bluuebunny/crossref_metadata_2025 huggingface dataset:
Workshop on Tracking Quality of Experience in the Internet
Authors: Bustamante Fabian E. , Clark David , Feamster Nick
Published: January 2017

This is a report on the Workshop on Tracking Quality of Experience in the Internet, held at Princeton, October 21--22, 2015, jointly sponsored by the National Science Foundation and the Federal Communication Commission. The term Quality of Experience (QoE) describes a user's subjective assessment of their experience when using a particular application. In the past, network engineers have typically focused on Quality of Service (QoS): performance metrics such as throughput, delay and jitter, packet loss, and the like. Yet, performance as measured by QoS parameters only matters if it affects the experience of users, as they attempt to use a particular application. Ultimately, the user's experience is determined by QoE impairments (e.g., rebuffering). Although QoE and QoS are related---for example, a video rebuffering event may be caused by high packet-loss rate---QoE metrics ultimately affect a user's experience. Identifying the causes of QoE impairments is complex, since the impairments may arise in one or another region of the network, in the home network, on the user's device, in servers that are part of the application, or in supporting services such as the DNS. Additionally, metrics for QoE continue to evolve, as do the methods for relating QoE impairments to underlying causes that could be measurable using standard network measurement techniques. Finally, as the capabilities of the underlying network infrastructure continues to evolve, researchers should also consider how to design infrastructure and tools can best support measurements that can better identify the locations and causes of QoE impairments. The workshop's aim was to understand the current state of QoE research and to contemplate a community agenda to integrate ongoing threads of QoE research into a collaboration. This summary report describes the topics discussed and summarize the key points of the discussion. Materials related to the workshop are available at http://aqualab.cs.northwestern.edu/NSFWorkshop-InternetQoE.
Update on Alzheimer's Disease Therapy and Prevention Strategies
Authors: Graham W. Vallen , Bonito-Oliva Alessandra , Sakmar Thomas P.
Published: January 2017

Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology. Although clinical trial design is challenging, due in part to a lack of robust biomarkers with predictive value, some optimism has come from the identification and study of inherited forms of early-onset AD and genetic risk factors that provide insights about molecular pathophysiology and potential drug targets. In addition, better understanding of the Aβ amyloid pathway and the tau pathway—leading to amyloid plaques and neurofibrillary tangles, respectively, which are histopathological hallmarks of AD—continues to drive significant drug research and development programs. The main focus of this review is to summarize the most recent basic biology, biochemistry, and pharmacology that serve as a foundation for more than 50 active advanced-phase clinical trials for AD prevention and therapy.
Controversies in the Treatment of Ductal Carcinoma in Situ
Authors: Barrio Andrea V. , Van Zee Kimberly J.
Published: January 2017

Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with “low-risk” DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.
Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models
Authors: Milewicz Dianna M. , Prakash Siddharth K. , Ramirez Francesco
Published: January 2017

Thoracic aortic diseases, including aneurysms and dissections of the thoracic aorta, are a major cause of morbidity and mortality. Risk factors for thoracic aortic disease include increased hemodynamic forces on the ascending aorta, typically due to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease either disrupt smooth muscle cell (SMC) contraction or adherence to an impaired extracellular matrix, or decrease canonical transforming growth factor beta (TGF-β) signaling. Paradoxically, TGF-β hyperactivity has been postulated to be the primary driver for the disease. More recently, it has been proposed that the response of aortic SMCs to the hemodynamic load on a structurally defective aorta is the primary driver of thoracic aortic disease, and that TGF-β overactivity in diseased aortas is a secondary, unproductive response to restore tissue function. The engineering of mouse models of inherited aortopathies has identified potential therapeutic agents to prevent thoracic aortic disease.
Adropin acts in the rat paraventricular nucleus to influence neuronal excitability
Authors: Loewen Spencer P. , Ferguson Alastair V.
Published: January 2017

