bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA13: Engineered T cells for cancer therapy
Authors: June Carl 
Published: May 2016

Abstract
Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a limited survival. Chimeric antigen receptor (CAR)-modified T cells targeting CD19 may overcome the limitation of low complete response rates with conventional therapies with the potential to induce sustained remissions in patients with refractory B-cell malignancies. We previously reported preliminary results on three patients with refractory CLL. Here we report the mature results from our initial trial using CAR modified T cells to treat 14 patients with relapsed and refractory CLL (1). Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14–11 ×108 CTL019 cells (median 1.6 x 108 cells). Patients were monitored for toxicity, response, expansion and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8/14 (57%), with 4 complete remissions (CR), and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and CAR T cells have persisted and remain functional beyond 4 years in the first two patients achieving CR; no patient in CR has relapsed. All responding patients have developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease is not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL.
In separate studies we have asked whether the same CD19 CAR may have activity in tumors that do not express CD19. A patient with refractory multiple myeloma was treated with CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, following myeloablative chemotherapy (melphalan 140 mg/m2) and autologous stem cell transplantation (2). Four years earlier, autologous transplantation with a higher melphalan dose (200 mg/m2) had induced only a partial, transient response. Autologous transplantation followed by CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at last evaluation, 12 months after treatment. This response was achieved despite absence of CD19 expression in 99.95% of this patient's neoplastic plasma cells.
References:
1. Porter DL, et al. Science Transl Med, 2015 (in press)
2. Garfall A, et al. N Engl J Med, 2015 (in press)
Citation Format: Carl June. Engineered T cells for cancer therapy. [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 IA13.
Abstract IA14: Engaging T cells against cancer: BLINCYTO® and beyond – the BiTE® platform
Authors: Nagorsen Dirk 
Published: May 2016

Abstract
T-cell-based cancer immunotherapies are at the forefront of a new era in cancer treatment. Engaging T cells through BiTE® (bispecific T-cell engager) antibody constructs is one of the most advanced immunotherapeutic approaches.
BiTE® antibody constructs have a unique design and mechanism of action. They are constructed by genetically linking the minimal binding domains of monoclonal antibodies for a tumor-associated surface antigen and for the T-cell receptor-associated molecule CD3 onto a single polypeptide chain. Concurrent engagement of the target cell antigen and CD3 leads to activation of polyclonal cytotoxic T-cells, resulting in target cell lysis.
The first BiTE®, blinatumomab, targeting CD19 and CD3, is being investigated in a broad range of B-cell malignancies and has recently received an accelerated approval by the US FDA for Philadelphia chromosome-negative relapsed/refractory B-acute lymphoblastic leukemia under the trade name BLINCYTO®. In addition, several BiTE® antibody constructs targeting other tumor antigens have entered the clinical stage of development. Most recent updates about the BiTE® platform will be presented.
Citation Format: Dirk Nagorsen. Engaging T cells against cancer: BLINCYTO® and beyond – the BiTE® platform. [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 IA14.
Reassessing the Stroke Belt
Authors: Karp David N. , Wolff Catherine S. , Wiebe Douglas J. , Branas Charles C. , Carr Brendan G. , Mullen Michael T. 
Published: May 2016

Background and Purpose—
The stroke belt is described as an 8-state region with high stroke mortality across the southeastern United States. Using spatial statistics, we identified clusters of high stroke mortality (hot spots) and adjacent areas of low stroke mortality (cool spots) for US counties and evaluated for regional differences in county-level risk factors.

Methods—
A cross-sectional study of stroke mortality was conducted using Multiple Cause of Death data (Centers for Disease Control and Prevention) to compute age-adjusted adult stroke mortality rates for US counties. Local indicators of spatial association statistics were used for hot-spot mapping. County-level variables were compared between hot and cool spots.

Results—
Between 2008 and 2010, there were 393 121 stroke-related deaths. Median age-adjusted adult stroke mortality was 61.7 per 100 000 persons (interquartile range=51.4–74.7). We identified 705 hot-spot counties (22.4%) and 234 cool-spot counties (7.5%); 44.5% of hot-spot counties were located outside of the stroke belt. Hot spots had greater proportions of black residents, higher rates of unemployment, chronic disease, and healthcare utilization, and lower median income and educational attainment.

