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Despite efforts to implement universal health care coverage (UHC) in the Philippines, income poor households continue to face barriers to health care access and use. In light of recent UHC legislation, the aim of this study was to explore how gender and social networks shape health care access and use among women experiencing poverty in Negros Occidental, Philippines. Semi-structured interviews were conducted with women (n = 35) and health care providers (n = 15). Descriptive statistical analyses were performed to report demographic information. Interview data were analyzed thematically using a hybrid deductive-inductive approach and guided by the Patient-Centred Access to Health Care framework. Women's decisions regarding health care access were influenced by their perceptions of illness severity, their trust in health care facilities, and their available financial resources. Experiences of health care use were shaped by interactions with health professionals, resource availability at facilities, health care costs, and health insurance acquisition. Women drew upon social networks throughout their lifespan for social and financial support to facilitate healthcare access and use. These findings indicate that social networks may be an important complement to formal supports (eg, UHC) in improving access to health care for women experiencing poverty in the Philippines., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: Many studies have evaluated the effectiveness of topical intraoperative mitomycin (MCC) usage in a wide range of otolaryngologic procedures with variable conclusions on effectiveness. This systematic review aims to provide a qualitative estimation of mitomycin C's treatment effectiveness in maintaining or preventing stenosis after surgical interventions., Design and Setting: Following the PRISMA guideline, a comprehensive systematic search of MEDLINE, EMBASE and CINAHL databases was performed including hand-searching and cross-reference checking., Participants: The search was limited to humans, sample size greater than two and study designs including a comparative arm., Main Outcome Measures: Outcome measures varied but included rates of restenosis, number of procedures, and post-surgical patency., Results: A total of 571 unique abstracts and 109 full articles were reviewed. Seventy-seven studies were included in the final analysis. The available evidence ranged from case series to randomized control studies. Meta-analysis was deemed inappropriate due to heterogeneity of study design. Thirty-eight studies assessed the effective of MCC in dacryocystorhinostomy, which is reported in a separate meta-analysis. All other studies were categorized into otolaryngologic site and pathology including choanal atresia (n = 5), endoscopic sinus surgery (n = 12), airway procedures (n = 9), esophageal procedures (n = 8) and other (n = 2)., Conclusions: The published literature on the effectiveness of MMC was mixed, but suggested topical MMC improved surgical outcomes in many otolaryngologic procedures compared to controls. This was the first review to assemble literature on MMC usage for different surgical procedures. Comprehensive interpretation of the data was limited due to heterogeneity in primary outcome, procedure type and study quality. High-quality prospective and randomized controlled studies are required to further confirm the positive effect of MMC use on surgical outcomes., (© 2021 John Wiley & Sons Ltd.)

Developing neural circuits, including GABAergic circuits, switch receptor types. But the role of early GABA receptor expression for establishment of functional inhibitory circuits remains unclear. Tracking the development of GABAergic synapses across axon terminals of retinal bipolar cells (BCs), we uncovered a crucial role of early GABA A receptor expression for the formation and function of presynaptic inhibitory synapses. Specifically, early α3-subunit-containing GABA A (GABA A α3) receptors are a key developmental organizer. Before eye opening, GABA A α3 gives way to GABA A α1 at individual BC presynaptic inhibitory synapses. The developmental downregulation of GABA A α3 is independent of GABA A α1 expression. Importantly, lack of early GABA A α3 impairs clustering of GABA A α1 and formation of functional GABA A synapses across mature BC terminals. This impacts the sensitivity of visual responses transmitted through the circuit. Lack of early GABA A α3 also perturbs aggregation of LRRTM4, the organizing protein at GABAergic synapses of rod BC terminals, and their arrangement of output ribbon synapses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Studies of the ocular microbiome have used a variety of sampling techniques, but no study has directly compared different sampling methods applied to the same eyes to one another or to a reference standard of corneal epithelial biopsy. We addressed this lack by comparing the microbiome from three conjunctival swabs with those of corneal epithelial biopsy., Methods: Twelve eyes (11 patients) were swabbed by calcium alginate swab, cotton-tipped applicator, and Weck-Cel cellulose sponge before a corneal epithelial biopsy (48 samples). We then performed 16S rRNA gene sequencing and universal 16S rRNA gene real-time polymerase chain reaction. Negative/blank controls were used to eliminate contaminants. An analysis was performed to examine the concordance of the three swab types to corneal epithelial biopsy. The effect of patient age on the ocular microbiome as determined by epithelial biopsy was also examined., Results: The ocular microbiome from corneal epithelial biopsies consisted of 31 genera with a relative abundance of 1% or more, including Weisella, Corynebacterium, and Pseudomonas. Of the three swab types, Weck-Cel differed the most from corneal biopsies based on beta-diversity analysis. Cotton swabs were unable to capture the Bacteroides population seen on epithelial biopsy. Therefore, calcium alginate swabs seemed to be the closest to epithelial biopsies. Older patients (≥65 years old) had higher alpha diversity (P < 0.05) than younger patients. Differential abundance testing showed that there were 18 genera that were differentially abundant between the two age groups, including Streptococcus and eight members of the Proteobacteria phylum., Conclusions: We demonstrate that ocular sampling method and patient age can greatly affect the outcome of sequencing-based analysis of the ocular microbiome., Translational Relevance: By understanding the impact of different sampling methods on the results obtained from the ocular surface microbiome, future research on the topic will be more reproducible, leading to a better understanding of ocular surface microbiome in health and disease.

Deep reinforcement learning (DRL) augments the reinforcement learning framework, which learns a sequence of actions that maximizes the expected reward, with the representative power of deep neural networks. Recent works have demonstrated the great potential of DRL in medicine and healthcare. This paper presents a literature review of DRL in medical imaging. We start with a comprehensive tutorial of DRL, including the latest model-free and model-based algorithms. We then cover existing DRL applications for medical imaging, which are roughly divided into three main categories: (i) parametric medical image analysis tasks including landmark detection, object/lesion detection, registration, and view plane localization; (ii) solving optimization tasks including hyperparameter tuning, selecting augmentation strategies, and neural architecture search; and (iii) miscellaneous applications including surgical gesture segmentation, personalized mobile health intervention, and computational model personalization. The paper concludes with discussions of future perspectives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Given that the success of vaccines against coronavirus disease 2019 (COVID-19) relies on herd immunity, identifying patients at risk for vaccine hesitancy is imperative-particularly for those at high risk for severe COVID-19 (i.e., minorities and patients with neurological disorders)., Methods: Among patients from a large neuroscience institute in Hawaii, vaccine hesitancy was investigated in relation to over 30 sociodemographic variables and medical comorbidities, via a telephone quality improvement survey conducted between 23 January 2021 and 13 February 2021., Results: Vaccine willingness ( n = 363) was 81.3%. Univariate analysis identified that the odds of vaccine acceptance reduced for patients who do not regard COVID-19 as a severe illness, are of younger age, have a lower Charlson Comorbidity Index, use illicit drugs, or carry Medicaid insurance. Multivariable logistic regression identified the best predictors of vaccine hesitancy to be: social media use to obtain COVID-19 information, concerns regarding vaccine safety, self-perception of a preexisting medical condition contraindicated with vaccination, not having received the annual influenza vaccine, having some high school education only, being a current smoker, and not having a prior cerebrovascular accident. Unique amongst males, a conservative political view strongly predicted vaccine hesitancy. Specifically for Asians, a higher body mass index, while for Native Hawaiians and other Pacific Islanders (NHPI), a positive depression screen, both reduced the odds of vaccine acceptance., Conclusion: Upon identifying the variables associated with vaccine hesitancy amongst patients with neurological disorders, our clinic is now able to efficiently provide ancillary COVID-19 education to sub-populations at risk for vaccine hesitancy. While our results may be limited to the sub-population of patients with neurological disorders, the findings nonetheless provide valuable insight to understanding vaccine hesitancy.

