bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes
Authors: Ko Jennifer S. , Matharoo-Ball Balwir , Billings Steven D. , Thomson Brian J. , Tang Jean Y. , Sarin Kavita Y. , Cai Emily , Kim Jinah , Rock Colleen , Kimbrell Hillary Z. , Flake Darl D. , Warf M. Bryan , Nelson Jonathan , Davis Thaylon , Miller Catherine , Rushton Kristen , Hartman Anne-Renee , Wenstrup Richard J. , Clarke Loren E. 
Published: April 2017

Abstract
Background: Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.
Methods: Archival tissue from primary cutaneous melanomas and melanocytic nevi was obtained from four independent institutions and tested with the gene signature. Cases were selected according to pre-defined clinical outcome measures. Malignant lesions were defined as stage I–III primary cutaneous melanomas that produced distant metastases (metastatic to sites other than proximal sentinel lymph node(s)) following diagnosis of the primary lesion. Melanomas that were metastatic at the time of diagnosis, all re-excisions, and lesions with &lt;10% tumor volume were excluded. Benign lesions were defined as cutaneous melanocytic lesions with no adverse long-term events reported.
Results: Of 239 submitted samples, 182 met inclusion criteria and produced a valid gene expression result. This included 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. Median time to melanoma metastasis was 18 months. Median follow-up time for nevi was 74.9 months. The gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%.
Conclusions: The results of gene expression testing closely correlate with long-term clinical outcomes of patients with melanocytic neoplasms.
Impact: Collectively, this provides strong evidence that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma. Cancer Epidemiol Biomarkers Prev; 26(7); 1107–13. ©2017 AACR.
U1 Adaptors Suppress the KRAS-MYC Oncogenic Axis in Human Pancreatic Cancer Xenografts
Authors: Tsang Ashley T. , Dudgeon Crissy , Yi Lan , Yu Xin , Goraczniak Rafal , Donohue Kristen , Kogan Samuel , Brenneman Mark A. , Ho Eric S. , Gunderson Samuel I. , Carpizo Darren R. 
Published: April 2017

Abstract
Targeting KRAS and MYC has been a tremendous challenge in cancer drug development. Genetic studies in mouse models have validated the efficacy of silencing expression of both KRAS and MYC in mutant KRAS-driven tumors. We investigated the therapeutic potential of a new oligonucleotide-mediated gene silencing technology (U1 Adaptor) targeting KRAS and MYC in pancreatic cancer. Nanoparticles in complex with anti-KRAS U1 Adaptors (U1-KRAS) showed remarkable inhibition of KRAS in different human pancreatic cancer cell lines in vitro and in vivo. As a nanoparticle-free approach is far easier to develop into a drug, we refined the formulation of U1 Adaptors by conjugating them to tumor-targeting peptides (iRGD and cRGD). Peptides coupled to fluorescently tagged U1 Adaptors showed selective tumor localization in vivo. Efficacy experiments in pancreatic cancer xenograft models showed highly potent (&gt;90%) antitumor activity of both iRGD and (cRGD)2-KRAS Adaptors. U1 Adaptors targeting MYC inhibited pancreatic cancer cell proliferation caused by apoptosis in vitro (40%–70%) and tumor regressions in vivo. Comparison of iRGD-conjugated U1 KRAS and U1 MYC Adaptors in vivo revealed a significantly greater degree of cleaved caspase-3 staining and decreased Ki67 staining as compared with controls. There was no significant difference in efficacy between the U1 KRAS and U1 MYC Adaptor groups. Our results validate the value in targeting both KRAS and MYC in pancreatic cancer therapeutics and provide evidence that the U1 Adaptor technology can be successfully translated using a nanoparticle-free delivery system to target two undruggable genes in cancer. Mol Cancer Ther; 16(8); 1445–55. ©2017 AACR.
Intraosseous Venous Malformations of the Zygoma: Report of 4 Cases and Literature Review
Authors: Huang Xiuling , An Jingang , Zhang Yi , Cai Zhigang 
Published: April 2017

