bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade
Authors: Gu Yi-Feng , Cohn Shannon , Christie Alana , McKenzie Tiffani , Wolff Nicholas , Do Quyen N. , Madhuranthakam Ananth J. , Pedrosa Ivan , Wang Tao , Dey Anwesha , Busslinger Meinrad , Xie Xian-Jin , Hammer Robert E. , McKay Renée M. , Kapur Payal , Brugarolas James
Published: May 2017

Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1-deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1-deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1, in Pbrm1-deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells.

Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900–17. ©2017 AACR.

See related commentary by Leung and Kim, p. 802.

This article is highlighted in the In This Issue feature, p. 783
Caruncular Oncocytoma Mimicking Malignant Melanoma
Authors: Surakiatchanukul Thamolwan , Sioufi Kareem , Pointdujour-Lim Renelle , Eagle Jr. Ralph C. , Shields Jerry A. , Shields Carol L.
Published: May 2017

Purpose: To report a case of pigmented caruncular oncocytoma that simulated malignant melanoma and discuss the associated ultrasonographic and pathologic features. Method: Case report. Results: An 81-year-old female presented with a painless caruncular mass with a smooth brown surface suspicious for melanoma. Ultrasound biomicroscopy revealed a round mass with a large central cavity, more suggestive of a cystic rather than solid lesion. Following complete surgical resection, histopathology revealed a cystadenomatous lesion composed of bland cells with copious eosinophilic cytoplasm consistent with oncocytoma that had a central blood-filled cavity. Conclusions: Oncocytoma is a benign tumor that can appear pigmented clinically and resemble melanoma. The definitive diagnosis requires histopathologic evaluation. Oncocytoma should be considered in the differential diagnosis of a pigmented caruncular mass.
Precision Genetic and Genomic Medicine in the Middle East and North Africa Region: Are We There Yet?
Authors: Bilani Nadeem , Dagher Michael , Zgheib Nathalie K.
Published: May 2017

Purpose: As precision medicine continues its expansion into clinical practice and research settings, it is time to investigate genetic and genomic research in the Middle East and North Africa (MENA) region to identify the strengths and deficits and to provide suggestions for future development. Methods: We performed a literature review of any genetic or genomic publications on breast cancer and type 2 diabetes for the years 2000-2015 and evaluated the translational value of the research using multiple evaluation metrics, including the “continuum of translation” and the Health Impact Pyramid. Results: A total of 138 type 2 diabetes and 231 breast cancer publications were included. There were few cohort studies or randomized controlled trials, and there was a distinct lack of pharmacogenetic or pharmacogenomic papers. Most studies were not interventional but instead evaluated susceptibility, and when placed on the continuum of translation, more than 90% of the studies were T1. Conclusion: This study suggests that the translational value of genetic and genomic research in the MENA region is currently suboptimal. Moving forward requires international cooperation and a collaborative cohort program in order to implement precision medicine in this area of the world.
PDGF-BB/KLF4/VEGF Signaling Axis in Pulmonary Artery Endothelial Cell Angiogenesis
Authors: Liang Songhe , Yu Hao , Chen Xinxin , Shen Tingting , Cui Zhongqi , Zhang JunTing , Cheng Yue , Jia Shiwei , Song Shasha , Zhang Xiang , Yu Xiufeng
Published: May 2017

Background: Accumulating evidence suggests that platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor(VEGF) play a role in the progression of pulmonary arterial hypertension (PAH).Since chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary arteries, which are histological hallmarks of PAH, we explored the role of the PDGF-BB/KLF4/VEGF signaling axis in the angiogenesis of pulmonary artery endothelial cells (PAECs). Methods: Adult male Wistar rats were used to study hypoxia-induced or monocrotaline (MCT)-induced right ventricular (RV) remodeling as well as systolic function and hemodynamics using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV vessels were performed. Results: The results revealed that both the PDGF receptor-tyrosine kinase inhibitor imatinib and the multi-targeted VEGF and PDGF receptor inhibit or sunitinib malate reversed hypoxia-induced increases in right ventricular systolic pressure (RVSP), right ventricular function and thickening of the medial walls. Mechanistically VEGF/VEGFR and PDGF/PDGFR formed a biological complex. We also showed that PDGF-BBincreasedKLF4 promoter activity transcriptionally activating VEGF expression, which regulates PAEC proliferation; migration; and the cell-cycle transition from G0/G1phase to S phase and G2/M-phase and eventually leads to PAEC angiogenesis Conclusion: Our study indicates that hypoxia-induced angiogenesis of PAECs is associated with increased levels of PDGF-BB/KLF4/VEGF, which contribute to pulmonary vascular remodeling. Overall, our study contributes to a better understanding of PAH pathogenesis.
Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation
Authors: McRobb Lucinda S. , McGrath Kristine C.Y. , Tsatralis Tania , Liong Eleanore C. , Tan Joanne T.M. , Hughes Gillian , Handelsman David J. , Heather Alison K.
Published: May 2017

Objective—

Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro.