Medical image segmentation is one of the most challenging tasks in medical image analysis and widely developed for many clinical applications. While deep learning-based approaches have achieved impressive performance in semantic segmentation, they are limited to pixel-wise settings with imbalanced-class data problems and weak boundary object segmentation in medical images. In this paper, we tackle those limitations by developing a new two-branch deep network architecture which takes both higher level features and lower level features into account. The first branch extracts higher level feature as region information by a common encoder-decoder network structure such as Unet and FCN, whereas the second branch focuses on lower level features as support information around the boundary and processes in parallel to the first branch. Our key contribution is the second branch named Narrow Band Active Contour (NB-AC) attention model which treats the object contour as a hyperplane and all data inside a narrow band as support information that influences the position and orientation of the hyperplane. Our proposed NB-AC attention model incorporates the contour length with the region energy involving a fixed-width band around the curve or surface. The proposed network loss contains two fitting terms: (i) a high level feature (i.e., region) fitting term from the first branch; (ii) a lower level feature (i.e., contour) fitting term from the second branch including the (ii1) length of the object contour and (ii2) regional energy functional formed by the homogeneity criterion of both the inner band and outer band neighboring the evolving curve or surface. The proposed NB-AC loss can be incorporated into both 2D and 3D deep network architectures. The proposed network has been evaluated on different challenging medical image datasets, including DRIVE, iSeg17, MRBrainS18 and Brats18. The experimental results have shown that the proposed NB-AC loss outperforms other mainstream loss functions: Cross Entropy, Dice, Focal on two common segmentation frameworks Unet and FCN. Our 3D network which is built upon the proposed NB-AC loss and 3DUnet framework achieved state-of-the-art results on multiple volumetric datasets.

Background: The microbiome has been shown in pre-clinical and epidemiological studies to be important in both the development and treatment of obesity and metabolic associated fatty liver disease (MAFLD). However, few studies have examined the role of the microbiome in the clinical response to calorie restriction. To explore this area, we performed a prospective study examining the association of the intestinal microbiome with weight loss and change in hepatic steatosis on a calorie-restricted diet. Methods: A prospective dietary intervention study of 80 overweight and obese participants was performed at the Greater West Los Angeles Veterans Affair Hospital. Patients were placed on a macronutrient standardized diet for 16 weeks, including 14 weeks of calorie restriction (500 calorie deficit). Body composition analysis by impedance, plasma lipid measurements, and ultrasound elastography to measure hepatic steatosis were performed at baseline and week 16. Intestinal microbiome composition was assessed using 16S rRNA gene sequencing. A per protocol analysis was performed on all subjects completing the trial ( n = 46). Results: Study completers showed significant reduction in weight, body mass index, total cholesterol, low density lipoprotein, and triglyceride. Subjects who lost at least 5% of their body weight had significantly greater reduction in serum triglyceride and hepatic steatosis than those with <5% body weight loss. Enterococcus and Klebsiella were reduced at the end of the trial while Coprococcus and Collinsella were increased. There were also significant baseline microbiome differences between patients who had at least 5% weight loss as compared to those that did not. Lachnoclostridium was positively associated with hepatic steatosis and Actinomyces was positively associated with hepatic steatosis and weight. Baseline microbiome profiles were able to predict which patients lost at least 5% of their body weight with an AUROC of 0.80. Conclusion: Calorie restriction alters the intestinal microbiome and improves hepatic steatosis in those who experience significant weight loss. Baseline microbiome differences predict weight loss on a calorie-restricted diet and are associated with improvement in hepatic steatosis, suggesting a role of the gut microbiome in mediating the clinical response to calorie restriction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dong, Luu, Lagishetty, Sedighian, Woo, Dreskin, Katzka, Chang, Zhou, Arias-Jayo, Yang, Ahdoot, Ye, Li, Pisegna and Jacobs.)

This work aimed to assist physicians by improving their speed and diagnostic accuracy when interpreting portable CXRs as well as monitoring the treatment process to see whether a patient is improving or deteriorating with treatment. These objectives are in especially high demand in the setting of the ongoing COVID-19 pandemic. With the recent progress in the development of artificial intelligence (AI), we introduce new deep learning frameworks to align and enhance the quality of portable CXRs to be more consistent, and to more closely match higher quality conventional CXRs. These enhanced portable CXRs can then help the doctors provide faster and more accurate diagnosis and treatment planning. The contributions of this work are four-fold. Firstly, a new database collection of subject-pair radiographs is introduced. For each subject, we collected a pair of samples from both portable and conventional machines. Secondly, a new deep learning approach is presented to align the subject-pairs dataset to obtain a pixel-pairs dataset. Thirdly, a new PairFlow approach is presented, an end-to-end invertible transfer deep learning method, to enhance the degraded quality of portable CXRs. Finally, the performance of the proposed system is evaluated by UAMS doctors in terms of both image quality and topological properties. This work was undertaken in collaboration with the Department of Radiology at the University of Arkansas for Medical Sciences (UAMS) to enhance portable/mobile COVID-19 CXRs, to improve the speed and accuracy of portable CXR images and aid in urgent COVID-19 diagnosis, monitoring and treatment.

The discovery of immune checkpoints highlights the complexity of T cell signalling during an immune response. Upon activation, T cells express several molecules to regulate their function and to prevent overactivation. B7 homolog 7 (B7-H7) is expressed in tumours and associated with a worse prognosis. However, conflicting data regarding its function suggest that it can be both stimulatory and inhibitory. In this study we report that B7-H7 is also expressed on T cells upon cross-linking of CD3 and CD28 and that additional stimulation via CD137 further enhances the expression of B7-H7. B7-H7 is preferentially expressed on exhausted Th1 and Tc1 cells with an impaired secretion of TNF-α and IFN-γ. Blockade of B7-H7 with its natural receptor, recombinant CD28H, enhances T cell proliferation and activation. Thus, B7-H7 represents another target for immunotherapy and a biomarker to select for active effector T cells with relevance for adoptive cell transfer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luu, Schwarz and Lundqvist.)

Objective: To systematically review the literature to determine the difference in complications between standard twill and Velcro ties following pediatric tracheostomy., Data Sources: MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL Plus were searched up to August 2020., Review Methods: Two authors independently screened articles for eligibility. Retrospective and prospective studies were included as long as there was a direct comparison between twill and Velcro ties. Quantitative and qualitative analysis was performed. The main outcomes were skin-related complications and accidental decannulation., Results: Three studies were included in the final analysis: 1 randomized prospective trial and 2 retrospective studies. There were 238 patients total (137 twill, 101 Velcro). Combined analysis showed skin-related complications in 23% of the Velcro group and 44% of the twill group. Meta-analysis for skin-related complications showed no significant difference when comparing Velcro with standard twill ties (risk ratio, 0.53 [95% CI, 0.24-1.17]; P = .12, n = 238 participants from 3 studies, I 2 = 66%). Accidental decannulation rates were overall low and comparable between groups (1.0% of twill, 1.4% of Velcro)., Conclusion: Based on limited data, skin-related complications were not statistically different between Velcro and twill ties. Accidental decannulation is rare with Velcro and standard twill ties, and both are viable options following pediatric tracheostomy.

