bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and feasibility of every‐other‐week maintenance cetuximab after first‐line chemotherapy in patients with recurrent or metastatic head and neck squamous cell cancer
Authors: Bossi Paolo , Kornek Gabriela , Lanzetta Gaetano , Rozzi Antonio , Füreder Thorsten , Locati Laura , Licitra Lisa 
Published: October 2012

BackgroundIn patients with recurrent and/or metastatic head and neck squamous cell cancer (HNSCC), there are no data about an every‐other‐week cetuximab maintenance schedule after chemotherapy plus cetuximab as first‐line treatment.MethodsWe reviewed the safety and feasibility of every‐other‐week maintenance cetuximab administered at 3 different European centers.ResultsThirty‐one patients with recurrent or metastatic HNSCC were treated from 2006 to 2010. Mean cetuximab dose intensity in the maintenance phase was 93%. The major toxicities reported during every‐other‐week maintenance cetuximab were skin rash (grade 3, 16%; grade 2, 23%), fatigue (grade 3, 3%; grade 2, 16%), diarrhea (grade 3, 7%; grade 2, 13%), hypomagnesemia (grade 4, 3%; grade 3, 3%; grade 2, 19%), and mucositis (grade 3, 3%; grade 2, 23%).ConclusionsEvery‐other‐week maintenance cetuximab schedule was well tolerated and did not worsen toxicity that occurred during chemotherapy. In daily practice, this simplified schedule could improve compliance and possibly improve quality of life in patients with recurrent or metastatic HNSCC that showed no progression during first‐line chemotherapy. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1471–1474, 2013
Extracellular signal‐regulated kinase activation in the chronic constriction injury model of neuropathic pain in anaesthetized rats
Authors: Borges G.S. , Berrocoso E. , Ortega‐Alvaro A. , Mico J.A. , Neto F.L. 
Published: October 2012

AbstractBackgroundThe role of extracellular signal‐regulated kinases (ERKs) in nociception has been explored in the last years. While in spinal cord their activation is frequently correlated with pain or acute noxious stimuli, supraspinally, this association is not so evident and remains unclear. This study aims to evaluate ERK1/2 activation in the spinal cord and brainstem nuclei upon neuropathy and/or an additional mechanical stimulus.MethodsAcute noxious mechanical stimulation was applied in the left hindpaw of anaesthetized SHAM‐operated and chronic constriction injured (CCI, neuropathic pain model) rats. Other SHAM or CCI rats did not receive any stimulus. Immunohistochemistry against the phosphorylated isoforms of ERK1/2 (pERK1/2) was performed in lumbar spinal cord and brainstem sections to assess ERK1/2 activation.ResultsIn the spinal cord, stimulation promoted an increase in pERK1/2 expression in the superficial dorsal horn of SHAM rats. No significant effects were caused by CCI alone. At supraspinal level, changes in ERK1/2 activation induced by CCI were observed in A5, locus coeruleus (LC), raphe obscurus (ROb), raphe magnus, dorsal raphe (DRN), lateral reticular and paragigantocellularis nucleus. CCI increased pERK1/2 expression in all these nuclei, with exception of LC, where a significant decrease was verified. Mechanical noxious stimulation of CCI rats decreased pERK1/2 expression in ROb and DRN, but no further changes were detected in either SHAM‐ or CCI‐stimulated animals.ConclusionERK1/2 are differentially activated in the spinal cord and in selected brainstem nuclei implicated in nociception, in response to an acute noxious stimulus and/or to a neuropathic pain condition.
Suppression of mammalian bone growth by membrane transport inhibitors
Authors: Loqman Mohamad Y. , Bush Peter G. , Farquharson Colin , Hall Andrew C. 
Published: October 2012

