bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical model of thermal effects of blinking in human eye
Authors: Gurung D. B. , Gokul K. C. , Adhikary P. R.
Published: June 2015

Blinking is regarded as the continuous interrupted eyelid closure or opening and its thermal effect will compromise between these two. During a blink, the heat loss via convection, radiation and tear evaporation from cornea is prevented, warm tear is layered across corneal surface and the vessels of the palpebral conjunctiva provide heat to anterior eye. In most of the thermal models in human eye that are found in literatures, effect of blinking is not included, simulation is carried out only in open eye. Thus, in this paper, thermal effects of blinking are investigated using one-dimensional finite element method in transient state case. The bio-heat transfer process is simulated during different blinking rates, lid closure and opening. The simulation is carried out using normal and extreme values of ambient temperatures, blood temperatures, evaporation rates, blood perfusion rates, and lens thermal conductivities. Blinking is found to increase corneal and lens temperature by 1.29°C and 0.78°C respectively when compared to open eye. The results obtained from this model are useful in predicting temperature distribution in different laser eye surgeries, hyperthermia and cryosurgery treatment of eyelid carcinoma, choroidal melanoma and can be used for diagnosing temperature-related diseases.
Removal of Azo Dyes from Aqueous Solution by Composite HKUST-1/GO
Authors: Yi Qiong , Li Ling , Fan Lu , Sun Keke , Mao Lebao , Liang Keke , Liu Li
Published: June 2015

The adsorption of three kinds of azo dyes from aqueous solution on HKUST-1/graphene oxide (GO) composite was studied in view of the removal efficiency, adsorption isotherm, and regenerate of the sorbent. HKUST-1/GO was found to be with higher dyes removal efficiency than HKUST-1. All the adsorption isotherms of azo dyes on HKUST-1/GO composite followed Freundlich isotherm. The adsorbed azo dyes on HKUST-1/GO could be eluted by acetone, so HKUST-1/GO can also be used for enrichment of azo dyes as adsorbent.
MIL-101/GO Coated Stir Bar for SBSE to Determine Azo Dyes in Water Samples by UV–Vis Spectrophotometric Method
Authors: Yi Qiong , Li Ling , Hong Wei , Fan Lu
Published: June 2015

A composite of chromium (III) terephthalate metal-organic framework and graphene oxide (MIL-101/GO) coated stir bar was prepared by sol–gel technique for the first time and was employed for stir bar sorptive extraction (SBSE) of trace azo dyes amaranth, sunset yellow and carmine from water samples followed by UV–Vis spectrophotometric detection. A MIL-101/GO coating was first created on the glass bar surface. MIL-101/GO and MIL-101/GO coated stir bars were characterized. The enrichment factors of azo dyes by SBSE have been investigated in detail, and the optimized experimental parameters were obtained. Under the optimal conditions, a method for determination of trace amount of azo dyes was setup, and the detection limits of amaranth, sunset yellow and carmine were 2.3 ng/mL, 1.7 ng/mL and 1.6 ng/mL. The proposed method was successfully applied for the analysis of the three azo dyes in water samples.
Performance Investigation of Cascade Refrigeration System Using CO2 and Mixtures
Authors: Jemni Nourheine , Elakhdar Mouna , Nehdi Ezzedine , Kairouani Lakdar
Published: June 2015

This paper presents reports on simulation and comparative analysis of single stage vapor compression refrigeration system and cascade systems using carbon dioxide, hydrocarbons (HCs) and CO2/HCs mixture. Thermodynamic parameters of fluids are given using the software REFPROP 9.0. To select the most suitable HCs, three criteria have been fixed: Tc, Tt and Tb. It is found that the HCs chosen in low-stage are propane, propylene and ethane and those for the high-stage are propane, propylene and isobutane. The fraction mixture in the two loops has been varied and results are compared with single stage and cascade systems using CO2 and R22. The fraction x[Formula: see text] is varied in the two loops. Results are compared for single and cascade systems using CO2 and R22. For the single stage system, we find for xCO2 = 0.5, an improvement of COP of 14% for CO2/propane mixture and 36% for the CO2/propylene mixture. It is found that for xCO2 = 0.3, cascade system using propane/CO2 mixtures presents a COP lower than that of cascade system using pure CO2. About of 70% of unfriendly fluids like CFCs and HCFCs can be replaced with CO2, without affecting the performance of cascade refrigeration systems.
Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation
Authors: Lee Jungwoo , Kohl Nathaniel , Shanbhang Sachin , Parekkadan Biju
Published: June 2015

