bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimycin A-Induced Mitochondrial Damage Causes Human RPE Cell Death despite Activation of Autophagy
Authors: Hytti Maria , Korhonen Eveliina , Hyttinen Juha M. T. , Roehrich Heidi , Kaarniranta Kai , Ferrington Deborah A. , Kauppinen Anu
Published: March 2019

Mitochondrial dysfunction has been implicated in a wide variety of degenerative diseases, including age-related macular degeneration. Damage to mitochondria and mitochondrial DNA accumulates with age in the postmitotic retinal pigment epithelium (RPE), which could lead to RPE cell death and trigger disease. One possible mechanism for cells to avoid cell death is mitophagy, the targeted clearance of damaged mitochondria by autophagy. Here, we induced mitochondrial damage in human RPE cells (ARPE-19 and hRPE), using antimycin A, an inhibitor of complex III of the electron transport chain, and investigated cellular viability, mitochondrial structure and function, and autophagy activity. We observed that antimycin A evoked dose-dependent cell death, a rapid loss in mitochondrial membrane potential, and a collapse of oxidative phosphorylation. Mitochondria appeared swollen and there was clear damage to their cristae structure. At the same time, cells were undergoing active autophagy and were sensitive to autophagy inhibition by bafilomycin A1 or chloroquine. These results indicate that mitochondrial dysfunction can cause significant RPE damage and that autophagy is an important survival mechanism for cells suffering from mitochondrial damage.
Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat
Authors: Al-Jezani Nedaa , Cho Roger , Masson Anand O. , Lenehan Brian , Krawetz Roman , Lyons Frank G.
Published: March 2019

Study Design. Isolation and characterization of human epidural fat (HEF) stem/progenitor cells.Objective. To identify a progenitor population within HEF and to determine if they meet the minimal criteria of a mesenchymal stem cell (MSC).Summary of Background Data. The biological function, if any, has yet to be determined for HEF. The presence of MSCs within HEF may indicate a regenerative potential within the HEF.Methods. HEF was isolated from 10 patients during elective spinal surgery. HEF cells were differentiated along osteo-, adipo-, and chondrogenic lineages, with differentiation analyzed via qPCR and histology. The cell surface receptor profile of HEF cells was examined by flow cytometry. HEF cells were also assayed through the collagen contraction assay.Prx1CreERT2GFP:R26RTdTomatoMSC lineage-tracking mice were employed to identify EF MSCsin vivo.Results. HEF cell lines were obtained from all 10 patients in the study. Cells from 2/10 patients demonstrated full MSC potential, while cells from 6/10 patients demonstrated progenitor potential; 2/10 patients presented with cells that retained only adipogenic potential. HEF cells demonstrated MSC surface marker expression. All patient cell lines contracted collagen gels. APrx1-positive population in mouse epidural fat that appeared to contribute to the dura of the spinal cord was observedin vivo.Conclusions. MSC and progenitor populations are present within HEF. MSCs were not identified in all patients examined in the current study. Furthermore, all patient lines demonstrated collagen contraction capacity, suggesting either a contaminating activated fibroblast population or HEF MSCs/progenitors also demonstrating a fibroblast-like phenotype.In vivoanalysis suggests that these cell populations may contribute to the dura. Overall, these results suggest that cells within epidural fat may play a biological role within the local environment above providing a mechanical buffer.
Comparing the Potential of Near- and Mid-Infrared Spectroscopy in Determining the Freshness of Strawberry Powder from Freshly Available and Stored Strawberry
Authors: Wang Da , Wei Wenwen , Lai Yanhua , Yang Xiangzheng , Li Shaojia , Jia Lianwen , Wu Di
Published: March 2019

The quality of strawberry powder depends on the freshness of the fruit that produces the powder. Therefore, identifying whether the strawberry powder is made from freshly available, short-term stored, or long-term stored strawberries is important to provide consumers with quality-assured strawberry powder. Nevertheless, such identification is difficult by naked eyes, as the powder colours are very close. In this work, based on the measurement of near-infrared (NIR) spectroscopy and mid-infrared (MIR) spectra of strawberry powered, good classification results of 100.00% correct rates to distinguish whether the strawberry powder was made from freshly available or stored fruit was obtained. Furthermore, partial least squares regression and least squares support vector machines (LS-SVM) models were established based on NIR, MIR, and combination of NIR and MIR data with full variables or optimal variables of strawberry powder to predict the storage days of strawberries that produced the powder. Optimal variables were selected by successive projections algorithm (SPA), uninformation variable elimination, and competitive adaptive reweighted sampling, respectively. The best model was determined as the SPA-LS-SVM model based on MIR spectra, which had the residual prediction deviation (RPD) value of 11.198 and the absolute difference between root-mean-square error of calibration and prediction (AB_RMSE) value of 0.505. The results of this work confirmed the feasibility of using NIR and MIR spectroscopic techniques for rapid identification of strawberry powder made from freshly available and stored strawberry.
RAMHU: A New Robust Lightweight Scheme for Mutual Users Authentication in Healthcare Applications
Authors: Al-Zubaidie Mishall , Zhang Zhongwei , Zhang Ji
Published: March 2019