Adropin is a peptide hormone with cardiovascular and metabolic roles in the periphery, including effects on glucose and lipid homeostasis. Central administration of adropin has been shown to inhibit water intake in rats; however, the site at which central adropin acts has yet to be elucidated. The hypothalamic paraventricular nucleus (PVN), a critical autonomic control center, plays essential roles in the control of fluid balance, energy homeostasis, and cardiovascular regulation, and is, therefore, a potential target for centrally acting adropin. In the present study, we used whole cell patch-clamp techniques to examine the effects of adropin on the excitability of neurons within the PVN. All three neuronal subpopulations (magnocellular, preautonomic, and neuroendocrine) in the PVN were found to be responsive to bath-application of 10 nM adropin, which elicited responses in 68% of cells tested ( n = 57/84). The majority of cells (58%) depolarized (5.2 ± 0.3 mV; n = 49) in response to adropin, whereas the remaining responsive cells (10%) hyperpolarized (−3.4 ± 0.5 mV; n = 8), effects that were shown to be concentration-dependent. Additionally, responses were maintained in the presence of 1 μM TTX in 75% of cells tested ( n = 9/12), and voltage-clamp analysis revealed that adropin had no effect on the amplitude or frequency of excitatory or inhibitory postsynaptic currents (EPSCs and IPSCs) in PVN neurons, suggesting the peptide exerts direct, postsynaptic actions on these neurons. Collectively, these findings suggest central adropin may exert its physiological effects through direct actions on neurons in the PVN.
New CZM for Interfacial Crack Growth
Authors: Peng Huifen , Song Yujie , Xia Ye
Published: January 2017

The cohesive zone model (CZM) has been widely used for numerical simulations of interface crack growth. However, geometrical and material discontinuities decrease the accuracy and efficiency of the CZM when based on the conventional finite element method (CFEM). In order to promote the development of numerical simulation of interfacial crack growth, a new CZM, based on the wavelet finite element method (WFEM), is presented. Some fundamental issues regarding CZM of interface crack growth of double cantilever beam (DCB) testing were studied. The simulation results were compared with the experimental and simulation results of CFEM. It was found that the new CZM had higher accuracy and efficiency in the simulation of interface crack growth. At last, the impact of crack initiation length and elastic constants of material on interface crack growth was studied based on the new CZM. These results provided a basis for reasonable structure design of composite material in engineering.
Pricing Mining Concessions Based on Combined Multinomial Pricing Model
Authors: Xiao Chang , Zhou Jinsheng
Published: January 2017

A combined multinomial pricing model is proposed for pricing mining concession in which the annualized volatility of the price of mineral products follows a multinomial distribution. First, a combined multinomial pricing model is proposed which consists of binomial pricing models calculated according to different volatility values. Second, a method is provided to calculate the annualized volatility and the distribution. Third, the value of convenience yields is calculated based on the relationship between the futures price and the spot price. The notion of convenience yields is used to adjust our model as well. Based on an empirical study of a Chinese copper mine concession, we verify that our model is easy to use and better than the model with constant volatility when considering the changing annualized volatility of the price of the mineral product.
Improved KLT Algorithm for High-Precision Wavelength Tracking of Optical Fiber Bragg Grating Sensors
Authors: Tosi Daniele
Published: January 2017

Fiber Bragg Gratings (FBGs) are among the most popular optical fiber sensors. FBGs are well suited for direct detection of temperature and strain and can be functionalized for pressure, humidity, and refractive index sensing. Commercial setups for FBG interrogation are based on white-light sources and spectrometer detectors, which are capable of decoding the spectrum of an FBG array. Low-cost spectrometers record the spectrum on a coarse wavelength grid (typically 78–156 pm), whereas wavelength shifts of 1 pm or lower are required by most of the applications. Several algorithms have been presented for detection of small wavelength shift, even with coarse wavelength sampling; most notably, the Karhunen-Loeve Transform (KLT) was demonstrated. In this paper, an improved algorithm based on KLT is proposed, which is capable of further expanding the performances. Simulations show that, reproducing a commercial spectrometer with 156 pm grid, the algorithm estimates wavelength shift with accuracy well below 1 pm. In typical signal-to-noise ratio (SNR) conditions, the root mean square error is 22–220 fm, while the accuracy is 0.22 pm, despite the coarse sampling. Results have been also validated through experimental characterization. The proposed method allows achieving exceptional accuracy in wavelength tracking, beating the picometer level resolution proposed in most commercial and research software, and, due to fast operation (>5 kHz), is compatible also with structural health monitoring and acoustics.
A Novel 3D CAD Model Retrieval Method Based on Vertices Classification and Weights Combination Optimization
Authors: Zhuang Ting , Zhang Xutang , Hou Zhenxiu , Zuo Wangmeng , Liu Yan
Published: January 2017

