bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population
Authors: Wu Yongqin , Zhu Zhiling , Fang Xiaoxia , Yin Ling , Liu Yuxia , Xu Shouxia , Li Aixue
Published: December 2016

Endothelial NOS (NOS3) has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE). Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (correctedP=0.009). For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; correctedP=0.006) in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.
Real-Time Sensing of Hydrogen Peroxide by ITO/MWCNT/Horseradish Peroxidase Enzyme Electrode
Authors: Magyar Melinda , Rinyu László , Janovics Róbert , Berki Péter , Hernádi Klára , Hajdu Kata , Szabó Tibor , Nagy László
Published: December 2016

The accurate and sensitive determination of H2O2is very important in many cases because it is a product of reactions catalysed by several oxidase enzymes in living cells and it is essential in environmental and pharmaceutical analyses. The fabrication of enzyme protein activity based biosensors is a very promising way for this purpose because the function of biological molecules is very specific, sensitive, and selective. Horseradish peroxidase (HRP) is the most commonly used enzyme for H2O2detection because it can oxidize hydrogen atoms and, for example, xenobiotics in the presence of H2O2. In order to define the limit of detection (LOD) of H2O2we made calibrations with guaiacol and amplex red (AR), which are hydrogen donors of HRP. The accumulation of the reaction products, tetraguaiacol, and resorufin, respectively, then can be easily detected by absorption or emission (fluorescence) spectroscopy. In our experiments an enzyme electrode was fabricated from ITO (indium tin oxide), functionalized multiwalled carbon nanotubes (f-MWCNTs), and HRP. Although the enzyme activity was smaller by about two orders of magnitude when the enzyme was bound to the f-MWCNTs (ca. 10−2 M H2O2/(M HRP·sec) compared to ca. 2 M H2O2/(M HRP·sec) and 5 M H2O2/(M HRP·sec) with AR and guaiacol in buffer solution), LOD of the H2O2decomposition was about 6 pM H2O2/sec and 10 pM H2O2/sec in the case of AR and guaiacol, respectively.
Mullerian-Type Ciliated Cyst of the Thigh with PAX-8 and WT1 Positivity: A Case Report and Review of the Literature
Authors: Fabien-Dupuis Corinthia , Cooper Brian , Upperman Jeffrey , Zhou Shengmei , Shillingford Nick
Published: December 2016

Mullerian-type ciliated cysts are uncommon lesions usually found in the lower extremities and perineal region of young females. They have however been reported in males and in other anatomic sites. The cyst lining is typically positive for estrogen receptor (ER), progesterone receptor (PR), PAX-8, and WT1 immunohistochemical stains. This staining pattern has led to the notion that these cysts are of Müllerian origin. The vast majority of cases are located in the dermis where the preferred nomenclature is cutaneous ciliated cyst (CCC). We report a case of Müllerian-type ciliated cyst in the thigh of a 16-year-old girl. Unlike most of the cases reported in the English literature, this cyst was not centered in the dermis. Only a few other cases of Müllerian-type ciliated cysts with no cutaneous connection have been reported. We propose the term ectopic Müllerian cyst for this rare subset of lesions that are not skin based as is the current case.
Light Manipulation by Single Cells: The Case of Diatoms
Authors: De Tommasi Edoardo
Published: December 2016

Diatoms are ubiquitous monocellular microalgae, responsible for about 20–25% of the global oxygen produced by photosynthesis. Living in environments where sunlight is not so easily accessible, evolution shaped diatoms in order to exploit light with high efficiency. In particular, diatoms are provided with an external, micro- and nanopatterned silica shell, the frustule, surprisingly similar to artificial photonic crystals and able to manipulate light in many different ways. The present paper reviews the most relevant studies on optical and photonic properties of diatoms that have been performed throughout the last years making use of SEM characterizations, transmittance measurements at different wavelengths, holographic microscopy, Raman spectroscopy and imaging, photoluminescence spectroscopy, and the predictive support of different numerical simulation algorithms.
Strong Convergence Theorems for an Implicit Iterative Algorithm for the Split Common Fixed Point Problem
Authors: He Huimin , Liu Sanyang , Chen Rudong
Published: December 2016

The aim of this paper is to construct a novel implicit iterative algorithm for the split common fixed point problem for the demicontractive operatorsU,T, and  xn=αnfxn+1-αnUλxn-ρnA*I-TAxn,n≥0, whereUλ=(1-λ)I+λU, and we obtain the sequence which strongly converges to a solutionx^of this problem, and the solutionx^satisfies the variational inequality.〈x^-f(x^),x^-z〉≤0,∀z∈S, whereSdenotes the set of all solutions of the split common fixed point problem.
Phantom Validation of Tc-99m Absolute Quantification in a SPECT/CT Commercial Device
Authors: Gnesin Silvano , Leite Ferreira Paulo , Malterre Jerome , Laub Priscille , Prior John O. , Verdun Francis R.
Published: December 2016