Microfluidic technologies have substantially advanced cancer research by enabling the isolation of rare circulating tumor cells (CTCs) for diagnostic and prognostic purposes. The characterization of isolated CTCs has been limited due to the difficulty in recovering and growing isolated cells with high fidelity. Here, we present a strategy that uses a 3D scaffold, integrated into a microfludic device, as a transferable substrate that can be readily isolated after device operation for serial use in vivo as a transplanted tissue bed. Hydrogel scaffolds were incorporated into a PDMS fluidic chamber prior to bonding and were rehydrated in the chamber after fluid contact. The hydrogel matrix completely filled the fluid chamber, significantly increasing the surface area to volume ratio, and could be directly visualized under a microscope. Computational modeling defined different flow and pressure regimes that guided the conditions used to operate the chip. As a proof of concept using a model cell line, we confirmed human prostate tumor cell attachment in the microfluidic scaffold chip, retrieval of the scaffold en masse, and serial implantation of the scaffold to a mouse model with preserved xenograft development. With further improvement in capture efficiency, this approach can offer an end-to-end platform for the continuous study of isolated cancer cells from a biological fluid to a xenograft in mice.
Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors
Authors: Zhao Ming , Chen Xiaoli
Published: June 2015

The elevation of circulating LPS has been associated with obesity and aging. However, whether and how LPS contributes to adipose tissue dysfunction is unclear. In this study, we investigated the effect of LPS on the adipogenic capacity and cellular senescence of adipocyte progenitors. Stromal-vascular cells were isolated from inguinal adipose tissue of C57BL/6 mice and treated with LPS during the different time periods of adipocyte differentiation. We found that LPS treatment for 24 h prior to the induction of differentiation led to the most profound effect on the inhibition of adipogenesis, as evidenced by the morphological changes and the decreased mRNA expression of adipocyte marker genes. In addition, LPS induced features of premature senescence of SV cells, including the activation of p53, the elevation of SA-β-gal activity, and increased hydrogen peroxide production, but not telomere length. Upon LPS treatment, SV cells also developed senescence-associated secretory phenotype (SASP), as demonstrated by the increased expression of TNFα, IL-1β, IL-6, MCP-1, and VEGFα. Blocking LPS-induced NF-κB activation and cytokine production by Bay 11-7082 failed to rescue the impaired adipogenesis and the reduction in PPARγ and Zfp423 expression. On the contrary, rosiglitazone had little effect on cytokine production but corrected the defective adipogenic potential. In conclusion, we demonstrate that LPS inhibits adipogenesis by disrupting the differentiation of adipocyte progenitors in a NF-κB-independent manner; LPS also induces premature senescence of adipocyte progenitors. Our data suggest that LPS could be a potential contributor to the defective adipogenesis and the development of cellular senescence in adipose tissue during obesity and aging.
Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle
Authors: Trewin Adam J. , Lundell Leonidas S. , Perry Ben D. , Patil Kim Vikhe , Chibalin Alexander V. , Levinger Itamar , McQuade Leon R. , Stepto Nigel K.
Published: June 2015

—Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min−1·m2) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P < 0.05). Insulin sensitivity was reduced (−5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.
Failure to use corollary discharge to remap visual target locations is associated with psychotic symptom severity in schizophrenia
Authors: Rösler Lara , Rolfs Martin , van der Stigchel Stefan , Neggers Sebastiaan F. W. , Cahn Wiepke , Kahn René S. , Thakkar Katharine N.
Published: June 2015

Corollary discharge (CD) refers to “copies” of motor signals sent to sensory areas, allowing prediction of future sensory states. They enable the putative mechanisms supporting the distinction between self-generated and externally generated sensations. Accordingly, many authors have suggested that disturbed CD engenders psychotic symptoms of schizophrenia, which are characterized by agency distortions. CD also supports perceived visual stability across saccadic eye movements and is used to predict the postsaccadic retinal coordinates of visual stimuli, a process called remapping. We tested whether schizophrenia patients (SZP) show remapping disturbances as evidenced by systematic transsaccadic mislocalizations of visual targets. SZP and healthy controls (HC) performed a task in which a saccadic target disappeared upon saccade initiation and, after a brief delay, reappeared at a horizontally displaced position. HC judged the direction of this displacement accurately, despite spatial errors in saccade landing site, indicating that their comparison of the actual to predicted postsaccadic target location relied on accurate CD. SZP performed worse and relied more on saccade landing site as a proxy for the presaccadic target, consistent with disturbed CD. This remapping failure was strongest in patients with more severe psychotic symptoms, consistent with the theoretical link between disturbed CD and phenomenological experiences in schizophrenia.
Epstein-Barr Virus Association with Peptic Ulcer Disease
Authors: Cárdenas-Mondragón María G. , Torres Javier , Flores-Luna Lourdes , Carreón-Talavera Ricardo , Camorlinga-Ponce Margarita , Fuentes-Pananá Ezequiel M.
Published: June 2015