3D shape retrieval is a problem of current interest in different fields, especially in the mechanical engineering domain. According to our knowledge, multifeature based techniques achieve the best performance at present. However, the practicability of those methods is badly limited due to the high computational cost. To improve the retrieval efficiency of 3D CAD model, we propose a novel 3D CAD model retrieval algorithm called VSC_WCO which consists of a new 3D shape descriptor named VSC and Weights Combination Optimization scheme WCO. VSC represents a 3D model with three distance distribution histograms based on vertices classification. The weighted sum of L1 norm distances between corresponding distance histograms of two VSC descriptors is regarded as dissimilarity of two models. For higher retrieval accuracy on a classified 3D model database, WCO is proposed based on Particle Swarm Optimization and existing class information. Experimental results on ESB, PSB, and NTU databases show that the discriminative power of VSC is already comparable to or better than several typical shape descriptors. After WCO is employed, the performance of VSC_WCO is similar to the leading methods by all performance metrics and is much better by computational efficiency.
New JLS-Factor Model versus the Standard JLS Model: A Case Study on Chinese Stock Bubbles
Authors: Hu Zongyi , Li Chao
Published: January 2017

In this paper, we extend the Johansen-Ledoit-Sornette (JLS) model by introducing fundamental economic factors in China (including the interest rate and deposit reserve rate) and the historical volatilities of targeted and US equity indices into the original model, which is a flexible tool to detect bubbles and predict regime changes in financial markets. We then derive a general method to incorporate these selected factors in addition to the log-periodic power law signature of herding and compare the prediction accuracy of the critical time between the original and the new JLS models (termed the JLS-factor model) by applying these two models to fit two well-known Chinese stock indices in three bubble periods. The results show that the JLS-factor model with Chinese characteristics successfully depicts the evolutions of bubbles and “antibubbles” and constructs efficient end-of-bubble signals for all bubbles in Chinese stock markets. In addition, the results of standard statistical tests demonstrate the excellent explanatory power of these additive factors and confirm that the new JLS model provides useful improvements over the standard JLS model.
Determining Optimal Replacement Policy with an Availability Constraint via Genetic Algorithms
Authors: Zong Shengliang , Chai Guorong , Su Yana
Published: January 2017

We develop a model and a genetic algorithm for determining an optimal replacement policy for power equipment subject to Poisson shocks. If the time interval of two consecutive shocks is less than a threshold value, the failed equipment can be repaired. We assume that the operating time after repair is stochastically nonincreasing and the repair time is exponentially distributed with a geometric increasing mean. Our objective is to minimize the expected average cost under an availability requirement. Based on this average cost function, we propose the genetic algorithm to locate the optimal replacement policy N to minimize the average cost rate. The results show that the GA is effective and efficient in finding the optimal solutions. The availability of equipment has significance effect on the optimal replacement policy. Many practical systems fit the model developed in this paper.
Inflammation and Cancer: Extra- and Intracellular Determinants of Tumor-Associated Macrophages as Tumor Promoters
Authors: Szebeni Gabor J. , Vizler Csaba , Kitajka Klara , Puskas Laszlo G.
Published: January 2017

One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB, RORC1, and HIF-1α) of cell functions and drive the recruitment and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed in the context of the inflammatory myeloid tumor compartment. Accumulating evidence suggests that high TAM infiltration correlates with disease progression and overall poor survival of cancer patients. Identification of molecular targets to develop new therapeutic interventions targeting these harmful tumor infiltrating myeloid cells is emerging nowadays.
Compact Dual-Band Coupler for Vehicular Beam-Forming Array
Authors: Wu Dakui , Zheng Guoxin
Published: January 2017

A novel kind of compact dual-band quadrature patch coupler for vehicular beam-forming array is proposed for the first time in this paper. To keep the performance of the first operating frequency 2.4 GHz (for Bluetooth Low Energy (BLE)) and generate the second operating frequency 5.9 GHz (for Dedicated Short Range Communications (DSRC)) simultaneously, complementary triangular split resonant rings (CTSRRs) and splitting gaps are employed to improve the performance of this new coupler; final size of the proposed coupler is 0.24λg (for 2.4 GHz). To validate the performance and design method of the coupler this paper proposed, a 3D model is constructed and optimized with ANSOFT HFSS firstly and then a coupler prototype is fabricated and measured. The measured results show that the amplitude unbalance (AU) is 0.54 dB and 0.44 dB for 2.4 GHz and 5.9 GHz, respectively, and the corresponding phase unbalance (PU) is 93.5 and 92 degrees, respectively.
Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population
Authors: Ahern Thomas P. , Sprague Brian L. , Bissell Michael C.S. , Miglioretti Diana L. , Buist Diana S.M. , Braithwaite Dejana , Kerlikowske Karla
Published: January 2017

Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density.

Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1st-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density.

Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0–2.1 at age 40; RR, 1.5; 95% CI, 1.3–1.7 at age 50; RR, 1.4; 95% CI, 1.2–1.6 at age 60; RR, 1.3; 95% CI, 1.1–1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1–3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88–1.5 at age 70). Associations did not change substantially when adjusted for breast density.

Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history.

Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938–44. ©2017 AACR.
Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?
Authors: Nogueira Leticia M. , Newton Christina C. , Pollak Michael , Silverman Debra T. , Albanes Demetrius , Männistö Satu , Weinstein Stephanie J , Jacobs Eric J. , Stolzenberg-Solomon Rachael Z.
Published: January 2017

Background: Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers.

Methods: We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case–control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate ORs and 95% confidence intervals (CI).

Results: Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54–0.84; Pinteraction = 0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23–0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04–1.45; Pinteraction = 0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers.

Conclusions: Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers.

Impact: Future studies of these biomarkers and PDA should examine results by smoking status. Cancer Epidemiol Biomarkers Prev; 26(6); 914–22. ©2017 AACR.
Antileukemia Efficacy and Mechanisms of Action of SL-101, a Novel Anti-CD123 Antibody Conjugate, in Acute Myeloid Leukemia
Authors: Han Lina , Jorgensen Jeffrey L. , Brooks Chris , Shi Ce , Zhang Qi , Nogueras González Graciela M. , Cavazos Antonio , Pan Rongqing , Mu Hong , Wang Sa A. , Zhou Jin , AI-Atrash Gheath , Ciurea Stefan O. , Rettig Mike , DiPersio John F. , Cortes Jorge , Huang Xuelin , Kantarjian Hagop M. , Andreeff Michael , Ravandi Farhad , Konopleva Marina
Published: January 2017

Purpose: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and antileukemia potency of a novel antibody conjugate SL-101 in targeting CD123+ LSCs.

Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD and predicted shorter relapse-free survival in patients with poor-risk cytogenetics. Using flow cytometry, we explored the potential benefit of therapeutic targeting of CD34+CD38−CD123+ cells by SL-101, a novel antibody conjugate comprising an anti-CD123 single-chain Fv fused to Pseudomonas exotoxin A. The antileukemia potency of SL-101 was determined by the expression levels of CD123 antigen in a panel of AML cell lines. Colony-forming assay established that SL-101 strongly and selectively suppressed the function of leukemic progenitors while sparing normal counterparts. The internalization, protein synthesis inhibition, and flow cytometry assays revealed the mechanisms underlying the cytotoxic activities of SL-101 involved rapid and efficient internalization of antibody, sustained inhibition of protein synthesis, induction of apoptosis, and blockade of IL3-induced p-STAT5 and p-AKT signaling pathways. In a patient-derived xenograft model using NSG mice, the repopulating capacity of LSCs pretreated with SL-101 in vitro was significantly impaired.

Conclusions: Our data define the mechanisms by which SL-101 targets AML and warrant further investigation of the clinical application of SL-101 and other CD123-targeting strategies in AML. Clin Cancer Res; 23(13); 3385–95. ©2017 AACR.
Mutation-Enrichment Next-Generation Sequencing for Quantitative Detection of KRAS Mutations in Urine Cell-Free DNA from Patients with Advanced Cancers
Authors: Fujii Takeo , Barzi Afsaneh , Sartore-Bianchi Andrea , Cassingena Andrea , Siravegna Giulia , Karp Daniel D. , Piha-Paul Sarina A. , Subbiah Vivek , Tsimberidou Apostolia M. , Huang Helen J. , Veronese Silvio , Di Nicolantonio Federica , Pingle Sandeep , Vibat Cecile Rose T. , Hancock Saege , Berz David , Melnikova Vladislava O. , Erlander Mark G. , Luthra Rajyalakshmi , Kopetz E. Scott , Meric-Bernstam Funda , Siena Salvatore , Lenz Heinz-Josef , Bardelli Alberto , Janku Filip
Published: January 2017

Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS.

Experimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer.

Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03).

Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure. Clin Cancer Res; 23(14); 3657–66. ©2017 AACR.
IGF-1 Receptor Modulates FoxO1-Mediated Tamoxifen Response in Breast Cancer Cells
Authors: Vaziri-Gohar Ali , Zheng Yan , Houston Kevin D.
Published: January 2017

