bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent Clustering Models for Outlier Identification in Telecom Data
Authors: Ouyang Ye , Huet Alexis , Shim J. P. , Hu Mantian (Mandy)
Published: December 2016

Collected telecom data traffic has boomed in recent years, due to the development of 4G mobile devices and other similar high-speed machines. The ability to quickly identify unexpected traffic data in this stream is critical for mobile carriers, as it can be caused by either fraudulent intrusion or technical problems. Clustering models can help to identify issues by showing patterns in network data, which can quickly catch anomalies and highlight previously unseen outliers. In this article, we develop and compare clustering models for telecom data, focusing on those that include time-stamp information management. Two main models are introduced, solved in detail, and analyzed: Gaussian Probabilistic Latent Semantic Analysis (GPLSA) and time-dependent Gaussian Mixture Models (time-GMM). These models are then compared with other different clustering models, such as Gaussian model and GMM (which do not contain time-stamp information). We perform computation on both sample and telecom traffic data to show that the efficiency and robustness of GPLSA make it the superior method to detect outliers and provide results automatically with low tuning parameters or expertise requirement.
Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice
Authors: Ellman Ditte Gry , Degn Matilda , Lund Minna Christiansen , Clausen Bettina Hjelm , Novrup Hans Gram , Flæng Simon Bertram , Jørgensen Louise Helskov , Suntharalingam Lujitha , Svenningsen Åsa Fex , Brambilla Roberta , Lambertsen Kate Lykke
Published: December 2016

Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (mTNFΔ/Δ), to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI inmTNFΔ/Δmice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5), despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels inmTNFΔ/Δmice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.
Recursive Utility Maximization for Terminal Wealth under Partial Information
Authors: Ji Shaolin , Shi Xiaomin
Published: December 2016

This paper concerns the recursive utility maximization problem for terminal wealth under partial information. We first transform our problem under partial information into the one under full information. When the generator of the recursive utility is concave, we adopt the variational formulation of the recursive utility which leads to a stochastic game problem and characterization of the saddle point of the game is obtained. Then, we study the K-ignorance case and explicit saddle points of several examples are obtained. At last, when the generator of the recursive utility is smooth, we employ the terminal perturbation method to characterize the optimal terminal wealth.
CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity
Authors: Pereira Catia S. , Macedo M. Fatima
Published: December 2016

Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.
Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases
Authors: Li Sha , Hong Ming , Tan Hor-Yue , Wang Ning , Feng Yibin
Published: December 2016

The crucial roles of oxidative stress and inflammation in the development of hepatic diseases have been unraveled and emphasized for decades. From steatosis to fibrosis, cirrhosis and liver cancer, hepatic oxidative stress, and inflammation are sustained and participated in this pathological progressive process. Notably, increasing evidences showed that oxidative stress and inflammation are tightly related, which are regarded as essential partners that present simultaneously and interact with each other in various pathological conditions, creating a vicious cycle to aggravate the hepatic diseases. Clarifying the interaction of oxidative stress and inflammation is of great importance to provide new directions and targets for developing therapeutic intervention. Herein, this review is concerned with the regulation and interdependence of oxidative stress and inflammation in a variety of liver diseases. In addition to classical mediators and signaling, particular emphasis is placed upon immune suppression, a potential linkage of oxidative stress and inflammation, to provide new inspiration for the treatment of liver diseases. Furthermore, since antioxidation and anti‐inflammation have been extensively attempted as the strategies for treatment of liver diseases, the application of herbal medicines and their derived compounds that protect liver from injury via regulating oxidative stress and inflammation collectively were reviewed and discussed.
Outcomes of Radiofrequency Ablation for Dysplastic Barrett’s Esophagus: A Comprehensive Review
Authors: Luigiano Carmelo , Iabichino Giuseppe , Eusebi Leonardo Henry , Arena Monica , Consolo Pierluigi , Morace Carmela , Opocher Enrico , Mangiavillano Benedetto
Published: December 2016

Barrett’s esophagus is a condition in which the normal squamous lining of the esophagus has been replaced by columnar epithelium containing intestinal metaplasia induced by recurrent mucosal injury related to gastroesophageal reflux disease. Barrett’s esophagus is a premalignant condition that can progress through a dysplasia-carcinoma sequence to esophageal adenocarcinoma. Multiple endoscopic ablative techniques have been developed with the goal of eradicating Barrett’s esophagus and preventing neoplastic progression to esophageal adenocarcinoma. For patients with high-grade dysplasia or intramucosal neoplasia, radiofrequency ablation with or without endoscopic resection for visible lesions is currently the most effective and safe treatment available. Recent data demonstrate that, in patients with Barrett’s esophagus and low-grade dysplasia confirmed by a second pathologist, ablative therapy results in a statistically significant reduction in progression to high-grade dysplasia and esophageal adenocarcinoma. Treatment of dysplastic Barrett’s esophagus with radiofrequency ablation results in complete eradication of both dysplasia and of intestinal metaplasia in a high proportion of patients with a low incidence of adverse events. A high proportion of treated patients maintain the neosquamous epithelium after successful treatment without recurrence of intestinal metaplasia. Following successful endoscopic treatment, endoscopic surveillance should be continued to detect any recurrent intestinal metaplasia and/or dysplasia. This paper reviews all relevant publications on the endoscopic management of Barrett’s esophagus using radiofrequency ablation.
The Influence of Tumor Size on Oncologic Outcomes for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy
Authors: Su Xiaohong , Fang Dong , Li Xuesong , Xiong Gengyan , Zhang Lei , Hao Han , Gong Yanqing , Zhang Zheng , Zhou Liqun
Published: December 2016