Conclusions—
Clusters of high stroke mortality exist beyond the 8-state stroke belt, and variation exists within the stroke belt. Reconsideration of the stroke belt definition and increased attention to local determinants of health underlying small area regional variability could inform targeted healthcare interventions.
Hamstring Reinjuries Occur at the Same Location and Early After Return to Sport
Authors: Wangensteen Arnlaug , Tol Johannes L. , Witvrouw Erik , Van Linschoten Robbart , Almusa Emad , Hamilton Bruce , Bahr Roald 
Published: May 2016

Background: Despite relatively high reinjury rates after acute hamstring injuries, there is a lack of detailed knowledge about where and when hamstring reinjuries occur, and studies including imaging-confirmed reinjuries are scarce. Purpose: To investigate the location, radiological severity, and timing of reinjuries on magnetic resonance imaging (MRI) compared with the index injury. Study Design: Case series; Level of evidence, 4. Methods: A MRI scan was obtained ≤5 days after an acute hamstring index injury in 180 athletes, and time to return to sport (RTS) was registered. Athletes with an MRI-confirmed reinjury in the same leg ≤365 days after RTS were included. Categorical grading and standardized MRI parameters of the index injury and reinjury were scored by a single radiologist (with excellent intraobserver reliability). To determine the location of the reinjury, axial and coronal views of the index injury and reinjury were directly compared on proton density–weighted fat-suppressed images. Results: In the 19 athletes included with reinjury, 79% of these reinjuries occurred in the same location within the muscle as the index injury. The median time to RTS after the index injury was 19 days (range, 5-37 days; interquartile range [IQR], 15 days). The median time between the index injury and reinjury was 60 days (range, 20-316 days; IQR, 131 days) and the median time between RTS after the index injury and the reinjury was 24 days (range, 4-311 days; IQR, 140 days). More than 50% of reinjuries occurred within 25 days (4 weeks) after RTS from the index injury and 50% occurred within 50 days after the index injury. All reinjuries with more severe radiological grading occurred in the same location as the index injury. Conclusion: The majority of the hamstring reinjuries occurred in the same location as the index injury, early after RTS and with a radiologically greater extent, suggesting incomplete biological and/or functional healing of the index injury. Specific exercise programs focusing on reinjury prevention initiated after RTS from the index injury are highly recommended.
Comparison of Indiana High School Football Injury Rates by Inclusion of the USA Football “Heads Up Football” Player Safety Coach
Authors: Kerr Zachary Y. , Dalton Sara L. , Roos Karen G. , Djoko Aristarque , Phelps Jennifer , Dompier Thomas P. 
Published: May 2016

Background: In Indiana, high school football coaches are required to complete a coaching education course with material related to concussion awareness, equipment fitting, heat emergency preparedness, and proper technique. Some high schools have also opted to implement a player safety coach (PSC). The PSC, an integral component of USA Football’s Heads Up Football (HUF) program, is a coach whose primary responsibility is to ensure that other coaches are implementing proper tackling and blocking techniques alongside other components of the HUF program. Purpose: To compare injury rates in Indiana high school football teams by their usage of a PSC or online coaching education only. Study Design: Cohort study; Level of evidence, 2. Methods: Athletic trainers (ATs) evaluated and tracked injuries at each practice and game during the 2015 high school football season. Players were drawn from 6 teams in Indiana. The PSC group, which used the PSC component, was comprised of 204 players from 3 teams. The “education only” group (EDU), which utilized coaching education only, was composed of 186 players from 3 teams. Injury rates and injury rate ratios (IRRs) were reported with 95% confidence intervals (CIs). Results: During 25,938 athlete-exposures (AEs), a total of 149 injuries were reported, of which 54 (36.2%) and 95 (63.8%) originated from the PSC and EDU groups, respectively. The practice injury rate was lower in the PSC group than the EDU group (2.99 vs 4.83/1000 AEs; IRR, 0.62; 95% CI, 0.40-0.95). The game injury rate was also lower in the PSC group than the EDU group (11.37 vs 26.37/1000 AEs; IRR, 0.43; 95% CI, 0.25-0.74). When restricted to concussions only, the rate was lower in the PSC group (0.09 vs 0.73/1000 AEs; IRR, 0.12; 95% CI, 0.01-0.94), although only 1 concussion was reported in the PSC group. No differences were found in game concussion rates (0.60 vs 4.39/1000 AEs; IRR, 0.14; 95% CI, 0.02-1.11). Conclusion: Findings support the PSC as an effective method of injury mitigation in high school football. Future research should seek to replicate this study using larger samples from additional states.
Perioperative Supplemental Oxygen Does Not Worsen Long-Term Mortality of Colorectal Surgery Patients
Authors: Podolyak Attila , Sessler Daniel I. , Reiterer Christian , Fleischmann Edith , Akça Ozan , Mascha Edward J. , Greif Robert , Kurz Andrea 
Published: May 2016

BACKGROUND:
A follow-up analysis from a large trial of oxygen and surgical-site infections reported increased long-term mortality among patients receiving supplemental oxygen, especially those having cancer surgery. Although concerning, there is no obvious mechanism linking oxygen to long-term mortality. We thus tested the hypothesis that supplemental oxygen does not increase long-term mortality in patients undergoing colorectal surgery. Secondarily, we evaluated whether the effect of supplemental oxygen on mortality depended on cancer status.

