bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a novel dengue virus serotype‐specific multiplex real‐time reverse transcription–polymerase chain reaction assay for blood screening
Authors: Tezuka Kenta , Kuramitsu Madoka , Okuma Kazu , Nojima Kiyoko , Araki Kumiko , Shinohara Naoya , Matsumoto Chieko , Satake Masahiro , Takasaki Tomohiko , Saijo Masayuki , Kurane Ichiro , Hamaguchi Isao 
Published: October 2016

BACKGROUNDDengue fever is caused by four related RNA viruses of the genus Flavivirus, dengue virus (DENV)‐1, ‐2, ‐3, and ‐4, which are transmitted to humans by mosquitoes. Although DENV is not endemic in Japan, an autochthonous dengue outbreak occurred in 2014. Several transfusion‐transmitted cases have also been reported after the use of blood and plasma products in DENV‐endemic countries. The aim of this study was to develop a novel multiplex reverse transcription–polymerase chain reaction (RT‐PCR) assay for DENV blood screening.STUDY DESIGN AND METHODSLarge‐scale oligonucleotide screening was performed to obtain DENV‐specific primers and probes using a variety of DENV clinical isolates. A multiplex RT‐PCR assay was then developed using the identified oligonucleotides and the ability of this assay to detect DENV RNA was evaluated.RESULTSA number of oligonucleotides suitable for DENV RNA detection were identified and a novel DENV serotype‐specific multiplex RT‐PCR assay was successfully established. Comparative analysis revealed that the multiplex assay could detect levels of viral contamination as low as 100 viral copies/mL.CONCLUSIONThis established serotype‐specific multiplex RT‐PCR assay provides a simple, sensitive, and quantitative detection method for DENV, which could be applied in the screening of blood samples to prevent transfusion‐transmitted DENV infection.
Blood component transfusion and wastage rates in the setting of massive transfusion in three regional trauma centers
Authors: Dunbar Nancy M. , Olson Nicholas J. , Szczepiorkowski Zbigniew M. , Martin Eric D. , Tysarcyk Ryan M. , Triulzi Darrell J. , Alarcon Louis H. , Yazer Mark H. 
Published: October 2016

BACKGROUNDThe purpose of massive transfusion protocols (MTPs) is to provide large quantities of blood products rapidly to exsanguinating patients. The expected rates of blood product transfusion and wastage in this setting have not been defined. This study was undertaken to assess the transfusion and wastage rates for bleeding patients requiring emergency issue of blood components at three American Level I trauma centers.STUDY DESIGN AND METHODSThree hospitals participated, all of which are Level I trauma centers that have MTPs in place where uncrossmatched red blood cells (RBCs) can be ordered with or without platelets (PLTs), plasma, and cryoprecipitate. Data on the transfusion, return to blood bank, and wastage rates were recorded on all products issued within 3 hours after MTP activation.RESULTSThe majority of products were issued to the emergency department and/or operating room at all three institutions (84%‐95%). The percentage of RBCs, plasma, and PLTs transfused during MTPs were 39% to 65%, 43% to 66%, and 75% to 100%, respectively. Wastage rates were comparable for RBCs (0%‐9%), plasma (0%‐7%), and PLTs (0%‐7%). Cryoprecipitate had the highest wastage rates at all three sites (7%‐33%).CONCLUSIONA large portion of blood products issued during MTPs are not transfused. Some are wasted due to stringent storage requirements and/or limited shelf lives. The optimum ratio of transfused to returned products in these patients is likely to be determined more by clinical need than by transfusion service policy.
A randomized trial to evaluate the use of text messaging, letter, and telephone call reminders to improve return of blood donors with reactive serologic tests
Authors: Porto‐Ferreira Francisco Augusto , de Almeida‐Neto Cesar , Murphy Edward L. , Montebello Sandra de Camargo , Nogueira Fátima Aparecida Hangai , Koga da Silva Edina Mariko , MacFarland William , Custer Brian 
Published: October 2016

