bluuebunny/crossref_metadata_2025 huggingface dataset:
ISU201 Enhances the Resolution of Airway Inflammation in a Mouse Model of an Acute Exacerbation of Asthma
Authors: Hiroshima Yuka , Garthwaite Linda , Hsu Kenneth , Yoo Hyouna , Park Sang-Ho , Geczy Carolyn L. , Kumar Rakesh K. , Herbert Cristan
Published: February 2015

Glucocorticoids are commonly used for treating asthma and its exacerbations but have well‐recognised adverse effects and are not always effective. Few alternative treatments exist. Using a murine model of an acute exacerbation of asthma, we assessed the ability of ISU201, a novel protein drug, to suppress the inflammatory response when administered after induction of an exacerbation. Sensitised mice were chronically challenged with a low mass concentration of aerosolised ovalbumin, and then received a single moderate‐level challenge to simulate an allergen‐induced exacerbation. ISU201 was administered to mice 2 and 8 hours later, while pulmonary inflammation and expression of mRNA for chemokines and proinflammatory cytokines were assessed after 4, 12, and 24 hours. Relative to vehicle‐treated controls, ISU201 suppressed accumulation of pulmonary neutrophils and eosinophils, while accelerating the decline in CXCL1, TNF‐α, and IL‐6 in lavage fluid and lung tissue. ISU201 significantly reduced peak expression of mRNA for the chemokines Cxcl9 and Cxcl10, the adhesion molecules Icam1 and Vcam1, and the proinflammatory cytokines Il1b, Il12p40, and Csf1. The ability of ISU201 to promote resolution of inflammation suggests that it may have potential as an alternative to glucocorticoids in the management of asthma, including when administered after the onset of an acute exacerbation.
Development of Silver Ion Doped Antibacterial Clays and Investigation of Their Antibacterial Activity
Authors: Karel Filiz B. , Koparal Ali S. , Kaynak Elif
Published: February 2015

Kaolinite, sepiolite, and clinoptilolite were used as carriers to develop antibacterial materials. The materials were enriched in sodium by ion exchange. Silver ion exchange by silver nitrate followed by phosphoric acid treatment enabled the controlled release of silver. The antibacterial function of the materials was investigated by halo test and the amount of silver released was investigated by energy dispersive X-ray spectroscopy. The enhanced antibacterial efficiency was obtained by minimizing the silver release which further provided longevity to the material and prevented the health risks posed by excess silver release.
Ergonomic Study and Design of the Pulpit of a Wire Rod Mill at an Integrated Steel Plant
Authors: Dewangan Chandra P. , Singh Arun K.
Published: February 2015

This paper presents ergonomic study and design of the pulpit in a wire rod mill at an integrated steel plant. The mill was facing problem of less productivity of workers due to lack of proper work posture and working conditions. The study data were collected from the interview of seven operators involved with the pulpit. Relevant ergonomic tools were used for assessing the survey data for identifying the risk factors involved with these operators. Ergonomically improved pulpit was proposed for reducing the musculoskeletal disorders (MSDs) thereby increasing the productivity of the plant.
Predicting Radiative Heat Transfer in Oxy-Methane Flame Simulations: An Examination of Its Sensitivities to Chemistry and Radiative Property Models
Authors: Abdul-Sater Hassan , Krishnamoorthy Gautham , Ditaranto Mario
Published: February 2015

Measurements from confined, laminar oxy-methane flames at different O2/CO2dilution ratios in the oxidizer are first reported with measurements from methane-air flames included for comparison. Simulations of these flames employing appropriate chemistry and radiative property modeling options were performed to garner insights into the experimental trends and assess prediction sensitivities to the choice of modeling options. The chemistry was modeled employing a mixture-fraction based approach, Eddy dissipation concept (EDC), and refined global finite rate (FR) models. Radiative properties were estimated employing four weighted-sum-of-gray-gases (WSGG) models formulated from different spectroscopic/model databases. The mixture fraction and EDC models correctly predicted the trends in flame length and OH concentration variations, and the O2, CO2, and temperature measurements outside the flames. The refined FR chemistry model predictions of CO2and O2deviated from their measured values in the flame with 50% O2in the oxidizer. Flame radiant power estimates varied by less than 10% between the mixture fraction and EDC models but more than 60% between the different WSGG models. The largest variations were attributed to the postcombustion gases in the temperature range 500 K–800 K in the upper sections of the furnace which also contributed significantly to the overall radiative transfer.
Polymeric Graphitic Carbon Nitride Doped with CuO Dispersed on Dealuminated Clinoptilolite (CuO/HCP): Synthesis and Characterisation
Authors: Sanni Saheed Olalekan , Idemudia Omoruyi Gold
Published: February 2015

