bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification, Diagnosis and Treatment of Sinusitis: Evidence‐Based Clinical Practice Guidelines
Authors: Noyek Arnold , Brodovsky David , Coyle Stephen , Desrosiers Martin , Frenkiel Saul , Hawke Michael , Kellner James D , Kirkpatrick David A , Krajden Sigmund , Low Donald E , Mandell Lionel , Marlow Bernard , Martin Gerald F , Rival Richard , Shankar Lalitha , Vaughan David , Witterick Ian J 
Published: August 2016

OBJECTIVE: To provide evidence‐based recommendations for classification, diagnosis and treatment of acute, chronic and recurrent acute sinusitis in adults and children.DATA SOURCES: Review articles, textbooks, other published guidelines and recommendations of task force members.STUDY SELECTION: One hundred and seventy‐one papers addressing one or all of the objectives.DATA EXTRACTION: Relevant data were collated under each objective.DATA SYNTHESIS: Validity of diagnostic and treatment evidence was assessed by using the methodological recommendations of Sackett et al and the canadian Task Force on Periodic Health Examination, respectively. Where there was a paucity of data, consensus of task force members was reached.CONCLUSIONS: Sinusitis is classified as acute, chronic or recurrent acute disease according to duration and frequency of symptoms and response to therapy (expert opinion). Potential risk factors, concomitant diseases and complications are identified (limited evidence). Diagnosis is based on symptoms, history and physical examination. For adults, independentpredictors of acute sinusitis include maxillary toothache, coloured nasal discharge, poor response to nasal decongestants/antihistamines and mucopurulent nasal secretions (good evidence); for children, cough, nasal discharge and fever are common (good evidence). For chronic disease that persists despite adequate therapy and recurrent acutedisease, referral to a specialist for investigative measures (nasal endoscopy, computed tomography) is often necessary to determine predisposing anatomical features. Level I evidence supports the use of antibiotics for the treatment of sinusitis; selection is based on the local pattern of bacterial resistance, relative efficacy, safety and cost. Amoxicillinclavulanate, cefuroxime axetil, cefixime, ciprofloxacin and clarithromycin are approved for the treatment of acute sinusitis in canada. Amoxicillin, amoxicillin‐clavulanate and cefuroxime axetil have been shown to be effective in children. Ciprofloxacin, amoxicillin‐clavulanate, clarithromycin and erythromycin have been shown to be effective in chronic disease, although no agents have been approved for this indication. Given changing patterns of bacterial resistance, more up‐to‐date comparative efficacy data are needed.
WWOX and p53 Dysregulation Synergize to Drive the Development of Osteosarcoma
Authors: Del Mare Sara , Husanie Hussam , Iancu Ortal , Abu-Odeh Mohammad , Evangelou Konstantinos , Lovat Francesca , Volinia Stefano , Gordon Jonathan , Amir Gail , Stein Janet , Stein Gary S. , Croce Carlo M. , Gorgoulis Vassilis , Lian Jane B. , Aqeilan Rami I. 
Published: August 2016

Abstract
Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts. Mice with conditional deletion of Wwox in preosteoblasts (WwoxΔosx1) displayed a severe inhibition of osteogenesis accompanied by p53 upregulation, effects that were not observed in mice lacking Wwox in mature osteoblasts. Deletion of p53 in WwoxΔosx1 mice rescued the osteogenic defect. In addition, the Wwox;p53Δosx1 double knockout mice developed poorly differentiated osteosarcomas that resemble human osteosarcoma in histology, location, metastatic behavior, and gene expression. Strikingly, the development of osteosarcomas in these mice was greatly accelerated compared with mice lacking p53 only. In contrast, combined WWOX and p53 inactivation in mature osteoblasts did not accelerate osteosarcomagenesis compared with p53 inactivation alone. These findings provide evidence that a WWOX–p53 network regulates normal bone formation and that disruption of this network in osteoprogenitors results in accelerated osteosarcoma. The Wwox;p53Δosx1 double knockout establishes a new osteosarcoma model with significant advancement over existing models. Cancer Res; 76(20); 6107–17. ©2016 AACR.
Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells
Authors: Baghdadi Muhammad , Wada Haruka , Nakanishi Sayaka , Abe Hirotake , Han Nanumi , Putra Wira Eka , Endo Daisuke , Watari Hidemichi , Sakuragi Noriaki , Hida Yasuhiro , Kaga Kichizo , Miyagi Yohei , Yokose Tomoyuki , Takano Atsushi , Daigo Yataro , Seino Ken-ichiro 
Published: August 2016

Abstract
The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030–42. ©2016 AACR.
Biospecimen Complexity—the Next Challenge for Cancer Research Biobanks?
Authors: Watson Peter H. 
Published: August 2016

