bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomistic Simulation of ZrNi Metallic Glasses Under Torsion Test
Authors: Sung Po-Hsien , Chen Tei-Chen , Wu Cheng-Da
Published: June 2017

ZrNi metallic glass alloy nanowires (NWs) under torsion are studied using molecular dynamics simulations based on the many-body embedded-atom potential. The effect of cooling rate on the deformation mechanism and mechanical properties of ZrNi NWs is evaluated in terms of shear strain, torque, potential energy and radial distribution function. Simulation results show that for slower cooling rates, the NWs have larger packing density, whereas for faster cooling rates, the packing density of atoms decreases. The amount of deformation increases with increasing torsional angle before it reaches a critical torsional angle ([Formula: see text]. The torque required for deformation and the [Formula: see text] value increase with decreasing cooling rate, indicating a larger mechanical strength. Localized shear bands concentrate at regions with high shear strains, leading to the formation of torsional buckling.
Mixing in regional-structure model about the influence of floating population and optimal control about TB in Guangdong province of China
Authors: Xu Chuanqing , Wei Xiaoxiao , Cui Jingan , Wang Xiaojing , Xu Dashun
Published: June 2017

In the last 60 years, great progress has been made in controlling and preventing tuberculosis in China. However, the number of tuberculosis cases has increased dramatically in the last 25 years, mainly due to the lack of effective control measures of immigrating populations with tuberculosis. In order to explore the effective control and prevention measures we propose a deterministic model to study the transmission dynamics of tuberculosis in Guangdong province of China in this paper. The model consists of susceptible, exposed and infectious recovered subpopulations of immigrating populations from other provinces and the local population of Guangdong. We obtain the effective reproduction number. Based on the analysis, we also establish an optimal immune programming model, and get the optimal proportion of vaccine coverage with control of the effective reproduction number. Simulation is used to determine the validation and reliability. Our study demonstrates that the immigrating population from different provinces needs to be vaccinated according to the incidence rate of TB in their original provinces, and it is an effective way to prevent the outbreak of tuberculosis in Guangdong.
Stance and Sentiment in Tweets
Authors: Mohammad Saif M. , Sobhani Parinaz , Kiritchenko Svetlana
Published: June 2017

We can often detect from a person’s utterances whether he or she is in favor of or against a given target entity—one’s stance toward the target. However, a person may express the same stance toward a target by using negative or positive language. Here for the first time we present a dataset of tweet–target pairs annotated for both stance and sentiment. The targets may or may not be referred to in the tweets, and they may or may not be the target of opinion in the tweets. Partitions of this dataset were used as training and test sets in a SemEval-2016 shared task competition. We propose a simple stance detection system that outperforms submissions from all 19 teams that participated in the shared task. Additionally, access to both stance and sentiment annotations allows us to explore several research questions. We show that although knowing the sentiment expressed by a tweet is beneficial for stance classification, it alone is not sufficient. Finally, we use additional unlabeled data through distant supervision techniques and word embeddings to further improve stance classification.
Development and Evaluation of a Similarity Measure for Medical Event Sequences
Authors: Mannino Michael , Fredrickson Joel , Banaei-Kashani Farnoush , Linck Iris , Raghda Raghda Alqurashi
Published: June 2017

We develop a similarity measure for medical event sequences (MESs) and empirically evaluate it using U.S. Medicare claims data. Existing similarity measures do not use unique characteristics of MESs and have never been evaluated on real MESs. Our similarity measure, the Optimal Temporal Common Subsequence for Medical Event Sequences (OTCS-MES), provides a matching component that integrates event prevalence, event duplication, and hierarchical coding, important elements of MESs. The OTCS-MES also uses normalization to mitigate the impact of heavy positive skew of matching events and compact distribution of event prevalence. We empirically evaluate the OTCS-MES measure against two other measures specifically designed for MESs, the original OTCS and Artemis, a measure incorporating event alignment. Our evaluation uses two substantial data sets of Medicare claims data containing inpatient and outpatient sequences with different medical event coding. We find a small overlap in nearest neighbors among the three similarity measures, demonstrating the superior design of the OTCS-MES with its emphasis on unique aspects of MESs. The evaluation also provides evidence about the impact of component weights, neighborhood size, and sequence length.
Burden and Correlates of Falls among Rural Elders of South India: Mobility and Independent Living in Elders Study
Authors: Sharma Pawan Kumar , Bunker Clareann H. , Singh Tushar , Ganguly Enakshi , Reddy P. Sudhakar , Newman Anne B. , Cauley Jane A.
Published: June 2017