CuO dispersed on dealuminated clinoptilolite (CuO/HCP) and further doped with polymeric graphitic carbon nitride (CuO/HCP‐g‐C3N4) was synthesized through 2 facile routes: precipitation method for CuO/HCP and impregnation through ultrasonication method for the hybrid composite material. The hybrid composite material crystalline phase, surface morphology, and structural and thermal properties were investigated by X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy‐dispersive X‐ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR), and thermal analysis. The formation of the hybrid composite material was confirmed by XRD showing crystalline phase of CuO and g‐C3N4 present on the surface of dealuminated clinoptilolite (HCP). SEM images analysis depicts no aggregation of the mixed metal oxide semiconductor nanoparticles at the center of HCP. The hybrid composite material, CuO/HCP‐g‐C3N4, with a good homogeneously dispersed metal oxide conductor having excellent catalytic activities has been synthesized.
Osteoma Presenting as a Painless Solitary Mastoid Swelling
Authors: Abdel Tawab Hazem M. , Kumar V Ravi , Tabook Salim M. Sloma
Published: February 2015

Introduction.Osteoma of the temporal bone is a very uncommon benign tumor of bone. Osteomas may occur in the external auditory canals but are reported to be very rare in the mastoid bone.Case Report.A 36-year-old male presented to our department with a hard swelling behind the right ear diagnosed as osteoma. Complete excision was done through a postauricular approach. Histopathology confirmed the diagnosis of osteoma.Conclusion.Osteomas, although rare, should be considered when dealing with any hard mastoid swelling. Complete removal can be ensured by drilling till the normal cortical bone is reached to avoid recurrence. A cortical mastoidectomy should be done if the mastoid air cell system is involved.
Early-Onset Neutropenia Induced by Rituximab in a Patient with Lupus Nephritis and Hemolytic Anemia
Authors: Arroyo-Ávila Mariangelí , Fred-Jiménez Ruth M. , Vilá Luis M.
Published: February 2015

Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections.
Ultrastructural Analysis of Leishmania infantum chagasi Promastigotes Forms Treated In Vitro with Usnic Acid
Authors: da Luz João S. B. , de Oliveira Erwelly B. , Martins Monica C. B. , Silva Nicácio H. da , Alves Luiz C. , dos Santos Fábio A. B. , da Silva Luiz L. S. , Silva Eliete C. , de Medeiros Paloma L.
Published: February 2015

Leishmaniasis is considered by the World Health Organization as one of the infectious parasitic diseases endemic of great relevance and a global public health problem. Pentavalent antimonials used for treatment of this disease are limited and new phytochemicals emerge as an alternative to existing treatments, due to the low toxicity and cost reduction. Usnic acid is uniquely found in lichens and is especially abundant in genera such as Alectoria, Cladonia, Evernia, Lecanora, Ramalina, and Usnea. Usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti‐inflammatory, and analgesic activity. The aim of this study was to evaluate the antileishmanial activity of usnic acid on Leishmania infantum chagasi promastigotes and the occurrence of drug‐induced ultrastructural damage in the parasite. Usnic acid was effective against the promastigote forms (IC50 = 18.30 ± 2.00 µg/mL). Structural and ultrastructural aspects of parasite were analyzed. Morphological alterations were observed as blebs in cell membrane and shapes given off, increasing the number of cytoplasmic vacuoles, and cellular and mitochondrial swelling, with loss of cell polarity. We concluded that the usnic acid presented antileishmanial activity against promastigote forms of Leishmania infantum chagasi and structural and ultrastructural analysis reinforces its cytotoxicity. Further, in vitro studies are warranted to further evaluate this potential.
Race, Socioeconomic Status, and Age: Exploring Intersections in Preterm Birth Disparities among Teen Mothers
Authors: Coley Sheryl L. , Nichols Tracy R. , Rulison Kelly L. , Aronson Robert E. , Brown-Jeffy Shelly L. , Morrison Sharon D.
Published: February 2015

Few studies have examined disparities in adverse birth outcomes and compared contributing socioeconomic factors specifically between African-American and White teen mothers. This study examined intersections between neighborhood socioeconomic status (as defined by census-tract median household income), maternal age, and racial disparities in preterm birth (PTB) outcomes between African-American and White teen mothers in North Carolina. Using a linked dataset with state birth record data and socioeconomic information from the 2010 US Census, disparities in preterm birth outcomes for 16,472 teen mothers were examined through bivariate and multilevel analyses. African-American teens had significantly greater odds of PTB outcomes than White teens (OR = 1.38, 95% CI 1.21, 1.56). Racial disparities in PTB rates significantly varied by neighborhood income; PTB rates were 2.1 times higher for African-American teens in higher income neighborhoods compared to White teens in similar neighborhoods. Disparities in PTB did not vary significantly between teens younger than age 17 and teens ages 17–19, although the magnitude of racial disparities was larger between younger African-American and White teens. These results justify further investigations using intersectional frameworks to test the effects of racial status, neighborhood socioeconomic factors, and maternal age on birth outcome disparities among infants born to teen mothers.
Lucas Polynomial Approach for System of High-Order Linear Differential Equations and Residual Error Estimation
Authors: Çetin Muhammed , Sezer Mehmet , Güler Coşkun
Published: February 2015

