bluuebunny/crossref_metadata_2025_split huggingface dataset:
Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma
Authors: Pirazzoli Valentina , Ayeni Deborah , Meador Catherine B. , Sanganahalli Basavaraju G. , Hyder Fahmeed , de Stanchina Elisa , Goldberg Sarah B. , Pao William , Politi Katerina 
Published: September 2015

Abstract
Purpose: The EGFR tyrosine kinase inhibitors (TKIs), erlotinib and afatinib, have transformed the treatment of advanced EGFR-mutant lung adenocarcinoma. However, almost all patients who respond develop acquired resistance on average approximately 1 year after starting therapy. Resistance is commonly due to a secondary mutation in EGFR (EGFRT790M). We previously found that the combination of the EGFR TKI afatinib and the EGFR antibody cetuximab could overcome EGFRT790M-mediated resistance in preclinical models. This combination has shown a 29% response rate in a clinical trial in patients with acquired resistance to first-generation TKIs. An outstanding question is whether this regimen is beneficial when used as first-line therapy.
Experimental Design: Using mouse models of EGFR-mutant lung cancer, we tested whether the combination of afatinib plus cetuximab delivered upfront to mice with TKI-naïve EGFRL858R-induced lung adenocarcinomas delayed tumor relapse and drug-resistance compared with single-agent TKIs.
Results: Afatinib plus cetuximab markedly delayed the time to relapse and incidence of drug-resistant tumors, which occurred in only 63.6% of the mice, in contrast to erlotinib or afatinib treatment where 100% of mice developed resistance. Mechanisms of tumor escape observed in afatinib plus cetuximab resistant tumors include the EGFRT790M mutation and Kras mutations. Experiments in cell lines and xenografts confirmed that the afatinib plus cetuximab combination does not suppress the emergence of EGFRT790M.
Conclusions: These results highlight the potential of afatinib plus cetuximab as an effective treatment strategy for patients with TKI-naïve EGFR-mutant lung cancer and indicate that clinical trial development in this area is warranted. Clin Cancer Res; 22(2); 426–35. ©2015 AACR.
Loss of SMAD4 Promotes Colorectal Cancer Progression by Accumulation of Myeloid-Derived Suppressor Cells through the CCL15–CCR1 Chemokine Axis
Authors: Inamoto Susumu , Itatani Yoshiro , Yamamoto Takamasa , Minamiguchi Sachiko , Hirai Hideyo , Iwamoto Masayoshi , Hasegawa Suguru , Taketo Makoto Mark , Sakai Yoshiharu , Kawada Kenji 
Published: September 2015

AbstractPurpose: We previously reported that loss of SMAD4 promotes chemokine CCL15 expression to recruit CCR1+ myeloid cells via the CCL15–CCR1 axis, which facilitates metastasis of colorectal cancer to the liver. The purposes of this study were to investigate whether essentially the same mechanism works in tumor invasion of the primary colorectal cancer and to evaluate the clinical importance of CCL15 expression and CCR1+ cell accumulation.Experimental Design: Using human colorectal cancer cell lines with reduced expression of SMAD4 or CCL15, we investigated tumor growth activities in vivo. We used immunohistochemistry (IHC) to investigate expression of SMAD4, CCL15, and CCR1 with 333 clinical specimens of primary colorectal cancer. We next characterized the CCR1+ cells using double immunofluorescence staining with several specific cell-type markers. Finally, we determined the serum CCL15 levels in 132 colorectal cancer patients.Results: In an orthotopic xenograft model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, resulting in aggressive tumor growth. IHC indicated that loss of SMAD4 was significantly associated with CCL15 expression, and that CCL15-positive primary colorectal cancers recruited approximately 2.2 times more numbers of CCR1+ cells at their invasion front than CCL15-negative colorectal cancers. Importantly, these CCR1+ cells were of the myeloid-derived suppressor cell (MDSC) phenotype (CD11b+, CD33+, and HLA-DR−). Most CCR1+ cells showed the granulocytic-MDSC phenotype (CD15+), whereas some showed the monocytic-MDSC phenotype (CD14+). Serum CCL15 levels in colorectal cancer patients were significantly higher than in controls.Conclusions: Blocking the recruitment of CCR1+ MDSCs may represent a novel molecular-targeted therapy, and serum CCL15 concentration can be a novel biomarker for colorectal cancer. Clin Cancer Res; 22(2); 492–501. ©2015 AACR.
MAPRE1 as a Plasma Biomarker for Early-Stage Colorectal Cancer and Adenomas
Authors: Taguchi Ayumu , Rho Jung-hyun , Yan Qingxiang , Zhang Yuzheng , Zhao Yang , Xu Hanwen , Tripathi Satyendra Chandra , Wang Hong , Brenner Dean E. , Kucherlapati Melanie , Kucherlapati Raju , Boutin Adam T. , Wang Y. Alan , DePinho Ronald A. , Feng Ziding , Lampe Paul D. , Hanash Samir M. 
Published: September 2015

