bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflectance confocal microscopy for the noninvasive diagnosis of cutaneous juvenile xanthogranuloma
Authors: Pimenta R. , Leal‐Filipe P. , Oliveira A. 
Published: July 2018

AbstractJuvenile xanthogranuloma is the most common type of non‐Langerhans cell histiocytosis. It appears primarily in infancy, where its differential diagnosis includes Spitz nevus, dermal nevus and molluscum contagiosum. We report the case of a 2‐year‐old boy with juvenile xanthogranuloma, as diagnosed using real‐time, in vivo reflectance confocal microscopy.
U.S. Citizens’ Current Attitudes Toward Immigrants and Immigration: A Study From the General Social Survey*
Authors: Pryce Daniel K. 
Published: July 2018

ObjectiveThis study tests U.S. citizens’ attitudes toward immigrants and immigration. Immigrants and immigration educe strong, divergent sentiments in the U.S. population. While these sentiments, which are tied to public policy, have been examined in prior studies, it is important to test them regularly in empirical studies to observe any changes in attitudes toward immigrants and immigration.MethodsI rely on the 2014 General Social Survey and employ hierarchical multivariate regression models to test the effects of patriotism, nationalism, xenophobia, and “world citizenship” on pro‐immigration attitudes.ResultsFemales, respondents with higher education, and respondents who were more patriotic were more likely to hold pro‐immigration attitudes. Conversely, older respondents and respondents who held greater xenophobic attitudes were less likely to hold pro‐immigration attitudes. Finally, respondents who viewed themselves more as citizens of the world than citizens of a particular country were more likely to hold pro‐immigration attitudes.ConclusionThe study's results are generally consistent with findings from prior research, and point to a general invariability in Americans’ views about immigrants and immigration. The policy implications of the findings are discussed.
Introducing V&V&C in Nuclear Thermal-Hydraulics
Authors: D’Auria Francesco , Lanfredini Marco 
Published: July 2018

V&V constitutes a powerful framework to demonstrate the capability of computational tools in several technological areas. Passing V&V requirements is a needed step before applications. Let’s focus hereafter to the area of (transient) Nuclear Thermal-hydraulic (NTH) and let’s identify V1 and V2 as acronyms for Verification and Validation, respectively.
Now, V1 is performed within NTH according to the best available techniques and may not suffer of important deficiencies if compared with other technological areas. This is not the case of V2. Three inherent limitations shall be mentioned in the case of Validation in NTH:
1. Validation implies comparison with experimental data: available experimental data cover a (very) small fraction of the parameter range space expected in applications of the codes; this can be easily seen if one considers data in large diameter pipe, high velocity and high pressure or high power and power density. Noticeably, the scaling issue must be addressed in the framework of V2 which may result in controversial findings.
2. Water is at the center of the attention: the physical properties of water are known to a reasonable extent as well as large variations in values of quantities like density or various derivatives are expected within the range of variation of pressure inside application fields. Although not needed for current validation purposes (e.g. validation ranges may not include a situation of critical pressure and large heat flux) physically inconsistent values predicted by empirical correlations outside validation ranges, shall not be tolerated.
3. Occurrence of complex situations like transition from two-phase critical flow to ‘Bernoulli-flow’ (e.g. towards the end of blow-down) and from film boiling to nucleate boiling, possibly crossing the minimum film boiling temperature (e.g. during reflood).
Therefore, whatever can be mentioned as classical V2 is not or cannot be performed in NTH. So, the idea of the present paper is to add a component to the V&V. This component, or step in the process, is called ‘Consistency with Reality’, or with the expected phenomenological evidence. The new component may need to be characterized in some cases and is indicated by the letter ‘C’. Then, the V&V becomes V&V&C.
The purpose of the paper is to clarify the motivations at the bases of the V&V&C.
Predictive tool for intravenous immunoglobulin resistance of Kawasaki disease in Beijing
Authors: Yang Shuai , Song Ruixia , Zhang Junmei , Li Xiaohui , Li Caifeng 
Published: July 2018