Tamoxifen is a common adjuvant treatment for estrogen receptor (ER)α-positive patients with breast cancer; however, acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein–coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor–binding protein-1 (IGFBP-1) to inhibit IGF-1–dependent signaling. To determine whether dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment. IGFBP-1 transcription was not stimulated in tamoxifen-treated TamR cells whereas decreased expression of FoxO1, a known modulator of IGFBP-1, was observed. Exogenous expression of FoxO1 rescued the ability of tamoxifen to induce IGFBP-1 transcription in TamR cells. As decreased IGF-1R expression is observed in tamoxifen-resistant cells, the requirement for IGF-1R expression on tamoxifen-stimulated IGFBP-1 transcription was investigated. In TamR and SK-BR-3 cells, both characterized by low IGF-1R levels, exogenous IGF-1R expression increased FoxO1 levels and IGFBP-1 expression, whereas IGF-1R knockdown in MCF-7 cells decreased tamoxifen-stimulated IGFBP-1 transcription. Interestingly, both 17β-estradiol (E2)-stimulated ERα phosphorylation and progesterone receptor (PR) expression were altered in TamR. PR is a transcription factor known to modulate FoxO1 transcription. In addition, IGF-1R knockdown decreased FoxO1 protein levels in MCF-7 cells. Furthermore, IGF-1R or FoxO1 knockdown inhibited the ability of tamoxifen to induce IGFBP-1 transcription and tamoxifen sensitivity in MCF-7 cells. These data provide a molecular mechanistic connection between IGF-1R expression and the FoxO1-mediated mechanism of tamoxifen action in breast cancer cells.

Implications: Loss of IGF-1R expression is associated with decreased tamoxifen efficacy in patients with breast cancer and the development of tamoxifen resistance. This contribution identifies potential molecular mechanisms of altered tamoxifen sensitivity in breast cancer cells resulting from decreased IGF-1R expression. Mol Cancer Res; 15(4); 489–97. ©2017 AACR.
Inhibitory Effects of γ- and δ-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo
Authors: Bak Min Ji , Das Gupta Soumyasri , Wahler Joseph , Lee Hong Jin , Li Xiaowei , Lee Mao-Jung , Yang Chung S. , Suh Nanjoo
Published: January 2017

Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress, and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert antitumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ-, and δ-tocopherols as well as a natural γ-tocopherol–rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo. For the in vivo studies, MCF-7 cells were injected into the mammary fat pad of immunodeficient mice previously implanted with estrogen pellets. Mice were then administered diets containing 0.2% α-, γ-, δ-tocopherol, or γ-TmT for 5 weeks. Treatment with α-, γ-, δ-tocopherols, and γ-TmT reduced tumor volumes by 29% (P < 0.05), 45% (P < 0.05), 41% (P < 0.05), and 58% (P < 0.01), as well as tumor weights by 20%, 37% (P < 0.05), 39% (P < 0.05), and 52% (P < 0.05), respectively. γ- and δ-tocopherols and γ-TmT inhibited the expression of cell proliferation–related genes such as cyclin D1 and c-Myc, and estrogen-related genes such as TFF/pS2, cathepsin D, and progesterone receptor in estrogen-stimulated MCF-7 cells in vitro. Further, γ- and δ-tocopherols decreased the levels of estrogen-induced oxidative stress and nitrosative stress markers, 8-hydroxy-2′-deoxyguanosine and nitrotyrosine, as well as the DNA damage marker, γ-H2AX. Our results suggest that γ- and δ-tocopherols and the γ-tocopherol–rich mixture are effective natural agents for the prevention and treatment of estrogen-mediated breast cancer. Cancer Prev Res; 10(3); 188–97. ©2017 AACR.
Somatosensory Tinnitus: Correlation between Cranio-Cervico-Mandibular Disorder History and Somatic Modulation
Authors: Ralli Massimo , Altissimi Giancarlo , Turchetta Rosaria , Mazzei Filippo , Salviati Massimo , Cianfrone Francesca , Orlando Maria Patrizia , Testugini Valeria , Cianfrone Giancarlo
Published: January 2017