BACKGROUNDLow return rates for notification and counseling among donors with reactive serologic screening tests have been reported worldwide. A randomized trial to test the effectiveness of text message, letter, or telephone call reminders to improve return among nonresponding first‐time blood donors with reactive serologic tests was conducted.STUDY DESIGN AND METHODSDonors with serologically reactive screening test results who had a cell phone and resided in the metropolitan telephone area code of São Paulo in the period from August 2013 through July 2014 were eligible. A consecutive sample of first‐time donors with reactive screening tests who had not responded to a standard letter requesting the donor return to the blood center were randomly assigned to receive a text, a new letter, or a telephone call requesting return for notification and counseling. Return rates were measured over the subsequent 30 days.RESULTSThe return rate after a phone call reminder was better than that for a text message (39.8% vs. 28.4%; odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05‐2.64) but not better than that for a letter (39.8% vs. 34.4%; OR, 1.26; 95% CI, 0.80‐1.99). Older age was a predictor of higher rate of return with each year increase in age associated with a 2% increase in the odds of return (OR, 1.02; 95% CI, 1.01‐1.04).CONCLUSIONIn nonresponding serologic reactive donors, telephone call led to a higher return rate than text message. The results of this study suggest that use of text messages, while attractive for its simplicity, will not lead to increased donor notification success after serologically reactive marker results from blood donation in Brazil.
Outreach of Pro-poor Housing Programs and Projects: Is it sustained?
Authors: Dubagunta Gowthami Sai , Patel Sejal 
Published: October 2016

Affordable housing for urban poor is one among the hot button issues among all policy makers and planners in countries of global south. Grand schemes with extravagant promises in the formal sector and gigantic hope for informal sector, to capture the opportunity at bottom of pyramid, are simultaneously trying to curb the problem of affordable housing shortage for urban poor. Even though private sector does not purposely seek to cater housing for lower income sections, yet large quantum of investment have been witnessed in housing for the urban poor. It is well known that in a free market tussle, the highest bidder is always the winner. This has been a major reason for creation of artificial shortage of housing for poor. And the scenario is worse in case of public housing, where, half of the units are either left purposeless or used by ineligible users, largely due to risk of impoverishment and improper post occupancy vigilance. The magnitude of post occupancy problems being unexplored, the objective of paper pertains to looks at the challenges and issues in sustaining targeted outreach to intended beneficiaries in housing supply models for urban poor. The paper elaborates distinct challenges through three housing supply models in Ahmedabad, India. The models are Rehabilitation Housing, Subsidized Housing by government and market provided Housing. The method is mixed method i.e. qualitative and quantitative research using primary and secondary data sources. The critical analysis of effective outreach is carried by studying policy rhetoric in each of the models to on ground veracity in the post occupancy stage of model by assessing end user satisfaction in each model.
Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility
Authors: Devenyi Ryan A. , Ortega Francis A. , Groenendaal Willemijn , Krogh‐Madsen Trine , Christini David J. , Sobie Eric A. 
Published: October 2016

Key points
Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood.
We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated.
A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model.
The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias.
AbstractImbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information‐rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re‐parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K+ current and a drastic decrease in the slow delayed rectifier K+ current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro‐arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K+ currents influences ventricular arrhythmia susceptibility.
Probing the Higgs with angular observables at future e+e− colliders
Authors: Liu Zhen 
Published: October 2016

I summarize our recent works on using differential observables to explore the physics potential of future [Formula: see text] colliders in the framework of Higgs effective field theory. This proceeding is based upon Refs. 1 and 2. We study angular observables in the [Formula: see text] channel at future circular [Formula: see text] colliders such as CEPC and FCC-ee. Taking into account the impact of realistic cut acceptance and detector effects, we forecast the precision of six angular asymmetries at CEPC (FCC-ee) with center-of-mass energy [Formula: see text] GeV and 5 (30) ab[Formula: see text] integrated luminosity. We then determine the projected sensitivity to a range of operators relevant for the Higgsstrahlung process in the dimension-6 Higgs EFT. Our results show that angular observables provide complementary sensitivity to rate measurements when constraining various tensor structures arising from new physics. We further find that angular asymmetries provide a novel means of constraining the “blind spot” in indirect limits on supersymmetric scalar top partners. We also discuss the possibility of using [Formula: see text]-fusion at [Formula: see text] machines at different energies to probe new operators.
Abstract A07: Plinabulin: Evidence for an immune-mediated mechanism of action
Authors: Lloyd George Kenneth , Mueller Philipp , Zippelius ALfred , Huang Lan 
Published: October 2016

