Improving Patch-Based Convolutional Neural Networks for MRI Brain Tumor Segmentation by Leveraging Location Information.

The manual brain tumor annotation process is time consuming and resource consuming, therefore, an automated and accurate brain tumor segmentation tool is greatly in demand. In this paper, we introduce a novel method to integrate location information with the state-of-the-art patch-based neural networks for brain tumor segmentation. This is motivated by the observation that lesions are not uniformly distributed across different brain parcellation regions and that a locality-sensitive segmentation is likely to obtain better segmentation accuracy. Toward this, we use an existing brain parcellation atlas in the Montreal Neurological Institute (MNI) space and map this atlas to the individual subject data. This mapped atlas in the subject data space is integrated with structural Magnetic Resonance (MR) imaging data, and patch-based neural networks, including 3D U-Net and DeepMedic, are trained to classify the different brain lesions. Multiple state-of-the-art neural networks are trained and integrated with XGBoost fusion in the proposed two-level ensemble method. The first level reduces the uncertainty of the same type of models with different seed initializations, and the second level leverages the advantages of different types of neural network models. The proposed location information fusion method improves the segmentation performance of state-of-the-art networks including 3D U-Net and DeepMedic. Our proposed ensemble also achieves better segmentation performance compared to the state-of-the-art networks in BraTS 2017 and rivals state-of-the-art networks in BraTS 2018. Detailed results are provided on the public multimodal brain tumor segmentation (BraTS) benchmarks

Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection.

HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection, and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection

Ozone Inhalation Attenuated the Effects of Budesonide on Aspergillus fumigatus-Induced Airway Inflammation and Hyperreactivity in Mice.

Inhaled glucocorticoids form the mainstay of asthma treatment because of their anti-inflammatory effects in the lung. Exposure to the air pollutant ozone (O3) exacerbates chronic airways disease. We and others showed that presence of the epithelial-derived surfactant protein-D (SP-D) is important in immunoprotection against inflammatory changes including those induced by O3 inhalation in the airways. SP-D synthesis requires glucocorticoids. We hypothesized here that O3 exposure impairs glucocorticoid responsiveness (including SP-D production) in allergic airway inflammation. The effects of O3 inhalation and glucocorticoid treatment were studied in a mouse model of allergic asthma induced by sensitization and challenge with Aspergillus fumigatus (Af) in vivo. The role of O3 and glucocorticoids in regulation of SP-D expression was investigated in A549 and primary human type II alveolar epithelial cells in vitro. Budesonide inhibited airway hyperreactivity, eosinophil counts in the lung and bronchoalveolar lavage (BAL) and CCL11, IL-13, and IL-23p19 release in the BAL of mice sensitized and challenged with Af (p < 0.05). The inhibitory effects of budesonide were attenuated on inflammatory changes and were completely abolished on airway hyperreactivity after O3 exposure of mice sensitized and challenged with Af. O3 stimulated release of pro-neutrophilic mediators including CCL20 and IL-6 into the airways and impaired the inhibitory effects of budesonide on CCL11, IL-13 and IL-23. O3 also prevented budesonide-induced release of the immunoprotective lung collectin SP-D into the airways of allergen-challenged mice. O3 had a bi-phasic direct effect with early (<12 h) inhibition and late (>48 h) activation of SP-D mRNA (sftpd) in vitro. Dexamethasone and budesonide induced sftpd transcription and translation in human type II alveolar epithelial cells in a glucocorticoid receptor and STAT3 (an IL-6 responsive transcription factor) dependent manner. Our study indicates that O3 exposure counteracts the effects of budesonide on airway inflammation, airway hyperreactivity, and SP-D production. We speculate that impairment of SP-D expression may contribute to the acute O3-induced airway inflammation. Asthmatics exposed to high ambient O3 levels may become less responsive to glucocorticoid treatment during acute exacerbations

Actinomyces Infection Leading to Pseudoepitheliomatous Hyperplasia Within a Tattoo

