bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA46: Towards implementation of T-cell therapy in pancreatic cancer
Authors: Offringa Rienk , Poschke Isabel , Volkmar Michael , Strobel Oliver , Bergmann Frank , Halama Niels , Jäger Dirk , Sahin Ugur , Büchler Markus 
Published: May 2016

Abstract
In contrast to the general belief that pancreatic ductal adenocarcinoma is a poorly immunogenic tumor, we found cumulative evidence for an adaptive immune response in this aggressive cancer type. Immunohistochemistry reveals prominent T-cell infiltrates in the majority (~ 70%) of tumor biopsies, and these tumor-infiltrating lymphocytes (TILs) can be isolated and expanded ex vivo with similar efficiency as those isolated from melanoma. Furthermore, comparison of the T-cell receptor repertoire between TIL and PBMC isolates from patients points at the selective expansion of T-cell subsets in the tumors. Finally, in ~ 50% of tumor specimen, T-cell infiltration is accompanied by the presence of tertiary lymphoid structures that comprise areas rich in CD3+ T-cells and CD208+ dendritic cells as well as areas rich in B-cells and follicular dendritic cells.
Based on these findings, our current efforts aim at:
- Evaluating neoadjuvant treatment with agonist immunostimulatory antibodies as a means to mobilize this pre-existing immune response in patients with primary resectable disease*
- Analysis of the anti-tumor reactivity and antigen-specificity of TCR-species that are prominently enriched in the tumor as compared to PBMC.
- Exploration of TIL therapy for treatment of recurrent disease.
* Clinical trial in context of FP7 EU IACT program; Immunostimulatory Antibodies for Cancer Treatment
Citation Format: Rienk Offringa, Isabel Poschke, Michael Volkmar, Oliver Strobel, Frank Bergmann, Niels Halama, Dirk Jäger, Ugur Sahin, Markus Büchler. Towards implementation of T-cell therapy in pancreatic cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA46.
Abstract PR002: Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens
Authors: Prickett Todd D. , Crystal Jessica , Gartner Jared , Yao Xin , Pasetto Anna , Gros Alena , Lu Yong-Chen , Li Yong F. , El-Gamil Mona , Rosenberg Steven A. , Robbins Paul 
Published: May 2016

Abstract
Durable complete response rates of 20% have been observed in clinical trials of patients with metastatic melanoma employing adoptive cell transfer (ACT) of patient derived tumor infiltrating lymphocytes (TIL). Here we provide a detailed analysis of the response of TIL administered to a patient with metastatic melanoma who exhibited a complete response ongoing greater than 3 years. Using whole-exome and RNA-Seq sequencing and bioinformatic analysis of the patient's matched tumor and normal gDNA we identified over 4,000 non-synonymous somatic mutation variants. We screened 745 somatically mutated genes using tandem minigene constructs expressing transcripts expressed in autologous tumor cells whose expression levels were greater than 0.1% of the levels of beta actin. These tandem minigenes were then transfected into autologous B cells and then analyzed for their ability to stimulate the administered T cells. Our results indicated that the autologous TIL distinctly recognized 10 somatically mutated gene products, each of which was recognized in the context of three different HLA class I restriction elements expressed by the patient's tumor. Detailed T cell clonal analysis revealed that 9 of the top 20 most prevalent clones present in the infused TIL, comprised over ¼ of total infused cells and recognized mutated antigens. These results further supported our efforts to identify and enrich mutation-reactive T cells for the treatment of patients with metastatic cancer.
Citation Format: Todd D. Prickett, Jessica Crystal, Jared Gartner, Xin Yao, Anna Pasetto, Alena Gros, Yong-Chen Lu, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul Robbins. Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr PR002.
Abstract PR003: Hypoxia is an essential driver of immune suppression in the tumor microenvironment
Authors: Ai Midan , Budhani Pratha , Curran Michael A. 
Published: May 2016