Aim. Falls are an important contributor to loss of function, morbidity, and mortality in elders. Little is known about falls in Indian populations. The objective of this cross-sectional report was to identify the prevalence and correlates of falls in a cohort of 562 rural southern Indian men and women.Methods. Risk factors included demographics, anthropometrics, self-reported health, medical history, physical function, vision, depression, and lifestyle. Odds ratios were calculated using logistic regression.Results. 71 (13%) subjects reported at least 1 fall in the past year. Prevalence was higher among women (17%) than men (8%),P=0.003. Sex and age showed significant interaction (P=0.04) whereby falls prevalence increased with age among women but decreased among men. Correlates of falls among men included a history of osteoarthritis (OA) (odds ratio (OR): 6.91; 95% CI: 1.4–33.1), depression (OR:9.6; 3.1–30.1), and greater height (OR per 1 standard deviation increase: 2.33; 1.1–5.1). Among women, poor physical performance (OR: 3.33; 1.13–9.86) and history of cardiovascular disease (CVD) (OR: 2.42; 1.01–5.80) were independently associated with falls.Implications. Prevalence of falls in elderly South Indians was lower than published reports from western countries and likely reflects low exposure to fall risks. Patterns with age differed in men and women and may reflect sex differences in the accuracy of age recall. Presence of comorbidities specifically OA, CVD, and depression was independent correlate of falling.
Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields
Authors: Chen Linjie , Chen Changyou , Wang Pingping , Song Tao
Published: June 2017

The interaction of magnetic nanoparticles (MNPs) with various magnetic fields could directly induce cellular effects. Many scattered investigations have got involved in these cellular effects, analyzed their relative mechanisms, and extended their biomedical uses in magnetic hyperthermia and cell regulation. This review reports these cellular effects and their important applications in biomedical area. More importantly, we highlight the underlying mechanisms behind these direct cellular effects in the review from the thermal energy and mechanical force. Recently, some physical analyses showed that the mechanisms of heat and mechanical force in cellular effects are controversial. Although the physical principle plays an important role in these cellular effects, some chemical reactions such as free radical reaction also existed in the interaction of MNPs with magnetic fields, which provides the possible explanation for the current controversy. It is anticipated that the review here could provide readers with a deeper understanding of mechanisms of how MNPs contribute to the direct cellular effects and thus their biomedical applications under various magnetic fields.
The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia
Authors: Tanaka Yoshinori , Tanuma Yasushi , Masumori Naoya
Published: June 2017

Objectives. The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice.Methods. A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined.Results. The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years.Conclusions. 35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment.Trial Registration. This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910).
Star Formation Law at Sub-kpc Scale in the Elliptical Galaxy Centaurus A as Seen by ALMA
Authors: Azeez Jazeel H. , Abidin Zamri Z. , Hwang C.-Y. , Ibrahim Zainol A.
Published: June 2017

We present an extensive analysis of the relationship between star formation rate surface density (∑SFR) and molecular gas surface density (∑H2) at sub-kpc scale in the elliptical galaxy Centaurus A (also known as NGC 5128) at the distance 3.8 Mpc. 12CO (J = 2-1) data from Atacama Large Millimetre/Sub-Millimetre Array SV data with very high resolution (2.9′′, 0.84′′), as well as 24 μm data from the Spitzer Space Telescope, were used. This is one of the first studies of the SF law on Centaurus A at this very high spatial resolution. The results showed a breakdown in star formation law with a 0.49±0.05 index relating ∑SFR and ∑H2 at 185 pc. A significant correlation exists between surface densities of molecular gas and SFR with very long depletion time (68 Gy). In addition we examined the spatially resolved relationship between velocity dispersion and star formation rate surface density for the outer disk of this galaxy and we found that the average velocity dispersion is equal to 11.78 km/s. The velocity dispersion of the molecular ISM for the outer disk is found to follow a power relation with the star formation rate surface density σ∝∑SFRβ, where β is the slope from the ordinary least square fitting. The value of β is about 1/n≈2.16±0.40 and n is the power law index of the star formation law.
Absorption-Modulated Crossed-Optical Fiber-Sensor Platform for Measurements in Liquid Environments and Flow Streams
Authors: Henning Paul E. , Geissinger Peter
Published: June 2017

A new evanescent-wave fiber sensor is described that utilizes absorption-modulated luminescence (AML) in combination with a crossed-fiber sensor platform. The luminescence signals of two crossed-fiber reference regions, placed on opposite sides of the stretch of fiber supporting the absorbance sensor, monitor the optical intensity in the fiber core. Evanescent absorption of the sensor reduces a portion of the excitation light and modulates the luminescence of the second reference region. The attenuation is determined from the luminescence intensity of both reference regions similar to the Beer-Lambert Law. The AML-Crossed-Fiber technique was demonstrated using the absorbance of the Zn(II)-PAN2 complex at 555 nm. A linear response was obtained over a zinc(II) concentration range of 0 to 20 μM (approximately 0 to 1.3 ppm). A nonlinear response was observed at higher zinc(II) concentrations and was attributed to depletion of higher-order modes in the fiber. This was corroborated by the measured induced repopulation of these modes.
Trabectedin Overrides Osteosarcoma Differentiative Block and Reprograms the Tumor Immune Environment Enabling Effective Combination with Immune Checkpoint Inhibitors
Authors: Ratti Chiara , Botti Laura , Cancila Valeria , Galvan Silvia , Torselli Ilaria , Garofalo Cecilia , Manara Maria Cristina , Bongiovanni Lucia , Valenti Cesare F. , Burocchi Alessia , Parenza Mariella , Cappetti Barbara , Sangaletti Sabina , Tripodo Claudio , Scotlandi Katia , Colombo Mario P. , Chiodoni Claudia
Published: June 2017

Purpose: Osteosarcoma, the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested.