Abstract
Blood-based biomarkers for early detection of colorectal cancer could complement current approaches to colorectal cancer screening. We previously identified the APC-binding protein MAPRE1 as a potential colorectal cancer biomarker. Here, we undertook a case–control validation study to determine the performance of MAPRE1 in detecting early colorectal cancer and colon adenoma and to assess the potential relevance of additional biomarker candidates. We analyzed plasma samples from 60 patients with adenomas, 30 with early colorectal cancer, 30 with advanced colorectal cancer, and 60 healthy controls. MAPRE1 and a set of 21 proteins with potential biomarker utility were assayed using high-density antibody arrays, and carcinoembryonic antigen (CEA) was assayed using ELISA. The biologic significance of the candidate biomarkers was also assessed in colorectal cancer mouse models. Plasma MAPRE1 levels were significantly elevated in both patients with adenomas and patients with colorectal cancer compared with controls (P &lt; 0.0001). MAPRE1 and CEA together yielded an area under the curve of 0.793 and a sensitivity of 0.400 at 95% specificity for differentiating early colorectal cancer from controls. Three other biomarkers (AK1, CLIC1, and SOD1) were significantly increased in both adenoma and early colorectal cancer patient plasma samples and in plasma from colorectal cancer mouse models at preclinical stages compared with controls. The combination of MAPRE1, CEA, and AK1 yielded sensitivities of 0.483 and 0.533 at 90% specificity and sensitivities of 0.350 and 0.467 at 95% specificity for differentiating adenoma and early colorectal cancer, respectively, from healthy controls. These findings suggest that MAPRE1 can contribute to the detection of early-stage colorectal cancer and adenomas together with other biomarkers. Cancer Prev Res; 8(11); 1112–9. ©2015 AACR.
Tumor Interstitial Fluid Promotes Malignant Phenotypes of Lung Cancer Independently of Angiogenesis
Authors: Li Hong , Li Ganggang , Liu Linxin , Guo Zhenzhen , Ma Xiaofang , Cao Ning , Lin Haihong , Han Guang , Duan Yongjian , Du Gangjun 
Published: September 2015

Abstract
Angiogenesis is necessary for cancer progression, but antiangiogenic therapy actually promotes tumor recurrence, progression, and metastasis. This study focused on the contribution of the tumor interstitial fluid (TIF) to lung cancer progression. TIF was isolated and quantified for 10 μg protein/mL. Malignant driver characteristics of TIF were examined by tumor-initiating cells (TIC), self-renewal, epithelial–mesenchymal transition (EMT), autophagy, and apoptosis in vitro. In vivo tumor model was used to investigate the mechanistic roles of TIF in lung cancer progression. In vitro, TIF exhibited distinct malignant driver characteristics, which led to increased numbers of TICs, increased self-renewal and EMT, as well as to decreased autophagy and apoptosis under cell starvation conditions. In vivo, the contribution of TIF was similar, as judged by increased TICs indicated by the cancer stem cell marker Nanog, the proliferation marker proliferating cell nuclear antigen, and the EMT marker N-cadherin; TIF also increased the formation of pulmonary tumors. Interestingly, the blockers of inflammation, Na-K-ATPase, and aldosterone receptor decreased TIF-induced tumor progression but increased angiogenesis. Further, we found that the water content of the tissue was positively correlated with the levels of plasma 5-hydroxyindoleacetic acid or tissue aquaporin-1 but not with CD31. However, vadimezan reduced angiogenesis but promoted TIF-induced tumor progression. Our results suggested that TIF could provide better nutrition to the tumor than angiogenesis and that it could promote the development of malignant phenotypes of lung cancer independently of angiogenesis. Cancer Prev Res; 8(11); 1120–9. ©2015 AACR.
Prediction of Cardiac and Noncardiac Mortality After Percutaneous Coronary Intervention
Authors: Spoon Daniel B. , Lennon Ryan J. , Psaltis Peter J. , Prasad Abhiram , Holmes David R. , Lerman Amir , Rihal Charanjit S. , Gersh Bernard J. , Ting Henry H. , Singh Mandeep , Gulati Rajiv 
Published: September 2015