Background.Helicobacter pylori(HP) infection and nonsteroidal anti-inflammatory drugs (NSAID) use are considered the main risk to develop peptic ulcer disease (PUD). However, PUD also occurs in the absence ofHPinfection and/or NSAID use. Recently, we have found evidence that Epstein-Barr virus (EBV) reactivation increases the risk to develop premalignant and malignant gastric lesions.Objective. To study a possible association between EBV and PUD.Methods. Antibodies against an EBV reactivation antigen,HP, and theHPvirulence factor CagA were measured in sera from 207 Mexican subjects, controls (healthy individuals,n= 129), and PUD patients (n= 78, 58 duodenal and 20 gastric ulcers). Statistical associations were estimated.Results. Duodenal PUD was significantly associated with high anti-EBV IgG titers (p= 0.022, OR = 2.5), while anti-EBV IgA was positively associated with gastric PUD (p= 0.002, OR = 10.1).Conclusions. Our study suggests that EBV reactivation in gastric and duodenal epithelium increases the risk to develop PUD.
Scrotal Swelling as a Complication of Hydrochlorothiazide Induced Acute Pancreatitis
Authors: Nikiforov Ivan , Mansoora Qurat , Al-Khalisy Hassan , Joseph Sarah , Cheriyath Pramil
Published: June 2015

Background. Scrotal swelling is a rare complication of acute pancreatitis with few reported cases in the literature. In this case report, we present a 59-year-old male with hydrochlorothiazide induced pancreatitis who developed scrotal swelling.Case Presentation. A 59-year-old male presented to the emergency department with sharp epigastric abdominal pain that radiated to the back and chest. On physical examination, he had abdominal tenderness and distention with hypoactive bowel sounds. Computed tomography (CT) scan of the abdomen showed acute pancreatitis. The patient’s condition deteriorated and he was admitted to the intensive care unit (ICU). After he improved and was transferred out of the ICU, the patient developed swelling of the scrotum and penis. Ultrasound (US) of the scrotum showed large hydrocele bilaterally with no varicoceles or testicular masses. Good blood flow was observed for both testicles. The swelling diminished over the next eight days with the addition of Lasix and the patient was discharged home in stable condition.Conclusion. Scrotal swelling is a rare complication of acute pancreatitis. It usually resolves spontaneously with conservative medical management such as diuretics and elevation of the legs.
Genotoxicity of Anesthetics EvaluatedIn Vivo(Animals)
Authors: Braz Mariana G. , Karahalil Bensu
Published: June 2015

The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia.
Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule Endoscopy
Authors: Saito Keita , Nomura Eiki , Sasaki Yu , Abe Yasuhiko , Kanno Nana , Mizumoto Naoko , Shibuya Rika , Sakuta Kazuhiro , Yagi Makoto , Yoshizawa Kazuya , Iwano Daisuke , Sato Takeshi , Nishise Shoichi , Ueno Yoshiyuki
Published: June 2015

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2–5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.
Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy
Authors: Zhao Yue , Feng Yue , Zhang Yun-Mei , Ding Xiao-Xue , Song Yu-Zhu , Zhang A-Mei , Liu Li , Zhang Hong , Ding Jia-Huan , Xia Xue-Shan
Published: June 2015

As a common cardiac disease mainly caused by gene mutations in sarcomeric cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription factor genes, inherited cardiomyopathy is becoming one of the major etiological factors of sudden cardiac death (SCD) and heart failure (HF). This disease is characterized by remarkable genetic heterogeneity, which makes it difficult to screen for pathogenic mutations using Sanger sequencing. In the present study, three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with familial dilated cardiomyopathy (FDCM), were recruited together with their respective family members. Using next-generation sequencing technology (NGS), 24 genes frequently known to be related to inherited cardiomyopathy were screened. Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA-p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be highly correlated with familial cardiomyopathy. FDCM patients with doubly heterozygous mutations show a notably severe phenotype as we could confirm in our study; this indicates that the double mutations had a dose effect. In addition, it is proposed that genetic testing using NGS technology can be used as a cost-effective screening tool and help guide the treatment of patients with familial cardiomyopathy particularly regarding the risk of family members who are clinically asymptomatic.
A New Twist to a Chronic HCV Infection: Occult Hepatitis C
Authors: Attar Bashar M. , Van Thiel David
Published: June 2015

Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later.Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions.Data Sources. SearchingMEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014).Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues.Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.
Inventory of a Neurological Intensive Care Unit: Who Is Treated and How Long?
Authors: Backhaus Roland , Aigner Franz , Schlachetzki Felix , Steffling Dagmar , Jakob Wolfgang , Steinbrecher Andreas , Kaiser Bernhard , Hau Peter , Boy Sandra , Fuchs Kornelius , Bogdahn Ulrich , Ritzka Markus
Published: June 2015