Abstract
Tumor hypoxia predicts poor outcomes across all cancers and has long been recognized as a critical source of resistance to both chemotherapy and radiotherapy. Despite the success of T cell immune checkpoint blockade in treating melanoma, aggressive adenocarcinomas of the prostate and pancreas are largely resistant to CTLA-4 and PD-1 antibody therapy in the mouse and in man. We find that hypoxic zones of these tumors resist infiltration by T cells even in the context of robust infiltration of normoxic areas of the same tumor (e.g. in the context of T cell checkpoint blockade). Beyond this lack of accessibility to tumor-specific T cells, hypoxia drives the establishment of a highly interdependent network of immunosuppressive stromal cells. Among these, we find myeloid-derived suppressor cells and myofibroblasts to be the critical populations which act together to suppress T cell responses and mediate immunotherapy resistance.
Using the hypoxia-specific prodrug Evofosfamide, we show that disruption of hypoxia in both transplantable and genetically-engineered murine models of prostate cancer sensitizes them to antibody blockade of CTLA-4 and PD-1. Loss of immune resistance is a consequence of re-oxygenation of hypoxia zones which results in 1) loss of myeloid suppressors, 2) reduced capacity to suppressively polarize new myeloid immigrants, and 3) loss of suppressive activation of myofibroblasts. This combination of hypoxia disruption and T cell checkpoint blockade has immense potential to render some of the most therapeutically resistant cancers sensitive to immunotherapy.
Citation Format: Midan Ai, Pratha Budhani, Michael A. Curran. Hypoxia is an essential driver of immune suppression in the tumor microenvironment. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr PR003.
Endovascular Hypothermia in Acute Ischemic Stroke
Authors: Chen Jian , Liu Liqiang , Zhang Hongqi , Geng Xiaokun , Jiao Liqun , Li Guilin , Coutinho Jonathan M. , Ding Yuchuan , Liebeskind David S. , Ji Xunming 
Published: May 2016

Background and Purpose—
We conducted a pilot feasibility and safety study of selective brain cooling with intra-arterial infusion of cold saline combined with endovascular reperfusion for acute ischemic stroke.

Methods—
Patients with large-vessel occlusion within 8 hours after symptom onset were enrolled. All patients received intra-arterial recanalization combined with infusion of cold isotonic saline (4°C) in the ischemic territory through the angiographic catheter.

Results—
Twenty-six patients underwent the procedure, which was technically successful in all. The temperature of ischemic cerebral tissue was decreased by at least 2°C during infusion of the cold solution, and systemic temperature was mildly reduced (maximum 0.3°C). No obvious complications related to intra-arterial hypothermia were observed.

Conclusions—
Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke seems feasible and safe.
Electroluminescent Materials Can Further Enhance the Nighttime Conspicuity of Pedestrians Wearing Retroreflective Materials
Authors: Fekety Drea K. , Edewaard Darlene E. , Stafford Sewall Ashley A. , Tyrrell Richard A. 
Published: May 2016

Objective: We investigated the nighttime conspicuity benefits of adding electroluminescent (EL) panels to pedestrian clothing that contains retroreflective elements. Background: Researchers have repeatedly documented that pedestrians are too often not sufficiently conspicuous to drivers at night and that retroreflective materials can enhance the conspicuity of pedestrians. However, because retroreflective elements in clothing are effective only when they are illuminated by the headlamps of an approaching driver, they are not useful for pedestrians who are positioned outside the beam pattern of an approaching vehicle’s headlamps. Electroluminescent materials—flexible luminous panels that can be attached to clothing—have the potential to be well suited for these conditions. Method: Using an open-road course at night, we compared the distances at which observers responded to pedestrians who were positioned at one of three lateral positions (relative to the vehicle’s path) wearing one of two high-visibility garments. Results: The garment that included both EL and retroreflective materials yielded longer response distances than the retroreflective-only garment. This effect was particularly strong when the test pedestrian was positioned farthest outside of the area illuminated by headlamps. Conclusion: These findings suggest that EL materials can further enhance the conspicuity of pedestrians who are wearing retroreflective materials. Application: EL materials can be applied to garments. They may be especially valuable to enhance the conspicuity of roadway workers, emergency responders, and traffic control officers.
Andrés Wood’s Machuca and Violeta Went to Heaven
Authors: Vilches Patricia 
Published: May 2016

