bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Rapid Detection and Serotyping of Cronobacter sakazakii Serotypes O1, O2, and O3 by Using Specific Monoclonal Antibodies
Authors: Scharinger Eva J. , Dietrich Richard , Kleinsteuber Ina , Märtlbauer Erwin , Schauer Kristina 
Published: February 2016

ABSTRACT

Cronobacter sakazakii
is a foodborne pathogen associated with rare but often lethal infections in neonates. Powdered infant formula (PIF) represents the most frequent source of infection. Out of the identified serotypes (O1 to O7), O1, O2, and O3 are often isolated from clinical and PIF samples. Serotype-specific monoclonal antibodies (MAbs) suitable for application in enzyme immunoassays (EIAs) for the rapid detection of
C. sakazakii
have not yet been developed. In this study, we created specific MAbs with the ability to bind to
C. sakazakii
of serotypes O1, O2, and O3. Characterization by indirect EIAs, immunofluorescence, motility assays, and immunoblotting identified lipopolysaccharide (LPS) and exopolysaccharide (EPS) as the antigenic determinants of the MAbs. The established sandwich EIAs were highly sensitive and were able to detect between 2 × 10
3
and 9 × 10
6
CFU/ml. Inclusivity tests confirmed that 93% of serotype O1 strains, 100% of O2 strains, and 87% of O3 strains were detected at low cell counts. No cross-reactivity with >100 strains of
Cronobacter
spp. and other
Enterobacteriaceae
was observed, except for that with
C. sakazakii
serotype O3 and
Cronobacter
muytjensii
serotype O1. Moreover, the sandwich EIAs detected
C. sakazakii
in PIF samples artificially contaminated with 1 to 10 bacterial cells per 10 g of sample after 15 h of preenrichment. The use of these serotype-specific MAbs not only allows the reliable detection of
C. sakazakii
strains but also enables simultaneous serotyping in a simple sandwich EIA method.
Technical and clinical accuracy of three blood glucose meters: clinical impact assessment using error grid analysis and insulin sliding scales
Authors: Sutheran Hannah Lise , Reynolds Timothy 
Published: February 2016

AimsManufacturers of point-of-care testing (POCT) glucose systems must adhere to International Organisation for Standardisation (ISO) 15197 performance standards, a tightened version of which becomes mandatory in May 2016. Using methods deviating from the evaluation requirements of ISO 15197, we investigated the accuracy and clinical utility of three glucose testing systems.MethodsWhole blood glucose was measured on 62 EDTA-preserved samples with each system followed by plasma glucose determination with a laboratory hexokinase method. Technical accuracy was assessed using linear regression, Bland-Altman plots and bias. Clinical utility was evaluated using consensus error grid analysis and insulin dosing algorithms.ResultsThe correlation coefficient of the glucose measuring devices with the comparator method was between 0.979 and 0.993 (n=61). Bias against the reference method was +0.7–+4.4%. The FreeStyle Lite (0.7±4.4%) and ACCU-CHEK Aviva (1.3±7.3%) systems had the least bias to the reference. Error grid analysis depicts all meters to be clinically accurate, with all results falling within Zones A and B.ConclusionsConformité Européene-marked devices are presumed to have adequate accuracy, but postmarket evaluations are imperative to assess total system accuracy and whether regulatory targets are achieved.
Continuing medical education for general practitioners: a practice format
Authors: VanNieuwenborg Lena , Goossens Martine , De Lepeleire Jan , Schoenmakers Birgitte 
Published: February 2016

AbstractIntroductionOur current knowledge-based society and the many actualisations within the medical profession require a great responsibility of physicians to continuously develop and refine their skills. In this article, we reflect on some recent findings in the field of continuing education for professional doctors (continuing medical education, CME). Second, we describe the development of a CME from the Academic Center for General Practice (ACHG) of the KU Leuven.MethodsFirst, we performed a literature study and we used unpublished data of a need assessment performed (2013) in a selected group of general practitioners. Second, we describe the development of a proposal to establish a CME programme for general practitioners.ResultsCME should go beyond the sheer acquisition of knowledge, and also seek changes in practice, attitudes and behaviours of physicians. The continuing education offerings are subject to the goals of the organising institution, but even more to the needs and desires of the end user.ConclusionsIntegrated education is crucial to meet the conditions for efficient and effective continuing education. The ACHG KU Leuven decided to offer a postgraduate programme consisting of a combination of teaching methods: online courses (self-study), contact courses (traditional method) and a materials database.
Cardiac manifestations in alcoholic liver disease
Authors: Milić Sandra , Lulić Davorka , Štimac Davor , Ružić Alen , Zaputović Luka 
Published: February 2016

AbstractAlcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%–20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.
Importance of pre-existing fault size for the evolution of an inverted fault system
Authors: Reilly Cathal , Nicol Andrew , Walsh John 
Published: February 2016

Abstract
Fault inversion has been documented in many basins worldwide, yet the details of how the initial extensional faults impact on the geometry and growth of the reactivated contractional system is often poorly resolved by the available data. Two-dimensional (2D) and 3D seismic reflection, and well data have been used to chart the evolution of inverted faults from the Taranaki Basin, offshore New Zealand. Sedimentary rocks up to 8 km thick record Late Cretaceous–Paleocene normal faults inverted during Miocene and younger shortening. The displacement and length of early normal faults is a key determinant for the reactivation and size of the subsequent reverse faults. All normal faults with maximum vertical displacements ≥600 m and lengths ≥9 km were inverted along their entire length, while smaller faults were not inverted. The proportion of the total basin-wide strain accommodated on each fault is comparable between deformational episodes. The hierarchy of reverse fault lengths was established rapidly, with longer faults accruing a greater proportion of the total strain from an early stage of shortening. The reverse fault system is dominated by inverted normal faults, which accrue displacement at the expense of smaller faults, and utilize the largest crustal-scale elements of the pre-existing system. The size of pre-existing heterogeneities is an important control for the magnitude and spatial extent of elevated stresses during contraction, which, in turn, control the dimensions, locations and displacements of subsequent fault growth.
The geometry and dimensions of fault-core lenses
Authors: Gabrielsen Roy H. , Braathen Alvar , Kjemperud Magnus , Valdresbråten Marie Lovise R. 
Published: February 2016

Abstract
Field analysis shows that fault cores of brittle, extensional faults at a medium to mature stage of development are commonly dominated by lozenge-shaped horses (fault-core lenses) characterized by a variety of lithologies, including intact, mildly to strongly deformed country rock derived from the footwalls and hanging walls, various types of fault rocks of the protocatalasite and breccia series, breccia, fault gouge and clay smear. The lenses are sometimes stacked to form complex duplexes. These structures are commonly separated by high-strain zones of sheared cataclasite, and/or clay smear/clay gouge. The geometry and distribution of clay gouge in high-strain zones sometimes display evidence of intrusion, indicating high fluid pressure.

Although the sizes of the horses vary over several orders of magnitude, they frequently display a length:thickness (
a
:
c
) ratio of between 1:4 and 1:15.

The high-strain zones of fault rocks commonly constitute unbroken, 3D membranes that are likely to constrain fluid communication both across and along the fault zone.
There are significant contrasts in fault core architecture that are probably related to processes associated with contrasting fluid pressure, strain intensity and strain hardening/strain softening. Faults associated with strain softening are characterized by less abundant brittle deformation products and are less likely to be conduits for fluid flow compared to those that are affected by strain hardening.
Post-Caledonian extension in the West Norway–northern North Sea region: the role of structural inheritance
Authors: Fossen Haakon , Khani Hamed Fazli , Faleide Jan Inge , Ksienzyk Anna K. , Dunlap W. James 
Published: February 2016

Abstract
The northern North Sea region has experienced repeated phases of post-Caledonian extension, starting with extensional reactivation of the low-angle basal Caledonian thrust zone, then the formation of Devonian extensional shear zones with 10–100 km-scale displacements, followed by brittle reactivation and the creation of a plethora of extensional faults. The North Sea Rift-related approximately east–west extension created a new set of rift-parallel faults that cut across less favourably orientated pre-rift structures. Nevertheless, fault rock dating shows that onshore faults and shear zones of different orientations were active throughout the history of rifting. Several of the reactivated major Devonian extensional structures can be extrapolated offshore into the rift, where they appear as bands of dipping reflectors. They coincide with large-scale boundaries separating 50–100 km-wide rift domains of internally uniform fault patterns. Major north–south-trending rift faults, such as the Øygarden Fault System, bend or terminate against these boundaries, clearly influenced by their presence during rifting. Hence, the North Sea is one of several examples where pre-rift basement structures oblique to the rift extension direction can significantly influence rift architecture, even if most of the rift faults are newly-formed structures.
Spatial characteristics of the Pliocene to modern alluvial fan successions in the uplifted sedimentary basins of Almería, SE Spain: review and regional synthesis
Authors: M. Harvey Adrian , Stokes Martin , Mather Anne , Whitfield Elizabeth 
Published: February 2016