ObjectiveTo construct a predictive tool for the efficacy of intravenous immunoglobulin (IVIG) therapy in children with Kawasaki disease (KD) in Beijing, China.DesignThis was a cohort study. Data set (including clinical profiles and laboratory findings) of children with KD diagnosed between 1 January 2010 and 31 December 2015 was used to analyse the risk factors and construct a scoring system. Data set of children with KD diagnosed between 1 January 2016 and 1 December 2016 was used to validate this model.SettingChildren’s Hospital Capital Institute of Pediatrics and Beijing Children’s Hospital.Patients2102 children diagnosed with KD.InterventionsNo.Main outcome measuresResponsiveness to IVIG.ResultsThe predictive tool included C reactive protein ≥90 mg/L (3 points), neutrophil percentage ≥70% (2.5 points), sodium ion concentration <135 mmol/L (3 points), albumin <35 g/L (2.5 points) and total bilirubin >20 μmol/L (5 points), which generated an area under the the receiver operating characteristic curve of 0.77 (95% CI 0.71 to 0.82) for the internal validation data set, and 0.69 (95% CI 0.58 to 0.81) and 0.63 (95% CI 0.53 to 0.72) for two external validation data sets, respectively. If a total of ≥6 points were considered high-risk for IVIG resistance, sensitivity and specificity were 56% and 79% in the internal verification, and the predictive ability was similar in the external validation.ConclusionsThe predictive tool is helpful in early screening of high-risk IVIG resistance of KD in the Beijing area. Consequently, it will guide the clinician in selecting appropriate individualised regimens for the initial treatment of this disease, which is important for the prevention of coronary complications.
Drug monitoring in long-term treatment with adalimumab for juvenile idiopathic arthritis-associated uveitis
Authors: Skrabl-Baumgartner Andrea , Seidel Gerald , Langner-Wegscheider Beate , Schlagenhauf Axel , Jahnel Jörg 
Published: July 2018

ObjectivesAssessing influence of anti-adalimumab (ADA) antibodies (AAA) on serum trough ADA levels and uveitis activity in long-term ADA treatment of juvenile idiopathic arthritis (JIA)-associated uveitis.Patients and interventionsThis prospective observational study included 20 patients from a single centre treated with ADA for active uveitis refractory to conventional disease-modifying antirheumatic drugs. AAA, serum ADA trough levels and uveitis activity were evaluated at regular intervals up to 6 years.ResultsAAA were detected in nine patients (45%). Permanent AAA in seven were associated with undetectable ADA trough levels and loss of response (LOR). Transient AAA were detected in four with measurable ADA trough levels and response of uveitis to treatment, followed in two by permanent AAA associated with LOR. Use of concomitant immunosuppression was significantly higher in patients without AAA (p<0.05).ConclusionsAAA-associated LOR frequently occurs in long-term treatment with ADA for JIA-associated uveitis. Concomitant immunosuppressive therapy significantly reduces the risk of LOR due to AAA.
Managing accidental hypothermia: a UK-wide survey of prehospital and search and rescue providers
Authors: Freeman Samuel , Deakin Charles D , Nelson Magnus J , Bootland Duncan 
Published: July 2018

AimThe management of hypothermic casualties is a challenge faced by all prehospital and search and rescue (SAR) teams. It is not known how the practice of these diverse teams compare. The aim of this study was to review prehospital hypothermia management across a wide range of SAR providers in the UK.MethodsA survey of ground ambulances (GAs), air ambulances (AAs), mountain rescue teams (MRTs, including Ministry of Defence), lowland rescue teams (LRTs), cave rescue teams (CRTs), and lifeboats and lifeguard organisations (LLOs) across the UK was conducted between May and November 2017. In total, 189 teams were contacted. Questions investigated packaging methods, temperature measurement and protocols for managing hypothermic casualties.ResultsResponse rate was 59%, comprising 112 teams from a wide range of organisations. Heavyweight (>3 kg) casualty bags were used by all CRTs, 81% of MRTs, 29% of LRTs, 18% of AAs and 8% of LLOs. Specially designed lightweight (<0.5 kg) blankets or wraps were used by 93% of LRTs, 85% of LLOs, 82% of GAs, 71% of AAs and 50% of MRTs. Bubble wrap was used mainly by AAs, with 35% of AAs reporting its use. Overall, 94% of packaging methods incorporated both insulating and vapour-tight layers. Active warming by heated pads or blankets was used by 65% of AAs, 60% of CRTs, 54% of MRTs, 29% of LRTs and 9% of GAs, with no LLO use. Temperature measurement was reported by all AAs and GAs, 93% of LRTs, 80% of CRTs, 75% of MRTs and 31% of LLOs. The favoured anatomical site for temperature measurement was tympanic. Protocols for packaging hypothermic casualties were reported by 73% of services.ConclusionsThis survey describes current practice in prehospital hypothermia management, comparing the various methods used by different teams, and provides a basis to direct further education and research.
Reciprocal relations between care-related emotional burden and sleep problems in healthcare professionals: a multicentre international cohort study
Authors: Cheval Boris , Mongin Denis , Cullati Stéphane , Winz Carole , von Arx Martina , Schmidt Ralph Erich , Agoritsas Thomas , Chopard Pierre , Courvoisier Delphine Sophie 
Published: July 2018