Aim. Similar to PET, absolute quantitative imaging is becoming available in commercial SPECT/CT devices. This study’s goal was to assess quantitative accuracy of activity recovery as a function of image reconstruction parameters and count statistics in a variety of phantoms. Materials and Methods. We performed quantitative Tc99m-SPECT/CT acquisitions (Siemens Symbia Intevo, Erlangen, Germany) of a uniform cylindrical, NEMA/IEC, and an anthropomorphic abdominal phantom. Background activity concentrations tested ranged: 2–80 kBq/mL. SPECT acquisitions used 120 projections (20 s/projection). Reconstructions were performed with the proprietary iterative conjugate gradient algorithm. NEMA phantom reconstructions were obtained as a function of the iteration number (range: 4–48). Recovery coefficients, hot contrast, relative lung error (NEMA phantom), and image noise were assessed. Results. In all cases, absolute activity and activity concentration were measured within 10% of the expected value. Recovery coefficients and hot contrast in hot inserts did not vary appreciably with count statistics. RC converged at 16 iterations for insert size > 22 mm. Relative lung errors were comparable to PET levels indicating the efficient integration of attenuation and scatter corrections with adequate detector modeling. Conclusions. The tested device provided accurate activity recovery within 10% of correct values; these performances are comparable to current generation PET/CT systems.
Comparative Genomics Analysis of Two Different Virulent Bovine Pasteurella multocida Isolates
Authors: Du Huihui , Fang Rendong , Pan Tingting , Li Tian , Li Nengzhang , He Qiang , Wu Rui , Peng Yuanyi , Zhou Zeyang
Published: December 2016

The Pasteurella multocida capsular type A isolates can cause pneumonia and bovine respiratory disease (BRD). In this study, comparative genomics analysis was carried out to identify the virulence genes in two different virulent P. multocida capsular type A isolates (high virulent PmCQ2 and low virulent PmCQ6). The draft genome sequence of PmCQ2 is 2.32 Mbp and contains 2,002 protein-coding genes, 9 insertion sequence (IS) elements, and 1 prophage region. The draft genome sequence of PmCQ6 is 2.29 Mbp and contains 1,970 protein-coding genes, 2 IS elements, and 3 prophage regions. The genome alignment analysis revealed that the genome similarity between PmCQ2 and PmCQ6 is 99% with high colinearity. To identify the candidate genes responsible for virulence, the PmCQ2 and PmCQ6 were compared together with that of the published genomes of high virulent Pm36950 and PmHN06 and avirulent Pm3480 and Pm70 (capsular type F). Five genes and two insertion sequences are identified in high virulent strains but not in low virulent or avirulent strains. These results indicated that these genes or insertion sequences might be responsible for the virulence of P. multocida, providing prospective candidates for further studies on the pathogenesis and the host-pathogen interactions of P. multocida.
A Community-Based Assessment of Hypertension and Some Other Cardiovascular Disease Risk Factors in Ngaoundéré, Cameroon
Authors: Pancha Mbouemboue Olivier , Derew Diana , Tsougmo Jacques Olivier Ngoufack , Tangyi Tamanji Marcel
Published: December 2016

Background and Objective. Cardiovascular diseases are primary causes of death worldwide with well documented risk factors whose varying impacts added to the complexity in CVD management dictate the need for region-specific studies. We aimed at investigating the interactions between CVD risk factors and hypertension in Ngaoundéré.Methods. A cross-sectional survey was carried out from March to August 2014. Sociodemographic, fasting blood glucose, blood pressure, and anthropometric data were recorded. Statistical analyses were carried out using SAS software version 9.1.Results. 700 adults resident in Ngaoundéré for at least two years consented and were included in the survey. Abdominal obesity, physical inactivity, and hypertension were the dominant risk factors recording 51.1%, 35.4%, and 20.4%, respectively. The prevalence of hyperglycaemia, tobacco consumption, obesity, and alcohol consumption was 5.6%, 8.3%, 9.6%, and 18.1%, respectively. Advanced age, hyperglycaemia, a divorced marital status, and alcohol consumption were independent determinants of high blood pressure.Conclusion. Physical inactivity, abdominal obesity, and hypertension were the most prevalent CVD risk factors, and the role of advanced age and hyperglycaemia in the occurrence of high blood pressure was reiterated. Health programs need to focus on effective screening, prevention, and control of CVDs in the Adamawa Region and Cameroon at large.
Novel Handover Optimization with a Coordinated Contiguous Carrier Aggregation Deployment Scenario in LTE-Advanced Systems
Authors: Shayea Ibraheem , Ismail Mahamod , Nordin Rosdiadee , Mohamad Hafizal , Abd Rahman Tharek , Abdullah Nor Fadzilah
Published: December 2016

