bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Resolution Particle Image Velocimetry and CH-PLIF Measurements and Analysis of a Shear Layer Stabilized Flame
Authors: Foley C. W. , Chterev I. , Seitzman J. , Lieuwen T. 
Published: August 2015

Abstract
Understanding the mechanisms and physics of flame stabilization and blowoff of premixed flames is critical toward the design of high velocity combustion devices. In the high bulk flow velocity situation typical of practical combustors, the flame anchors in shear layers where the local flow velocities are much lower. Within the shear layer, fluid strain deformation rates are very high and the flame can be subjected to significant stretch levels. The main goal of this work was to characterize the flow and stretch conditions that a premixed flame experiences in a practical combustor geometry and to compare these values to calculated extinction values. High resolution, simultaneous particle image velocimetry (PIV) and planar laser induced fluorescence of CH radicals (CH-PLIF) measurements are used to capture the flame edge and near-field stabilization region. When approaching lean limit extinction conditions, we note characteristic changes in the stretch and flow conditions experienced by the flame. Most notably, the flame becomes less critically stretched when fuel/air ratio is decreased. However, at these lean conditions, the flame is subject to higher mean flow velocities at the edge, suggesting less favorable flow conditions are present at the attachment point of the flame as blowoff is approached. These measurements suggest that blowoff of the flame from the shear layer is not directly stretch extinction induced, but rather the result of an imbalance between the speed of the flame edge and local tangential flow velocity.
Sparsity‐based acoustic inversion in cross‐sectional multiscale optoacoustic imaging
Authors: Han Yiyong , Tzoumas Stratis , Nunes Antonio , Ntziachristos Vasilis , Rosenthal Amir 
Published: August 2015

Purpose:With recent advancement in hardware of optoacoustic imaging systems, highly detailed cross‐sectional images may be acquired at a single laser shot, thus eliminating motion artifacts. Nonetheless, other sources of artifacts remain due to signal distortion or out‐of‐plane signals. The purpose of image reconstruction algorithms is to obtain the most accurate images from noisy, distorted projection data.Methods:In this paper, the authors use the model‐based approach for acoustic inversion, combined with a sparsity‐based inversion procedure. Specifically, a cost function is used that includes the L1 norm of the image in sparse representation and a total variation (TV) term. The optimization problem is solved by a numerically efficient implementation of a nonlinear gradient descent algorithm. TV–L1 model‐based inversion is tested in the cross section geometry for numerically generated data as well as for in vivo experimental data from an adult mouse.Results:In all cases, model‐based TV–L1 inversion showed a better performance over the conventional Tikhonov regularization, TV inversion, and L1 inversion. In the numerical examples, the images reconstructed with TV–L1 inversion were quantitatively more similar to the originating images. In the experimental examples, TV–L1 inversion yielded sharper images and weaker streak artifact.Conclusions:The results herein show that TV–L1 inversion is capable of improving the quality of highly detailed, multiscale optoacoustic images obtained in vivo using cross‐sectional imaging systems. As a result of its high fidelity, model‐based TV–L1 inversion may be considered as the new standard for image reconstruction in cross‐sectional imaging.
Consequences of low birth weight, maternal illiteracy and poor access to medical care in rural India: infantile iatrogenic Cushing syndrome
Authors: Karande Sunil 
Published: August 2015

Home delivery, low birth weight babies and maternal illiteracy among the poor in rural India are frequent. The rural poor prefer to seek healthcare from private providers, most of whom have no formal medical training and buy medicines from private pharmacies without a prescription owing to a weakly regulated environment. This report is of a 4-month-old baby from a remote village in northern India, who presented with exogenous Cushing syndrome. This baby was a full-term low birth weight home delivery. As the baby was not growing well, treatment was started at 1 month by a private doctor with betamethasone drops The mother on her own volition continued giving the betamethasone drops by buying the medicine over the counter from a private pharmacy. This case highlights the gaps in essential health services in rural India and the steps being taken to improve the situation.
AGXT2L1 is down-regulated in heptocellular carcinoma and associated with abnormal lipogenesis
Authors: Ding Qianshan , Kang Jian , Dai Jinfen , Tang Meng , Wang Qi , Zhang Haotian , Guo Wenyi , Sun Rongze , Yu Honggang 
Published: August 2015