An approximation method based on Lucas polynomials is presented for the solution of the system of high-order linear differential equations with variable coefficients under the mixed conditions. This method transforms the system of ordinary differential equations (ODEs) to the linear algebraic equations system by expanding the approximate solutions in terms of the Lucas polynomials with unknown coefficients and by using the matrix operations and collocation points. In addition, the error analysis based on residual function is developed for present method. To demonstrate the efficiency and accuracy of the method, numerical examples are given with the help of computer programmes written inMapleandMatlab.
Inverted Lymphoglandular Polyp in Descending Colon
Authors: Zhou Shengmei , Ma Yanling , Chandrasoma Parakrama
Published: February 2015

A 47-year-old male with a history of left colon cancer, status post left colon resection for 12 years, presented with rectal bleeding. Colonoscopic examination revealed an 8 mm sessile polyp in the proximal descending colon. Microscopic examination showed that the surface of this polyp was covered with a layer of normal colonic mucosa with focal surface erosion. In the submucosal layer, an intimate admixture of multiple cystically dilated glands and prominent lymphoid aggregates with germinal centers was seen. The glands were lined by columnar epithelium. Immunohistochemical staining showed the glands were positive for CK20 and CDX2 and negative for CK7, with a low proliferative index, mostly consistent with reactive colonic glands. The patient remained asymptomatic after one-year follow-up. A review of the literature shows very rare descriptions of similar lesions, but none fits exactly this pattern. We would designate this inverted lymphoglandular polyp and present this case to raise the awareness of recognizing this unusual histological entity.
An Image Steganography Method Hiding Secret Data into Coefficients of Integer Wavelet Transform Using Pixel Value Differencing Approach
Authors: Gulve Avinash K. , Joshi Madhuri S.
Published: February 2015

The image steganography systems use either the spatial domain or the frequency domain to hide the secret information. The proposed technique uses spatial domain technique to hide secret information in the frequency domain. The cover image is transformed using integer wavelet transform to obtain four subbands: LL, LH, HL, and HH. Then, the PVD approach is used to hide the secret information in the wavelet coefficients of all the four subbands. For improving the security of the hidden information, the proposed method first modifies the difference between two wavelet coefficients of a pair and then uses the modified difference to hide the information. This makes extraction of secret data from the stego image difficult even if the steganography method fails. The result shows that the proposed technique outperforms other PVD based techniques in terms of security of secret information and hiding capacity of cover image.
Identifying the Prevalence, Trajectory, and Determinants of Psychological Distress in Extremity Sarcoma
Authors: Tang Melissa H. , Castle David J. , Choong Peter F. M.
Published: February 2015

Objective. Extremity sarcoma (ES) is a rare cancer that presents with unique challenges. This study was performed to identify the prevalence, trajectory, and determinants of distress and characterise sources of stress in this cohort.Methods. Consecutive patients with ES were prospectively recruited between May 2011 and December 2012. Questionnaires were administered during initial diagnosis and then six months and one year after surgery.Results. Distress was reported by about a third of our cohort and associated with poorer physical function, poorer quality of life, and pain. In addition to fears regarding mortality and life role changes, the most common sources of stress were centered on dissatisfaction with the healthcare system, such as frustrations with a lack of communication with the hospital regarding appointments and lack of education regarding management and outcomes.Conclusions. Psychological distress presents early in the cancer journey and persists up to one year after surgery. Distress is associated with negative outcomes. Active screening and effective interventions are necessary to improve outcomes. Sources of stress have been identified that may be amenable to targeted interventions.
The Olive Oil‐Based Lipid Clinoleic Blocks Leukocyte Recruitment and Improves Survival during Systemic Inflammation: A Comparative In Vivo Study of Different Parenteral Lipid Emulsions
Authors: Buschmann Kirsten , Poeschl Johannes , Braach Natascha , Hudalla Hannes , Kuss Navina , Frommhold David
Published: February 2015

