bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trafficking of T Cells into Tumors
Authors: Slaney Clare Y. , Kershaw Michael H. , Darcy Phillip K. 
Published: December 2014

AbstractT cells are a crucial component of the immune response to infection and cancer. In addition to coordinating immunity in lymphoid tissue, T cells play a vital role at the disease site, which relies on their efficient and specific trafficking capabilities. The process of T-cell trafficking is highly dynamic, involving a series of distinct processes, which include rolling, adhesion, extravasation, and chemotaxis. Trafficking of T cells to the tumor microenvironment is critical for the success of cancer immunotherapies such as adoptive cellular transfer. Although this approach has achieved some remarkable responses in patients with advanced melanoma and hematologic malignancy, the success against solid cancers has been more moderate. One of the major challenges for adoptive immunotherapy is to be able to effectively target a higher frequency of T cells to the tumor microenvironment, overcoming hurdles associated with immunosuppression and aberrant vasculature. This review summarizes recent advances in our understanding of T-cell migration in solid cancer and immunotherapy based on the adoptive transfer of natural or genetically engineered tumor-specific T cells and discusses new strategies that may enhance the trafficking of these cells, leading to effective eradication of solid cancer and metastases. Cancer Res; 74(24); 7168–74. ©2014 AACR.
When Will Resistance Be Futile?
Authors: Borden Katherine L.B. 
Published: December 2014

Abstract
Cancer cells rapidly evolve a multitude of defense mechanisms to evade the effects of the oncologist's drug arsenal. Unfortunately, clinical strategies to overcome these lag far behind. This mismatch likely underlies our inability to implement new durable treatment strategies. Here, a new form of multidrug resistance, inducible drug glucuronidation, is discussed. This form was discovered while developing means to target a specific oncogene, the eukaryotic translation initiation factor 4E (eIF4E), with its inhibitor ribavirin. In two clinical studies, ribavirin treatment led to substantial clinical responses, but all responding patients eventually relapsed. In most cases, this was due to the overexpression of the sonic hedgehog transcription factor Gli1, which elevated the UDP glucuronsyltransferase UGT1A enzymes. UGT1As add glucuronic acid to many drugs. Indeed, these cells are resistant to not only ribavirin, but also Ara-C, and likely other drugs. Inhibition of Gli1 reduced UGT1As, eliminated drug glucuronides, and renewed sensitivity to ribavirin and Ara-C. These studies highlight that cancer cells and their resistant counterparts metabolize drugs differently from each other as well as from normal cells. Likely, these inducible modifications go beyond glucuronidation. Understanding the extent of inducible drug modifications and the pathways that drive expression of the corresponding enzymatic machinery will better position us to finally make resistance futile. Cancer Res; 74(24); 7175–80. ©2014 AACR.
Putative Linkage Signals Identified for Breast Cancer in African American Families
Authors: Ochs-Balcom Heather M. , Sun Xiangqing , Chen Yanwen , Barnholtz-Sloan Jill , Erwin Deborah O. , Jandorf Lina , Sucheston-Campbell Lara , Elston Robert C. 
Published: December 2014

Abstract
Background: Genome-wide association studies have identified polymorphisms associated with breast cancer subtypes and across multiple population subgroups; however, few studies to date have applied linkage analysis to other population groups.
Methods: We performed the first genome-wide breast cancer linkage analysis in 106 African American families (comprising 179 affected and 79 unaffected members) not known to be segregating BRCA mutations to search for novel breast cancer loci. We performed regression-based model-free multipoint linkage analyses of the sibling pairs using SIBPAL, and two-level Haseman–Elston linkage analyses of affected relative pairs using RELPAL.
Results: We identified −log10 P values that exceed 4 on chromosomes 3q and 12q, as well as a region near BRCA1 on chromosome 17 (−log10 P values in the range of 3.0–3.2) using both sibling-based and relative-based methods; the latter observation may suggest that undetected BRCA1 mutations or other mutations nearby such as HOXB13 may be segregating in our sample.
Conclusions: In summary, these results suggest novel putative regions harboring risk alleles in African Americans that deserve further study.
Impact: We hope that our study will spur further family-based investigation into specific mechanisms for breast cancer disparities. Cancer Epidemiol Biomarkers Prev; 24(2); 442–7. ©2014 AACR.
Molecular Pathways: Cbl Proteins in Tumorigenesis and Antitumor Immunity—Opportunities for Cancer Treatment
Authors: Liyasova Mariya S. , Ma Ke , Lipkowitz Stanley 
Published: December 2014