In a subpopulation of patients, tinnitus can be modulated by movements of the jaw or head and neck due to complex somatosensory-auditory interactions. In some of these subjects, tinnitus could be related to an underlying temporomandibular (TMJ) or craniocervical (NECK) dysfunction that, if correctly identified, could streamline treatment and increase chances of tinnitus improvement. However, it is still unclear whether somatic modulation of tinnitus could be used as a screening tool for identifying such patients. In this study, we included 310 tinnitus patients with normal hearing, no psychiatric comorbidities, and a positive history of TMJ and/or NECK dysfunction and/or a positive modulation of tinnitus to evaluate the characteristics of somatic modulation, investigate the relationship between positive history and positive modulation, and identify factors most strongly associated with somatic modulation. Tinnitus modulation was present in 79.67% of the patients. We found a significant association within the same subjects between a positive history and a positive tinnitus modulation for the same region, mainly for TMJ in unilateral tinnitus patients and for TMJ + NECK in bilateral tinnitus patients. A strong correlation between history and modulation in the same somatic region within the same subgroups of subjects was also identified. Most TMJ maneuvers resulted in an increased loudness, while NECK maneuvers showed an increase in tinnitus loudness in about 59% of cases. High-pitched tinnitus and male gender were associated with a higher prevalence of modulation; no differences were found for tinnitus onset, Tinnitus Handicap Inventory score, and age. In this paper, we report a strong association between history and modulation for the same regions within the same patients; such an association should always be investigated to improve chances of a correct diagnosis of somatosensory tinnitus.
Perineural Invasion Is Associated with Poor Survival after Preoperative Chemoradiation Therapy for Advanced Lower Rectal Cancer
Authors: Yokoyama Shozo , Matsuda Kenji , Watanabe Takashi , Mitani Yasuyuki , Ieda Junji , Iwamoto Hiromitsu , Hotta Tsukasa , Takifuji Katsunari , Yamaue Hiroki
Published: January 2017

Background: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. Methods: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study. The first 51 patients (October 2008-August 2010) underwent curative resection without pCRT. The latter 51 patients (September 2010-May 2015) underwent curative resection after pCRT. Pathological factors of patients were evaluated to assess the association between local and distant recurrences. Results: Multivariate analyses for local and distant recurrences of patients without pCRT revealed that the independent risk factors were tumor deposit and perineural invasion respectively. pCRT was able to diminish circumferential resection margin, tumor deposit, venous invasion, and lymphatic permeation but not neural invasion and lymph node involvement. Kaplan-Meier curve of local and distant recurrence-free survival of patients with pCRT illustrated that tumor deposit is controllable, whereas perineural invasion is uncontrollable by pCRT. Conclusion: pCRT-uncontrollable perineural invasion may be a factor for distant recurrence of advanced rectal cancer patients, leading to poor survival.
Advancing Age Decreases Pressure-Sensitive Modulation of Calcium Signaling in the Endothelium of Intact and Pressurized Arteries
Authors: Wilson Calum , Saunter Christopher D. , Girkin John M. , McCarron John G.
Published: January 2017

Aging is the summation of many subtle changes which result in altered cardiovascular function. Impaired endothelial function underlies several of these changes and precipitates plaque development in larger arteries. The endothelium transduces chemical and mechanical signals into changes in the cytoplasmic calcium concentration to control vascular function. However, studying endothelial calcium signaling in larger arteries in a physiological configuration is challenging because of the requirement to focus through the artery wall. Here, pressure- and agonist-sensitive endothelial calcium signaling was studied in pressurized carotid arteries from young (3-month-old) and aged (18-month-old) rats by imaging from within the artery using gradient index fluorescence microendoscopy. Endothelial sensitivity to acetylcholine increased with age. The number of cells exhibiting oscillatory calcium signals and the frequency of oscillations were unchanged with age. However, the latency of calcium responses was significantly increased with age. Acetylcholine-evoked endothelial calcium signals were suppressed by increased intraluminal pressure. However, pressure-dependent inhibition of calcium signaling was substantially reduced with age. While each of these changes will increase endothelial calcium signaling with increasing age, decreases in endothelial pressure sensitivity may manifest as a loss of functionality and responsiveness in aging.
Social Networks among the Older Chinese Population in the USA: Findings from the PINE Study
Authors: Dong XinQi , Chang E-Shien
Published: January 2017

Background: Social network research has become central to studies of health and aging. Its results may yield public health insights that are actionable and improve the quality of life of older adults. However, little is known about the social networks of older immigrant adults, whose social relationships often develop in the context of migration, compounded by cultural and linguistic barriers. Objectives: This report aims to describe the structure, composition, and emotional components of social networks in the Chinese aging population of the USA, and to explore ways in which their social networks may be critical to their health decision-making. Methods: Our data come from the PINE study, a population-based epidemiological study of community-dwelling older Chinese American adults, aged 60 years and above, in the greater Chicago area. We conducted individual interviews in participants' homes from 2011 until 2013. Based on sociodemographic and socioeconomic characteristics, this study computed descriptive statistics and trend tests for the social network measures adapted from the National Social Life, Health, and Aging Project study. Results: The findings show that older Chinese adults have a relatively small social network in comparison with their counterparts from other ethnic and racial backgrounds. Only 29.6% of the participants could name 5 close network members, and 2.2% could name 0 members. Their network composition was more heavily kin oriented (95.0%). Relationships with network members differed according to the older adults' sociodemographic and socioeconomic characteristics. Subgroup variations included the likelihood of discussing health-related issues with network members. Conclusion: This study highlights the dynamic nature of social networks in later-life Chinese immigrants. For healthcare practitioners, developing cost-effective strategies that can mobilize social network support remains a critical undertaking in health intervention. Longitudinal studies are needed to examine the causal impact of social networks on various domains of health.
Recurrent Paronychia as a Presenting Manifestation of Pemphigus Vulgaris: A Case Report
Authors: Zawar Vijay , Pawar Manoj , Kumavat Shrikant
Published: January 2017