Abstract
The purpose of this study was to investigate the evidence for an immune-mediated mechanism of action for plinabulin. Plinabulin, a novel compound for use in oncology, is an inhibitor of tubulin polymerization, induces direct tumor cell apoptosis (Nicholson et al, 2006), inhibits angiogenesis and activates the JNK pathway (Singh et al, 2011) and is in Phase 3 trials for NSCLC (Bazhenova, 2015). The methods for the in vitro and in vivo studies performed are described by Martin et al (2014) and Müller et al (2014). Recent data from in vitro studies demonstrate that plinabulin enhances immune responses as (1) it increases dendritic cell maturation as evidenced by elevated levels of CD40, MHCII, CD80 and CD86 and (2) the release of pro-inflammatory cytokines such as IL-1beta, IL-6 and IL12p40. These increases were similar to those observed with LPS. Paclitaxel and etoposide were inactive in these assays. In the MC-38 syngeneic colon tumor model in the C57BL/6 immunocompetent mouse, plinabulin (7.5 mg/kg, IP, BIW) significantly enhanced the therapeutic effect of combined PD-1/CTLA-4 inhibition on tumor volume, with a maximal effect occurring between days 13-20 after initiation of treatment. When tumor weight was measured at necropsy, plinabulin significantly enhanced the effect of both PD-1 inhibition and combined PD-1 + CTLA-4 inhibition. In this regard, evidence has been provided that agents which interfere with tubulin polymerization (e.g. ansamytocin-P3, dolastatin-10), but not microtubule stabilizing agents (e.g. docetaxel, paclitaxel) promote anti-tumor immunity as demonstrated by dendritic cell maturation and enhanced T-cell activation both in vitro and in vivo. In addition, the microtubule depolymerizing agents act synergistically with immune checkpoint inhibitors (Martin et al, 2014, Müller et al, 2014). These data indicate an immune mediated mechanism of action of plinabulin and provide the basis for initiating a clinical trial of plinabulin with the PD-1 mAb Nivolumab in metastatic NSCLC (Yeh et al, 2015).
Citation Format: George Kenneth Lloyd, Philipp Mueller, ALfred Zippelius, Lan Huang. Plinabulin: Evidence for an immune-mediated mechanism of action. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A07.
Abstract A08: Imaging in cancer immunology: Phenotyping of multiple immune cell subsets in-situ in FFPE tissue sections
Authors: Mansfield James R. , Hoyt Clifford C. , Stack Edward , Lin Steven H. , Feldman Michael , Bifulco Carlo , Fox Bernard A. 
Published: October 2016

Abstract
There has been a rapid grown in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies, and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry, but from cells imaged in situ in FFPE tissue sections.
This methodology combines: the sequential multi-marker labeling of up to 6 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue autofluorescence and correct cross-talk between fluorescent channels; and an automated image analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions.
We present here several examples of this new methodology in breast, lung and head and neck cancers. Each application example will show 6-plex multiplexed staining, per-cell quantitation of each marker and multi-marker cellular phenotyping from multispectral images of standard clinical biopsy sections, as well as methods to explore the spatial distributions of the phenotyped cells in and around the tumor.
Citation Format: James R. Mansfield, Clifford C. Hoyt, Edward Stack, Steven H. Lin, Michael Feldman, Carlo Bifulco, Bernard A. Fox. Imaging in cancer immunology: Phenotyping of multiple immune cell subsets in-situ in FFPE tissue sections. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A08.
Abstract A12: The immune composition of a spontaneous mouse breast cancer
Authors: Velica Pedro , Rundqvist Helene , Gojkovic Milos , Johnson Randall S. 
Published: October 2016

