bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental Occupational Exposure to Heavy Metals and Welding Fumes and Risk of Testicular Germ Cell Tumors in Offspring: A Registry-Based Case–Control Study
Authors: Togawa Kayo , Le Cornet Charlotte , Feychting Maria , Tynes Tore , Pukkala Eero , Hansen Johnni , Olsson Ann , Oksbjerg Dalton Susanne , Nordby Karl-Christian , Uuksulainen Sanni , Wiebert Pernilla , Woldbæk Torill , Skakkebæk Niels E. , Fervers Béatrice , Schüz Joachim 
Published: July 2016

AbstractBackground: Data are scarce on the association between prenatal/preconception environmental exposure and testicular germ cell tumor (TGCT) in offspring. We examined parental occupational exposures to heavy metals and welding fumes in relation to TGCT in offspring in a registry-based case–control study (NORD-TEST Study).Methods: We identified TGCT cases diagnosed at ages 14–49 years in Finland (1988–2012), Norway (1978–2010), and Sweden (1979–2011) through nationwide cancer registries. These cases were individually matched by country and year of birth to controls selected from population registries. Information on parental occupations was retrieved from censuses. From this, we estimated prenatal/preconception exposures of chromium, iron, nickel, lead, and welding fumes (all three countries), and cadmium (Finland only) for each parent using job-exposure matrices specifying prevalence (P) and mean exposure level (L). Exposure indices were calculated as a product of P and L (P × L), and exposure categories were based on P × L or different combinations of P and L.Results: The study comprised 8,112 cases and 26,264 controls. We observed no statistically significant TGCT risk associated with presence of heavy metals/welding fumes (P × L &gt; 0) and no dose-response relationship (Ptrend ≥ 0.32). A statistically significant elevated TGCT risk was found in paternal exposure category where both P and L of chromium were high (vs. no chromium; OR = 1.37, 95% confidence interval; 1.05–1.79).Conclusions: Our study provides little evidence of associations between parental exposures to heavy metals/welding fumes and TGCT in offspring with the potential exception of high paternal chromium exposure.Impact: Further research on paternal chromium exposure is warranted. Cancer Epidemiol Biomarkers Prev; 25(10); 1426–34. ©2016 AACR.
Sustained Mutant KIT Activation in the Golgi Complex Is Mediated by PKC-θ in Gastrointestinal Stromal Tumors
Authors: Kim Won Kyu , Yun SeongJu , Park Cheol Keun , Bauer Sebastian , Kim Jiyoon , Lee Min Goo , Kim Hoguen 
Published: July 2016

Abstract
Purpose: Tumorigenesis of gastrointestinal stromal tumors (GIST) is driven by gain-of-function mutations in the KIT gene, which result in overexpression of activated mutant KIT proteins (MT-KIT). However, the mechanism of MT-KIT overexpression is poorly understood.
Experimental Design: By protein expression analysis and immunofluorescent microscopic analysis, we determine the stability and localization of MT-KIT in four GIST cell lines with different mutations and HeLa cells transfected with mutant KIT model vectors. We also used 154 human GIST tissues to analyze the relationship between the expression of PKC-θ and MT-KITs, and correlations between PKC-θ overexpression and clinicopathological parameters.
Results: We report that four different MT-KIT proteins are intrinsically less stable than wild-type KIT due to proteasome-mediated degradation and abnormally localized to the endoplasmic reticulum (ER) or the Golgi complex. By screening a MT-KIT-stabilizing factor, we find that PKC-θ is strongly and exclusively expressed in GISTs and interacts with intracellular MT-KIT to promote its stabilization by increased retention in the Golgi complex. In addition, Western blotting analysis using 50 GIST samples shows strong correlation between PKC-θ and MT-KIT expression (correlation coefficient = 0.682, P &lt; 0.000001). Immunohistochemical analysis using 154 GISTs further demonstrates that PKC-θ overexpression significantly correlates with several clinicopathological parameters such as high tumor grade, frequent recurrence/metastasis, and poor patient survival.
Conclusions: Our findings suggest that sustained MT-KIT overexpression through PKC-θ-mediated stabilization in the Golgi contributes to GIST progression and provides a rationale for anti-PKC-θ therapy in GISTs. Clin Cancer Res; 23(3); 845–56. ©2016 AACR.
Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer
Authors: Duran Rafael , Mirpour Sahar , Pekurovsky Vasily , Ganapathy-Kanniappan Shanmugasundaram , Brayton Cory F. , Cornish Toby C. , Gorodetski Boris , Reyes Juvenal , Chapiro Julius , Schernthaner Rüdiger E. , Frangakis Constantine , Lin MingDe , Sun Jessica D. , Hart Charles P. , Geschwind Jean-François 
Published: July 2016