Experimental Design: We have developed immunocompetent osteosarcoma models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human osteosarcoma. These models have been used to test the efficacy of trabectedin, a chemotherapeutic drug utilized clinically for sarcomas and ovarian cancer.

Results: Trabectedin, as monotherapy, significantly inhibited osteosarcoma primary tumor growth and lung metastases by both targeting neoplastic cells and reprogramming the tumor immune microenvironment. Specifically, trabectedin induced a striking differentiation of tumor cells by favoring the recruitment of Runx2, the master genetic regulator of osteoblastogenesis, on the promoter of genes involved in the physiologic process of terminal osteoblast differentiation. Differentiated neoplastic cells, as expected, showed reduced proliferation rate. Concomitantly, trabectedin enhanced the number of tumor-infiltrating T lymphocytes, with local CD8 T cells, however, likely post-activated or exhausted, as suggested by their high expression of the inhibitory checkpoint molecule PD-1. Accordingly, the combination with a PD-1–blocking antibody significantly increased trabectedin efficacy in controlling osteosarcoma progression.

Conclusions: These results demonstrate the therapeutic efficacy of trabectedin in osteosarcoma treatment, unveiling its multiple activities and providing a solid rationale for its combination with immune checkpoint inhibitors. Clin Cancer Res; 23(17); 5149–61. ©2017 AACR.
miR-193a-3p is a Key Tumor Suppressor in Ulcerative Colitis–Associated Colon Cancer and Promotes Carcinogenesis through Upregulation of IL17RD
Authors: Pekow Joel , Meckel Katherine , Dougherty Urszula , Huang Yong , Chen Xindi , Almoghrabi Anas , Mustafi Reba , Ayaloglu-Butun Fatma , Deng Zifeng , Haider Haider I. , Hart John , Rubin David T. , Kwon John H. , Bissonnette Marc
Published: June 2017

Purpose: Patients with ulcerative colitis are at increased risk for colorectal cancer, although mechanisms underlying neoplastic transformation are poorly understood. We sought to evaluate the role of microRNAs in neoplasia development in this high-risk population.

Experimental Design: Tissue from 12 controls, 9 ulcerative colitis patients without neoplasia, and 11 ulcerative colitis patients with neoplasia was analyzed. miRNA array analysis was performed and select miRNAs assayed by real-time PCR on the discovery cohort and a validation cohort. DNA methylation of miR-193a was assessed. Following transfection of miR-193a-3p, proliferation, IL17RD expression, and luciferase activity of the 3′UTR of IL17RD were measured. Tumor growth in xenografts as well as EGFR signaling were assessed in HCT116 cells expressing IL17RD with either a mutant 3′ untranslated region (UTR) or wild-type (WT) 3′UTR.

Results: miR-31, miR-34a, miR-106b, and miR-193a-3p were significantly dysregulated in ulcerative colitis-neoplasia and adjacent tissue. Significant down-regulation of miR-193a-3p was also seen in an independent cohort of ulcerative colitis cancers. Changes in methylation of miR-193a or expression of pri-miR-193a were not observed in ulcerative colitis cancer. Transfection of miR-193a-3p resulted in decreased proliferation, and identified IL17RD as a direct target of miR-193a-3p. IL17RD expression was increased in ulcerative colitis cancers, and miR-193a-3p treatment decreased growth and EGFR signaling of HCT116 cells in xenografts expressing both IL17RD with WT 3′UTR compared with cells expressing IL17RD with mutant 3′UTR.

Conclusions: miR-193a-3p is downregulated in ulcerative colitis neoplasia, and its loss promotes carcinogenesis through upregulation of IL17RD. These findings provide novel insight into inflammation-driven colorectal cancer and could suggest new therapeutic targets in this high-risk population. Clin Cancer Res; 23(17); 5281–91. ©2017 AACR.
Use of Angiotensin System Inhibitors Is Associated with Immune Activation and Longer Survival in Nonmetastatic Pancreatic Ductal Adenocarcinoma
Authors: Liu Hao , Naxerova Kamila , Pinter Matthias , Incio Joao , Lee Hang , Shigeta Kohei , Ho William W. , Crain Jonathan A. , Jacobson Alex , Michelakos Theodoros , Dias-Santos Daniella , Zanconato Andrea , Hong Theodore S. , Clark Jeffrey W. , Murphy Janet E. , Ryan David P. , Deshpande Vikram , Lillemoe Keith D. , Fernandez-del Castillo Carlos , Downes Michael , Evans Ronald M. , Michaelson James , Ferrone Cristina R. , Boucher Yves , Jain Rakesh K.
Published: June 2017

Purpose: Angiotensin system inhibitors (ASI) can improve prognosis in multiple cancer types, including pancreatic ductal adenocarcinoma (PDAC). However, no study has examined the effect of ASIs alone or combined with adjuvant chemotherapy in resected PDAC patients.