Approach and Results—

Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERβ]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus independently of plaque growth or lipid levels and occurred in association with a site-specific decrease in the proportion of ERβ-positive intimal cells. Calcified lesions expressed collagen I and bone sialoprotein, with decreased matrix Gla protein. In vitro, E2 suppressed ERβ expression and increased VSMC mineralization, demonstrating increased collagen I and II, osteocalcin and bone sialoprotein, and reduced matrix Gla protein and osteopontin. Antagonism or RNA silencing of estrogen receptor alpha, ERβ, or both further increased VSMC mineralization.

Conclusions—

We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERβ activity.
Human Plasma Thioredoxin-80 Increases With Age and in ApoE
−/−
Mice Induces Inflammation, Angiogenesis, and Atherosclerosis
Authors: Couchie Dominique , Vaisman Boris , Abderrazak Amna , Mahmood Dler Faieeq Darweesh , Hamza Magda M. , Canesi Fanny , Diderot Vimala , El Hadri Khadija , Nègre-Salvayre Anne , Le Page Aurélie , Fulop Tamas , Remaley Alan T. , Rouis Mustapha
Published: May 2017

Background:

Thioredoxin (TRX)-1, a ubiquitous 12-kDa protein, exerts antioxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces upregulation of proinflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a proinflammatory M1 phenotype.

Methods:

TRX1 and TRX80 plasma levels were determined with a specific ELISA. A disintegrin and metalloproteinase domain-containing protein (ADAM)-10, ADAM-17, and ADAM-10 activities were measured with SensoLyte 520 ADAM10 Activity Assay Kit, Fluorimetric, and InnoZyme TACE Activity Kit, respectively. Western immunoblots were performed with specific antibodies to ADAM-10 or ADAM-17. Angiogenesis study was evaluated in vitro with human microvascular endothelial cells-1 and in vivo with the Matrigel plug angiogenesis assay in mice. The expression of macrophage phenotype markers was investigated with real-time polymerase chain reaction. Phosphorylation of Akt, mechanistic target of rapamycin, and 70S6K was determined with specific antibodies. The effect of TRX80 on NLRP3 inflammasome activity was evaluated by measuring the level of interleukin-1β and -18 in the supernatants of activated macrophages with ELISA. Hearts were used for lesion surface evaluation and immunohistochemical studies, and whole descending aorta were stained with Oil Red O. For transgenic mice generation, the human scavenger receptor (SR-A) promoter/enhancer was used to drive macrophage-specific expression of human TRX80 in mice.

Results:

In this study, we observed a significant increase of plasma levels of TRX80 in old subjects compared with healthy young subjects. In parallel, an increase in expression and activity of ADAM-10 and ADAM-17 in old peripheral blood mononuclear cells compared with those of young subjects was observed. Furthermore, TRX80 was found to colocalize with tumor necrosis factor-α, a macrophage M1 marker, in human atherosclerotic plaque. In addition, TRX80 induced the expression of murine M1 macrophage markers through Akt2/mechanistic target of rapamycin–C1/70S6K pathway and activated the inflammasome NLRP3, leading to the release of interleukin-1β and -18, potent atherogenic cytokines. Moreover, TRX80 exerts a powerful angiogenic effect in both in vitro and in vivo mouse studies. Finally, transgenic mice that overexpress human TRX80 specifically in macrophages of apoE
−/−
mice have a significant increase of aortic atherosclerotic lesions.

Conclusions:

TRX80 showed an age-dependent increase in human plasma. In mouse models, TRX80 was associated with a proinflammatory status and increased atherosclerosis.
Twenty-seven new species of the goblin spider genus Neoxyphinus Birabén, 1953 (Araneae: Oonopidae) from Brazil
Authors: FEITOSA NÍTHOMAS M. , MOSS DANIELLA F. , RUIZ GUSTAVO R. S. , BONALDO ALEXANDRE B.
Published: May 2017