Previous studies have reached diverse conclusions about the influence of tumor size on the oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC). In this study, we retrospectively analyzed the records of 687 patients and evaluated how tumor size affected the prognosis of patients with UTUC after surgery. Clinicopathologic characteristics and oncological outcomes were compared according to tumor size (≤3 cm versus >3 cm). During a median follow-up period of 65 months (range 3–144 months), 225 patients (32.8%) died from UTUC and 228 patients (33.2%) experienced intravesical recurrence (IVR). Patients with a larger tumor size tended to have a significantly higher percentage of being male (p=0.011), tobacco consumption (p=0.036), lack of preoperative ureteroscopy history (p=0.003), renal pelvic location (p<0.001), tumor necrosis (p=0.003), advanced tumor stage (p<0.001), higher tumor grade (p=0.003), and lymph node metastasis (p=0.018). Univariate analysis revealed that a tumor size >3 cm was significantly associated with worse cancer-specific survival (p=0.002) and IVR (p=0.011). However, the influence was not statistically significant after controlling for other factors in the multivariate analysis (hazard ratio [HR] 1.124, p=0.414 and HR 1.196, p=0.219). In conclusion, UTUC patients with a larger tumor present aggressive biological characteristics and tend to have a worse prognosis.
Time-Aware IoE Service Recommendation on Sparse Data
Authors: Qi Lianyong , Xu Xiaolong , Dou Wanchun , Yu Jiguo , Zhou Zhili , Zhang Xuyun
Published: December 2016

With the advent of “Internet of Everything” (IoE) age, an excessive number of IoE services are emerging on the web, which places a heavy burden on the service selection decision of target users. In this situation, various recommendation techniques are introduced to alleviate the burden, for example, Collaborative Filtering- (CF-) based recommendation. Generally, CF-based recommendation approaches utilize similar friends or similar services to achieve the recommendation goal. However, due to the sparsity of user feedback, it is possible that a target user has no similar friends and similar services; in this situation, traditional CF-based approaches fail to produce a satisfying recommendation result. Besides, recommendation accuracy would be decreased if time factor is overlooked, as IoE service quality often varies with time. In view of these challenges, a time-aware service recommendation approach named Ser_Rectime is proposed in this paper. Concretely, we first calculate the time-aware user similarity; afterwards, indirect friends of the target user are inferred by Social Balance Theory (e.g., “enemy’s enemy is a friend” rule); finally, the services preferred by indirect friends of the target user are recommended to the target user. At last, through a set of experiments deployed on dataset WS-DREAM, we validate the feasibility of our proposal.
Surgical Outcome of Two-Level Transforaminal Percutaneous Endoscopic Lumbar Discectomy for Far-Migrated Disc Herniation
Authors: Wu Xinbo , Fan Guoxin , Gu Xin , Guan Xiaofei , He Shisheng
Published: December 2016

Objective.To describe the two-level percutaneous endoscopic lumbar discectomy (PELD) technique in transforaminal approach for highly migrated disc herniation and investigate its clinical outcomes.Methods.A total of 22 consecutive patients with highly migrated lumbar disc herniation were enrolled for the study from June 2012 to February 2014.Results.There were 12 males and 10 females, with a mean age of 41.1 (range 23–67) years. The mean follow-up period was 18.05 (range 14–33) months. According to the modified MacNab criteria, the clinical outcome at the final follow-up was excellent in 14, good in 6, and fair in 2 patients and the satisfactory rate (excellent and good) was 90.9%. The improvements in VAS and ODI were statistically significant. One patient had recurrent herniation in 18 months after the first surgery and underwent open discectomy. One patient showed symptoms of postoperative dysesthesia (POD), but the POD symptom was transient and partial remission was achieved in two months after conservative treatment.Conclusion.Two-level PELD in transforaminal approach can be a safe and effective procedure for highly migrated disc herniation.
Application of Multivariable Analysis and FTIR-ATR Spectroscopy to the Prediction of Properties in Campeche Honey
Authors: Anguebes Francisco , Pat Lucio , Ali Bassam , Guerrero Armando , Córdova Atl V. , Abatal Mohamed , Garduza José P.
Published: December 2016

