bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B35: Use of random peptide array to discover cancer neo-antigens for vaccines and diagnostics
Authors: Stafford Phillip , Richer Josh , Johnston Stephen Albert , Shen Luhui 
Published: October 2015

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR10) of the Conference Proceedings.
Citation Format: Phillip Stafford, Josh Richer, Stephen Albert Johnston, Luhui Shen. Use of random peptide array to discover cancer neo-antigens for vaccines and diagnostics. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B35.
Abstract B42: Cyclic dinucleotides (CDNs) activated DC and NK cells in antitumor immunotherapy
Authors: Fu Juan , Zhen Qi , Pardoll Drew , Dubensky Tom , Kim Young 
Published: October 2015

Abstract
Abstract Our laboratory developed cell based cancer vaccines (STINGVAX) that was formulated with cyclic dinucleotides that and sensed by STING to phosphorylate interferon regulatory factor3 (IRF3) and nuclear factor kappa-light-chain-enhancer (NF-κB) to induce B cells and myeloid cells to secrete IFN-β. IFN-β can active NK cells through Tyk2-STAT1 signaling pathway, and we found increased number of activated NK cells in tumor bearing mice treated with STINGVAX. In the context of formulation with GM-CSF secreting cellular vaccines, the anti-tumor effect of CDN was dependent on IFNα/β receptors. We found that CDN activated NK cells both in vitro and in vivo, and at the molecular level, CDN increased TYK2-STAT1 signaling. When we tested STINGVAX's anti-tumor efficacy with NK depletion, its anti-tumor effect was abrogated.
Citation Format: Juan Fu, Qi Zhen, Drew Pardoll, Tom Dubensky, Young Kim. Cyclic dinucleotides (CDNs) activated DC and NK cells in antitumor immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B42.
Abstract B48: Homer3 regulates the establishment of neutrophil polarity
Authors: Wu Julie , Pipathsouk Anne , Keizer-Gunnink A , Alkema Wynand , Fusetti Fabrizia , Liu Shanshan , Atschuler Steve , Wu Lani , Kortholt Arjan , Weiner Orion 
Published: October 2015

Abstract
Neutrophils migrate towards developing tumors where they promote angiogenesis, setting the stage for metastasis. Investigating neutrophil migration should lead to novel drug targets to prevent neutrophil accumulation in tumors. Neutrophils and other cells rely on activation of the heterotrimeric G-protein Gai to regulate directional cell migration, but few links from Gai to chemotactic effectors are known. Through affinity chromatography using primary neutrophil lysate, we identify Homer3 as a novel Gai2-binding protein. RNAi-mediated knockdown of Homer3 in neutrophil-like HL-60 cells impairs chemotaxis and the establishment of polarity of the actin cytoskeleton. Most previously-characterized proteins that are required for cell polarity are needed for actin assembly or activation of core chemotactic effectors such as the Rac GTPase. In contrast, Homer3 knockdown cells show a normal magnitude and kinetics of chemoattractant-induced activation of PI3K and Rac effectors. Chemoattractant-stimulated Homer3 knockdown cells also exhibit a normal initial magnitude of actin polymerization, but they fail to polarize actin assembly and are defective in the initiation of cell polarity and motility. Our data suggest that Homer3 acts as a scaffold that spatially organizes actin assembly to support neutrophil polarity and motility downstream of GPCR activation.
Citation Format: Julie Wu, Anne Pipathsouk, A Keizer-Gunnink, Wynand Alkema, Fabrizia Fusetti, Shanshan Liu, Steve Atschuler, Lani Wu, Arjan Kortholt, Orion Weiner. Homer3 regulates the establishment of neutrophil polarity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B48.
Abstract IA05: Breaking immune privilege in pancreatic cancer
Authors: Vonderheide Robert H. 
Published: October 2015

