bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B135: Chemotherapy for esophageal cancer: Off-target effect and biomarker
Authors: Takeoka Tomohira , Goto Kumiko , Matsumoto Mitsunobu , Miyazaki Yasuhiro , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Takiguchi Shuji , Mori Masaki , Doki Yuichiro , Wada Hisashi 
Published: November 2016

Abstract
Background/Purpose: For esophageal cancer patients, combination chemotherapy with docetaxel, cisplatin, and 5FU (DCF therapy) is adopted for neoadjuvant chemotherapy (NAC). Although the response rate is high (72.5%), further investigation of indicators to predict its therapeutic effects is needed because of its side effects, and few have been reported. In this study, we obtained peripheral blood before and after the DCF therapy, analyzed various immune related cells by flow cytometry and tried to identify indicators to predict its therapeutic effects.
Subjects/Methods: Peripheral blood were obtained from 20 esophageal cancer patients before and after preoperative DCF therapy. During two cycles of one-week-on and three-week-off administration, peripheral blood was collected before and after each “on” and before and after the surgical treatment followed by. By flow cytometry, CD15+CD14− granulocytes and CD15−CD14+ monocytes were observed. The effectiveness of NAC was determined hisitopathologically in accordance with the grading system of the Japanese Classification of Esophageal Carcinoma. Grading was as follows: Grade 0, no part of the tumor was affected; Grade1, less than two-thirds of the tumor was affected; Grade2, between two-thirds and the entire tumor was affected; and Grade 3, no residual tumor was present (Pathologically complete response) and clinically RECIST. Then their association were analyzed.
Results/Discussion: Of 20 patients with esophageal cancer, 13 patients were responders and 7 patients were non-responders to the DCF therapy. Just after the first “on” course, the ratio of monocytes to myelocytes was observed in 25.4 ± 32.0% in the non-responders and 7.8 ± 10.3% in the responders (p = 0.073). The numbers of monocytes calculated were 229.4 ± 212.2 /μL in the non-responders and 51.1 ± 71.1 /μL in the responders (p = 0.01). Patients with better pathological or clinical responses showed lower ratio of monocytes to myelocytes and fewer number of monocytes in peripheral blood. No relationship was observed between granulocytes and the therapeutic response.
Conclusion: These results suggest that analyzing immune related cells in peripheral blood might be useful for identification of predictive indicators for the response of preoperative DCF therapy.
Citation Format: Tomohira Takeoka, Kumiko Goto, Mitsunobu Matsumoto, Yasuhiro Miyazaki, Tomoki Makino, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada. Chemotherapy for esophageal cancer: Off-target effect and biomarker [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B135.
Abstract IA15: Microbiota and cancer immunosurveillance: An introduction
Authors: Kroemer Guido 
Published: November 2016

Abstract
Anticancer immune responses can be considered a desirable form of autoimmunity that may be profoundly shaped by the microbiome. Such anticancer immune responses may occur as part of the natural immunosurveillance system as well as a result of therapeutic interventions including chemotherapy, radiotherapy, and immuotherapy. I will discuss evidence for the microbiome's influence on antitumor immunosurveillance, including those that are indirect and can act at a distance. I will put forward hypotheses regarding mechanisms of how these effects are implemented. These may involve cross-reactivity between microbial and tumor antigens shaping T cell repertoires and/or microbial products stimulating pattern recognition receptors that influence the type and intensity of immune responses. Understanding how the microbiome impacts natural cancer immunosurveillance as well as treatment-induced immune responses will pave the way for more effective therapies and prophylactics.
References
1. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell 2015;28(6):690-714.
2. Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S,Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, Buque A, Falzoni S, Ryffel B, Apetoh L, Di Virgilio F, Madeo F, Maiuri MC, Zitvogel L, Levine B, Penninger JM, Kroemer G. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell 2016;30(1):147-60.
3. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and Anticancer Immunosurveillance. Cell 2016;165(2):276-87.
Citation Format: Guido Kroemer. Microbiota and cancer immunosurveillance: An introduction [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA15.
Abstract IA26: Combinatorial immunotherapies with the potential to reverse the carcinogenesis process
Authors: Jaffee Elizabeth M. 
Published: November 2016