AbstractPurpose: To evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intra-arterial therapy (HAIAT) with evofosfamide in a rabbit model.Experimental Design: VX2-tumor-bearing rabbits were assigned to 4 intra-arterial therapy (IAT) groups (n = 7/group): (i) saline (control); (ii) evofosfamide (Evo); (iii) doxorubicin–lipiodol emulsion followed by embolization with 100–300 μm beads (conventional, cTACE); or (iv) cTACE and evofosfamide (cTACE + Evo). Blood samples were collected pre-IAT and 1, 2, 7, and 14 days post-IAT. A semiquantitative scoring system assessed hepatocellular damage. Tumor volumes were segmented on multidetector CT (baseline, 7/14 days post-IAT). Pathologic tumor necrosis was quantified using manual segmentation on whole-slide images. Hypoxic fraction (HF) and compartment (HC) were determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia, and metabolism were quantified (γ-H2AX, Annexin V, caspase-3, Ki-67, HIF1α, VEGF, GAPDH, MCT4, and LDH).Results: cTACE + Evo showed a similar profile of liver enzymes elevation and pathologic scores compared with cTACE. Neither hematologic nor renal toxicity were observed. Animals treated with cTACE + Evo demonstrated smaller tumor volumes, lower tumor growth rates, and higher necrotic fractions compared with cTACE. cTACE + Evo resulted in a marked reduction in the HF and HC. Correlation was observed between decreases in HF or HC and tumor necrosis. cTACE + Evo promoted antitumor effects as evidenced by increased expression of γ-H2AX, apoptotic biomarkers, and decreased cell proliferation. Increased HIF1α/VEGF expression and tumor glycolysis supported HAIAT.Conclusions: HAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and enhanced anticancer effects of evofosfamide in combination with cTACE pave the way towards clinical trials in patients with liver cancer. Clin Cancer Res; 23(2); 536–48. ©2016 AACR.
Debio 0617B Inhibits Growth of STAT3-Driven Solid Tumors through Combined Inhibition of JAK, SRC, and Class III/V Receptor Tyrosine Kinases
Authors: Murone Maximilien , Vaslin Chessex Anne , Attinger Antoine , Ramachandra Raghuveer , Shetty Shankar J. , Daginakatte Girish , Sengupta Saumitra , Marappan Sivapriya , Dhodheri Samiulla , Rigotti Stefania , Bachhav Yogeshwar , Brienza Silvano , Traxler Peter , Lang Marc , Aguet Michel , Zoete Vincent , Michielin Olivier , Nicholas Courtney , Johnson Faye M. , Ramachandra Murali , McAllister Andres 
Published: July 2016

Abstract
Tumor survival, metastases, chemoresistance, and escape from immune responses have been associated with inappropriate activation of STAT3 and/or STAT5 in various cancers, including solid tumors. Debio 0617B has been developed as a first-in-class kinase inhibitor with a unique profile targeting phospho-STAT3 (pSTAT3) and/or pSTAT5 in tumors through combined inhibition of JAK, SRC, ABL, and class III/V receptor tyrosine kinases (RTK). Debio 0617B showed dose-dependent inhibition of pSTAT3 in STAT3-activated carcinoma cell lines; Debio 0617B also showed potent antiproliferative activity in a panel of cancer cell lines and in patient-derived tumor xenografts tested in an in vitro clonogenic assay. Debio 0617B showed in vivo efficacy by inhibiting tumor growth in several mouse xenograft models. To increase in vivo efficacy and STAT3 inhibition, Debio 0617B was tested in combination with the EGFR inhibitor erlotinib in a non–small cell lung cancer xenograft model. To evaluate the impact of in vivo STAT3 blockade on metastases, Debio 0617B was tested in an orthotopic tumor model. Measurement of primary tumor weight and metastatic counts in lung tissue demonstrated therapeutic efficacy of Debio 0617B in this model. These data show potent activity of Debio 0617B on a broad spectrum of STAT3-driven solid tumors and synergistic activity in combination with EGFR inhibition. Mol Cancer Ther; 15(10); 2334–43. ©2016 AACR.
Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth
Authors: Smith Michele C. , Mader Mary M. , Cook James A. , Iversen Philip , Ajamie Rose , Perkins Everett , Bloem Laura , Yip Yvonne Y. , Barda David A. , Waid Philip P. , Zeckner Douglas J. , Young Debra A. , Sanchez-Felix Manuel , Donoho Gregory P. , Wacheck Volker 
Published: July 2016