Although fish oil‐based and olive oil‐based lipid emulsions have been shown to exert anti‐inflammatory functions, the immunomodulating properties of lipids are still controversial. Therefore, we investigated the anti‐inflammatory effect of three different parenterally administered lipid emulsions in vivo: olive oil‐based Clinoleic, fish oil‐based Smoflipid, and soybean oil‐based Lipofundin. We observed leukocyte recruitment in inflamed murine cremaster muscle using intravital microscopy and survival in a murine model of LPS‐induced systemic inflammation and analyzed expression of leukocyte and endothelial adhesion molecules. Olive oil‐based Clinoleic and fish oil‐based Smoflipid profoundly inhibited leukocyte adhesion compared to Lipofundin during LPS‐induced inflammation of the murine cremaster muscle. In the trauma model of cremaster muscle inflammation, Lipofundin was the only lipid emulsion that even augmented leukocyte adhesion. In contrast to Smoflipid and Lipofundin, Clinoleic effectively blocked leukocyte recruitment and increased survival during lethal endotoxemia. Flow chamber experiments and analysis of adhesion molecule expression suggest that both endothelial and leukocyte driven mechanisms might contribute to anti‐inflammatory effects of Clinoleic. We conclude that the anti‐inflammatory properties of Clinoleic are superior to those of Smoflipid and Lipofundin even during systemic inflammation. Thus, these results should stimulate further studies investigating parenteral lipids as an anti‐inflammatory strategy in critically ill patients.
Effects of Selected Physicochemical Parameters on Zerumbone Production ofZingiber zerumbetSmith Cell Suspension Culture
Authors: Jalil Mahanom , Annuar Mohamad Suffian Mohamad , Tan Boon Chin , Khalid Norzulaani
Published: February 2015

Zingiber zerumbetSmith is an important herb that contains bioactive phytomedicinal compound, zerumbone. To enhance cell growth and production of this useful compound, we investigated the growth conditions of cell suspension culture. Embryogenic callus generated from shoot bud was used to initiate cell suspension culture. The highest specific growth rate of cells was recorded when it was cultured in liquid Murashige and Skoog basal medium containing 3% sucrose with pH 5.7 and incubated under continuous shaking condition of 70 rpm for 16 h light and 8 h dark cycle at 24°C. Our results also revealed that the type of carbohydrate substrate, light regime, agitation speed, and incubation temperature could affect the production of zerumbone. Although the zerumbone produced in this study was not abundant compared to rhizome ofZ. zerumbet, the possibility of producing zerumbone during early stage could serve as a model for subsequent improvement.
Effect of Lidocaine and Epinephrine on Human Erythrocyte Shape and Vesiculability of Blood Cells
Authors: Slokar Tanja , Lopez-Mariscal Carlos , Krek Judita Lea , Štukelj Roman , Zupanc Oskar , Kralj-Iglič Veronika
Published: February 2015

The effect of local anesthetic composed of lidocaine and epinephrine on vesiculability of blood cells and erythrocyte shape was studied. Whole blood and plasma were incubated with lidocaine/epinephrine. Extracellular vesicles were isolated by centrifugation and washing and counted by flow cytometry. Lidocaine/epinephrine and each component alone were added to diluted blood. Shape changes were recorded by micrographs. An ensemble of captured frames was analyzed for populations of discocytes, echinocytes, and stomatocytes by using statistical methods. Incubation of whole blood and blood plasma with lidocaine/epinephrine considerably increased concentration of extracellular vesicles in isolates (for an average factor 3.4 in blood and 2.8 in plasma). Lidocaine/epinephrine caused change of erythrocyte shape from mainly discocytic to mainly stomatocytic (higher than 50%). Lidocaine alone had even stronger stomatocytic effect (the percent of stomatocytes was higher than 95%) while epinephrine had echinocytic effect (the percent of echinocytes was higher than 80%). The differences were highly statistically significantp<10-8with statistical powerP=1. Lidocaine/epinephrine induced regions of highly anisotropically curved regions indicating that lidocaine and epinephrine interact with erythrocyte membrane. It was concluded that lidocaine/epinephrine interacts with cell membranes and increases vesiculability of blood cellsin vitro.
Statistical Methods for the Investigation of Solvolysis Mechanisms Illustrated by the Chlorides of the Carbomethoxy Protecting Groups NVOC and FMOC
Authors: D’Souza Malcolm J. , Deol Jasbir K. , Pavey Maryeah T. , Kevill Dennis N.
Published: February 2015

The solvolysis of 4,5-dimethoxy-2-nitrobenzyl chloroformate (NVOC-Cl,1) is followed at 25.0°C in twenty hydroxylic solvents. A comparison with previously published rates for benzyl chloroformate andp-nitrobenzyl chloroformate indicates that the inductive effect of the nitro and the two methoxy groups strongly influences the rate of reaction. For1, the specific rates of solvolysis are correlated using an extended Grunwald-Winstein (G-W) treatment. A direct comparison with the data for phenyl chloroformate (PhOCOCl) in identical solvents strongly suggests that the addition step within an addition-elimination mechanism is rate-determining for both substrates. A reevaluation of the kinetic data for 9-fluorenylmethyl chloroformate (FMOC-Cl,2) involves a correlation oflog⁡k/ko2versuslog⁡(k/ko)PhOCOCl. In this plot, deviations were observed in solvents rich in a hydrogen-bonding fluoroalcohol component. Omitting the aqueous fluoroalcohol rate measurements for2in an analysis using the extended G-W equation suggested the occurrence of dual pathways differing in the dependences upon the ionizing power and nucleophilicity of the solvent. In addition, the fluorenyl ring is rotated out of the plane containing the ether oxygen and, as a result, PhOCOCl is found to solvolyze 20 times faster than2in ethanol and methanol.
Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β
Authors: Alamino Vanina A. , Mascanfroni Iván D. , Montesinos María M. , Gigena Nicolás , Donadio Ana C. , Blidner Ada G. , Milotich Sonia I. , Cheng Sheue-yann , Masini-Repiso Ana M. , Rabinovich Gabriel A. , Pellizas Claudia G.
Published: February 2015

Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8+ T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy. Cancer Res; 75(7); 1265–74. ©2015 AACR.
VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy
Authors: Schwaederlé Maria , Lazar Vladimir , Validire Pierre , Hansson Johan , Lacroix Ludovic , Soria Jean-Charles , Pawitan Yudi , Kurzrock Razelle
Published: February 2015

Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non–small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P = 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types. Cancer Res; 75(7); 1187–90. ©2015 AACR.
Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma
Authors: Xie Xiaoqi , Koh Ju Yong , Price Sandy , White Eileen , Mehnert Janice M.
Published: February 2015

Macroautophagy (autophagy hereafter) may promote survival and growth of spontaneous tumors, including melanoma. We utilized a genetically engineered mouse model of melanoma driven by oncogenic BrafV600E and deficiency in the Pten tumor suppressor gene in melanocytes to test the functional consequences of loss of the essential autophagy gene autophagy-related-7, Atg7. Atg7 deficiency prevented melanoma development by BrafV600E and allelic Pten loss, indicating that autophagy is essential for melanomagenesis. Moreover, BrafV600E-mutant, Pten-null, Atg7-deficient melanomas displayed accumulation of autophagy substrates and growth defects, which extended animal survival. Atg7-deleted tumors showed increased oxidative stress and senescence, a known barrier to melanomagenesis. Treatment with the BRAF inhibitor dabrafenib decreased tumor growth and induced senescence that was more pronounced in tumors with Atg7 deficiency. Thus, Atg7 promotes melanoma by limiting oxidative stress and overcoming senescence, and autophagy inhibition may be of therapeutic value by augmenting the antitumor activity of BRAF inhibitors.

Significance: The essential autophagy gene Atg7 promotes development of BrafV600E-mutant, Pten-null melanomas by overcoming senescence, and deleting Atg7 facilitated senescence induction and antitumor activity of BRAF inhibition. This suggests that combinatorial BRAFV600E and autophagy inhibition may improve therapeutic outcomes in patients whose tumors have BRAFV600E/K mutations, an approach currently being explored in clinical trials. Cancer Discov; 5(4); 410–23. ©2015 AACR.

See related commentary by Thorburn and Morgan, p. 353

This article is highlighted in the In This Issue feature, p. 333
Assessing the Effects of Concurrent versus Sequential Cisplatin/Radiotherapy on Immune Status in Lung Tumor–Bearing C57BL/6 Mice
Authors: Kao Chiao-Jung , Wurz Gregory T. , Lin Yi-Chen , Vang Daniel P. , Griffey Stephen M. , Wolf Michael , DeGregorio Michael W.
Published: February 2015

Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy. Cancer Immunol Res; 3(7); 741–50. ©2015 AACR.
Innate Hypothermia after Hypoxic Ischaemic Delivery
Authors: Jayasinghe Dulip
Published: February 2015

The focus of this review is to collate the literature on the phenomenon of impaired thermal adaptation after hypoxic ischaemic (HI) delivery often culminating in hypothermia. This phenomenon appears different in severity and duration to a spontaneous postnatal fall in temperature observed after normal delivery. The original observation and contemporary descriptions of the temperature response to HI are described and a mechanism of action is proposed that may be utilised as a novel biomarker for HI.
Synergistic Toxicity of Gentamicin- and Nanosilver-Doped Polymethylmethacrylate Bone Cement on Primary Human Osteoclasts
Authors: Pauksch Linda , Franke Jörg , Schnettler Reinhard , Lips Katrin S.
Published: February 2015

Bacterial colonization of implant surfaces is a feared complication in surgery and orthopedics. Due to the increasing number of periprosthetic infections caused by multidrug-resistant microorganisms, new antibacterial coatings for biomaterials must be developed. The excellent antibacterial properties of silver nanoparticles (AgNPs) against multidrug-resistant bacteria, for example, have been repeatedly described. For this reason, we tested a nanosilver-doped polymethylmethacrylate (PMMA) bone cement and a nanosilver-coated titanium alloy regarding their influence on osteoclastogenesis of primary human peripheral blood mononuclear cells. Both implant variants did not inhibit osteoclast differentiation. Excellent cell attachment and unaltered podosomal structures were confirmed. Additionally, no induction of oxidative or endoplasmic reticulum stress could be observed. However, PMMA loaded with gentamicin and nanosilver inhibited preosteoclast fusion and further osteoclastogenesis. The material also led to decreased clathrin-dependent endocytosis as well as decreased levels of endoplasmic reticulum stress. Therefore, biomaterial functionalization with AgNPs did not disturb osteoclastogenesis, while addition of gentamicin reduced the cytocompatibility of nanosilver-doped materials towards human osteoclasts.
Higher Expression of miR-182 in Cytology Specimens of High-Grade Urothelial Cell Carcinoma: A Potential Diagnostic Marker
Authors: Wei Shuanzeng , Bing Zhanyong , Yao Yuan , Master Stephen R. , Gupta Prabodh
Published: February 2015