AbstractBone lengthening during skeletal growth is driven primarily by the controlled enlargement of growth plate (GP) chondrocytes. The cellular mechanisms are unclear but membrane transporters are probably involved. We investigated the role of the Na+/H+ antiporter (NHE1) and anion exchanger (AE2) in bone lengthening and GP chondrocyte hypertrophy in Sprague–Dawley 7‐day‐old rat (P7) bone rudiments using the inhibitors EIPA (5‐(N‐ethyl‐N‐isopropyl)amiloride) and DIDS (4,4‐diidothiocyano‐2,2‐stilbenedisulphonate), respectively. We have also determined cell‐associated levels of these transporters along the GP using fluorescent immunohistochemistry (FIHC). Culture of bones with EIPA or DIDS inhibited rudiment growth (50% at approx. 250 and 25 µM, respectively). Both decreased the size of the hypertrophic zone (P < 0.05) but had no effect on overall length or cell density of the GP. In situ chondrocyte volume in proliferative and hypertrophic zones was decreased (P < 0.01) with EIPA but not DIDS. FIHC labeling of NHE1 was relatively high and constant along the GP but declined steeply in the late hypertrophic zone. In contrast, AE2 labeling was relatively low in proliferative zone cells but increased (P < 0.05) reaching a maximum in the early hypertrophic zone, before falling rapidly in the late hypertrophic zone suggesting AE2 might regulate the transition phase of chondrocytes between proliferative and hypertrophic zones. The inhibition of bone growth by EIPA may be due to a reduction to chondrocyte volume set‐point. However the effect of DIDS was unclear but could result from inhibition of AE2 and blocking of the transition phase. These results demonstrate that NHE1 and AE2 are important regulators of bone growth. J. Cell. Biochem. 114: 658–668, 2013. © 2012 Wiley Periodicals, Inc.
Autocrine fibroblast growth factor 2‐mediated interactions between human mesenchymal stem cells and the extracellular matrix under varying oxygen tension
Authors: Kim Junho , Ma Teng 
Published: October 2012

AbstractHuman mesenchymal stromal or stem cells (hMSCs) are being investigated for cell therapy in a wide range of diseases. MSCs are a potent source of trophic factors and actively remodel their immediate microenvironment through the secretion of bioactive factors in response to external stimuli such as oxygen tension. In this study, we examined the hypothesis that hypoxia influences hMSC properties in part through the regulation of extracellular milieu characterized by the extracellular matrix (ECM) matrices and the associated fibroblast growth factor‐2 (FGF‐2). The decellularized ECM matrices derived from hMSC culture under both hypoxic (e.g., 2% O2) and the standard culture (e.g., 20% O2) conditions have different binding capacities to the cell‐secreted and exogenenous FGF‐2. The reduced hMSC proliferation in the presence of FGF‐2 inhibitor and the differential capacity of the decellularized ECM matrices in regulating hMSC osteogeneic and adipogenic differentiation suggest an important role of the endogenous FGF‐2 in sustaining hMSC proliferation and regulating hMSC fate. Additionally, the combination of the ECM adhesion and hypoxic culture preserved hMSC viability under serum withdrawal. Together, the results suggest the synergistic effect of hypoxia and the ECM matrices in sustaining hMSC ex vivo expansion and preserving their multi‐potentiality and viability under nutrient depletion. The results have important implication in optimizing hMSC expansion and delivery strategies to obtain hMSCs in sufficient quantity with required potency and to enhance survival and function upon transplantation. J. Cell. Biochem. 114: 716–727, 2013. © 2012 Wiley Periodicals, Inc.
Sharp threshold for the appearance of certain spanning trees in random graphs
Authors: Hefetz Dan , Krivelevich Michael , Szabó Tibor 
Published: October 2012

AbstractWe prove that a given tree T on n vertices with bounded maximum degree is contained asymptotically almost surely in the binomial random graph
\documentclass{article}\usepackage{mathrsfs, amsmath, amssymb}\pagestyle{empty}\begin{document}\begin{align*}G(n,\frac{(1+\varepsilon) \log n}{n})\end{align*}\end{document}
provided that T belongs to one of the following two classes: (1)
T has linearly many leaves; (2) T has a path of linear length all of whose vertices have degree two in T. © 2012 Wiley Periodicals, Inc. Random Struct. Alg., 2012
Docosahexanoic Acid Improves Chemotherapy Efficacy by Inducing CD95 Translocation to Lipid Rafts in ER− Breast Cancer Cells
Authors: Ewaschuk Julia B. , Newell Marnie , Field Catherine J. 
Published: October 2012