Attenuated total reflectance-Fourier transform infrared spectrometry and chemometrics model was used for determination of physicochemical properties (pH, redox potential, free acidity, electrical conductivity, moisture, total soluble solids (TSS), ash, and HMF) in honey samples. The reference values of 189 honey samples of different botanical origin were determined using Association Official Analytical Chemists, (AOAC), 1990; Codex Alimentarius, 2001, International Honey Commission, 2002, methods. Multivariate calibration models were built using partial least squares (PLS) for the measurands studied. The developed models were validated using cross-validation and external validation; several statistical parameters were obtained to determine the robustness of the calibration models: (PCs) optimum number of components principal, (SECV) standard error of cross-validation, (R2cal) coefficient of determination of cross-validation, (SEP) standard error of validation, and (R2val) coefficient of determination for external validation and coefficient of variation (CV). The prediction accuracy for pH, redox potential, electrical conductivity, moisture, TSS, and ash was good, while for free acidity and HMF it was poor. The results demonstrate that attenuated total reflectance-Fourier transform infrared spectrometry is a valuable, rapid, and nondestructive tool for the quantification of physicochemical properties of honey.
Discrepancies between Skinned Single Muscle Fibres and Whole Thigh Muscle Function Characteristics in Young and Elderly Human Subjects
Authors: Jee Hyunseok , Lim Jae-Young
Published: December 2016

We aimed to analyse the mechanical properties of skinned single muscle fibres derived from the vastus lateralis (VL) muscle in relation to those of the whole intact thigh muscle and to compare any difference between young and older adults. Sixteen young men (29.25±4.65years), 11 older men (71.45±2.94years), 11 young women (29.64±4.88years), and 7 older women (67.29±1.70years) were recruited. In vivo analyses were performed for mechanical properties such as isokinetic performance, isometric torque, and power. Specific force and maximum shortening velocity (Vo) were measured with single muscle fibres. Sex difference showed greater impact on the functional properties of both the whole muscle (p<0.01) and single muscle fibres than aging (p<0.05). Sex difference, rather than aging, yielded more remarkable differences in gross mechanical properties in the single muscle fibre study in which significant differences between young men and young women were found only in the cross-sectional area and Vo (p<0.05). Age and sex differences reflect the mechanical properties of both single muscle fibres and whole thigh muscle, with the whole muscle yielding more prominent functional properties.
Dyslipidemia and Diabetes Increase the OPG/TRAIL Ratio in the Cardiovascular System
Authors: Toffoli Barbara , Fabris Bruno , Bartelloni Giacomo , Bossi Fleur , Bernardi Stella
Published: December 2016

Background. Dyslipidemia and diabetes are two of the most well established risk factors for the development of cardiovascular disease (CVD). Both of them usually activate a complex range of pathogenic pathways leading to organ damage. Here we hypothesized that dyslipidemia and diabetes could affect osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) expression in the vessels and the heart. Materials and Methods. Gene and protein expression of OPG, TRAIL, and OPG/TRAIL ratio were quantified in the aorta and the hearts of control mice, dyslipidemic mice, and diabetic mice. Results. Diabetes significantly increased OPG and the OPG/TRAIL ratio expression in the aorta, while dyslipidemia was the major determinant of the changes observed in the heart, where it significantly increased OPG and reduced TRAIL expression, thus increasing cardiac OPG/TRAIL ratio. Conclusions. This work shows that both dyslipidemia and diabetes affect OPG/TRAIL ratio in the cardiovascular system. This could contribute to the changes in circulating OPG/TRAIL which are observed in patients with diabetes and CVD. Most importantly, these changes could mediate/contribute to atherosclerosis development and cardiac remodeling.
Analysis of Polyphenolic Compounds in Extracts from Leaves of SomeMalus domesticaCultivars: Antiradical and Antimicrobial Analysis of These Extracts
Authors: Sowa Alina , Zgórka Grażyna , Szykuła Aleksandra , Franiczek Roman , Żbikowska Beata , Gamian Andrzej , Sroka Zbigniew
Published: December 2016

In this study, methanol, ethyl acetate, water extracts, and precipitate were obtained from leaves ofMalus domesticacultivars: Golden delicious, Jonagold, Elstar, Ligol, and Mutsu. Antiradical activity of these extracts was measured using theABTS+∙radical, and antimicrobial activity was measured with the disk-diffusion method. Phenolic compounds were measured with the colorimetric method and identified with high performance liquid chromatography (HPLC). The highest antiradical activity was observed for the Jonagold variety, and in particular strong activity was noted for ethyl acetate extracts. Antimicrobial activity was observed against strains ofStaphylococcus aureus,Enterococcus faecalis, and the fungusCandida glabrata. Particularly susceptible to the extracts activity appeared to beStaphylococcus aureus, but the growth ofCandida glabratawas inhibited in the presence of ethyl acetate extracts. With the HPLC method we identified a high amount of phloridzin (above 500 mg per g of ethyl acetate extracts), lower amounts of hyperoside, isoquercitrin, and quercitrin, and traces ofp-hydroxybenzoic and chlorogenic acids. The contribution of phloridzin to antiradical activity of methanol and ethyl acetate extracts was very high (above 90%). In water extract the contribution of phloridzin was between 38.9 and 55.2%, chlorogenic acid 22.7 and 36.1%, and hyperoside 12.2 and 13.3%.
A Novel Sample Selection Strategy for Imbalanced Data of Biomedical Event Extraction with Joint Scoring Mechanism
Authors: Lu Yang , Ma Xiaolei , Lu Yinan , Zhou Yuxin , Pei Zhili
Published: December 2016