Abstract
The PI3K/AKT/mTOR pathway is among the most frequently altered pathways in cancer cell growth and survival. LY3023414 is a complex fused imidazoquinolinone with high solubility across a wide pH range designed to inhibit class I PI3K isoforms and mTOR kinase. Here, we describe the in vitro and in vivo activity of LY3023414. LY3023414 was highly soluble at pH 2–7. In biochemical testing against approximately 266 kinases, LY3023414 potently and selectively inhibited class I PI3K isoforms, mTORC1/2, and DNA-PK at low nanomolar concentrations. In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 caused G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In vivo, LY3023414 demonstrated high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours, reflecting the drug's half-life of 2 hours. Of note, equivalent total daily doses of LY3023414 given either once daily or twice daily inhibited tumor growth to similar extents in multiple xenograft models, indicating that intermittent target inhibition is sufficient for antitumor activity. In combination with standard-of-care drugs, LY3023414 demonstrated additive antitumor activity. The novel, orally bioavailable PI3K/mTOR inhibitor LY3023414 is highly soluble and exhibits potent in vivo efficacy via intermittent target inhibition. It is currently being evaluated in phase I and II trials for the treatment of human malignancies. Mol Cancer Ther; 15(10); 2344–56. ©2016 AACR.
Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response
Authors: Bordet Jean-Claude , Negrier Claude , Dargaud Yesim , Quellec Sandra Le 
Published: July 2016

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.
Biogeography of Abyssocythere and Dutoitella (Ostracoda), with descriptions of three new species
Authors: BRANDÃO SIMONE N. , STUHLMANN ANNALENA , VITAL HELENICE , BRANDT ANGELIKA 
Published: July 2016

Ostracods have an extensive fossil record and are widely applied in palaeoenvironmental reconstructions. Here, we investigate the biogeography of two common and widespread genera, Abyssocythere and Dutoitella. Both appeared in the Cretaceous and are widely distributed in modern deep seas, but all species are restricted in distribution. The earliest record of Dutoitella is from shallow water, while the earliest Abyssocythere is from the deep sea. The Southern Ocean/Southern Atlantic seem to have been the area where both genera originated, and from which they eventually colonised other oceans. Dutoitella diversified into at least eleven species during Campanian-Eocene times, and by the end of the Eocene, the genus had spread to the Indian Ocean. This pattern continued after the establishment of the psychrosphere into the Neogene, with the development of numerous Miocene species. Abyssocythere, with 15 species, while also diversifying in the late Cretaceous South Atlantic, appears to have developed fewer species than Dutoitella. Finally, we describe three new species from the Southern Ocean (Abyssocythere bensoni sp. nov., Dutoitella karanovicae sp. nov. and Dutoitella richarddinglei sp. nov.), re-illustrate the types of Abyssocythere squalidentata (Brady, 1880) and Dutoitella suhmi (Brady, 1880), and study the soft parts of the genus Dutoitella, which were previously undocumented.
A Closer Look at the ABI on the GOES-R Series
Authors: Schmit Timothy J. , Griffith Paul , Gunshor Mathew M. , Daniels Jaime M. , Goodman Steven J. , Lebair William J. 
Published: July 2016

Abstract
The Advanced Baseline Imager (ABI) on board the Geostationary Operational Environmental Satellite-R (GOES-R) is America’s next-generation geostationary advanced imager. GOES-R launched on 19 November 2016. The ABI is a state-of-the-art 16-band radiometer, with spectral bands covering the visible, near-infrared, and infrared portions of the electromagnetic spectrum. Many attributes of the ABI—such as spectral, spatial, and temporal resolution; radiometrics; and image navigation/registration—are much improved from the current series of GOES imagers. This paper highlights and discusses the expected improvements of each of these attributes. From ABI data many higher-level-derived products can be generated and used in a large number of environmental applications. The ABI’s design allows rapid-scan and contiguous U.S. imaging automatically interleaved with full-disk scanning. In this paper the expected instrument attributes are covered, as they relate to signal-to-noise ratio, image navigation and registration, the various ABI scan modes, and other parameters. There will be several methods for users to acquire GOES-R imagery and products depending on their needs. These include direct reception of the imagery via the satellite downlink and an online-accessible archive. The information from the ABI on the GOES-R series will be used for many applications related to severe weather, tropical cyclones and hurricanes, aviation, natural hazards, the atmosphere, the ocean, and the cryosphere.
The ABI on the GOES-R series is America’s next-generation geostationary advanced imager and will dramatically improve the monitoring of many phenomena at finer time and space scales.
Convective Outbreak over the Red Sea and Downstream Easterly Waves
Authors: Jury Mark R. 
Published: July 2016

Abstract
This study analyzes a convective outbreak over the Red Sea on 25 August 2009 that generated easterly waves over the Sahel, floods in Ouagadougou, and a hurricane in the east Atlantic. The convective outbreak occurred on the equatorward flank of the African easterly jet 18°–22°N and associated meridional heating gradients over the Arabian Peninsula. The Rift Valley mountains induced a vertical orographic undulation and cyclonic perturbation. Two thunderstorm clusters over the southern Red Sea received moist inflow from the Ethiopian highlands and northern Red Sea. This group of three easterly waves intensified downstream over the Sahel. One of the convective triggers was enhancement of the Arabian Ridge by the northern subtropical jet. Statistical analyses indicate that African easterly waves and subsequent tropical storms are more influenced by upstream kinematic shear than thermodynamic energy. The work offers new insights on the formation of easterly waves over the northern Rift Valley.
The Intraseasonal Oscillation of Eastern Tibetan Plateau Precipitation in Response to the Summer Eurasian Wave Train
Authors: Hu Wenting , Duan Anmin , Li Yun , He Bian 
Published: July 2016