Twenty-seven new species of the genus Neoxyphinus are described, all from Brazil, raising the total number of species of the genus to 48. The new species with the respective geographic distribution and known sexes are: N. capiranga sp. nov. (♂♀) from Amazonas, Pará, Mato Grosso and Rondônia; N. caprichoso sp. nov. (♂♀) and N. garantido sp. nov. (♂♀) from Amazonas and Pará; N. crasto sp. nov. (♂♀) from Bahia and Sergipe; N. murici sp. nov. (♂♀) from Alagoas and Sergipe; N. meurei sp. nov. (♀) from Bahia and Mato Grosso; N. belterra sp. nov. (♂♀) from Pará and Mato Grosso; N. ornithogoblin sp. nov. (♂♀), N. sax sp. nov. (♂♀), N. coari sp. nov. (♂♀), N. tucuma sp. nov. (♂♀), N. ducke sp. nov. (♂) and N. carigoblin sp. nov. (♀) from Amazonas; N. almerim sp. nov. (♂), N. mutum sp. nov. (♂♀), N. caxiuana sp. nov. (♂♀), N. cachimbo sp. nov. (♂) and N. jacareacanga sp. nov. (♀) from Pará; N. paraty sp. nov. (♂♀) and N. rio sp. nov. (♂♀) from Rio de Janeiro; N. novalima sp. nov. (♂♀) and N. celluliticus sp. nov. (♂) from Minas Gerais; N. paraiba sp. nov. (♂) and N. simsinho sp. nov. (♂♀) from Paraíba; N. cantareira sp. nov. (♂) from São Paulo; N. cavus sp. nov. (♂) from Espírito Santo and N. stigmatus sp. nov. (♂) from Bahia. A key for identification of all 48 known species of Neoxyphinus is provided and possible monophyletic lineages within the genus are discussed.
Water Budget and Intensity Change of Tropical Cyclones over the Western North Pacific
Authors: Gao Si , Zhai Shunan , Chen Baiqing , Li Tim
Published: May 2017

Three satellite observational datasets and a reanalysis dataset during the period 2001–09 are used to examine four water budget components (total precipitable water, surface evaporation, precipitation, and column-integrated moisture flux convergence) associated with western North Pacific tropical cyclones (TCs) of different intensity change categories: rapidly intensifying, slowly intensifying, neutral, and weakening. The results show that surface evaporation plays an important role in storm rapid intensification (RI) and the highest evaporation associated with rapidly intensifying TCs is associated with the highest sea surface temperature. Total precipitable water in the outer environment, where moisture is mainly provided by surface evaporation, is also vital to storm RI because RI is favored when there is less dry air intruded into the storm circulation. The roles of surface evaporation and total precipitable water in storm RI are related to the enhanced convective available potential energy by moistening and warming the boundary layer. The largest amount of column-integrated moisture flux convergence associated with weakening TCs, which results in the heaviest precipitation, is because their strongest mean intensity promotes moisture transport. It is suggested that different water budget components play different roles in TC intensity change. The results agree with the notion that TC intensity change results from a competition between surface moisture and heat fluxes and low-entropy downdrafts into the boundary layer.
Aggressive Salivary Malignancies at Early Stage: Outcomes and Implications for Treatment
Authors: Eppsteiner Robert W. , Fowlkes Jonathan W. , Anderson Carryn M. , Robinson Robert A. , Pagedar Nitin A.
Published: May 2017

Background:

Few studies have examined whether the use of adjuvant treatment impacts survival for early stage high-grade salivary tumors.

Methods:

A retrospective review of the SEER database between 1973 and 2012 was performed. Patients with high-grade major salivary gland tumors including salivary duct carcinoma, carcinoma ex-pleomorphic adenoma, high-grade mucoepidermoid carcinoma, or adenocarcinoma, NOS were identified. Only stage I-II tumors were included. The impact of radiation status on observed and relative survival was examined.

Results:

Five hundred seventy-four patients with high-grade, early stage salivary tumors met inclusion criteria. Sixty-seven percent of patients received radiation therapy. There was no difference in observed or relative survival based on having received radiation.

Conclusions:

Adjuvant radiation is indicated for advanced stage tumors or early stage tumors with adverse features. For early stage tumors without adverse features, there was no survival benefit from radiation therapy. Adjuvant radiation should be decided on a case-by-case basis for these patients.
Is a Multidisciplinary Aerodigestive Clinic More Effective at Treating Recalcitrant Aerodigestive Complaints Than a Single Specialist?
Authors: Rotsides Janine M. , Krakovsky Gina M. , Pillai Dinesh K. , Sehgal Sona , Collins Maura E. , Noelke Carolyn E. , Bauman Nancy M.
Published: May 2017

Objective:

To determine the utility of a pediatric multidisciplinary aerodigestive clinic (ADC) in treating recalcitrant aerodigestive conditions.

Methods:

Longitudinal observational study of presenting complaints, evaluation, management, and outcome of patients seen during 12 monthly ADCs beginning August 2013.

