical properties of the microcapsules, which were characterized by nanoindentation, were greatly dependent on the protein secondary structure, particularly the α-helix structure. The morphology of the microcapsules was evaluated by image analysis. An extensive wrinkle was observed on the surfaces of the microcapsules with high viscoplasticity. Among the three acids used in this study, phytic acid significantly increased the degree of wrinkling and viscoplasticity of the microcapsules. Further characterization with circular dichroism and wide-angle X-ray scattering suggested that a less ordered zein secondary structure was formed in the samples prepared using phytic acid than in those prepared using other acids or without acid, which further supports the hypothesis that the nanomechanical properties and degree of wrinkling are associated with the protein secondary structures.

Background Mast cells are a key effector cell in the pathogenesis of chronic spontaneous urticaria (CSU) and activated by circulating FcεRI-specific IgG as well as IgE. This study evaluated the prevalence of circulating autoantibodies to FcεRIα in the sera of CSU patients. Methods Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled. To detect circulating autoantibodies (IgG/IgA/IgM) to FcεRIα, ELISA was done using YH35324 (as a solid phase antigen), and its binding specificity was confirmed by the ELISA inhibition test. The antibody levels were presented by the ratio of YH35324-preincubated to mock-preincubated absorbance values. Clinical and autoimmune parameters, including atopy, urticaria activity score (UAS), serum total/free IgE levels, serum antinuclear antibody (ANA) and autologous serum skin test (ASST) results, were assessed. The autoimmune group was defined if CSU patients had positive results to ASST and/or ANA. Results The ratio of serum IgG to FcεRIα was significantly lower in CSU patients than in HCs (P<0.05), while no differences were noted in serum levels of IgG to recombinant FcεRIα or IgA/IgM autoantibodies. The autoimmune CSU group had significantly lower ratios of IgG/IgA (not IgM) autoantibodies to FcεRIα than the nonautoimmune CSU group (P Conclusions This study confirmed the presence of IgG to FcεRIα in the sera of CSU patients, especially those with the autoimmune phenotype.

This study experimentally investigated the impact of CO2 miscible flooding on oil recovery and alteration of rock properties in two carbonate cores consisting of more than 98% calcite: Edwards white representing a homogenous medium mainly consisted of micropores, and Indiana limestone representing a heterogeneous medium mostly composed of macropores. Several methods were applied to investigate the alteration of rock properties by CO2-water-carbonate minerals interactions: 1) Core flooding to measure overall changes, 2) MICP and X-ray CT to analyze small pores and large pores, respectively, 3) SEM, PCM, and ICP to verify physical and chemical reactions. Oil recovery was higher in Edwards white than in Indiana limestone, since characteristic of Edwards white contributes to sufficient contact time and stable displacement between oil and CO2. From the analysis of the alteration of rock properties in homogenous sample, dissolution facilitates the enlargement of pore sizes. Therefore, fluid flow becomes more favorable. The precipitation is not critical determinant of alteration process, despite the high proportion of small pores. For heterogeneous sample, both dissolution and precipitation significantly affect to alteration of pore structure. Particularly, the precipitation seriously damaged to the main flow channels. These undesirable effects on fluid flow appeared at injection point, which was exposed to fresh CO2 for a long time. This study suggests that pore structure analysis allows a more exact interpretation and judgment of the alteration of pore structure by dissolution and precipitation and can assist in designing injection plans, particularly near the injection area or in complex pore structure.

It has been known that a high serum total immunoglobulin E (IgE) level is a predisposing factor of allergic asthma; however, there are considerable limitations to apply it in clinical practice.To determine the clinical significance of the serum-free IgE level in patients with adult asthma.We measured free IgE levels using our homemade enzyme-linked immunosorbent assay by applying a novel IgE TRAP protein (GI innovation, Seoul, Republic of Korea) in sera of adults with asthma (n = 116) compared with healthy controls (n = 32); enzyme-linked immunosorbent assay inhibition test was performed to validate its binding specificity. Associations between asthma-related clinical and laboratory parameters were analyzed. The diagnostic value and cutoff point for detecting atopy and type 2 asthma were determined using receiver operating characteristic curve analysis.The serum-free IgE levels were significantly higher in adults with asthma than in healthy controls and were significantly associated with atopic status and type 2 asthma (all P.001). In the receiver operating characteristic analysis, serum-free IgE had a significantly greater area under the curve (AUC) than serum total IgE for assessing asthma, especially type 2 asthma (AUC, 0.810 vs 0.743; P = .006 and AUC, 0.729 vs 0.572; P.001). The optimal cutoff points for predicting atopy and type 2 asthma were 82.8 and 120.8 ng/mL, respectively.It is suggested that a higher serum-free IgE level may be a useful biomarker of atopy and type 2 asthma in adults with asthma.

Modern image files are usually progressively transmitted and provide a preview before downloading the entire image for improved user experience to cope with a slow network connection. In this paper, with a similar goal, we propose a progressive transmission framework for deep learning models, especially to deal with the scenario where pre-trained deep learning models are transmitted from servers and executed at user devices (e.g., web browser or mobile). Our progressive transmission allows inferring approximate models in the middle of file delivery, and quickly provide an acceptable intermediate outputs. On the server-side, a deep learning model is divided and progressively transmitted to the user devices. Then, the divided pieces are progressively concatenated to construct approximate models on user devices. Experiments show that our method is computationally efficient without increasing the model size and total transmission time while preserving the model accuracy. We further demonstrate that our method can improve the user experience by providing the approximate models especially in a slow connection., Comment: 6 pages, 8 figures

Microfluidics has been studied as a rapid detection tool for food safety related applications for a long time. Recently, more and more interests have been attracted to use microfluidics as microreactors to assemble biopolymers to achieve desirable functionalities. Attributed to the accurate flow control and unique bottom-up mechanism, the properties of the assembled biopolymer structures could be well-controlled. To date, several food-grade biopolymers, including proteins and carbohydrates, have been found suitable for the microfluidic process. However, challenges remain, notably the scale-up of the process. In this chapter, the fundamental principles of microfluidics and their feasibility to process food materials and design food structures are thoroughly covered and discussed.