Abstract
Disabling the function of immune checkpoint molecules can unlock T cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. Certain tumors, especially pancreatic ductal adenocarcinoma (PDA), are fully refractory to these antibodies. Using a genetically engineered mouse model of PDA in which spontaneous immunity is minimal, we found that PD-L1 is prominent in the tumor microenvironment, a phenotype confirmed in patients. Tumor T cells express PD-1 as prominently as in classical models of chronic infection, but treatment with PD-1 mAb, with or without CTLA-4 mAb, fails in well-established tumors, recapitulating clinical results. Two “vaccine strategies” can be used to induce T cell immunity and reverse resistance of PDA to PD-1 and CTLA-4. These approaches include hypofractionated radiation or chemotherapy in conjunction with a CD40 agonisitc antibody. Data suggest that in non immunogenic tumors, manifesting as immune privilege in PDA, baseline refractoriness to checkpoint inhibitors may be rescued by the priming of a T cell response.
Citation Format: Robert H. Vonderheide. Breaking immune privilege in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA05.
Abstract IA09: Molecular mechanisms controlling the T cell-inflamed tumor microenvironment: Implications for therapy
Authors: Gajewski Thomas 
Published: October 2015

Abstract
Two major categories of melanoma metastases have been observed based on gene expression profiling and confirmatory technologies. One subgroup of patients has T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN gene signature. In contrast, the other major subset lacks this phenotype and these tumors show a behavior of immune “exclusion”. The optimal immunotherapeutic intervention may be distinct for these two general subsets. The T cell-inflamed tumor microenvironment subset contains the highest expression of negative regulatory factors, including PD-L1, IDO, and FoxP3+ Tregs, and evidence for T cell-intrinsic anergy has also emerged. In addition, the mechanism of induction of these inhibitory mechanisms has been elucidated—PD-L1 and IDO are induced by IFN-γ, and Tregs are largely recruited by chemokines such as CCL22, produced by activated CD8+ effector T cells. Preclinical experiments have confirmed a critical role for all 4 of these mechanisms in limiting anti-tumor T cell efficacy in vivo, giving a mechanism base for translation back into the clinic. These include anti-PD-1/PD-L1 mAbs, IDO inhibitors, and approaches to deplete CD25+ Tregs and/or reverse anergy. The presence of multiple inhibitory mechanisms in the same tumor microenvironment argues that combination therapies may be advantageous to overcome compensatory effects. Preclinical data indicated synergy between anti-CTLA-4 +/- anti-PD-L1 +/- IDO inhibition. The mechanism of synergy is striking, as it correlates with a marked improvement of IL-2 production and proliferation of tumor-infiltrating CD8+ T cells. Clinical translation of these combination immunotherapies is promising and ongoing. In contrast to the T cell-inflamed melanomas, a new paradigm may be needed to promote de novo inflammation in cases of the non-T cell-infiltrated tumor microenvironment. Recent work has indicated that successful innate immune sensing of tumors involves the STING pathway and type I IFN production. Therefore, STING agonists are being developed to promote effective innate immune activation and generation of an adaptive immune response. Molecular mechanisms that explain the presence or absence of a T cell-inflamed tumor microenvironment in patients are being elucidated, which is opening up new concepts for therapies that may overcome immune exclusion and render patients responsive to immunotherapies.
Citation Format: Thomas Gajewski. Molecular mechanisms controlling the T cell-inflamed tumor microenvironment: Implications for therapy. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA09.
Abstract PR01: The heat shock protein-CD91 pathway is necessary for tumor immunosurveillance
Authors: Zhou Yu Jerry , Binder Robert J. 
Published: October 2015

Abstract
Many tumors are capable of generating immune response in the bearing host. Since tumors lack the typical (foreign) PAMPs that provide signal 2 for T cell priming, the mechanism of how concomitant immunity is established remains a mystery. We provide evidence here that, heat shock proteins (HSPs), when released into the tumor microenvironment, is the immunogen necessary for tumor immunosurveillance. This response requires CD91- the endocytic and signaling receptor for the immunogenic HSPs. In our study, we generated CD11c-specific CD91 knockout mice and showed that transplantable tumors grew faster in those knockout mice, compared to wild type mice. In addition, we abrogated the interaction of tumor-derived HSP with CD91 in vivo by over-expression of Receptor Associated Protein (RAP), an endogenous inhibitor of CD91. The loss of CD91 funtion through antagonism or its deletion was shown to negatively affect cross-priming. While initial studies were performed on transplantable tumors, these experiments have now been carried out in chemically induced tumor models. In summary, our study demonstrates that the HSP-CD91 pathway is critical for establishment tumor immunity. Considering that elevated RAP levels have been reported in colon cancer patients, we propose a novel mechanism of immune evasion for tumors expressing competing ligands for immune receptors such as CD91.
Citation Format: Yu Jerry Zhou, Robert J. Binder. The heat shock protein-CD91 pathway is necessary for tumor immunosurveillance. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr PR01.
Abnormal Left Ventricular Mechanics of Ventricular Ectopic Beats
Authors: Potfay Jonathan , Kaszala Karoly , Tan Alex Y. , Sima Adam P. , Gorcsan John , Ellenbogen Kenneth A. , Huizar Jose F. 
Published: October 2015