AimsTo clarify the clinical implications and functional role of the alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1) gene in hepatocellular carcinoma (HCC).Methods and resultsWe confirmed that AGXT2L1 was down-regulated in liver cancer samples by immunohistochemical (IHC) staining. We also demonstrated that this down-regulation was associated with several clinicopathological features such as alpha fetoprotein (AFP) serum level and T stage. Furthermore, we showed with Kaplan-Meier analysis that expression of AGXT2L1 in tumour samples was significantly correlated with patient prognosis. The bioinformatic tool indicated that AGXT2L1 plays a role in the lipid metabolic process of HCC tissue, while siRNA silenced the expression of AGXT2L1 in HCC 97H and LM3 cells, confirming that down-regulation of AGXT2L1 promotes the lipogenesis of cancer cells.ConclusionsFor the first time, we have shown that AGXT2L1 is down-regulated in HCC and its low expression indicates a poor prognosis. Our findings also demonstrated that AGXT2L1 is a crucial gene in the abnormal lipogenesis of HCC tissue.
Thou shalt not tweet unprofessionally: an appreciative inquiry into the professional use of social media
Authors: Pereira Ian , Cunningham Anne Marie , Moreau Katherine , Sherbino Jonathan , Jalali Alireza 
Published: August 2015

ABSTRACT

Background
Social media may blur the line between socialisation and professional use. Traditional views on medical professionalism focus on limiting motives and behaviours to avoid situations that may compromise care. It is not surprising that social media are perceived as a threat to professionalism.

Objective
To develop evidence for the professional use of social media in medicine.

Methods
A qualitative framework was used based on an appreciative inquiry approach to gather perceptions and experiences of 31 participants at the 2014 Social Media Summit.

Results
The main benefits of social media were the widening of networks, access to expertise from peers and other health professionals, the provision of emotional support and the ability to combat feelings of isolation.

Conclusions
Appreciative inquiry is a tool that can develop the positive practices of organisations and individuals. Our results provide evidence for the professional use of social media that may contribute to guidelines to help individuals realise benefits and avoid harms.
CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine Model of Esophageal Cancer
Authors: Karakasheva Tatiana A. , Waldron Todd J. , Eruslanov Evgeniy , Kim Sang-Bae , Lee Ju-Seog , O'Brien Shaun , Hicks Philip D. , Basu Devraj , Singhal Sunil , Malavasi Fabio , Rustgi Anil K. 
Published: August 2015

AbstractMyeloid-derived suppressor cells (MDSC) are an immunosuppressive population of immature myeloid cells found in advanced-stage cancer patients and mouse tumor models. Production of inducible nitric oxide synthase (iNOS) and arginase, as well as other suppressive mechanisms, allows MDSCs to suppress T-cell–mediated tumor clearance and foster tumor progression. Using an unbiased global gene expression approach in conditional p120-catenin knockout mice (L2-cre;p120ctnf/f), a model of oral–esophageal cancer, we have identified CD38 as playing a vital role in MDSC biology, previously unknown. CD38 belongs to the ADP-ribosyl cyclase family and possesses both ectoenzyme and receptor functions. It has been described to function in lymphoid and early myeloid cell differentiation, cell activation, and neutrophil chemotaxis. We find that CD38 expression in MDSCs is evident in other mouse tumor models of esophageal carcinogenesis, and CD38high MDSCs are more immature than MDSCs lacking CD38 expression, suggesting a potential role for CD38 in the maturation halt found in MDSC populations. CD38high MDSCs also possess a greater capacity to suppress activated T cells, and promote tumor growth to a greater degree than CD38low MDSCs, likely as a result of increased iNOS production. In addition, we have identified novel tumor–derived factors, specifically IL6, IGFBP3, and CXCL16, which induce CD38 expression by MDSCs ex vivo. Finally, we have detected an expansion of CD38+ MDSCs in peripheral blood of advanced-stage cancer patients and validated targeting CD38 in vivo as a novel approach to cancer therapy. Cancer Res; 75(19); 4074–85. ©2015 AACR.
Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression
Authors: Hurley Paula J. , Hughes Robert M. , Simons Brian W. , Huang Jessie , Miller Rebecca M. , Shinder Brian , Haffner Michael C. , Esopi David , Kimura Yasunori , Jabbari Javaneh , Ross Ashley E. , Erho Nicholas , Vergara Ismael A. , Faraj Sheila F. , Davicioni Elai , Netto George J. , Yegnasubramanian Srinivasan , An Steven S. , Schaeffer Edward M. 
Published: August 2015

