bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY08-02: Normal and neoplastic stem cells
Authors: Weissman Irving L. 
Published: July 2016

Abstract
The transition from single cell species to multicellular organisms led to organ and tissue development. The development and maintenance of organs/tissues in multicellular organisms has resulted in the emergence of specialized cells that self-renew as well as differentiate; these rare cells are stem cells. Following embryonic development, most of our tissues and organs are continuously regenerated from tissue/organ specific stem cells. The principal property that distinguishes such stem cells from their daughter cells is self-renewal; when stem cells divide they give rise to stem cells (by self-renewal) and progenitors (by differentiation). In most tissues only the primitive stem cells self-renew. Even within a particular tissue, stem cells may be diverse, and subject to stem cell competition for their niche. We have documented both germline stem cell and somatic stem cell competition in species as diverse as colonial protochordates and humans. Stem cell isolation and transplantation is the basis for regenerative medicine. Self-renewal is dangerous, and therefore strictly regulated. Poorly regulated self-renewal can lead to the genesis of cancer stem cells, the only self-renewing cells in the cancerous tumor. The Weissman lab has followed the progression from hematopoietic stem cells (HSCs) to myelogenous leukemias. They have found that the developing cancer clones progress at the stage of HSCs, until they become fully malignant. At this point, the “leukemia” stem cell is at a stage of a downstream oligolineage or multilineage progenitor that has evaded programmed cell death and programmed cell removal, while acquiring or keeping self-renewal. In the case of chronic myeloid leukemia, bcr-abl+ HSC clones outcompete normal HSCs in the chronic phase. The transition from the chronic phase to myeloid blast crisis results in the leukemia stem cells appearing in the granulocyte-macrophage progenitor (GMP) stage. While there are many ways to defeat programmed cell death and senescence, there appears to be one dominant method to avoid programmed cell removal—the expression of the cell surface “don't eat me” protein CD47, the ligand for macrophage SIRPα. All cancers tested express CD47 to overcome expression of “eat me” signals such as calreticulin. Antibodies that block the CD47-SIRPα interaction enable phagocytosis and killing of the tumor cells in vitro and in vivo. All tested human solid tumors and lymphomas/leukemias/myelomas express CD47 and are susceptible to phagocytosis in the presence of anti-CD47 blocking antibodies.
Citation Format: Irving L. Weissman. Normal and neoplastic stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY08-02.
Abstract SY16-03: Targeting Bcl-2 as a therapeutic strategy and predictive biomarker in CLL
Authors: Davids Matthew S. 
Published: July 2016

Abstract
The selective BCL-2 antagonist venetoclax has recently demonstrated striking efficacy in patients with CLL, even those with high risk, refractory disease. This presentation will review the preclinical data that supported exploring BCL-2 inhibition in CLL and the clinical trial results of venetoclax monotherapy in this disease. Tumor lysis syndrome and how this risk can be mitigated will also be discussed. Mitochondrial priming reflects the proximity of a cell to the threshold of apoptosis and can be measured using a functional technique known as BH3 profiling. Data will also be presented which suggest that BH3 profiling may serve as a predictive biomarker of response to venetoclax in CLL, and that the change in priming in response to ex vivo drug treatments may help identify optimal combination partners for venetoclax to inform the design of clinical trials for CLL patients.
Citation Format: Matthew S. Davids. Targeting Bcl-2 as a therapeutic strategy and predictive biomarker in CLL. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY16-03.
Abstract SY20-03: Metastatic latency and immune evasion by cancer stem cells
Authors: Massague Joan 
Published: July 2016