A suppressed collective memory of the 1960s and early 1970s is now emergent among all Chileans, at home and abroad, including those who once wished to forget or to deny the violence, division, and injustice of the Chilean dictatorship. The treatment of class conflict and social division in two films directed by Andrés Wood— Machuca and Violeta Went to Heaven—has contributed to this awakening, pointing out that cultural experiences and economic destiny in Chile have been determined by divided geographical spaces. La memoria colectiva de los años 60 y principios de los 70 en Chile, que había estado suprimida hasta ahora, está surgiendo entre todos los chilenos, dentro y fuera del país, incluso entre aquellos que una vez desearon olvidar o negar la violencia, las divisiones y las injusticias de la dictadura chilena. El tratamiento de los conflictos de clase y las divisiones sociales en dos películas dirigidas por Andrés Wood— Machuca y Violeta se fue a los cielos—ha contribuido a este despertar, al señalar que las experiencias culturales y el destino económico de Chile han sido determinados por unos espacios geográficos divididos.
The Effect of “Opt-Out” Regulation on Access to Surgical Care for Urgent Cases in the United States: Evidence from the National Inpatient Sample
Authors: Sun Eric , Dexter Franklin , Miller Thomas R. 
Published: May 2016

BACKGROUND:
In 2001, the Center for Medicare and Medicaid Services issued a rule permitting states to “opt-out” of federal regulations requiring physician supervision of nurse anesthetists. We examined the extent to which this rule increased access to anesthesia care for urgent cases.

METHODS:
Using data from a national sample of inpatient discharges, we examined whether opt-out was associated with an increase in the percentage of patients receiving a therapeutic procedure among patients admitted for appendicitis, bowel obstruction, choledocholithiasis, or hip fracture. We chose these 4 diagnoses because they represent instances where urgent access to a procedure requiring anesthesia is often indicated. In addition, we examined whether opt-out was associated with a reduction in the number of appendicitis patients who presented with a ruptured appendix. In addition to controlling for patient morbidities and demographics, our analysis incorporated a difference-in-differences approach, with additional controls for state-year trends, to reduce confounding.

RESULTS:
Across all 4 diagnoses, opt-out was not associated with a statistically significant change in the percentage of patients who received a procedure (0.0315 percentage point increase, 95% confidence interval [CI] −0.843 to 0.906 percentage point increase). When broken down by diagnosis, opt-out was also not associated with statistically significant changes in the percentage of patients who received a procedure for bowel obstruction (0.511 percentage point decrease, 95% CI −2.28 to 1.26), choledocholithiasis (2.78 percentage point decrease, 95% CI −6.12 to 0.565), and hip fracture (0.291 percentage point increase, 95% CI −1.76 to 2.94). Opt-out was associated with a small but statistically significant increase in the percentage of appendicitis patients receiving an appendectomy (0.876 percentage point increase, 95% CI 0.194 to 1.56); however, there was no significant change in the percentage of patients presenting with a ruptured appendix (−0.914 percentage point decrease, 95% CI −2.41 to 0.582). Subanalyses showed that the effects of opt-out did not differ in rural versus urban areas.