Biomedical event extraction is an important and difficult task in bioinformatics. With the rapid growth of biomedical literature, the extraction of complex events from unstructured text has attracted more attention. However, the annotated biomedical corpus is highly imbalanced, which affects the performance of the classification algorithms. In this study, a sample selection algorithm based on sequential pattern is proposed to filter negative samples in the training phase. Considering the joint information between the trigger and argument of multiargument events, we extract triplets of multiargument events directly using a support vector machine classifier. A joint scoring mechanism, which is based on sentence similarity and importance of trigger in the training data, is used to correct the predicted results. Experimental results indicate that the proposed method can extract events efficiently.
Cancer Survival Disparities Between First Nation and Non-Aboriginal Adults in Canada: Follow-up of the 1991 Census Mortality Cohort
Authors: Withrow Diana R. , Pole Jason D. , Nishri E. Diane , Tjepkema Michael , Marrett Loraine D.
Published: December 2016

Background: The burden of cancer among indigenous people in Canada has been understudied due to a lack of ethnic identifiers in cancer registries. We compared cancer survival among First Nations to that among non-Aboriginal adults in Canada in the first national study of its kind to date.

Methods: A population-based cohort of approximately 2 million respondents to the 1991 Canadian Long Form Census was followed for cancer diagnoses and deaths using probabilistic linkage to cancer and death registries until 2009. Excess mortality rate ratios (EMRR) and 5-year age-standardized relative survival rates were calculated for 15 cancers using age, sex, ethnicity, and calendar-time–specific life tables derived from the cohort at large.

Results: First Nations diagnosed with cancers of the colon and rectum, lung and bronchus, breast, prostate, oral cavity and pharynx, cervix, ovary, or with non-Hodgkin lymphoma and leukemia all had significantly poorer 5-year survival than their non-Aboriginal peers. For colorectal cancer, a significant disparity was only present between 2001 and 2009 (EMRR: 1.52; 95% CI, 1.28–1.80). For prostate cancer, a significant disparity was only present between 1992 and 2000 (EMRR: 2.76; 95% CI, 1.81–4.21). Adjusting for income and rurality had little impact on the EMRRs.

Conclusions: Compared with non-Aboriginals, First Nations people had poorer survival for 14 of 15 of the most common cancers, and disparities could not be explained by income and rurality.

Impact: The results of this study can serve as a benchmark for monitoring progress toward narrowing the gap in survival. Cancer Epidemiol Biomarkers Prev; 26(1); 145–51. ©2016 AACR.
Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody
Authors: Dominguez George A. , Condamine Thomas , Mony Sridevi , Hashimoto Ayumi , Wang Fang , Liu Qin , Forero Andres , Bendell Johanna , Witt Robert , Hockstein Neil , Kumar Prasanna , Gabrilovich Dmitry I.
Published: December 2016

Purpose: Myeloid-derived suppressor cells (MDSC) are one of the major contributors to immune suppression in cancer. We recently have demonstrated in preclinical study that MDSCs are sensitive to TRAIL receptor 2 (TRAIL-R2) agonist. The goal of this study was to clinically test the hypothesis that targeting TRAIL-R2 can selectively eliminate MDSCs.

Experimental Design: The TRAIL-R2 agonistic antibody (DS-8273a) has been tested in 16 patients with advanced cancers enrolled in a phase I trial. The antibody (24 mg/kg) was administered intravenously once every 3 weeks till disease progression, unacceptable toxicities, or withdrawal of consent. The safety and the presence of various populations of myeloid and lymphoid cells in peripheral blood and tumor tissues were evaluated.

Results: The treatment was well tolerated with only mild to moderate adverse events attributable to the study drug. Treatment with DS-8273a resulted in reduction of the elevated numbers of MDSCs in the peripheral blood of most patients to the levels observed in healthy volunteers. However, in several patients, MDSCs rebounded back to the pretreatment level by day 42. In contrast, DS-8273a did not affect the number of neutrophils, monocytes, and other populations of myeloid and lymphoid cells. Decrease in MDSCs inversely correlated with the length of progression-free survival. In tumors, DS-8273a treatment resulted in a decrease of MDSCs in 50% of the patients who were able to provide pre- and on-treatment biopsies.