Abstract
Metastasis frequently develops, years after the removal of a primary tumor, from a minority of disseminated cancer cells that survived as latent entities. An improved understanding of the location and survival mechanisms of disseminated cancer cells, and their ability to enter a quiescent state, evade immune surveillance, and retain tumor reinitiating capacity is needed in order to better prevent and treat metastasis. To this end, we developed latency competent cancer cell (LCC) models from early stage human lung and breast carcinoma cell lines and defined the mechanisms that prevent the outgrowth, support the long-term survival, and maintain the tumor-initiating potential of these cells during latent metastasis. LCC cells show stem cell-like characteristics and express Sox transcription factors, which are essential for their survival in host organs under restrictive conditions and for metastatic outgrowth under permissive conditions. Through autocrine suppression of WNT signaling and heightened TGF-β signaling, LCC cells self-impose a slow-cycling state with broad downregulation of NK cell activators. By actively entering quiescence, metastatic stem cells can evade innate immunity to remain latent for extended periods. By persistently reentering the proliferative state, these cells may evolve organ-specific colonization traits to take over the host stroma.
Citation Format: Joan Massague. Metastatic latency and immune evasion by cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY20-03.
Abstract SY43-01: Precision cancer medicine using BH3 profiling
Authors: Letai Anthony G. 
Published: July 2016

Abstract
The job of precision medicine is to match the right patient to the right drug(s). While the term “precision medicine” is often considered synonymous with “cancer genomics,” -omics approaches have thus far enjoyed only inconsistent success in assigning therapy to patients, despite the abundance of data such approaches generate. We favor functional approaches that allow for perturbation of the cancer cells of interest. BH3 profiling can measure the state of the apoptotic pathway of a cancer cell before and after brief exposures to drugs. By identifying drugs that enhance apoptotic signaling in brief ex vivo exposures, we can identify agents that are active in vivo. An advantage to dynamic BH3 profiling is that its measurements can be made in less than 24 hours, removing the requirement for longer term ex vivo culture that has typically proved a major stumbling block for ex vivo approaches.
Citation Format: Anthony G. Letai. Precision cancer medicine using BH3 profiling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY43-01.
Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment
Authors: Nguyen Daniel P. , Xiong Peter L. , Liu He , Pan Samuel , Leconet Wilhem , Navarro Vincent , Guo Ming , Moy Jonathan , Kim Sae , Ramirez-Fort Marigdalia K. , Batra Jaspreet S. , Bander Neil H. 
Published: July 2016

AbstractAngiogenesis is critical for tumor growth and survival and involves interactions between cancer and endothelial cells. Prostate-specific membrane antigen (PSMA/FOLH1) is expressed in the neovasculature of several types of cancer. However, the study of neovascular PSMA expression has been impeded as human umbilical vein endothelial cell (HUVEC) cultures are PSMA-negative and both tumor xenografts and patient-derived xenograft (PDX) models are not known to express PSMA in their vasculature. Therefore, PSMA expression was examined in HUVECs, in vitro and in vivo, and we tested the hypothesis that cancer cell–HUVEC crosstalk could induce the expression of PSMA in HUVECs. Interestingly, conditioned media from several cancer cell lines induced PSMA expression in HUVECs, in vitro, and these lines induced PSMA, in vivo, in a HUVEC coimplantation mouse model. Furthermore, HUVECs in which PSMA expression was induced were able to internalize J591, a mAb that recognizes an extracellular epitope of PSMA as well as nanoparticles bearing a PSMA-binding ligand/inhibitor. These findings offer new avenues to study the molecular mechanism responsible for tumor cell induction of PSMA in neovasculature as well as the biological role of PSMA in neovasculature. Finally, these data suggest that PSMA-targeted therapies could synergize with antiangiogenic and/or other antitumor agents and provide a promising model system to test therapeutic modalities that target PSMA in these settings.Implications: Cancer cells are able to induce PSMA expression in HUVECs, in vitro and in vivo, allowing internalization of PSMA-specific mAbs and nanoparticles bearing a PSMA-binding ligand/inhibitor. Mol Cancer Res; 14(11); 1045–53. ©2016 AACR.
Diagnostic Performance of a Smartphone‐Based Photoplethysmographic Application for Atrial Fibrillation Screening in a Primary Care Setting
Authors: Chan Pak‐Hei , Wong Chun‐Ka , Poh Yukkee C. , Pun Louise , Leung Wangie Wan‐Chiu , Wong Yu‐Fai , Wong Michelle Man‐Ying , Poh Ming‐Zher , Chu Daniel Wai‐Sing , Siu Chung‐Wah 
Published: July 2016

Background

Diagnosing atrial fibrillation (
AF
) before ischemic stroke occurs is a priority for stroke prevention in
AF
. Smartphone camera–based photoplethysmographic (
PPG
) pulse waveform measurement discriminates between different heart rhythms, but its ability to diagnose
AF
in real‐world situations has not been adequately investigated. We sought to assess the diagnostic performance of a standalone smartphone
PPG
application, Cardiio Rhythm, for
AF
screening in primary care setting.