Abstract
Until recently, barriers to immunotherapy clinical successes for pancreatic cancer have been due to a lack of understanding of the immune pathways within the pancreatic tumor microenvironment that hinder successful immune responses. Recent advances have identified new targets for developing cancer specific vaccines and new targets for modulating the tumor microenvironment to allow more potent activation and improved access of vaccine induced immune responses. We are just learning that non-neoplastic cells, including cancer-associated myofibroblasts, regulatory T cells, dendritic cells, myeloid-derived suppressor cells, and tumor-associated macrophages, are hijacked by pre-invasive and invasive cancer cells to create a tolerogenic tumor microenvironment. Current research is focused on elucidating the mechanisms of this tolerogenic polarization within the tumor microenvironment with the goal of tipping the balance in favor of an anticancer immune response. With the recent advances in molecular technologies and the development of relevant pancreatic cancer mouse models, it is now within our reach to dissect the inhibitory pathways within the pancreatic tumor microenvironment. This will in turn, lead to new therapeutic opportunities that will eliminate these barriers and convert this deadly cancer into a treatable disease.
References
1. Keenan et al. A Listeria vaccine and depletion of Tregs activate immunity against early pancreatic intraepithelial neoplasms and prolong the survival of mice. Gastronterology 2014;146:1784-994.
2. Lutz et al. Immunotherapy converts nonimmunogenic pancreatic tumors into foci of immune regulation. Cancer Immunology Research 2014; 2(7):616-31.
3. Kouo et al. Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunology Research 2015;3(4):412-23.
[Supported by grants from the National Cancer Institute, National Institutes of Health (P50CA062924, R01CA122081, P30CA006973, and U19CA113341 to E.M.J.), and supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer.]
Citation Format: Elizabeth M. Jaffee. Combinatorial immunotherapies with the potential to reverse the carcinogenesis process [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA26.
Abstract PR02: A personalized neoantigen vaccine in patients with high risk melanoma
Authors: Ott Patrick A. , Hu Zhuting , Keskin Derin B. , Shukla Sachet A. , Sun Jing , Fritsch Ed , Hacohen Nir , Wu Catherine J. 
Published: November 2016

Abstract
Neoantigens arise from somatic tumor mutations and can encode amino acid changes, generating peptides with the potential to bind to HLA molecules. Since these neoepitopes provide exquisite tumor specificity and are expected to be highly immunogenic as they are not subject to central tolerance, they were long-envisioned as highly valuable tumor antigens. Growing evidence has supported tumor neoepitopes as key antigens triggering immune-mediated tumor killing in vivo across settings of effective cancer immunotherapy, including checkpoint blockade and adoptive transfer with tumor-infiltrating lymphocytes. Vaccination is a potentially effective approach for inducing tumor-specific immune responses, but has been limited by the lack of a sufficiently potent vaccine immunogen. By leveraging next-generation sequencing technologies and new analytical pipelines to systematically identify personal tumor neoantigens, in a phase 1 trial we tested the feasibility, safety, and immunogenicity of a multi-epitope cancer vaccine targeting personal tumor neoantigens in patients with high-risk melanoma. Mutations were identified by DNA and RNA sequencing; epitopes were selected based on class I HLA binding prediction algorithms. The vaccines, comprised of up to 20 long peptides spanning mutated tumor epitopes and admixed with the Toll-Like Receptor 3 agonist poly-ICLC, were administered using a prime-boost approach. Of 12 patients enrolled, the initial 6 patients who received the full set of priming and booster vaccinations experienced only minimal adverse events, consisting of mild and transient injection site reaction, flu-like symptoms, and rash. We identified strong, polyfunctional CD4+ and CD8+ T cell responses against multiple neoepitopes in all dosed patients. Processing and presentation of neoantigens on autologous tumors was confirmed by mass spectrometry and recognition of autologous tumor by vaccine-induced neoantigen-specific T cells was verified. These studies show that a personalized neoantigen vaccine is safe, feasible, and strongly immunogenic in cancer patients. The data should reinvigorate the field of cancer vaccines, providing a rational path for the building of combinatorial approaches to extend their efficacy.
Citation Format: Patrick A. Ott, Zhuting Hu, Derin B. Keskin, Sachet A. Shukla, Jing Sun, Ed Fritsch, Nir Hacohen, Catherine J. Wu. A personalized neoantigen vaccine in patients with high risk melanoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR02.
Abstract PR15: Engineering phagocytic signaling
Authors: Williamson Adam , Vale Ron 
Published: November 2016