Aim: The microbiome has been shown to be pivotal in the development of metabolic associated fatty liver disease (MAFLD). Few have examined the relationship of the microbiome specifically with steatosis grade. Therefore, our aim was to characterize the association of the microbiome with MAFLD steatosis severity while adjusting for metabolic comorbidities including diabetes., Methods: We enrolled patients with MAFLD at the West Los Angeles Veterans Affair Hospital. All patients underwent ultrasound elastography, fasting serum collection, and fecal sampling for 16S sequencing. We examined the associations of microbial diversity and composition with advanced steatosis, defined as a CAP score of ≥ 300 dB/m, with or without the presence of metabolic comorbidities., Results: Seventy-five patients were enrolled. African American were less likely to have advanced steatosis than either Hispanics or Whites ( P = 0.001). Patients with more advanced steatosis had higher fasting serum triglyceride (192.6 ± 157.1 mg/dL vs . 122.5 ± 57.4 mg/dL), HbA1c (6.7% ± 1.4% vs . 6.1% ± 0.8%), transaminases, and were more likely to have metabolic syndrome (52.4% vs . 24.2%, P = 0.02). Advanced steatosis and diabetes were associated with altered microbial composition. Bacteroides was negatively associated with advanced steatosis while Megasphaera was positively associated with steatosis. Akkermansia was negatively associated with diabetes, while Anaerostipes and Parabacteroides were positively associated with diabetes., Conclusion: Diabetes and metabolic syndrome are associated with hepatic steatosis severity in MAFLD patients and both advanced steatosis and comorbid diabetes are independently associated with microbiome changes. These results provide insight into the role of the gut microbiome in MAFLD associated with metabolic syndrome., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.

CD137 is a costimulatory molecule expressed on activated T cells. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), which use the CD137-CD137L system to enhance immune responses. It was, therefore, surprising to discover CD137 expression on regulatory T cells (Treg). The function of CD137 in Treg are controversial. While some studies report that CD137 signalling converts Treg to effector T cells (Teff), other studies find that CD137-expressing Treg display a stronger inhibitory activity than CD137 - Treg. Here, we describe that CD137 on Treg binds to CD137L on APC, upon which one of the two molecules is transferred via trogocytosis to the other cell, where CD137-CD137L forms a complex that is internalized and deprives APC of the immune-stimulatory CD137L. Truncated forms of CD137 that lack the cytoplasmic domain of CD137 are also able to downregulate CD137L, demonstrating that CD137 signalling is not required. Comparable data have been obtained with human and murine cells, indicating that this mechanism is evolutionarily conserved. These data describe trogocytosis of CD137 and CD137L as a new mechanism employed by Treg to control immune responses by downregulating the immunostimulatory CD137L on APC.

Shifts in the microbiome have been correlated with the physiology and pathophysiology of many organ systems both in humans and in mouse models. The gut microbiome has been typically studied through fecal specimen collections. The ease of obtaining fecal samples has resulted in many studies that have revealed information concerning the distal luminal gastrointestinal tract. However, few studies have addressed the importance of the microbiome in the proximal gut. Given that the duodenum is a major site for digestion and absorption, its microbiome is relevant to nutrition and liver disease and warrants further investigation. Here we detail a novel method for sampling the proximal luminal and mucosal gut microbiome in human subjects undergoing upper endoscopy by obtaining duodenal aspirate and biopsies. Specimen procurement is facile and unaffected by artifacts such as patient preparatory adherence, as might be the case in obtaining colonic samples during colonoscopy. The preliminary results show that the luminal and mucosal microbiomes differ significantly, which is likely related to environmental conditions and barrier functions. Therefore, a combination of duodenal aspirate and biopsies reveal a more comprehensive picture of the microbiome in the duodenum. Biopsies are obtained from the descending and horizontal segments of the duodenum, which are anatomically close to the liver and biliary tree. This is important in studying the role of bile acid biology and the gut-liver axis in liver disease. Biopsies and aspirate can be used for 16S ribosomal RNA sequencing, metabolomics, and other similar applications.

Objective: To review the otologic outcomes of infants who failed the newborn hearing screen (NBHS) and received early tympanostomy tubes for otitis media with effusion (OME)., Study Design: Retrospective case series., Setting: Tertiary care pediatric hospital., Subjects and Methods: Consecutive patients (2007-2018) who failed an NBHS and required tympanostomy tubes before 6 months of age were included. Variables including hearing loss and otitis media risk factors, episodes of acute otitis media (AOM), number of subsequent tympanostomy tubes, and posttympanostomy tube audiogram results were recorded., Results: The cohort included 171 patients. Median age at referral to otolaryngology was 2.7 months. Sensorineural hearing loss (SNHL) was subsequently identified in 22 (12.9%) of infants after resolution of the effusion. The peak incidence of AOM was during the second year of life (1-1.9 years), with a median of 1 episode. Ninety-five patients (55.6%) had replacement of tubes, 41 of 171 (24.0%) had 2 or more additional sets of tubes, and long-term tubes were eventually placed in 8 of 95 (8.4%) patients. Craniofacial anomalies were identified in 43.3% of patients. Tube replacement (hazard ratio, 3.00; 95% CI, 1.95-4.63; P < .01, log-rank) and AOM (β, 1.04; 95% CI, 0.43-1.65; P = .04, ordered logistic regression) were more common, and SNHL less common (odds ratio, 0.17; 95% CI, 0.031-0.61; P < .01, logistic regression), in children with craniofacial anomalies., Conclusion: OME is a common cause of failed NBHS. A notable proportion was subsequently found to have SNHL, reiterating the need for postoperative hearing assessments. Infants meeting indication for early tympanostomy tubes for resolution of OME have a high incidence of recurrent AOM and require subsequent tubes.

Background: High protein calorie restriction diets have shown clinical efficacy for obesity, but the mechanisms are not fully known. The intestinal microbiome is a mediator of obesity and preclinical data support an effect of high protein diet (HPD) on the gut microbiome of obesity, but there are few studies in humans., Methods: To address this, we conducted a dietary intervention trial of 80 overweight and obese subjects who were randomized to a calorie-restricted high protein diet (HPD) (30% calorie intake) or calorie-restricted normal protein diet (NPD) (15%) for 8 weeks. Baseline dietary intake patterns were assessed by the Diet History Questionnaire III. Longitudinal fecal sampling was performed at baseline, week 1, week 2, week 4, week 6, and week 8, for a total of 365 samples. Intestinal microbiome composition was assessed by 16S rRNA gene sequencing., Results: At baseline, microbial composition was associated with fiber and protein intake. Subjects on the HPD showed a significant increase in microbial diversity as measured by the Shannon index compared to those on the NPD. The HPD was also associated with significant differences in microbial composition after treatment compared to the NPD. Both diets induced taxonomic shifts compared to baseline, including enrichment of Akkermansia spp. and Bifidobacterium spp. and depletion of Prevotella spp. Conclusion: These findings provide evidence that weight loss diets alter the gut microbiome in obesity and suggest differential effects of HPDs compared to NPDs which may influence the clinical response to HPD.