AbstractThe Cbl proteins are a family of ubiquitin ligases (E3s) that regulate signaling through many tyrosine kinase–dependent pathways. A predominant function is to negatively regulate receptor tyrosine kinase (RTK) signaling by ubiquitination of active RTKs, targeting them for trafficking to the lysosome for degradation. Also, Cbl-mediated ubiquitination can regulate signaling protein function by altered cellular localization of proteins without degradation. In addition to their role as E3s, Cbl proteins play a positive role in signaling by acting as adaptor proteins that can recruit signaling molecules to the active RTKs. Cbl-b, a second family member, negatively regulates the costimulatory pathway of CD8 T cells and also negatively regulates natural killer cell function. The different functions of Cbl proteins and their roles both in the development of cancer and the regulation of immune responses provide multiple therapeutic opportunities. Mutations in Cbl that inactivate the negative E3 function while maintaining the positive adaptor function have been described in approximately 5% of myeloid neoplasms. An improved understanding of how the signaling pathways [e.g., Fms-like tyrosine kinase 3 (Flt3), PI3K, and signal transducer and activator of transcription (Stat)] are dysregulated by these mutations in Cbl has helped to identify potential targets for therapy of myeloid neoplasms. Conversely, the loss of Cbl-b leads to increased adaptive and innate antitumor immunity, suggesting that inhibiting Cbl-b may be a means to increase antitumor immunity across a wide variety of tumors. Thus, targeting the pathways regulated by Cbl proteins may provide attractive opportunities for treating cancer. Clin Cancer Res; 21(8); 1789–94. ©2014 AACR.
Optimizing the Sequence of Anti-EGFR–Targeted Therapy in EGFR-Mutant Lung Cancer
Authors: Meador Catherine B. , Jin Hailing , de Stanchina Elisa , Nebhan Caroline A. , Pirazzoli Valentina , Wang Lu , Lu Pengcheng , Vuong Huy , Hutchinson Katherine E. , Jia Peilin , Chen Xi , Eisenberg Rosana , Ladanyi Marc , Politi Katerina , Zhao Zhongming , Lovly Christine M. , Cross Darren A.E. , Pao William 
Published: December 2014

Abstract
Metastatic EGFR-mutant lung cancers are sensitive to the first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib, and afatinib, but resistance develops. Acquired resistance to gefitinib or erlotinib occurs most commonly (&gt;50%) via the emergence of a second-site EGFR mutation, T790M. Two strategies to overcome T790M-mediated resistance are dual inhibition of EGFR with afatinib plus the anti-EGFR antibody cetuximab (A+C), or mutant-specific EGFR inhibition with AZD9291. A+C and AZD9291 are now also being tested as first-line therapies, but whether these therapies will extend progression-free survival or induce more aggressive forms of resistance in this setting remains unknown. We modeled resistance to multiple generations of anti-EGFR therapies preclinically to understand the effects of sequential treatment with anti-EGFR agents on drug resistance and determine the optimal order of treatment. Using a panel of erlotinib/afatinib-resistant cells, including a novel patient-derived cell line (VP-2), we found that AZD9291 was more potent than A+C at inhibiting cell growth and EGFR signaling in this setting. Four of four xenograft-derived A+C-resistant cell lines displayed in vitro and in vivo sensitivity to AZD9291, but four of four AZD9291-resistant cell lines demonstrated cross-resistance to A+C. Addition of cetuximab to AZD9291 did not confer additive benefit in any preclinical disease setting. This work, emphasizing a mechanistic understanding of the effects of therapies on tumor evolution, provides a framework for future clinical trials testing different treatment sequences. This paradigm is applicable to other tumor types in which multiple generations of inhibitors are now available. Mol Cancer Ther; 14(2); 542–52. ©2014 AACR.
Cell-free Tumor Microparticle Vaccines Stimulate Dendritic Cells via cGAS/STING Signaling
Authors: Zhang Huafeng , Tang Ke , Zhang Yi , Ma Ruihua , Ma Jingwei , Li Yong , Luo Shunqun , Liang Xiaoyu , Ji Tiantian , Gu Zhichao , Lu Jinzhi , He Wei , Cao Xuetao , Wan Yonghong , Huang Bo 
Published: December 2014