Abstract
Conventional sedimentological models of alluvial fan sequences tend to be based on fans in subsiding sedimentary basins. Fans in uplifting terrains are rather different. We examined the sequence of fan delta and alluvial fan deposition from the Pliocene to the Late Quaternary in the uplifting terrain of the Neogene sedimentary basins of Almería, Betic Cordillera, SE Spain. There were three phases of fan deposition, each yielding particular morpho-sedimentological characteristics and each having distinctive spatial distributions. The first phase was the Pliocene fan deltas, deposited where the larger river systems entered the receding early Pliocene seas. This phase was followed during the late Pliocene–Early Pleistocene by a phase of extensive alluvial fan deposition extending from the mountain fronts to the basin centres. Continued uplift occurred during the Pleistocene, resulting in incision of the drainage network and dissection of the Plio-Pleistocene fan systems. The third phase, during the Quaternary, involved much smaller mountain front alluvial fans set well below the Plio-Pleistocene fans, except in local areas of tectonic subsidence where extensive fans were formed. The older fans exhibit stacked sedimentary successions with very little evidence of sustained vertical incision. However, the Quaternary fans show much evidence of sustained incision between major aggradational phases, often resulting in inset rather than stacked stratigraphic relationships. We interpret this to imply that, although the tectonic context was the primary temporal control on variations within the older fan successions, within the Quaternary fans the overall tectonic control has been modified by responses to the Quaternary climatic sequence.
Circulating Estrogens and Postmenopausal Ovarian Cancer Risk in the Women's Health Initiative Observational Study
Authors: Trabert Britton , Brinton Louise A. , Anderson Garnet L. , Pfeiffer Ruth M. , Falk Roni T. , Strickler Howard D. , Sliesoraitis Sarunas , Kuller Lewis H. , Gass Margery L. , Fuhrman Barbara J. , Xu Xia , Wentzensen Nicolas 
Published: February 2016

AbstractBackground: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case–control study in the Women's Health Initiative (WHI) Observational Study (OS).Methods: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years.Results: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82–2.90), Ptrend = 0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06–3.88), Ptrend = 0.02; 1.86 (0.98–3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09–6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04–7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors.Conclusions: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers.Impact: These findings further support the heterogeneous etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 648–56. ©2016 AACR.
A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis
Authors: Hawkins Robert E. , Gore Martin , Shparyk Yaroslav , Bondar Vladimir , Gladkov Oleg , Ganev Tosho , Harza Mihai , Polenkov Serhii , Bondarenko Igor , Karlov Petr , Karyakin Oleg , Khasanov Rustem , Hedlund Gunnar , Forsberg Goran , Nordle Örjan , Eisen Timothy 
Published: February 2016

AbstractPurpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC).Experimental Design: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 μg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS).Results: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile.Conclusions: The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup. Clin Cancer Res; 22(13); 3172–81. ©2016 AACR.
Epithelial–Mesenchymal Transition Is Associated with a Distinct Tumor Microenvironment Including Elevation of Inflammatory Signals and Multiple Immune Checkpoints in Lung Adenocarcinoma
Authors: Lou Yanyan , Diao Lixia , Cuentas Edwin Roger Parra , Denning Warren L. , Chen Limo , Fan You Hong , Byers Lauren A. , Wang Jing , Papadimitrakopoulou Vassiliki A. , Behrens Carmen , Rodriguez Jaime Canales , Hwu Patrick , Wistuba Ignacio I. , Heymach John V. , Gibbons Don L. 
Published: February 2016

