bluuebunny/crossref_metadata_2025_split huggingface dataset:
Republished: Value of white cell count in predicting serious bacterial infection in febrile children under 5 years of age
Authors: De Sukanya , Williams Gabrielle J , Hayen Andrew , Macaskill Petra , McCaskill Mary , Isaacs David , Craig Jonathan C 
Published: March 2015

ABSTRACTObjectiveThe leukocyte count is frequently used to evaluate suspected bacterial infections but estimates of its test performance vary considerably. We evaluated its accuracy for the detection of serious bacterial infections in febrile children.DesignProspective cohort study.SettingPaediatric emergency department.PatientsFebrile 0–5-year-olds who had a leukocyte count on presentation.Outcome measuresAccuracy of total white blood cell and absolute neutrophil counts for the detection of urinary tract infection, bacteraemia, pneumonia and a combined (‘any serious bacterial infection’) category. Logistic regression models were fitted for each outcome. Reference standards were microbiological/radiological tests and clinical follow-up.ResultsSerious bacterial infections were present in 714 (18.3%) of 3893 illness episodes. The area under the receiver operating characteristic curve for ‘any serious bacterial infection’ was 0.653 (95% CI 0.630 to 0.676) for the total white blood cell count and 0.638 (95% CI 0.615 to 0.662) for absolute neutrophil count. A white blood cell count threshold &gt;15×109/L had a sensitivity of 47% (95% CI 43% to 50%), specificity 76% (95% CI 74% to 77%), positive likelihood ratio 1.93 (95% CI 1.75 to 2.13) and negative likelihood ratio 0.70 (95% CI 0.65 to 0.75). An absolute neutrophil count threshold &gt;10×109/L had a sensitivity of 41% (95% CI 38% to 45%), specificity 78% (95% CI 76% to 79%), positive likelihood ratio 1.87 (95% CI 1.68 to 2.09) and negative likelihood ratio 0.75 (95% CI 0.71 to 0.80).ConclusionsThe total white blood cell count and absolute neutrophil count are not sufficiently accurate triage tests for febrile children with suspected serious bacterial infection.
Republished: Gastric neuroendocrine neoplasms and related precursor lesions
Authors: La Rosa Stefano , Vanoli Alessandro 
Published: March 2015

ABSTRACT
Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours showing different clinicopathological features and behaviour, implying a wide spectrum of therapeutic options. They are currently classified using the 2010 WHO classification of digestive neuroendocrine neoplasms into G1-neuroendocrine tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and dysplastic lesions, whose oncologic potential has not yet been completely elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on the proliferative status and clinicopathological background. The integration of both aspects in the diagnostic pathway may help to better classify tumours in different prognostic categories, especially when diagnosing them in small bioptic specimens. NECs are all poorly differentiated, highly aggressive carcinomas, while MANECs can show different morphological features that are directly associated with different prognoses. Precursor lesions of such carcinomas are not entirely understood. In this review, the clinicopathological features of gastric NENs and related precursor lesions will be described to give the reader a comprehensive overview on this topic.
Genetic Events That Limit the Efficacy of MEK and RTK Inhibitor Therapies in a Mouse Model of KRAS-Driven Pancreatic Cancer
Authors: Pettazzoni Piergiorgio , Viale Andrea , Shah Parantu , Carugo Alessandro , Ying Haoqiang , Wang Huamin , Genovese Giannicola , Seth Sahil , Minelli Rosalba , Green Tessa , Huang-Hobbs Emmet , Corti Denise , Sanchez Nora , Nezi Luigi , Marchesini Matteo , Kapoor Avnish , Yao Wantong , Francesco Maria E. Di , Petrocchi Alessia , Deem Angela K. , Scott Kenneth , Colla Simona , Mills Gordon B. , Fleming Jason B. , Heffernan Timothy P. , Jones Philip , Toniatti Carlo , DePinho Ronald A. , Draetta Giulio F. 
Published: March 2015