A Caucasian woman in her 40s presented with a one-year history of raised, dry, pruritic papules on the tattoo on the left medial lower leg she received six months prior. Examination revealed multiple open comedones and pustules coalescing into an edematous plaque, limited to the red portions of the tattoo. Histological examination revealed pseudoepitheliomatous hyperplasia, tattoo ink, and brisk lymphohistiocytic inflammation, suggestive of an infectious process. A wound culture grew Actinomyces neuii, and she was subsequently started on amoxicillin 500 mg TID for six months. Topically, she applied mupirocin ointment daily. Subsequent clinic visits demonstrated flattening and resolution of the papules and comedones on this regimen. Tattoos have risen in popularity since the 1970s, and some estimates have found that 10-20% of people of Western cultures have at least one tattoo. Tattoo complications may occur with a broad spectrum of clinical findings. Allergies, pigment foreign body granulomatous reactions, and infections are the most common complications in tattoo. Tattoo infections are commonly due to endogenous bacteria such as Streptococci and Staphylococci species or exogenous agents, leading to viral hepatitis or HIV. This report describes a case of an Actinomyces infection involving the red pigment of a tattoo. Red pigment within tattoos is the most common cause of cutaneous reactions to tattoos. The most common reaction patterns include allergic dermatitis, photosensitivity, granulomatous, lichenoid, and pseudolymphomatous reactions. We describe a case of PEH secondary to Actinomyces neuii infection limited to the red portions of a tattoo. To our knowledge, this is the first case in which Actinomyces species has been implicated in a tattoo infection. Actinomyces species are naturally found in mucous membranes of the mouth, gastrointestinal, and genitourinary tract. Potential niduses for infection in this case could include the use of dirtied instruments, contaminated pigments, or lack of sterility during the procedure. While Actinomyces rarely cause infections in humans, cutaneous infections typically manifest as a soft tissue infection often located on the head or neck, requiring treatment with antibiotics and incision and drainage. Primary cutaneous Actinomycosis is rare; they are typically chronic, recur after short courses of antibiotic treatment and lead to the formation of granules. Actinomyces neuii infection has only been reported in approximately one hundred cases, most commonly associated with abscesses, infected atheromas and diabetic ulcers. One case of A. neuii has been reported as a superinfection of hidradenitis suppurativa. Bacterial infections of tattoos are most commonly associated with Staphylococci or Streptococci infections. Mycobacteria infections of tattoos have also been reported; M. haemophilum is thought to have a predilection for tattoos and extremities as it requires low incubation temperature and iron supplementation for growth. While reactions within red tattoos and bacterial infections of tattoos may be relatively common, infection of the red component of a tattoo with Actinomyces has not yet been described. Biopsy and evaluation for bacterial infections such as Actinomyces should be considered within the differential of a red tattoo reaction.https://scholarlycommons.henryford.com/merf2020caserpt/1059/thumbnail.jp

Yellow Nail Syndrome

HISTORY: A 62-year-old Caucasian female presented for finger and toenail yellowing with associated poor nail growth and intermittent nail shedding over the past 10 years. She also has a history of recurrent pulmonary effusions and lower extremity lymphedema that was diagnosed at approximately the same time. EXAMINATION: There was yellow discoloration of all fingernails and toenails with prominent distal onycholysis without subungual debris. Lunula and cuticles were absent. Fingernails were more affected than toenails. Some nails had slightly thickened and overly curved nail plates without other dystrophic changes. The bilateral lower legs (left worse than right) demonstrated lymphedema. COURSE AND THERAPY: Nail PAS and fungal culture were negative. Prior to presentation, patient received courses of oral terbinafine and fluconazole without improvement. She was placed on vitamin E 1000 units daily and pulse fluconazole for 3 months. Due to minimal improvement, fluconazole was stopped; however, vitamin E was continued. She also performs dilute vinegar soaks to reduce potential superinfection in the setting of onycholysis. Recently, she underwent pulmonary wedge resection and right partial pleurectomy. With regards to her lymphedema, she has been using home pneumatic compression pumps with transient relief. DISCUSSION: Yellow nail syndrome (YNS) is a rare idiopathic disorder characterized by the triad of yellow nails, lymphedema, and respiratory tract problems, however this classic triad occurs only in about one-third of patients. The diagnosis only requires the presence of the typical nail changes. Lymphedema and respiratory tract involvement may develop before, during, or after the nail dystrophy. YNS affects men and women equally, and typically presents in the fourth to sixth decade of life. All nails may be affected, and nails are usually slow growing or appear to have stopped growing. Nails become thicker and turn a pale yellow or green-yellow color with slightly darker edges. Nails can remain smooth, develop cross-ridging, or prominent curvature transversely and longitudinally. There is a loss of cuticles, and the lunula is no longer visible. Onycholysis may affect one or more nails and may extend proximally to the distal matrix, causing nail shedding. The cause of yellow nail syndrome is relatively unknown with most cases occurring sporadically. Possible etiologies include microangiopathy with protein leakage or dysfunctional lymphatic drainage. Lymphedema occurs in about 80% of patients and most frequently affects legs. Respiratory tract involvement usually manifests as pleural effusions, affecting 36% of patients. Patients can also provide a history of recurrent attacks of bronchitis, chronic sinusitis, and pneumonia. Improvement in respiratory disease has been linked to improvement in the appearance and growth of nails. Vitamin E, recommended at 1200 IU daily, has been reported to improve the appearance of nails. Additionally, pulse therapy with itraconazole or fluconazole has been reported to stimulate nail growth and may be given in combination with vitamin E.https://scholarlycommons.henryford.com/merf2019caserpt/1012/thumbnail.jp