Experimental Design: We performed an analysis of the records of ASI users and nonuser patients with PDAC seen at Massachusetts General Hospital (Boston, MA) between January 2006 and December 2010. To identify mechanisms of ASIs in PDAC, we performed RNA sequencing (RNA-Seq) of resected primary lesions.

Results: A total of 794 consecutive patients were included. In 299 resected patients, ASI users experienced longer overall survival (OS) in both univariate (median OS, 36.3 vs. 19.3 months, P = 0.011) and adjusted multivariate [HR, 0.505; 95% confidence interval (CI), 0.339–0.750; P = 0.001] analyses. Propensity score–adjusted analysis also showed a longer median OS for chronic ASI users. In unresected patients, the beneficial effect of ASIs was significant in patients with locally advanced disease, but not in metastatic patients. RNA-Seq analysis revealed in tumors of ASI users (lisinopril) a normalized extracellular matrix, a reduced expression of genes involved in PDAC progression (e.g., WNT and Notch signaling), and an increased expression of genes linked with the activity of T cells and antigen-presenting cells. Finally, chronic use of ASI was associated with a gene expression signature that is predictive of survival in independent validation cohorts.

Conclusions: In patients with nonmetastatic PDAC, chronic ASI use is associated with longer OS independently of chemotherapy. Our RNA-Seq analysis suggests that ASIs reduce the malignant potential of cancer cells and stimulate the immune microenvironment in primary PDAC. Clin Cancer Res; 23(19); 5959–69. ©2017 AACR.
Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay
Authors: Wang Lisha , Harms Paul W. , Palanisamy Nallasivam , Carskadon Shannon , Cao Xuhong , Siddiqui Javed , Patel Rajiv M. , Zelenka-Wang Sylvia , Durham Alison B. , Fullen Douglas R. , Harms Kelly L. , Su Fengyun , Shukla Sudhanshu , Mehra Rohit , Chinnaiyan Arul M.
Published: June 2017

Purpose: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCCs. Detection of MCPyV in MCCs has diagnostic utility and prognostic potential. We investigated whether RNAscope, an RNA in situ hybridization (ISH) assay for detection of RNA transcripts in tissues, is useful for MCPyV detection.

Experimental Design: We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMA) and whole-tissue sections encompassing 87 MCCs from 75 patients, 14 carcinomas of other types, and benign tissues. For comparison, qPCR was performed on 57 cases of MCC from 52 patients.

Results: RNA-ISH demonstrated the presence of MCPyV in 37 of 75 cases (49.3%). Notably, tumors from younger patients (<73 years) had a significantly higher virus positivity than those from elderly patients (≥73 years; 64.9% vs. 34.2%, P = 0.011). Female patients had a higher positive rate of MCPyV than male patients (66.7% vs. 39.6%, P = 0.032). Data from both RNA-ISH and qPCR were available for 57 samples. Considering MCPyV qPCR as the gold standard for determining MCPyV status, RNAscope had 100% sensitivity and 100% specificity. There was a strong correlation between qPCR copy number and RNA-ISH product score (Spearman correlation coefficient R2 = 0.932, P < 0.0001).

Conclusions: RNA-ISH is comparably sensitive to qPCR for detection of MCPyV and allows for correlation with tissue morphology. This study also reveals a significant association between age, gender, and MCPyV positivity. Clin Cancer Res; 23(18); 5622–30. ©2017 AACR.
Targeting the Wnt Pathway and Cancer Stem Cells with Anti-progastrin Humanized Antibodies as a Potential Treatment for K-RAS-Mutated Colorectal Cancer
Authors: Prieur Alexandre , Cappellini Monica , Habif Guillaume , Lefranc Marie-Paule , Mazard Thibault , Morency Eric , Pascussi Jean-Marc , Flacelière Maud , Cahuzac Nathalie , Vire Bérengère , Dubuc Benjamin , Durochat Amandine , Liaud Pierre , Ollier Jérémy , Pfeiffer Caroline , Poupeau Sophie , Saywell Véronique , Planque Chris , Assenat Eric , Bibeau Frédéric , Bourgaux Jean-François , Pujol Pascal , Sézeur Alain , Ychou Marc , Joubert Dominique
Published: June 2017

Purpose: Patients with metastatic colorectal cancer suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct β-catenin/TCF4 target gene. In this study, we aimed to develop a novel targeted therapy to neutralize secreted progastrin to inhibit Wnt signaling, CSCs, and reduce relapses.

Experimental Design: Antibodies (monoclonal and humanized) directed against progastrin were produced and selected for target specificity and affinity. After validation of their effectiveness on survival of colorectal cancer cell lines harboring B-RAF or K-RAS mutations, their efficacy was assessed in vitro and in vivo, alone or concomitantly with chemotherapy, on CSC self-renewal capacity, tumor recurrence, and Wnt signaling.