Objective: MicroRNAs (miRs) are short noncoding RNA molecules that posttranscriptionally modulate protein expression. There are distinct miR alterations characterizing urothelial cell carcinoma (UCC) of the urinary bladder. Study Design: In this study, we investigate the possibility of using miR as a noninvasive marker in the screening of UCC. The total RNA was extracted from 75 cytology specimens including bladder or renal washings and voided urines. Cases comprise UCC (21 high grade and 6 low grade), 25 normal controls and 23 cases with a history of UCC but negative at the time of testing (negative with a positive history). The expressions of miR-96, miR-182, miR-183, miR-200c, miR-21, miR-141 and miR-30b were determined using quantitative TaqMan real-time PCR. Results and Conclusion: This study shows that the level of miR-182 is higher in cytology specimens from high-grade UCC patients as compared to normal controls. Measuring miR-182 may provide a potential alternative or adjunct approach for screening high-grade UCC.
Differences in Clinical Features and Outcomes between Group A- and Group G Streptococcus-Induced Cellulitis
Authors: Komatsu Yurie , Okazaki Aki , Hirahara Kazuhisa , Araki Koji , Shiohara Tetsuo
Published: February 2015

Background: Streptococci are the main causative agents of cellulitis, and group G Streptococcus (GGS) shares many important virulent factors with group A Streptococcus (GAS). The difference in the clinical features of GAS- and GGS-induced cellulitis, however, has not been thoroughly characterized. Objective: Our aim was to recognize the differences in the clinical manifestations and outcomes of lower limb cellulitis caused by GAS and GGS. Methods: We retrospectively analyzed a total of 29 patients diagnosed with GAS- or GGS-induced lower limb cellulitis during the period from January 2008 to September 2013. Results: While the clinical manifestations of GAS-induced cellulitis were likely to be uniform, those of GGS-induced cellulitis were variable, depending on the predisposing factors. GGS-induced cellulitis occurred more frequently in older person who had chronic underlying illness. Conclusion: We identified clinical predisposing factors that can predict the clinical course and outcomes of GGS-induced cellulitis.
Reasons for Excision of Skin Tumors: A One-Year Prospective Study in a Tertiary Skin Cancer Unit
Authors: Lallas Aimilios , Longo Caterina , Moscarella Elvira , Lombardi Mara , Specchio Francesca , Raucci Margherita , Zalaudek Iris , Argenziano Giuseppe
Published: February 2015

Background: Biopsies and surgical excisions represent routine procedures in clinical settings dealing with skin cancer. Objective: To evaluate the impact of clinical examination, dermoscopy, reflectance confocal microscopy and digital monitoring on the decision to excise or biopsy a lesion in routine practice. Methods: Patients scheduled for biopsy or excision of a skin lesion were prospectively enrolled. The expert dermatologist was asked to select the main factor that prompted him/her to excise or biopsy the lesion. Results: The most common reason for melanoma excision was clinical and dermoscopic morphology (70.3%), followed by dermoscopy (11.4%), monitoring (8.9%) and clinical context (8.2%). Most basal and squamous cell carcinomas were recognized both clinically and dermoscopically, while 18.6 and 15.0%, respectively, could only be detected with dermoscopic examination. Conclusion: Each part of the clinical examination has a contributory role in the diagnosis of melanoma and other skin cancers.
Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases
Authors: Le Rhun Emilie , Taillibert Sophie , Boulanger Thomas , Zairi Fahed , Bonneterre Jacques , Chamberlain Marc C.
Published: February 2015

Background: Survival of patients with leptomeningeal metastases (LM) and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar) and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.
Arrhythmogenic Remodeling of β
2
Versus β
1
Adrenergic Signaling in the Human Failing Heart
Authors: Lang Di , Holzem Katherine , Kang Chaoyi , Xiao Mengqian , Hwang Hye Jin , Ewald Gregory A. , Yamada Kathryn A. , Efimov Igor R.
Published: February 2015

Background—

Arrhythmia is the major cause of death in patients with heart failure, for which β-adrenergic receptor blockers are a mainstay therapy. But the role of β-adrenergic signaling in electrophysiology and arrhythmias has never been studied in human ventricles.