Background—
Left ventricular (LV) dyssynchrony caused by premature ventricular contractions (PVCs) has been proposed as a mechanism of PVC-induced cardiomyopathy. We sought to understand the impact of different PVC locations and coupling intervals (prematurity) on LV regional mechanics and global function of the PVC beat itself.

Methods and Results—

Using our premature pacing algorithm, pentageminal PVCs at coupling intervals of 200 to 375 ms were delivered from the epicardial right ventricular apex, RV outflow tract, and LV free wall, as well as premature atrial contractions, from the left atrial appendage at a coupling interval of 200 ms in 7 healthy canines. LV short-axis echocardiographic images, LV stroke volume, and dP/dt
max
were obtained during all ectopic beats and ventricular pacing. LV dyssynchrony was assessed by dispersion of QRS-to-peak strain (earliest—last QRS-to-peak strain) between 6 different LV segments during each of the aforementioned beats (GE, EchoPac). LV dyssynchrony was greater during long-coupled rather than short-coupled PVCs and PVCs at 375 ms compared with rapid ventricular pacing at 400 ms (
P
<0.0001), whereas no difference was found between PVC locations. Longer PVC coupling intervals were associated with greater stroke volume and dP/dt
max
despite more pronounced dyssynchrony (
P
<0.001).

Conclusions—
PVCs with longer coupling intervals demonstrate more pronounced LV dyssynchrony, whereas PVC location has minimal impact. LV dyssynchrony cannot be attributed to prematurity or abnormal ventricular activation alone, but rather to a combination of both. This study suggests that late-coupled PVCs may cause a more severe cardiomyopathy if dyssynchrony is the leading mechanism responsible for PVC-induced cardiomyopathy.
Summary of Evidence on Early Carotid Intervention for Recently Symptomatic Stenosis Based on Meta-Analysis of Current Risks
Authors: De Rango Paola , Brown Martin M. , Chaturvedi Seemant , Howard Virginia J. , Jovin Tudor , Mazya Michael V. , Paciaroni Maurizio , Manzone Alessandra , Farchioni Luca , Caso Valeria 
Published: October 2015

Background and Purpose—
This study aimed to assess the evidence on the periprocedural (<30 days) risks of carotid intervention in relation to timing of procedure in patients with recently symptomatic carotid stenosis.

Methods—
A systematic literature review of studies published in the past 8 years reporting periprocedural stroke/death after carotid endarterectomy (CEA) and carotid stenting (CAS) related to the time between qualifying neurological symptoms and intervention was performed. Pooled estimates of periprocedural risk for patients treated within 0 to 48 hours, 0 to 7 days, and 0 to 15 days were derived with proportional meta-analyses and reported separately for patients with stroke and transient ischemic attack as index events.

Results—
Of 47 studies included, 35 were on CEA, 7 on CAS, and 5 included both procedures. The pooled risk of periprocedural stroke was 3.4% (95% confidence interval [CI], 2.6–4.3) after CEA and 4.8% (95% CI, 2.5–7.8) after CAS performed <15 days; stroke/death rates were 3.8% and 6.9% after CEA and CAS, respectively. Pooled periprocedural stroke risk was 3.3% (95% CI, 2.1–4.6) after CEA and 4.8% (95% CI, 2.5–7.8) after CAS when performed within 0 to 7 days. In hyperacute surgery (<48 hours), periprocedural stroke risk after CEA was 5.3% (95% CI, 2.8–8.4) but with relevant risk differences among patients treated after transient ischemic attack (2.7%; 95% CI, 0.5–6.9) or stroke (8.0%; 95% CI, 4.6–12.2) as index.