Conclusions: Targeting TRAIL-R2 resulted in elimination of different populations of MDSCs without affecting mature myeloid or lymphoid cells. These data support the use of this antibody in combination immmunotherapy of cancer. Clin Cancer Res; 23(12); 2942–50. ©2016 AACR.
Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model
Authors: Kitson Sarah J. , Evans D. Gareth , Crosbie Emma J.
Published: December 2016

Already the fourth most common cancer in women in the developed world, the incidence of endometrial cancer is increasing rapidly, in line with the increasing prevalence of obesity. Relatively few studies have been undertaken of risk-reducing interventions aimed at limiting the impact of the disease on both individuals and the health service. Those that have been performed have demonstrated only modest results due to their application in relatively unselected populations. A validated risk prediction model is therefore urgently required to identify individuals at particularly high risk of endometrial cancer who may benefit from targeted primary prevention strategies and to guide trial eligibility. On the basis of a systematic review of the literature, the evidence for inclusion of measures of obesity, reproduction, insulin resistance, and genetic risk in such a model is discussed, and the strength of association between these risk factors and endometrial cancer is used to guide the development of a pragmatic risk prediction scoring system that could be implemented in the general population. Provisional cutoff values are described pending refinement of the model and external validation in large prospective cohorts. Potential risk-reducing interventions are suggested, highlighting the need for future studies in this area if the increasing tide of endometrial cancer is to be stemmed. Cancer Prev Res; 10(1); 1–13. ©2016 AACR.
Outcome of Combination Therapy with Sofosbuvir and Ledipasvir for Chronic Type C Liver Disease
Authors: Hagiwara Satoru , Nishida Naoshi , Watanabe Tomohiro , Sakurai Toshiharu , Ida Hiroshi , Minami Yasunori , Takita Masahiro , Minami Tomohiro , Iwanishi Mina , Chishina Hirokazu , Ueshima Kazuomi , Komeda Yoriaki , Arizumi Tadaaki , Kudo Masatoshi
Published: December 2016

Introduction: Recently, the treatment of chronic hepatitis C has markedly advanced. A phase III clinical study of combination therapy with sofosbuvir (SOF) and ledipasvir (LDV) was conducted in Japan, and the additive therapeutic effects were reported. In this study, we report the results of treatment in our hospital. Methods: Of 147 patients with chronic type C liver disease who had consulted our hospital since September 2015 and received SOF/LDV therapy, in 91 subjects a sustained virological response of 12 weeks (SVR12) could be evaluated. Results: In all 91 patients, end treatment response was achieved. Subsequently, recrudescence was noted in 1 before the completion of treatment (week 12); an SVR12 was achieved in 90 patients (99%). The following adverse reactions were observed in 3 patients (3.3%): bradycardia, paroxysmal atrial fibrillation, and heart failure with QT prolongation, which were associated with heart disease. Conclusion: A favorable SVR was achieved by SOF/LDV therapy even in elderly patients, those with liver cirrhosis, or those having undergone radical treatment of liver cancer. Furthermore, a high tolerance was demonstrated, but adverse reactions associated with the heart may appear in patients with heart disease as an underlying disease; strict management during treatment is necessary.
Adenovirus-Mediated Overexpression of Septin 2 Attenuates α-Smooth Muscle Actin Expression and Adventitial Myofibroblast Migration Induced by Angiotensin II
Authors: Guo Shu-Jie , Zhang Peng , Wu Ling-Yun , Zhang Guan-Nan , Chen Wen-Dong , Gao Ping-Jin
Published: December 2016

Phenotypic transformation from adventitial fibroblasts (AFs) to myofibroblasts (MFs) is critical for vascular remodeling. Septin 2 was found to be downregulated during the differentiation of AFs to MFs induced by angiotensin II (Ang II); however, the role of septin 2 in this process is still unknown. In this study, we investigate whether septin 2 contributes to the adventitial MF phenotypic modulation caused by Ang II. The decreased level of septin 2 and the increased expression of α-smooth muscle actin (α-SMA), a marker of MFs, were readily observed in Ang II-stimulated MF differentiation. After gene transfer of septin 2, the expression of α-SMA was markedly decreased and the MF migration response to Ang II was inhibited. Furthermore, the inhibition of RhoA, another molecule involved in MF phenotypic modulation, decreased the motility of MFs and the expression of septin 2 triggered in Ang II. Finally, transfection of septin 2 rescued the level of acetyl-α-tubulin in MFs. These findings demonstrate that, as a downstream molecule of RhoA, septin 2 blunted the responses of AFs to Ang II by protecting α-tubulin acetylation, which suggests that septin 2 may serve as a potential therapeutic target for vascular injury.
HIV Drug Resistance and Phylogeny Profile in Naïve and Antiretroviral-Experienced Patients in Tehran, Iran
Authors: Farrokhi Molood , Moallemi Samaneh , Baesi Kazem , Ahsani-Nasab Sara , Gholami Mohammad , Sadeghi Leila , Mohraz Minoo
Published: December 2016