Nail involvement in pemphigus vulgaris (PV) is an unusual clinical finding. The most common clinical manifestations include chronic paronychia and onychomadesis. We report an adult female patient with PV who initially presented with chronic paronychia of multiple fingernails and toenails before the onset of vesiculobullous eruptions. Later on, after complete resolution, there was recurrence of pemphigus presenting as hemorrhagic paronychia of the left index finger. Systemic treatment with corticosteroids and azathioprine led to complete resolution of mucocutaneous lesions as well as nail manifestations. Thus, chronic treatment-resistant paronychia may be an early and important sign of generalized pemphigus in certain patients.
Increased chance of metabolic syndrome in women living with HIV/AIDS and lipodystrophic syndrome
Authors: Alves Thiago Cândido , Moraes Camila de , Santos André Pereira dos , Venturini Ana Cláudia Rossini , Santana Rodrigo de Carvalho , Navarro Anderson Marliere , Machado Dalmo Roberto Lopes
Published: January 2017

Study design: cross-sectional and prevalence study. Objective: compare symptoms criteria for Metabolic Syndrome (MS) in men and women living with HIV/aids, patients with lipodystrophy syndrome on antiretroviral therapy. Method: Forty-one patients of both sexes (18-69 years), from an exercise guidance program as alternative therapy. They had their body composition (DXA), height, weight, abdomen circumference, and lipid profile, blood glucose, blood pressure, and CD4+ count, determined. The IDF criteria for diagnosis of MS were used. Results: Women showed greater relative fat (p = 0.001), central obesity (p = 0.005), total cholesterol (p = 0.043) and LDL cholesterol (p = 0.034), and CD4+ count (p = 0.034) when compared to men. The mean values for both sexes showed high levels of triglycerides (> 211.4 mg.dL-1) and low HDL (< 39.5 mg.dL-1). The prevalence ratio of MS was twice in women than men (p = 0.005). Conclusion: The prevalence ratio (PR = 0.465) of sex metabolic syndrome-associated, shown that woman patients have higher relative risk and therefore require alternative actions to reduce the chances of developing this syndrome
Clinical-epidemiological profile, diagnostic criteria and treatment of patients with hairy cell leukemia in the State of Pernambuco: analysis of 50 consecutive cases in 12 years
Authors: Galindo Amanda V. , Torquato Ana Claudia S. , Leitão Paula C. A. , Galindo Clívia M. B. S. , Machado Cíntia G. F.
Published: January 2017

Study’s model: series of cases. Problem’s relevance: Describing the clinical-epidemiological profile, standard diagnostics and hairy cell leukemia’s (HCL) treatment inside a reference service of hematology in the state of Pernambuco/Brazil, considering that HCL is a little common condition in the related statethat, when suspected, is forwarded to Pernambuco’s Foundation of Hematology and Hemotherapy (HEMOPE).Thereby, a study about HCL will permit the elaboration of investigation’s protocols about the clinic as well as premature and therapeutic diagnostics, according to the laboratory and clinical-epidemiological characters of the patients of the state of Pernambuco/Brazil, propitiating a better assistance to them. Comments: It was realizeda retrospective and descriptive study involving all patients with HCL attended at HEMOPE from January 2002 to April 2014. More than 50 (fifty) cases were analysed. The age group was 54,3± 12,3 (16% women and 84% men). The symptonsverified were dizziness, hemorrhage, asthenia, anorexia, nightly sweat, recurrent infection, splenomegaly, hepatomegaly and adenomegaly. It was observed macrocytosis (22,0%), anemia (88,0%) and thrombocytopenia (98%).In the standard diagnostics, there were hairy cells in the peripheral blood of all patients and the reaction of the phosphatase’s tartar resistant was positive in 81,8% of the cases.The bone marrow’s biopsy revealed hairy cells infiltration in all patients and reticulin fibrosis in 92,0% of the cases. In the immunophenotyping, was found CD11 in 57,1% of the cases, CD25 in 89,8%, CD103 in 77,5%, FMC7 in 81,6%, Kappa in 24,5% and Lambda in 18,3%.As initial treatment, it was realized splenectomy + interferon (4,0%), splenectomy (4,0%), interferon (3,5%) and cladribine (58,0%)
Giant ovarian immature teratoma with bilateral mature teratoma: case report
Authors: Dan Vanderson J. L. , Zacharias Raquel , Martins Júnior Valdir R. , Genaro André
Published: January 2017