CONCLUSIONS:
Based on 2 measures of access, opt-out does not appear to have significantly increased access to anesthesia for urgent inpatient conditions.
DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C
Authors: Klein Sarah , Dieterich Lothar C. , Mathelier Anthony , Chong Chloé , Sliwa-Primorac Adriana , Hong Young-Kwon , Shin Jay W. , Lizio Marina , Itoh Masayoshi , Kawaji Hideya , Lassmann Timo , Daub Carsten O. , Arner Erik ,   The FANTOM consortium, Carninci Piero , Hayashizaki Yoshihide , Forrest Alistair R. R. , Wasserman Wyeth W. , Detmar Michael 
Published: May 2016

ABSTRACT
Lymphangiogenesis plays a crucial role during development, in cancer metastasis and in inflammation. Activation of VEGFR-3 (also known as FLT4) by VEGF-C is one of the main drivers of lymphangiogenesis, but the transcriptional events downstream of VEGFR-3 activation are largely unknown. Recently, we identified a wave of immediate early transcription factors that are upregulated in human lymphatic endothelial cells (LECs) within the first 30 to 80 min after VEGFR-3 activation. Expression of these transcription factors must be regulated by additional pre-existing transcription factors that are rapidly activated by VEGFR-3 signaling. Using transcription factor activity analysis, we identified the homeobox transcription factor HOXD10 to be specifically activated at early time points after VEGFR-3 stimulation, and to regulate expression of immediate early transcription factors, including NR4A1. Gain- and loss-of-function studies revealed that HOXD10 is involved in LECs migration and formation of cord-like structures. Furthermore, HOXD10 regulates expression of VE-cadherin, claudin-5 and NOS3 (also known as e-NOS), and promotes lymphatic endothelial permeability. Taken together, these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability.
A qualitative meta-synthesis of young peoples' experiences of ‘sexting’
Authors: Wilkinson Yvonne , Whitfield Clare , Hannigan Sue , Azam Ali Parveen , Hayter Mark 
Published: May 2016

Objective: To conduct a meta-synthesis of the qualitative research to explore young people's experiences and use of smart phones to send and receive sexually focused messages and images. Design: A qualitative meta-synthesis was conducted on the retrieved papers following a systematic search of PUBMED, Cumulative Index to Nursing and Allied Health Literature (CINAHL), COCHRANE, Embase, Medline and Psycinfo. The sample included five qualitative studies with a total sample size of 480 participants. Results: The meta-synthesis of the papers resulted in the development of four central themes: gender inequity, popularity with peers, relationship context, and costs and benefits. Conclusions: Drawing the qualitative work together highlights the manner in which ‘sexting’ is more nuanced than traditional ‘cyber-bullying’. The consensual sending of intimate images is a highly gendered activity. The gender issues require work with female students to explore the issue of ‘sexting’ and how it can be harmful. Work with male students around the issues of respect and gender harassment in relation to ‘sexting’ is also required and should contribute to sex and relationships education. The results indicate that school nurses working with young people need to build discussions about the use of technology within relationships into their work with young people.
Organizational factors influencing journalists’ use of user-generated content: A case of Canadian radio newsrooms
Authors: Bonin Geneviève A. 
Published: May 2016

Abstract
Using an evaluation framework, this study sheds light on the organizational factors that influence the use of user-generated content (UGC) in radio newsrooms. Although communication research is consistently emphasizing rapid changes in technology and the need for journalists to adapt to their multi-platform environments, this study shows that some radio journalists and managers, at least, are still quite conservative in their innovative practices. Through the use of semi-structured interviews with radio managers and journalists in a major Canadian market, five main uses of UGC were identified in the newsroom. These factors were directly related to the perceived notion of the audience and its value to news reporting. Financial pressures, company policy and professional standards are the three main organizational factors that influence these uses and the extent to which the practices were observed. Age, language and sectorial differences did not appear to be influential in this study. These results, however, suggest that work still needs to be done to establish which factors are most relevant in overcoming fears and challenges with respect to innovative UGC use. A better knowledge of the audience could also influence future behaviour.
Towards Clinical Bioinformatics: Redux 2015
Authors: Altman R. B. 
Published: May 2016