Providing a mechanism to authenticate users in healthcare applications is an essential security requirement to prevent both external and internal attackers from penetrating patients’ identities and revealing their health data. Many schemes have been developed to provide authentication mechanisms to ensure that only legitimate users are authorised to connect, but these schemes still suffer from vulnerable security. Various attacks expose patients’ data for malicious tampering or destruction. Transferring health-related data and information between users and the health centre makes them exposed to penetration by adversaries as they may move through an insecure channel. In addition, previous mechanisms have suffered from the poor protection of users’ authentication information. To ensure the protection of patients’ information and data, we propose a scheme that authenticates users based on the information of both the device and the legitimate user. In this paper, we propose a Robust Authentication Model for Healthcare Users (RAMHU) that provides mutual authentication between the server and clients. This model utilizes an Elliptic Curve Integrated Encryption Scheme (ECIES) and PHOTON to achieve strong security and good overall performance. RAMHU relies on multiple-pseudonym, physical address, and one-time password mechanisms to authenticate legitimate users. Moreover, extensive informal and formal security analysis with the automated validation of Internet security protocols and applications (AVISPA) tool demonstrate that our model offers a high level of security in repelling a wide variety of possible attacks.
Influence of Different Production Systems on the Quality and Shelf Life of Poultry Meat: A Case Study in the German Sector
Authors: Albrecht Antonia , Hebel Martin , Mittler Maureen , Hurck Carola , Kustwan Katharina , Heitkönig Barbara , Bitschinski Daniel , Kreyenschmidt Judith
Published: March 2019

Production-specific factors, such as breeding, diet, and stress, are known to influence meat quality, but the effect of different husbandry systems on the development of quality parameters and shelf life has hardly been investigated. Thus, the aim of the study was the investigation of an alternative production system based on a slow-growing, corn-fed, and antibiotics-free chicken line compared with conventional poultry production. Additionally, the effect on meat quality, microbiology, and spoilage was analyzed. In total, 221 breast filets from a German poultry meat producer were investigated. Nutritional, biochemical, and cooking loss analyses were conducted on a subset of samples 24 h after storage. The rest of the samples were stored aerobically at 4°C, and the spoilage process was characterized by investigating pH, color, lipid oxidation, microbiology, and sensory attributes subsequently every two days during storage. The alternative production line showed a significantly healthier nutritional profile with a higher protein and lower fat content. Additionally, the amount of L-lactic acid and D-glucose was significantly higher than in the conventional production line. The color values differed between both production lines, with the corn-fed line displaying more yellowish filets. The lipid oxidation and microbial spoilage were not affected by the production line. The shelf life did not differ between the investigation groups and was deemed 7 days in both cases. Despite the highest severity of white striping being observed most in the conventional production line, there was no overall difference in the incidence among groups. The purchase decision was affected by the occurrence of white striping and showed a tendency for a higher acceptance for the alternative production line.
Anti-Atopic Dermatitis Effect of Seaweed Fulvescens Extract via Inhibiting the STAT1 Pathway
Authors: Gil Tae-Young , Kang Yun-Mi , Eom Ye-Jin , Hong Chul-Hee , An Hyo-Jin
Published: March 2019

Seaweed fulvescens (SF) is a green alga rich in chlorophyll with unique flavor and taste. It is also called Maesaengi which has antioxidant and other physiological activities. In the present study, we evaluated the therapeutic effects of SF in a mouse model of Dermatophagoides farinae body-induced atopic dermatitis (AD) and in tumor necrosis factor-α and interferon-γ-stimulated HaCaT keratinocytes. SF treatment (200 mg/mouse) inhibited the development of AD symptoms, compared to that in the control group, as evidenced from the improved dorsal skin lesion, reduced thickness and infiltration of inflammatory cells and smaller lymph nodes, and reduced levels of proinflammatory cytokines. In HaCaT keratinocytes, SF (10, 25, and 50 μg/mL) suppressed the production of proinflammatory cytokines in a dose-dependent manner. In addition, SF reduced the phosphorylation of signal transducer and activator of transcription 1, which is one of the major signaling molecules involved in cellular inflammation. These results suggested that SF could be a potential therapeutic alternative for the treatment of AD.
Interactions between Germline and Somatic Mutated Genes in Aggressive Prostate Cancer
Authors: Mamidi Tarun Karthik Kumar , Wu Jiande , Hicks Chindo
Published: March 2019

Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the USA. Advances in high-throughput genotyping and next generation sequencing technologies have enabled discovery of germline genetic susceptibility variants and somatic mutations acquired during tumor formation. Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the possible oncogenic interactions and cooperation between germline and somatic variation and their role in aggressive PCa remain largely unexplored. Here we investigated the possible oncogenic interactions and cooperation between genes containing germline variation from genome-wide association studies (GWAS) and genes containing somatic mutations from tumor genomes of 305 men with aggressive tumors and 52 control samples from The Cancer Genome Atlas (TCGA). Network and pathway analysis were performed to identify molecular networks and biological pathways enriched for germline and somatic mutations. The analysis revealed 90 functionally related genes containing both germline and somatic mutations. Transcriptome analysis revealed a 61-gene signature containing both germline and somatic mutations. Network analysis revealed molecular networks of functionally related genes and biological pathways including P53, STAT3, NKX3-1, KLK3, and Androgen receptor signaling pathways enriched for germline and somatic mutations. The results show that integrative analysis is a powerful approach to uncovering the possible oncogenic interactions and cooperation between germline and somatic mutations and understanding the broader biological context in which they operate in aggressive PCa.
Screening and Early Identification of Spinal Deformities and Posture in 311 Children: Results from 16 Districts in Slovakia
Authors: Rusnák Róbert , Kolarová Marina , Aštaryová Ivana , Kutiš Peter
Published: March 2019

Objective. In our study, we wanted to identify the number of existing deformities of the spine and posture in primary schoolers. Methods. The sample consisted of 311 healthy pupils aged 6-7. We used Klein, Thomas, and Mayer method to evaluate the posture. The spine curvature was evaluated by plumb line. Muscle imbalance was evaluated by standardized manual tests by Professor Janda. The results were evaluated by the basic population abundance and the use of the ANOVA program. We determined the level of statistical significance at p = 0.05. Results. The statistically significant occurrence of poor posture was found. Poor posture occurred in more than 50% of the pupils studied. Spine deformities in the sagittal plane have exceeded 30% (C = 37.94212%; Th = 32.15434%; L = 30.22508%). In the frontal plane deformities were present in 13.18328% of pupils. Spinae and postural disorders were accompanied by the muscle imbalance (muscle stiffness and weakness). Conclusion. Screening is a well-founded technique for the early detection of spinae and posture disorders. Based on the results of screening, professionals can take preventive measures. As in our research prevalence of spine deformities and poor posture in children was high, we recommend regular screening in clinical practice.
Effect of Dissimilatory Iron Reduction on the Reduction of CH4Production in Landfill Conditions
Authors: Hu Lifang , Long Yuyang , Fang Chengran
Published: March 2019

A high solid anaerobic incubation system was used to study the effect of dissimilatory iron reduction on the inhibition of methanogenesis in a landfill. Different iron sources including FeC6H5O7, Fe2(SO4)3, Fe2O3, and Fe0were studied. The different iron sources significantly affected the methanogenesis process in the simulated landfill system. FeC6H5O7and Fe2(SO4)3inhibited methanogenesis but Fe0and Fe2O3increased it. The dissimilatory iron reduction with FeC6H5O7as the iron source demonstrates an anaerobic mineralization process, which enhances the biodegradation but inhibits methanogenesis. The highest rate of reduction of CH4production (51.9%) was obtained at a dosage rate of 16,000 mg·kg−1, which corresponded to a reduction of 0.86 g of CH4per kg of organic matrix. Active inhibition by methanogens using both the hydrogenotrophic and acetoclastic pathways is considered to be the main mechanism underlying the reduction of CH4production by dissimilatory iron reduction with FeC6H5O7as the iron source. This is the first report on the effect of different iron forms on the reduction of CH4production during landfilling with organic solid waste.
Bridge Structure Dynamic Analysis under Vessel Impact Loading considering Soil‐Pile Interaction and Linear Soil Stiffness Approximation
Authors: Zhang Jingfeng , Li Xiaozhen , Jing Yuan , Han Wanshui
Published: March 2019