Abstract
Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model of KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition of MEK1 in tumor spheres and in vivo. KRAS* ablation blocked proliferation and induced apoptosis, whereas MEK1 inhibition exerted cytostatic effects. Proteomic analysis evidenced that MEK1 inhibition was accompanied by a sustained activation of the PI3K–AKT–MTOR pathway and by the activation of AXL, PDGFRa, and HER1–2 receptor tyrosine kinases (RTK) expressed in a large proportion of human PDAC samples analyzed. Although single inhibition of each RTK alone or plus MEK1 inhibitors was ineffective, a combination of inhibitors targeting all three coactivated RTKs and MEK1 was needed to inhibit proliferation and induce apoptosis in both mouse and human low-passage PDAC cultures. Importantly, constitutive AKT activation, which may mimic the fraction of AKT2-amplified PDAC, was able to bypass the induction of apoptosis caused by KRAS* ablation, highlighting a potential inherent resistance mechanism that may inform the clinical application of MEK inhibitor therapy. This study suggests that combinatorial-targeted therapies for pancreatic cancer must be informed by the activation state of each putative driver in a given treatment context. In addition, our work may offer explanative and predictive power in understanding why inhibitors of EGFR signaling fail in PDAC treatment and how drug resistance mechanisms may arise in strategies to directly target KRAS. Cancer Res; 75(6); 1091–101. ©2015 AACR.
Increased and Mistimed Sex Hormone Production in Night Shift Workers
Authors: Papantoniou Kyriaki , Pozo Oscar J. , Espinosa Ana , Marcos Josep , Castaño-Vinyals Gemma , Basagaña Xavier , Juanola Pagès Elena , Mirabent Joan , Martín Jordi , Such Faro Patricia , Gascó Aparici Amparo , Middleton Benita , Skene Debra J. , Kogevinas Manolis 
Published: March 2015

AbstractBackground: Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes.Methods: We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over 24 hours on a working day. Urinary concentrations of 16 sex steroid hormones and metabolites (estrogens, progestagens, and androgens) and 6-sulfatoxymelatonin were measured in all samples. Mean levels and peak time of total and individual metabolite production were compared between night and day workers.Results: Night workers had higher levels of total progestagens [geometric mean ratio (GMR) 1.65; 95% confidence intervals (CI), 1.17–2.32] and androgens (GMR: 1.44; 95% CI, 1.03–2.00), compared with day workers, after adjusting for potential confounders. The increased sex hormone levels among night shift workers were not related to the observed suppression of 6-sulfatoxymelatonin. Peak time of androgens was significantly later among night workers, compared with day workers (testosterone: 12:14 hours; 10:06-14:48 vs. 08:35 hours; 06:52-10:46).Conclusions: We found increased levels of progestagens and androgens as well as delayed peak androgen production in night shift workers compared with day workers.Impact: The increase and mistiming of sex hormone production may explain part of the increased risk for hormone-related cancers observed in night shift workers. Cancer Epidemiol Biomarkers Prev; 24(5); 854–63. ©2015 AACR.
High-Risk Human Papillomavirus (HPV) Infection and Cervical Cancer Prevention in Britain: Evidence of Differential Uptake of Interventions from a Probability Survey
Authors: Tanton Clare , Soldan Kate , Beddows Simon , Mercer Catherine H. , Waller Jo , Field Nigel , Clifton Soazig , Copas Andrew J. , Panwar Kavita , Manyenga Precious , da Silva Filomeno , Wellings Kaye , Ison Catherine A. , Johnson Anne M. , Sonnenberg Pam 
Published: March 2015

Abstract
Background: The third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) provides an opportunity to explore high-risk human papillomavirus (HR-HPV) and uptake of cervical screening and HPV vaccination in the general population.
Methods: Natsal-3, a probability sample survey of men and women ages 16 to 74, resident in Britain, interviewed 8,869 women in 2010 to 2012. We explored risk factors for HR-HPV (in urine from 2,569 sexually experienced women ages 16 to 44), nonattendance for cervical screening in the past 5 years, and noncompletion of HPV catch-up vaccination.
Results: HR-HPV was associated with increasing numbers of lifetime partners, younger age, increasing area-level deprivation, and smoking. Screening nonattendance was associated with younger and older age, increasing area-level deprivation (age-adjusted OR 1.91, 95% confidence interval, 1.48–2.47 for living in most vs. least deprived two quintiles), Asian/Asian British ethnicity (1.96, 1.32–2.90), smoking (1.97, 1.57–2.47), and reporting no partner in the past 5 years (2.45, 1.67–3.61 vs. 1 partner) but not with HR-HPV (1.35, 0.79–2.31). Lower uptake of HPV catch-up vaccination was associated with increasing area-level deprivation, non-white ethnicity, smoking, and increasing lifetime partners.
Conclusions: Socioeconomic markers and smoking were associated with HR-HPV positivity, nonattendance for cervical screening, and noncompletion of catch-up HPV vaccination.
Impact: The cervical screening program needs to engage those missing HPV catch-up vaccination to avoid a potential widening of cervical cancer disparities in these cohorts. As some screening nonattenders are at low risk for HR-HPV, tailored approaches may be appropriate to increase screening among higher-risk women. Cancer Epidemiol Biomarkers Prev; 24(5); 842–53. ©2015 AACR.
Intratumoral Heterogeneity in a Trp53-Null Mouse Model of Human Breast Cancer
Authors: Zhang Mei , Tsimelzon Anna , Chang Chi-Hsuan , Fan Cheng , Wolff Andrew , Perou Charles M. , Hilsenbeck Susan G. , Rosen Jeffrey M. 
Published: March 2015