Abstract
Tumor antigens and innate signals are vital considerations in developing new therapeutic or prophylactic antitumor vaccines. The role or requirement of intact tumor cells in the development of an effective tumor vaccine remains incompletely understood. This study reveals the mechanism by which tumor cell–derived microparticles (T-MP) can act as a cell-free tumor vaccine. Vaccinations with T-MPs give rise to prophylactic effects against the challenge of various tumor cell types, while T-MP–loaded dendritic cells (DC) also exhibit therapeutic effects in various tumor models. Such antitumor effects of T-MPs are perhaps attributable to their ability to generate immune signaling and to represent tumor antigens. Mechanically, T-MPs effectively transfer DNA fragments to DCs, leading to type I IFN production through the cGAS/STING-mediated DNA-sensing pathway. In turn, type I IFN promotes DC maturation and presentation of tumor antigens to T cells for antitumor immunity. These findings highlight a novel tumor cell-free vaccine strategy with potential clinical applications. Cancer Immunol Res; 3(2); 196–205. ©2014 AACR.
Use of Lipoprotein Particle Measures for Assessing Coronary Heart Disease Risk Post-American Heart Association/American College of Cardiology Guidelines
Authors: Steffen Brian T. , Guan Weihua , Remaley Alan T. , Paramsothy Pathmaja , Heckbert Susan R. , McClelland Robyn L. , Greenland Philip , Michos Erin D. , Tsai Michael Y. 
Published: December 2014

Objective—
The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants.

Approach and Results—

Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25–2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32–2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21–2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54–3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18;
P
=0.007) and LDL-P/high-density lipoprotein-P (0.15;
P
<0.001).
C
-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure.

Conclusions—

Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding
c
-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out.
Practices of ambiguity: Becoming “information literate” in two Norwegian schools
Authors: Søvik Margrethe B. 
Published: December 2014

The purpose of this study is to examine the establishment of information literacy (IL) practices among secondary school pupils aged 14 to16 (grades 9-10) in two Norwegian schools. In Norway, a new curriculum introduced in 2006 emphasised digital skills, aiming to develop IL relating to digital texts in particular. Despite the fact that an ambitious national curriculum has been in place for quite some time, not much is known about how this works in practice in the subject group of this study. The main purpose of this article is to identify the kind of IL practices that have been established and how the pupils experience and reproduce these practices.
It seems that the pupils become information literate but not to the extent the curriculum anticipates. The study used mixed methods in order to reveal general trends and to explore certain issues in more depth. The material consists of data from a questionnaire and interviews. The study has a sociocultural perspective as its theoretical point of departure, resting on an understanding of how IL practices in school are formed through interaction and/or the lack of interaction between pupils and their teachers. Without interaction guiding the pupils, their IL practices are at the risk of becoming practices of ambiguity. The implications of this study is that one must go beyond national curricula and examine the way IL or digital literacy is actually performed in schools in order to understand how these practices are shaped.
Laubieriopsis petersenae n. sp. and L. cf. cabiochi (Amoureux, 1982) (Polychaeta: Fauveliopsidae) from dredge disposal sites off Honolulu, Hawaii
Authors: MAGALHÃES WAGNER F. , BAILEY-BROCK JULIE H. , RIZZO ALEXANDRA E. 
Published: December 2014