Purpose. To characterize indications, treatment, and length of stay in a stand-alone neurological intensive care unit with focus on comparison between ventilated and nonventilated patient.Methods. We performed a single-center retrospective cohort study of all treated patients in our neurological intensive care unit between October 2006 and December 2008.Results. Overall, 512 patients were treated in the surveyed period, of which 493 could be included in the analysis. Of these, 40.8% had invasive mechanical ventilation and 59.2% had not. Indications in both groups were predominantly cerebrovascular diseases. Length of stay was 16.5 days in mean for ventilated and 3.6 days for nonventilated patient.Conclusion. Most patients, ventilated or not, suffer from vascular diseases with further impairment of other organ systems or systemic complications. Data reflects close relationship and overlap of treatment on nICU with a standardized stroke unit treatment and suggests, regarding increasing therapeutic options, the high impact of acute high-level treatment to reduce consequential complications.
Obtaining Ionospheric Conditions according to Data of Navigation Satellites
Authors: Maltseva Olga , Mozhaeva Natalia
Published: June 2015

Defining ionospheric conditions, the deviation of the observational value of the total electron content TEC(obs), measured by means of navigation satellites, from a median is a bench mark. According to more than 40 ionospheric stations during April 2014 it is shown that synchronism of change of deviations of TEC and critical frequency foF2 of the ionosphere is kept under quiet and moderate disturbed conditions. This fact allows to use a median of the equivalent slab thicknessτ(med) as a reliable calibration factor to calculate foF2 from TEC(obs). The efficiency coefficient of joint use ofτ(med) and TEC(obs) changes from 1.5 to 4 with average value 2.2 across the globe. The highest coefficient corresponds to middle latitudes, however the estimations obtained for high- and low-latitude areas indicate possibility to useτ(med) and TEC(obs) in these areas.
A Microstructural Study of Load Distribution in Cartilage: A Comparison of Stress Relaxation versus Creep Loading
Authors: Thambyah Ashvin , van Heeswijk V. M. , van Donkelaar C. C. , Broom Neil
Published: June 2015

The compressive response of articular cartilage has been extensively investigated and most studies have focussed largely on the directly loaded matrix. However, especially in relation to the tissue microstructure, less is known about load distribution mechanisms operating outside the directly loaded region. We have addressed this issue by using channel indentation and DIC microscopy techniques that provide visualisation of the matrix microstructural response across the regions of both direct and nondirect loading. We hypothesise that, by comparing the microstructural response following stress relaxation and creep compression, new insights can be revealed concerning the complex mechanisms of load bearing. Our results indicate that, with stress relaxation, the initial mode of stress decay appears to primarily involve relaxation of the surface layer. In the creep loading protocol, the main mode of stress release is a lateral distribution of load via the mid matrix. While these two modes of stress redistribution have a complex relationship with the zonally differentiated tissue microstructure and the depth of strain, fourmechanostructuralmechanisms are proposed to describe succinctly the load responses observed.
Cluster-Randomized Trial to Increase Hepatitis B Testing among Koreans in Los Angeles
Authors: Bastani Roshan , Glenn Beth A. , Maxwell Annette E. , Jo Angela M. , Herrmann Alison K. , Crespi Catherine M. , Wong Weng K. , Chang L. Cindy , Stewart Susan L. , Nguyen Tung T. , Chen Moon S. , Taylor Victoria M.
Published: June 2015

Background: In the United States, Korean immigrants experience a disproportionately high burden of chronic hepatitis B (HBV) viral infection and associated liver cancer compared with the general population. However, despite clear clinical guidelines, HBV serologic testing among Koreans remains persistently suboptimal.

Methods: We conducted a cluster-randomized trial to evaluate a church-based small group intervention to improve HBV testing among Koreans in Los Angeles. Fifty-two Korean churches, stratified by size (small, medium, large) and location (Koreatown versus other), were randomized to intervention or control conditions. Intervention church participants attended a single-session small-group discussion on liver cancer and HBV testing, and control church participants attended a similar session on physical activity and nutrition. Outcome data consisted of self-reported HBV testing obtained via 6-month telephone follow-up interviews.

Results: We recruited 1,123 individuals, 18 to 64 years of age, across the 52 churches. Ninety-two percent of the sample attended the assigned intervention session and 86% completed the 6-month follow-up. Sample characteristics included were as follows: mean age 46 years, 65% female, 97% born in Korea, 69% completed some college, and 43% insured. In an intent-to-treat analysis, the intervention produced a statistically significant effect (OR = 4.9, P < 0.001), with 19% of intervention and 6% of control group participants reporting a HBV test.

Conclusion: Our intervention was successful in achieving a large and robust effect in a population at high risk of HBV infection and sequelae.