AbstractDocosahexanoic acid (DHA) and eicosapentanoic acid (EPA) have been shown to possess anti‐carcinogenic properties in mammary cancers, both in vitro and in vivo. The objective of this study was to investigate the effect of treating three different breast cancer cell lines with DHA or EPA on cellular growth, chemotherapy efficacy, and CD95 expression and localization in the cell. MDA‐MB‐231, MCF‐7 and SKBr‐3 cells were incubated with EPA or DHA with or without chemotherapy agents [doxorubicin (dox), Herceptin]. Cell growth was assessed by WST‐1 assay and CD95 expression was investigated using flow cytometry, Western blotting and confocal microscopy. DHA and EPA inhibited the growth of all three breast cancer cell lines in a dose‐dependent fashion (P < 0.05). DHA, and to a lesser extent EPA, induced the movement and raft clustering of CD95 in the cell membrane (via confocal microscopy) and the surface expression (via flow cytometry) in MDA‐MB‐231 cells. Neither fatty acid altered the growth/metabolic activity of the non‐transformed MCF‐12A breast cell line. Pre‐treatment with DHA, but not EPA, improved the efficacy of dox in estrogen receptor negative MDA‐MB‐231 cells (P < 0.05), but not in the other two cell lines. Pre‐treating cells with DHA increased CD95 surface expression (threefold) and the plasma membrane raft content of CD95 (2fold) and FADD (>4‐fold) after dox treatment, compared to dox treatment alone (P < 0.05). This study demonstrated that pre‐treatment of estrogen receptor negative MDA‐MB‐231 cells with DHA increased the anti‐cancer effects of dox and presents evidence to suggest that this may be mediated in part by CD95‐induced apoptosis.
Characterization of Oxidative Stability of Fish Oil‐ and Plant Oil‐Enriched Skimmed Milk
Authors: Saga Linda C. , Kristinova Vera , Kirkhus Bente , Jacobsen Charlotte , Skaret Josefine , Liland Kristian Hovde , Rukke Elling‐Olav 
Published: October 2012

AbstractThe objective of this research was to determine the oxidative stability of fish oil blended with crude plant oils rich in naturally occurring antioxidants, camelina oil and oat oil, respectively, in bulk and after supplementation of 1 wt% of oil blends to skimmed milk emulsions. Ability of crude oat oil and camelina oil to protect fish oil in bulk and as fish oil‐enriched skimmed milk emulsions was evaluated. Results of oxidative stability of bulk oils and blends assessed by the Schaal oven weight gain test and by the rancimat method showed significant increase in oxidative stability when oat oil was added to fish oil in only 5 and 10 %, whereas no protective effect of camelina oil was observed when evaluated by these methods. Moreover, fish oil blended with oat oil conferred the lowest PV and lower amounts of volatile compounds during the storage period of 14 days at 4 °C. Surprisingly, skimmed milk supplemented with fish‐oat oil blend gave the highest scores for off‐flavors in the sensory evaluation, demonstrating that several methods, including sensory analysis, should be combined to illustrate the complete picture of lipid oxidation in emulsions.
Ichnological evidence of jökulhlaup deposit recolonization from the Touchet Beds, Mabton, WA, USA
Authors: MacEachern James A. , Roberts Michael C. 
Published: October 2012

AbstractThe late Wisconsinan Touchet Beds section at Mabton, Washington reveals at least seven stacked jökulhlaup deposits, five showing evidence of post-flood recolonization by vertebrates. Tracemakers are attributed to voles or pocket mice (1–3 cm diameter burrows) and pocket gophers or ground squirrels (3–6 cm diameter burrows). The Mount St. Helens S tephra deposited between flood beds contains the invertebrate-generated burrows Naktodemasis and Macanopsis. Estimates of times between floods are based on natal dispersal distances of the likely vertebrate tracemakers (30–50 m median distances; 127–525 m maximum distances) from upland areas containing surviving populations to the Mabton area, a distance of about 7.9 km. Tetrapods would have required at least two to three decades to recolonize these flood beds, based on maximum dispersal distances. Invertebrate recolonization was limited by secondary succession and estimated at only a few years to a decade. These ichnological data support multiple floods from failure of the ice dam at glacial Lake Missoula, separated by hiatal surfaces on the order of decades in duration. Ichnological recolonization times are consistent with published estimates of refill times for glacial Lake Missoula, and complement the other field evidence that points to repeated, autogenically induced flood discharge.
Tephrochronology, magnetostratigraphy and mammalian faunas of Middle and Early Pleistocene sediments at two sites on the Old Crow River, northern Yukon Territory, Canada
Authors: Westgate John A. , Pearce G. William , Preece Shari J. , Schweger Charles E. , Morlan Richard E. , Pearce Nicholas J.G. , Perkins T. William 
Published: October 2012