SummaryIn 2004, medical informatics as a scientific community recognized an emerging field of “clinical bioinformatics” that included work bringing bioinformatics data and knowledge into the clinic. In the intervening decade, “translational biomedical informatics” has emerged as the umbrella term for the work that brings together biological entities and clinical entities. The major challenges continue: understanding the clinical significance of basic ‘omics’ (and other) measurements, and communicating this to increasingly empowered patients/consumers who often have access to this information outside usual medical channels. It has become clear that basic molecular information must be combined with environmental and lifestyle data to fully define, predict, and manage health status..
Preface - Access to Knowledge Revisited
Authors: Humphreys Betsy L. , Lindberg Donald A.B. 
Published: May 2016

Summary
Objective: To review and update the Preface to the 1998 Yearbook of Medical Informatics, which had as its Special Topic “Health Informatics and the Internet”.
Method: Assessment of the accuracy of predictions made in 1998 and consideration of key developments in informatics since that time.
Results: Predictions made in 1998 were generally accurate regarding reduced dependence on keyboards, expansion of multimedia, medical data privacy policy development, impact of molecular biology on knowledge and treatment of neoplasms, and use of imaging and informatics to advance understanding of brain structure and function. Key developments since 1998 include the huge increase in publicly available electronic information; acknowledgement by leaders in government and science of the importance of biomedical informatics to societal goals for health, health care, and scientific discovery; the influence of the public in promoting clinical research transparency and free access to government-funded research results; the long-awaited arrival of electronic health records; and the “Cloud” as a 21st century reformulation of contracting out the computer center. Conclusions: There are many challenging and important problems that deserve the attention of the informatics community. Informatics researchers will be best served by embracing a very broad definition of medical informatics and by promoting public understanding of the field.
Development of a stability-indicating HPLC method and a dissolution test for rivaroxaban dosage forms
Authors: Souri Effat , Mottaghi Siavash , Zargarpoor Mohammad , Ahmadkhaniha Reza , Jalalizadeh Hassan 
Published: May 2016

Rivaroxaban is an inhibitor of factor Xa, which is used as an oral anticoagulant for the prevention of thromboembolism. The objective of this study was to develop a stability-indicating high-performance liquid chromatographic method for the quantitative determination of rivaroxaban in pharmaceutical dosage forms. Rivaroxaban was subjected to acidic, basic, oxidative, photolytic, and thermal conditions for forced stress degradation studies. Considerable degradation was observed in all stress degradation tests. Rivaroxaban and its degradation products were separated on a Nova-Pak C8 column utilizing a mixture of acetonitrile and KH2PO4 50 mM (pH 3.0) (40:60, v/v) as the mobile phase, and the chromatogram was recorded at 270 nm using a general ultraviolet (UV) detector.
The developed method was linear over the concentration range of 1–50 μg mL−1 showing acceptable within-day and between-day precision and accuracy values (CV <2% and Error <2%). The dissolution profile of rivaroxaban tablets was also studied in the presence of a surfactant using optimized conditions. The validated method was successfully used for the determination of rivaroxaban in dosage forms and also in dissolution medium indicating the specificity of the assay method.
Young People’s More Permissive Views About Marijuana: Local Impact of State Laws or National Trend?
Authors: Schmidt Laura A. , Jacobs Laurie M. , Spetz Joanne 
Published: May 2016

Objectives. To determine whether state medical marijuana laws “send the wrong message,” that is, have a local influence on the views of young people about the risks of using marijuana. Methods. We performed multilevel, serial, cross-sectional analyses on 10 annual waves of the US National Survey on Drug Use and Health (2004–2013) nationally and for states with marijuana laws using individual- and state-level controls. Results. Living in medical marijuana states was associated with more permissive views regarding marijuana across 5 different measures. However, these associations became non–statistically significant after we adjusted for state-level differences. By contrast, there was a consistent and significant national time trend toward more permissive attitudes, which was less pronounced among children of middle school age than it was among their older counterparts. Conclusions. Passing medical marijuana laws does not seem to directly affect the views of young people in medical marijuana states. However, there is a national trend toward young people taking more permissive views about marijuana independent of any effects within states.