Motivation: Principal component analysis (PCA) of genetic data is routinely used to infer ancestry and control for population structure in various genetic analyses. However, conducting PCA analyses can be complicated and has several potential pitfalls. These pitfalls include (i) capturing linkage disequilibrium (LD) structure instead of population structure, (ii) projected PCs that suffer from shrinkage bias, (iii) detecting sample outliers and (iv) uneven population sizes. In this work, we explore these potential issues when using PCA, and present efficient solutions to these. Following applications to the UK Biobank and the 1000 Genomes project datasets, we make recommendations for best practices and provide efficient and user-friendly implementations of the proposed solutions in R packages bigsnpr and bigutilsr., Results: For example, we find that PC19-PC40 in the UK Biobank capture complex LD structure rather than population structure. Using our automatic algorithm for removing long-range LD regions, we recover 16 PCs that capture population structure only. Therefore, we recommend using only 16-18 PCs from the UK Biobank to account for population structure confounding. We also show how to use PCA to restrict analyses to individuals of homogeneous ancestry. Finally, when projecting individual genotypes onto the PCA computed from the 1000 Genomes project data, we find a shrinkage bias that becomes large for PC5 and beyond. We then demonstrate how to obtain unbiased projections efficiently using bigsnpr. Overall, we believe this work would be of interest for anyone using PCA in their analyses of genetic data, as well as for other omics data., Availability and Implementation: R packages bigsnpr and bigutilsr can be installed from either CRAN or GitHub (see https://github.com/privefl/bigsnpr). A tutorial on the steps to perform PCA on 1000G data is available at https://privefl.github.io/bigsnpr/articles/bedpca.html. All code used for this paper is available at https://github.com/privefl/paper4-bedpca/tree/master/code., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

Detection of microbial components such as lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) on macrophages induces a robust pro-inflammatory response that is dependent on metabolic reprogramming. These innate metabolic changes have been compared to aerobic glycolysis in tumour cells. However, the mechanisms by which TLR4 activation leads to mitochondrial and glycolytic reprogramming are unknown. Here we show that TLR4 activation induces a signalling cascade recruiting TRAF6 and TBK-1, while TBK-1 phosphorylates STAT3 on S727. Using a genetically engineered mouse model incapable of undergoing STAT3 Ser727 phosphorylation, we show ex vivo and in vivo that STAT3 Ser727 phosphorylation is critical for LPS-induced glycolytic reprogramming, production of the central immune response metabolite succinate and inflammatory cytokine production in a model of LPS-induced inflammation. Our study identifies non-canonical STAT3 activation as the crucial signalling intermediary for TLR4-induced glycolysis, macrophage metabolic reprogramming and inflammation.

R package pcadapt is a user-friendly R package for performing genome scans for local adaptation. Here, we present version 4 of pcadapt which substantially improves computational efficiency while providing similar results. This improvement is made possible by using a different format for storing genotypes and a different algorithm for computing principal components of the genotype matrix, which is the most computationally demanding step in method pcadapt. These changes are seamlessly integrated into the existing pcadapt package, and users will experience a large reduction in computation time (by a factor of 20-60 in our analyses) as compared with previous versions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

CD137 is a potent costimulatory receptor. Several agonistic anti-CD137 antibodies are currently in clinical trials for tumor immunotherapy. Soluble forms of CD137 (sCD137) are generated by differential splicing and antagonize the activities of membrane-bound CD137 (mCD137) and of therapeutic CD137 agonists. sCD137 is found in sera of patients suffering from autoimmune diseases where it is a natural regulator of immune responses, and which has therapeutic potential for immune-mediated diseases. This review summarizes the current knowledge on sCD137, highlights its potential role in immunotherapy against cancer and in autoimmune diseases, and presents important issues to be addressed by future research., (©2020 Society for Leukocyte Biology.)

The presence of advanced fibrosis is an important measure of the severity of chronic liver disease. Prior works that have examined the gut microbiome as a novel biomarker for advanced fibrosis have only examined patients with nonalcoholic fatty liver disease. Therefore, our goal was to examine the gut microbiome across varying etiologies of liver disease to create a predictive model for liver fibrosis based upon a microbial signature. Stool samples were obtained from patients with chronic liver disease (n = 50) undergoing FibroScan (ultrasound elastography) at the VA Greater Los Angeles Healthcare System. Healthy control patients (n = 25) were also recruited as a reference population. Fecal samples underwent 16S ribosomal RNA sequencing. Using differentially abundant microbes, a random forest classifier model was created to distinguish advanced fibrosis from mild/moderate fibrosis. The findings were then validated in a separate cohort of chronic liver disease patients (n = 37). Etiologies for liver disease included non-alcoholic liver disease (58.0%), hepatitis C (26.0%), hepatitis B (10.0%), and alcohol (6.0%). Microbiome composition was distinct in liver patients with advanced fibrosis compared to those with minimal fibrosis and healthy controls (p = 0.003). In multivariate negative binomial modeling, 26 bacterial taxa were differentially abundant in patients with advanced fibrosis as compared to those with minimal/moderate fibrosis (q-value < 0.05). A random forests classifier based on these taxa had an AUROC of 0.90 to predict advanced fibrosis. Prevotella copri, which was enriched in patients with advanced fibrosis, was the most strongly predictive microbe in the classifier. The classifier had an AUROC of 0.82 for advanced fibrosis in the validation cohort and Prevotella copri remained the strongest predictive microbe for advanced fibrosis. There is a distinct microbial signature for patients with advanced fibrosis independent of liver disease etiology and other comorbidities. These results suggest that microbial profiles can be used as a non-invasive marker for advanced fibrosis and support the hypothesis that microbes and their metabolites contribute to hepatic fibrosis.

The mucosal-to-serosal flux of 14 C 3- O -methyl-d-glucose was compared against the electrogenic transport of d-glucose across ex vivo intestinal segments of Nile tilapia, rainbow trout, and pig in Ussing chambers. The difference in affinities ( K m "fingerprints") between pig flux and electrogenic transport of glucose, and the absence of this difference in tilapia and trout, suggest two absorptive pathways in the pig and one in the fish species examined. More specifically, the total mucosal-to-serosal flux revealed a super high-affinity, high-capacity (sHa/Hc) total glucose transport system in tilapia; a super high-affinity, low-capacity (sHa/Lc) total glucose transport system in trout and a low-affinity, low-capacity (La/Lc) total glucose transport system in pig. Comparatively, electrogenic glucose absorption revealed similar K m in both fish species, with a super high-affinity, high capacity (sHa/Hc) system in tilapia; a super high-affinity/super low-capacity (sHa/sLc) system in trout; but a different K m fingerprint in the pig, with a high-affinity, low-capacity (Ha/Lc) system. This was supported by different responses to inhibitors of sodium-dependent glucose transporters (SGLTs) and glucose transporter type 2 (GLUT2) administered on the apical side between species. More specifically, tilapia flux was inhibited by SGLT inhibitors, but not the GLUT2 inhibitor, whereas trout lacked response to inhibitors. In contrast, the pig responded to inhibition by both SGLT and GLUT2 inhibitors with a higher expression of GLUT2. Altogether, it would appear that two pathways are working together in the pig, allowing it to have continued absorption at high glucose concentrations, whereas this is not present in both tilapia and trout.