Objectives:As intraosseous venous malformations (IVMs) of the zygoma are very rare and clinical features are not typical, a correct preoperative diagnosis may be difficult to make. This study presents 4 cases of IVM of the zygoma and gives a review of their clinical manifestations, radiographic features, preoperative diagnosis, and differentials.Methods:The report of 4 cases was performed with an average 6-year follow-up. Medical records including clinical, radiographic, and histopathological information were reviewed.Results:All the patients were mid-aged women with a complaint of an enlarging mass over the midface. They all failed to receive a definite preoperative diagnosis, and the diagnoses of IVM in all patients were made via pathological evidence. Although they received different surgical treatments, all the follow-up results (2~12 years) were satisfactory.Conclusion:Intraosseous venous malformations of the zygoma are benign lesions caused by abnormal vessel morphogenesis. Patients usually present in their 40s with a tender or painless swelling of the zygoma. The key to the diagnosis is the typical sunburst pattern of radiating trabeculae with intact cortices on computed tomographic scans. Intraosseous venous malformations should be differentiated from other lesions, including intraosseous meningioma, fibrous dysplasia, osteochondroma, osteosarcoma, and ossifying fibroma.
An indoor environment evaluation by gender and age using an advanced personalized ventilation system
Authors: Kalmár Ferenc 
Published: April 2017

In a closed space, appropriate thermal comfort and proper indoor air quality are extremely important in order to obtain the optimal work performance and to avoid health problems of the occupants. Using advanced personalized ventilation systems, different comfort needs can be locally satisfied even in case of warm environments. Thermal sensation and the subjective evaluation of indoor air quality of young and elderly people, men and women respectively, were studied in warm environment using advanced personalized ventilation system combined with total volume ventilation system. Using an advanced personalized ventilation system, 20 m3 h−1 air flow was alternately introduced by three air terminal devices built-in the desk and placed on a horizontal plane at the head level of the sitting subject. Thermal sensation was significantly cooler in case of young women in comparison with the other groups. Odor intensity was evaluated to be significantly lower in case of elderly women in comparison with the other groups. Evaluation of air freshness is in correlation with the general thermal sensation. Variation of the direction of the air velocity vector has a cooling side-effect, which, in warm environments, might be useful in order to improve the thermal comfort sensation. Practical application: From the basic factors that influence the thermal comfort sensation, air velocity is the one and only parameter that must be treated as a vector. The air flow velocity has an important effect on the convective heat quantity released by the human body, but the changes in the air velocity direction have a cooling side-effect. This cooling side-effect should be exploited properly in warm environments by advanced personalized ventilation systems to improve the thermal comfort sensation of the occupants without supplementary energy use.
Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing
Authors: Wu Song , Deng Liang , Hsia Hanson , Xu Kai , He Yu , Huang Qiangru , Peng Yi , Zhou Zhihua , Peng Cheng 
Published: April 2017

Excellent wound dressings maintain a warm and moist environment, thus accelerating wound healing. In this study, we cross-linked gelatin and hyaluronic acid with ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in different ratios (gelatin/hyaluronic acid = 8:2, gelatin/hyaluronic acid = 5:5, gelatin/hyaluronic acid = 2:8), and explored the effects and mechanisms of gelatinhyaluronic acid hydrogels on wound healing. This was done by examining dressing properties, such as fluid uptake ability, water vapor transmission rate, and the rate of water evaporation. We further verified biological function by using in vitro and in vivo wound models. The hydrogels display appropriate fluid uptake ability and good water vapor transmission rate and rate of water evaporation all of which can provide an adequate moisture environment for wound healing. Cell cytotoxicity and proliferation tests show that the hydrogels have no cytotoxicity, furthermore, gelatin/hyaluronic acid = 8:2 hydrogels have the potential to promote cell proliferation. Animal wound models demonstrate that the hydrogels can effectively promote wound healing in vivo, in particular, the gelatin/hyaluronic acid = 8:2 group which promoted the most rapid healing. Accordingly, gelatin-hyaluronic acid dressings, especially the gelatin/hyaluronic acid = 8:2 hydrogels, have a promising outlook for clinical applications in wound healing.
Have individual medical savings accounts accumulated meaningful balances after 10 years of enrolment? Empirical evidence from China
Authors: Yu Hao , Chen Jiaying 
Published: April 2017

Objectives To examine whether medical savings accounts in China have achieved the intended goal of promoting individual savings for medical care. Method Longitudinal data were obtained from one of the first Chinese cities that implemented medical savings accounts. The sample includes 246,681 enrolees with participation of at least 10 years by the end of 2010. We conducted descriptive analyses of medical savings account balances and a series of multivariate logistic analyses of risk factors for having low medical savings account accumulation. Results Medical savings account accumulation was low, with 41% of the enrolees having a balance below the average cost per outpatient visit, and the proportion increased to 54% and 58% when the deductible for inpatient care at secondary and tertiary hospitals was used as the threshold, respectively. Factors associated with having low medical savings account accumulation include female, old age, below high school education, retired and having a lower salary. Conclusion Medical savings accounts have not achieved the intended goal of encouraging personal savings for medical care. Given the low medical savings account accumulation, China’s decision-makers need to adjust policies, especially during the current healthcare reform.
Improving Care for Patients With or at Risk for Chronic Kidney Disease Using Electronic Medical Record Interventions: A Pragmatic Cluster-Randomized Trial Protocol
Authors: Nash Danielle M. , Ivers Noah M. , Young Jacqueline , Jaakkimainen R. Liisa , Garg Amit X. , Tu Karen 
Published: April 2017