The carrier aggregation (CA) technique and Handover Parameters Optimization (HPO) function have been introduced in LTE-Advanced systems to enhance system performance in terms of throughput, coverage area, and connection stability and to reduce management complexity. Although LTE-Advanced has benefited from the CA technique, the low spectral efficiency and high ping-pong effect with high outage probabilities in conventional Carrier Aggregation Deployment Scenarios (CADSs) have become major challenges for cell edge User Equipment (UE). Also, the existing HPO algorithms are not optimal for selecting the appropriate handover control parameters (HCPs). This paper proposes two solutions by deploying a Coordinated Contiguous-CADS (CC-CADS) and a Novel Handover Parameters Optimization algorithm that is based on the Weight Performance Function (NHPO-WPF). The CC-CADS uses two contiguous component carriers (CCs) that have two different beam directions. The NHPO-WPF automatically adjusts the HCPs based on the Weight Performance Function (WPF), which is evaluated as a function of the Signal-to-Interference Noise Ratio (SINR), cell load, and UE’s velocity. Simulation results show that the CC-CADS and the NHPO-WPF algorithm provide significant enhancements in system performance over that of conventional CADSs and HPO algorithms from the literature, respectively. The integration of both solutions achieves even better performance than scenarios in which each solution is considered independently.
Combination of Intravitreal Injection of Ranibizumab and Photocoagulation for the Treatment of Aggressive Posterior Retinopathy of Prematurity with Vitreous Hemorrhage
Authors: Xu Yu , Kang Xiaoli , Zhang Qi , Huang Qiujing , Lv Jiao , Zhao Peiquan
Published: December 2016

To investigate the efficacy of intravitreal ranibizumab (IVR) combined with laser photocoagulation for aggressive posterior retinopathy of prematurity (AP-ROP) patients with vitreous hemorrhage, we conducted a retrospective observational case series study. A total of 37 eyes of 20 patients’ medical records were reviewed. Patients first received IVR (0.25 mg/0.025 mL) and later photocoagulation. The mean postconceptual age of injection was 34.6 ± 1.4 weeks, and the mean follow-up period was 39.3 ± 8.3 weeks. During the follow-up, 96.6% eyes had various degree of rapid absorption of vitreous hemorrhage after IVR. The mean time of received first photocoagulation after IVR was 4.8 ± 2.9 weeks. Ten (27.0%) eyes received second laser therapy and the mean time of second laser therapy after IVR was 3.2 ± 0.8 weeks. All eyes exhibited adequate regression of ROP and were stable with attached retina. Fibrosis membrane was observed in seven eyes (18.9%) and three of them demonstrated mild ectopic macula. No significant side effects related to IVR were observed. So IVR could be conducted as primary treatment of AP-ROP associated with vitreous hemorrhage, which can improve the fundus visibility, followed by conventional photocoagulation. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with conventional interventions.
Custom-Made Synthetic Scaffolds for Bone Reconstruction: A Retrospective, Multicenter Clinical Study on 15 Patients
Authors: Luongo Fabrizia , Mangano Francesco Guido , Macchi Aldo , Luongo Giuseppe , Mangano Carlo
Published: December 2016

Purpose. To present a computer-assisted-design/computer-assisted-manufacturing (CAD/CAM) technique for the design, fabrication, and clinical application of custom-made synthetic scaffolds, for alveolar ridge augmentation. Methods. The CAD/CAM procedure consisted of (1) virtual planning/design of the custom-made scaffold; (2) milling of the scaffold into the exact size/shape from a preformed synthetic bone block; (3) reconstructive surgery. The main clinical/radiographic outcomes were vertical/horizontal bone gain, any biological complication, and implant survival. Results. Fifteen patients were selected who had been treated with a custom-made synthetic scaffold for ridge augmentation. The scaffolds closely matched the shape of the defects: this reduced the operation time and contributed to good healing. A few patients experienced biological complications, such as pain/swelling (2/15: 13.3%) and exposure of the scaffold (3/15: 20.0%); one of these had infection and complete graft loss. In all other patients, 8 months after reconstruction, a well-integrated newly formed bone was clinically available, and the radiographic evaluation revealed a mean vertical and horizontal bone gain of 2.1±0.9 mm and 3.0±1.0 mm, respectively. Fourteen implants were placed and restored with single crowns. The implant survival rate was 100%. Conclusions. Although positive outcomes have been found with custom-made synthetic scaffolds in alveolar ridge augmentation, further studies are needed to validate this technique.
A Rare Subcutaneous Manifestation of Metastatic Renal Cell Carcinoma
Authors: Chan Darren Yak Leong , Chua Wei Jin
Published: December 2016