Background: Increasing the accessibility of antiretroviral therapy (ART) has caused the emergence of drug resistance in patients receiving ART and in naïve patients. The aim of this study was to evaluate HIV subtype and drug resistance between naïve patients and ART-experienced patients. Methods: Blood samples were collected from 78 antiretroviral and naïve HIV-1 patients; antiretroviral-resistant mutations and subtyping were then determined by sequencing pol regions. Results: Phylogenetic analysis revealed that 96.1% of sequences belong to the CRF35-AD subtype. Transmitted drug resistance was determined in 14% of drug-naïve patients and 40% of ART-experienced patients. Conclusion: The findings of this study illustrated the importance of resistance testing before and during ART treatment. This study can be used to set up a best medicine strategy in Iranian guidelines.
Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation
Authors: Chen Ting , Yang Chengzhong , Li Manman , Tan Xiaoling
Published: December 2016

Pulmonary hypertension (PH) is a pathological condition with high mortality and morbidity. Hypoxic PH (HPH) is a common form of PH occurring mainly due to lung disease and/or hypoxia. Most causes of HPH are associated with persistent or intermittent alveolar hypoxia, including exposure to high altitude and chronic obstructive respiratory disease. Recent evidence suggests that inflammation is a critical step for HPH initiation and development. A detailed understanding of the initiation and progression of pulmonary inflammation would help in exploring potential clinical treatments for HPH. In this review, the mechanism for alveolar hypoxia-induced local lung inflammation and its progression are discussed as follows: (1) low alveolar PO2 levels activate resident lung cells, mainly the alveolar macrophages, which initiate pulmonary inflammation; (2) systemic inflammation is induced by alveolar hypoxia through alveolar macrophage activation; (3) monocytes are recruited into the pulmonary circulation by alveolar hypoxia-induced macrophage activation, which then contributes to the progression of pulmonary inflammation during the chronic phase of alveolar hypoxia, and (4) alveolar hypoxia-induced systemic inflammation contributes to the development of HPH. We hypothesize that a combination of alveolar hypoxia-induced local lung inflammation and the initiation of systemic inflammation (“second hit”) is essential for HPH progression.
Acetylcholinesterase Activity Measurement and Clinical Features of Delirium
Authors: Jackson Thomas A. , Moorey Hannah C. , Sheehan Bart , Maclullich Alasdair M.J. , Gladman John R. , Lord Janet M.
Published: December 2016

Aims: Cholinergic deficiency is commonly implicated in the pathophysiology of delirium. We aimed to investigate the relationship between directly measured serum acetylcholinesterase (AChE) activity and (1) clinical features of delirium and (2) outcomes among older hospital patients with delirium. Methods: Hospitalised patients with delirium were recruited, and delirium motor subtype, severity and duration of delirium were measured. Serum AChE activity was measured using a colorimetric assay. Results: The mean AChE activity for the whole sample was 2.46 μmol/μL/min (standard deviation 1.75). Higher AChE activity was associated with increased likelihood of hypoactive delirium rather than the hyperactive or mixed subtype (odds ratio 1.98, 95% confidence interval 1.10-3.59). Conclusion: Higher AChE activity was associated with hypoactive delirium but did not predict outcomes. Simple enhancement of cholinergic neurotransmission may not be sufficient to treat delirium.
Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease
Authors: Lau Cia-Hin , Suh Yousin
Published: December 2016

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.
c-Myb Overexpression in Cytology Smears of Tracheobronchial and Pulmonary Adenoid Cystic Carcinomas
Authors: Vallonthaiel Archana George , Jain Deepali , Singh Varsha , Kaur Kavneet , Madan Karan , Kumar Vinay , Iyer Venkateswaran K. , Sharma Mehar Chand
Published: December 2016

Aims: Adenoid cystic carcinoma (AdCC) is a malignant epithelial neoplasm that occurs rarely in the lower respiratory tract (LRT). AdCC at various sites is associated with the novel fusion transcript MYB-NFIB, along with the overexpression of the Myb protein. The expression of the Myb protein in AdCC of the LRT has not been evaluated much. Study Design: Cases of AdCC of the LRT diagnosed on cytology or histology were retrieved from our institutional archives. c-Myb expression was analyzed on immunocytochemistry/immunohistochemistry (ICC/IHC) and was correlated with clinicopathological parameters. Results: Twenty-three samples of AdCC originating from the LRT were included in the study. Four cases were diagnosed on cytology, 3 of which had corresponding histology specimens. The remaining 19 cases had either biopsy or resection. Most of the patients presented with endobronchial mass. The mean age was 49.4 years and a male predominance was seen. ICC and IHC for c-Myb showed positivity in 75 and 59% of the cases, respectively. Western blot was used to validate IHC results. Conclusion: AdCC of the LRT is rare and hence poses diagnostic difficulty. Cytology smears can be utilized for c-Myb ICC. The presence of c-Myb immunopositivity in most cases may possibly make Myb a diagnostic biomarker and a therapeutic target for personalized treatment.
Down-Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by Glycogen Synthase Kinase GSK3ß
Authors: Fezai Myriam , Jemaà Mohamed , Fakhri Hajar , Chen Hong , Elsir Bhaeldin , Pelzl Lisann , Lang Florian
Published: December 2016