Conclusions—
CEA within 15 days from stroke/transient ischemic attack can be performed with periprocedural stroke risk <3.5%. CAS within the same period may carry a stroke risk of 4.8%. Similar periprocedural risks occur after CEA and CAS performed earlier, within 0 to 7 days. Carotid revascularization can be safely performed within the first week (0–7 days) after symptom onset.
Leveraging social networks to support reproductive health and economic wellbeing among Guatemalan Maya women
Authors: Prescott Alexandra S , Luippold-Roge Genevieve P , Gurman Tilly A 
Published: October 2015

Objective: Maya women in Guatemala are disproportionately affected by poverty and negative reproductive health outcomes. Although social networks are valued in many Indigenous cultures, few studies have explored whether health education programmes can leverage these networks to improve reproductive health and economic wellbeing. Design: This qualitative study explored the role that social networks play in both health education and economic empowerment among women involved in a Maya reproductive health women’s group. Setting: Western highlands region of Guatemala. Method: Semi-structured in-depth interviews, each lasting 2–3 hours, were conducted with 19 women (aged 18–40 years) who had participated in a formal women’s network. Topics addressed included personal experience with the group, aspirations for the future and attitudes towards reproductive health and economic wellbeing. Results: Respondents stated that by engaging in formal group activities and interacting with others in the network, they were able to find their voice. They described gaining self-confidence needed to speak about reproductive health with pre-adolescent and adolescent girls as well as other community members. Respondents also discussed learning new ideas/skills and detailed future aspirations of planning their family and reaching educational/career goals. Conclusion: The study illustrates the potential of social networks to provide individuals with knowledge and skills, along with new ways of thinking about themselves and their futures. Health education programmes aspiring to improve the reproductive health and economic wellbeing of vulnerable groups, such as Maya women, should seek to leverage the benefits of such social networks.
Symmetric and asymmetric tilt grain boundary structure and energy in Cu and Al (and transferability to other fcc metals)
Authors: Tschopp Mark A. , Coleman Shawn P. , McDowell David L. 
Published: October 2015

AbstractSymmetric and asymmetric tilt grain boundaries in Cu and Al were generated using molecular statics energy minimization in a classical molecular dynamics code with in-plane grain boundary translations and an atom deletion criterion. The following dataset (NIST repository, http://hdl.handle.net/11256/358) contains atomic coordinates for minimum energy grain boundaries in three-dimensional periodic simulation cells, facilitating their use in future simulations. This grain boundary dataset is used to show the relative transferability of grain boundary structures from one face-centered cubic system to another; in general, there is good agreement in terms of grain boundary energies (R2 > 0.99). Some potential applications and uses of this tilt grain boundary dataset in nanomechanics and materials science are discussed.
Estrogen Therapy Delays Autoimmune Diabetes and Promotes the Protective Efficiency of Natural Killer T-Cell Activation in Female Nonobese Diabetic Mice
Authors: Gourdy Pierre , Bourgeois Elvire A. , Levescot Anaïs , Pham Linh , Riant Elodie , Ahui Marie-Louise , Damotte Diane , Gombert Jean-Marc , Bayard Francis , Ohlsson Claes , Arnal Jean-François , Herbelin André 
Published: October 2015

Abstract
Therapeutic strategies focused on restoring immune tolerance remain the main avenue to prevent type 1 diabetes (T1D). Because estrogens potentiate FoxP3+ regulatory T cells (Treg) and invariant natural killer T (iNKT) cells, two regulatory lymphocyte populations that are functionally deficient in nonobese diabetic (NOD) mice, we investigated whether estradiol (E2) therapy influences the course of T1D in this model. To this end, female NOD mice were sc implanted with E2- or placebo-delivering pellets to explore the course of spontaneous and cyclophosphamide-induced diabetes. Treg-depleted and iNKT-cell-deficient (Jα18−/−) NOD mice were used to assess the respective involvement of these lymphocyte populations in E2 effects. Early E2 administration (from 4 wk of age) was found to preserve NOD mice from both spontaneous and cyclophosphamide-induced diabetes, and a complete protection was also observed throughout treatment when E2 treatment was initiated after the onset of insulitis (from 12 wk of age). This delayed E2 treatment remained fully effective in Treg-depleted mice but failed to entirely protect Jα18−/− mice. Accordingly, E2 administration was shown to restore the cytokine production of iNKT cells in response to in vivo challenge with the cognate ligand α-galactosylceramide. Finally, transient E2 administration potentiated the previously described protective action of α-galactosylceramide treatment in NOD females. This study provides original evidence that E2 therapy strongly protects NOD mice from T1D and reveals the estrogen/iNKT cell axis as a new effective target to counteract diabetes onset at the stage of insulitis. Estrogen-based therapy should thus be considered for T1D prevention.
Intramolecular C–H···H–C Contacts in Diheteroaryl Ketones and Thioketones: A Theoretical Analysis
Authors: Matczak Piotr 
Published: October 2015