Abstract
Intratumoral heterogeneity correlates with clinical outcome and reflects the cellular complexity and dynamics within a tumor. Such heterogeneity is thought to contribute to radio- and chemoresistance because many treatments may target only certain tumor cell subpopulations. A better understanding of the functional interactions between various subpopulations of cells, therefore, may help in the development of effective cancer treatments. We identified a unique subpopulation of tumor cells expressing mesenchymal-like markers in a Trp53-null mouse model of basal-like breast cancer using fluorescence-activated cell sorting and microarray analysis. Both in vitro and in vivo experiments revealed the existence of cross-talk between these “mesenchymal-like” cells and tumor-initiating cells. Knockdown of genes encoding ligands upregulated in the mesenchymal cells and their corresponding receptors in the tumor-initiating cells resulted in reduced tumorigenicity and increased tumor latency. These studies illustrate the non–cell-autonomous properties and importance of cooperativity between tumor subpopulations.
Significance: Intratumoral heterogeneity has been considered one important factor in assessing a patient's initial response to treatment and selecting drug regimens to effectively increase tumor response rate. Elucidating the functional interactions between various subpopulations of tumor cells will help provide important new insights in understanding treatment response and tumor progression. Cancer Discov; 5(5); 520–33. ©2015 AACR.
See related commentary by Brooks and Wicha, p. 469
This article is highlighted in the In This Issue feature, p. 453
The Killer Cell Ig-like Receptor 2DL4 Expression in Human Mast Cells and Its Potential Role in Breast Cancer Invasion
Authors: Ueshima Chiyuki , Kataoka Tatsuki R. , Hirata Masahiro , Furuhata Ayako , Suzuki Eiji , Toi Masakazu , Tsuruyama Tatsuaki , Okayama Yoshimichi , Haga Hironori 
Published: March 2015

AbstractThe killer-cell Ig-like receptor (KIR) 2DL4 (CD158d) acts as a receptor for human leukocyte antigen (HLA)-G and is expressed on almost all human natural killer (NK) cells. The expression and function of KIR2DL4 in other hematopoietic cells is poorly understood. Here, we focused on human mast cells, which exhibit cytotoxic activity similar to that of NK cells. KIR2DL4 was detected in all examined human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), the human mast cell line LAD2, and human nonneoplastic mast cells, including those on pathologic specimens. An agonistic antibody against KIR2DL4 decreased KIT-mediated and IgE-triggered responses, and enhanced the granzyme B production by PB-mast and LAD2 cells, by activating Src homology 2–containing protein tyrosine phosphatase (SHP-2). Next, we performed a coculture assay between LAD2 cells and the HLA-G+ cancer cells, MCF-7 and JEG-3, and showed that KIR2DL4 on LAD2 cells enhanced MMP-9 production and the invasive activity of both cell lines via HLA-G. Immunohistochemical analysis revealed that the direct interaction between HLA-G+ breast cancer cells and KIR2DL4+ tissue mast cells (observed in 12 of 36 cases; 33.3%) was statistically correlated with the presence of lymph node metastasis or lymph-vascular invasion (observed in 11 of 12 cases; 91.7%; χ2 = 7.439; P &lt; 0.01; degrees of freedom, 1) in the clinical samples. These findings suggest that the KIR2DL4 on human mast cells facilitates HLA-G–expressing cancer invasion and the subsequent metastasis. Cancer Immunol Res; 3(8); 871–80. ©2015 AACR.
Reporting and Replicating Trials of Exercise-Based Cardiac Rehabilitation
Authors: Abell Bridget , Glasziou Paul , Hoffmann Tammy 
Published: March 2015

Background—
Complete reporting of all components of complex interventions is essential for translation of research evidence into clinical practice. Previous work has highlighted deficiencies in the reporting of nonpharmacological interventions; however, the reporting quality of exercise-based interventions for coronary heart disease has not been examined.

Methods and Results—
A systematic search strategy was used to identify randomized controlled trials of exercise-based cardiac rehabilitation published until December 2013. Fifty-seven trials were included, reporting on 74 interventions. Intervention description completeness was assessed using the Template for Intervention Description and Replication checklist. Missing intervention details were then sought from additional published material and also by emailing corresponding authors. Only 6 interventions (8%) sufficiently described all required items within the main publication; this increased to 11 (15%) after searching for additional published material and 32 (43%) after contacting trial authors. Although location/setting and duration were consistently well reported in publications, complete descriptions of the exercise schedule, as well as details about its tailoring and progression, were missing for over half of interventions (complete for 42% and 36% of interventions, respectively). Although some authors (25/61) were able to provide missing intervention details when contacted, others could not be located (20) or did not respond (16).