New evidence indicates the importance of CD137 for controlling Epstein-Barr virus (EBV) infections. (1) Mutations in CD137 predispose to EBV-associated diseases. (2) EBV induces ectopic CD137 expression, thereby activating a negative feed-back regulation and reducing T cell costimulation. These findings suggest CD137 agonists as new treatments for EBV-associated diseases., (© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Objective: The objective of this study is to describe the clinical and pathologic features of a rare congenital neck anomaly, a sternoclavicular sinus, and review the literature on this topic., Study Design: This study is a retrospective case series of four subjects diagnosed with a sternoclavicular sinus., Methods: Patients with a congenital neck anomaly, distinct from common branchial cleft anomalies, were identified through a 10-year retrospective chart review of a tertiary care pediatric otolaryngology practice., Results: We describe four patients with a congenital neck anomaly with common features of a sternoclavicular anomaly. All patients presented with a superficial neck anomaly adjacent to the sternoclavicular joint. Surgical excision through an external approach was successfully performed in three out of the four patients with subsequent resolution of symptoms. The literature review compiles all the cases presented. Theories on embryologic origin include incomplete fusion of sternum and clavicle or unusual remnant of a fourth branchial cleft. Commonalities include left sided predominance, squamous epithelium lined sinus tract ending at the sternoclavicular junction, and successful surgical excision in almost all cases., Conclusion: A sternoclavicular sinus is a rarely described congenital neck abnormality. Presentation and management is similar to branchial cleft anomaly but with a distinct anatomical pathway that is important for surgeons to recognize., Level of Evidence: This manuscript presents a case series. The level of evidence proposed is Level 4., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Advances in pediatric otology have provided new tools to diagnose and manage complex otologic disease. Diffusion-weighted MRI provides the surgeon with a tool to detect recurrent or residual cholesteatoma that may obviate a second look surgery. Surgical trends move toward less invasive surgery. The literature provides good evidence to advocate for preserving the posterior ear canal and single stage ossiculoplasty. The growing popularity and increasing evidence in the literature supports otoendoscopy as a means to minimize invasiveness while eradicating disease in previously difficult to reach anatomic locations. These advances have allowed the otologic surgeon to improve surgical outcomes while minimizing intervention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The availability of large amounts of high-throughput genomic, transcriptomic and epigenomic data has provided opportunity to understand regulation of the cellular transcriptome with an unprecedented level of detail. As a result, research has advanced from identifying gene expression patterns associated with particular conditions to elucidating signalling pathways that regulate expression. There are over 1,000 transcription factors (TFs) in vertebrates that play a role in this regulation. Determining which of these are likely to be controlling a set of genes can be assisted by computational prediction, utilising experimentally verified binding site motifs. Here we present CiiiDER, an integrated computational toolkit for transcription factor binding analysis, written in the Java programming language, to make it independent of computer operating system. It is operated through an intuitive graphical user interface with interactive, high-quality visual outputs, making it accessible to all researchers. CiiiDER predicts transcription factor binding sites (TFBSs) across regulatory regions of interest, such as promoters and enhancers derived from any species. It can perform an enrichment analysis to identify TFs that are significantly over- or under-represented in comparison to a bespoke background set and thereby elucidate pathways regulating sets of genes of pathophysiological importance., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Many patients with cirrhosis who undergo esophagogastroduodenoscopy (EGD) screening for esophageal varices (EVs) are found to have no or only small EVs. Endoscopic screening for EVs is therefore a potentially deferrable procedure that increases patient risk and healthcare cost. We developed and validated a scoring system, based on readily-available data, to reliably identify patients with EVs that need treatment., Methods: We collected data from 238 patients with cirrhosis undergoing screening EGD from January 2016 through December 2017 at 3 separate hospitals in Los Angeles (training cohort). We abstracted data on patient sex, age, race/ethnicity, platelet counts, and levels of hemoglobin, serum sodium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, international normalized ratio, albumin, urea nitrogen, and creatinine. We also included etiology of cirrhosis, presence of ascites, and presence of hepatic encephalopathy. We used a random forest algorithm to identify factors significantly associated with the presence of EVs and varices needing treatment (VNT) and calculated area under the receiver operating characteristic curve (AUROC). We called the resulting formula the EVendo score. We tested the accuracy of EVendo in a prospective study of 109 patients undergoing screening EGDs at the same medical centers from January 2018 through December 2018 (validation cohort)., Results: We developed an algorithm that identified patients with EVs and VNT based on international normalized ratio, level of aspartate aminotransferase, platelet counts, urea nitrogen, hemoglobin, and presence of ascites. The EVendo score identified patients with EVs in the training set with an AUROC of 0.84, patients with EVs in the validation set with and AUROC of 0.82, and EVs in patients with cirrhosis Child-Turcotte-Pugh class A (n = 235) with an AUROC of 0.81. The score identified patients with VNT in the training set with an AUROC of 0.74, VNT in the validation set with and AUROC of 0.75, and VNT in patients with cirrhosis Child-Turcotte-Pugh class A with and AUROC of 0.75. An EVendo score below 3.90 would have spared 30.5% patients from EGDs, missing only 2.8% of VNT. The same cutoff would have spared 40.0% of patients with Child-Turcotte-Pugh class A cirrhosis from EGDs, missing only 1.1% of VNT., Conclusions: We algorithmically developed a formula, called the EVendo score, that can be used to predict EVs and VNT based on readily available data in patients with cirrhosis. This score could help patients at low risk for VNT avoid unnecessary EGDs., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In plants, strict regulation of stomatal pores is critical for modulation of CO 2 fixation and transpiration. Under certain abiotic and biotic stressors, pore closure is initiated through anionic flux, with calcium (Ca 2+ ) playing a central role. The aluminum-activated malate transporter 12 (ALMT12) is a malate-activated, voltage-dependent member of the aluminum-activated malate transporter family that has been implicated in anionic flux from guard cells controlling the stomatal aperture. Herein, we report the characterization of the regulatory mechanisms mediating channel activities of an ALMT from the grass Brachypodium distachyon (BdALMT12) that has the highest sequence identity to Arabidopsis thaliana ALMT12. Electrophysiological studies in a heterologous cell system confirmed that this channel is malate- and voltage-dependent. However, this was shown to be true only in the presence of Ca 2+ Although a general kinase inhibitor increased the current density of BdALMT12, a calmodulin (CaM) inhibitor reduced the Ca 2+ -dependent channel activation. We investigated the physiological relevance of the CaM-based regulation in planta , where stomatal closure, induced by exogenous Ca 2+ ionophore and malate, was shown to be inhibited by exogenous application of a CaM inhibitor. Subsequent analyses revealed that the double substitutions R335A/R338A and R335A/K342A, within a predicted BdALMT12 CaM-binding domain (CBD), also decreased the channels' ability to activate. Using isothermal titration calorimetry and CBD-mimetic peptides, as well as CaM-agarose affinity pulldown of full-length recombinant BdALMT12, we confirmed the physical interaction between the CBD and CaM. Together, these findings support a co-regulatory mechanism of BdALMT12 activation by malate, and Ca 2+ /CaM, emphasizing that a complex regulatory network modulates BdALMT12 activity.

Background: 3-Dimensional (3D) printing can be applied to virtual planning and creation of surgical guides for mandibular reconstruction. Such systems are becoming increasingly prevalent in head and neck reconstruction. However, third party access to this technology is costly and removes the opportunity to design, create, and modify the bony reconstructions, as third party technology is a black box. This series is a pilot study to document the feasibility of an in-house software tool. The objectives of this study are to describe the design of an automated in house system and assess the accuracy of this in house automated software tool for mandibular reconstruction in a simulated environment., Methods: Software was written to automate the preoperative planning and surgical guide creation process. In a simulation lab, Otolaryngology residents were tasked with resecting and reconstructing a simulated mandible using the 3D-printed cutting guides. A control group of residents performed resection and reconstruction using the traditional method without cutting guides. T-test analysis was performed to compare specific aspects of the final reconstructions including: change from native mandibular width and projection, segment gap distance, and reconstruction time., Results: Mandibular reconstruction was successful in all participants using the 3D printed system. The guided group performed significantly better on the measurement of change in Mandibular overlap, projection, segment gap volume. There was a non-significant trend towards better mandibular width and operative time for the guided group., Conclusions: This study confirms functionality and feasibility of using an in house automated software for planning and creating surgical guides.