AbstractAlluvial and lacustrine sediments exposed beneath late Pleistocene glaciolacustrine silt and clay at two sites along the Old Crow River, northern Yukon Territory, are rich in fossils and contain tephra beds. Surprise Creek tephra (SZt) occurs in the lower part of the alluvial sequence at CRH47 and Little Timber tephra (LTt) is present near the base of the exposure at CRH94. Surprise Creek tephra has a glass fission-track age of 0.17 ± 0.07 Ma and Little Timber tephra is 1.37 ± 0.12 Ma. All sediments at CRH47 have a normal remanent magnetic polarity and those near LTt at CRH94 have a reversed polarity — in agreement with the geomagnetic time scale. Small mammal remains from sediments near LTt support an Early Pleistocene age but the chronology is not so clear at CRH47 because of the large error associated with the SZt age determination. Tephrochronological and paleomagnetic considerations point to an MIS 7 age for the interglacial beds just below SZt at CRH47 and at Chester Bluffs in east-central Alaska, but mammalian fossils recovered from sediments close to SZt suggest a late Irvingtonian age, therefore older than MIS 7. Further studies are needed to resolve this problem.
Intrinsic work motivation and pension reform preferences
Authors: HEINEMANN FRIEDRICH , HENNIGHAUSEN TANJA , MOESSINGER MARC-DANIEL 
Published: October 2012

AbstractAlthough demographic change leaves pay-as-you-go pension systems unsustainable, reforms, such as a higher pension age, are highly unpopular. This contribution looks into the role of intrinsic motivation as a driver for pension reform preferences. Theoretical reasoning suggests that this driver should be relevant as it decreases the subjective costs of a higher pension age. We test this key hypothesis on the basis of the German General Social Survey (ALLBUS). The results are unambiguous: in addition to factors such as age or education, the inclusion of intrinsic work motivation helps improving our prediction of an individual's reform orientation.
DAC Is Involved in the Accumulation of the Cytochrome b
6/f Complex in Arabidopsis
Authors: Xiao Jianwei , Li Jing , Ouyang Min , Yun Tao , He Baoye , Ji Daili , Ma Jinfang , Chi Wei , Lu Congming , Zhang Lixin 
Published: October 2012

Abstract
The biogenesis and assembly of photosynthetic multisubunit protein complexes is assisted by a series of nucleus-encoded auxiliary protein factors. In this study, we characterize the dac mutant of Arabidopsis (Arabidopsis thaliana), which shows a severe defect in the accumulation of the cytochrome b 6/f complex, and provide evidence suggesting that the efficiency of cytochrome b 6/f complex assembly is affected in the mutant. DAC is a thylakoid membrane protein with two predicted transmembrane domains that is conserved from cyanobacteria to vascular plants. Yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitation analyses revealed a specific interaction between DAC and PetD, a subunit of the cytochrome b 6/f complex. However, DAC was found not to be an intrinsic component of the cytochrome b 6/f complex. In vivo chloroplast protein labeling experiments showed that the labeling rates of the PetD and cytochrome f proteins were greatly reduced, whereas that of the cytochrome b 6 protein remained normal in the dac mutant. DAC appears to be a novel factor involved in the assembly/stabilization of the cytochrome b 6/f complex, possibly through interaction with the PetD protein.
Differential Control of Ethylene Responses byGREEN-RIPEandGREEN-RIPE LIKE1Provides Evidence for Distinct Ethylene Signaling Modules in Tomato
Authors: Ma Qian , Du Wenyan , Brandizzi Federica , Giovannoni James J. , Barry Cornelius S. 
Published: October 2012