Background: The Na+,Cl- coupled creatine transporter CreaT (SLC6A8) is expressed in a variety of tissues including the brain. Genetic defects of CreaT lead to mental retardation with seizures. The present study explored the regulation of CreaT by the ubiquitously expressed glycogen synthase kinase GSK3ß, which contributes to the regulation of neuroexcitation. GSK3ß is phosphorylated and thus inhibited by PKB/Akt. Moreover, GSK3ß is inhibited by the antidepressant lithium. The present study thus further tested for the effects of PKB/Akt and of lithium. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type GSK3ß or inactive K85RGSK3ß. CreaT and GSK3ß were further expressed without and with additional expression of wild type PKB/Akt. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes, co-expression of GSK3ß but not of K85RGSK3ß, resulted in a significant decrease of creatine induced current. Kinetic analysis revealed that GSK3ß significantly decreased the maximal creatine transport rate. Exposure of CreaT and GSK3ß expressing oocytes for 24 hours to Lithium was followed by a significant increase of the creatine induced current. The effect of GSK3ß on CreaT was abolished by co-expression of PKB/Akt. Conclusion: GSK3ß down-regulates the creatine transporter CreaT, an effect reversed by treatment with the antidepressant Lithium and by co-expression of PKB/Akt.
Triggering of Suicidal Erythrocyte Death by Bexarotene
Authors: Al Mamun Bhuyan Abdulla , Bissinger Rosi , Cao Hang , Lang Florian
Published: December 2016

Background/Aims: The retinoid X receptor agonist bexarotene is utilized for the treatment of cutaneous T-cell lymphoma and is effective in several further malignancies. The substance counteracts tumor growth in part by triggering suicidal death or apoptosis of tumor cells. Side effects of bexarotene treatment include anemia. Theoretically, bexarotene induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling potentially stimulating eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), induction of oxidative stress, increase of ceramide abundance, as well as activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases. The present study explored, whether bexarotene induces eryptosis and, if so, whether its effect involves Ca2+ entry, oxidative stress, ceramide, kinases and/or caspases. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to bexarotene (≥ 0.4 µg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying forward scatter. Bexarotene significantly increased Fluo3-fluorescence and DCFDA fluorescence. Bexarotene tended to increase ceramide abundance, an effect, however, not reaching statistical significance. The effect of bexarotene on annexin-V-binding was significantly blunted by removal of extracellular Ca2+ and by addition of D4476 (10 µM), but not by addition of staurosporine (1 µM), SB203580 (2 µM), or zVAD (10 µM). Conclusions: Bexarotene triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca2+ entry, oxidative stress, and activation of D4476 sensitive casein kinase.
A Patient with Supraclavicular Lymphadenopathy and Anterior Mediastinal Mass Presenting as a Rare Case of Composite Lymphoma: A Case Report and Literature Review
Authors: Raufi Alex , Jerkins James , Lyou Yung , Jeyakumar Deepa
Published: December 2016

Composite lymphoma (CL) is a rare disease with 2 distinct lymphomas concurrently arising in a single patient with an estimated incidence of 1–4.7% of newly diagnosed lymphomas per year. CL most commonly involves 2 B-cell non-Hodgkin lymphomas (NHL) or a B-cell NHL with a Hodgkin lymphoma. Our case is unique in that it was a bilineage CL with both a T-cell and B-cell NHL, which has only been reported in a few case reports. A 49-year-old woman presented with several months of progressive cough, weight loss, dyspnea, and supraclavicular lymphadenopathy. Computed tomographic imaging done upon admission to the hospital found that she had extensive anterior and middle mediastinal lymphadenopathy as well as bilateral supraclavicular lymphadenopathy. The patient underwent an excisional biopsy on the supraclavicular lymph node and was found to have a composite lymphoma involving both a T-cell and B-cell NHL. Her final pathological diagnosis was peripheral T-cell lymphoma and lymphoplasmacytic lymphoma. The patient was found to have stage IIIB disease. Her HIV, hepatitis panel, and tuberculosis tests were all negative. She then underwent chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The patient showed a complete response and was then referred to a bone marrow transplant center for an autologous hematopoietic stem cell transplant. CL is a rare disease composed of at least 2 distinct lymphomas concurrently arising in a single patient. Due to the complexity in having to treat multiple types of lymphoma simultaneously CL presents challenges with treatment and assessing prognosis.
One-Year Follow-Up after Endobronchial Valve Treatment in Patients with Emphysema without Collateral Ventilation Treated in the STELVIO Trial
Authors: Klooster Karin , Hartman Jorine E. , ten Hacken Nick H.T. , Slebos Dirk-Jan
Published: December 2016