Methods and Results—

We used optical imaging of action potentials and [Ca
2+
]
i
transients to compare the β
1
- and β
2
-adrenergic responses in left ventricular wedge preparations of human donor and failing hearts. β
1
-Stimulation significantly increased conduction velocity, shortened action potential duration, and [Ca
2+
]
i
transients duration (CaD) in donor but not in failing hearts, because of desensitization of β
1
-adrenergic receptor in heart failure. In contrast, β
2
-stimulation increased conduction velocity in both donor and failing hearts but shortened action potential duration only in failing hearts. β
2
-Stimulation also affected transmural heterogeneity in action potential duration but not in [Ca
2+
]
i
transients duration. Both β
1
- and β
2
-stimulation augmented the vulnerability and frequency of ectopic activity and enhanced substrates for ventricular tachycardia in failing, but not in donor, hearts. Both β
1
- and β
2
-stimulation enhanced Purkinje fiber automaticity, whereas only β
2
-stimulation promoted Ca-mediated premature ventricular contractions in heart failure.

Conclusions—

During end-stage heart failure, β
2
-stimulation creates arrhythmogenic substrates via conduction velocity regulation and transmurally heterogeneous repolarization. β
2
-Stimulation is, therefore, more arrhythmogenic than β
1
-stimulation. In particular, β
2
-stimulation increases the transmural difference between [Ca
2+
]
i
transients duration and action potential duration, which facilitates the formation of delayed afterdepolarizations.
Long Noncoding RNAs and MicroRNAs in Cardiovascular Pathophysiology
Authors: Thum Thomas , Condorelli Gianluigi
Published: February 2015

RNAs not encoding proteins have gained prominence over the last couple of decades as fundamental regulators of cellular function. Not surprisingly, their dysregulation is increasingly being linked to pathology. Here, we review recent reports investigating the pathophysiological relevance of this species of RNA for the cardiovascular system, concentrating mainly on recent findings on long noncoding RNAs and microRNAs in cardiac hypertrophy and failure.
Atherosclerotic Plaque Inflammation Varies Between Vascular Sites and Correlates With Response to Inhibition of Lipoprotein‐Associated Phospholipase A
2
Authors: Fenning Robert S. , Burgert Mark E. , Hamamdzic Damir , Peyster Eliot G. , Mohler Emile R. , Kangovi Shreya , Jucker Beat M. , Lenhard Stephen C. , Macphee Colin H. , Wilensky Robert L.
Published: February 2015

Background

Despite systemic exposure to risk factors, the circulatory system develops varying patterns of atherosclerosis for unclear reasons. In a porcine model, we investigated the relationship between site‐specific lesion development and inflammatory pathways involved in the coronary arteries (
COR
s) and distal abdominal aortas (
AA
s).

Methods and Results

Diabetes mellitus (
DM
) and hypercholesterolemia (
HC
) were induced in 37 pigs with 3 healthy controls. Site‐specific plaque development was studied by comparing plaque severity, macrophage infiltration, and inflammatory gene expression between
COR
s and
AA
s of 17
DM
/
HC
pigs. To assess the role of lipoprotein‐associated phospholipase A
2
(Lp‐
PLA
2
) in plaque development, 20
DM
/
HC
pigs were treated with the Lp‐
PLA
2
inhibitor darapladib and compared with the 17
DM
/
HC
untreated pigs.
DM
/
HC
caused site‐specific differences in plaque severity. In the
AA
s, normalized plaque area was 4.4‐fold higher (
P
<0.001) and there were more fibroatheromas (9 of the 17 animals had a fibroatheroma in the
AA
and not the
COR
,
P
=0.004), while normalized macrophage staining area was 1.5‐fold higher (
P
=0.011) compared with
COR
s.
DM
/
HC
caused differential expression of 8 of 87 atherosclerotic genes studied, including 3 important in inflammation with higher expression in the
COR
s. Darapladib‐induced attenuation of normalized plaque area was site‐specific, as
COR
s responded 2.9‐fold more than
AA
s (
P
=0.045).

Conclusions

While plaque severity was worse in the
AA
s, inflammatory genes and inflammatory pathways that use Lp‐
PLA
2
were more important in the
COR
s. Our results suggest fundamental differences in inflammation between vascular sites, an important finding for the development of novel anti‐inflammatory therapeutics.
The Issues Concerning the Continental Shelf: Reflections
Authors: Lucky Anthony
Published: February 2015