Ordination is a common tool in ecology that aims at representing complex biological information in a reduced space. In landscape genetics, ordination methods such as principal component analysis (PCA) have been used to detect adaptive variation based on genomic data. Taking advantage of environmental data in addition to genotype data, redundancy analysis (RDA) is another ordination approach that is useful to detect adaptive variation. This study aims at proposing a test statistic based on RDA to search for loci under selection. We compare redundancy analysis to pcadapt, which is a nonconstrained ordination method, and to a latent factor mixed model (LFMM), which is a univariate genotype-environment association method. Individual-based simulations identify evolutionary scenarios where RDA genome scans have a greater statistical power than genome scans based on PCA. By constraining the analysis with environmental variables, RDA performs better than PCA in identifying adaptive variation when selection gradients are weakly correlated with population structure. In addition, we show that if RDA and LFMM have a similar power to identify genetic markers associated with environmental variables, the RDA-based procedure has the advantage to identify the main selective gradients as a combination of environmental variables. To give a concrete illustration of RDA in population genomics, we apply this method to the detection of outliers and selective gradients on an SNP data set of Populus trichocarpa (Geraldes et al., ). The RDA-based approach identifies the main selective gradient contrasting southern and coastal populations to northern and continental populations in the north-western American coast., (© 2018 John Wiley & Sons Ltd.)

Background: To describe and evaluate a four step systematic approach to dissecting the recurrent laryngeal nerve (RLN) starting at the cricothyroid junction during thyroid surgery (subsequently referred to as the retrograde medial approach)., Methods: All thyroidectomies completed by the senior author between August 2014 and January 2016 were retrospectively reviewed. Patients were excluded if concurrent lateral or central neck dissection was performed. A follow up period of 1 year was included., Results: Surgical photographs and illustrations demonstrate the four steps in the retrograde medial approach to dissection of the RLN in thyroid surgery. Three hundred forty-two consecutive thyroid surgeries were performed in 17 months, including 213 hemithyroidectomies, 91 total thyroidectomies, and 38 completion thyroidectomies. The rate of temporary and permanent hypocalcemia was 13% (95% confidence interval [CI]: 8-20%) and 3% (95% CI: 1-8%) respectively. The rate of temporary and permanent vocal cord palsy was 9% (95% CI: 6-12%) and 0.3% (95%CI: 0.01-2%) respectively. The median surgical times for hemithyroidectomy, total thyroidectomy, and completion thyroidectomy were 39 min (Interquartile range [IQR]: 33-47 min), 48 min (IQR: 40-60 min), and 40 min (IQR: 35-51 min) respectively. 1% of cases required conversion to an alternative surgical approach., Conclusion: In a tertiary endocrine head and neck practice, the routine use of the retrograde medial approach to RLN dissection is safe and results in a short operative time, and a low conversion rate to other RLN dissection approaches.

Objective: Anatomic abnormalities in the larynx can cause significant and bothersome symptoms. Identified here is an anatomical variant of the thyroid cartilage., Study Design: This study is a retrospective case series of 11 subjects diagnosed with an anatomic variant of the thyroid cartilage., Methods: Patients with an anatomic inward buckling of the thyroid cartilage, termed here as buckled thyroid cartilage, were identified through a 20-year retrospective chart review of a tertiary care laryngology practice., Results: We describe 11 patients with fullness or asymmetry in the area of the false vocal fold and an associated inward buckling of the thyroid cartilage on computed tomography scan. All patients presented with a bothersome voice-related complaint. The most common presenting complaints were hoarseness (54%), globus sensation (45%), or vocal fatigue (27%). One patient was found to have a history of known laryngeal trauma. Surgical correction through an external approach on one patient was successfully performed with subsequent resolution of symptoms., Conclusion: We postulate that deformity and protrusion of the false vocal fold can result in a dampening effect on the vibratory capacity of the vocal fold that can lead to symptomatic hoarseness and vocal fatigue. Buckled thyroid cartilage is, therefore, an important anatomical variant to be aware of and be able to recognize., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Chronic Rhinosinusitis (CRS) can suffer from a significant decline in their quality of life. CRS patients have a high prevalence of comorbid conditions and it is important to understand the impact of these conditions on their CRS-related quality of life. This study measures the impacts of chronic pulmonary comorbidities on quality of life, pain, and depression scores among patients with CRS awaiting Endoscopic Sinus Surgery (ESS)., Methods: This study is based on cross-sectional analysis of prospectively collected patient-reported outcome data collected pre-operatively from patients waiting for ESS. Surveys were administered to patients to assess sino-nasal morbidity (SNOT-22), depression and pain. The impact of pulmonary comorbidity on SNOT-22 scores, pain and depression was measured., Results: Two hundred fifthy-three patients were included in the study, 91 with chronic pulmonary comorbidity. The mean SNOT-22 scores were significantly higher among patients with chronic pulmonary comorbidities than among patients without (37 and 48, respectively). This difference is large enough to be clinically significant. Patients with chronic pulmonary comorbidities reported slightly higher depression scores than those without., Conclusions: This study found that among CRS patients waiting for ESS, chronic pulmonary comorbidities are strongly associated with significantly higher symptom burden.

Variational Level Set (LS) has been a widely used method in medical segmentation. However, it is limited when dealing with multi-instance objects in the real world. In addition, its segmentation results are quite sensitive to initial settings and highly depend on the number of iterations. To address these issues and boost the classic variational LS methods to a new level of the learnable deep learning approaches, we propose a novel definition of contour evolution named Recurrent Level Set (RLS) 1 to employ Gated Recurrent Unit under the energy minimization of a variational LS functional. The curve deformation process in RLS is formed as a hidden state evolution procedure and updated by minimizing an energy functional composed of fitting forces and contour length. By sharing the convolutional features in a fully end-to-end trainable framework, we extend RLS to Contextual RLS (CRLS) to address semantic segmentation in the wild. The experimental results have shown that our proposed RLS improves both computational time and segmentation accuracy against the classic variational LS-based method whereas the fully end-to-end system CRLS achieves competitive performance compared to the state-of-the-art semantic segmentation approaches.

Although widely used, Multilinear PCA (MPCA), one of the leading multilinear analysis methods, still suffers from four major drawbacks. First, it is very sensitive to outliers and noise. Second, it is unable to cope with missing values. Third, it is computationally expensive since MPCA deals with large multi-dimensional datasets. Finally, it is unable to maintain the local geometrical structures due to the averaging process. This paper proposes a novel approach named Compressed Submanifold Multifactor Analysis (CSMA) to solve the four problems mentioned above. Our approach can deal with the problem of missing values and outliers via SVD-L1. The Random Projection method is used to obtain the fast low-rank approximation of a given multifactor dataset. In addition, it is able to preserve the geometry of the original data. Our CSMA method can be used efficiently for multiple purposes, e.g. noise and outlier removal, estimation of missing values, biometric applications. We show that CSMA method can achieve good results and is very efficient in the inpainting problem as compared to [1], [2]. Our method also achieves higher face recognition rates compared to LRTC, SPMA, MPCA and some other methods, i.e. PCA, LDA and LPP, on three challenging face databases, i.e. CMU-MPIE, CMU-PIE and Extended YALE-B.

The R package pcadapt performs genome scans to detect genes under selection based on population genomic data. It assumes that candidate markers are outliers with respect to how they are related to population structure. Because population structure is ascertained with principal component analysis, the package is fast and works with large-scale data. It can handle missing data and pooled sequencing data. By contrast to population-based approaches, the package handle admixed individuals and does not require grouping individuals into populations. Since its first release, pcadapt has evolved in terms of both statistical approach and software implementation. We present results obtained with robust Mahalanobis distance, which is a new statistic for genome scans available in the 2.0 and later versions of the package. When hierarchical population structure occurs, Mahalanobis distance is more powerful than the communality statistic that was implemented in the first version of the package. Using simulated data, we compare pcadapt to other computer programs for genome scans (BayeScan, hapflk, OutFLANK, sNMF). We find that the proportion of false discoveries is around a nominal false discovery rate set at 10% with the exception of BayeScan that generates 40% of false discoveries. We also find that the power of BayeScan is severely impacted by the presence of admixed individuals whereas pcadapt is not impacted. Last, we find that pcadapt and hapflk are the most powerful in scenarios of population divergence and range expansion. Because pcadapt handles next-generation sequencing data, it is a valuable tool for data analysis in molecular ecology., (© 2016 John Wiley & Sons Ltd.)