The appropriate modeling of the soil‐pile interaction (SPI) is critical to get the reasonable dynamic responses of bridge structure under impact loading. Of various SPI modeling approaches, utilizing p-y and t-z curves is a common method to represent the nonlinear lateral resistance and skin friction of pile‐surrounding soil. This paper accomplished SPI modeling for the bridge pylon impact analysis with compression‐only nonlinear springs and linear dashpots. The kinematic interaction and pile group effect were incorporated into the SPI. A variety of pylon impact analyses were conducted under energy‐variation impact loads. The structure dynamic responses were compared and discussed considering the influences of pile group effect, soil damping, and axial t-z spring. An approximate approach was proposed to derive the linearized stiffness of soil for the purpose of engineering calculation. It was concluded from the extensive simulations that the impact load generated from higher initial energy induced more significant structural responses and larger soil inelastic deformation than smaller initial energy. The piles in the leading row possessed larger bending moments, whereas they exhibited smaller pile deformation than the responses of trailing row piles. Soil damping applied in SPI played positive roles on the reduction of structural responses. Replacing the t-z spring by fixing the degree‐of‐freedom (DOF) in the vertical direction was capable to yield satisfactory results of structural responses. The proposed linear soil stiffness was demonstrated to be applicable in the SPI modeling of structure impact analysis.
Compressed Sensing-Based Sparsity Adaptive Doubly Selective Channel Estimation for Massive MIMO Systems
Authors: Kong Weisi , Li Hui , Zhang Wenjie
Published: March 2019

By exploiting the sparsity of the channel in the delay and angle domains, compressed sensing (CS) algorithms can be used for channel estimation of massive multiple-input multiple-output (MIMO) systems to reduce pilot overhead. Due to the Doppler frequency shift, however, the intercarrier interference (ICI) and the rapid change of the channel state result in the poor estimation effect of doubly selective (DS) channel. In this paper, we propose the block sparsity adaptive matching pursuit (B-SAMP) algorithm to solve this problem. Firstly, the complex exponential basis expansion model (CE-BEM) is used to convert numerous channel tap coefficients into BEM parameter vectors and then the sparsity adaptive channel estimation scheme based on compressed sensing is proposed. Specifically, the ICI-free model is obtained by using the proposed equally placed pilot group scheme, and the B-SAMP algorithm is proposed by using the spatio-temporal common sparsity of the channel to complete the estimation of DS channel. Finally, a linear smoothing method is used to reduce the error caused by CE-BEM, thereby further improving the accuracy of the estimation. The simulation results show that the proposed method not only improves the estimation accuracy compared with the existing scheme but also requires fewer pilots.
Multiobjective Based Resource Allocation and Scheduling for Postdisaster Management Using IoT
Authors: Choksi Meghavi , Zaveri Mukesh A.
Published: March 2019

Disaster is an uncertain phenomenon that arises due to natural as well as man-made calamities. Disaster often causes a high degree of destruction, especially in a very densely populated region. To handle such a situation, efficient resource management strategies are required. Resource management is the most crucial phase of disaster management. Efficient and in-time allocation of resources is very important; otherwise, it may result in more fatalities. In this context, we propose the resource management algorithm, which deals with both over- and underdemand for resources. Resource management requires efficient resource allocation, and in case of overdemand for resources, it must be followed by resource scheduling. In this paper, we introduce a resource allocation technique which is based on multiple objectives having a different set of constraints. We also propose the resource scheduling algorithm based on various parameters. The proposed algorithm uses multiobjective theory for resource allocation which is followed by the implementation of priority-based scheduling technique, in the case of overdemand for resources. Our proposed methods are compared to the existing approaches in the literature. From the simulation results, it is clear that our methods perform optimum resource allocation and scheduling operations.
The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer
Authors: Wu Mingxia , Leng Weiling , Pan Hang , Lei Xiaotian , Chen Liu , Ouyang Xinshou , Liang Ziwen
Published: March 2019

Background. Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism. Methods. The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease≤4 weeks and the chronic wound (CW) group with the course of disease>4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-κB (NF-κB), and interleukin-6 (IL-6) were detected by western blot. Results. A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group (P<0.05), and the expression of NF-κB and IL-6 was obviously increased (P<0.05). Conclusion. The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.
Rare Primary Pulmonary Marginal Zone Lymphoma Presenting with Incidental Pulmonary Nodules
Authors: Ullah Saad , Ali Mirza , Song Mingchen
Published: March 2019

Pulmonary malignancies carry a significant morbidity and mortality and are one of the leading causes of cancer-related deaths worldwide. Primary pulmonary lymphoma is a rare malignancy which should be considered in the differential of solitary pulmonary nodule or lung mass especially in a low-risk patient presenting with constitutional symptoms. Here, we describe a case of an elderly male who presented to our clinic with incidental pulmonary nodules and subsequent workup revealed low grade B cell non-Hodgkin's lymphoma consistent with diagnosis of primary pulmonary marginal zone lymphoma.
Unusual Case of Malignant Struma Ovarii and Cervical Thyroid Cancer Preceded by Ovarian Teratoma: Case Report and Review of the Literature
Authors: Tzelepis Elias G. , Barengolts Elena , Garzon Steven , Shulan Joseph , Eisenberg Yuval
Published: March 2019