Abstract
Purpose: Biospecimens (e.g., tissues, bloods, fluids) are critical for translational cancer research to generate the necessary knowledge to guide implementation of precision medicine. Rising demand and the need for higher quality biospecimens are already evident.
Experimental Design: The recent increase in requirement for biospecimen complexity in terms of linked biospecimen types, multiple preservation formats, and longitudinal data was explored by assessing trends in cancer research publications from 2000 to 2014.
Results: A PubMed search shows that there has been an increase in both raw numbers and the relative proportion (adjusted for total numbers of articles in each period) of the subgroups of articles typically associated with the use of biospecimens and both dense treatment and/or outcomes data and multiple biospecimen formats.
Conclusions: Increasing biospecimen complexity is a largely unrecognized and new pressure on cancer research biobanks. New approaches to cancer biospecimen resources are needed such as the implementation of more efficient and dynamic consent mechanisms, stronger participant involvement in biobank governance, development of requirements for registration of collections, and models to establish stock targets for biobanks. In particular, the latter two approaches would enable funders to establish a better balance between biospecimen supply and research demand, reduce expenditure on duplicate collections, and encourage increased efficiency of biobanks to respond to the research need for more complex cases. This in turn would also enable biobanks to focus more on quality and standardization that are surely factors in the even more important arena of research reproducibility. Clin Cancer Res; 23(4); 894–8. ©2016 AACR.
The Discovery and Preclinical Development of ASG-5ME, an Antibody–Drug Conjugate Targeting SLC44A4-Positive Epithelial Tumors Including Pancreatic and Prostate Cancer
Authors: Mattie Michael , Raitano Arthur , Morrison Kendall , Morrison Karen , An Zili , Capo Linnette , Verlinsky Alla , Leavitt Monica , Ou Jimmy , Nadell Rossana , Aviña Hector , Guevara Claudia , Malik Faisal , Moser Ruth , Duniho Steven , Coleman Jeffrey , Li Ying , Pereira Daniel S. , Doñate Fernando , Joseph Ingrid B.J. , Challita-Eid Pia , Benjamin Dennis , Stover David R. 
Published: August 2016

AbstractHere, we report the development of an antibody–drug conjugate, ASG-5ME, which targets the solute carrier receptor SLC44A4. SLC44A4 is a member of a family of putative choline transporters that we show to be markedly upregulated in a variety of epithelial tumors, most notably prostate and pancreatic cancer. SLC44A4 is normally expressed on the apical surface of secretory epithelial cells, but in cancer we show expression is not restricted to the luminal surface in advanced and undifferentiated tumors. ASG-5ME consists of a human IgG2 anti-SLC44A4 antibody conjugated through a cleavable linker to the microtubule-disrupting agent monomethylauristatin E. It has potent antitumor activity in both cell line – and patient-derived xenograft models of pancreatic and prostate cancers. Combination studies with ASG-5ME and nab-paclitaxel demonstrated combination effect in both pancreatic and prostate tumor models. Altogether, the data presented here suggest that ASG-5ME may have the potential to offer a new therapeutic option for the treatment of pancreatic and prostate cancers. Mol Cancer Ther; 15(11); 2679–87. ©2016 AACR.
Identification of Pharmacodynamic Transcript Biomarkers in Response toFGFRInhibition by AZD4547
Authors: Delpuech Oona , Rooney Claire , Mooney Lorraine , Baker Dawn , Shaw Robert , Dymond Michael , Wang Dennis , Zhang Pei , Cross Sarah , Veldman-Jones Margaret , Wilson Joanne , Davies Barry R. , Dry Jonathan R. , Kilgour Elaine , Smith Paul D. 
Published: August 2016

AbstractThe challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers. Mol Cancer Ther; 15(11); 2802–13. ©2016 AACR.
TLR4-Dependent Claudin-1 Internalization and Secretagogue-Mediated Chloride Secretion Regulate Irinotecan-Induced Diarrhea
Authors: Wardill Hannah R. , Bowen Joanne M. , Van Sebille Ysabella Z.A. , Secombe Kate R. , Coller Janet K. , Ball Imogen A. , Logan Richard M. , Gibson Rachel J 
Published: August 2016