Abstract
Prostate cancer is a leading cause of cancer death in men due to the subset of cancers that progress to metastasis. Prostate cancers are thought to be hardwired to androgen receptor (AR) signaling, but AR-regulated changes in the prostate that facilitate metastasis remain poorly understood. We previously noted a marked reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) expression during invasive phases of androgen-induced prostate growth, suggesting that this may be a novel invasive program governed by AR. Herein, we show that SPARCL1 loss occurs concurrently with AR amplification or overexpression in patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is directly suppressed by androgen-induced AR activation and binding at the SPARCL1 locus via an epigenetic mechanism, and these events can be pharmacologically attenuated with either AR antagonists or HDAC inhibitors. We establish using the Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1−/− mice, SPARCL1 functions to suppress cancer formation. Moreover, metastatic progression of Myc-CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment. Specifically, we show that SPARCL1 both tethers to collagen in the extracellular matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the assembly of focal adhesions, thereby constraining the transmission of cell traction forces. Our findings establish a new insight into AR-regulated prostate epithelial movement and provide a novel framework whereby SPARCL1 in the ECM microenvironment restricts tumor progression by regulating the initiation of the network of physical forces that may be required for metastatic invasion of prostate cancer. Cancer Res; 75(20); 4322–34. ©2015 AACR.
The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients
Authors: Bartolini Alice , Di Paolo Daniela , Noghero Alessio , Murgia Daniele , Sementa Angela R. , Cilli Michele , Pasqualini Renata , Arap Wadih , Bussolino Federico , Ponzoni Mirco , Pastorino Fabio , Marchiò Serena 
Published: August 2015

Abstract
Neuronal pentraxins (NPTX) and their corresponding receptors (NPTXR) have been studied as synapse-associated proteins in the nervous system, but their role in cancer is largely unknown. By applying a multidisciplinary, high-throughput proteomic approach, we have recently identified a peptide ligand motif for targeted drug delivery to neuroblastoma. Here, we report the sequence similarity between this peptide and a conserved portion of the pentraxin domain that is involved in the homo- and hetero-oligomerization of NPTX2 and NPTXR. We show that, in comparison with normal tissues, NPTX2 and NPTXR are overexpressed in vivo in mouse models, as well as in human Schwannian stroma-poor, stage IV neuroblastoma. Both proteins are concentrated in the vicinity of tumor blood vessels, with NPTXR also present on neuroblastic tumor cells. In vivo targeting of NPTX2 and NPTXR with the selected peptide or with specific antibodies reduces tumor burden in orthotopic mouse models of human neuroblastoma. In vitro interference with this ligand/receptor system inhibits the organization of neuroblastoma cells in tumor-like masses in close contact with vascular cells, as well as their adhesion to normal microenvironment-derived cells, suggesting a role in the cross-talk between tumor and normal cells in the early steps of neuroblastoma development. Finally, we show that NPTX2 is a marker of poor prognosis for neuroblastoma patients. Cancer Res; 75(20); 4265–71. ©2015 AACR.
Akt Kinase-Interacting Protein 1 Signals through CREB to Drive Diffuse Malignant Mesothelioma
Authors: Yamada Tadaaki , Amann Joseph M. , Fukuda Koji , Takeuchi Shinji , Fujita Naoya , Uehara Hisanori , Iwakiri Shotaro , Itoi Kazumi , Shilo Konstantin , Yano Seiji , Carbone David P. 
Published: August 2015

