Feedback linearization control for uncertain nonlinear systems via generative adversarial networks.

This article presents a novel approach to leverage generative adversarial networks(GANs) techniques to learn a feedback linearization controller(FLC) for a class of uncertain nonlinear systems. By estimating uncertainty through the adversarial process, where ground truth samples are exclusively obtained from a predefined integral model, the feedback linearization controller, learned through a minimax two-player optimization framework, enhances the reference tracking performance of the input-output uncertain nonlinear system. Furthermore, we provide theoretical guarantee of convergence and stability, demonstrating the safe recovery of robust FLC. We also address the common challenge of mode collapse in GANs training through the strict convexity of our synthesized generator structure and an enhanced adversarial loss. Comprehensive simulations and practical experiments are conducted to underscore the superiority and efficacy of our proposed approach.

Homogeneous and heterogeneous atmospheric ozonolysis of chlorobenzene:Mechanism, kinetics and ecotoxicity assessment.

The reactions between chlorobenzene(CB) and ozone have been studied comprehensively in this paper. Chlorobenzene is a commonly found chlorinated aromatic volatile organic compound(VOC), and its emission into the atmosphere can cause harm to the ecosystem and human health. The frequent occurrence of mineral particles from sandstorms exerts a significant influence on the atmospheric chemistry of the troposphere. Mineral particles are abundant in SiO2 and Al2O3 content. Therefore, we investigated the homogeneous and heterogeneous reaction processes of CB and ozone in the atmosphere by using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The atmospheric fate, reaction rate and toxicity evaluation of CB ozonation were studied in the gas-phase section. Toxicity evaluation results showed that ozonation of CB could effectively reduce its toxicity. For the heterogeneous process, we simulated three types of SiO2 clusters and nine types of (Al2O3)n clusters, and studied the configurations of CB adsorbed on the cluster surfaces. We found that adsorption of CB on the SiO2 clusters was achieved through hydrogen bonding, while adsorption of CB on the Al2O3 clusters was achieved through both hydrogen bonding and metal bonding. The energy for CB adsorption on the (Al2O3)n cluster surface was higher than that for the SixOy(OH)z cluster surface, and both types of clusters exhibited efficient adsorption of CB. As the SixOy(OH)z clusters grew larger, the rates for the reactions between O3 and CB increased. CB travelled long distances along the Al2O3 clusters, leading to an extended influence range.

Pharmacotherapy for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.

Preparation of g-C3N4/TCNQ Composite and Photocatalytic Degradation of Pefloxacin.

g-C3N4 and g-C3N4/TCNQ composites with different doping levels were prepared using the copolymerization thermal method with melamine as a precursor. XRD, FT-IR, SEM, TEM, DRS, PL, and I-T characterized them. The composites were successfully prepared in this study. The photocatalytic degradation of pefloxacin (PEF), enrofloxacin (ciprofloxacin), and ciprofloxacin (ciprofloxacin) under visible light (λ > 550 nm) showed that the composite material had the best degradation effect on PEF. When TCNQ doping is 20 mg and catalyst dosage is 50 mg, the catalytic effect is the best, and the degradation rate reaches 91.6%, k = 0.0111 min-1, which is four times that of g-C3N4. Repeated experiments found that the cyclic stability of the g-C3N4/TCNQ composite was good. The XRD images were almost unchanged after five reactions. The radical capture experiments revealed that ·O2- was the main active species in the g-C3N4/TCNQ catalytic system, and h+ also played a role in PEF degradation. And the possible mechanism for PEF degradation was speculated.

PSS-dispersed dopamine triggered formation of PAA adhesive hydrogel as flexible wearable sensors.

Catechol-based hydrogels have good adhesion properties; however, since the concentration of catechol is low and it can be easily oxidized to quinone, the adhesion performance of the hydrogels is reduced, which limits their application as self-adhesive flexible wearable sensors. In this work, a dopamine: poly(sodium 4-styrenesulfonate) (DA:PSS)-initiated strategy was proposed to construct adhesive hydrogels, where the semiquinone radicals present in DA:PSS were used to initiate radical polymerization to obtain the DA:PSS/poly(acrylic acid) (DA:PSS/PAA) hydrogel. This hydrogel exhibited good stretchability and adhesion with various substrates. We observed that, even after exposure to air for 21 days under certain relative humidity (76%), the catechol groups hardly oxidized and the DA:PSS/PAA hydrogel presented good adhesion. The DA:PSS/PAA hydrogel also showed good electrical conductivity and fast response ability. Thus, the general strategy of triggering monomer polymerization to form hydrogels based on the semiquinone radical present in DA:PSS offers great potential for their application in flexible electronic devices and wearable sensors.