Abstract
We have previously shown increased intestinal permeability, to 4-kDa FITC-dextran, in BALB/c mice treated with irinotecan. Importantly, genetic deletion of Toll-like receptor 4 (TLR4; Tlr4−/−) protected against loss of barrier function, indicating that TLR4 is critical in tight junction regulation. The current study aimed (i) to determine the molecular characteristics of intestinal tight junctions in wild-type and Tlr4−/− BALB/c mice and (ii) to characterize the secretory profile of the distal colon. Forty-two female wild-type and 42 Tlr4−/− BALB/c mice weighing between 18 and 25 g received a single 270 mg/kg [intraperitoneal (i.p.)] dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. The secretory profile of the distal colon, following carbachol and forksolin, was assessed using Ussing chambers at all time points. Tight junction integrity was assessed at 24 hours, when peak intestinal permeability and diarrhea were reported, using immunofluorescence, Western blotting, and RT-PCR. Irinotecan caused internalization of claudin-1 with focal lesions of ZO-1 and occludin proteolysis in the ileum and colon of wild-type mice. Tlr4−/− mice maintained phenotypically normal tight junctions. Baseline conductance, a measure of paracellular permeability, was increased in irinotecan-treated wild-type mice at 24 hours (53.19 ± 6.46 S/cm2; P = 0.0008). No change was seen in Tlr4−/− mice. Increased carbachol-induced chloride secretion was seen in irinotecan-treated wild-type and Tlr4−/− mice at 24 hours (wild-type: 100.35 ± 18.37 μA/cm2; P = 0.022; Tlr4−/−: 102.72 ± 18.80 μA/cm2; P = 0.023). Results suggest that TLR4-dependent claudin-1 internalization and secondary anion secretion contribute to irinotecan-induced diarrhea. Mol Cancer Ther; 15(11); 2767–79. ©2016 AACR.
Тютюнокуріння: розповсюдженість та вплив на органи і тканини порожнини рота (огляд літератури)
Authors: Shcherba V. V. , Lavrin O. Ya. 
Published: August 2016

<p>Smoking is a global problem of humanity, and its impact on the organs and tissues of the oral cavity is a major health and social problem. Smoking is associated with significantly increased risk of the oral cavity diseases, especially with paradont pathology and cancer. Persons who have extensive experience of smoking, use tobacco products for oral use, except of smoking alcohol abuse belong to risk group of the oral cavity cancer. The severity of periodontal disease depends on the age of onset of smoking, duration of smoking and number of cigaretteswhich are smoked daily. In the literature many papers are devoted to research the impact of smoking on periodontal status. However, a number of aspects, including free radical oxidation state is left without proper attention, which is the aim of our further investigation.</p>
The Draupner Event: The Large Wave and the Emerging View
Authors: Cavaleri L. , Benetazzo A. , Barbariol F. , Bidlot J.-R. , Janssen P. A. E. M. 
Published: August 2016

Abstract
In a parallel paper mainly focused on the meteorological and oceanographic aspects, the conditions were described for the storm during which the iconic Draupner wave was recorded. Because of increased spatial resolution and improved model physics, the results provided new and previously unrecognized features of the storm, in particular of the wave spectra, features relevant for assessing the wave’s conditions nearby the Draupner platform. Starting from these, and after briefly summarizing the relevant information, the focus of this paper is on the nonlinear analysis of the local situation, with the main purpose of assessing if and how the conditions existed for the possible appearance of very large waves. An intensive analysis of the related probability is carried out, attacking the problem with two different statistical approaches, both briefly described: a completely new one working from the point of view of envelope heights, and a recent, though established, one based on space–time extreme waves. It is remarkable, and certainly supports this line of work, that the two different approaches lead independently to consistent results, supporting the idea, already derived from the meteo-oceanographic hindcast, that the wave conditions were indeed special at the position of the Draupner platform. This is related to a general analysis of high waves showing, also on the basis of 3D (2D space + time) measured wave data at open sea, how, given the severe sea state, the Draupner wave features represent what is expected at certain times and positions as the natural documented temporal evolution of wave groups.
Overturning in the Subpolar North Atlantic Program: A New International Ocean Observing System
Authors: Susan Lozier M. , Bacon Sheldon , Bower Amy S. , Cunningham Stuart A. , Femke de Jong M. , de Steur Laura , deYoung Brad , Fischer Jürgen , Gary Stefan F. , Greenan Blair J. W. , Heimbach Patrick , Holliday Naomi P. , Houpert Loïc , Inall Mark E. , Johns William E. , Johnson Helen L. , Karstensen Johannes , Li Feili , Lin Xiaopei , Mackay Neill , Marshall David P. , Mercier Herlé , Myers Paul G. , Pickart Robert S. , Pillar Helen R. , Straneo Fiammetta , Thierry Virginie , Weller Robert A. , Williams Richard G. , Wilson Chris , Yang Jiayan , Zhao Jian , Zika Jan D. 
Published: August 2016