ObjectiveTo determine whether there are reciprocal relations between care-related regret and insomnia severity among healthcare professionals, and whether the use of different coping strategies influences these associations.MethodsThis is a multicentre international cohort study of 151 healthcare professionals working in acute care hospitals and clinics (87.4% female; mean age=30.4±8.0 years, 27.2% physicians, 48.3% nurses and 24.5% other professions) between 2014 and 2017. Weekly measures of regret intensity, number of regrets, and use of coping strategies (Regret Coping Scale) and sleep problems (Insomnia Severity Index) were assessed using a web survey.ResultsThe associations between regret and insomnia severity were bidirectional. In a given week, regret intensity (bregret intensity→sleep=0.26, 95% credible interval (CI) (0.14 to 0.40)) and number of regrets (bnumber of regrets→sleep=0.43, 95% CI (0.07 to 0.53)) were significantly associated with increased insomnia severity the following week. Conversely, insomnia severity in a given week was significantly associated with higher regret intensity (bsleep→regret intensity=0.14, 95% CI (0.11 to 0.30)) and more regrets (bsleep→number of regrets=0.04, 95% CI (0.02 to 0.06)) the week after. The effects of regret on insomnia severity were much stronger than those in the opposite direction. The use of coping strategies, especially if they were maladaptive, modified the strength of these cross-lagged associations.ConclusionsThe present study showed that care-related regret and sleep problems are closely intertwined among healthcare professionals. Given the high prevalence of these issues, our findings call for the implementation of interventions that are specifically designed to help healthcare professionals to reduce their use of maladaptive coping strategies.
Effects of threshold energy on reconstructions of properties of low-mass WIMPs in direct dark matter detection experiments
Authors: Bai Yu , Sun Weichao , Shan Chung-Lin 
Published: July 2018

In this paper, we revisit our model-independent methods developed for reconstructing properties of Weakly Interacting Massive Particles (WIMPs) by using measured recoil energies from direct Dark Matter detection experiments directly and take into account more realistically non-negligible threshold energy. All expressions for reconstructing the mass and the (ratios between the) spin-independent and the spin-dependent WIMP–nucleon couplings have been modified. We focus on low-mass ([Formula: see text] GeV) WIMPs and present the numerical results obtained by Monte Carlo simulations. Constraints caused by non-negligible threshold energy and technical treatments for improving reconstruction results will also be discussed.
Oncogenic BRAFV600E Governs Regulatory T-cell Recruitment during Melanoma Tumorigenesis
Authors: Shabaneh Tamer B. , Molodtsov Aleksey K. , Steinberg Shannon M. , Zhang Peisheng , Torres Gretel M. , Mohamed Gadisti A. , Boni Andrea , Curiel Tyler J. , Angeles Christina V. , Turk Mary Jo 
Published: July 2018