Surface Defect Detection System for Carrot Combine Harvest Based on Multi-Stage Knowledge Distillation.

Carrots are a type of vegetable with high nutrition. Before entering the market, the surface defect detection and sorting of carrots can greatly improve food safety and quality. To detect defects on the surfaces of carrots during combine harvest stage, this study proposed an improved knowledge distillation network structure that took yolo-v5s as the teacher network and a lightweight network that replaced the backbone network with mobilenetv2 and completed channel pruning as a student network (mobile-slimv5s). To make the improved student network adapt to the image blur caused by the vibration of the carrot combine harvester, we put the ordinary dataset Dataset (T) and dataset Dataset (S), which contains motion blurring treatment, into the teacher network and the improved lightweight network, respectively, for learning. By connecting multi-stage features of the teacher network, knowledge distillation was carried out, and different weight values were set for each feature to realize that the multi-stage features of the teacher network guide the single-layer output of the student network. Finally, the optimal lightweight network mobile-slimv5s was established, with a network model size of 5.37 MB. The experimental results show that when the learning rate is set to 0.0001, the batch size is set to 64, and the dropout is set to 0.65, the model accuracy of mobile-slimv5s is 90.7%, which is significantly higher than other algorithms. It can synchronously realize carrot harvesting and surface defect detection. This study laid a theoretical foundation for applying knowledge distillation structures to the simultaneous operations of crop combine harvesting and surface defect detection in a field environment. This study effectively improves the accuracy of crop sorting in the field and contributes to the development of smart agriculture.

Palatal hybrid surgery for obstructive sleep apnea-state-of-the-art annotation of uvulopalatopharyngoplasty.

BACKGROUND: Surgery for obstructive sleep apnea (OSA) has changed in concept and technique that transformed from radical excision to functional reconstruction. The aim of this study was to investigate the safety and effectiveness of palatal hybrid surgery in OSA patients. METHODS: Palatal hybrid surgery is a tissue-specific technique (mucosa-preservation, tonsil-excision, fat-ablation, muscle-relocation/suspension) used in treating OSA patients with velopharyngeal obstruction. The study included 46 consecutive adults OSA patients. The palatal hybrid surgery annotates uvulopalatopharyngoplasty in stereoscopic reconstruction of tonsillar fossa (pharyngoplasty), omni-suspension of the soft palate (palatoplasty) and advancement of uvula (uvuloplasty). RESULTS: No patient experienced airway compromise, voice change or persistent nasal regurgitation following palatal hybrid surgery. One patient existed postoperative tonsillar fossa bleeding received conservative treatment. Postoperative pain in visual analogue scale (VAS) showed average score of 3, 3, 2, 0 at the 1st, 3rd, 7th, 14th day, respectively. Perioperative snoring severity (VAS) (8.7 vs 2.6) and daytime sleepiness (Epworth Sleepiness Scale) (11.3 vs 5.5) all improved significantly (p < 0.001). Posterior air space in retropalatal area increased from 8.4 to 11.1 mm (p < 0.001). Home sleep test showed that apnea-hypopnea index significantly reduced from 41.8 to 18.2 event/h and minimal oxygen saturation increased from 72.4 to 81.5% (p < 0.001). The success rate in individual Friedman stage was 100% (stage I), 63% (stage II) and 58% (stage III) with a total success rate of 63%. CONCLUSION: Palatal hybrid surgery using tissue-specific maneuver annotates UPPP in concept and technique. The results show that palatal hybrid surgery is mini-invasive with low morbid and is effective in improving subjective clinic symptoms, objective sleep parameters and success rate of OSA.

Combined Airway and Bariatric Surgery (CABS) for Obstructive Sleep Apnea Patients with Morbid Obesity: A Comprehensive Alternative Preliminary Study.

Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive technique­combined airway and bariatric surgery (CABS)­to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea−hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgery­LSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p < 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.

Transoral Tongue Suspension for Obstructive Sleep Apnea-A Preliminary Study.

Objectives: To evaluate the safety and efficacy of a novel technique for transoral tongue suspension (TOTS) in obstructive sleep apnea (OSA) patients. Material and Methods: The retrospective study enrolled 24 consecutive OSA patients (21 males; average age, 43 years; average apnea−hypopnea index (AHI), 42.2 event/h; average body mass index (BMI), 25.7 kg/m2) with tongue obstruction confirmed by drug-induced sleep endoscopy. All patients received TOTS as the main procedure in conjunction with uvulopalatopharyngoplasty (UPPP). Key procedures of TOTS included a transoral sublabial approach, drilling two holes on the mandible, passing the polypropylene through the hole to the tongue base using a suture passer and returning the polypropylene through loop traction, and tying the polypropylene to the mandible. Lingual tonsil ablation (n = 8) was also implemented in hypertrophic lingual tonsils (grades III and IV). Results: The operation time for TOTS was around 30 min. No wound bleeding or airway compromise occurred throughout the postoperative period. Minor complications were temporary and included swelling of the tongue, numbness of the lower incisor, and sublabial wound dehiscence (n = 2). The quality of life improved significantly in the patients' subjective daytime sleepiness according to the Epworth Sleepiness Scale (11.4 ± 3.2 vs. 5.7 ± 1.6, p < 0.001). The objective parameters of OSA also improved significantly in the apnea/hypopnea index (42.2 ± 21.8 vs. 19.5 ± 16.2, p < 0.001), minimal oxygen saturation (77.1 ± 12.2 vs. 81.7 ± 8.1, p = 0.026), and snoring index (207 ± 141 vs. 101 ± 91, p = 0.03). Conclusions: The demonstrated TOTS showed its advantage in low morbidity with a scarless exterior and easy performance with free availability in treating adult OSA patients with tongue obstruction. TOTS combined with UPPP significantly improved AHI and daytime sleepiness. TOTS can be implemented with lingual tonsillectomy to achieve both stabilization of the tongue and widening of hypopharyngeal airway.

The Impact of Mouth-Taping in Mouth-Breathers with Mild Obstructive Sleep Apnea: A Preliminary Study.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. METHOD: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A "responder" was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. RESULTS: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = -0.52, p = 0.02), oxygen desaturation index (ODI) (r = -0.54, p = 0.01), and SI (r = -0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = -0.77, p = 0.001). CONCLUSIONS: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.

Imaging features of primary mucinous adenocarcinoma of bladder outlet and urethra: a case report and literature review.

Background: Primary bladder adenocarcinoma (PBA) only accounts for 2% of primary bladder cancers. PBA symptoms vary according to the volume, location, and the metastasis of the tumor. The most common symptoms include suprapubic pain, hematuria, dysuria, and bladder irritation. In the initial stage, the diagnosis of PBA is possibly delayed due to the lack of obvious symptoms. When diagnosed, up to 40% of patients are reported to have metastatic disease. PBA can occur anywhere in the bladder, especially the bottom, neck, and roof. However, the mass at the bladder outlet and urethra is a rare presentation of PBA. Through this rare case, when clinicians encounter similar patients, they can have richer ideas for diagnosis and treatment, which is helpful for the timely diagnosis and effective treatment. Case Description: A 62-year-old female was referred to an outpatient urology surgery service due to a 1-year history of narrowing of the urinary route and difficulties in urination. No significant abnormalities were found in other surgical examinations, and the patient denied having a genetic history or similar history in her family. Ultrasonography revealed a hypoechoic mass of 6.5 cm × 3.8 cm × 4.4 cm at the bladder outlet and urethra. Computed tomography (CT) plain scan and enhancing scan displayed that the wall of bladder was thickened, and soft tissue density was seen at the bladder outlet and urethra with slight enhancement and an unclear partial boundary. The mass was confirmed to be PBA. Conclusions: Primary mucinous adenocarcinoma of bladder usually detected in the posterior wall and trigone, but at the bladder outlet and urethra was rare. In this report, Imaging examination showed that the mass was located at the bladder outlet and urethra, and was finally confirmed by surgery. Due to the location of the growth, our patient's only symptoms were dysuria and urinary tract thinning, without hematuria, suprapubic pain, or bladder irritation. Timely diagnosis and treatment of this case depend on the findings of imaging examination. We describe the imaging features of this rare disease entity and the relevant literature review.