Abstract
Phagocytosis of specific targets in clinically-relevant settings, including engulfment of tumor cells and removal of cell corpses following aggressive cancer treatment, has been hampered by an incomplete understanding of phagocytic signaling. Therefore, we developed a cellular reconstitution platform amenable to direct, real-time imaging to dissect phagocytic signaling in molecular detail. Our gain-of-function system converts inept phagocytes into efficient ones, enabling us to appreciate the signaling behaviors associated with phagocytic proficiency. We report that 1) phagocytosis receptors form mobile microclusters in response to ligation, 2) microclusters recruit cytosolic collaborators to the plasma membrane and spatially organize actin dynamics at the phagocytic synapse, and 3) the natural ligand-receptor pair can be replaced by an engineered module, indicating that phagocytic signaling can be reprogrammed towards specific targets. Thus, we have discovered that a conserved signaling system required for recognition and removal of altered self bears unexpected mechanistic similarity to adaptive immune responses directed towards pathogens and tumor cells. In addition, our ability to replace the endogenous receptor with a heterologous system indicates that phagocytosis can be programmed in a manner conceptually similar to the Chimeric Antigen Receptor used in the clinic to program cytotoxic T cells to kill tumor cells. Our ability to engineer the process suggests that methods to re-direct phagocytes towards targets of clinical importance are possible, approaches that may enable recognition and removal of tumor cells and boost the anti-tumor immune response.
Citation Format: Adam Williamson, Ron Vale. Engineering phagocytic signaling [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR15.
Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair
Authors: Sörelius Karl , Wanhainen Anders , Furebring Mia , Björck Martin , Gillgren Peter , Mani Kevin , Lindström David , Hultgren Rebecka , Wahlgren Carl-Magnus , Roos Håkan , Langenskiöld Marcus , Resch Timothy , Vaccarino Roberta , Bilos Linda , Pirouzram Artai , Arnerlöv Conny , Simo Gabor , Svensson Mats , Magnusson Johan , Astrand Håkan , Gilgen Nils-Peter , Mellander Stefan , Korman David , Djavani-Gidlund Khatereh , Palm Markus , Huss Mårten , Bertszel Adam , Docter Michael , Drott Christer , Öjersjö Andreas , Nelzén Olle , Wetterling Tomas , Chu Ming 
Published: November 2016

Background:
No reliable comparative data exist between open repair (OR) and endovascular aneurysm repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort.

Methods:
All patients treated for MAAAs in Sweden between 1994 and 2014 were identified in the Swedish vascular registry. The primary aim was to assess survival after MAAA with OR and EVAR. Secondary aims were analyses of the rate of recurrent infections and reoperations, and time trends in surgical treatment. Survival was analyzed using Kaplan-Meier and log-rank tests. A propensity score–weighted correction for risk factor differences in the 2 groups was performed, including the operation year to account for differences in treatment and outcomes over time.

Results:

We identified 132 patients (0.6% of all operated abdominal aortic aneurysms in Sweden). Mean age was 70 years (standard deviation, 9.2), and 50 presented with rupture. Survival at 3 months was 86% (95% confidence interval, 80%–92%), at 1 year 79% (72%–86%), and at 5 years 59% (50%–68%). The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994–2000 0%, 2001–2007 58%, 2008–2014 60%). Open repair was performed in 62 patients (47%): aortic resection and extra-anatomic bypass (n=7), in situ reconstruction (n=50), and patch plasty (n=3); 2 patients died intraoperatively. EVAR was performed in 70 patients (53%): standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stent grafting (n=7); no deaths occurred intraoperatively. Survival at 3 months was lower for OR than for EVAR (74% versus 96%,
P
<0.001), with a similar trend present at 1 year (73% versus 84%,
P
=0.054). A propensity score–weighted risk-adjusted analysis confirmed the early better survival associated with EVAR. During median follow-up of 36 and 41 months for OR and EVAR, respectively, there was no difference in long-term survival (5 years 60% versus 58%,
P
=0.771), infection-related complications (18% versus 24%,
P
=0.439), or reoperation (21% versus 24%,
P
=0.650).

Conclusion:
This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR was associated with improved short-term survival in comparison with OR, without higher associated incidence of serious infection-related complications or reoperations.
Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation
Authors: Salimi Shabnam , Lewis Joshua P. , Yerges‐Armstrong Laura M. , Mitchell Braxton D. , Saeed Faisal , O'Connell Jeffry R. , Perry James A. , Ryan Kathleen A. , Shuldiner Alan R. , Parsa Afshin 
Published: November 2016

Background
Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function.

Methods and Results

Microcirculatory endothelial function was quantified by laser Doppler flowmetry (
LDF
) mediated by thermal hyperemia (
TH
) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons.
LDF
and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post‐ versus preclopidogrel
LDF
measures. Preclopidogrel
TH
‐
LDF
and platelet aggregation were higher in women than in men (
P
<0.001). Clopidogrel administration was associated with ≈2‐fold higher percentage change in
TH
‐
LDF
in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%,
P
=0.03). Clopidogrel also increased absolute
TH
‐
LDF
measures in persons with high platelet aggregation (1757±766 to 2154±1055,
P
=0.03), with a more prominent effect in women (1909±846 to 2518±1048,
P
=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia
LDF
measures.