The effect of lipoprotein-associated phospholipase A2 deficiency on pulmonary allergic responses in Aspergillus fumigatus sensitized mice.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) has been implicated in the pathogenesis of cardiovascular disease. A therapeutic targeting of this enzyme was challenged by the concern that increased circulating platelet activating factor (PAF) may predispose to or increase the severity of the allergic airway response. The aim of this study was to investigate whether Lp-PLA2 gene deficiency increases the risk of PAF and IgE-mediated inflammatory responses in vitro and in vivo using mouse models.MethodsLp-PLA2-/- mice were generated and back crossed to the C57BL/6 background. PAF-AH activity was measured using a hydrolysis assay in serum and bronchoalveolar lavage (BAL) samples obtained from mice. Aspergillus fumigatus (Af)-specific serum was prepared for passive allergic sensitization of mice in vivo and mast cells in vitro. β- hexosaminidase release was studied in bone marrow derived mast cells sensitized with Af-specific serum or DNP-IgE and challenged with Af or DNP, respectively. Mice were treated with lipopolysaccharide (LPS) and PAF intratracheally and studied 24 hours later. Mice were sensitized either passively or actively against Af and were studied 48 hours after a single intranasal Af challenge. Airway responsiveness to methacholine, inflammatory cell influx in the lung tissue and BAL, immunoglobulin (ELISA) and cytokine (Luminex) profiles were compared between the wild type (WT) and Lp-PLA2-/- mice.ResultsPAF-AH activity was reduced but not completely abolished in Lp-PLA2-/- serum or by in vitro treatment of serum samples with a high saturating concentration of the selective Lp-PLA2 inhibitor, SB-435495. PAF inhalation significantly enhanced airway inflammation of LPS treated WT and Lp-PLA2-/- mice to a similar extent. Sensitized WT and Lp-PLA2-/- bone-marrow derived mast cells released β-hexosaminidase following stimulation by allergen or IgE crosslinking to equivalent levels. Wild type and Lp-PLA2-/- mice responded to passive or active allergic sensitization by significant IgE production, airway inflammation and hyperresponsiveness after Af challenge. BAL cell influx was not different between these strains while IL-4, IL-5, IL-6 and eotaxin release was attenuated in Lp-PLA2-/- mice. There were no differences in the amount of total IgE levels in the Af sensitized WT and Lp-PLA2-/- mice.ConclusionsWe conclude that Lp-PLA2 deficiency in C57BL/6 mice did not result in a heightened airway inflammation or hyperresponsiveness after PAF/LPS treatment or passive or active allergic sensitization and challenge

Precipitation, Circulation, and Cloud Variability Over the Past Two Decades

To better understand the variability of precipitation, circulation, and cloud, we examine the precipitation, vertical velocity, total cloud fraction, condensed water path, and ice water path from observations and 13 Coupled Model Intercomparison Project 5 (CMIP5) models over 1988–2008. All variables are averaged over wet areas and dry areas to investigate temporal variations of different variables over these regions. We found that all models demonstrate similar temporal variations of precipitation as the observational data from the Global Precipitation Climatology Project, with positive trend over wet areas (6.22 ± 3.75 mm/mon/decade) and negative trend over dry areas (−0.77 ± 0.54 mm/mon/decade). Positive trends of vertical velocity, total cloud fraction, condensed water path, and ice water path are also found in the observations and models over the wet areas. Observations also demonstrate decreasing trends of vertical velocity, total clouds, condensed water path, and ice water path over the dry areas, which can be simulated by most models with a few exceptions. The qualitatively consistent trends in these variables (i.e., vertical velocity, cloud, liquid, and ice water contents) as revealed from the observations and CMIPS models provide a clearer picture of the dynamics and physics behind the temporal variations of precipitation over different areas