Background—
Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention.

Methods and Results—

We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected
c
-statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected
c
-statistic of 0.77.

Conclusions—
We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.
XBT Science: Assessment of Instrumental Biases and Errors
Authors: Cheng Lijing , Abraham John , Goni Gustavo , Boyer Timothy , Wijffels Susan , Cowley Rebecca , Gouretski Viktor , Reseghetti Franco , Kizu Shoichi , Dong Shenfu , Bringas Francis , Goes Marlos , Houpert Loïc , Sprintall Janet , Zhu Jiang 
Published: September 2015

Abstract
Expendable bathythermograph (XBT) data were the major component of the ocean temperature profile observations from the late 1960s through the early 2000s, and XBTs still continue to provide critical data to monitor surface and subsurface currents, meridional heat transport, and ocean heat content. Systematic errors have been identified in the XBT data, some of which originate from computing the depth in the profile using a theoretically and experimentally derived fall-rate equation (FRE). After in-depth studies of these biases and discussions held in several workshops dedicated to discussing XBT biases, the XBT science community met at the Fourth XBT Science Workshop and concluded that XBT biases consist of 1) errors in depth values due to the inadequacy of the probe motion description done by standard FRE and 2) independent pure temperature biases. The depth error and temperature bias are temperature dependent and may depend on the data acquisition and recording system. In addition, the depth bias also includes an offset term. Some biases affecting the XBT-derived temperature profiles vary with manufacturer/probe type and have been shown to be time dependent. Best practices for historical XBT data corrections, recommendations for future collection of metadata to accompany XBT data, impact of XBT biases on scientific applications, and challenges encountered are presented in this manuscript. Analysis of XBT data shows that, despite the existence of these biases, historical XBT data without bias corrections are still suitable for many scientific applications, and that bias-corrected data can be used for climate research.
Rapid detection of wild-type and mutated transthyretins
Authors: Tasaki Masayoshi , Ueda Mitsuharu , Obayashi Konen , Motokawa Hiroaki , Kinoshita Yumiko , Suenaga Genki , Yanagisawa Akihiro , Toyoshima Risa , Misumi Yohei , Masuda Teruaki , Yamashita Taro , Ando Yukio 
Published: September 2015

Background Familial amyloid polyneuropathy is caused by a variant transthyretin, which is a serum protein secreted by the liver. We previously reported that mutated transthyretins were detected in serum samples by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The aim of this study was to evaluate the clinical usefulness of SELDI-TOF MS for diagnosis of transthyretin-related amyloidosis. Methods We used 106 serum samples obtained from patients who were clinically suspected of having amyloidosis between February 2011 and April 2014. SELDI-TOF MS allowed analysis for transthyretin via a 3-h one-step procedure. Results Of the 106 patients, 51 are transthyretin amyloidosis. Mutated transthyretins were detected in serum samples from 30 of 51 patients with transthyretin amyloidosis. The results of genetic analysis showed that all of those patients had mutations in the transthyretin gene. For all 18 patients with senile systemic amyloidosis of 51 patients with transthyretin amyloidosis, SELDI-TOF MS detected only wild-type transthyretin peaks, not mutated transthyretin peaks. Conclusion SELDI-TOF MS is a clinically useful tool for diagnosis of transthyretin-related amyloidosis.
Experimental and analytical study of surface fatigue life in dental composites
Authors: Marandu S I , Gu G , Bicker R 
Published: September 2015