Results: We show that anti-progastrin antibodies decrease self-renewal of CSCs both in vitro and in vivo, either alone or in combination with chemotherapy. Furthermore, migration and invasion of colorectal cancer cells are diminished; chemosensitivity is prolonged in SW620 and HT29 cells and posttreatment relapse is significantly delayed in T84 cells, xenografted nude mice. Finally, we show that the Wnt signaling activity in vitro is decreased, and, in transgenic mice developing Wnt-driven intestinal neoplasia, the tumor burden is alleviated, with an amplification of cell differentiation in the remaining tumors.

Conclusions: Altogether, these data show that humanized anti-progastrin antibodies might represent a potential new treatment for K-RAS–mutated colorectal patients, for which there is a crucial unmet medical need. Clin Cancer Res; 23(17); 5267–80. ©2017 AACR.
Synergistic Activity with NOTCH Inhibition and Androgen Ablation in ERG-Positive Prostate Cancer Cells
Authors: Mohamed Ahmed A. , Tan Shyh-Han , Xavier Charles P. , Katta Shilpa , Huang Wei , Ravindranath Lakshmi , Jamal Muhammad , Li Hua , Srivastava Meera , Srivatsan Eri S. , Sreenath Taduru L. , McLeod David G. , Srinivasan Alagarsamy , Petrovics Gyorgy , Dobi Albert , Srivastava Shiv
Published: June 2017

The oncogenic activation of the ETS-related gene (ERG) due to gene fusions is present in over half of prostate cancers in Western countries. Because of its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for prostate cancer. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified, confirming that NOTCH factors are direct transcriptional targets of ERG. Inhibition of ERG in TMPRSS2-ERG–positive VCaP cells led to decreased levels of NOTCH1 and 2 proteins and downstream transcriptional targets and partially recapitulated the phenotypes associated with ERG inhibition. Regulation of NOTCH1 and 2 genes by ERG were also noted with ectopic ERG expression in LNCaP (ERG-negative prostate cancer) and RWPE-1 (benign prostate–derived immortalized) cells. Furthermore, inhibition of NOTCH by the small-molecule γ-secretase inhibitor 1, GSI-1, conferred an increased sensitivity to androgen receptor (AR) inhibitors (bicalutamide and enzalutamide) or the androgen biosynthesis inhibitor (abiraterone) in VCaP cells. Combined treatment with bicalutamide and GSI-1 showed strongest inhibition of AR, ERG, NOTCH1, NOTCH2, and PSA protein levels along with decreased cell growth, cell survival, and enhanced apoptosis. Intriguingly, this effect was not observed in ERG-negative prostate cancer cells or immortalized benign/normal prostate epithelial cells. These data underscore the synergy of AR and NOTCH inhibitors in reducing the growth of ERG-positive prostate cancer cells.

Implications: Combinational targeting of NOTCH and AR signaling has therapeutic potential in advanced ERG-driven prostate cancers. Mol Cancer Res; 15(10); 1308–17. ©2017 AACR.
Third-Trimester Conditional Reference Values for Longitudinal Fetal Growth Assessment
Authors: Basuki Tri Rahmat , Triunfo Stefania , Caradeux Javier , Eixarch Elisenda , Hansson Stefan , Gratacos Eduard , Figueras Francesc
Published: June 2017

Objectives: The aim of this study was to derive longitudinal reference values of fetal growth (estimated fetal weight [EFW] and abdominal circumference [AC]) during the third trimester and to develop coefficients for conditional growth assessment. Patients and Methods: A prospective cohort study was conducted involving consecutive singleton pregnancies in a low-risk population for a routine third-trimester scan at 30+0-34+6 weeks and follow-up at 37+0-38+6 weeks for an additional ultrasound. Statistical analysis was based on multilevel modeling using MLwiN software. Unconditional centiles were calculated from z-values at each gestational age, and conditional centiles were calculated from z-values at a given measurement (30-34 weeks) and the expected measurement (37-38 weeks). Results: At 30-34 weeks, 8 and 9.3% of the fetuses had an unconditional EFW below the 10th and above the 90th centile, respectively. At 37-38 weeks, these figures were 10.3 and 9.3%, respectively. Regarding the unconditional AC, at the first scan, 8.9 and 9.6% had values below the 10th and above the 90th centile, while at the second scan 10.5 and 10.5% had values below the 10th and above the 90th centile, respectively. The proportion with a conditional EFW below the 10th and above the 90th centile was 10.2 and 9.4% at the second scan, respectively. For conditional AC, these figures were 10.7 and 10.3%, respectively. Conclusion: We have produced reference centiles for EFW and AC growth during the third trimester as a useful tool for quantifying growth.
Increased Toll-Like Receptor-Myeloid Differentiation Factor 88 Expression at the Maternal-Fetal Interface Is Associated with Spontaneous Abortion
Authors: He Mengzhou , Zhou Yuan , Jiang Min , Li Fanfan , Yang Meitao , Fan Yao , Deng Dongrui
Published: June 2017