METHODS:
Mortality data were obtained for 927 patients who participated in 2 randomized trials evaluating the effect of supplemental oxygen on wound infection. We assessed the effect of 80% vs 30% oxygen on long-term mortality across 4 clinical sites in the 2 trials using a Cox proportional hazards regression model stratified by study and site. Kaplan-Meier survival estimates were calculated for each trial. Finally, we report site-stratified hazard ratios for patients with and without cancer at baseline.

RESULTS:
There was no effect of 80% vs 30% oxygen on mortality, with an overall site-stratified hazard ratio of 0.93 (95% confidence interval [CI], 0.72–1.20; P = 0.57). The treatment effect was consistent across the 2 original studies (interaction P = 0.88) and across the 4 sites (P = 0.84). There was no difference between patients with (n = 451) and without (n = 450) cancer (interaction P = 0.51), with hazard ratio of 0.85 (95% CI, 0.64–1.1) for cancer patients and 0.97 (0.53–1.8) for noncancer patients.

CONCLUSIONS:
In contrast to the only previous publication, we found that supplemental oxygen had no influence on long-term mortality in the overall surgical population or in patients having cancer surgery.
T cell adhesion triggers an early signaling pole distal to the immune synapse
Authors: Guedj Chloé , Abraham Nicolas , Jullié Damien , Randriamampita Clotilde 
Published: May 2016

ABSTRACT
The immunological synapse forms at the interface between a T cell and an antigen-presenting cell after foreign antigen recognition. The immunological synapse is considered to be the site where the signaling cascade leading to T lymphocyte activation is triggered. Here, we show that another signaling region can be detected before formation of the synapse at the opposite pole of the T cell. This structure appears during the first minute after the contact forms, is transient and contains all the classic components that have been previously described at the immunological synapse. Its formation is independent of antigen recognition but is driven by adhesion itself. It constitutes a reservoir of signaling molecules that are potentially ready to be sent to the immunological synapse through a microtubule-dependent pathway. The antisynapse can thus be considered as a pre-synapse that is triggered independently of antigen recognition.
Cdk-dependent phosphorylation regulates TRF1 recruitment to PML bodies and promotes C-circle production in ALT cells
Authors: Wilson Florence R. , Ho Angus , Walker John R. , Zhu Xu-Dong 
Published: May 2016

ABSTRACT
TRF1, a duplex telomeric DNA binding protein, is implicated in homologous-recombination-based alternative lengthening of telomeres, known as ALT. However, how TRF1 promotes ALT activity has yet to be fully characterized. Here we report that Cdk-dependent TRF1 phosphorylation on T371 acts as a switch to create a pool of TRF1, referred to as (pT371)TRF1, which is recruited to ALT-associated PML bodies (APBs) in S and G2 phases independently of its binding to telomeric DNA. We find that phosphorylation of T371 is essential for APB formation and C-circle production, both of which are hallmarks of ALT. We show that the interaction of (pT371)TRF1 with APBs is dependent upon ATM and homologous-recombination-promoting factors Mre11 and BRCA1. In addition, (pT371)TRF1 interaction with APBs is sensitive to transcription inhibition, which also reduces DNA damage at telomeres. Furthermore, overexpression of RNaseH1 impairs (pT371)TRF1 recruitment to APBs in the presence of campothecin, an inhibitor that prevents topoisomerase I from resolving RNA–DNA hybrids. These results suggest that transcription-associated DNA damage, perhaps arising from processing RNA–DNA hybrids at telomeres, triggers (pT371)TRF1 recruitment to APBs to facilitate ALT activity.
Making ‘Maximum Fun’ for fans: Examining podcast listener participation online
Authors: Wrather Kyle 
Published: May 2016

Abstract
This article analyses how three podcasts from the independent podcast network Maximum Fun use online spaces to cultivate audience engagement and listener interest. While some of these listener engagement techniques are not unique to podcasting, they offer examples of how podcasters have built strong audience connections by expanding interaction beyond their episodes and into the online spaces young, tech-savvy listeners often frequent. Specifically, this article compares how three podcast shows on the Maximum Fun network promote and use different online spaces (forums, social networks and blogs) to engage listeners and cultivate community.
Negotiating the Boundaries of Power: Abdoulaye Wade, the Muridiyya, and State Politics in Senegal, 2000–2012
Authors: Babou Cheikh Anta 
Published: May 2016