Objective. To present a rare case of malignant struma ovarii (MSO) and synchronous thyroid cancer, review the medical literature, and present the latest trends in management.Methods. The case of a woman with MSO and concomitant thyroid cancer is presented, including clinical presentation, treatment, and follow-up care. A search of the English-language literature was conducted using MEDLINE and Google Scholar data bases.Results. We found 10 publications (one abstract) describing 10 patients with MSO and concomitant thyroid cancer. Six additional patients were reported by a study that analyzed the SEER (cancer registry) database. The median age of women was 42 years, with the majority of them presenting with abdominal symptoms. Histologically, most tumors were papillary carcinomas in both organs. In 5 patients, there was extrathyroidal tumor extension at time of surgery.Conclusion. MSO can occasionally coexist with highly aggressive eutopic thyroid cancer. Although this concurrence is even rarer than MSO, clinicians should routinely investigate for possible synchronous thyroid cancer in all cases of MSO and also consider aggressive postoperative treatment including thyroidectomy and radioiodine ablation therapy in cases of MSO.
Mass-Forming Ischemic Colitis: A Potential Mimicker of Malignancy
Authors: Danakas Alexandra M. , Fazili Bushra G. , Huber Aaron R.
Published: March 2019

Ischemic colitis (IC) results from reduced colonic vascular perfusion, accounting for 50-60% of all gastrointestinal ischemic episodes. IC leads to mucosal damage with clinical symptom severity developing based on the duration and extent of colonic injury. In rare cases IC may form a mass-like lesion mimicking malignancy. Here we present the case of a 55-year-old female with hematochezia and diarrhea, who on workup was found to have a mass-like lesion at the ileocecal valve. Multiple biopsies demonstrated ischemic change and mucosal injury without evidence of dysplasia or carcinoma. Two months later on follow-up imaging, after supportive treatment the lesion was completely resolved. It is critical for gastroenterologists and pathologists to be aware of this variant of IC to avoid unnecessary surgical procedures and treatment of patients.
Minimalistic Approach to Coreference Resolution in Lithuanian Medical Records
Authors: Žitkus Voldemaras , Butkienė Rita , Butleris Rimantas , Maskeliūnas Rytis , Damaševičius Robertas , Woźniak Marcin
Published: March 2019

Coreference resolution is a challenging part of natural language processing (NLP) with applications in machine translation, semantic search and other information retrieval, and decision support systems. Coreference resolution requires linguistic preprocessing and rich language resources for automatically identifying and resolving such expressions. Many rarer and under-resourced languages (such as Lithuanian) lack the required language resources and tools. We present a method for coreference resolution in Lithuanian language and its application for processing e-health records from a hospital reception. Our novelty is the ability to process coreferences with minimal linguistic resources, which is important in linguistic applications for rare and endangered languages. The experimental results show that coreference resolution is applicable to the development of NLP-powered online healthcare services in Lithuania.
Adaptive Optics (rtx1) High-Resolution Imaging of Photoreceptors and Retinal Arteries in Patients with Diabetic Retinopathy
Authors: Zaleska-Żmijewska Anna , Wawrzyniak Zbigniew M. , Dąbrowska Anna , Szaflik Jacek P.
Published: March 2019

Background. Diabetic retinopathy (DR) is the leading cause of impaired vision in patients with diabetes mellitus. An adaptive optics retinal camera (rtx1™; Imagine Eyes, France) was used to capture images of cones and retinal arteries from patients with DR. Objective. Cone parameters (density, interphotoreceptor distance, and regularity) and retinal artery parameters (wall thickness, lumen diameter, WLR, and WCSA) were analyzed in 36 patients with nonproliferative DR (NPDR; 22 with mild NPDR and 14 with moderate NPDR) and in 20 healthy volunteers (the control group). Results. Cone density at 2° eccentricities was significantly lower in the DR compared to the control group (19822±4342 cells/mm2 vs. 24722±3507 cells/mm2, respectively). Cone density and regularity decreased with increasing severity of DR. The artery walls were significantly thicker in the DR group. The WLR and WCSA differed significantly between the DR and the control groups (WLR 0.339±0.06 vs. 0.254±0.04; WCSA 5567±1140 vs. 4178±944, respectively). Conclusions. Decreased cone regularity and density are seen in patients with mild and moderate NPDR. Abnormalities of retinal arterioles show signs of arteriolar dysfunction in DR. Retinal image analysis with the rtx1 offers a novel noninvasive measurement of early changes in the neural cells and retina vasculature in diabetic eyes.
Negative Regulation of p53-Induced Senescence by N-WASP Is Crucial for DMBA/TPA-Induced Skin Tumor Formation
Authors: Li Hui , Petersen Simon , Garcia Mariscal Alberto , Brakebusch Cord
Published: March 2019