Results:

Fifty-five patients were seen by the ADC team (otolaryngology/gastroenterology/pulmonology/speech pathology/nurse practitioner) and followed for a mean 17.6 months (range, 12-26 months). Mean age was 4.3 years (range, 0.5-19 years). All were seen by at least 1 specialist before ADC referral but without significant improvement. Chronic cough was the most common primary symptom (44%). Clinic evaluation included flexible nasopharyngolaryngoscopy (FFL, 53%) and pulmonary function testing (36%.) FFL influenced management in 79%. An operative procedure usually combined endoscopy was warranted in 58%. Endoscopy provided high diagnostic yield, detecting laryngeal cleft (8), adenoid hypertrophy (8), vocal cord dysfunction (4), pulmonary infection (4), reflux disease (3), laryngomalacia (3), tracheomalacia (2), cilia abnormality (2), celiac disease (1), Helicobacter pylori (1), duodenal web (1), and eosinophilic esophagitis (1). Outcome was available for 48 of 55 patients, with 73% reporting resolved to markedly improved symptoms and 27% minimal to no improvement.

Conclusions:

The ADC team approach resulted in resolved to markedly improved symptoms in 73% of patients whose symptoms persisted despite seeing a single specialist prior to referral.
Examining the Temporal Development of Phonetic and Lexical Learning in Second Language
Authors: Han Jeong-Im , Jeon Moongee , Oh Sujin
Published: May 2017

The purpose of this study was to investigate how second-language (L2) learners lexically encode confusable phonemes. Given the inconsistency of previous studies on whether and if so how learners can establish separate lexical representations of confusable categories, we examined (1) how phonetic categorization and lexical encoding abilities were developed at the early stage of learning and (2) whether there are any differences in those abilities between the words with a sound pair from a corresponding native language (L1)-dominant category and those lacking such category. Native speakers of Korean learned Arabic words with these two types of sound pairs for four days and then their phonetic categorization and lexical processing abilities were evaluated in AXB discrimination and lexical decision tasks, respectively. The results showed that phonetic categorization of the words with a sound pair from an L1-dominant category developed very early. With success in their discrimination abilities, L2 learners began to overcome lexical competition from the words with such a sound pair. By contrast, learners showed poor sound discrimination and lexical encoding skills for words with a sound pair lacking an L1-dominant category. This suggests that (1) L2 learners’ accurate phonetic categorization abilities are prerequisite to success in L2 lexical encoding and (2) lexical representations of the L2 words with confusable phonemes depend on the distinct types of sound category matchup between L1 and L2.
(Post-)bordering Galicia in Ukrainian and Polish post-colonial discourse: The cases of Yurii Andrukhovych and Andrzej Stasiuk
Authors: Wierzejska Jagoda
Published: May 2017

This article is devoted to the analysis of literary representations of Galicia in two discourses of the region: Ukrainian and Polish. They are discussed on the basis of essays by Yurii Andrukhovych and Andrzej Stasiuk. For both writers, the narrative of Galicia, understood concurrently as a bordering and post-bordering space, is the starting point for reflection on the epistemology and ontology of Polish–Ukrainian borderlands and Central Europe. A disparity emerges from the perspectives of the two writers which can be described by way of the opposition city/province. Andrukhovych explores the palimpsestic and heterotopic character of the Galician urban sphere, while Stasiuk focuses on the most peripheral regions. The meaning generated by that difference evokes disparate ideological concepts regarding both former Galicia and Central Europe.
Urban theory with an outside
Authors: Jazeel Tariq
Published: May 2017

This paper critically engages planetary urbanization’s claim that it generates ‘Urban Theory Without an Outside’. It argues planetary urbanization is part of the broader ideological terrain of urban studies whose textual field reifies the city, the urban and urbanization as objects and processes of analyses through a kind of ‘methodological urbanization’. The paper argues the conceptual and political value of delineating views from outside urban studies and planetary urbanization – in particular from domains like area studies – that unmoor the primacy of the city, the urban and particularly urbanization in understandings of socio-spatial processes across planetary space. It suggests how these perspectives can usefully act as ‘supplements’ indifferent to urban studies, reminding urban studies of the limits of its own forms of knowledge production in relation to socio-spatial process and city formation. To do this, the paper sketches an anti-colonial history of Colombo, Sri Lanka.
Interpreting the relationships between TOEFL iBT scores and GPA: Language proficiency, policy, and profiles
Authors: Ginther April , Yan Xun
Published: May 2017

This study examines the predictive validity of the TOEFL iBT with respect to academic achievement as measured by the first-year grade point average (GPA) of Chinese students at Purdue University, a large, public, Research I institution in Indiana, USA. Correlations between GPA, TOEFL iBT total and subsection scores were examined on 1990 mainland Chinese students enrolled across three academic years (N2011 = 740, N2012 = 554, N2013 = 696). Subsequently, cluster analyses on the three cohorts’ TOEFL subsection scores were conducted to determine whether different score profiles might help explain the correlational patterns found between TOEFL subscale scores and GPA across the three student cohorts. For the 2011 and 2012 cohorts, speaking and writing subscale scores were positively correlated with GPA; however, negative correlations were observed for listening and reading. In contrast, for the 2013 cohort, the writing, reading, and total subscale scores were positively correlated with GPA, and the negative correlations disappeared. Results of cluster analyses suggest that the negative correlations in the 2011 and 2012 cohorts were associated with a distinctive Reading/Listening versus Speaking/Writing discrepant score profile of a single Chinese subgroup. In 2013, this subgroup disappeared in the incoming class because of changes made to the University’s international undergraduate admissions policy. The uneven score profile has important implications for admissions policy, the provision of English language support, and broader effects on academic achievement.
Matricide in Ghana: Victims, Offenders, and Offense Characteristics
Authors: Adinkrah Mensah
Published: May 2017