The surface fatigue life of a dental composite is studied using in vitro tests and analytic models. A mechatronic rolling-ball device with condition monitoring and automated data sampling is used to measure the fatigue life. The Hertzian stress theory is used to analytically estimate the deformation stress induced in the specimen, then the Basquin equation is used to predict the fatigue life based on the deformation stress. The experimental and analytic results are in good agreement. The results are also consistent with previous researches using the conventional rolling-ball device. The study shows that analytic models can bridge the gap between in vivo and in vitro testing by providing accurate estimates of fatigue lifetime and guiding the design of in vitro experiments.
Anxiety and concerns in Spanish living kidney donor candidates
Authors: Pérez-San-Gregorio María Ángeles , Fernández-Jiménez Eduardo , Luque-Budia Asunción , Martín-Rodríguez Agustín 
Published: September 2015

Objectives Donating a kidney while alive is an experience associated with important benefits for donors and recipients. In view of the inexistence of Spanish investigations, we aimed: (a) to compare the anxiety and concerns of Spanish living kidney donor candidates relating to themselves as a function of gender and their level of concern about potential kidney recipients, and (b) to analyze whether the results regarding anxiety symptoms were clinically significant compared with a representative sample of the general Spanish population. Methods We selected 67 donor candidates whom we evaluated using the State Trait Anxiety Inventory (STAI) and the Scale of Concerns Regarding Living Kidney Donation. Results (1) The donor candidates who were more concerned about the recipients, in comparison with those who were less concerned, showed more state-anxiety and more concerns about themselves as donors, (2) the subgroup of more concerned females exhibited greater anxiety symptoms and concern about the consequences that nephrectomy could have on themselves, and (3) for all donor candidates, regardless of gender or level of concern about the recipient, the anxiety levels were not clinically significant. Conclusions Anxiety in donor candidates is similar to or lower than the normative levels.
The effect of distraction on pain perception during an endovenous thermal ablation procedure
Authors: van Zandvoort Carina EG , Toonder Irwin M , Stoopendaal Irma AJ , Wittens Cees HA 
Published: September 2015

Objectives To determine whether audio and visual distraction can affect the pain perception of a patient undergoing endovenous thermal ablation under tumescent anesthesia. Methods Patients underwent an endovenous thermal ablation procedure and were randomized into two groups: non-distraction (AVD−) and with distraction (AVD+). Visual analogue scale pain score and hospital anxiety depression scale scores were used to measure outcome. The recruited patients were asked to submit an anticipated visual analogue scale pain score prior to treatment as well as the actual experienced post-operative visual analogue scale pain score. Results There was no significant difference between the AVD− and AVD+ groups post-operative pain score 2.85 (SD 1.7) versus 2.60 (SD 2.3), p = 0.68. Pain score in women with distraction (AVD+) decreased from 3.81 to 2.42. The pain score in men with distraction (AVD+) increases from 1.88 to 2.82. In the AVD− group, a significant difference was found between men and women ( p = 0.014). Disregarding gender, a significant difference was found between the anticipated pain score and the actual pain score in both the AVD− group ( p = 0.009) and AVD+ group ( p = 0.021). There was a correlation between depression and the pain score, which was not seen between pain and anxiety score. Conclusion The results suggested that audiovisual distraction has no influence on the visual analogue scale pain score during endovenous thermal ablation under tumescent anesthesia. Despite this, patients appreciate and evaluate audio and visual distraction as pleasant to extremely pleasant when applied.
The twist axis of frames with particular application to motorcycles
Authors: Doria Alberto , Taraborrelli Luca 
Published: September 2015