Mice with a keratinocyte-restricted deletion of the actin polymerization–promoting molecule, N-WASP, display cyclic hair loss and skin inflammation. Here, we showed that these mice were also resistant to 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin tumor formation. This resistance correlated with decreased expression of the senescence regulator, DNMT1, and increased expression of the senescence marker, p16Ink4a, in N-WASP–deficient epidermis. Moreover, primary N-WASP–null keratinocytes displayed a premature senescence phenotype in vitro. Expression and activation of p53, a major inducer of senescence, was not significantly altered in N-WASP–null keratinocytes. However, impairment of p53 function effectively rescued the senescence phenotype, indicating that N-WASP was an inhibitor of p53-induced senescence. Mechanistically, N-WASP regulated senescence by preventing p53-dependent degradation of the H3K9 methyltransferases, G9a/GLP, and the DNA methyltransferase, DNMT1, which both control keratinocyte senescence. This pathway collaborated with other N-WASP–independent, senescence-promoting signaling downstream of p53 and allowed the fine tuning of p53-induced senescence by N-WASP. Collectively, these data reveal N-WASP as an inhibitor of p53-induced senescence, which might be of importance for skin tumor formation and cellular aging of keratinocytes.

Significance:

These findings demonstrate that N-WASP regulates p53-dependent senescence in keratinocytes in vitro and in vivo.
Inhibition of EphB4–Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers
Authors: Bhatia Shilpa , Oweida Ayman , Lennon Shelby , Darragh Laurel B. , Milner Dallin , Phan Andy V. , Mueller Adam C. , Van Court Benjamin , Raben David , Serkova Natalie J. , Wang Xiao-Jing , Jimeno Antonio , Clambey Eric T. , Pasquale Elena B. , Karam Sana D.
Published: March 2019

Identifying targets present in the tumor microenvironment that contribute to immune evasion has become an important area of research. In this study, we identified EphB4–ephrin-B2 signaling as a regulator of both innate and adaptive components of the immune system. EphB4 belongs to receptor tyrosine kinase family that interacts with ephrin-B2 ligand at sites of cell–cell contact, resulting in bidirectional signaling. We found that EphB4–ephrin-B2 inhibition alone or in combination with radiation (RT) reduced intratumoral regulatory T cells (Tregs) and increased activation of both CD8+ and CD4+Foxp3− T cells compared with the control group in an orthotopic head and neck squamous cell carcinoma (HNSCC) model. We also compared the effect of EphB4–ephrin-B2 inhibition combined with RT with combined anti-PDL1 and RT and observed similar tumor growth suppression, particularly at early time-points. A patient-derived xenograft model showed reduction of tumor-associated M2 macrophages and favored polarization towards an antitumoral M1 phenotype following EphB4–ephrin-B2 inhibition with RT. In vitro, EphB4 signaling inhibition decreased Ki67-expressing Tregs and Treg activation compared with the control group. Overall, our study is the first to implicate the role of EphB4–ephrin-B2 in tumor immune response. Moreover, our findings suggest that EphB4–ephrin-B2 inhibition combined with RT represents a potential alternative for patients with HNSCC and could be particularly beneficial for patients who are ineligible to receive or cannot tolerate anti-PDL1 therapy.

Significance:

These findings present EphB4–ephrin-B2 inhibition as an alternative to anti-PDL1 therapeutics that can be used in combination with radiation to induce an effective antitumor immune response in patients with HNSCC.
Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer
Authors: Srivastava Amit K. , Banerjee Ananya , Cui Tiantian , Han Chunhua , Cai Shurui , Liu Lu , Wu Dayong , Cui Ri , Li Zaibo , Zhang Xiaoli , Xie Guozhen , Selvendiran Karuppaiyah , Patnaik Srinivas , Karpf Adam R. , Liu Jinsong , Cohn David E. , Wang Qi-En
Published: March 2019

Cancer stem cells (CSC) play a central role in cancer metastasis and development of drug resistance. miRNA are important in regulating CSC properties and are considered potential therapeutic targets. Here we report that miR-328–3p (miR-328) is significantly upregulated in ovarian CSC. High expression of miR-328 maintained CSC properties by directly targeting DNA damage binding protein 2, which has been shown previously to inhibit ovarian CSC. Reduced activity of ERK signaling in ovarian CSC, mainly due to a low level of reactive oxygen species, contributed to the enhanced expression of miR-328 and maintenance of CSC. Inhibition of miR-328 in mouse orthotopic ovarian xenografts impeded tumor growth and prevented tumor metastasis. In summary, our findings provide a novel mechanism underlying maintenance of the CSC population in ovarian cancer and suggest that targeted inhibition of miR-328 could be exploited for the eradication of CSC and aversion of tumor metastasis in ovarian cancer.

