bluuebunny/crossref_metadata_2025_split huggingface dataset:
Travel health and pretravel preparation in the patient with inflammatory bowel disease
Authors: Greveson Kay , Shepherd Thomas , Mulligan John P , Hamilton Mark , Woodward Sue , Norton Christine , Murray Charles 
Published: April 2015

Background and aimsForeign travel for people with inflammatory bowel disease (IBD) carries an increased risk of travel-related morbidity. There is limited research looking specifically at travel-associated health risks and travel preparation in patients with IBD. The aims of this study are to explore the experience of travel, pretravel preparation undertaken by the patient with IBD and examine IBD healthcare professionals’ (HCP) confidence at providing travel advice and the content of that advice.MethodsA survey of patients with IBD attending an outpatient clinic with a separate online survey sent to IBD HCPs recruited using regional and international network databases.ResultsA total of 132 patients with IBD, Crohn's disease (67/132, 51%), male (60/132, 45%) and 128 HCPs (IBD nurse specialist 113, 88%; IBD physician 15, 12%) completed the questionnaires. IBD affected travel to some extent in 62% (82/132) of patients, and 64% (84/132) had experienced an IBD flare, of whom 64% still travelled overseas during this time. Only 23% (31/132) travellers sought pretravel medical advice and 40% (53/132) obtained travel insurance. Forty-eight per cent of respondents on immunomodulator therapy were unaware of the need to avoid live vaccines. Twenty-seven per cent (34/128) of IBD HCPs are not confident at providing pretravel advice; vaccination advice (54%), obtaining travel insurance (61%) and healthcare abroad (78%) are the areas of most uncertainty.ConclusionsPatients do not seek adequate pretravel advice and consultations for those who do are often deficient. The majority of IBD professionals are not confident to provide comprehensive travel advice. Greater IBD-specific travel education and awareness is needed for both patients with IBD and professionals.
Disease-related pregnancy concerns and reproductive planning in women with inflammatory bowel diseases
Authors: Gawron Lori M , Goldberger Adina R , Gawron Andrew J , Hammond Cassing , Keefer Laurie 
Published: April 2015

BackgroundWomen with inflammatory bowel diseases (IBD) endorse disease-related pregnancy concerns that influence parity. Improvements in IBD management have potentially altered reproductive planning. Additionally, the proportion of American women who choose not to have children is increasing.AimTo explore the effect of disease-related pregnancy concerns on parity and reproductive planning in a subset of women with IBD.Design and settingCross-sectional qualitative phone survey in an academic gastroenterology practice.MethodsQuestions included demographics, medical and reproductive history, future pregnancy plans, and if IBD affected pregnancy decision-making. Qualitative data were coded and frequencies and proportions calculated.ResultsThe 129 female participants (31% response rate) were predominately white (85%), had at least some college education (97%) and a mean age of 34.3 years [standard deviation 6.2]. Some 60% had Crohn's disease and 30% had undergone IBD-related surgery. Half were nulliparae, 53% reported IBD-related pregnancy concerns and 57% desired future pregnancy. Women who desired a future pregnancy and had IBD-related concerns had higher parity than those without concerns (p=0.02). Women desiring a future pregnancy and those with Crohn's disease had increased IBD-related concerns. Only four (3.1%) women identified IBD-related concerns that led to a smaller family size than desired.ConclusionsIBD-related concerns appear to be less likely to affect a woman's planned family size than previously reported. Concern about adverse pregnancy outcomes is more common in women with Crohn's disease and those desiring future pregnancy, suggesting a need for targeted counselling to moderate risk perception.
The late field life of the East Midlands Petroleum Province; a new geothermal prospect?
Authors: Hirst Catherine M. , Gluyas Jon G. , Mathias Simon A. 
Published: April 2015

Modification of existing oilfield infrastructure could deliver a cost-effective way to extend the economic life of depleted onshore oilfields. Naturally warm connate and injection water contained within these fields could be initially co-produced with remaining oil reserves and used to deliver clean, cheap, non-intermittent heating. The East Midlands Petroleum Province contains over 30 fields with a production history spanning 95 years, and we have chosen to examine the Welton field in detail. Well data for the Welton field have been analysed to ascertain extractable heat within both oil- and non-oil-bearing (water-bearing) strata within the field. Production rates were calculated to be 728 m
3
d
−1
oil and 854 m
3
d
−1
water. These values also include productivity of intervening largely water-bearing intervals. Target formation temperature at 1500 m was determined to be 52.5°C, allowing an extractable heat energy calculation to be undertaken for a range of temperature differentials. For a 30°C depletion in temperature, 1.6 MW
t
extractable heat is available within the Welton field alone. This equates to 14040 MWh of heat energy available for consumption by the domestic market or within commercial greenhouses.
Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation
Authors: Veliça Pedro , Zech Mathias , Henson Sian , Holler Angelika , Manzo Teresa , Pike Rebecca , Santos e Sousa Pedro , Zhang Lei , Schiedlmeier Bernhard , Pule Martin , Stauss Hans , Chakraverty Ronjon 
Published: April 2015