The static and dynamic properties of the frame and the front fork of a single track vehicle play a critical role from the point of view of vehicle stability. A turning point in the study of motorcycle stability was established by the introduction of lumped stiffness elements to characterize the critical compliances of the motorcycle elements, this approach being still in use with advanced multibody codes. Nonetheless, up to now very few scientific studies have been carried out to identify the parameters that account for the stiffness and damping properties of motorcycle front forks and frames. This work addresses the problem of identifying the parameters needed for developing lumped element models of motorcycles from experimental results. Two motorcycle frames are studied performing static, dynamic, and modal tests by means of a specific testing equipment. The frames have been tested in two different conditions: fixing them at the steering head or at the swing-arm pivot. In the first section of the paper a general definition of the twist axis, based on the concept of “Mozzi” or instantaneous screw axis, is presented. The twist axis is used for characterizing the deformation patterns of the tested frames. The static twist axis is identified loading the frames at low rate by means of a servo-hydraulic actuator and measuring the deformation of a reference plate by means of three laser sensors; the dynamic twist axis is identified exerting an impulsive excitation and measuring the vibration of a reference plate by means of three accelerometers. In the last section of the paper, experimental results obtained on motorcycle frames are shown. A method to identify the stiffness properties of the frames from the measured twist axes is presented. Results obtained with the proposed method are in good agreement with the ones presented in literature.
Gender Differences in Outcome After Modified Broström Procedure for Chronic Lateral Ankle Instability
Authors: Xu He-Xing , Choi Min-Sun , Kim Myung-Sun , Park Kyung-Soon , Lee Keun-Bae 
Published: September 2015

Background: The modified Broström procedure is commonly used for anatomic repair of chronic lateral ankle instability. However, no studies have compared outcomes of gender-based differences after the modified Broström procedure. We compared outcomes of the modified Broström procedure in men and women. Methods: A total of 155 patients (155 ankles) treated with the modified Broström procedure for chronic lateral ankle instability constituted the study cohort. The 155 ankles were divided into 2 groups: a men’s group (94 ankles) and a women’s group (61 ankles). The Karlsson score, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, talar tilt, and anterior talar translation were used to evaluate clinical and radiographic outcomes. The mean follow-up duration was 42.8 months (range, 24-101). Results: Mean preoperative Karlsson scores were 53.6 points (39-65) in the men’s group and 54.9 points (39-65) in the women’s group, and these improved to 93.2 (72-100) and 92.2 (80-100), respectively, at the final follow-up. Mean preoperative AOFAS ankle-hindfoot scores were 62.4 points (44-79) in men and 63.6 points (49-77) in women and 93.7 (72-100) and 92.3 (79-100), respectively, at the final follow-up. Mean preoperative talar tilt angles decreased from 11.9 degrees (2.5-27.5) in men and 11.4 degrees (0.9-24.7) in women to 6.0 (1.0-11.5) and 6.0 (2.3-11.9), respectively, at the final follow-up. Mean preoperative anterior talar translation in men and women improved from 8.6 mm (5.1-14.6) and 8.7 mm (2.3-11.9) to 6.0 (4.3-8.7) and 5.8 (3.3-9.9), respectively, at the final follow-up. No significant differences were found between men and women in terms of Karlsson scores, AOFAS scores, talar tilt angle, and anterior talar translation. Conclusions: The modified Broström procedure showed similar good functional and radiographic outcomes in men and women. These results suggest that the modified Broström procedure is effective and reliable for treating chronic lateral ankle instability regardless of gender. Level of Evidence: Level III, retrospective comparative cohort study.
Perspectives About Health Care Provision in Dementia Care in Spain
Authors: Risco Ester , Cabrera Esther , Farré Marta , Alvira Carme , Miguel Susana , Zabalegui Adelaida 
Published: September 2015

Background: The aim of this study is to identify the barriers and facilitators in dementia care with respect to information provision, communication, and collaboration from the perspectives of the person with dementia, family caregivers, and health care professionals over the course of the illness. Methods: A qualitative study using Focus-Group methodology was carried out in people with dementia, family caregivers, and health care providers. Results: The categories that emerged from the analysis were insufficient information provided, specific dementia care needs, and acceptance of long-term care institutionalization from the people with dementia and caregivers’ groups and insufficient communication between health care providers, differential information according to disease stage, and home care coordination from the health care providers’ groups. Conclusion: The family is a key element in successful care coordination during dementia care provision. New effective strategies including self-management and emergent roles, such as case managers, could bring great benefits to people with dementia, caregivers, and health care providers.