Targeting Induced Local Lesions in the Wheat DEMETER and DRE2 Genes, Responsible for Transcriptional Derepression of Wheat Gluten Proteins in the Developing Endosperm.

Wheat is a major source of energy and nutrition worldwide, but it is also a primary cause of frequent diet-induced health issues, specifically celiac disease, for which the only effective therapy so far is strict dietary abstinence from gluten-containing grains. Wheat gluten proteins are grouped into two major categories: high-molecular-weight glutenin subunits (HMWgs), vital for mixing and baking properties, and gliadins plus low-molecular-weight glutenin subunits (LMWgs) that contain the overwhelming majority of celiac-causing epitopes. We put forth a hypothesis that eliminating gliadins and LMWgs while retaining HMWgs might allow the development of reduced-immunogenicity wheat genotypes relevant to most gluten-sensitive individuals. This hypothesis stems from the knowledge that the molecular structures and regulatory mechanisms of the genes encoding the two groups of gluten proteins are quite different, and blocking one group's transcription, without affecting the other's, is possible. The genes for gliadins and LMWgs have to be de-methylated by 5-methylcytosine DNA glycosylase/lyase (DEMETER) and an iron-sulfur (Fe-S) cluster biogenesis enzyme (DRE2) early during endosperm development to permit their transcription. In this study, a TILLING (Targeting Induced Local Lesions IN Genomes) approach was undertaken to identify mutations in the homoeologous DEMETER (DME) and DRE2 genes in common and durum wheat. Lines with mutations in these genes were obtained that displayed reduced content of immunogenic gluten proteins while retaining essential baking properties. Although our data at first glance suggest new possibilities for treating celiac disease and are therefore of medical and agronomical interest, it also shows that inducing mutations in the DME and DRE2 genes analyzed here affected pollen viability and germination. Hence there is a need to develop other approaches in the future to overcome this undesired effect.

Carbon price forecasting: a novel deep learning approach.

Carbon emission trading market promotes carbon emission reduction effectively. Accurate carbon price forecasting is crucial for relevant policy makers and investors. However, due to the non-linearity, uncertainty, and complexity of carbon prices, the current predication models fail to predict carbon prices accurately. In this paper, an advanced deep neural network model named TCN-Seq2Seq is proposed to forecast carbon prices. The novelty of the proposed model focuses on the "sequence to sequence" layout to learn temporal data dependencies using only fully convolutional layers. Being provided with parallel training for fewer parameters, TCN-Seq2Seq forecasting model is more suitable for small carbon price dataset in few-shot learning way. Qualitatively and quantitatively, we find that the proposed framework consistently and significantly outperforms traditional statistical forecasting models and state-of-the-art deep learning prediction model with respect to predictive ability and robustness. Particularly, our proposed model achieves forecasting accuracy with the highest DA value (0.9697), the lowest MAPE value (0.0027), and the lowest RMSE value (0.0149), showing superior prediction performance compared with the traditional statistical forecasting models. The accuracy of carbon price forecasting gives insight to policy makers and carbon market investors.

Serum inter-alpha-trypsin inhibitor heavy chain 4 in patients with inflammatory bowel disease: correlation with disease risk, inflammation, activity, and its variation after treatment.