Abstract
Research on the state and governance in Senegal emphasizes the political role of Muslim orders (brotherhoods). These orders, and especially the Muridiyya, are at the center of the so-called “Senegalese social contract,” which, according to many observers, is the reason for the remarkable political stability of the postcolonial state. This contract, which has been thoroughly discussed by scholars, functions as a system for the exchange of services in which the state and the Sufi orders, even though apparently situated in different sociopolitical spaces, collaborate in preserving peace and stability. Along with other scholars, I have criticized the notion of “social contract,” especially the underlying assumption that shaykhs have total control over disciples, who are prepared to follow the path laid out by their spiritual guides without concern for their own interests. In this article, I explore the impact that the momentous political change in the year 2000 had on the relations between temporal and spiritual power in Senegal. I suggest that President Wade’s attempt to turn the Muridiyya into a political base is best understood as an experiment in caesaropapism and his failure portends a return to the apparent political neutrality and behind-the- scenes political transactions that have marked the history of the relations between the state and Sufi orders.
Rights, Equality and Procreation
Authors: Casal Paula , Williams Andrew 
Published: May 2016

Abstract
Individual decisions about how to exercise the legal right to procreative liberty may generate either positive or negative externalities. From within a resource egalitarian perspective, such as that of Ronald Dworkin, it can be argued that procreative justice is asymmetric in the following respect. Justice need not require that parents be subsidised if they produce a public good, yet its ideal achievement may require their activities be taxed if they threaten to produce a public bad.
Human Altruism – Proximate Patterns and Evolutionary Origins
Authors: Fehr Ernst , Fischbacher Urs 
Published: May 2016

Abstract
Are people selfish or altruistic? Throughout history this question has been answered on the basis of much introspection and little evidence. It has been at the heart of many controversial debates in politics, science, and philosophy. Some of the most fundamental questions concerning our evolutionary origins, our social relations, and the organization of society are centered around issues of altruism and selfishness. Experimental evidence indicates that human altruism is a powerful force and unique in the animal world. However, there is much individual heterogeneity and the interaction between altruists and selfish individuals is key for understanding the evolutionary dynamics as well as the proximate patterns of human cooperation. Depending on the environment, a minority of altruists can force a majority of selfish individuals to cooperate or, conversely, a few egoists can induce a large number of altruists to defect. Current gene-based evolutionary theories cannot explain important patterns of human altruism pointing towards the need for theories of cultural evolution and gene-culture coevolution.
Reconsidering Relational Autonomy. Personal Autonomy for Socially Embedded and Temporally Extended Selves
Authors: Baumann Holger 
Published: May 2016

Abstract
Most recent accounts of personal autonomy acknowledge that the social environment a person lives in, and the personal relationships she entertains, have some impact on her autonomy. Two kinds of conceptualizing social conditions are traditionally distinguished in this regard: Causally relational accounts hold that certain relationships and social environments play a causal role for the development and on-going exercise of autonomy. Constitutively relational accounts, by contrast, claim that autonomy is at least partly constituted by a person’s social environment or standing. The central aim of this paper is to raise the question how causally and constitutively relational approaches relate to the fact that we exercise our autonomy over time. I argue that once the temporal scope of autonomy is opened up, we need not only to think differently about the social dimension of autonomy. We also need to reconsider the very distinction between causally and constitutively relational accounts, because it is itself a synchronic (and not a diachronic) distinction.
The Renewed Promise of Medical Informatics
Authors: van Bemmel J. H. , McCray A. T. 
Published: May 2016

SummaryThe promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier. Each expert was also invited to comment on what might be expected in the future. In the present paper, these areas are briefly reviewed again. Where did these early papers have an impact and where were they not as successful as originally expected? It should be noted that the extraordinary developments in computer technology observed in the last two decades could not have been foreseen by these early researchers. In closing, some of the possibilities and limitations of research in medical informatics are outlined in the context of a framework that considers six levels of computer applications in medicine and health care. For each level, some predictions are made for the future, concluded with thoughts on fruitful areas for ongoing research in the field.
Silver Anniversary: 25 Editions of the IMIA Yearbook
Authors: Lehmann Christoph , Jaulent Marie-Christine , Séroussi Brigitte 
Published: May 2016

Summary
Objectives: To provide an editorial introduction into the special 25th anniversary edition of the IMIA Yearbook of Medical Informatics with discussion of the significance of the Yearbook, past and current editorial teams, and a look into the future. Methods: A brief overview of the 2016 anniversary edition of the Yearbook allows for a discussion of the significance and value of the Yearbook to the Biomedical Informatics community as well as a review of changes in Yearbook team and format over time. Results: The IMIA Yearbook celebrates its 25th edition bearing witness to the quality of the IMIA brand, the Yearbook content, as well as to the dedication of and the inordinate amount of labor from the authors and editors of the Yearbook. Editorial teams are to be applauded for their hard work and for their foresight in steering the Yearbook from a paperback to an open access online publication. The special edition provides reviews of past editorials with the knowledge of today.
Conclusions: The IMIA Yearbook celebrates a remarkable milestone providing a testament to the maturity of the Biomedical Informatics field. Informaticians across the world are encouraged to thank past editorial teams and celebrate with IMIA.