Methods and Results

Patients with hypertension, with diabetes mellitus, and/or aged ≥65 years were recruited. A single‐lead
ECG
was recorded by using the AliveCor heart monitor with tracings reviewed subsequently by 2 cardiologists to provide the reference standard.
PPG
measurements were performed by using the Cardiio Rhythm smartphone application.
AF
was diagnosed in 28 (2.76%) of 1013 participants. The diagnostic sensitivity of the Cardiio Rhythm for
AF
detection was 92.9% (95%
CI
] 77–99%) and was higher than that of the AliveCor automated algorithm (71.4% [95%
CI
51–87%]). The specificities of Cardiio Rhythm and the AliveCor automated algorithm were comparable (97.7% [95%
CI
: 97–99%] versus 99.4% [95%
CI
99–100%]). The positive predictive value of the Cardiio Rhythm was lower than that of the AliveCor automated algorithm (53.1% [95%
CI
38–67%] versus 76.9% [95%
CI
56–91%]); both had a very high negative predictive value (99.8% [95%
CI
99–100%] versus 99.2% [95%
CI
98–100%]).

Conclusions

The Cardiio Rhythm smartphone
PPG
application provides an accurate and reliable means to detect
AF
in patients at risk of developing
AF
and has the potential to enable population‐based screening for
AF
.
Using the SAL Technique for Spatial Verification of Cloud Processes: A Sensitivity Analysis
Authors: Weniger Michael , Friederichs Petra 
Published: July 2016

AbstractThe feature-based spatial verification method named for its three score components: structure, amplitude, and location (SAL) is applied to cloud data, that is, two-dimensional spatial fields of total cloud cover and spectral radiance. Model output is obtained from the German-focused Consortium for Small-Scale Modeling (COSMO-DE) forward operator Synthetic Satellite Simulator (SynSat) and compared with SEVIRI satellite data. The aim of this study is twofold: first, to assess the applicability of SAL to this kind of data and, second, to analyze the role of external object identification algorithms (OIA) and the effects of observational uncertainties on the resulting scores. A comparison of three different OIA shows that the threshold level, which is a fundamental part of all studied algorithms, induces high sensitivity and unstable behavior of object-dependent SAL scores (i.e., even very small changes in parameter values lead to large changes in the resulting scores). An in-depth statistical analysis reveals significant effects on distributional quantities commonly used in the interpretation of SAL, for example, median and interquartile distance. Two sensitivity indicators that are based on the univariate cumulative distribution functions are derived. They make it possible to assess the sensitivity of the SAL scores to threshold-level changes without computationally expensive iterative calculations of SAL for various thresholds. The mathematical structure of these indicators connects the sensitivity of the SAL scores to parameter changes with the effect of observational uncertainties. Last, the discriminating power of SAL is studied. It is shown that—for large-scale cloud data—changes in the parameters may have larger effects on the object-dependent SAL scores (i.e., the S and L2 scores) than does a complete loss of temporal collocation.
A Variational Method for Estimating Surface Turbulent Heat Fluxes with a Consideration of Energy Storage
Authors: Zhang Shuwen , Cao Bangjun , Zhang Weidong , Cao Qian , Liu Yuan , Qiu Chongjian 
Published: July 2016

Abstract
Two approaches are proposed to introduce the surface energy storage into the cost function in a variational method for improving the estimates of surface turbulent heat fluxes. In the first approach, each of the energy storage terms is directly calculated based on available observations, and in the second approach, the total energy storage is fitted by the piecewise linear regression function. The heat flux estimates are validated with the eddy correlation (EC) measurements at two carefully selected stations with different land covers and weather conditions in northwestern China and east of the Tibetan Plateau, respectively. In contrast to the variational method without considering the energy storage in the cost function, two new approaches have improved the heat flux estimates, with the first approach being slightly better, especially around midday and/or under strong unstable conditions. It is also reasonable that the calculated/fitted energy storage with the measurements in the previous time period can be transferred for the heat flux estimates in the later time period. Furthermore, the heat flux estimates with both approaches are less sensitive to the errors in the profiles of temperature, humidity, and wind, as well as energy storage, so they may be more reliable.
Time Scales of Southern Ocean Eddy Equilibration
Authors: Sinha Anirban , Abernathey Ryan P. 
Published: July 2016