Abstract
For decades oceanographers have understood the Atlantic meridional overturning circulation (AMOC) to be primarily driven by changes in the production of deep-water formation in the subpolar and subarctic North Atlantic. Indeed, current Intergovernmental Panel on Climate Change (IPCC) projections of an AMOC slowdown in the twenty-first century based on climate models are attributed to the inhibition of deep convection in the North Atlantic. However, observational evidence for this linkage has been elusive: there has been no clear demonstration of AMOC variability in response to changes in deep-water formation. The motivation for understanding this linkage is compelling, since the overturning circulation has been shown to sequester heat and anthropogenic carbon in the deep ocean. Furthermore, AMOC variability is expected to impact this sequestration as well as have consequences for regional and global climates through its effect on the poleward transport of warm water. Motivated by the need for a mechanistic understanding of the AMOC, an international community has assembled an observing system, Overturning in the Subpolar North Atlantic Program (OSNAP), to provide a continuous record of the transbasin fluxes of heat, mass, and freshwater, and to link that record to convective activity and water mass transformation at high latitudes. OSNAP, in conjunction with the Rapid Climate Change–Meridional Overturning Circulation and Heatflux Array (RAPID–MOCHA) at 26°N and other observational elements, will provide a comprehensive measure of the three-dimensional AMOC and an understanding of what drives its variability. The OSNAP observing system was fully deployed in the summer of 2014, and the first OSNAP data products are expected in the fall of 2017.
Changes in Wind Speed under Heat Waves Enhance Urban Heat Islands in the Beijing Metropolitan Area
Authors: Li Dan , Sun Ting , Liu Maofeng , Wang Linlin , Gao Zhiqiu 
Published: August 2016

AbstractThe interaction between urban heat islands (UHIs) and heat waves (HWs) is studied using measurements collected at two towers in the Beijing, China, metropolitan area and an analytical model. Measurements show that 1) the positive interaction between UHIs and HWs not only exists at the surface but also persists to higher levels (up to ~70 m) and 2) the urban wind speed is enhanced by HWs during daytime but reduced during nighttime as compared with its rural counterpart. A steady-state advection–diffusion model coupled to the surface energy balance equation is then employed to understand the implication of changes in wind speed on UHIs, which reveals that the observed changes in wind speed positively contribute to the interaction between UHIs and HWs in both daytime and nighttime. The vertical structure of the positive interaction between UHIs and HWs is thus likely an outcome resulting from a combination of changes in the surface energy balance and wind profile.
Diurnal Variations of the Land–Sea Breeze and Its Related Precipitation over South China
Authors: Chen Xingchao , Zhang Fuqing , Zhao Kun 
Published: August 2016

Abstract
Convection-permitting numerical experiments using the Weather Research and Forecasting (WRF) Model are performed to examine the diurnal cycles of land and sea breeze and its related precipitation over the south China coastal region during the mei-yu season. The focus of the analyses is a 10-day simulation initialized with the average of the 0000 UTC gridded global analyses during the 2007–09 mei-yu seasons (11 May–24 June) with diurnally varying cyclic lateral boundary conditions. Despite differences in the rainfall intensity and locations, the simulation verified well against averages of 3-yr ground-based radar, surface, and CMORPH observations and successfully simulated the diurnal variation and propagation of rainfall associated with the land and sea breeze over the south China coastal region. The nocturnal offshore rainfall in this region is found to be induced by the convergence line between the prevailing low-level monsoonal wind and the land breeze. Inhomogeneity of rainfall intensity can be found along the coastline, with heavier rainfall occurring in the region with coastal orography. In the night, the mountain–plain solenoid produced by the coastal terrain can combine with the land breeze to enhance offshore convergence. In the daytime, rainfall propagates inland with the inland penetration of the sea breeze, which can be slowed by the coastal mountains. The cold pool dynamics also plays an essential role in the inland penetration of precipitation and the sea breeze. Dynamic lifting produced by the sea-breeze front is strong enough to produce precipitation, while the intensity of precipitation can be dramatically increased with the latent heating effect.
The Impact of the Extreme Winter 2015/16 Arctic Cyclone on the Barents–Kara Seas
Authors: Boisvert Linette N. , Petty Alek A. , Stroeve Julienne C. 
Published: August 2016

AbstractAtmospheric data from the Atmospheric Infrared Sounder (AIRS) were used to study an extreme warm and humid air mass transported over the Barents–Kara Seas region by an Arctic cyclone at the end of December 2015. Temperature and humidity in the region was ~10°C (>3σ above the 2003–14 mean) warmer and ~1.4 g kg−1 (>4σ above the 2003–14 mean) wetter than normal during the peak of this event. This anomalous air mass resulted in a large and positive flux of energy into the surface via the residual of the surface energy balance (SEB), compared to the weakly negative SEB from the surface to the atmosphere expected for that time of year. The magnitude of the downwelling longwave radiation during the event was unprecedented compared to all other events detected by AIRS in December/January since 2003. An approximate budget scaling suggests that this anomalous SEB could have resulted in up to 10 cm of ice melt. Thinning of the ice pack in the region was supported by remotely sensed and modeled estimates of ice thickness change. Understanding the impact of this anomalous air mass on a thinner, weakened sea ice state is imperative for understanding future sea ice–atmosphere interactions in a warming Arctic.