Conclusions

The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved
TH
‐induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
00799396.
Effects of Statin on Arrhythmia and Heart Rate Variability in Healthy Persons With 48‐Hour Sleep Deprivation
Authors: Chen Wei Ren , Liu Hong Bin , Sha Yuan , Shi Yang , Wang Hao , Yin Da Wei , Chen Yun Dai , Shi Xiang Min 
Published: November 2016

Background
It has been reported that sleep deprivation is associated with cardiac autonomic disorder, inflammation, and oxidative stress. Statins have significant cardiovascular protective effects in patients with cardiovascular disease. This study aimed to investigate the protective effect of statins on arrhythmia and heart rate variability in young healthy persons after 48‐hour sleep deprivation.

Methods and Results

This study enrolled 72 young healthy participants aged 26.5±3.5 years. All participants received 48‐hour continuous ambulatory electrocardiogram monitoring. Arrhythmia, time, and frequency domain parameters were analyzed for all participants. The primary end point, low/high frequency ratio, was significantly lower in the statin group than in the control group (2.48±1.12 versus 3.02±1.23,
P
<0.001). After 48‐hour sleep deprivation, low frequency—the frequency of premature atrial complexes and premature ventricular complexes—was significantly decreased in the statin group compared with the control group (
P<
0.05). There was also a significant increase in high frequency in the statin group compared with the control group (
P<
0.05). There was a significant decrease in serum high‐sensitivity C‐reactive protein and malondialdehyde levels after 48‐hour sleep deprivation in the statin group compared with the control group (
P
<0.05).

Conclusions
Statin use might be associated with improvement in arrhythmia and heart rate variability in healthy persons with 48‐hour sleep deprivation. This finding should be confirmed by larger scale trials.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02496962.
Seasonally Resolved Distributional Trends of North American Temperatures Show Contraction of Winter Variability
Authors: Rhines Andrew , McKinnon Karen A. , Tingley Martin P. , Huybers Peter 
Published: November 2016

AbstractThere is considerable interest in determining whether recent changes in the temperature distribution extend beyond simple shifts in the mean. The authors present a framework based on quantile regression, wherein trends are estimated across percentiles. Pointwise trends from surface station observations are mapped into continuous spatial fields using thin-plate spline regression. This procedure allows for resolving spatial dependence of distributional trends, providing uncertainty estimates that account for spatial covariance and varying station density. The method is applied to seasonal near-surface temperatures between 1979 and 2014 to unambiguously assess distributional changes in the densely sampled North American region. Strong seasonal differences are found, with summer trends exhibiting significant warming throughout the domain with little distributional dependence, while the spatial distribution of spring and fall trends show a dipole structure. In contrast, the spread between the 95th and 5th percentile in winter has decreased, with trends of −0.71° and −0.85°C decade−1, respectively, for daily maximum and minimum temperature, a contraction that is statistically significant over 84% of the domain. This decrease in variability is dominated by warming of the coldest days, which has outpaced the median trend by approximately a factor of 4. Identical analyses using ERA-Interim and NCEP-2 yield consistent estimates for winter (though not for other seasons), suggesting that reanalyses can be reliably used for relating winter trends to circulation anomalies. These results are consistent with Arctic-amplified warming being strongest in winter and with the influence of synoptic-scale advection on winter temperatures. Maps for all percentiles, seasons, and datasets are provided via an online tool.
Response of the North Pacific Tropical Cyclone Climatology to Global Warming: Application of Dynamical Downscaling to CMIP5 Models
Authors: Zhang Lei , Karnauskas Kristopher B. , Donnelly Jeffrey P. , Emanuel Kerry 
Published: November 2016

Abstract
A downscaling approach is applied to future projection simulations from four CMIP5 global climate models to investigate the response of the tropical cyclone (TC) climatology over the North Pacific basin to global warming. Under the influence of the anthropogenic rise in greenhouse gases, TC-track density, power dissipation, and TC genesis exhibit robust increasing trends over the North Pacific, especially over the central subtropical Pacific region. The increase in North Pacific TCs is primarily manifested as increases in the intense and relatively weak TCs. Examination of storm duration also reveals that TCs over the North Pacific have longer lifetimes under global warming.
Through a genesis potential index, the mechanistic contributions of various physical climate factors to the simulated change in TC genesis are explored. More frequent TC genesis under global warming is mostly attributable to the smaller vertical wind shear and greater potential intensity (primarily due to higher sea surface temperature). In contrast, the effect of the saturation deficit of the free troposphere tends to suppress TC genesis, and the change in large-scale vorticity plays a negligible role.