AbstractStratification in the Southern Ocean is determined primarily by a competition between westerly wind-driven upwelling and baroclinic eddy transport. This study investigates the time scales of equilibration of the Southern Ocean in response to changing winds through an idealized channel model. An analytical framework describing the energetic pathways between wind input, available potential energy (APE), eddy kinetic energy (EKE), and dissipation provides a simple theory of the phase and amplitude response to oscillating wind stress. The transient ocean response to variable winds lies between the two limits of Ekman response (high frequency), characterized by the isopycnal slope responding directly to wind stress, and “eddy saturation” (low frequency), wherein a large fraction of the anomalous wind work goes into mesoscale eddies. The crossover time scale is the time scale of meridional eddy diffusive transport across the Antarctic Circumpolar Current (ACC) front. For wind variability with a period of 3 months (high-frequency forcing), the relative conversion of wind work to APE/EKE is 11, while for a period of 16 years (low-frequency forcing), the relative conversion to APE/EKE reduces to 3. The system’s frequency response is characterized by a complex transfer function. Both the phase and amplitude response of EKE and APE predicted by the linear analytic framework are verified using multiple ensemble experiments in an eddy-resolving (4-km horizontal resolution) isopycnal coordinate model. The results from the numerical experiments show agreement with the linear theory and can be used to explain certain features observed in previous modeling studies and observations.
RETRACTED: Sluggish Cognitive Tempo, Internalizing Symptoms, and Executive Function in Adults With ADHD
Authors: Leikauf John E. , Solanto Mary V. 
Published: July 2016

Leikauf, J. E., & Solanto, M. V. (2016). Sluggish Cognitive Tempo, Internalizing Symptoms, and Executive Function in Adults With ADHD. Journal of Attention Disorders. Advance online publication. doi: 10.1177/1087054716659361 The article was revised after its original publication in OnlineFirst. The original publication has now been removed, and the final OnlineFirst version of the article can be accessed at http://journals.sagepub.com/doi/full/10.1177/1087054716682337
Low-Dose 0.5% 5-Fluorouracil/10% Salicylic Acid Topical Solution in the Treatment of Actinic Keratoses
Authors: Herranz Pedro , Morton Colin , Dirschka Thomas , Azeredo Rosario Rodríguez , Roldán-Marín Rodrigo 
Published: July 2016

Background: Actinic keratosis (AK) lesions have the potential to develop into invasive squamous cell carcinomas (SCCs), and approaches to treatment are evolving to try to reduce the burden of SCC. Objective: To present the published clinical research surrounding the use of 0.5% 5-fluorouracil with 10% salicylic acid (low-dose 5-FU/SA) for the treatment of hyperkeratotic AKs. Method: A review of published clinical evidence for low-dose 5-FU/SA for the treatment of AKs. The articles were selected following a MEDLINE database search of the combined terms fluorouracil, salicylic acid and actinic keratosis which represent the peer review publications of clinical studies that primarily investigate the use of Actikerall in AK. Results: Combining low-dose 5-FU with keratolytic SA is associated with high rates of histologic clearance, reduction in lesion number/area, and sustained clinical response in clinical study and the clinical practice setting. Low-dose 5-FU/SA has also been evaluated using imaging to detect the progression of subclinical AK lesions through a course of the field-directed treatment. Conclusion: Low-dose 5-FU/SA is an effective and well-tolerated treatment option licensed for the lesion-directed treatment of mild-to-moderate hyperkeratotic AK lesions.
Diffuse reflectance spectra of methylene blue adsorbed on different types of clay samples
Authors: Milošević M. , Logar M. , Dojčinović B. , Rosić A. , Erić S. 
Published: July 2016