AbstractThe factors that mediate specific responses to the plant hormone ethylene are not fully defined. In particular, it is not known how signaling at the receptor complex can control distinct subsets of ethylene responses. Mutations at the Green-ripe (Gr) and reversion to ethylene sensitivity1 (rte1) loci, which encode homologous proteins of unknown function, influence ethylene responses in tomato (Solanum lycopersicum) and Arabidopsis (Arabidopsis thaliana), respectively. In Arabidopsis, AtRTE1 is required for function of the ETR1 ethylene receptor and acts predominantly through this receptor via direct protein-protein interaction. While most eudicot families including the Brassicaceae possess a single gene that is closely related to AtRTE1, we report that members of the Solanaceae family contain two phylogenetically distinct genes defined by GR and GREEN-RIPE LIKE1 (GRL1), creating the possibility of subfunctionalization. We also show that SlGR and SlGRL1 are differentially expressed in tomato tissues and encode proteins predominantly localized to the Golgi. A combination of overexpression in tomato and complementation of the rte1-3 mutant allele indicates that SlGR and SlGRL1 influence distinct but overlapping ethylene responses. Overexpression of SlGRL1 in the Gr mutant background provides evidence for the existence of different ethylene signaling modules in tomato that are influenced by GR, GRL1, or both. In addition, overexpression of AtRTE1 in tomato leads to reduced ethylene responsiveness in a subset of tissues but does not mimic the Gr mutant phenotype. Together, these data reveal species-specific heterogeneity in the control of ethylene responses mediated by members of the GR/RTE1 family.
Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations
Authors: Bench Anthony J. , White Helen E. , Foroni Letizia , Godfrey Anna L. , Gerrard Gareth , Akiki Susanna , Awan Abida , Carter Ian , Goday‐Fernandez Andrea , Langabeer Stephen E. , Clench Tim , Clark Jordan , Evans Paul A. , Grimwade David , Schuh Anna , McMullin Mary F. , Green Anthony R. , Harrison Claire N. , Cross Nicholas C. P. 
Published: October 2012

SummaryMolecular genetic assays for the detection of the JAK2 V617F (c.1849G>T) and other pathogenetic mutations within JAK2 exon 12 and MPL exon 10 are part of the routine diagnostic workup for patients presenting with erythrocytosis, thrombocytosis or otherwise suspected to have a myeloproliferative neoplasm. A wide choice of techniques are available for the detection of these mutations, leading to potential difficulties for clinical laboratories in deciding upon the most appropriate assay, which can lead to problems with inter‐laboratory standardization. Here, we discuss the most important issues for a clinical diagnostic laboratory in choosing a technique, particularly for detection of the JAK2 V617F mutation at diagnosis. The JAK2 V617F detection assay should be both specific and sensitive enough to detect a mutant allele burden as low as 1–3%. Indeed, the use of sensitive assays increases the detection rate of the JAK2 V617F mutation within myeloproliferative neoplasms. Given their diagnostic relevance, it is also beneficial and relatively straightforward to screen JAK2 V617F negative patients for JAK2 exon 12 mutations (in the case of erythrocytosis) or MPL exon 10 mutations (thrombocytosis or myelofibrosis) using appropriate assays. Molecular results should be considered in the context of clinical findings and other haematological or laboratory results.
Multiple brain infarcts in young adults: clues for etiologic diagnosis and prognostic impact
Authors: Mustanoja S. , Putaala J. , Haapaniemi E. , Strbian D. , Kaste M. , Tatlisumak T. 
Published: October 2012

Background and purposeThere are little data on the etiology of multiple brain infarcts (MBI) and their impact on clinical outcome in young patients.MethodsWe studied 548 MRI‐imaged patients (15–49 years) with a first‐ever ischaemic stroke. Ischaemic lesions were categorized into three groups: single lesions, MBI in one or >1 circulation territories. Outcomes were unfavorable 3‐month modified Rankin Scale (mRS) score of ≥2 and, during long‐term follow‐up (mean 8.20 ± 4.01 years), recurrent ischaemic stroke or death from any cause.ResultsMultiple brain infarcts occurred in 185 patients (33.8%; mean age 39.2 ± 8.2), of which 144 patients (26.3%) had lesions located in a single territory and 41 patients (7.5%) in multiple territories. Patients with MBI in a single territory were more likely than patients with single lesions to have a high‐risk source of cardioembolism (CE) (9.0% vs. 3.0%; P = 0.001), large‐artery atherosclerosis (8.3% vs. 4.9%; P = 0.012), vertebral (22% vs. 10%; P < 0.001) or carotid artery dissections (8.3% vs. 6.3%; P = 0.036), and MBI in multiple territories a high‐risk source of CE (34% vs. 3.0%, P < 0.001). Adjusted for age, gender, baseline stroke severity, size of the largest lesion, and stroke subtype, MBI remained independently associated with an unfavorable 3‐month outcome (odds ratio 2.84, 95% confidence interval 1.22–6.61). In multivariate Cox proportional hazards analysis, MBI had independent influence on the risk for death (hazard ratio 3.75, 1.58–8.86), but not on recurrent ischaemic stroke.ConclusionsCompared with the elderly, young stroke patients have a distinct stroke etiology underlying MBI, being an independent indicator of poor short‐term outcome and long‐term risk of death.