Ambient pressure upregulates nitric oxide synthase in a phosphorylated-extracellular regulated kinase– and protein kinase C–dependent manner

PurposeUsing endothelial cell/smooth muscle cell (SMC) cocultures, we have demonstrated that pressurized endothelial cell coculture inhibits SMC proliferation and promotes apoptosis, and that this effect is transferable through pressurized endothelial medium. We now hypothesized that endothelial nitric oxide synthase (eNOS) plays a significant role in mediating these pressure-induced effects.MethodsConditioned media from endothelial cells and SMCs exposed to ambient and increased pressure were transferred to recipient SMCs. We counted cells after 5 days of incubation with these media and evaluated eNOS and inducible NOS (iNOS) levels by Western blot.ResultsConditioned media from pressurized endothelial cells significantly decreased recipient SMC counts. This effect was sustained when N-nitro-L-arginine-methyl ester (L-NAME) was added to recipient cells but abolished when L-NAME was added to donor cells. SMCs were then exposed to control and pressurized conditions in monoculture or in coculture with endothelial cells. Pressure and coculture caused similar increase in iNOS levels but had no additive effect in combination. Finally, endothelial cells were exposed to control and pressurized environments. Pressure caused a 24% ± 1.6% increase in eNOS protein (P = .04, n = 12). This effect was sustained when cells were treated with L-NAME (32% ± 1.6% increase, P = .02) but abolished when endothelial cells were treated with calphostin C or PD98059 to block protein kinase C (PKC) or extracellular regulated kinase (ERK). Pressure also increased endothelial phosphorylated ERK (p-ERK) by 1.8-fold to 2.6-fold compared with control conditions after exposure of 2, 4, and 6 hours (P = .02, n = 4). This increase was sustained after pretreatment with calphostin C.ConclusionPressure modulates endothelial cell effects on SMC growth by increasing eNOS in an ERK-dependent and PKC-dependent manner.Clinical RelevanceIntimal hyperplasia is the main cause for restenosis that complicates 10% to 30% of all such vascular procedures and 30% to 40% of endovascular procedures. This article provides some novel information about smooth muscle cell/endothelial cell interaction, one of the main regulators of vascular remodeling and intimal hyperplasia. The role of endothelial cell/smooth muscle cell interaction cannot be studied well in vivo because these interactions cannot be distinguished from other factors that coexist in vivo, such as flow dynamics, matrix proteins, inflammatory factors, and interactions with other cells in the vascular wall and in the bloodstream. In this work, we use pressure as a triggering stimulus to alter in vitro endothelial behavior and identify important changes in endothelial regulation of smooth muscle cell biology. The pathways involved in this process and discussed in this article could ultimately be used to manipulate endothelial cell/smooth muscle cell interaction in clinical disease

Applications and Modeling Techniques of Wind Turbine Power Curve for Wind Farms - A Review

In the wind energy industry, the power curve represents the relationship between the “wind speed” at the hub height and the corresponding “active power” to be generated. It is the most versatile condition indicator and of vital importance in several key applications, such as wind turbine selection, capacity factor estimation, wind energy assessment and forecasting, and condition monitoring, among others. Ensuring an effective implementation of the aforementioned applications mostly requires a modeling technique that best approximates the normal properties of an optimal wind turbines operation in a particular wind farm. This challenge has drawn the attention of wind farm operators and researchers towards the “state of the art” in wind energy technology. This paper provides an exhaustive and updated review on power curve based applications, the most common anomaly and fault types including their root-causes, along with data preprocessing and correction schemes (i.e., filtering, clustering, isolation, and others), and modeling techniques (i.e., parametric and non-parametric) which cover a wide range of algorithms. More than 100 references, for the most part selected from recently published journal articles, were carefully compiled to properly assess the past, present, and future research directions in this active domain