Impact: The intervention was fairly resource efficient and thus has high potential for replication in other high-risk Asian groups. Cancer Epidemiol Biomarkers Prev; 24(9); 1341–9. ©2015 AACR.
Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2–SN-38 Antibody Conjugate (Sacituzumab Govitecan)
Authors: Sharkey Robert M. , McBride William J. , Cardillo Thomas M. , Govindan Serengulam V. , Wang Yang , Rossi Edmund A. , Chang Chien-Hsing , Goldenberg David M.
Published: June 2015

Purpose: This study examined the delivery of SN-38 to Trop-2–expressing tumors and assessed the constitutive products in the serum, liver, and small intestine in nude mice bearing human tumor xenografts (Capan-1 or NCI-N87) given a single injection of irinotecan (40 mg/kg; ∼0.8 mg/mouse, containing ∼460 μg SN-38 equivalents) or sacituzumab govitecan (IMMU-132), an antibody–drug conjugate composed of a humanized anti-Trop-2 IgG coupled site specifically with an average of 7.6 molecules of SN-38.

Experimental Design: At select times, tissues were extracted and concentrations of the products measured by reversed-phase high-performance liquid chromatography (HPLC).

Results: In serum, >98% irinotecan cleared within 5 minutes; peak levels of SN-38 and SN-38G (glucuronidated SN-38) were detected in equal amounts at this time, and no longer detected after 6 to 8 hours. IMMU-132 was detected in the serum over 3 days, and at each interval, ≥95% of total SN-38 was bound to the antibody. Intact IMMU-132 cleared with a half-life of 14 hours, which closely reflected the in vitro rate of SN-38 released from the conjugate in mouse serum (i.e., 17.5 hours), whereas the IgG portion of the conjugate cleared with a half-life of 67.1 hours. In vitro and in vivo studies disclosed IgG-bound SN-38 was protected from glucuronidation. Area under the curve (AUC) analysis indicated that IMMU-132 delivers 20-fold to as much as 136-fold more SN-38 to tumors than irinotecan, with tumor:blood ratios favoring IMMU-132 by 20- to 40-fold. Intestinal concentrations of SN-38/SN-38G also were 9-fold lower with IMMU-132.

Conclusions: These studies confirm a superior SN-38 tumor delivery by IMMU-132 compared with irinotecan. Clin Cancer Res; 21(22); 5131–8. ©2015 AACR.
Amino Acids Attenuate Insulin Action on Gluconeogenesis and Promote Fatty Acid Biosynthesis via mTORC1 Signaling Pathway in trout Hepatocytes
Authors: Dai Weiwei , Panserat Stéphane , Plagnes-Juan Elisabeth , Seiliez Iban , Skiba-Cassy Sandrine
Published: June 2015

Background/Aims: Carnivores exhibit poor utilization of dietary carbohydrates and glucose intolerant phenotypes, yet it remains unclear what are the causal factors and underlying mechanisms. We aimed to evaluate excessive amino acids (AAs)-induced effects on insulin signaling, fatty acid biosynthesis and glucose metabolism in rainbow trout and determine the potential involvement of mTORC1 and p38 MAPK pathway. Methods: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Results: Increased AA levels enhanced the phosphorylation of ribosomal protein S6 kinase (S6K1), S6, and insulin receptor substrate 1 (IRS-1) on Ser302 but suppressed Akt and p38 phosphorylation; up-regulated the expression of genes related to gluconeogenesis and fatty acid biosynthesis. mTORC1 inhibition not only inhibited the phosphorylation of mTORC1 downstream targets, but also blunted IRS-1 Ser302 phosphorylation and restored excessive AAs-suppressed Akt phosphorylation. Rapamycin also inhibited fatty acid biosynthetic and gluconeogenic gene expression. Conclusion: High levels of AAs up-regulate hepatic fatty acid biosynthetic gene expression through an mTORC1-dependent manner, while attenuate insulin-mediated repression of gluconeogenesis through elevating IRS-1 Ser302 phosphorylation, which in turn impairs Akt activation and thereby weakening insulin action. We propose that p38 MAPK probably also involves in these AAs-induced metabolic changes.
Differential Proteomic Analysis of Syncytiotrophoblast Extracellular Vesicles from Early-Onset Severe Preeclampsia, using 8-Plex iTRAQ Labeling Coupled with 2D Nano LC-MS/MS
Authors: Li Hongmei , Han Lei , Yang Zhiling , Huang Wei , Zhang Xin , Gu Yan , Li Yinfeng , Liu Xiaojie , Zhou Lijuan , Hu Jiongyu , Yu Meijia , Yang Jing , Li Yilin , Zheng Yingru , Guo Jianxin , Han Jian , Li Li
Published: June 2015