AbstractRegulatory T cells (Treg) are critical mediators of immunosuppression in established tumors, although little is known about their role in restraining immunosurveillance during tumorigenesis. Here, we employ an inducible autochthonous model of melanoma to investigate the earliest Treg and CD8 effector T-cell responses during oncogene-driven tumorigenesis. Induction of oncogenic BRAFV600E and loss of Pten in melanocytes led to localized accumulation of FoxP3+ Tregs, but not CD8 T cells, within 1 week of detectable increases in melanocyte differentiation antigen expression. Melanoma tumorigenesis elicited early expansion of shared tumor/self-antigen–specific, thymically derived Tregs in draining lymph nodes, and induced their subsequent recruitment to sites of tumorigenesis in the skin. Lymph node egress of tumor-activated Tregs was required for their C-C chemokine receptor 4 (Ccr4)–dependent homing to nascent tumor sites. Notably, BRAFV600E signaling controlled expression of Ccr4-cognate chemokines and governed recruitment of Tregs to tumor-induced skin sites. BRAFV600E expression alone in melanocytes resulted in nevus formation and associated Treg recruitment, indicating that BRAFV600E signaling is sufficient to recruit Tregs. Treg depletion liberated immunosurveillance, evidenced by CD8 T-cell responses against the tumor/self-antigen gp100, which was concurrent with the formation of microscopic neoplasia. These studies establish a novel role for BRAFV600E as a tumor cell–intrinsic mediator of immune evasion and underscore the critical early role of Treg-mediated suppression during autochthonous tumorigenesis.Significance: This work provides new insights into the mechanisms by which oncogenic pathways impact immune regulation in the nascent tumor microenvironment. Cancer Res; 78(17); 5038–49. ©2018 AACR.
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Lopez Sambrooks Cecilia , Baro Marta , Quijano Amanda , Narayan Azeet , Cui Wei , Greninger Patricia , Egan Regina , Patel Abhijit , Benes Cyril H. , Saltzman W. Mark , Contessa Joseph N. 
Published: July 2018

Abstract
Asparagine (N)-linked glycosylation is a posttranslational modification essential for the function of complex transmembrane proteins. However, targeting glycosylation for cancer therapy has not been feasible due to generalized effects on all glycoproteins. Here, we perform sensitivity screening of 94 lung cancer cell lines using NGI-1, a small-molecule inhibitor of the oligosaccharyltransferase (OST) that partially disrupts N-linked glycosylation, and demonstrate a selective loss of tumor cell viability. This screen revealed NGI-1 sensitivity in just 11 of 94 (12%) cell lines, with a significant correlation between OST and EGFR inhibitors. In EGFR-mutant non-small cell lung cancer with EGFR tyrosine kinase inhibitor (TKI) resistance (PC9-GR, HCC827-GR, and H1975-OR), OST inhibition maintained its ability to induce cell-cycle arrest and a proliferative block. Addition of NGI-1 to EGFR TKI treatment was synthetic lethal in cells resistant to gefitinib, erlotinib, or osimertinib. OST inhibition invariably disrupted EGFR N-linked glycosylation and reduced activation of receptors either with or without the T790M TKI resistance mutation. OST inhibition also dissociated EGFR signaling from other coexpressed receptors like MET via altered receptor compartmentalization. Translation of this approach to preclinical models was accomplished through synthesis and delivery of NGI-1 nanoparticles, confirmation of in vivo activity through molecular imaging, and demonstration of significant tumor growth delay in TKI-resistant HCC827 and H1975 xenografts. This therapeutic strategy breaks from kinase-targeted approaches and validates N-linked glycosylation as an effective target in tumors driven by glycoprotein signaling.
Significance: EGFR-mutant NSCLC is incurable despite the marked sensitivity of these tumors to EGFR TKIs. These findings identify N-linked glycosylation, a posttranslational modification common to EGFR and other oncogenic signaling proteins, as an effective therapeutic target that enhances tumor responses for EGFR-mutant NSCLC. Cancer Res; 78(17); 5094–106. ©2018 AACR.
Matrix Stiffening and EGFR Cooperate to Promote the Collective Invasion of Cancer Cells
Authors: Grasset Eloise M. , Bertero Thomas , Bozec Alexandre , Friard Jonas , Bourget Isabelle , Pisano Sabrina , Lecacheur Margaux , Maiel Majdi , Bailleux Caroline , Emelyanov Alexander , Ilie Marius , Hofman Paul , Meneguzzi Guerrino , Duranton Christophe , Bulavin Dmitry V. , Gaggioli Cedric 
Published: July 2018