Immature teratoma of the ovary is a malignant neoplasm composed of undifferentiated tissue that arises from embryonic cells. And the mature teratoma is a benign neoplasm composed of differentiated tissues. This paper aims to report the case of a 21-year-old pacient with giant immature teratoma in left ovary associated with mature ovarian teratoma bilateral, due to the association of teratoma with mature teratoma ipsilateral and contralaterally, combined with its outstanding increased size (36 cm), is unusual. Exploratory laparotomy, with cytoreductive pan-hysterectomy and bilateral salpingooferectomia were performed. The patient received adjuvant chemotherapy with BEP regimen (bleomycin, etoposide and cisplatin) in four cycles with intervals of 21 days, coursing with good evolution
Improving Door-to-Needle Times for Acute Ischemic Stroke
Authors: Kamal Noreen , Holodinsky Jessalyn K. , Stephenson Caroline , Kashayp Devika , Demchuk Andrew M. , Hill Michael D. , Vilneff Renee L. , Bugbee Erin , Zerna Charlotte , Newcommon Nancy , Lang Eddy , Knox Darren , Smith Eric E.
Published: January 2017

Background—

The effectiveness of specific systems changes to reduce DTN (door-to-needle) time has not been fully evaluated. We analyzed the impact of 4 specific DTN time reduction strategies implemented prospectively in a staggered fashion.

Methods and Results—

The HASTE (Hurry Acute Stroke Treatment and Evaluation) project was implemented in 3 phases at a single academic medical center. In HASTE I (June 6, 2012 to June 5, 2013), baseline performance was analyzed. In HASTE II (June 6, 2013 to January 24, 2015), 3 changes were implemented: (1) a STAT stroke protocol to prenotify the stroke team about incoming stroke patients; (2) administering alteplase at the computed tomography (CT) scanner; and (3) registering the patient as unknown to allow immediate order entry. In HASTE III (January 25, 2015 to June 29, 2015), we implemented a process to bring the patient directly to CT on the emergency medical services stretcher. Log-transformed DTN time was modeled. Data from 350 consecutive alteplase-treated patients were analyzed. Multivariable regression showed the following factors to be significant: giving alteplase in the CT (32% decrease in DTN time, 95% confidence interval [CI] 38%–55%), stretcher to CT (30% decrease in DTN time, 95% CI 16%–42%), patient registered as unknown (12% decrease in DTN time, 95% CI 3%–20%), STAT stroke protocol (11% decrease in DTN time, 95% CI 1%–20%), and stroke severity (National Institutes of Health Stroke Scale score 6–8: 19% decrease in DTN time, 95% CI 6%–31%; National Institutes of Health Stroke Scale score >8: 27% decrease in DTN time, 95% CI 17%–37%).

Conclusions—

Taking the patient to CT on the emergency medical services stretcher, registering the patient as unknown, STAT stroke protocol, and administering alteplase in CT are associated with lower DTN time.
Norwegian in the American Midwest: A Common Dialect?
Authors: Johannessen Janne Bondi , Laake Signe
Published: January 2017

The American Midwest is an area that stretches over huge distances. Yet it seems that the Norwegian language in this whole area has some similarities, particularly at the lexical level. Comparisons of three types of vocabulary across the whole area, as well as across time, building on accounts in the previous literature from Haugen (1953) onwards, are carried out. The results of these comparisons convince the authors that it is justified to refer to this language as one lexically defined dialect, which we call lexicolect.
A Model of Underspecified Recognition for Phonological Integration: English Loan Vowels in American Norwegian
Authors: Natvig David
Published: January 2017

Using loanword data from Haugen (1953), this paper investigates variation in vowel integrations of English loanwords in the Norwegian among 19th century Norwegian immigrants to the United States, as first-language Norwegian and second-language English speakers. Previous research, most notably Flege (1995), has argued that speakers make use of L1 categories that are the most similar to the integrated L2 sound. In contrast, this research argues that the “most similar,” as well as less similar but attested, L1 integrated phonemes can be understood through the Lahiri and Reetz (2002) Underspecified Recognition model, where phonetic features of L2 input sounds are mapped onto hierarchically organized L1 distinctive features (i.e., Dresher, 2009).