Finding genetic signatures of local adaptation is of great interest for many population genetic studies. Common approaches to sorting selective loci from their genomic background focus on the extreme values of the fixation index, F ST , across loci. However, the computation of the fixation index becomes challenging when the population is genetically continuous, when predefining subpopulations is a difficult task, and in the presence of admixed individuals in the sample. In this study, we present a new method to identify loci under selection based on an extension of the F ST statistic to samples with admixed individuals. In our approach, F ST values are computed from the ancestry coefficients obtained with ancestry estimation programs. More specifically, we used factor models to estimate F ST , and we compared our neutrality tests with those derived from a principal component analysis approach. The performances of the tests were illustrated using simulated data and by re-analysing genomic data from European lines of the plant species Arabidopsis thaliana and human genomic data from the population reference sample, POPRES., (© 2016 John Wiley & Sons Ltd.)

To characterize natural selection, various analytical methods for detecting candidate genomic regions have been developed. We propose to perform genome-wide scans of natural selection using principal component analysis (PCA). We show that the common FST index of genetic differentiation between populations can be viewed as the proportion of variance explained by the principal components. Considering the correlations between genetic variants and each principal component provides a conceptual framework to detect genetic variants involved in local adaptation without any prior definition of populations. To validate the PCA-based approach, we consider the 1000 Genomes data (phase 1) considering 850 individuals coming from Africa, Asia, and Europe. The number of genetic variants is of the order of 36 millions obtained with a low-coverage sequencing depth (3×). The correlations between genetic variation and each principal component provide well-known targets for positive selection (EDAR, SLC24A5, SLC45A2, DARC), and also new candidate genes (APPBPP2, TP1A1, RTTN, KCNMA, MYO5C) and noncoding RNAs. In addition to identifying genes involved in biological adaptation, we identify two biological pathways involved in polygenic adaptation that are related to the innate immune system (beta defensins) and to lipid metabolism (fatty acid omega oxidation). An additional analysis of European data shows that a genome scan based on PCA retrieves classical examples of local adaptation even when there are no well-defined populations. PCA-based statistics, implemented in the PCAdapt R package and the PCAdapt fast open-source software, retrieve well-known signals of human adaptation, which is encouraging for future whole-genome sequencing project, especially when defining populations is difficult., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Introduction: Recent reviews have documented the beneficial effects of seated meditation on executive function (EF). However, there has yet to be a comprehensive review on the effects of Hatha yoga, a moving meditation, on EF., Objective: To examine the empirical literature on the effects of Hatha yoga on EF., Methods: MEDLINE, Scopus, and PsycINFO databases were searched for experimental studies (between- or within-subject designs) testing the effects of Hatha yoga (acute bouts, short-term interventions, longer-term interventions) on EF., Results: A total of 11 published studies met eligibility criteria: Three studies involved healthy adults, 2 studies involved healthy older adults (n = 2), 1 study involved children and adolescents, and 5 studies involved medical (n = 4) or forensic (n = 1) populations. In healthy adults, 2 of 3 studies suggested that acute bouts of Hatha yoga improved EF; however, 1 study using a short-term intervention found no improvements in EF. Among healthy older adults, 1 study provided evidence that Hatha yoga improves EF. In child/adolescent samples, 1 study supported the contention that Hatha yoga improves EF after short-term interventions. Among medical populations, EF improved in patients with type 2 diabetes mellitus and in 1 of 3 studies involving patients with multiple sclerosis. The sole study involving impulsive prisoners showed positive effects on EF with a short-term intervention., Conclusion: Hatha yoga shows promise of benefit for EF in healthy adults, children, adolescents, healthy older adults, impulsive prisoners, and medical populations (with the exception of multiple sclerosis). However, more good-quality studies that evaluate the efficacy of Hatha yoga's effects on EF are essential to build on this evidence base.

The present study was undertaken to explore the possible mechanisms of the behavioral alterations that develop in response to cancer and to cancer therapy. For this purpose we used a syngeneic heterotopic mouse model of human papilloma virus (HPV)-related head and neck cancer in which cancer therapy is curative. Mice implanted or not with HPV+ tumor cells were exposed to sham treatment or a regimen of cisplatin and radiotherapy (chemoradiation). Sickness was measured by body weight loss and reduced food intake. Motivation was measured by burrowing, a highly prevalent species specific behavior. Tumor-bearing mice showed a gradual decrease in burrowing over time and increased brain and liver inflammatory cytokine mRNA expression by 28 days post tumor implantation. Chemoradiation administered to healthy mice resulted in a mild decrease in burrowing, body weight, and food intake. Chemoradiation in tumor-bearing mice decreased tumor growth and abrogated liver and brain inflammation, but failed to attenuate burrowing deficits. PCR array analysis of selected hypoxia and mitochondrial genes revealed that both the tumor and chemoradiation altered the expression of genes involved in mitochondrial energy metabolism within the liver and brain and increased expression of genes related to HIF-1α signaling within the brain. The most prominent changes in brain mitochondrial genes were noted in tumor-bearing mice treated with chemoradiation. These findings indicate that targeting mitochondrial dysfunction following cancer and cancer therapy may be a strategy for prevention of cancer-related symptoms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: To determine the effectiveness of currently available medical and surgical interventions for treating symptoms of Patulous Eustachian Tube (PET)., Data Sources: A comprehensive search of MEDLINE (January 1948 to July 8, 2015), EMBASE (January 1974 to July 8, 2015), gray literature, hand searches, and cross-reference checking., Study Selection: Original published reports evaluating an intervention to treat the symptoms of patulous eustachian tube in patients 18 years and older., Data Extraction: Quality-of-case reviews were assessed with the National Institute of Health (NIH) Quality Assessment Tool for Case Series Studies., Data Synthesis: The search strategy identified 1,104 unique titles; 39 articles with 533 patients are included. The available evidence consists of small case series and case reports. The most common medical treatment was nasal instillation of normal saline. Surgical treatments were categorized as mass loading of the tympanic membrane, eustachian tube plugging, and manipulation of eustachian tube musculature., Conclusions: The available evidence for management of patients with PET is poor in quality and consists predominantly of small case series. Further research is needed to determine the comparative efficacy of the current treatments.

In this paper, we investigate a single-sample periocular-based alignment-robust face recognition technique that is pose-tolerant under unconstrained face matching scenarios. Our Spartans framework starts by utilizing one single sample per subject class, and generate new face images under a wide range of 3D rotations using the 3D generic elastic model which is both accurate and computationally economic. Then, we focus on the periocular region where the most stable and discriminant features on human faces are retained, and marginalize out the regions beyond the periocular region since they are more susceptible to expression variations and occlusions. A novel facial descriptor, high-dimensional Walsh local binary patterns, is uniformly sampled on facial images with robustness toward alignment. During the learning stage, subject-dependent advanced correlation filters are learned for pose-tolerant non-linear subspace modeling in kernel feature space followed by a coupled max-pooling mechanism which further improve the performance. Given any unconstrained unseen face image, the Spartans can produce a highly discriminative matching score, thus achieving high verification rate. We have evaluated our method on the challenging Labeled Faces in the Wild database and solidly outperformed the state-of-the-art algorithms under four evaluation protocols with a high accuracy of 89.69%, a top score among image-restricted and unsupervised protocols. The advancement of Spartans is also proven in the Face Recognition Grand Challenge and Multi-PIE databases. In addition, our learning method based on advanced correlation filters is much more effective, in terms of learning subject-dependent pose-tolerant subspaces, compared with many well-established subspace methods in both linear and non-linear cases.