Aims: Toll-like receptors (TLRs) form a group of pattern recognition receptors that play a major role in maintaining innate host immunity. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule that is essential for signaling via the TLR family. To analyze the mechanism of the imbalance in the innate immune system mediated by TLRs-MyD88 in spontaneous abortion, we detected the expression of TLR-2, TLR-4, TLR-7, and MyD88 in placentae and deciduas. Methods: The expression of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas of abortion-prone mice (n = 10) and normal pregnant mice (n = 10) were analyzed by immunochemistry, western blot, and real-time polymerase chain reaction. Results: There were higher protein expression levels of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas in the abortion-prone group than in the normal pregnant group. However, TLR-2, TLR-4, and TLR-7 showed lower gene expression, while MyD88 manifested higher gene expression in placentae and deciduas of abortion-prone mice matings. Conclusions: TLR-2, TLR-4, TLR-7, and MyD88 were expressed in the placenta and decidua of both the abortion-prone pregnant and normal pregnant mice. The overexpression of TLRs may excessively activate the innate immune system mediated by MyD88, which is considered to be related to the pathogenesis of spontaneous abortion.
The Curvilinear Effect of BMI on Functional Health - Evidence of the Long-Running German Ageing Survey
Authors: Hajek André , König Hans-Helmut
Published: June 2017

Aims: We aimed at determining the effect of BMI on functional health among older Germans longitudinally. Methods: Data from four waves (2002-2014) of the German Ageing Survey (‘Deutscher Alterssurvey'; DEAS), a representative sample of community-dwelling individuals aged 40 years and above, were used. Functional health was quantified by the subscale ‘physical functioning' of the 36-Item Short Form Health Survey (SF-36). Fixed effects regressions were used to estimate the predictors of functional health. Linear, quadratic, and cubic terms were included for BMI (self-reported). Results: Fixed effects regressions showed significant linear, quadratic, and cubic effects of BMI on functional health in the total sample and in both sexes. Furthermore, regressions revealed that functional health decreased with increasing age in the total sample and in both sexes. In addition, changes in marital and employment status were significantly associated with changes in functional health in men, but not in women. Conclusion: Our data indicate that the greater the extreme of BMI (either higher or lower), the greater the risk for functional decline. Nutrition programs aimed at preventing changes to extreme BMI might be productive.
Restricted Ventilation Associated with Reduced Neurodevelopmental Impairment in Preterm Infants
Authors: Vliegenthart Roseanne J.S. , Onland Wes , van Wassenaer-Leemhuis Aleid G. , De Jaegere Anne P.M. , Aarnoudse-Moens Cornelieke S.H. , van Kaam Anton H.
Published: June 2017

Background and Objective: Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its effect on neurodevelopmental impairment (NDI) at 24 months' corrected age (CA). Methods: This retrospective single-center cohort study included all patients with a gestational age <30 weeks born in 2004/2005 (epoch 1) and 2010/2011 (epoch 2). In epoch 2, we introduced a policy of restriction on IMV and liberalized the use of respiratory stimulants in the delivery room and neonatal intensive care. Data on patient characteristics, respiratory management, short-term outcomes, mortality, BPD, and NDI at 24 months' CA were collected. Results: Four hundred and four preterm infants were included. Compared to those in epoch 1, infants in epoch 2 were less likely to be intubated and the duration of IMV was shorter. Other noninvasive adjuvant therapies such as caffeine, doxapram, and nasal ventilation were more often used during epoch 2. There was a trend to less BPD in epoch 2 compared to epoch 1 (17 vs. 23%, adjusted OR = 0.75, 95% CI: 0.48, 1.16). Mortality did not change over time. The combined outcome death or NDI at 24 months' CA was significantly lower in epoch 2 compared to epoch 1 (24.7 vs. 33.9%, adjusted OR = 0.71, 95% CI: 0.53, 0.97). Conclusions: Restricted use of IMV is feasible in preterm infants and might be associated with a reduced risk of the combined outcome death or NDI at 24 months' CA. Larger studies are needed to confirm these findings.
Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany
Authors: Rosenbaum Clemens M. , Reiss C. Philip , Borgmann Hendrik , Salem Johannes , Fisch Margit , Huber Johannes , Schmid Marianne , Ahyai Sascha A.
Published: June 2017

Introduction: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. Methods: We conducted a survey on the management of urethral strictures among German urologists. Results: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). Conclusion: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys.
Skin-Homing IL-13-Producing T Cells Expand in the Circulation of Patients with Drug Rash with Eosinophilia and Systemic Symptoms
Authors: Teraki Yuichi , Fukuda Tomoo
Published: June 2017