Abstract
Diffuse malignant mesothelioma (DMM) is a tumor of serosal membranes with propensity for progressive local disease. Because current treatment options are largely ineffective, novel therapeutic strategies based on molecular mechanisms and the disease characteristics are needed to improve the outcomes of patients with this disease. Akt kinase interacting protein 1 (Aki1; Freud-1/CC2D1A) is a scaffold protein for the PI3K–PDK1–Akt signaling module that helps determine receptor signal selectivity for EGFR. Aki1 has been suggested as a therapeutic target, but its potential has yet to be evaluated in a tumor setting. Here, we report evidence supporting its definition as a therapeutic target in DMM. In cell-based assays, Aki1 silencing decreased cell viability and caused cell-cycle arrest of multiple DMM cell lines via effects on the PKA–CREB1 signaling pathway. Blocking CREB activity phenocopied Aki1 silencing. Clinically, Aki1 was expressed in most human DMM specimens where its expression correlated with phosphorylated CREB1. Notably, Aki1 siRNA potently blocked tumor growth in an orthotopic implantation model of DMM when administered directly into the pleural cavity of tumor-bearing mice. Our findings suggest an important role for the Aki1–CREB axis in DMM pathogenesis and provide a preclinical rationale to target Aki1 by intrathoracic therapy in locally advanced tumors. Cancer Res; 75(19); 4188–97. ©2015 AACR.
Integrating Image-Based High-Content Screening with Mouse Models Identifies 5-Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy
Authors: Chen Li-Hsien , Sun Yuan-Ting , Chen Yih-Fung , Lee Mei-Yi , Chang Lian-Yun , Chang Jang-Yang , Shen Meng-Ru 
Published: August 2015

Abstract
Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. This study aimed to discover potential neuroprotective drugs for paclitaxel-induced neurotoxicity. An image-based high-content platform was first developed to screen for potential neuroprotective drugs. The screening system comprised of automated image acquisition and multiparameter analysis, including neuronal viability, neurite outgrowth, and synaptogenesis. By this platform, we obtained a candidate list from compound libraries. In the drug screening from compound libraries of ion channel ligands, REDOX and GABAergic ligands, 5-hydroxydecanoate (5-HD) exhibited the most significant neuroprotective effects against paclitaxel-induced neurotoxicity in both cortical and dorsal root ganglion (DRG) neurons. In mouse behavioral tests, 5-HD restored the thermal sensitivity and alleviated mechanical allodynia induced by paclitaxel. Electron micrographs of sciatic nerve revealed that 5-HD reduced the damages caused by paclitaxel in the nonmyelinated and smaller myelinated fibers. The mechanistic study on DRG neurons suggested that 5-HD rescued the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, 5-HD did not jeopardize the antitumor effect of paclitaxel in tumor xenograft models. In conclusion, we established an imaged-based high-content screening platform and a protocol for verifying the neuroprotective effect in vivo, by which 5-HD was identified and validated as a potential neuroprotective drug for paclitaxel-induced neuropathy. Mol Cancer Ther; 14(10); 2206–14. ©2015 AACR.
A Novel Inhibitor of AKT1–PDPK1 Interaction Efficiently Suppresses the Activity of AKT Pathway and Restricts Tumor Growth In Vivo
Authors: Mäemets-Allas Kristina , Viil Janeli , Jaks Viljar 
Published: August 2015