Aims: Previous studies have revealed that the increased shedding of syncytiotrophoblast extracellular vesicles (STBM) may lead to preeclampsia (PE). We aimed to identify the proteins carried by STBM and their potential pathological roles in early-onset severe PE. Methods: In this study, we performed a differential proteomic analysis of STBM from early-onset severe PE patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS. STBM were generated by the in vitro explant culture method, and then verified by electron microscopy and western blot analysis. Results: A total of 18 533 unique peptides and 3 317 proteins were identified, 3 292 proteins were quantified. We identified 194 differentially expressed proteins in STBM from early-onset severe PE patients, 122 proteins were up-regulated and 72 proteins were down-regulated. Further bioinformatics analysis revealed that mitochondrion, transmembrane transport and transmembrane transporter activity were the most abundant categories in gene ontology (GO) annotation. Glycolysis/ gluconeogenesis, citrate cycle, fatty acid elongation, steroid hormone biosynthesis and oxidative phosphorylation were the five significantly represented pathways. Four differentially expressed proteins (siglec-6, calnexin, CD63 and S100-A8) related to inflammation, coagulation or immunoregulation were independently verified using western blot. Conclusions: The identification of key proteins carried by STBM may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early-onset severe PE(sPE).
Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a
Authors: Chang Yuewen , Zhao Yongfang , Gu Wei , Cao Yuelong , Wang Shuqiang , Pang Jian , Shi Yinyu
Published: June 2015

Background/Aims: Osteosarcoma (OS) is the second leading cause of cancer-related death in children and young adults. Chemoresistance is the most important cause of treatment failure in OS, largely resulting from presence of cancer stem cells (CSCs). However, CSCs isolated from cancer cell lines do not necessarily represent those from primary human tumors due to accumulation of genetic aberrations that increase with passage number. Therefore, studies on CSCs from primary OS may be more important for understanding the mechanisms driving the chemoresistance of CSCs in OS. Methods: We established a primary culture of OS cells, known as C1OS, from freshly resected tumor tissue. We further isolated CSCs from C1OS cells (C1OS-CSCs). We analyzed the effects of bufalin, a traditional Chinese medicine, on the stemness of C1OS-CSCs. We also analyzed the microRNA (miR) targets of bufalin on the stemness of C1OS-CSCs. Moreover, we examined these findings in the OS specimen. Results: Bufalin inhibited the stemness of C1OS-CSCs. Moreover, we found that miR-148a appeared to be a target of bufalin, and miR-148a further regulated DNMT1 and p27 to control the stemness of OS cells. This mechanism was further confirmed in OS specimen. Conclusion: Our data suggest that bufalin may be a promising treatment for OS, and its function may be conducted through regulation of miR-148a.
Treatment of HAE Attacks in the Icatibant Outcome Survey: An Analysis of Icatibant Self-Administration versus Administration by Health Care Professionals
Authors: Hernández Fernandez de Rojas Dolores , Ibañez Ethel , Longhurst Hilary , Maurer Marcus , Fabien Vincent , Aberer Werner , Bouillet Laurence , Zanichelli Andrea , Caballero Teresa ,   on behalf of the IOS Study Group
Published: June 2015

Background: Icatibant, a selective bradykinin B2 receptor antagonist for the treatment of acute hereditary angio-oedema (HAE) attacks in adults, can be administered by health care professionals (HCPs) or self-administered. This analysis compared characteristics and outcomes of acute HAE attacks treated with self-administered and HCP-administered icatibant in a real-world setting. Methods: The Icatibant Outcome Survey (Shire, Zug, Switzerland; NCT01034969) is an international observational study monitoring the safety and effectiveness of icatibant treatment. Descriptive retrospective analyses were performed (February 2008 to December 2012). Results: Icatibant was used in 652 attacks in 170 patients with HAE type I/II. Most icatibant injections were self-administered (431/652, 68.5%). The proportion of self-treated attacks increased over time (40.3% in 2009 vs. 89.7% in 2012). The median time to administration was significantly shorter in self- versus HCP-treated attacks (1.5 vs. 2.4 h; p = 0.016). Earlier treatment (<2 h after onset) was significantly associated with a shorter median time to resolution (2.5 vs. 5.0 h; p = 0.032) and attack duration (3.0 vs. 14.0 h; p < 0.0001), regardless of administration method. Patients self-administered icatibant for attacks of all severities; overall, 34.7% of severe and 30.2% of very severe attacks were HCP treated. Logistic regression analysis did not find use of long-term prophylaxis, attack location or gender to be predictive for self-administration. Conclusions: The proportion of HAE attacks treated with self-administered icatibant increased over time. Patients successfully self-administered icatibant for a wide variety of HAE attacks, demonstrating that icatibant is generally well tolerated and effective for self-administration. Self-administration of icatibant provides a complementary option to HCP administration, enabling optimization of patient care.
β-Blocker Therapy in the Era of Primary Percutaneous Intervention for ST Elevation Myocardial Infarction
Authors: Lee You-Hong , Park Jin-Sun , Tahk Seung-Jea , Hwang Gyo-Seung , Yoon Myeong-Ho , Choi So-Yeon , Choi Byoung-Joo , Lim Hong-Seok , Yang Hyoung-Mo , Seo Kyoung-Woo , Shin Joon-Han
Published: June 2015