Background: Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS. Objective and Methods: Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS. Results: The proportions of circulating IL-4- and IL-13-producing CD4+ T cells, but not CD8+ T cells, were significantly higher in patients with DRESS during the active stage of the disease than in healthy subjects, and these proportions declined during the recovery stage. No differences in the proportions of circulating IFN-γ-, IL-17-, and IL-22-producing CD4+ and CD8+ T cells were observed between patients with DRESS and healthy subjects. A strong correlation between the proportion of IL-13-producing CD4+ T cells and serum levels of thymus and activation-regulated chemokine was observed. The proportion of CLA-expressing CD4+ T cells was significantly higher during the active stage of the disease. Moreover, the proportion of IL-13-producing CD4+ T cells was higher in the CLA+ subset than in the CLA- subset. Conclusions: Skin-homing IL-13-producing CD4+ T cells may be involved in the pathogenesis of DRESS.
Weight Bias: A Systematic Review of Characteristics and Psychometric Properties of Self-Report Questionnaires
Authors: Lacroix Emilie , Alberga Angela , Russell-Mathew Shelly , McLaren Lindsay , von Ranson Kristin
Published: June 2017

Background: People living with overweight and obesity often experience weight-based stigmatization. Investigations of the prevalence and correlates of weight bias and evaluation of weight bias reduction interventions depend upon psychometrically-sound measurement. Our paper is the first to comprehensively evaluate the psychometric properties, use of people-first language within items, and suitability for use with various populations of available self-report measures of weight bias. Methods: We searched five electronic databases to identify English-language self-report questionnaires of weight bias. We rated each questionnaire's psychometric properties based on initial validation reports and subsequent use, and examined item language. Results: Our systematic review identified 40 original self-report questionnaires. Most questionnaires were brief, demonstrated adequate internal consistency, and tapped key cognitive and affective dimensions of weight bias such as stereotypes and blaming. Current psychometric evidence is incomplete for many questionnaires, particularly with regard to the properties of test-retest reliability, sensitivity to change as well as discriminant and structural validity. Most questionnaires were developed prior to debate surrounding terminology preferences, and do not employ people-first language in the items administered to participants. Conclusions: We provide information and recommendations for clinicians and researchers in selecting psychometrically sound measures of weight bias for various purposes and populations, and discuss future directions to improve measurement of this construct.
Successful Treatment of Neonatal Respiratory Transitional Disorder with Pulmo/Vivianit comp. in 2 Cases
Authors: Huber Benedikt M. , Bassler Dirk
Published: June 2017

Background: Disorders of the respiratory transition at birth are major reasons for neonates being admitted to intensive care units and separated from their mothers. This has potential long-lasting consequences for the mother-infant interaction as well as the long-term development of the child. There is an urgent need for effective preventive and therapeutic measures for this frequent disorder. Case Report: We report the cases of 2 newborn infants with respiratory transitional disorder treated off-label with the anthroposophic medicament Pulmo/Vivianit comp. based on pathophysiological considerations and on particular parental request. In both cases, an immediate and sustainable response could be documented without adverse effects. Conclusion: This new therapeutic approach merits further attention in clinical research but cannot be recommended for routine practice before more high-level evidence is available.
Comparative Retinal Vessel Size Study of Intravitreal Ranibizumab and Bevacizumab in Eyes with Neovascular Age-Related Macular Degeneration
Authors: Kurt Muhammed Mustafa , Çekiç Osman , Akpolat Çetin , Aslankurt Murat , Elçioğlu Mustafa Nuri
Published: June 2017

Purpose: The aim of this paper was to assess and compare the effects of intravitreal ranibizumab and bevacizumab on retinal vessel diameter in eyes with neovascular age-related macular degeneration (AMD). Methods: Patients with neovascular AMD who underwent intravitreal injection of either ranibizumab or bevacizumab were included. Noninjected fellow eyes served as a control. The main outcome measures were central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and the artery-vein ratio (AVR). Results: In the ranibizumab group, the mean CRAE value decreased significantly at 1 week and 1 month (p = 0.002). The AVR value decreased significantly at 1 month (p = 0.028). CRVE values did not change at 1 week and 1 month (p = 0.083). In the bevacizumab group, the preinjection CRAE, CRVE, and AVR values did not change through the study period (p = 0.128, p = 0.600, and p = 0.734, respectively). Conclusion: These results suggest that intravitreal ranibizumab led to significant retinal arteriolar vasoconstriction in eyes with neovascular AMD.
Fatigue and Excessive Daytime Sleepiness in Sarcoidosis: Prevalence, Predictors, and Relationships between the Two Symptoms
Authors: Bosse-Henck Andrea , Koch Rainer , Wirtz Hubert , Hinz Andreas
Published: June 2017