Abstract
The MMTV-PyMT mouse strain is a widely used model for the study of breast cancer. In this strain, the mouse mammary tumor virus (MMTV) promoter drives expression of the polyoma middle T (PyMT) oncogene in breast epithelium resulting in widespread transformation of the tissue and formation of progressive tumors that eventually metastasize to the lungs and lymph nodes, closely recapitulating the human disease.
It is know that MMTV-PyMT tumors are infiltrated by large numbers of immune cells and the role of some immune populations in cancer progression and metastasis has been described. However a detailed characterization of the myeloid and lymphoid populations infiltrating MMTV-PyMT during tumor progression is yet to be performed.
In this study we used comprehensive flow cytometry panels to enumerate and quantify B cells, αβ T cells (CD4 and CD8), γδ T cells, NK T cells, NK cells, neutrophils, monocytes, dendritic cells and macrophages within MMTV-PyMT tumors in different stages of progression. Given that hypoxia is a prominent aspect of breast cancer we extended this characterization to strains with targeted deletion of hypoxia-inducible factor (HIF) 1α and HIF2α in myeloid cells.
We found lymphoid cells to be the predominant immune populations within PyMT tumors particularly B cells and αβ T cells (CD4+ and CD8+) but their frequencies did not markedly change with progression or tumor mass. Surprisingly the majority of CD8 T cells expressed the NK cell marker NK1.1 (&gt;80%).
In addition we found dendritic cells (CD11chigh, MHC IIhigh) to be the prevalent myeloid population and that the frequency of this population had a strong positive correlation with tumor mass.
Myeloid deletion of HIF1a, but not HIF2a, resulted in increased tumor mass and dendritic cell infiltration while other immune population frequencies remained unchanged.
Whether dendritic cells directly affect tumor growth and to what extent HIF1α is involved in this process remains to be elucidated. We expect that this immune characterization of PyMT tumors will serve as a reference for future breast cancer immunology studies and possibly assist in the development of new immunotherapies.
Citation Format: Pedro Velica, Helene Rundqvist, Milos Gojkovic, Randall S. Johnson. The immune composition of a spontaneous mouse breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A12.
Abstract B05: N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer
Authors: Yao Libo , Li Xia , Liu Xiping , Ru Yi , Zhang Mei 
Published: October 2016

Abstract
Background and Aims: Oncogene activation and tumor suppressor gene inactivation alter multiple intracellular signaling pathways that affect metabolism of cancer cells. NDRG2 (N-Myc downstream regulated gene 2) is a newly identified tumor suppressor gene in our lab and others. We reported previously that NDRG2 functions as an essential regulator in glycolysis and glutaminolysis via repression of c-MYC, and acts as a suppressor of carcinogenesis through coordinately targeting glucose and glutamine transporter, multiple catalytic enzymes involved in glycolysis and glutaminolysis, which fuels the bioenergy and biomaterials needed for cancer proliferation and progress. Our recent studies showed that NDRG2 is involved in cell apoptosis or survival when the cells are challenged by various stress factors such as hypoxia and lipotoxicity. However, whether NDRG2 is implicated in lipid metabolism and other cellular process is unknown.
Methods: We explored the role of NDRG2 in lipid metabolism by using Oil red staining of the liver tissues from Ndrg2 mouse v.s. wild-type counterpart. We also examined the effect of Ndrg2 on the transcription of the proteasome subunits by RT-PCR, its effect on the proteasome activity by protease activity assay, as well as Nrf1 relevance in such regulation, through using the liver tissues of mouse and NDRG2-overxepressing HepG2 cells.
Results: Ndrg2 mice exhibited lipid accumulation in liver compared with the wild-type counterpart. Besides, the proteasome genes transcription were upregulated in Ndrg2 liver tissue but downregulated in NDRG2-overexpressing HepG2 cells. Moreover, NDRG2-overexpression suppressed the proteasome activity in HepG2 cells. Such effect is comparable to, but not additive with, siRNA-mediated silence of Nrf1, a well-known proteasome regulator that coordinately induces proteasome gene transcription. This implies that NDRG2 exerts its role by inhibiting Nrf1. Finally, we demonstrated that NDRG2 interacts with Nrf1 and promotes its downregulation.
Conclusion: We demonstrated for the first time that NDRG2 is a critical regulator of lipid metabolism and proteasome activity. NDRG2 inhibits the proteasome activity probably by interacting with Nrf1 and promoting its downregulation.
Note: This abstract was not presented at the conference.
Citation Format: Libo Yao, Xia Li, Xiping Liu, Yi Ru, Mei Zhang. N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B05.