We report a rare case of advanced metastatic renal cell carcinoma which initially presented to the clinic with back and forehead lumps. Ultrasound imaging of the lumps and later of the abdomen picked up a right renal tumour which led to further computed tomography and bone scans. The bone scan confirmed that the forehead lump was a calvarial metastasis and such a presentation for metastatic RCC is very rare which bears a significantly poorer prognosis.
The Prognostic Role of SIRT1-Autophagy Axis in Gastric Cancer
Authors: Qiu Guanglin , Li Xuqi , Wei Chao , Che Xiangming , He Shicai , Lu Jing , Wang Shufeng , Pang Ke , Fan Lin
Published: December 2016

Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients’ samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC.
Prevalence, Characteristics, and One-Year Follow-Up of Congenital Cytomegalovirus Infection in Isfahan City, Iran
Authors: Karimian Pegah , Yaghini Omid , Nasr Azadani Hossein , Mohammadizadeh Majid , Arabzadeh Seyed Ali Mohammad , Adibi Atosa , Rahimi Hamid
Published: December 2016

Introduction.Need of neonatal screening forCytomegalovirus(CMV) infection is under debate, in part because of limited data on importance of the disease regarding the prevalence of congenital CMV (cCMV) infection and associated morbidity and mortality. We aimed to evaluate the prevalence and prognosis of cCMV infection in Iran, where there is high maternal seroprevalence of CMV.Methodology. This prospective study was conducted in Isfahan city, Iran, from 2014 to 2016. CMV was investigated in urine specimens by using the real-time polymerase chain reaction (RT-PCR) method. CMV-infected infants were examined for clinical and laboratory findings attributed to CMV infection and followed up for one year.Results.Among 1617 studied neonates, eight (0.49%) were positive for CMV infection. CMV-infected neonates were more likely to be preterm than noninfected ones (25% versus 4.5%,p=0.0508), and they had lower birth weight. Three out of the eight CMV-infected neonates had transient symptoms at birth. At follow-up, one case had mild hearing loss. Most patients had impaired growth during the one-year follow-up.Conclusions.The primary object of this study was determination of prevalence of cCMV infection in Iran as a developing country, which was at the lower range compared with other such countries. cCMV infection may result in short-term impairment in growth.
A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data
Authors: Hintzsche Jennifer D. , Robinson William A. , Tan Aik Choon
Published: December 2016

Whole Exome Sequencing (WES) is the application of the next-generation technology to determine the variations in the exome and is becoming a standard approach in studying genetic variants in diseases. Understanding the exomes of individuals at single base resolution allows the identification of actionable mutations for disease treatment and management. WES technologies have shifted the bottleneck in experimental data production to computationally intensive informatics-based data analysis. Novel computational tools and methods have been developed to analyze and interpret WES data. Here, we review some of the current tools that are being used to analyze WES data. These tools range from the alignment of raw sequencing reads all the way to linking variants to actionable therapeutics. Strengths and weaknesses of each tool are discussed for the purpose of helping researchers make more informative decisions on selecting the best tools to analyze their WES data.
Bone Healing Improvements Using Hyaluronic Acid and Hydroxyapatite/Beta-Tricalcium Phosphate in Combination: An Animal Study
Authors: Chang Yen-Lan , Lo Yi-June , Feng Sheng-Wei , Huang Yu-Chih , Tsai Hsin-Yuan , Lin Che-Tong , Fan Kan-Hsin , Huang Haw-Ming
Published: December 2016

The purpose of this study was to investigate whether the use of HLA as an aqueous binder of hydroxyapatite/beta-tricalcium phosphate (HA-βTCP) particles can reduce the amount of bone graft needed and increase ease of handling in clinical situations. In this study, HA/βTCP was loaded in commercially available crosslinking HLA to form a novel HLA/HA-βTCP composite. Six New Zealand White rabbits (3.0–3.6 kg) were used as test subjects. Four 6 mm defects were prepared in the parietal bone. The defects were filled with the HLA/HA-βTCP composite as well as HA-βTCP particle alone. New bone formation was analyzed by micro-CT and histomorphometry. Our results indicated that even when the HA-βTCP particle numbers were reduced, the regenerative effect on bone remained when the HLA existed. The bone volume density (BV/TV ratio) of HLA/HA-βTCP samples was 1.7 times larger than that of the control sample at week 2. The new bone increasing ratio (NBIR) of HLA/HA-βTCP samples was 1.78 times higher than the control group at week 2. In conclusion, HA-βTCP powder with HLA contributed to bone healing in rabbit calvarial bone defects. The addition of HLA to bone grafts not only promoted osteoconduction but also improved handling characteristics in clinical situations.
Effect of Endolymphatic Hydrops on Sound Transmission in Live Guinea Pigs Measured with a Laser Doppler Vibrometer
Authors: Ding Chen-Ru , Xu Xin-Da , Wang Xin-Wei , Jia Xian-Hao , Cheng Xiang , Liu Xiang , Yang Lin , Tong Bu-Sheng , Chi Fang-Lu , Ren Dong-Dong
Published: December 2016