Significance:

These findings present inhibition of miR-328 as a novel strategy for efficient elimination of CSC to prevent tumor metastasis and recurrence in patients with epithelial ovarian cancer.
Relief of Procedural Pain in Critically Ill Patients by Music Therapy: A Randomized Controlled Trial
Authors: Yaman Aktaş Yeşim , Karabulut Neziha
Published: March 2019

Background: This study aimed to determine the effectiveness of music listening for procedural pain relief using two different observational pain tools during endotracheal suctioning. Materials and Methods: This study was a randomized controlled trial. The sample of the study included 98 patients with mechanical ventilation support who met the selection criteria. The patients were randomly assigned to control and music therapy groups. Patients in the control group were routinely suctioned as usual. Patients in the music group received music therapy 20 min before, during, and 20 min after endotracheal suctioning. The primary outcome was the pain relief during suctioning. Results: Forty patients in each arm completed the study. Pain scores in the Critical Care Pain Observation Tool and Behavioral Pain Scale were lower in the music group than in the control group during endotracheal suctioning (group: F = 14.85, p = 0.000; F = 9.04, p = 0.000, respectively). It was also found to be a significant interaction effect between the groups and time (group × time: F = 17.35, p = 0.000; F = 18.00, p = 0.000, respectively). Conclusion: The Critical Care Pain Observation Tool and Behavioral Pain Scale in the current study generally demonstrated similar pain scores during the painful procedure. Our findings support that music therapy may act as a nonpharmacological therapy to relieve procedural pain in patients on mechanical ventilation.
Surgical Superior Sagittal Sinus Thrombectomy in Refractory Thrombosis: A Technical Note
Authors: Westwick Harrison J. , Obaid Sami , Bordeleau-Roy Frederique , Truffer Eric , Weil Alexander G.
Published: March 2019

Objective: Surgical treatment options are limited for medically and endovascular refractory cerebral venous sinus thrombosis (CVT). We describe the technical feasibility of open, direct sinus thrombectomy in a pediatric patient with medically and endovascular refractory CVT. Methods: A 15-year-old patient with superior sagittal sinus (SSS) thrombosis refractory to medical and endovascular treatment experienced clinical deterioration with the progression of bifrontal hematomas and cerebral edema. The patient was treated surgically with a decompressive hemicraniectomy and burr hole SSS thrombectomy with a Fogarty balloon and direct sinus injection of tissue plasminogen activator. Results: Surgical treatment with decompressive craniotomy and direct sinus thrombectomy was technically feasible with excellent intracranial pressure control, and radiological recanalization of the superior sagittal sinus with a good clinical outcome. Conclusion: Direct surgical sinus thrombectomy is a potential concomitant treatment strategy with decompressive craniectomy for medically refractory CVT in a pediatric setting.
Fine-Needle Aspiration Biopsy Management of the Axilla in Primary Breast Carcinoma
Authors: Gibbons Ciara Ellen , Quinn Cecily Mary , Gibbons David
Published: March 2019

Context: Fine-needle aspiration biopsy (FNAB) is frequently used to stage the axilla preoperatively in patients with primary breast carcinoma. In the light of the ACOSOG-Z0011 and AMAROS trials that specified sentinel lymph node biopsy as an inclusion criterion, the role of FNAB in axillary staging is changing. Objective: This article will review the diagnostic accuracy of FNAB in staging of the axilla in patients with primary breast carcinoma. The efficacy of axillary FNAB compared with core-needle biopsy will be evaluated. The evolving approach to staging of the axilla, in the light of ACOSOG-Z0011 and AMAROS trials, will be discussed. Data Sources: Data were sourced from published peer-reviewed articles in PubMed (US National Library of Medicine) and published guidelines including the European Guidelines for Quality Assurance in Breast Cancer and those from the European Society of Medical Oncology (ESMO), Union for International Cancer (UICC), American Society of Clinical Oncology (ASCO), and the American Society of Breast Surgeons. Conclusions: FNAB of the axilla is almost 100% specific with a sensitivity between 40 and 90%. A positive FNAB reduces the need for a second axillary procedure by up to 20% with reduced morbidity and cost. The recent ACOSOG-Z0011 and AMAROS trials have reduced the use of FNAB axilla in American protocols, but it remains the standard of care in Europe.
Comparison of Cortisol Stress Response in Patients with Panic Disorder, Cannabis-Induced Panic Disorder, and Healthy Controls
Authors: Petrowski Katja , Conrad Rupert
Published: March 2019