Background: One-way endobronchial valve (EBV) treatment has shown safety and efficacy at 6 months after treatment in patients with severe emphysema and confirmed absence of interlobar collateral ventilation. Longer follow-up in this subgroup is not available. Objectives: To investigate the efficacy and safety of EBV treatment of the STELVIO cohort at a 1-year follow-up. Methods: Emphysema patients who have been treated with EBV in the STELVIO trial were invited for a voluntary 1-year follow-up visit. Both the original treatment group and the control group who crossed over to treatment have been included. Analyses are performed on the patients who attended the 1-year follow-up visit. Results: Sixty-four patients received EBV treatment. At 1 year, 40 patients (26 female; mean age 59 ± 8 years; FEV1 0.86 ± 0.29 L; RV 4.56 ± 1.00 L; 6MWD 367 ± 78 m; and SGRQ 56 ± 13 points) visited the hospital. Significant improvements (p < 0.001) were found for FEV1 (+17%, 95% CI, 11 to 24), RV (-687 mL, 95% CI, -918 to -456), 6MWD (+61 m, 95% CI, 42 to 80), and SGRQ (-11 points, 95% CI, −17 to −6). Two patients died: 1 after 58 days due to progressive respiratory failure and 1 after 338 days of follow-up due to a myocardial infarction. Seventeen percent of the patients underwent valve replacement and 22% of the initially treated patients had permanent valve removal. In 22% of the patients, pneumothoraces occurred before 6 months, and none occurred between 6 and 12 months. Conclusions: EBV treatment results in clinically relevant benefits at 1 year of follow-up. Maintenance bronchoscopies to achieve this are needed. This study supports the use of EBV treatment in carefully selected patients with severe emphysema without collateral ventilation.
Naturalmente filmados: modos de atuar e viver nos postos indígenas do SPI em Mato Grosso
Authors: Arruda Lucybeth Camargo de
Published: December 2016

Este artigo realiza um exercício de olhar e pensar a partir de uma seleção de fotografias de três coleções fotográficas produzidas pela Seção de Estudos (SE) do Serviço de Proteção aos Índios (SPI) em cinco Postos Indígenas localizados no Estado de Mato Grosso, nos anos de 1942 e 1943. A partir de abordagens e métodos de investigação que abarcam os campos da Antropologia, Fotografia e História, analisamos imagens produzidas pela equipe de Foto-Cinematografia, tendo como suporte a documentação produzida pelo spi no período de 1910 a 1945. O objetivo central é perceber a presença e a participação indígenas dentro do bloco monolítico chamado de “Posto Indígena”. Buscamos problematizar contextos inscritos na fotografia por sua ambiguidade inerente e encontrar os grupos indígenas Bororo, Bakairi, Terena, etc., atuando e participando do seu processo histórico. Concluímos que imagens e palavras se complementam e compõem narrativas da História dos Índios, através do SPI, nas primeiras décadas do século XX.
Espaço, pessoa e movimento na socialidade ameríndia: sobre os modos Huni Kuin de relacionalidade
Authors: McCallum Cecilia
Published: December 2016

O artigo explora as práticas huni kuin constitutivas de socialidade, das pessoas e, simultaneamente, das suas relações com o ambiente. Ao criar a si mesmos num sentido material e social em processos intersubjetivos ocorridos em configurações específicas do espaço-tempo, forjam conexões contingentes de posse entre pessoas e lugares, e criam as condições para abrir clareiras temporárias de espaço humano num mundo vigiado e cuidado por entidades não-humanas. Num primeiro momento, o artigo relembra o empenho das lideranças huni kuin em defender seus direitos de propriedade e insistir na demarcação das terras indígenas, conforme especificado pela legislação brasileira, para o qual usam uma linguagem discursiva não-indígena. O enfoque principal deste ensaio, no entanto, recai sobre as práticas indígenas da vida diária. Explora-se a noção de que, em um sentido proeminente, para este povo da Amazônia, o território não é fixo, mas depende da constante transformação da copresença huni kuin envolvida nas relações entre si e com outras entidades e pessoas do mundo circundante.
No princípio era a terra: A territorialização das lutas agrárias no contexto de expansão da acumulação capitalista na Amazônia
Authors: Assis Wendell Ficher
Published: December 2016

O trabalho procura analisar as complementaridades e dissonâncias entre as lutas camponesas por terra, mais associadas à reforma agrária e aos mecanismos de redistribuição, e os embates protagonizados por indígenas, quilombolas e populações tradicionais, que lutam pela manutenção e conquista de territórios, ao mesmo tempo em que demandam do Estado o reconhecimento de seus modos específicos de ser, viver e produzir. Para tanto, empreendeu-se a realização de trabalhos de campo na região Oeste do Pará, que desde a última década tem sido locus de intensos conflitos fundiários envolvendo as novas frentes de acumulação capitalista e as populações tradicionais e camponesas. Poder-se-ia sugerir de forma preliminar que uma demanda por terra não desafia, necessariamente, as regulações com que se administra o direito à propriedade, ao passo que uma demanda territorial evoca questões de poder, de afirmação de identidade, de autogestão e controle dos recursos naturais, procurando impor uma nova territorialização.