Objective. This study aimed at describing the mechanism of hearing loss in low frequency and the different dynamic behavior of the umbo, the stapes head, and the round window membrane (RWM) between normal guinea pigs and those with endolymphatic hydrops (EH), using a laser Doppler vibrometer (LDV).Methods. Cochlear sections were stained with hematoxylin and eosin (HE) to evaluate the hydropic ratio (HR). Auditory brainstem responses (ABR) and whole-mount immunostaining were measured. Displacement of the umbo, stapes head, and RWM in response to ear-canal sound was evaluated using a LDV.Results. Mean HR values in EH model of all the turns are larger than the control group. The ABR threshold of the EH group was significantly higher than that of the control. Strong positive correlation was found between HR at apical turn and ABR threshold elevation at 1000 Hz and at subapical turn and ABR threshold elevation at 2000 Hz. FITC-phalloidin immunostaining of the cochlear basilar membrane in the apical, subapical, and suprabasal turns showed missing and derangement stereocilia of third-row outer hair cells. The umbo, stapes head, and RWM displacement in ears with EH was generally lower than that of normal ears. The EH-induced differences in stapes head and RWM motion were significant at 0.5 kHz.Conclusion. The LDV results suggested that the higher inner ear impedance in EH affected the dynamic behavior of the two opening windows of the cochlea and then reduced the vibration of the ossicular chain by increasing the afterload, resulting in acoustic dysfunction. The vibration reduction mainly occurred at low frequencies, which has related with the morphology changes of the apical and subapical turns in EH model.
Deoxycholic Acid Could Induce Apoptosis and Trigger Gastric Carcinogenesis on Gastric Epithelial Cells by Quantitative Proteomic Analysis
Authors: Shi Yanyan , Wei Ying , Zhang Ting , Zhang Jing , Wang Ye , Ding Shigang
Published: December 2016

Background.Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown.Methods.To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs.Results.We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins.Conclusion.These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa.
Cell-Specific Computational Modeling of the PIM Pathway in Acute Myeloid Leukemia
Authors: Silverbush Dana , Grosskurth Shaun , Wang Dennis , Powell Francoise , Gottgens Berthold , Dry Jonathan , Fisher Jasmin
Published: December 2016

Personalized therapy is a major goal of modern oncology, as patient responses vary greatly even within a histologically defined cancer subtype. This is especially true in acute myeloid leukemia (AML), which exhibits striking heterogeneity in molecular segmentation. When calibrated to cell-specific data, executable network models can reveal subtle differences in signaling that help explain differences in drug response. Furthermore, they can suggest drug combinations to increase efficacy and combat acquired resistance. Here, we experimentally tested dynamic proteomic changes and phenotypic responses in diverse AML cell lines treated with pan-PIM kinase inhibitor and fms-related tyrosine kinase 3 (FLT3) inhibitor as single agents and in combination. We constructed cell-specific executable models of the signaling axis, connecting genetic aberrations in FLT3, tyrosine kinase 2 (TYK2), platelet-derived growth factor receptor alpha (PDGFRA), and fibroblast growth factor receptor 1 (FGFR1) to cell proliferation and apoptosis via the PIM and PI3K kinases. The models capture key differences in signaling that later enabled them to accurately predict the unique proteomic changes and phenotypic responses of each cell line. Furthermore, using cell-specific models, we tailored combination therapies to individual cell lines and successfully validated their efficacy experimentally. Specifically, we showed that cells mildly responsive to PIM inhibition exhibited increased sensitivity in combination with PIK3CA inhibition. We also used the model to infer the origin of PIM resistance engineered through prolonged drug treatment of MOLM16 cell lines and successfully validated experimentally our prediction that this resistance can be overcome with AKT1/2 inhibition. Cancer Res; 77(4); 827–38. ©2016 AACR.
Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial
Authors: Lowenfeld Lea , Mick Rosemarie , Datta Jashodeep , Xu Shuwen , Fitzpatrick Elizabeth , Fisher Carla S. , Fox Kevin R. , DeMichele Angela , Zhang Paul J. , Weinstein Susan P. , Roses Robert E. , Czerniecki Brian J.
Published: December 2016

Purpose: Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection.