At present, scholarship on matricide across many regions of the non-Western world is lacking. For instance, in Ghana, despite the intermittent, yet recurrent, availability of media reports describing matricidal acts over the past quarter century, no existing study has systematically analyzed matricidal killings in the West African nation. To contribute to the literature and extend knowledge about matricide and other forms of lethal violence in Ghana, this article presents the results of an analysis of 21 matricidal acts that occurred in Ghana from 1990 to 2016. Issues studied include demographic characteristics of assailants and victims, modus operandi, temporal and spatial aspects, as well as the motives and circumstances surrounding the crime. The results show that sons were substantially more likely than daughters to kill their mothers, matricide offenders were more likely to suffer from serious psychiatric disorders, matricide offenses generally occurred in the victim’s home, and all cases of matricide were characterized by massive physical force and extreme violence. Matricide offenses in Ghana differed from matricides in Western nations in four important respects: (a) none of the 21 matricides was perpetrated with a firearm, (b) in none of the cases did the offender act with a co-offender (accomplice or accessory), (c) none of the matricide offenses was perpetrated by a juvenile or adolescent offender, and (d) suspicion that the mother-victim was a maleficent witch was an important trigger in matricide perpetration.
Fear of Crime in the Sanctuary: Comparing American and Ghanaian University Students’ Fearfulness
Authors: Boateng Francis D.
Published: May 2017

While much is known about fear of crime in the West, little is known about how fearfulness of crime develops in non-Western societies, especially among university students. Representing the first attempt to empirically compare levels of fear of crime between Ghanaian and U.S. college students, this article examined students’ levels of fear of crime on campus, and tested the applicability of two evolving models of fear of crime—the vulnerability and reassurance models—using comparative data. The general finding is that Ghanaian and U.S. college students differ in terms of their rates of fearfulness on campus. This significant difference adds to the already existing differences between the two countries.
Carbon monoxide inhalation induces headache in a human headache model
Authors: Arngrim Nanna , Schytz Henrik Winther , Britze Josefine , Vestergaard Mark Bitsch , Sander Mikael , Olsen Karsten Skovgaard , Olesen Jes , Ashina Messoud
Published: May 2017

Introduction

Carbon monoxide (CO) is an endogenously produced signalling molecule that has a role in nociceptive processing and cerebral vasodilatation. We hypothesized that inhalation of CO would induce headache and vasodilation of cephalic and extracephalic arteries.

Methods

In a randomized, double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0–10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial Doppler, diameter of the superficial temporal artery (STA) and radial artery (RA) by high-resolution ultrasonography and facial skin blood flow by laser speckle contrast imaging.

Results

Ten volunteers developed headache after CO compared to six after placebo. The area under the curve for headache (0–12 hours) was increased after CO compared with placebo ( p = 0.021). CO increased VMCA ( p = 0.002) and facial skin blood flow ( p = 0.012), but did not change the diameter of the STA ( p = 0.060) and RA ( p = 0.433).

Conclusion

In conclusion, the study demonstrated that CO caused mild prolonged headache but no arterial dilatation in healthy volunteers. We suggest this may be caused by a combination of hypoxic and direct cellular effects of CO.
Psychometric Characteristics of Strengths Knowledge Scale and Strengths Use Scale Among Adolescents
Authors: Duan Wenjie , Li Jinxia , Mu Wenlong
Published: May 2017

This study examined the psychometric properties of Strengths Knowledge Scale (SKS) and Strengths Use Scale (SUS) in a sample of 442 adolescents by the exploratory structural equation modeling. Correlations between strength use/strength knowledge and flourish, positive affect, negative affect, depression, anxiety, stress, and GPA were examined to illustrate criterion-related validities. Results showed good internal consistency reliability, expected structure factor, and convergent validity of the SKS and the SUS in the current sample.
Hardware-in-the-loop attitude control via a high-order sliding mode controller/observer
Authors: Malekzadeh Maryam , Rezayati Maryam , Saboohi Mobin
Published: May 2017