Abstract
A key challenge in the field of T-cell immunotherapy for cancer is creating a suitable platform for promoting differentiation of effector cells while at the same time enabling self-renewal needed for long-term memory. Although transfer of less differentiated memory T cells increases efficacy through greater expansion and persistence in vivo, the capacity of such cells to sustain effector functions within immunosuppressive tumor microenvironments may still be limiting. We have therefore directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR. Ectopic expression of RAS homolog enriched in brain (RHEB) increased mTORC1 signaling, promoted a switch to aerobic glycolysis, and increased expansion of effector T cells. By rapidly infiltrating tumors, RHEB-transduced T cells significantly reduced the emergence of immunoedited escape variants. In contrast, expression of proline-rich Akt substrate of 40 kDa (PRAS40) inhibited mTORC1, promoted quiescence, and blocked tumor infiltration. Fate mapping studies following transient expression of PRAS40 demonstrated that mTORC1low T cells made no contribution to initial tumor control but instead survived to become memory cells proficient in generating recall immunity. Our data support the design of translational strategies for generating heterogeneous T-cell immunity against cancer, with the appropriate balance between promoting effector differentiation and self-renewal. Unlike pharmacologic inhibitors, the genetic approach described here allows for upregulation as well as inhibition of the mTORC1 pathway and is highly selective for the therapeutic T cells without affecting systemic mTORC1 functions. Cancer Res; 75(13); 2641–52. ©2015 AACR.
Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort
Authors: Elebro Karin , Borgquist Signe , Simonsson Maria , Markkula Andrea , Jirström Karin , Ingvar Christian , Rose Carsten , Jernström Helena 
Published: April 2015

Abstract
Purpose: To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response.
Experimental Design: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups.
Results: AR expression was assessable in 913 tumors. AR+ tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR+ status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted Pinteraction ≤ 0.024). Tumors with discordant hormone receptor expressions (ER+AR− or ER−AR+) demonstrated worse prognosis compared with concordant tumor expressions (ER+AR+ or ER−AR−) in multivariable models [adjusted HRs (95% confidence intervals); ≥1.99 (1.28–3.10), P ≤ 0.002]. ER+AR− indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older.
Conclusions: Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators. Clin Cancer Res; 21(16); 3640–50. ©2015 AACR.
Development and Validation of a Novel Radiosensitivity Signature in Human Breast Cancer
Authors: Speers Corey , Zhao Shuang , Liu Meilan , Bartelink Harry , Pierce Lori J. , Feng Felix Y. 
Published: April 2015

Abstract
Purpose: An unmet clinical need in breast cancer management is the accurate identification of patients who will benefit from adjuvant radiotherapy. We hypothesized that integration of postradiation clonogenic survival data with gene expression data across breast cancer cell (BCC) lines would generate a radiation sensitivity signature (RSS) and identify patients with tumors refractive to conventional therapy.
Experimental Design: Using clonogenic survival assays, we identified the surviving fraction (SF-2Gy) after radiation across a range of BCC lines. Intrinsic radiosensitivity was correlated to gene expression using Spearman correlation. Functional analysis was performed in vitro, and enriched biologic concepts were identified. The RSS was generated using a Random Forest model and was refined, cross-validated, and independently validated in additional breast cancer datasets.
Results: Clonogenic survival identifies a range of radiosensitivity in human BCC lines (SF-2Gy 77%-17%) with no significant correlation to the intrinsic breast cancer subtypes. One hundred forty-seven genes were correlated with radiosensitivity. Functional analysis of RSS genes identifies previously unreported radioresistance-associated genes. RSS was trained, cross-validated, and further refined to 51 genes that were enriched for concepts involving cell-cycle arrest and DNA damage response. RSS was validated in an independent dataset and was the most significant factor in predicting local recurrence on multivariate analysis, outperfoming all clinically used clinicopathologic features.
Conclusions: We derive a human breast cancer–specific RSS with biologic relevance and validate this signature for prediction of locoregional recurrence. By identifying patients with tumors refractory to standard radiation this signature has the potential to allow for personalization of radiotherapy. Clin Cancer Res; 21(16); 3667–77. ©2015 AACR.
Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer
Authors: Rosenthal Eben L. , Warram Jason M. , de Boer Esther , Chung Thomas K. , Korb Melissa L. , Brandwein-Gensler Margie , Strong Theresa V. , Schmalbach Cecelia E. , Morlandt Anthony B. , Agarwal Garima , Hartman Yolanda E. , Carroll William R. , Richman Joshua S. , Clemons Lisa K. , Nabell Lisle M. , Zinn Kurt R. 
Published: April 2015