Experimental Design: Fifty-four HER2pos patients [42 pure ductal carcinoma in situ (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL (n = 19), IN (n = 19), or ILN (n = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or in vitro sensitization assay. Pathologic response was assessed in resected surgical specimens.

Results: Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%; P = 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR (n = 12) and who did not achieve pCR (n = 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire (P = 0.03) and cumulative response (P = 0.04).

Conclusions: Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2pos patients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity. Clin Cancer Res; 23(12); 2961–71. ©2016 AACR.
Clinical Challenges Associated with Universal Screening for Lynch Syndrome–Associated Endometrial Cancer
Authors: Bruegl Amanda S. , Ring Kari L. , Daniels Molly , Fellman Bryan M. , Urbauer Diana L. , Broaddus Russell R.
Published: December 2016

Universal testing for Lynch syndrome is now a routine component of the diagnostic work-up of endometrial cancer patients. The purpose of this study was to identify prospectively the barriers to universal screening based on a tissue testing approach [microsatellite instability (MSI) analysis, IHC for DNA mismatch repair proteins, and MLH1 methylation analysis]. Endometrial carcinoma patients (n = 213) prospectively underwent microsatellite instability and IHC testing for expression of DNA mismatch repair (MMR) proteins. Patients with low (MSI-L) or high (MSI-H) levels of tumor MSI or immunohistochemical loss of MLH1 (and absent MLH1 methylation), MSH2, MSH6, or PMS2 were referred to a genetic counselor for consideration of germline testing. Six discordances (3.1% of tested cases) between IHC and MSI were identified. Half of these exhibited heterogeneous immunohistochemical loss of MLH1/PMS2 and were microsatellite stable (MSS). Of the remaining cases, one was MSS with immunohistochemical loss of MSH6, one was MSS with immunohistochemical loss of MLH1/PMS2 and absent MLH1 promoter methylation, and one was MSI-H with intact expression of DNA MMR proteins. Four patients had MSI-L tumors with intact immunohistochemical protein expression; the clinical significance of MSI-L in endometrial cancer is unclear. Eight patients did not have germline mutations despite tissue testing suggesting Lynch syndrome. Including cases with insufficient tissue for testing and patients declining tissue or germline testing, we encountered significant barriers to universal screening in 13.6% of screened patients (29/213) that preclude designation of a tumor as sporadic or hereditary. Cancer Prev Res; 10(2); 108–15. ©2016 AACR.
Identifying and Creating the Next Generation of Community-Based Cancer Prevention Studies: Summary of a National Cancer Institute Think Tank
Authors: McCaskill-Stevens Worta , Pearson Deborah C. , Kramer Barnett S. , Ford Leslie G. , Lippman Scott M.
Published: December 2016

In late 2015, the NCI Division of Cancer Prevention convened cancer prevention research experts and stakeholders to discuss the current state of cancer prevention research, identify key prevention research priorities for the NCI, and identify studies that could be conducted within the NCI Community Oncology Research Program. Goals included identifying cancer prevention research opportunities offering the highest return on investment, exploring the concept of precision prevention and what is needed to advance this area of research, and identifying possible targets for prevention. Four study populations were considered for cancer prevention research: healthy people, those at increased risk for a specific cancer, people with preneoplastic lesions, and children, adolescents, and young adults. Priorities that emerged include screening (e.g., surveillance intervals, tomosynthesis vs. digital mammography), a pre-cancer genome atlas (PreTCGA), HPV vaccines, immunoprevention of noninfectious origins, and overdiagnosis. Challenges exist, as the priority list is ambitious and potentially expensive. Clinical trials need to be carefully designed to include and maximize prospective tissue collection. Exploring existing cofunding mechanisms will likely be necessary. Finally, relationships with a new generation of physician specialists will need to be cultivated to reach the target populations. Cancer Prev Res; 10(2); 99–107. ©2016 AACR.
Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß
Authors: Abousaab Abeer , Lang Florian
Published: December 2016