Abstract
Intramolecular C–H···H–C contacts in a set of 10 molecules, being formaldehyde and thioformaldehyde disubstituted with such a heteroaryl group as 2-furanyl, 2-thiophenyl, 2-selenophenyl, 2-pyrrolyl, or 1-methyl-2-pyrrolyl, have been studied using density functional theory (DFT), natural bond orbital (NBO) analysis, quantum theory of atoms in molecules (QTAIM), noncovalent interactions (NCI) index, and interacting quantum atoms (IQA) theory. The results illustrate the fundamental difference in perceiving these contacts from a perspective based on QTAIM-defined atomic basins against the localized-orbital perspective of the NBO theory. The presence of the C–H···H–C contacts locally destabilizes the investigated molecules, although their characterization narrowed only to the interaction between the QTAIM basins of the H atoms in the contacts shows a very weak attraction between these atoms. We demonstrate some relationships between the results obtained from different theoretical methods in order to emphasize possible similarities in their pictures of the contacts. The indication of such similarities may be important for the interpretation of theoretical results in future studies utilizing the aforementioned methods to investigate C–H···H–C contacts in various molecules.
The factorial structure and validity of the Hospital Anxiety and Depression Scale (HADS) in Polish adolescents
Authors: Mihalca Andreea , Pilecka Władysława 
Published: October 2015

CelCelem niniejszego badania była analiza struktury czynnikowej oraz trafności i rzetelności polskiej wersji Szpitalnej Skali Lęku i Depresji (HADS) dla Młodzieży, w grupach adolescentów zdrowych oraz przewlekle chorych.Metoda146 przewlekle chorych (57,6% dziewcząt) oraz 309 zdrowych (45,9% dziewcząt) adolescentów w wieku od 12 do 16 lat (M = 14,03; SD = 1,3) wypełniło kwestionariusz HADS w wersji dla młodzieży (HADS-Teen) podczas pobytu w szpitalu lub w trakcie zajęć szkolnych. Rzetelność typu test-retest po upływie jednego tygodnia oraz trafność teoretyczna zostały oszacowane na podstawie wyników z dwóch prób częściowych, złożonych z młodzieży zdrowej.WynikiSkala HADS dla młodzieży wykazała dwuczynnikową strukturę w grupie młodzieży przewlekle chorej oraz trójczynnikową strukturę w grupie osób zdrowych. Podskala Lęku uzyskała wysoką zgodność wewnętrzną, rzetelność oraz satysfakcjonujący poziom korelacji z innym narzędziem do pomiaru lęku uogólnionego. Podskala Depresji ujawniła natomiast dobrą rzetelność, ale niską zgodność wewnętrzną w obu grupach. W grupie młodzieży zdrowej, itemy tej skali tworzyły dwa czynniki: depresyjny nastrój wraz z psychomotorycznym spowolnieniem/ pobudzeniem oraz anhedonia.WnioskiWyniki badań z użyciem skali HADS dla młodzieży potwierdziły nieprawidłowości w zakresie jej struktury czynnikowej, podobnie jak w przypadku badań z wykorzystaniem wersji narzędzia dla osób dorosłych. Struktura czynnikowa skali HADS dla młodzieży różni się w zależności od badanej grupy (młodzież zdrowa vs. przewlekle chora). Uzyskane wyniki dowodzą, że stosowanie skali HADS w badaniu młodzieży zdrowej wymaga szczególnej ostrożności w interpretowaniu rezultatów w podskali Depresji.