Background: Fatigue is common among patients with sarcoidosis. The etiology of this problem is unknown and multifactorial. Fatigue can be confounded with excessive daytime sleepiness (EDS). Fatigue and sleepiness have rarely been studied simultaneously in sarcoidosis patients. Objectives: The aim of this study was the confounder-adjusted estimation of risks for severe fatigue and EDS in a large population of sarcoidosis patients and the development of multivariate predictors from this population. Methods: 1,197 German sarcoidosis patients were examined using the Epworth Sleepiness Scale (ESS), the Fatigue Assessment Scale (FAS), the Hospital Anxiety and Depression Scale (HADS), and the Medical Research Council (MRC) dyspnea scale. Results: 16.5% (123 patients) had EDS (ESS ≥16), 16.4% had severe fatigue (FAS ≥35), and 6.3% had both extreme findings. In a multivariate logistic regression model, predictors of the risk of EDS were a history of sleep apnea (odds ratio [OR] 2.46, 95% confidence interval [CI] 1.5-3.9), dyspnea MRC grade ≥2 (OR 2.29, 95% CI 1.5-3.5), and organ involvement of 4-7 organs (OR 1.60, 95% CI 1.1-2.4). Significantly associated with higher risk of severe fatigue were the following: conspicuous depression (OR 5.95, 95% CI 4.1-8.7), conspicuous anxiety (OR 2.38, 95% CI 1.6-3.4), and muscle pain (OR 1.92, 95% CI 1.32-2.75). The logit models for severe fatigue with and without simultaneous EDS differed only slightly. Conclusion: An extreme form of fatigue and/or sleepiness was found in 27% of all sarcoidosis patients questioned. Because there is a certain overlap, both should be examined simultaneously to allow for a combined assessment.
Blue-White Veil as Novel Dermatoscopic Feature in Discoid Lupus Erythematosus in 2 African-American Patients
Authors: Cervantes Jessica , Hafeez Farhaan , Miteva Mariya
Published: June 2017

Dermoscopic features of discoid lupus erythematosus (DLE) depend on the stage of the lesions: active lesions include yellow-brown dots and red dots, whereas longstanding inactive lesions show absence of follicular openings, cicatricial milky red or white patches, structureless white and brown areas, and thick arborizing vessels. Loss of pinpoint white dots, blue-gray dots in a speckled pattern, and a peripheral pigmented network have been described on dermoscopy of DLE in dark skin. We report a blue-white veil as a novel dermoscopic feature in 2 cases of biopsy-proven DLE in African-American patients. Dry trichoscopy revealed a central white area surrounded by irregular patchy areas of confluent blue and brown pigment and an overlying white “ground-glass” hue. This corresponds on pathology to the hyperkeratosis overlying interface changes at the dermal-epidermal junction, with pigment incontinence and melanophages in the papillary dermis.
The urban crisis
Authors:   University of São Paulo. Faculty of Philosophy, Languages and Literature and Humanities. Department of Geography, Carlos Ana Fani Alessandri , Molsing Karina Veronica
Published: June 2017

Space is one of the main objects of study in Geography. In its complexity, it is more than just what we can see - for example, the place where we live - or simply a natural environment deformed by the presence of man. Since space is also the product of a social and historical representation. And, ultimately, one of the works of the civilization process. This book addresses space production and the role of Geography - in the necessary dialogue with other disciplines - in understanding the modern world in the face of a series of problems of a time in crisis, in which space has been taking on an unprecedented and prominent role. Resulting from a research project and some reflection (always open to debate and questions), this book is essential for professors and students who aim to deeply comprehend urban space today.
“The Museum is Yours”: Access to Virtual Visitation of Art Museums for All
Authors: Reily Lucia , Carvalho Jéssica Kelly Yacabo de , Brigatto Agda
Published: June 2017

Museus de arte são espaços culturais que recebem um público bastante diverso. Entre os visitantes, há pessoas com deficiências de várias naturezas que exigem alguns cuidados especiais para circular nos espaços museológicos e para acessar informações sobre o acervo. No atual contexto de inclusão, percebe-se uma crescente preocupação quanto ao acesso cultural das pessoas com necessidades especiais e muitas institui- ções culturais têm realizado ações voltadas especificamente para as pessoas com deficiência. Este texto apresenta uma síntese sobre políticas públicas que buscam assegurar o acesso à cultura para todas as pessoas. Com base num estudo de sites da internet de museus de arte, este artigo aborda as “Recomendações de Acessibilidade para Conteúdo Web” do World Wide Web Consortium (W3C) e discute a experiência de simular visitas com o monitor do computador desligado para sites de nove museus que indicam na página de abertura que atendem aos requisitos de acessibilidade digital
10 years of the Perception Garden of the Centre for Scientific and Cultural Dissemination
Authors: Mori Rafael Cava , Colombo Junior Pedro Donizete , Curvelo Antonio Aprigio Da Silva , Silva Cibelle Celestino
Published: June 2017

O Jardim da Percepção, exposição permanente do Centro de Divulgação Científica e Cultural (CDCC-USP), completa 10 anos em 2016. Em comemoração, este trabalho descreve os elementos expositivos presentes nesse espaço, especialmente os ambientes de imersão Casa Maluca e Cerrado/Mata de Galeria, e apresenta duas pesquisas que os tomaram como objetos. Os resultados reforçam a relevância dos museus e centros de ciências como espaços que contribuem para a elevação do nível cultural da comunidade de visitantes e também como loci de pesquisa