Objectives: With the present therapeutic advances in the era of primary percutaneous coronary intervention (PCI), the role of β-blockers in ST elevation acute myocardial infarction (STEMI) has remained contentious. Methods: We analyzed the data and clinical outcomes of 901 STEMI patients who had undergone primary PCI. We classified the patients into β-blocker (n = 598) and non-β-blocker groups (n = 303). Results: The cumulative incidence of all-cause death was 10.0% in the β-blocker group and 25.4% in the non-β-blocker group (p < 0.001). The incidence of major adverse cardiac events (MACE) was 22.1% in the β-blocker group and 34.3% in the non-β-blocker group (p < 0.001). The relative hazard ratio (HR) of β-blockers for all-cause death and MACE with low left ventricle ejection fraction (LVEF; <50%) was 0.55 [95% confidence interval (CI) 0.35-0.86, p = 0.009] and 0.75 (95% CI 0.51-1.09, p = 0.125), respectively. In patients with normal LVEF (≥50%), the relative HR of β-blockers for death and MACE were 0.50 (95% CI 0.29-0.88, p = 0.016) and 0.75 (95% CI 0.51-1.12, p = 0.162), respectively. After propensity score matching of the difference of the baseline characteristics, the Kaplan-Meier survival curve demonstrated lower mortality in the β-blocker group than in the non-β-blocker group with both low LVEF and normal LVEF (p = 0.02 and p = 0.001, respectively). Conclusions: β-Blockers have beneficial clinical outcomes in the era of primary PCI for STEMI, regardless of the LVEF.
Bronchoscopic Coil Treatment for Patients with Severe Emphysema: A Meta-Analysis
Authors: Slebos Dirk-Jan , Hartman Jorine E. , Klooster Karin , Blaas Stefan , Deslee Gaetan , Gesierich Wolfgang , Hetzel Juergen , Hetzel Martin , McNulty William , Kemp Samuel V. , Kessler Romain , Leroy Sylvie , Stanzel Franz , Witt Christian , Zoumot Zaid , Herth Felix J.F. , Shah Pallav L.
Published: June 2015

Background: Bronchoscopic coil treatment has been shown to improve pulmonary function, exercise capacity, and quality of life in patients with severe emphysema. Objectives: To perform a meta-analysis of the results of four independent European clinical trials investigating this coil therapy for emphysema. Methods: Data on all patients included in the four European clinical trials were analyzed for efficacy and safety outcomes. Results: A total of 2,536 coils were placed during 259 procedures in 140 patients. A total of 37 chronic obstructive pulmonary disease exacerbations and 27 pneumonias were recorded as serious adverse events up to 1 year after treatment. The pneumothorax rate was 6.4%. Both 6 and 12 months after treatment, significant (all p < 0.001) improvements were observed for: forced expiratory volume in 1 s [+0.08 liters (±0.19) and +0.08 liters (±0.21)], residual volume [RV; -510 ml (±850) and -430 ml (±720)], 6-min walking distance [6MWD; +44.1 m (±69.8) and +38.1 m (±71.9)], and St. George's Respiratory Questionnaire score [SGRQ; -9.5 points (±14.3) and -7.7 points (±14.2)]. No differences in any outcome measures were observed between heterogeneous and homogeneous emphysema patients. Only a high baseline RV was found to be an independent predictor of successful treatment. Conclusions: Bronchoscopic coil treatment improves pulmonary function, 6MWD, and quality of life in patients with severe emphysema up to 1 year after treatment, independent of the distribution of the disease.
Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease
Authors: Avezum Alvaro , Lopes Renato D. , Schulte Phillip J. , Lanas Fernando , Gersh Bernard J. , Hanna Michael , Pais Prem , Erol Cetin , Diaz Rafael , Bahit M. Cecilia , Bartunek Jozef , De Caterina Raffaele , Goto Shinya , Ruzyllo Witold , Zhu Jun , Granger Christopher B. , Alexander John H.
Published: June 2015

Background—

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves.

Methods and Results—

We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51–0.97 and HR, 0.84; 95%, CI 0.67–1.04; interaction
P
=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61–1.04 and HR, 0.65; 95% CI, 0.55–0.77; interaction
P
=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84–1.22 and HR, 0.84; 95% CI, 0.73–0.96; interaction
P
=0.10).