Abstract
Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer.
Experimental Design: A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology.
Results: There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels.
Conclusions: We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology. Clin Cancer Res; 21(16); 3658–66. ©2015 AACR.
Genetic Modulation of Neurocognitive Function in Glioma Patients
Authors: Liu Yanhong , Zhou Renke , Sulman Erik P. , Scheurer Michael E. , Boehling Nicholas , Armstrong Georgina N. , Tsavachidis Spiridon , Liang Fu-Wen , Etzel Carol J. , Conrad Charles A. , Gilbert Mark R. , Armstrong Terri S. , Bondy Melissa L. , Wefel Jeffrey S. 
Published: April 2015

Abstract
Purpose: Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients.
Experimental Design: To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test—Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined.
Results: Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive function. For processing speed, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.5 × 10−10), ERCC4 rs1573638 in the DNA repair pathway (P = 3.4 × 10−7), and ABCC1 rs8187858 in metabolism pathway (P = 6.6 × 10−7). For executive function, the strongest associations were in NOS1 rs11611788 (P = 1.8 × 10−8) and IL16 rs1912124 (P = 6.0 × 10−7) in the inflammation pathway, and POLE rs5744761 (P = 6.0 × 10−7) in the DNA repair pathway. Joint effect analysis found significant gene polymorphism-dosage effects for processing speed (Ptrend = 9.4 × 10−16) and executive function (Ptrend = 6.6 × 10−15).
Conclusions: Polymorphisms in inflammation, DNA repair, and metabolism pathways are associated with neurocognitive function in glioma patients and may affect clinical outcomes. Clin Cancer Res; 21(14); 3340–6. ©2015 AACR.
IMGN853, a Folate Receptor-α (FRα)–Targeting Antibody–Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors
Authors: Ab Olga , Whiteman Kathleen R. , Bartle Laura M. , Sun Xiuxia , Singh Rajeeva , Tavares Daniel , LaBelle Alyssa , Payne Gillian , Lutz Robert J. , Pinkas Jan , Goldmacher Victor S. , Chittenden Thomas , Lambert John M. 
Published: April 2015

Abstract
A majority of ovarian and non–small cell lung adenocarcinoma cancers overexpress folate receptor α (FRα). Here, we report the development of an anti-FRα antibody–drug conjugate (ADC), consisting of a FRα-binding antibody attached to a highly potent maytansinoid that induces cell-cycle arrest and cell death by targeting microtubules. From screening a large panel of anti-FRα monoclonal antibodies, we selected the humanized antibody M9346A as the best antibody for targeted delivery of a maytansinoid payload into FRα-positive cells. We compared M9346A conjugates with various linker/maytansinoid combinations, and found that a conjugate, now denoted as IMGN853, with the N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB) linker and N2′-deacetyl-N2′-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4) exhibited the most potent antitumor activity in several FRα-expressing xenograft tumor models. The level of expression of FRα on the surface of cells was a major determinant in the sensitivity of tumor cells to the cytotoxic effect of the conjugate. Efficacy studies of IMGN853 in xenografts of ovarian cancer and non–small cell lung cancer cell lines and of a patient tumor-derived xenograft model demonstrated that the ADC was highly active against tumors that expressed FRα at levels similar to those found on a large fraction of ovarian and non-small cell lung cancer patient tumors, as assessed by immunohistochemistry. IMGN853 displayed cytotoxic activity against FRα-negative cells situated near FRα-positive cells (bystander cytotoxic activity), indicating its ability to eradicate tumors with heterogeneous expression of FRα. Together, these findings support the clinical development of IMGN853 as a novel targeted therapy for patients with FRα-expressing tumors. Mol Cancer Ther; 14(7); 1605–13. ©2015 AACR.
Platelets from flowing blood attach to the inflammatory chemokine CXCL16 expressed in the endothelium of the human vessel wall
Authors: Santos Sascha Meyer dos , Blankenbach Kira , Scholich Klaus , Dörr Angela , Monsefi Nadejda , Keese Michael , Linke Bona , Deckmyn Hans , Nelson Karen , Harder Sebastian 
Published: April 2015