In this study, a hardware-in-the-loop implementation of attitude control algorithms based on high-order sliding mode theory is performed and then both compared in terms of performance and functionality. The spacecraft simulator consists of a free-floating platform hinged on a spherical air-bearing support. In order to compensate for the unreliable performance of the rate gyros, a super-twisting sliding mode observer is incorporated to estimate the angular velocities fed back to the controller unit. The proposed scheme makes full use of novel sliding mode methods to alleviate the chattering effects without increasing the control effort; both controllers and observer are tuned to deal with the saturation of reaction wheels with respect to momentum and its rate. The ab initio simulations compared well with the simulator responses, implying that involved instruments including actuators and sensors have been properly emulated. This also proved that the external disturbances were modeled in a reliable manner. The robustness and effectiveness of the proposed scheme have been validated experimentally under extreme circumstances of disturbances and levels of uncertainties.
Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives
Authors: Hu Jieping , Wang Gongxian , Sun Ting
Published: May 2017

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants’ formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.
Homeodomain-containing gene 10 inhibits cell apoptosis and promotes cell invasion and migration in osteosarcoma cell lines
Authors: Xiong Wen , Zhou Quan , Liu Gang , Liu Xiang-Sheng , Li Xin-Yu
Published: May 2017

Homeodomain-containing gene 10 (HOXC10) belongs to the homeobox family, which encodes a highly conserved family of transcription factors that plays an important role in morphogenesis in all multicellular organisms. Altered expressions of HOXC10 have been reported in several malignancies. This study was aimed to reveal the expression profile of HOXC10 in osteosarcoma and evaluated whether HOXC10 is a molecular target for cancer therapy. We found that HOXC10 was up-regulated in osteosarcoma tissues compared with bone cyst specimens from The Cancer Genome Atlas database. Osteosarcoma MG63 cells were infected with HOXC10 shRNA expressing vector, and 143B cells were infected with HOXC10 expressing vector. We found that reduced expression of HOXC10 markedly impaired the ability of proliferation, invasion, and migration, and promoted cell apoptosis in vitro and in vivo. Up-regulated expression of HOXC10 promoted the proliferation, invasion, and migration, and inhibited apoptosis of 143B cells. Additionally, HOXC10 regulated apoptosis and migration via modulating expression of Bax/Bcl-2, caspase-3, MMP-2/MMP-9, and E-cadherin in both MG63 and 143B cells and in vivo. These results indicated that HOXC10 might be a diagnostic marker for osteosarcoma and could be a potential molecular target for the therapy of osteosarcoma.
Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo
Authors: Wang Yahong , Shen Honghong , Yin Quangui , Zhang Tongxian , Liu Ziyu , Zhang Wei , Niu Yun
Published: May 2017

NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B−) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B− patients and 52.6% in NIMA-related kinase 2B++ patients ( p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.
Ectopic repression of receptor tyrosine kinase–like orphan receptor 2 inhibits malignant transformation of ovarian cancer cells by reversing epithelial–mesenchymal transition
Authors: Xu Ying , Ma Yan-Hui , Pang Ying-Xin , Zhao Zhe , Lu Jing-Jing , Mao Hong-Luan , Liu Pei-Shu
Published: May 2017

Receptor tyrosine kinase–like orphan receptor 2 is an enzyme-linked receptor which specifically modulates WNT5A signaling and plays an important role in tumorigenesis, invasion, and metastasis; however, the precise role of receptor tyrosine kinase–like orphan receptor 2 in cancer is controversial. The purpose of this study was to investigate the expression and role of receptor tyrosine kinase–like orphan receptor 2 in ovarian carcinoma and clarify the biological functions and interactions of receptor tyrosine kinase–like orphan receptor 2 with non-canonical Wnt pathways in ovarian cancer. The result of the human ovary tissue microarray revealed that the receptor tyrosine kinase–like orphan receptor 2–positive rate increased in malignant epithelial ovarian cancers and was extremely higher in the metastatic tumor tissues, which was also higher than that in the malignant ovarian tumor tissues. In addition, high expression of receptor tyrosine kinase–like orphan receptor 2 was closely related with ovarian cancer grading. The expression of receptor tyrosine kinase–like orphan receptor 2 protein was higher in SKOV3 and A2780 cells than OVCAR3 and 3AO cells. Knockdown of receptor tyrosine kinase–like orphan receptor 2 inhibited ovarian cancer cell proliferation, migration, invasion, and induced morphologic as well as digestive state alterations in stably transfected SKOV3 cells. Detailed study further revealed that silencing of receptor tyrosine kinase–like orphan receptor 2 reversed the epithelial–mesenchymal transition and inhibited non-canonical Wnt signaling. Our findings suggest that receptor tyrosine kinase–like orphan receptor 2 may be an important regulator of epithelial–mesenchymal transition, primarily regulated the non-canonical Wnt signaling pathway in ovarian cancer cells, and may display a promising therapeutic target for ovarian cancer.
Downregulation of miR-493 promoted melanoma proliferation by suppressing IRS4 expression
Authors: Cui Aili , Jin Zhehu , Gao Zhonggao , Jin Mingji , Zhu Lianhua , Li Lianhua , Jin Chenglong , An Yinghua
Published: May 2017