Abstract
This study examines the characteristics and mechanisms associated with the dominant intraseasonal oscillation (ISO) that controlled eastern Tibetan Plateau summer rainfall (ETPSR) over the period 1979–2011. The results of both power and wavelet spectrum analysis reveal that ETPSR follows a significant 7–20-day oscillation during most summers. The vertical structure of the ETPSR ISO in the dry phase is characterized by a vertical dipole pattern of geopotential height with a positive center on the eastern Tibetan Plateau (TP) and a negative center on the western TP. The wet phase shows the opposite characteristics to the dry phase. The transitions between the dry and wet phases during an ETPSR ISO cycle are related to a Rossby wave train that presents as large anomalous anticyclonic and cyclonic centers that alternate along the pathway from the eastern Atlantic to southern China via the TP. It corresponds to the evolution of the phase-independent wave-activity W, which implies an eastward/southeastward energy propagation of the ISO. The dominant modes of the daily 200-hPa geopotential height as identified by the rotated empirical orthogonal function (REOF) demonstrate that the different phases of the Rossby wave train influence the upper-level circulation over the eastern TP, which then impacts precipitation in the region. Furthermore, fluctuations in the eastern Atlantic may be the key factor for the propagation of the Rossby wave train that influences the upper-level circulation and rainfall variability over the eastern TP. Results from numerical experiments using an atmospheric general circulation model support the conclusion that the fluctuations over the eastern Atlantic contribute to the ISO of ETPSR.
Otopolyposis With Middle Ear Allergic Mucin in a Patient With Allergic Fungal Rhinosinusitis
Authors: Kumar Manvinder S. , Panella Nicholas J. , Magliocca Kelly R. , Vivas Esther X. 
Published: July 2016

Objective: The purpose of this study is to report a case of otopolyposis and middle ear allergic mucin in a patient with allergic fungal rhinosinusitis (AFRS) and no history of middle ear disease and introduce these as possible otologic manifestations of the AFRS. Methods: A case of a 31-year-old female with the aforementioned findings is reported. A review of the pertinent literature was performed. Results: We report a case of a 31-year-old female with a history of AFRS but no history of middle ear disease or hearing loss who presented to our institution complaining of aural fullness. Physical exam was significant for middle ear masses of unknown etiology. Surgical exploration revealed the presence of allergic mucin and middle ear polyposis histologically identical to tissue sampled during prior sinonasal surgeries at the same institution. Aspiration of the middle ear space did not resolve the otologic symptoms. Conclusion: Otopolyposis and middle ear allergic mucin are extremely rare but possible otologic manifestations of AFRS. We encourage otolaryngologists to consider this in the clinical differential diagnosis of patients with a history of AFRS with new onset otologic symptoms.
The Media and Power in Postliberal Venezuela
Authors: Sapiezynska Ewa 
Published: July 2016

Two narratives dominate the literature about the state of freedom of expression in postliberal Venezuela, and they have few points in common, since they depend on different conceptualizations of the notion of freedom of expression. While the traditional liberal narrative focuses on the negative freedom that prohibits state interference, the postliberal narrative is based on positive freedom that encompasses the collective right of self-realization, particularly for the previously marginalized. During the government of Hugo Chávez, the discourse of freedom of expression was renewed, placing it in the context of power relations, accentuating positive freedom, and emphasizing the role of the public and community media. The establishment of the international public channel TeleSUR has revived the 1970s debate about the right to communication and contributed to the creation of a new Latin American-ness. En la literatura predominan dos narrativas acerca del estado de la libertad de expresión en la Venezuela posliberal las que tienen pocos puntos en común porque parten de visiones distintas del concepto de la libertad de expresión. Mientras la narrativa liberal tradicional enfoca sólo en la libertad negativa que previene la injerencia estatal, la narrativa posliberal se centra en la libertad positiva que abarca la autorrealización del derecho colectivo, también de los previamente marginalizados. Durante el gobierno de Hugo Chávez el discurso acerca de la libertad de expresión se renueva, insertando el concepto en el contexto de las relaciones de poder, acentuando la libertad positiva y enfatizando el rol de los medios públicos y comunitarios. El establecimiento del medio público internacional TeleSUR revive los debates sobre el derecho a la comunicación de la década de los 70 y aporta a la creación de una nueva Latinoamericanidad.