Abstract
The serine/threonine kinase AKT/PKB has a critical role in the regulation of cell proliferation. Because AKT signaling is deregulated in numerous human malignancies, it has become an attractive anticancer drug target. A number of small molecule AKT kinase inhibitors have been developed; however, severe side effects have prevented their use in clinical trials. To find inhibitors of AKT1 signaling with principally novel mechanism of action, we carried out a live cell-based screen for small molecule inhibitors of physical interaction between AKT1 and its primary activator PDPK1. The screen revealed one molecule—NSC156529, which downregulated AKT1 signaling, efficiently decreased the proliferation of human cancer cells in vitro, and substantially inhibited the growth of prostate tumor xenografts in vivo. Interestingly, the treated tumor xenografts exhibited higher expression level of normal prostate differentiation markers but did not show augmented cell death, suggesting that the identified compound primarily enhances the differentiation of malignant cells toward normal prostate epithelium and thus poses as an attractive lead compound for developing novel antitumor agents with less cytotoxic side effects. Mol Cancer Ther; 14(11); 2486–96. ©2015 AACR.
Antibody Format and Drug Release Rate Determine the Therapeutic Activity of Noninternalizing Antibody–Drug Conjugates
Authors: Gébleux Rémy , Wulhfard Sarah , Casi Giulio , Neri Dario 
Published: August 2015

Abstract
The development of antibody–drug conjugates (ADC), a promising class of anticancer agents, has traditionally relied on the use of antibodies capable of selective internalization in tumor cells. We have recently shown that also noninternalizing antibodies, coupled to cytotoxic drugs by means of disulfide linkers that can be cleaved in the tumor extracellular environment, can display a potent therapeutic activity. Here, we have compared the tumor-targeting properties, drug release rates, and therapeutic performance of two ADCs, based on the maytansinoid DM1 thiol drug and on the F8 antibody, directed against the alternatively spliced Extra Domain A (EDA) domain of fibronectin. The antibody was used in IgG or in small immune protein (SIP) format. In both cases, DM1 was coupled to unpaired cysteine residues, resulting in a drug-antibody ratio of 2. In biodistribution studies, SIP(F8)-SS-DM1 accumulated in the tumor and cleared from circulation more rapidly than IgG(F8)-SS-DM1. However, the ADC based on the IgG format exhibited a higher tumor uptake at later time points (e.g., 33%IA/g against 8%IA/g at 24 hours after intravenous administration). In mouse plasma, surprisingly, the ADC products in IgG format were substantially more stable compared with the SIP format (half-lives &gt;48 hours and &lt;3 hours at 37°C, respectively), revealing a novel mechanism for the control of disulfide-based drug release rates. Therapy experiments in immunocompetent mice bearing murine F9 tumors revealed that SIP(F8)-SS-DM1 was more efficacious than IgG(F8)-SS-DM1 when the two products were compared either in an equimolar basis or at equal milligram doses. Mol Cancer Ther; 14(11); 2606–12. ©2015 AACR.
Abstract A04: The tumor microenvironment is the main source of IL-6 for plasmacytoma development in mice.
Authors: Rosean Timothy R. , Tompkins Van S. , Sompallae Ramakrishna , Norian Lyse A. , Morse Herbert C. , Waldschmidt Thomas J. , Janz Siegfried 
Published: August 2015

Abstract
The development of targeted interventions for hematopoietic neoplasms of the B-lymphocyte lineage, such as multiple myeloma (MM), may benefit from preclinical experimental model systems in which complex interactions of neoplastic and nonmalignant bystander cells in the tumor microenvironment (TME) can be genetically dissected. Here we employ peritoneal plasmacytomagenesis in mice, which is strictly dependent on the pro-inflammatory cytokine, interleukine 6 (IL-6), to demonstrate that the nonmalignant bystanders are the main source of IL-6 for tumor development. B cell derived IL-6 is dispensable. The finding that lack of IL-6 in the TME significantly delays tumor onset in mice supports translational research efforts to target IL-6 production in bone marrow stroma cells for myeloma treatment and prevention.
Citation Format: Timothy R. Rosean, Van S. Tompkins, Ramakrishna Sompallae, Lyse A. Norian, Herbert C. Morse, III, Thomas J. Waldschmidt, Siegfried Janz. The tumor microenvironment is the main source of IL-6 for plasmacytoma development in mice. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A04.