BACKGROUND: Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays vital roles in inflammatory and auto-immune diseases, but its correlations with disease risk and clinical features in inflammatory bowel disease (IBD) need further investigation. The present study intended to explore the correlation of ITIH4 with disease activity and inflammation, as well as its change after treatment in IBD patients. METHODS: Totally, 40 active Crohn's disease (A-CD) patients, 40 clinical-remission CD (R-CD) patients, 40 active ulcerative colitis (A-UC) patients, 40 clinical-remission UC (R-UC) patients, and 40 health controls (HCs) were enrolled. ITIH4 in serum was assessed by ELISA. RESULTS: ITIH4 was lower in A-CD, R-CD, A-UC, and R-UC patients than in HCs (P < 0.001). Notably, ITIH4 reduced in A-CD patients than in R-CD patients (P = 0.017), and in A-UC patients compared with R-UC patients (P = 0.010). Besides, in A-CD patients, ITIH4 negatively correlated with tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A, IL-1ß, C-reactive protein (CRP), and clinical disease activity index score (all P < 0.05). In A-UC patients, ITIH4 negatively correlated with TNF-α, IL-17A, IL-1ß, IL-6, CRP, and Mayo score (all P < 0.05). However, in R-CD and R-UC patients, these correlations were less obvious than in A-CD and A-UC patients. ITIH4 was increased after treatment (all P < 0.05), and its expression at W12 after treatment was higher in response patients compared with no response patients in A-CD (P = 0.022) and A-UC groups (P = 0.038). CONCLUSION: ITIH4 correlates with IBD susceptibility, active risk, inflammation level, and its elevation after treatment relates to clinical response in IBD patients.

How to manage continuous positive airway pressure (CPAP) failure -hybrid surgery and integrated treatment.

Obstructive sleep apnea (OSA) is a prevalent disease, which influences social relations and quality of life with major health impact. The etiology of OSA is multi-factorial involving both anatomical obstruction and physiological collapse of the upper airway during sleep with different proportion in individual patients. Continuous positive airway pressure (CPAP) is the gold standard and first-line treatment for OSA patients. The mechanism of CPAP is acting as air splint to avoid principal pharyngeal collapse during sleep. Consequently, extrapharyngeal collapse and significant pharyngeal obstructions can lower its compliance and lead to its failure. Adequate mask and pressure with thorough survey to eliminate side effects of CPAP from nasal, mask and flow-related problems are the prerequisite to improve CPAP compliance. For CPAP failure patients, multi-dimensional surgery is an alternative and salvage treatment that involves soft tissue surgery, skeletal surgery, and bariatric surgery. OSA patients with craniofacial anomaly are suggested to skeletal surgery. By contrast, OSA patients with pathological obesity are referred to bariatric surgery. Soft tissue surgery targets at the nose, soft palate, lateral pharyngeal wall, tongue and epiglottis that can be implemented by multi-level surgery with hybrid technique (mucosa-preservation, fat-ablation, muscle-suspension, tonsil-excision, cartilage-reconstruction) to maximize surgical outcomes and minimize complications. Some evolution in surgical concept and technique are noteworthy that include mini-invasive septoturbinoplasty, palatal suspension instead of excision, whole tongue treatment, and two-dimensional supraglottoplasty. Postoperative integrated treatment including myofunctional, positional therapy and body weight control reduces relapse of OSA and improves long-term treatment outcomes.

Directed-Mutagenesis of Flavobacterium meningosepticum Prolyl-Oligopeptidase and a Glutamine-Specific Endopeptidase From Barley.

Wheat gluten proteins are the known cause of celiac disease. The repetitive tracts of proline and glutamine residues in these proteins make them exceptionally resilient to digestion in the gastrointestinal tract. These indigested peptides trigger immune reactions in susceptible individuals, which could be either an allergic reaction or celiac disease. Gluten exclusion diet is the only approved remedy for such disorders. Recently, a combination of a glutamine specific endoprotease from barley (EP-B2), and a prolyl endopeptidase from Flavobacterium meningosepticum (Fm-PEP), when expressed in the wheat endosperm, were shown to reasonably detoxify immunogenic gluten peptides under simulated gastrointestinal conditions. However useful, these "glutenases" are limited in application due to their denaturation at high temperatures, which most of the food processes require. Variants of these enzymes from thermophilic organisms exist, but cannot be applied directly due to their optimum activity at temperatures higher than 37°C. Though, these enzymes can serve as a reference to guide the evolution of peptidases of mesophilic origin toward thermostability. Therefore, a sequence guided site-saturation mutagenesis approach was used here to introduce mutations in the genes encoding Fm-PEP and EP-B2. A thermostable variant of Fm-PEP capable of surviving temperatures up to 90°C and EP-B2 variant with a thermostability of up 60°C were identified using this approach. However, the level of thermostability achieved is not sufficient; the present study has provided evidence that the thermostability of glutenases can be improved. And this pilot study has paved the way for more detailed structural studies in the future to obtain variants of Fm-PEP and EP-B2 that can survive temperatures ~100°C to allow their packing in grains and use of such grains in the food industry.