Background: Cellular uptake of glutamate by the excitatory amino-acid transporters (EAATs) decreases excitation and thus participates in the regulation of neuroexcitability. Kinases impacting on neuronal function include Lithium-sensitive glycogen synthase kinase GSK3ß. The present study thus explored whether the activities of EAAT3 and/or EAAT4 isoforms are sensitive to GSK3ß. Methods: cRNA encoding wild type EAAT3 (SLC1A1) or EAAT4 (SLC1A6) was injected into Xenopus oocytes without or with additional injection of cRNA encoding wild type GSK3ß or the inactive mutant K85AGSK3ß. Dual electrode voltage clamp was performed in order to determine glutamate-induced current (IEAAT). Results: Appreciable IEAAT was observed in EAAT3 or EAAT4 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of GSK3ß but not by coexpression of K85AGSK3ß. Coexpression of GSK3ß increased significantly the maximal IEAAT in EAAT3 or EAAT4 expressing oocytes, without significantly modifying apparent affinity of the carriers. Lithium (1 mM) exposure for 24 hours decreased IEAAT in EAAT3 and GSK3ß expressing oocytes to values similar to IEAAT in oocytes expressing EAAT3 alone. Lithium did not significantly modify IEAAT in oocytes expressing EAAT3 without GSK3ß. Conclusions: Lithium-sensitive GSK3ß is a powerful regulator of excitatory amino acid transporters EAAT3 and EAAT4.
Azoospermia and Testicular Hypoplasia in a Boar Carrier of a Novel Y-Autosome Translocation
Authors: Villagómez Daniel A.F. , Revay Tamas , Donaldson Brendan , Rezaei Samira , Pinton Alain , Palomino Manuel , Junaidi Awang , Honaramooz Ali , King W. Allan
Published: December 2016

Few sex-autosome chromosome abnormalities have been documented in domestic animal species. In humans, Y-autosome chromosome abnormalities may occur at a rate of 1/2,000 live births, whereas in the domestic pig only 2 Y-autosome reciprocal translocations have been previously described. During a routine cytogenetic screening of young boars, we identified a new Y-autosome translocation carrier, which after puberty showed semen devoid of sperm and testicular hypoplasia with spermatogenesis arrest. Whole chromosome painting by FISH analysis corroborated the reciprocal nature of the chromosomal exchanges between the Y chromosome and SSC13. The possible causes for the observed meiotic arrest of the carrier are reviewed.
Fragile and Enduring Positive Affect: Implications for Adaptive Aging
Authors: Ong Anthony D. , Ram Nilam
Published: December 2016

There is robust evidence linking interindividual differences in positive affect (PA) with adaptive psychological and physical health outcomes. However, recent research has suggested that intraindividual variability or fluctuations in PA states over time may also be an important predictor of individual health outcomes. Here, we report on research that focuses on PA level and various forms of PA dynamics (variability, instability, inertia, and reactivity) in relation to health. PA level refers to the average level of positive feelings. In contrast, PA dynamics refer to short-term changes in PA that unfold over time. We discuss how consideration of both PA level and PA dynamics can provide a framework for reconciling when high PA is conducive or detrimental to health. We conclude that more work on PA dynamics is needed, especially in combination with PA level, and suggest productive questions for future inquiry in this area.
Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes
Authors: Johnson Eric D. , Gulbahce Evin , McNally Joseph , Buys Saundra S.
Published: December 2016

Introduction: Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.
Coisas com as quais os antropólogos se preocupam: grupos de descendência espacial entre os Panará
Authors: Ewart Elizabeth
Published: December 2016

Em 2010, os Panará construíram uma nova aldeia, situada rio acima em relação à aldeia em que viviam desde 1997. Essa foi a primeira vez desde o começo dos anos 70 que eles ocuparam múltiplas aldeias. Neste artigo, faço uma reflexão sobre alguns dos pontos que levaram à construção da nova aldeia e sobre o uso do novo espaço. Em particular, retomo a ideia de “grupos de descendência espacial” e a noção de que clãs se identificam com locais específicos na aldeia circular. Usando relatos do fim do século XIX e começo do XX, bem como etnografias mais recentes, indago se as conexões entre espaço e identidade entre os grupos falante de línguas jê seriam, afinal, “coisas com as quais antropólogos se preocupam”.
“Todo caboclo é parente”: espacialidades, história e parentesco entre os Potiguara
Authors: Vieira José Glebson
Published: December 2016

Este artigo analisa a organização social, a produção e articulação do parentesco com a forma social potiguara expressa nos ideais de “viver bem”, que traduzem a possibilidade de “viver nas aldeias” e entre parentes, demarcando a centralidade do parentesco no processo de socialidade. Trata-se de compreender as espacialidades e os regimes de territorialidade através da intersecção entre parentesco e política deslindada pela descrição dos usos da terra, da ocupação dos espaços e da temporalidade, da configuração das aldeias e dos padrões de habitação. O estudo é conduzido pelo entendimento da história (e do parentesco), da gestão política de relações e da efetivação da vida social. Assim, entendemos a composição e organização das famílias e dos círculos de aliança e cooperação, que se estabelecem na observância dos critérios de proximidades de parentesco (ou genealógicos) ou de residência como parte significativa do jogo de forças políticas.
Dos mercados informais às políticas não hegemônicas de valor: olhares cruzados entre Porto Alegre e Buenos Aires na produção de objetos e sujeitos camelôs
Authors: Kopper Moisés
Published: December 2016