Background/Aims: Little research effort has so far been dedicated to the analysis of the hypothalamic-pituitary-adrenal axis of aetiologically differing subgroups of patients with panic disorder (PD). The current study aimed at a deeper understanding of the cortisol stress response in cannabis-induced PD (CIPD) patients. Methods: Matched groups of 7 PD patients (mean age ± SD: 32.95 ± 9.04 years), 7 CIPD patients (31.94 ± 8.40 years), and 7 healthy controls (HC) (31.13 ± 8.57 years) were included in the study. The Trier Social Stress Test (TSST) was used for stress induction. Salivary cortisol samples were collected and panic- and depression-related questionnaires were applied. Results: A stress response to the TSST was found in 28.6% of PD patients, in 51.1% of CIPD patients, and in 100% of HC subjects. Statistical analyses revealed a cortisol hyporesponsiveness in PD and CIPD patients. While cortisol values of PD patients and HC participants differed significantly, CIPD patients’ cortisol courses balanced between those of PD patients and HC subjects. Conclusions: Current findings show a distinctive pattern of the stress-induced cortisol reaction in CIPD patients, which is markedly different from the hormonal response in PD patients as well as HC subjects. Previous findings of cortisol hyporesponsiveness in PD patients compared to HC subjects were confirmed.
Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study)
Authors: Sonmez Alper , Yumuk Volkan , Haymana Cem , Demirci Ibrahim , Barcin Cem , Kıyıcı Sinem , Güldiken Sibel , Örük Gonca , Ozgen Saydam Basak , Baldane Süleyman , Kutlutürk Faruk , Küçükler Ferit Kerim , Deyneli Oğuzhan , Çetinarslan Berrin , Sabuncu Tevfik , Bayram Fahri , Satman Ilhan ,   TEMD Study Group
Published: March 2019

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.
Triamcinolone Acetonide versus Fluticasone Propionate in the Treatment of Perennial Allergic Rhinitis: A Randomized, Parallel-Group Trial
Authors: Karaulov Alexander V. , Vylegzhanina Tamara , Ovchinnikov Andrey  , Chernikova Mariia , Nenasheva Nataiya
Published: March 2019

Background: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide. Objectives: In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults. Methods: In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events. Results: The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: –8.2 ± 3.0 in the triamcinolone acetonide arm versus –8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide – fluticasone propionate) for rTNSS change from baseline was –0.2 (95% confidence interval –0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate. Conclusions: Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile.
Torpedo Maculopathy Associated with NEXMIF Mutation
Authors: Alarcon-Martinez Tuğba , Khan Ayesha , Myers Kenneth A.
Published: March 2019

Mutations in the neurite extension and migration factor (NEXMIF) gene are associated with X-linked intellectual disability. Thus far, all males reported with NEXMIF mutations have mild to profound intellectual disability with varying combinations of autistic features, poor or absent speech, epilepsy, facial dysmorphism, and strabismus. Affected females tend to have milder intellectual disability but severe, drug-resistant epilepsy. Here, we present a 32-month-old boy with a novel de novo frameshift NEXMIF pathogenic variant (p.Glu375ArgfsX21) who has mild motor delay, language delay, autistic features, and strabismus. In addition to these commonly described findings of NEXMIF mutations, his fundus exam revealed a very rare ophthalmologic abnormality, torpedo maculopathy. This finding has not previously been reported with NEXMIF mutation; however, on literature review, 7/15 males with NEXMIF mutations had other ophthalmologic abnormalities. This patient expands the phenotypic spectrum for males with NEXMIF mutations and suggests that NEXMIF may play an important role in ocular development.
Microbiological Screening of Platelet Concentrates in Europe
Authors: Prax Marcel , Bekeredjian-Ding Isabelle , Krut Oleg
Published: March 2019

The risk of transfusion-associated sepsis due to transmission of bacteria is a persistent problem in the transfusion field. Despite numerous interventions to reduce the risk, cases of bacterial sepsis following transfusion are repeatedly being reported. Especially platelet concentrates are highly susceptible to bacterial contaminations due to the growth-promoting storage conditions. In Europe, blood establishments and national authorities have implemented individual precaution measures to mitigate the risk of bacterial transmission. To obtain an overview of the different approaches, we compiled information from national authorities, blood establishments, and the current literature. Several aspects such as the shelf life of platelets, time of sampling and the applied control measures are compared between the member states. The analysis of the data revealed a broad heterogeneity of procedures on a national level ranging from platelet release without any safety testing up to mandatory screening of all platelet concentrates prior to transfusion. Despite the substantial progress made in recent years, several bacterial reports on transfusion-associated sepsis indicate that further efforts are needed to increase the safety of blood transfusions in the long term.