Abstract
Purpose: Promising results in the treatment of non–small cell lung cancer (NSCLC) have been seen with agents targeting immune checkpoints, such as programmed cell death 1 (PD-1) or programmed death ligand-1 (PD-L1). However, only a select group of patients respond to these interventions. The identification of biomarkers that predict clinical benefit to immune checkpoint blockade is critical to successful clinical translation of these agents.
Methods: We conducted an integrated analysis of three independent large datasets, including The Cancer Genome Atlas of lung adenocarcinoma and two datasets from MD Anderson Cancer Center (Houston, TX), Profiling of Resistance Patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax (named PROSPECT) and Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (named BATTLE-1). Comprehensive analysis of mRNA gene expression, reverse-phase protein array, IHC, and correlation with clinical data were performed.
Results: Epithelial–mesenchymal transition (EMT) is highly associated with an inflammatory tumor microenvironment in lung adenocarcinoma, independent of tumor mutational burden. We found immune activation coexistent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, along with increases in tumor infiltration by CD4+Foxp3+ regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype. Furthermore, we identify B7-H3 as a prognostic marker for NSCLC.
Conclusions: The strong association between EMT status and an inflammatory tumor microenvironment with elevation of multiple targetable immune checkpoint molecules warrants further investigation of using EMT as a predictive biomarker for immune checkpoint blockade agents and other immunotherapies in NSCLC and possibly a broad range of other cancers. Clin Cancer Res; 22(14); 3630–42. ©2016 AACR.
See related commentary by Datar and Schalper, p. 3422
STAT3/5-Dependent IL9 Overexpression Contributes to Neoplastic Cell Survival in Mycosis Fungoides
Authors: Vieyra-Garcia Pablo A. , Wei Tianling , Naym David Gram , Fredholm Simon , Fink-Puches Regina , Cerroni Lorenzo , Odum Niels , O'Malley John T. , Gniadecki Robert , Wolf Peter 
Published: February 2016

Abstract
Purpose: Sustained inflammation is a key feature of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). Resident IL9–producing T cells have been found in skin infections and certain inflammatory skin diseases, but their role in MF is currently unknown.
Experimental Design: We analyzed lesional skin from patients with MF for the expression of IL9 and its regulators. To determine which cells were producing IL9, high-throughput sequencing was used to identify malignant clones and Vb-specific antibodies were employed to visualize malignant cells in histologic preparations. To explore the mechanism of IL9 secretion, we knocked down STAT3/5 and IRF4 by siRNA transfection in CTCL cell lines receiving psoralen+UVA (PUVA) ± anti-IL9 antibody. To further examine the role of IL9 in tumor development, the EL-4 T-cell lymphoma model was used in C57BL/6 mice.
Results: Malignant and reactive T cells produce IL9 in lesional skin. Expression of the Th9 transcription factor IRF4 in malignant cells was heterogeneous, whereas reactive T cells expressed it uniformly. PUVA or UVB phototherapy diminished the frequencies of IL9- and IL9r-positive cells, as well as STAT3/5a and IRF4 expression in lesional skin. IL9 production was regulated by STAT3/5 and silencing of STAT5 or blockade of IL9 with neutralizing antibodies potentiated cell death after PUVA treatment in vitro. IL9-depleted mice exhibited a reduction of tumor growth, higher frequencies of regulatory T cells, and activated CD4 and CD8 T lymphocytes.
Conclusions: Our results suggest that IL9 and its regulators are promising new targets for therapy development in mycosis fungoides. Clin Cancer Res; 22(13); 3328–39. ©2016 AACR.
miR-155 Overexpression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair
Authors: Czochor Jennifer R. , Sulkowski Parker , Glazer Peter M. 
Published: February 2016

Abstract
miR-155 is an oncogenic miRNA that is often overexpressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors, including RAD51, MLH1, and MSH6, and its overexpression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that overexpression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 overexpression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone nonhomologous end-joining pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 overexpression does not resemble that of a mismatch repair–deficient background. Further investigation revealed that all four subunits of polymerase delta, a high-fidelity DNA replication, and repair polymerase are downregulated at the mRNA level in the context of miR-155 overexpression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels.
Implications: Taken together, miR-155 overexpression drives an increase in mutation frequency via multifaceted impact on DNA damage response and DNA repair pathways. Mol Cancer Res; 14(4); 363–73. ©2016 AACR.