Fauveliopsid polychaetes have been collected at dredge disposal sites off Honolulu from 397–507 m depth. We report and describe the first Pacific record of Laubieriopsis cf. cabiochi (Amoureux, 1982), originally described from the North Atlantic. A new species, Laubieriopsis petersenae, n. sp. is described as being the species in the genus with the lowest number of body segments (15). Other distinctive features are the presence of bidentate aciculars on thoracic chaetigers, and unpaired genital papilla present on the right side of chaetiger 6/7. The new species is most similar to the L. brevis complex from the Atlantic and L. hartmanae and L. brevis japonica from the Pacific Ocean, but differs on the combination of the characters cited above. We provide an emended diagnosis for this genus to include the ultrastructure of the acicular with rows of spines, and a key to all described species.
Predicting Critical Transitions in ENSO models. Part II: Spatially Dependent Models
Authors: Mukhin Dmitry , Kondrashov Dmitri , Loskutov Evgeny , Gavrilov Andrey , Feigin Alexander , Ghil Michael 
Published: December 2014

Abstract
The present paper is the second part of a two-part study on empirical modeling and prediction of climate variability. This paper deals with spatially distributed data, as opposed to the univariate data of Part I. The choice of a basis for effective data compression becomes of the essence. In many applications, it is the set of spatial empirical orthogonal functions that provides the uncorrelated time series of principal components (PCs) used in the learning set. In this paper, the basis of the learning set is obtained instead by applying multichannel singular-spectrum analysis to climatic time series and using the leading spatiotemporal PCs to construct a reduced stochastic model. The effectiveness of this approach is illustrated by predicting the behavior of the Jin–Neelin–Ghil (JNG) hybrid seasonally forced coupled ocean–atmosphere model of El Niño–Southern Oscillation. The JNG model produces spatially distributed and weakly nonstationary time series to which the model reduction and prediction methodology is applied. Critical transitions in the hybrid periodically forced coupled model are successfully predicted on time scales that are substantially longer than the duration of the learning sample.
Do Immediate Cytology and Specialist Radiologists Improve the Adequacy of Ultrasound‐Guided Fine‐Needle Aspiration Cytology?
Authors: Sharma Sunil Dutt , Kumar Gaurav , Horsburgh Avril , Huq Mahmuda , Alkilani Raed , Chawda Sanjiv , Kaddour Hesham 
Published: December 2014

ObjectiveTo assess whether a dedicated “1‐stop” neck lump clinic has improved the percentage of adequate fine‐needle aspiration cytology (FNAC) samples and reduced the need for repeat FNAC.Study DesignRetrospective review.SettingDistrict General Hospital in the United Kingdom.Subjects and MethodsPatients attending for ultrasound‐guided FNAC over a 6‐month period from August 2012 to February 2013. Patients were placed in 4 groups: group 1, FNAC performed by any of the subspecialist radiologists with cytology support (n = 100); group 2, FNAC performed by general radiologists without cytology support (n = 112); group 3, FNAC performed by a particular subspecialist radiologist with cytology support (n = 61); and group 4, FNAC performed by the same subspecialist radiologist without cytology support (n = 125).ResultsThere was a significantly higher rate of adequacy of FNAC in the presence of a subspecialist radiologist with immediate cytology (group 1) versus a general radiologist without cytology support (group 2; 87/100 vs 63/112, P =. 0001), a significantly higher rate of adequacy of FNAC in the presence of cytology support with the same radiologist (group 3 vs group 4, 55/61 vs 97/125, P =. 04), and a significantly higher rate of adequacy of FNAC in the presence of a subspecialist radiologist versus a general radiologist without cytology support (group 4 vs group 2, 97/125 vs 63/112, P =. 0005).ConclusionImmediate cytology and the presence of a subspecialist radiologist increase the adequacy of FNAC. The adequacy rate of non–cytology‐supported FNAC or nonsubspecialist FNAC is below the adequate rate expected from the literature or as recommended in national guidelines.
Severe Vitamin D Deficiency
Authors: Al‐Khatib Talal , Althubaiti Abdulrahman M. , Althubaiti Alaa , Mosli Hala H. , Alwasiah Reem O. , Badawood Lojain M. 
Published: December 2014