Activation of the Toll-like receptor (TLR) family of innate immune sensors stimulates multiple signal transduction pathways. Previous studies have suggested that TLR2, TLR4 and TLR9 induce serine phosphorylation of Signal Transducers and Activators of Transcription-1 (STAT1) at residue 727 (S727), although its role in TLR signaling was unclear. We report here that STAT1 rapidly undergoes phosphorylation following TLR4 challenge with lipopolysaccharide (LPS) in a model of LPS hypersensitivity in vivo. Importantly, genetic ablation of STAT1 protected against LPS-induced lethality suggesting that STAT1 may have a key role in TLR-induced inflammation. We have found that multiple TLRs induce Ser727 phosphorylation of STAT1, which is dependent on MyD88 and TRIF signaling, but independent of interferon (IFN) regulatory factor (IRF)-3, IRF7 and the IFN receptor complex, suggesting that activation is a direct TLR response rather than autocrine activation via IFN. Importantly, we found that STAT1 interacts with tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6), a key mediator of TLR signaling after TLR challenge and that following activation, STAT1 translocates to the nucleus. Critically, macrophages generated from mice in which the S727 residue was replaced with alanine (STAT1 S727A mice) display significantly reduced TNFα protein production, but not reduced interleukin-6 or RANTES protein in response to multiple TLR challenges, as compared with wild-type macrophages. These results clearly demonstrate cross-talk between the TLR and JAK/STAT signaling pathways with direct recruitment of STAT1 by TRAF6 and that the direct activation of STAT1 by TLR signaling suggests a crucial role for STAT1 in TLR-induced inflammation.

Prior studies have demonstrated that a single session of aerobic exercise can enhance cognitive functioning; specifically, the inhibition facet of executive function (EF). Additionally, previous research has demonstrated that inhibitory abilities are essential for effective dietary self-control. However, it is currently unknown whether exercise induced enhancements in EF also facilitate self-control in the dietary domain. The present study sought to determine whether a single session of aerobic exercise enhances EF, and whether there is a transfer effect to dietary self-control. Thirty four undergraduate students were randomly assigned to one of three exercise conditions: (1) minimal exercise; (2) moderate intensity exercise (30% heart rate reserve); (3) vigorous intensity exercise (50% heart rate reserve). After the exercise bout, participants completed three standardized EF tasks followed by a bogus taste test for three appetitive snack foods (milk chocolate and potato chips) and two control foods (dark chocolate and crackers). The amount of food consumed during the taste test was covertly measured. The results revealed a significant main effect of treatment condition on the Stroop task performance, but not Go-NoGo (GNG) and Stop Signal task performance. Findings with respect to food consumption revealed that EF moderated the treatment effect, such that those with larger exercise effects on Stroop performance in the moderate intensity exercise condition consumed more control foods (but not less appetitive foods). These findings support the contention that a single bout of aerobic exercise enhances EF, and may have transfer effects to the dietary domain, but that such effects may be indirect in nature.

The glenohumeral joint is frequently dislocated resulting in injury to the glenohumeral capsule. Repair techniques that focus on restoring the capsule after dislocation to re-establish its stabilizing function could benefit from predictions of the location of failure in this continuous sheet of tissue with a random collagen fiber alignment in the unloaded state. Therefore, the objective of this study was to determine the collagen fiber alignment and maximum principal strain in all regions of the capsule during uniaxial extension to failure and to determine whether these parameters could predict the location of tissue failure. Collagen fiber alignment, quantified using a small-angle light-scattering device, and maximum principal strain in the capsule were determined at 5% increments of elongation until tissue failure. A contingency table analyzed with Fischer's exact test demonstrated that peak collagen fiber alignment, represented by the normalized orientation index (p < 0.001) and maximum principal strain (p < 0.001), is significant in predicting location of failure. The direct correlation between the maximum principal strain and collagen fiber alignment measured prior to failure to the location of tissue failure suggests these parameters can be used as a predictive tool to help locate the areas of the glenohumeral capsule that are susceptible to failure. In the future, changes in collagen fiber alignment following injury could be used to develop a constitutive model for injured capsular tissue.

The multiple mini-interview (MMI) has become an increasingly popular admissions method for selecting prospective students into professional programs (e.g., medical school). The MMI uses a series of short, labour intensive simulation stations and scenario interviews to more effectively assess applicants' non-cognitive qualities such as empathy, critical thinking, integrity, and communication. MMI data from 455 medical school applicants were analyzed using: (1) Generalizability Theory to estimate the generalizability of the MMI and identify sources of error; and (2) the Many-Facet Rasch Model, to identify misfitting examinees, items and raters. Consistent with previous research, our results support the reliability of MMI process. However, it appears that the non-cognitive qualities are not being measured as unique constructs across stations.

Robust facial hair detection and segmentation is a highly valued soft biometric attribute for carrying out forensic facial analysis. In this paper, we propose a novel and fully automatic system, called SparCLeS, for beard/moustache detection and segmentation in challenging facial images. SparCLeS uses the multiscale self-quotient (MSQ) algorithm to preprocess facial images and deal with illumination variation. Histogram of oriented gradients (HOG) features are extracted from the preprocessed images and a dynamic sparse classifier is built using these features to classify a facial region as either containing skin or facial hair. A level set based approach, which makes use of the advantages of both global and local information, is then used to segment the regions of a face containing facial hair. Experimental results demonstrate the effectiveness of our proposed system in detecting and segmenting facial hair regions in images drawn from three databases, i.e., the NIST Multiple Biometric Grand Challenge (MBGC) still face database, the NIST Color Facial Recognition Technology FERET database, and the Labeled Faces in the Wild (LFW) database.

Objectives/hypothesis: The objective of this study was to evaluate the long-term effectiveness of palatal implants as the treatment of primary snoring., Study Design: Prospective longitudinal cohort study., Methods: This study compared snoring outcomes before and after soft palate implantation for patients diagnosed with primary snoring (no sleep apnea). Snoring severity was obtained by the subjects' sleep partners on a 10-point Likert scale. A paired Student t test compared the mean scale values preoperatively at week 52 and at the current 4-year follow-up. Body mass index for each patient was also compared to evaluate for any significant confounders., Results: Data were obtained from 23 patients out of 26 who were followed for the full study term. The follow-up time was on average 4 years following palatal implantation. A statistically (P < .016) and clinically significant improvement in the snoring scale was noted when comparing snoring severity between the preoperative and 4-year period and between the 52-week and 4-year scores. Although statistically significant improvement was found between the preoperative period and 52 weeks, there was a clinical deterioration in snoring scale scores between 52 weeks and 4 years. The mean (standard deviation) preoperative score was 9.5 (0.5), mean week-52 score was 5.0 (1.6), and mean 4-year score was 7.0 (1.8). Body mass index did not change through the observation interval., Conclusions: Soft palate implantation is a possible surgical technique with which to attempt to achieve subjective improvement of primary snoring severity. Subjective improvement, however, deteriorates significantly over time, and is only minimally sustained at 4 years postoperatively. This study provides new information on long-term palatal implant effectiveness., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)