The concept and the process of development of the regime of the continental shelf began in the 1930s when the exploration for oil and natural gas extended to the submarine areas of some coastal states. An orderly process was prescribed in the Gulf of Paria Treaty of 1942. The doctrine of the Continental shelf received an impetus in the Truman Proclamation of 1945. In light of the unilateral declarations by coastal states, and to ensure an orderly process, States concluded the 1958 Geneva Convention on the Law of the Sea. The 1982 United Nations Convention on the Law of the Sea codified the existing laws and is still in force. In this age of rapid technological advancement, the law has provided the necessary guidelines and controls for orderly exploration and exploitation in the continental shelf and will continue to keep abreast of technological advancement.
Contribution to the knowledge of the genus Syndicus Motschulsky (Coleoptera: Staphylinidae: Scydmaeninae) in China
Authors: YIN ZI-WEI , LI LI-ZHEN
Published: February 2015

Two new species of the ant-like stone beetle genus Syndicus Motschulsky (Scydmaeninae: Cyrtoscydmini) from the Hainan Island, southern China are described: S. (Semisyndicus) grossepunctatus sp. n. and S. (Semisyndicus) hainanicus sp. n. The previously unknown female of S. (Semisyndicus) schuelkei is discovered, and its spermatheca is illustrated. Syndicus (s. str.) jaloszynskii is newly recorded from Hunan, central China. A single female of the nominotypical subgenus from Motuo, Xizang is listed; its identity remains unconfirmed until associated males become available.
Palaearctic species of the Hercostomus plagiatus group (Diptera: Dolichopodidae) with description of a new species from the Middle East
Authors: GRICHANOV IGOR YA.
Published: February 2015

The Hercostomus plagiatus species group is defined and distinguished from other Hercostomus groups by the following combination of features including: bulging clypeus in both sexes, anterodorsal comb-like row of setae on fore tibia, usually straight and weakly convergent veins R4+5 and M1+2, hypopygium without basiventral epandrial lobes, mostly free hypandrium, relatively poorly developed postgonite, and female terminalia with tergite 8 and sternite 8 fused anterolaterally forming a narrow process. A new species, Hercostomus golanensis sp. nov., is described from the Middle East (Golan Heights), differing from the other species of this group in the long-pubescent arista-like stylus, triangular rather than oval male cercus and epandrial lobe bearing a very long seta at the base of the stem. A key to species of the H. plagiatus group is provided.
Two new species of the genus Arboridia Zachvatkin (Hemiptera: Auchenorrhyncha: Cicadellidae: Typhlocybinae) from Korea
Authors: OH SUMIN , CHOE KWANG-RYUL , JUNG SUNGHOON
Published: February 2015

Two new species of the genus Arboridia Zachvatkin, A. koreana sp. nov., A. septempunctata sp. nov., are described from Korea. Photographs of dorsal habitus, illustrations of male genitalia, abdomens and forewings, and biological information such as host plants and distributional records and a key to the Korean Arboridia species are provided.
The Amazon Dense GNSS Meteorological Network: A New Approach for Examining Water Vapor and Deep Convection Interactions in the Tropics
Authors: Adams David K. , Fernandes Rui M. S. , Holub Kirk L. , Gutman Seth I. , Barbosa Henrique M. J. , Machado Luiz A. T. , Calheiros Alan J. P. , Bennett Richard A. , Kursinski E. Robert , Sapucci Luiz F. , DeMets Charles , Chagas Glayson F. B. , Arellano Ave , Filizola Naziano , Amorim Rocha Alciélio A. , Silva Rosimeire Araújo , Assunção Lilia M. F. , Cirino Glauber G. , Pauliquevis Theotonio , Portela Bruno T. T. , Sá André , de Sousa Jeanne M. , Tanaka Ludmila M. S.
Published: February 2015

The complex interactions between water vapor fields and deep atmospheric convection remain one of the outstanding problems in tropical meteorology. The lack of high spatial–temporal resolution, all-weather observations in the tropics has hampered progress. Numerical models have difficulties, for example, in representing the shallow-to-deep convective transition and the diurnal cycle of precipitation. Global Navigation Satellite System (GNSS) meteorology, which provides all-weather, high-frequency (5 min), precipitable water vapor estimates, can help. The Amazon Dense GNSS Meteorological Network experiment, the first of its kind in the tropics, was created with the aim of examining water vapor and deep convection relationships at the mesoscale. This innovative, Brazilian-led international experiment consisted of two mesoscale (100 km × 100 km) networks: 1) a 1-yr (April 2011–April 2012) campaign (20 GNSS meteorological sites) in and around Manaus and 2) a 6-week (June 2011) intensive campaign (15 GNSS meteorological sites) in and around Belem, the latter in collaboration with the Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud-Resolving Modeling and to the Global Precipitation Measurement (CHUVA) Project in Brazil. Results presented here from both networks focus on the diurnal cycle of precipitable water vapor associated with sea-breeze convection in Belem and seasonal and topographic influences in and around Manaus. Ultimately, these unique observations may serve to initialize, constrain, or validate precipitable water vapor in high-resolution models. These experiments also demonstrate that GNSS meteorology can expand into logistically difficult regions such as the Amazon. Other GNSS meteorology networks presently being constructed in the tropics are summarized.