Abstract
In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca2+) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca2+ through CaV1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche.
Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg. Cancer Res; 78(18); 5229–42. ©2018 AACR.
Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer
Authors: Villarreal Daniel O. , L'Huillier Andrew , Armington Susan , Mottershead Cristina , Filippova Elena V. , Coder Brandon D. , Petit Robert G. , Princiotta Michael F. 
Published: July 2018

AbstractCCR8 is a chemokine receptor expressed principally on regulatory T cells (Treg) and is known to be critical for CCR8+ Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of patients with breast, colon, and lung cancer when compared with normal tissue-resident Tregs. Therefore, CCR8+ tumor-resident Tregs are rational targets for cancer immunotherapy. Here, we demonstrate that mAb therapy targeting CCR8 significantly suppresses tumor growth and improves long-term survival in colorectal tumor mouse models. This antitumor activity correlated with increased tumor-specific T cells, enhanced infiltration of CD4+ and CD8+ T cells, and a significant decrease in the frequency of tumor-resident CD4+CCR8+ Tregs. Tumor-specific CD8+ T cells displayed lower expression of exhaustion markers as well as increased functionality upon restimulation. Treatment with anti-CCR8 mAb prevented de novo induction and suppressive function of Tregs without affecting CD8+ T cells. Initial studies explored a combinatorial regimen using anti-CCR8 mAb therapy and a Listeria monocytogenes–based immunotherapy. Anti-CCR8 mAb therapy synergized with L. monocytogenes–based immunotherapy to significantly delay growth of established tumors and to prolong survival. Collectively, these findings identify CCR8 as a promising new target for tumor immunotherapy and provide a strong rationale for further development of this approach, either as a monotherapy or in combination with other immunotherapies.Significance: Inhibition of CCR8 represents a promising new cancer immunotherapy strategy that modulates tumor-resident regulatory T cells to enhance antitumor immunity and prolong patient survival. Cancer Res; 78(18); 5340–8. ©2018 AACR.
Cancer Site–Specific Disparities in New York, Including the 1945–1965 Birth Cohort's Impact on Liver Cancer Patterns
Authors: Pinheiro Paulo S. , Callahan Karen E. , Boscoe Francis P. , Balise Raymond R. , Cobb Taylor R. , Lee David J. , Kobetz Erin 
Published: July 2018

Abstract
Background: Analyses of cancer patterns by detailed racial/ethnic groups in the Northeastern United States are outdated.
Methods: Using 2008–2014 death data from the populous and diverse New York State, mortality rates and regression-derived ratios with corresponding 95% confidence intervals (CIs) were computed to compare Hispanic, non-Hispanic white (NHW), non-Hispanic black (NHB), Asian populations, and specific Hispanic and NHB subgroups: Puerto Rican, Dominican, South American, Central American, U.S.-born black, and Caribbean-born black. Special analyses on liver cancer mortality, given the higher prevalence of hepatitis C infection among the 1945–1965 birth cohort, were performed.
Results: A total of 244,238 cancer-related deaths were analyzed. Mortality rates were highest for U.S.-born blacks and lowest for South Americans and Asians. Minority groups had higher mortality from liver and stomach cancer than NHWs; Hispanics and NHBs also had higher mortality from cervical and prostate cancers. Excess liver cancer mortality among Puerto Rican and U.S.-born black men was observed, particularly for the 1945–1965 birth cohort, with mortality rate ratios of 4.27 (95% CI, 3.82–4.78) and 3.81 (95% CI, 3.45–4.20), respectively.
Conclusions: U.S.-born blacks and Puerto Ricans, who share a common disadvantaged socioeconomic profile, bear a disproportionate burden for many cancers, including liver cancer among baby boomers. The relatively favorable cancer profile for Caribbean-born blacks contrasts with their U.S.-born black counterparts, implying that race per se is not an inevitable determinant of higher mortality among NHBs.
Impact: Disaggregation by detailed Hispanic and black subgroups in U.S. cancer studies enlightens our understanding of the epidemiology of cancer and is fundamental for cancer prevention and control efforts. Cancer Epidemiol Biomarkers Prev; 27(8); 917–27. ©2018 AACR.