Accumulating evidence indicated that aberrantly expressed microRNAs play critical roles in the initiation and progression of human cancers. However, the underlying functions of miR-493 in human melanoma remains unknown. Here, our study found that miR-493 expression was downregulated in human melanoma tissues and cells. Overexpression of miR-493 suppressed cell proliferation and cell cycle in human melanoma cell line A375. IRS4 was defined as a target for downregulation by miR-493 and was confirmed by luciferase assay. We also found that knockdown of IRS4 counteracted the proliferation promotion by miR-493 inhibitor. In summary, these results demonstrated that miR-493 acts as a tumor suppressor and inhibits cell proliferation and cell cycle in human melanoma by directly targeting IRS4.
Computational analysis of ABL kinase mutations allows predicting drug sensitivity against selective kinase inhibitors
Authors: Kamasani Swapna , Akula Sravani , Sivan Sree Kanth , Manga Vijjulatha , Duyster Justus , Vudem Dashavantha Reddy , Kancha Rama Krishna
Published: May 2017

The ABL kinase inhibitor imatinib has been used as front-line therapy for Philadelphia-positive chronic myeloid leukemia. However, a significant proportion of imatinib-treated patients relapse due to occurrence of mutations in the ABL kinase domain. Although inhibitor sensitivity for a set of mutations was reported, the role of less frequent ABL kinase mutations in drug sensitivity/resistance is not known. Moreover, recent reports indicate distinct resistance profiles for second-generation ABL inhibitors. We thus employed a computational approach to predict drug sensitivity of 234 point mutations that were reported in chronic myeloid leukemia patients. Initial validation analysis of our approach using a panel of previously studied frequent mutations indicated that the computational data generated in this study correlated well with the published experimental/clinical data. In addition, we present drug sensitivity profiles for remaining point mutations by computational docking analysis using imatinib as well as next generation ABL inhibitors nilotinib, dasatinib, bosutinib, axitinib, and ponatinib. Our results indicate distinct drug sensitivity profiles for ABL mutants toward kinase inhibitors. In addition, drug sensitivity profiles of a set of compound mutations in ABL kinase were also presented in this study. Thus, our large scale computational study provides comprehensive sensitivity/resistance profiles of ABL mutations toward specific kinase inhibitors.
Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway
Authors: Zheng Li , Chen Jiangtao , Zhou Zhongyong , He Zhikuan
Published: May 2017

Long non-coding RNA HOXD-AS1 (HOXD cluster antisense RNA 1) has been demonstrated to be closely associated with the progression of several tumors. However, the biological function of HOXD-AS1 and the underlying molecular mechanism in gastric cancer are still unclear. The expression of HOXD-AS1 in gastric cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association of HOXD-AS1 expression and clinical parameters was statistically analyzed by chi-square test. Cell viability, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in treated SGC-7901 and BGC-823 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and western blot analysis, respectively. The results indicated that HOXD-AS1 was significantly upregulated in gastric cancer cells and clinically involved in tumor size, invasion depth, tumor–node–metastasis stages, regional lymph nodes, lymphatic metastasis, as well as distant metastasis. HOXD-AS1 knockdown dramatically inhibited gastric cancer cell proliferation, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in vitro. In addition, HOXD-AS1 overexpression significantly promoted gastric cancer cell proliferation and colony formation capacity, whereas both Janus kinase small interfering RNAs and Janus kinase 2 inhibitor AG490 overturned these effects. Furthermore, xenograft assays confirmed the biological function of HOXD-AS1 in vivo. Taken together, our data elucidate that knockdown of HOXD-AS1 dramatically suppresses gastric cancer cell growth by inactivating the Janus kinase 2/signal transducer and activator of transcription 3 pathway in vitro and in vivo, contributing to a better understanding of gastric cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA–directed diagnosis and therapy against this disease.
A novel serum microRNA-based identification and classification biomarker of human glioma
Authors: Xing Wenli , Zeng Chun
Published: May 2017