SummaryEndothelial chemokine CXC motif ligand 16 (CXCL16) expression is associated with atherosclerosis, while platelets, particularly those attaching to atherosclerotic plaque, contribute to all stages of athero-sclerotic disease. This investigation was designed to examine the role of CXCL16 in capturing platelets from flowing blood. CXCL16 was expressed in human atherosclerotic plaques, and lesion severity in human carotid endarterectomy specimens was positively correlated with CXCL16 levels. CXCL16 expression in plaques was co-localised with platelets deposited to the endothelium. Immobilised CXCL16 promoted CXCR6-dependent platelet adhesion to the human vessel wall, endothelial cells and von Willebrand factor during physiologic flow. At low shear, immobilised CXCL16 captured platelets from flowing blood. It also induced irreversible platelet aggregation and a rise in intra-platelet calcium levels. These results demonstrate that endothelial CXCL16’s action on platelets is not only limited to platelet activation, but that immobilised CXCL16 also acts as a potent novel platelet adhesion ligand, inducing platelet adhesion to the human vessel wall.
Quantitative Assessment of Pericardial Delayed Hyperenhancement Predicts Clinical Improvement in Patients With Constrictive Pericarditis Treated With Anti-Inflammatory Therapy
Authors: Cremer Paul C. , Tariq Muhammad U. , Karwa Abhishek , Alraies M. Chadi , Benatti Rodolfo , Schuster Andres , Agarwal Shikhar , Flamm Scott D. , Kwon Deborah H. , Klein Allan L. 
Published: April 2015

Background—
Delayed hyperenhancement (DHE) of the pericardium usually represents ongoing inflammation and may identify patients with constrictive pericarditis that will improve with anti-inflammatory therapy. However, a quantitative assessment of pericardial DHE has not been performed, and the hierarchical relationship among clinical factors, inflammatory markers, and pericardial DHE is unknown.

Methods and Results—

We identified 41 consecutive patients with constrictive pericarditis who had a cardiovascular magnetic resonance study with DHE prior to the initiation of anti-inflammatory medications. Pericardial inflammation was quantified on short-axis DHE sequences by contouring the pericardium, selecting normal septal myocardium as a reference region, and then quantifying the pericardial signal that was >6 SD above the reference. Our primary outcome was clinical improvement with anti-inflammatory therapy. The mean age of our patients was 58 years, most patients were male (83%) with New York Heart Association Class II or III (59%) heart failure, and the median follow-up was 1 year. Chest pain, lower New York Heart Association class, higher Westergren sedimentation rates, and increased pericardial DHE were all significantly associated with clinical improvement (
P
<0.01 for all). When quantitative pericardial DHE was added to a model that included age, chest pain, New York Heart Association class, and Westergren sedimentation rates, the global χ
2
improved significantly (
P
=0.04 for DHE), and the area under the receiver operating characteristic curve was 0.96.

Conclusions—
In patients with constrictive pericarditis treated with anti-inflammatory therapy, a quantitative assessment of pericardial DHE can provide incremental information to predict clinical improvement when added to clinical factors and Westergren sedimentation rates.
Contributions of Increasing Obesity and Diabetes to Slowing Decline in Subclinical Coronary Artery Disease
Authors: Smith Carin Y. , Bailey Kent R. , Emerson Jane A. , Nemetz Peter N. , Roger Véronique L. , Palumbo Pasquale J. , Edwards William D. , Leibson Cynthia L. 
Published: April 2015

Background

Our previous study of nonelderly adult decedents with nonnatural (accident, suicide, or homicide) cause of death (96% autopsy rate) between 1981 and 2004 revealed that the decline in subclinical coronary artery disease (
CAD
) ended in the mid‐1990s. The present study investigated the contributions of trends in obesity and diabetes mellitus to patterns of subclinical
CAD
and explored whether the end of the decline in
CAD
persisted.

Methods and Results

We reviewed provider‐linked medical records for all residents of Olmsted County,
Minnesota
, who died from nonnatural causes within the age range of 16 to 64 years between 1981 and 2009 and who had
CAD
graded at autopsy. We estimated trends in
CAD
risk factors including age, sex, systolic blood pressure, diabetes (qualifying fasting glucose or medication), body mass index, smoking, and diagnosed hyperlipidemia. Using multiple regression, we tested for significant associations between trends in
CAD
risk factors and
CAD
grade and assessed the contribution of trends in diabetes and obesity to
CAD
trends. The 545 autopsied decedents with recorded
CAD
grade exhibited significant declines between 1981 and 2009 in systolic blood pressure and smoking and significant increases in blood pressure medication, diabetes, and body mass index ≥30 kg/m
2
. An overall decline in
CAD
grade between 1981 and 2009 was nonlinear and ended in 1994. Trends in obesity and diabetes contributed to the end of
CAD
decline.

Conclusions

Despite continued reductions in smoking and blood pressure values, the previously observed end to the decline in subclinical
CAD
among nonelderly adult decedents was apparent through 2009, corresponding with increasing obesity and diabetes in that population.