Risk of Alzheimer's Disease in Obstructive Sleep Apnea Patients With or Without Treatment: Real-World Evidence.

OBJECTIVE: To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real-world evidence. STUDY DESIGN: Retrospective cohort study. METHODS: Patients newly diagnosed with OSA during 1997-2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 1:4 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence. RESULTS: This study included 3,978 OSA patients and 15,912 non-OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio: 2.12; 95% confidence interval [CI], 1.27-3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation: 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06-0.98). CONCLUSION: OSA is independently associated with an increased risk of AD. Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development. LEVEL OF EVIDENCE: IV Laryngoscope, 130:2292-2298, 2020.

Alterations in Alzheimer's Disease-Associated Gene Expression in Severe Obstructive Sleep Apnea Patients.

BACKGROUND: Obstructive sleep apnea (OSA) increases the risk of Alzheimer's disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia. METHODS: This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson's correlation was used as the distance metric to simultaneously cluster subjects and genes. RESULTS: The expressions of CCL2, IL6, CXCL8, HLA-A, and IL1RN in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine-cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways. CONCLUSIONS: Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.

Distribution of Cereal Cyst Nematodes (Heterodera avenae and H. filipjevi) in Eastern Washington State.

Cereal cyst nematodes (CCN; Heterodera avenae and H. filipjevi), cause substantial worldwide yield loss in small grain cereals such as wheat, barley, and oat. H. avenae was first detected in the United States in western Oregon in 1974 and had spread to northeast Oregon by the mid-1980s. Although H. avenae was detected in eastern Washington in 1984, extensive infestations were not recognized until 2010. H. filipjevi, first detected in Oregon in 2008, was found in eastern Washington in 2014. To gain more information about the distribution of these two species, an extensive survey was undertaken in eastern Washington, and methods were developed to distinguish species using DNA sequencing of single cysts. In this study, we surveyed 356 wheat and barley fields in eastern Washington from 2007 to 2017. CCN from the infested locations were identified to species level by sequencing the ribosomal internal transcribed spacers (ITS) and/or 28S ribosomal RNA (rRNA) genes. The sequences were compared in the GenBank database in the National Center for Biotechnology Information (NCBI) to identify species. The results show that H. filipjevi is primarily confined to southern Whitman County, WA; and H. avenae has a wider distribution across the higher precipitation annual cropping area of eastern Whitman County. Knowledge of species identification is critical for deployment of host resistance as an effective means of management, since resistance genes for one species of CCN may not be effective against the other.

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease.

Ubiquitous nature of prolamin proteins dubbed gluten from wheat and allied cereals imposes a major challenge in the treatment of celiac disease, an autoimmune disorder with no known treatment other than abstinence diet. Administration of hydrolytic glutenases as food supplement is an alternative to deliver the therapeutic agents directly to the small intestine, where sensitization of immune system and downstream reactions take place. The aim of the present research was to evaluate the capacity of wheat grain to express and store hydrolytic enzymes capable of gluten detoxification. For this purpose, wheat scutellar calli were biolistically transformed to generate plants expressing a combination of glutenase genes for prolamin detoxification. Digestion of prolamins with barley endoprotease B2 (EP-HvB2) combined with Flavobacterium meningosepticum prolyl endopeptidase (PE-FmPep) or Pyrococcus furiosus prolyl endopeptidase (PE-PfuPep) significantly reduced (up to 67%) the amount of the indigestible gluten peptides of all prolamin families tested. Seven of the 168 generated lines showed inheritance of transgene to the T2 generation. Reversed phase high-performance liquid chromatography of gluten extracts under simulated gastrointestinal conditions allowed the identification of five T2 lines that contained significantly reduced amounts of immunogenic, celiac disease-provoking gliadin peptides. These findings were complemented by the R5 ELISA test results where up to 72% reduction was observed in the content of immunogenic peptides. The developed wheat genotypes open new horizons for treating celiac disease by an intraluminal enzyme therapy without compromising their agronomical performance.