Conclusions—

More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00412984.
Intensive Versus Distributed Aphasia Therapy
Authors: Dignam Jade , Copland David , McKinnon Eril , Burfein Penni , O’Brien Kate , Farrell Anna , Rodriguez Amy D.
Published: June 2015

Background and Purpose—

Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia.

Methods—

Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy.

Results—

Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (
P
=0.04) and at 1-month follow-up (
P
=0.002). We found comparable gains on measures of participants’ communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up.

Conclusions—

Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants’ functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models.
Ethnic Consciousness of Pashtun Tribal Rulers in Pre-Modern Times
Authors: Pelevin Mikhail
Published: June 2015

The article examines statements on Pashtun ethnicity from the original Pashto prose texts written by the Khaṯak tribal rulers Khūshḥāl Khān (d. 1689) and Afżal Khān (d. circa 1740/41) and included in the corpus of the historiographical compilation Tārīkh-i muraṣṣa‘ (The Ornamented History). Under discussion are conceptual roots of the Pashtun ethnic identity in tribal genealogical traditions and ethical regulations (Code of Honour) of the Pashtun customary law, main hierarchal levels (national, tribal, clannish) within the ethnic consciousness of the Khaṯak chiefs, and the early development of the concept of Homeland (watan) in Pashto literature. Textual material analysed in the article with reference to similar declarations from the national and patriotic poetry of Khūshḥāl Khān suggests that towards the beginning of the 18th century Pashtun tribes in the mass well recognised themselves as one people with common ethno-cultural heritage, and national self-identification was one of the key elements in their collective consciousness that provided necessary ideological ground for the creation of the Afghan national statehood in 1747.
From Caucasian Albanian to Udi
Authors: Schulze Wolfgang
Published: June 2015

Two palimpsest manuscripts founded in the Mt. Sinai monastery by Zaza Aleksidze and identified as Caucasian Albanian by the same researcher can be regarded as the earliest documentation of an East Caucasian language. The decipherment of the palimpsests dating back to probably the 6th or 7th century A.D. mainly by Jost Gippert and the author of this paper allow relating the language of these texts (fragments of the Gospel of John and parts of a Christian lectionary) to the world of modern East Caucasian languages. It soon became clear that the language conventionally termed Caucasian Albanian (CA; for lack of a known autochthonous name) can be regarded as a more or less direct ancestor of present-day Udi, a minotarian language spoken in one village in Azerbaijan (Nij), as well as in some other settlements and cities of the former USSR. The paper wants to illustrate the degree of relatedness between of CA and Udi by referring to aspects of phonology, morphosyntax, and the lexicon. The CA and (Vartashen) Udi versions of a short text passage (Matthew 17,1-3) are additionally used to show that although some major processes of language change have occurred since the times of CA, there still is enough evidence that ascertain the assumption of immediate relatedness.
The AK Party and Biopolitics: How a Transformation in Governmentality Affects Population Politics in Turkey
Authors: Ongur Hakan Ovunc
Published: June 2015

The political rise of the AK Party in Turkey since 2002 has been associated with a social transformation within the country. This article argues that the dynamics of this transformation is rooted in the simultaneously neoliberal and conservative character of the establishing governmentality. Foucauldian analysis of the AK Party’s practice of biopolitics suggests that the (historically very rare) development of harmony between the ruling governmentality and the majority of society during the AK Party era has facilitated the spread of a new regime of truth regarding the relationship between political power and the human body in Turkey. Examination of textual evidence demonstrates that, in place of Turkey’s previous discourses on eugenics or anatomo-politics of the body, the AK Party’s version of biopower manifests itself directly through population politics by concentrating on birth rates, abortion, universal healthcare, illnesses, and tobacco and alcohol consumption.
Two Modes of Contemporary Pragmatist Aesthetics
Authors: Pryba Russell
Published: June 2015

This paper identifies two central modes of discourse in contemporary pragmatist aesthetics: Cultural Emergentism and Experiential Somaesthetics. Whereas Cultural Emergentism focuses on developing a non-reductive ontology of culture, Experiential Somaesthetics preserves the traditional pragmatist emphasis on embodied experience and examines the place that the care and cultivation of the living soma has in improving our aesthetic transactions.
Preparations for a Theory of Interpretation
Authors: Margolis Joseph
Published: June 2015

This paper points to a more viable theory of interpretation on the basis of opposing the missteps in Arthur Danto’s theory. By noting the incongruities in Danto’s theories of art and interpretation, a theory of interpretation emerges which unifies its varieties on the basis of the view of the human person as a culturally embodied and enlanguaged primate. A feature notably absent from Danto’s own account.