Conclusions—
Inadequate reporting of cardiac rehabilitation interventions is a substantial problem, with essential information frequently missing, and for almost half of all interventions, unobtainable after publication. A conscientious effort to address this problem could facilitate an improvement in the quality of cardiac rehabilitation delivered in clinical practice.
In-Hospital Stroke Recurrence and Stroke After Transient Ischemic Attack
Authors: Erdur Hebun , Scheitz Jan F. , Ebinger Martin , Rocco Andrea , Grittner Ulrike , Meisel Andreas , Rothwell Peter M. , Endres Matthias , Nolte Christian H. 
Published: March 2015

Background and Purpose—
We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors.

Methods—
We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke.

Results—

The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4–8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%;
P
<0.001).

Conclusions—
In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms.
Global Supply Chain: A Conceptual Study of the Effect of Globalization on Product and Process Innovation
Authors: Skiver Ryan L. 
Published: March 2015

While successful performance in terms of cost savings for firms expanding beyond their home boundaries has been well noted in the literature. Other factors, such as product and process innovation gained through this global process, have not been well examined. The aim of this study is to answer four specific research questions: 1) What are the reasons for going global in today’s economy? 2) How can a global supply chain lead to increased innovation? 3) What are the specific ways that companies can gain product and process innovation in a global supply chain? 4) What is a model that can be examined for future research?This literature review examines areas of human resource management and supply chain management through the theory of absorptive capacity in a rapidly expanding global environment. In addressing the four main questions, this review will present emerging research issues for global supply chains.
Description of two new species of Neotanais Beddard, 1886 (Crustacea, Tanaidacea) from KODOS area
Authors: WI JIN HEE , SUH HAE LIP , YU OK HWAN 
Published: March 2015

Two new species of Neotanais Beddard, 1886 are described from the Korea Deep Ocean Study (KODOS) area in the Clarion–Clipperton Fracture Zone, based on the collections performed on board R/V Onnuri from a depth of 5180 m. Neotanais triqueturus n. sp. is similar to the ‘pfaffi group’ characterized by pereonites with a swollen distolateral margin, pleonites with mid-ventral spurs and tapered lateral margins but can be differentiated by a longer cephalothorax (length: width 1.6: 1), a cheliped with a large protrusion on the mid-dorsal margin of the fixed finger, and the presence of a ventral process on the cheliped carpus. Neotanais brevis n. sp. has the characteristics of the ‘micromopher’ group, with pleonites narrower than pereon, a cheliped carpus without a ventral process, and a uropod endopod with nine articles but can be differentiated by a combination of the pleonites without mid-ventral spurs, a relatively longer pleotelson (length: width 1: 1.5 vs. 1: 2), a uropod basis with one seta on each of the ventral and dorsal margins, and the cheliped fixed finger with proximal denticles. In this study, in order to prove N. triqueturus and N. brevis were new species, full descriptions and a comparison with the closely related species are given. In addition, comprehensive comparisons with the species of Neotanais from the east-central Pacific are tabulated and discussed.
Diagnosis and risk stratification in patients with anti-RNP autoimmunity
Authors: Carpintero M F , Martinez L , Fernandez I , Romero A C Garza , Mejia C , Zang Y J , Hoffman R W , Greidinger E L 
Published: March 2015

Introduction Anti-RNP autoantibodies occur either in mixed connective tissue disease (MCTD) (with a frequently favorable prognosis), or in systemic lupus erythematosus (SLE) cases with aggressive major organ disease. It is uncertain how to assess for the risk of severe disease in anti-RNP + patients. Methods Following institutional review board-approved protocols, clinical data and blood were collected from patients with known or suspected anti-RNP autoimmunity and normal controls in a cohort study. Samples were screened for parameters of immune activation. Groups were compared based on clinical diagnoses, disease classification criteria, disease activity and specific end-organ clinical manifestations. Results Ninety-seven per cent of patients satisfying Alarcon-Segovia MCTD criteria also met Systemic Lupus International Collaborating Clinic (SLICC) SLE criteria, while 47% of the anti-RNP + SLE patients also met MCTD criteria. Among SLICC SLE patients, MCTD criteria were associated with reduced rates of renal disease (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.3–14.0), increased rates of Raynaud's phenomenon (OR 3.5, 95% CI 1.3–9.5) and increased serum B-cell maturation antigen, transmembrane activator and CAML interactor and TNFα levels. Circulating immune markers and markers of type I interferon activation were not effective at distinguishing clinical subgroups. Conclusions Among anti-RNP patients, the question of MCTD versus SLE is not either/or: most MCTD patients also have lupus. MCTD classification criteria (but not a broad set of immune markers) distinguish a subset of SLE patients at reduced risk for renal disease.