Background: Many patients with or at risk for chronic kidney disease (CKD) in the primary care setting are not receiving recommended care. Objective: The objective of this study is to determine whether a multifaceted, low-cost intervention compared with usual care improves the care of patients with or at risk for CKD in the primary care setting. Design: A pragmatic cluster-randomized trial, with an embedded qualitative process evaluation, will be conducted. Setting: The study population comes from the Electronic Medical Record Administrative data Linked Database®, which includes clinical data for more than 140 000 rostered adults cared for by 194 family physicians in 34 clinics across Ontario, Canada. The 34 primary care clinics will be randomized to the intervention or control group. Intervention: The intervention group will receive resources from the “CKD toolkit” to help improve care including practice audit and feedback, printed educational materials for physicians and patients, electronic decision support and reminders, and implementation support. Measurements: Patients with or at risk for CKD within participating clinics will be identified using laboratory data in the electronic medical records. Outcomes will be assessed after dissemination of the CKD tools and after 2 rounds of feedback on performance on quality indicators have been sent to the physicians using information from the electronic medical records. The primary outcome is the proportion of patients aged 50 to 80 years with nondialysis-dependent CKD who are on a statin. Secondary outcomes include process of care measures such as screening tests, CKD recognition, monitoring tests, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescriptions, blood pressure targets met, and nephrologist referral. Hierarchical analytic modeling will be performed to account for clustering. Semistructured interviews will be conducted with a random purposeful sample of physicians in the intervention group to understand why the intervention achieved the observed effects. Conclusions: If our intervention improves care, then the CKD toolkit can be adapted and scaled for use in other primary care clinics which use electronic medical records. Trial Registration: ClinicalTrials.gov Identifier: NCT02274298
Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2–Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial
Authors: Sonnenblick Amir , Agbor-Tarh Dominique , Bradbury Ian , Di Cosimo Serena , Azim Hatem A. , Fumagalli Debora , Sarp Severine , Wolff Antonio C. , Andersson Michael , Kroep Judith , Cufer Tanja , Simon Sergio D. , Salman Pamela , Toi Masakazu , Harris Lyndsay , Gralow Julie , Keane Maccon , Moreno-Aspitia Alvaro , Piccart-Gebhart Martine , de Azambuja Evandro 
Published: April 2017

Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) –positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry—with or without metformin treatment—were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor–positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor–positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor–positive breast cancer.
Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry
Authors: Gautschi Oliver , Milia Julie , Filleron Thomas , Wolf Juergen , Carbone David P. , Owen Dwight , Camidge Ross , Narayanan Vignhesh , Doebele Robert C. , Besse Benjamin , Remon-Masip Jordi , Janne Pasi A. , Awad Mark M. , Peled Nir , Byoung Chul-Cho , Karp Daniel D. , Van Den Heuvel Michael , Wakelee Heather A. , Neal Joel W. , Mok Tony S.K. , Yang James C.H. , Ou Sai-Hong Ignatius , Pall Georg , Froesch Patrizia , Zalcman Gérard , Gandara David R. , Riess Jonathan W. , Velcheti Vamsidhar , Zeidler Kristin , Diebold Joachim , Früh Martin , Michels Sebastian , Monnet Isabelle , Popat Sanjay , Rosell Rafael , Karachaliou Niki , Rothschild Sacha I. , Shih Jin-Yuan , Warth Arne , Muley Thomas , Cabillic Florian , Mazières Julien , Drilon Alexander 
Published: April 2017

Purpose In addition to prospective trials for non–small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data—clinical, pathologic, and molecular features—were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.
Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study
Authors: Apolo Andrea B. , Infante Jeffrey R. , Balmanoukian Ani , Patel Manish R. , Wang Ding , Kelly Karen , Mega Anthony E. , Britten Carolyn D. , Ravaud Alain , Mita Alain C. , Safran Howard , Stinchcombe Thomas E. , Srdanov Marko , Gelb Arnold B. , Schlichting Michael , Chin Kevin , Gulley James L. 
Published: April 2017

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.