Malignant glioma is one of the most common primary brain tumors that develop via multiple pathways and gene deregulation. MicroRNAs are involved in human cancer development and progression, and their serum expression profiles of glioma patients may be useful for classifying cancers. However, the profile and molecular mechanism of serum microRNAs for human glioma are poorly understood. Thus, it is crucial to analyze microRNA expression in human glioma serum to identify molecular subclasses and early stage of glioma. In this study, we performed microRNA alteration that contributes to glioma profile via analysis of The Cancer Genome Atlas RNA sequencing data and other independent Gene Expression Omnibus microarray data. We identified the glioma-associated novel microRNA as a key regulator of human glioma development and progression. The putative novel miR-1825 was validated by real-time polymerase chain reaction and its expression was significantly decreased in the serum of glioma patients compared with healthy controls. Patients with high miR-1825 expression had a longer survival rate. Interestingly, we found that miR-1825 expression levels were dependent on tumor size and pathological grading in glioma patients, but not associated with other factors including age and T classification. MicroRNA–Gene Ontology network indicated that miR-1825 may play an important role in the development of human glioma including apoptosis, cell proliferation, and invasion. In vitro assays of miR-1825 inhibit U87 cell proliferation and invasion and induce apoptosis. Furthermore, we provide evidence that the tumor-suppressive microRNA miR-1825 controls KLF2 expression. Reporter gene analyses revealed that both microRNAs directly targeted the 3′-untranslated region of KLF2 messenger RNA. These data demonstrated that miR-1825 expression in serum of human glioma was associated with tumorigenesis and miR-1825 may be used as a biomarker for identification of the pathological grade of glioma.
Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle
Authors: Sun Jing , Shi Run , Zhao Sha , Li Xiaona , Lu Shan , Bu Hemei , Ma Xianghua
Published: May 2017

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.
Limits of Calcaneal Lengthening for Treating Planovalgus Foot Deformity in Children With Cerebral Palsy
Authors: Luo Chi-An , Kao Hsuan-Kai , Lee Wei-Chun , Yang Wen-E , Chang Chia-Hsieh
Published: May 2017

Background:

Calcaneal lengthening is used to correct symptomatic planovalgus foot deformity, but outcomes have been less satisfactory in children with cerebral palsy. This study aimed to define limits of calcaneal lengthening by analyzing the risk factors for undercorrection of deformity.

Methods:

We retrospectively reviewed 20 cases of children with cerebral palsy who underwent calcaneal lengthening of 30 planovalgus feet at a mean age of 11.9 years. Foot deformities were evaluated by the anteroposterior talo–first metatarsal angle (normal, 10 ± 7.0 degrees), lateral talo–first metatarsal angle (normal, 13 ± 7.5 degrees), and lateral calcaneal pitch angle (normal, 17 ± 6.0 degrees) on standing foot radiographs. Among these parameters, a corrected foot was defined as 2 or 3 parameters being corrected to within a normal range, and an undercorrected foot was only 1 or no parameter being corrected to within a normal range. Factors were compared between the corrected group and undercorrected group for significant predictors, and cutoff values of predictors were calculated for use as a clinical guideline.

Results:

Seventeen planovalgus feet were corrected satisfactorily by calcaneal lengthening, while the other 13 feet were undercorrected. Undercorrected feet had a greater preoperative anteroposterior talonavicular angle (33.7 vs 22.8 degrees, P = .001) and a smaller lateral calcaneal pitch (−1.7 vs 5.6 degrees, P = .03). A talonavicular angle of more than 24 degrees and calcaneal pitch less than −5 degrees were identified as cutoff values using a receiver operating characteristic curve. The predicted probability of undercorrection was 100% (9/9 feet) for 2 positive predictors, 50% (8/16 feet) for 1 positive predictor, and 0 (0/5 feet) for zero predictors.

Conclusion:

A talonavicular lateral subluxation of more than 24 degrees on the anteroposterior radiograph and a calcaneal pitch angle less than −5 degrees on the lateral radiograph were 2 independent predictors that could be used to identify a planovalgus deformity that would be beyond the corrective capacity of calcaneal lengthening to restore normal alignment.

Level of Evidence

Retrospective case control study, level III
Effect of ultrasound on some chemical and microbiological properties of sour cherry juice by response surface methodology
Authors: Türken Tuğba , Erge Hande S
Published: May 2017

In this study, it is aimed to determine effect of ultrasonication on some chemical and microbiological properties of sour cherry juice by response surface methodology, since ultrasound is known as an alternative method for thermal food processing. Sour cherry juice was sonicated at varying amplitude levels (50, 75, 100%); moderate temperatures (20, 30, 40 ℃); and treatment times of 2, 6, 10 min at a constant frequency of 20 kHz. Different ultrasonication amplitudes, temperatures, and times had no significant effect on pH,°Bx, and titratable acidity. A significant increase in total monomeric anthocyanins was observed as the amplitude level and temperature increased (p < 0.01). An increase in the total phenolics was also obtained as the temperature increased (p < 0.05). The effect of amplitude level on antioxidant capacity of sour cherry juice was also found significant (p < 0.05). Color parameters (L*, a*, b*, C, h) generally increased by increasing temperature, amplitude level, and treatment time. It was determined that Escherichia coli O157:H7 significantly affected by temperature and treatment time (p < 0.05).