ObjectiveTo assess the role of preoperative serum 25 hydroxyvitamin D as predictor of hypocalcemia after total thyroidectomy.Study DesignRetrospective cohort study.SettingUniversity teaching hospital.Subjects and MethodsAll consecutively performed total and completion thyroidectomies from February 2007 to December 2013 were reviewed through a hospital database and patient charts. The relationship between postthyroidectomy laboratory hypocalcemia (serum calcium ≤2 mmol/L), clinical hypocalcemia, and preoperative serum 25 hydroxyvitamin D level was evaluated.ResultsTwo hundred thirteen patients were analyzed. The incidence of postoperative laboratory and clinical hypocalcemia was 19.7% and 17.8%, respectively. The incidence of laboratory and clinical hypocalcemia among severely deficient (<25 nmol/L), deficient (<50 nmol/L), insufficient (<75 nmol/L), and sufficient (≥75 nmol/L) serum 25 hydroxyvitamin D levels was 54% versus 33.9%, 10% versus 18%, 2.9% versus 11.6%, and 3.1% versus 0%, respectively. Multiple logistic regression analysis revealed preoperative severe vitamin D deficiency as a significant independent predictor of postoperative hypocalcemia (odds ratio [OR], 7.3; 95% confidence interval [CI], 2.3‐22.9; P =. 001). Parathyroid hormone level was also found to be an independent predictor of postoperative hypocalcemia (OR, 0.6; 95% CI, 0.5‐0.8; P =. 002).ConclusionPostoperative clinical and laboratory hypocalcemia is significantly associated with low levels of serum 25 hydroxyvitamin D. Our findings identify severe vitamin D deficiency (<25 nmol/L) as an independent predictor of postoperative laboratory hypocalcemia. Early identification and management of patients at risk may reduce morbidity and costs.
It’s agony for us as well
Authors: Green Janet , Darbyshire Philip , Adams Anne , Jackson Debra 
Published: December 2014

Background: Improved techniques and life sustaining technology in the neonatal intensive care unit have resulted in an increased probability of survival for extremely premature babies. The by-product of the aggressive treatment is iatrogenic pain, and this infliction of pain can be a cause of suffering and distress for both baby and nurse. Research question: The research sought to explore the caregiving dilemmas of neonatal nurses when caring for extremely premature babies. This article aims to explore the issues arising for neonatal nurses when they inflict iatrogenic pain on the most vulnerable of human beings – babies ≤24 weeks gestation. Participants: Data were collected via a questionnaire to Australian neonatal nurses and semi-structured interviews with 24 neonatal nurses in New South Wales, Australia. Ethical consideration: Ethical processes and procedures set out by the ethics committee have been adhered to by the researchers. Findings: A qualitative approach was used to analyse the data. The theme ‘inflicting pain’ comprised three sub-themes: ‘when caring and torture are the same thing’, ‘why are we doing this!’ and ‘comfort for baby and nurse’. The results show that the neonatal nurses were passionate about the need for appropriate pain relief for extremely premature babies. Conclusion: The neonatal nurses experienced a profound sense of distress manifested as existential suffering when they inflicted pain on extremely premature babies. Inflicting pain rather than relieving it can leave the nurses questioning their role as compassionate healthcare professionals.
The Use of Research Syntheses and Nomological Networks to Develop HRD Theory
Authors: Newman Isadore , Hitchcock John H. , Newman David 
Published: December 2014

The Problem Research syntheses are rarely used in the field of human resource development (HRD). There are notable exceptions, but our search of the related literature found relatively few instances where procedures like meta-analyses are used to advance theory and empirically informed practice. The Solution To address this gap, this article provides a broad overview of different techniques for synthesizing literature. The article describes how research syntheses can be used to inform theory development; this is done via the description of a construct called nomological network. Such a network can be thought of as kind of minitheory, which is derived from the theoretical relationships among key constructs. The Stakeholders Readers interested in developing empirically informed HRD theory and practice should benefit from a description of how research syntheses can inform their work.