AbstractDiffuse reflectance (DR) spectra in the visible (VIS) and near-infrared (NIR) region of methylene blue (MB) adsorbed on clay samples of different mineral composition and varying MB/clay ratios were analyzed. This type of investigation is not affected by unadsorbed MB molecules and can be used in clay-mineral determination. When the MB dye/clay loading was increased, enhancement of bands in the DR-VIS and DR-NIR was observed. The distribution of various MB aggregates was interpreted according to mineral composition and MB loading. The NIR spectrum of H2O overtone provides insights about the intercalated MB aggregation, consistent with VIS spectra. Critical MB concentration for formation of dimeric structure was between 0.7 and 1.75 mmol/100 g followed with suppression of monomers. Different orientations of vectors of polarized light allowed calculations of the possible orientation and tilting angle of MB molecules on the surface of the clay particles in accordance with XRD data.
Fixed point theorems for almost generalized $\mathcal{C}$-contractive mappings in ordered complete metric spaces
Authors: Azizi Azizollah , Moosaei Mohammad , Zarei Gita 
Published: July 2016

AbstractThe purpose of this paper is to present some fixed point and common fixed point theorems for almost generalized $\mathcal{C}$
C
-contractive mappings in an ordered complete metric space. Finally, two examples are given to support our results.
Neurokinin B Receptor Antagonism in Women With Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial
Authors: George Jyothis T. , Kakkar Rahul , Marshall Jayne , Scott Martin L. , Finkelman Richard D. , Ho Tony W. , Veldhuis Johannes , Skorupskaite Karolina , Anderson Richard A. , McIntosh Stuart , Webber Lorraine 
Published: July 2016

Context:
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is characterized by high secretion levels of LH and T. Currently, there is no treatment licensed specifically for PCOS.

Objective:
The objective of this study was to investigate whether a targeted therapy would decrease LH pulse frequency in women with PCOS, subsequently reducing serum LH and T concentrations and thereby presenting a novel therapeutic approach to the management of PCOS.

Design:
This study is a double-blind, double-dummy, placebo-controlled, phase 2 trial.

Settings:
University hospitals and private clinical research centers were included.

Participants:
Women with PCOS aged 18–45 years participated.

Intervention:
Intervention included AZD4901 (a specific neurokinin-3 [NK3] receptor antagonist) at a dose of 20, 40, or 80 mg/day or matching placebo for 28 days.

Main Outcome Measure:
Change from baseline in the area under the LH serum concentration–time curve over 8 hours (area under the curve) on day 7 relative to placebo was measured.

Results:
Of a total 67 randomized patients, 65 were evaluable. On day 7, the following baseline-adjusted changes relative to placebo were observed in patients receiving AZD4901 80 mg/day: 1) a reduction of 52.0% (95% confidence interval [CI], 29.6–67.3%) in LH area under the curve; 2) a reduction of 28.7% (95% CI, 13.9–40.9%) in total T concentration; and 3) a reduction of 3.55 LH pulses/8 hours (95% CI, 2.0–5.1) (all nominal P &lt; .05).

Conclusions:
The NK3 receptor antagonist AZD4901 specifically reduced LH pulse frequency and subsequently serum LH and T concentrations, thus presenting NK3 receptor antagonism as a potential approach to treating the central neuroendocrine pathophysiology of PCOS.
Business Practices in Small Firms in Developing Countries
Authors: McKenzie David , Woodruff Christopher 
Published: July 2016

Management has a large effect on the productivity of medium and large firms. But does management matter in micro and small firms, where the majority of the labor force in developing countries works? We develop 26 questions that measure business practices in marketing, stock-keeping, record-keeping, and financial planning. These questions have been administered in surveys in Bangladesh, Chile, Ghana, Kenya, Mexico, Nigeria, and Sri Lanka. We show that variation in business practices explains as much of the variation in outcomes—sales, profits, and labor productivity and total factor productivity—in microenterprises as in larger enterprises. Panel data from three countries indicate that better business practices predict higher survival rates and faster sales growth. The association of business practices with firm outcomes is robust to including numerous measures of the owner’s human capital. We find that owners with higher human capital, children of entrepreneurs, and firms with employees employ better business practices. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2016.2492 . This paper was accepted by Toby Stuart, entrepreneurship and innovation.