A antropologia dos mercados informais sempre enfrentou com alguma dificuldade o problema básico de propor definições acerca do que seja o informal. Economistas e sociólogos propuseram conceituações por demais generalizantes, atrelando-as à economia formal; antropólogos esbarram em concepções excessivamente particularizantes, muitas vezes negando a capacidade heurística da noção. Esse artigo sugere uma terceira via para o problema, explorando as políticas econômicas de produção do valor de sujeitos, objetos e lugares, uns em relação de mútua definição com os outros. O enfoque recai sobre as disputas de sentido a partir de onde certos discursos sobre a informalidade – imaginados, móveis e incompletos – são materializados e performatizados. Etnograficamente, parte, de um lado, da transição do mercado de rua para um shopping popular, em Porto Alegre/RS; de outro, dos debates públicos entre jornalistas, empresários e mercadores acerca da expansão da feira informal “La Salada”, considerada a maior do mundo, em Buenos Aires.
“Onde” não interrogativo no português falado no Libolo (Angola) – cotejos com dados do cabo-verdiano de São Nicolau
Authors: Oliveira Márcia Santos Duarte de , Zanoli Maria de Lurdes , Andrade Vanderlei Maurer de
Published: December 2016

Nosso objetivo é ratificar a análise parcial sugerida por Andrade (2015a) de que, um conjunto de dados que atestam o “onde” não interrogativo no português falado no Libolo/Angola (PLb) não introduz sentenças relativas, mas sim sentenças com categoria sintático-discursiva. A fim de corroborar nossa análise, nós nos apoiamos em alguns estudos sobre o caboverdiano, variedade de São Nicolau (CSN), desenvolvidos dentro do modelo de interface fonológico-sintático. Nossa conclusão é a de que sentenças com “onde” não interrogativo no PLb, e que sempre são seguidos por “é que”, podem estar envolvidas pelo conceito de “highlighter”, um marcador sintático-discursivo. A comparação entre o PLb e o CSN, desenvolvida no trabalho, é feita entre “línguas reestruturadas” (no sentido de Holm, 2004): (i) o PLb, considerada uma língua “parcialmente reestruturada” – ver, entre outros, Figueiredo e Santos (2014); (ii) o CSN, considerada uma língua “completamente reestruturada” – ver, entre outros, Zanoli (2015).
Clinical Impact of Suboptimal Stenting and Residual Intrastent Plaque/Thrombus Protrusion in Patients With Acute Coronary Syndrome
Authors: Prati Francesco , Romagnoli Enrico , Gatto Laura , La Manna Alessio , Burzotta Francesco , Limbruno Ugo , Versaci Francesco , Fabbiocchi Franco , Di Giorgio Alessandro , Marco Valeria , Ramazzotti Vito , Di Vito Luca , Trani Carlo , Porto Italo , Boi Alberto , Tavazzi Luigi , Mintz Gary S.
Published: December 2016

Background—

Clinical consequences of optical coherence tomographic (OCT) high-definition visualization of plaque/stent structures in acute patients remain undefined. In this retrospective substudy, we assessed the prognostic impact of postprocedural culprit lesion OCT findings in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Methods and Results—

In the CLI-OPCI (Centro per la Lotta Contro L’Infarto-Optimization of Percutaneous Coronary Intervention) database collecting cases from 5 independent OCT-experienced centers, we retrospectively analyzed postprocedural OCT findings in acute coronary syndrome patients and explored its possible impact (specifically that of residual intrastent plaque/thrombus protrusion) on outcome. From 2009 to 2013, 507 patients (588 lesions) were evaluated. Patients experiencing device-oriented cardiovascular events showed more frequently the features of suboptimal stent implantation defined as the presence of significant residual intrastent plaque/thrombus protrusion (hazard ratio [HR], 2.35;
P
<0.01), in-stent minimum lumen area (MLA) <4.5 mm
2
(HR, 2.72;
P
<0.01), dissection >200 µm at distal stent edge (HR, 3.84;
P
<0.01), and reference lumen area <4.5 mm
2
at either distal (HR, 6.07;
P
<0.001) or proximal (HR, 8.50;
P
<0.001) stent edges. Postprocedural OCT assessment of treated culprit lesion revealed at least one of these parameters in 55.2% of cases, with an associated increased risk of device-oriented cardiovascular events during follow-up (17.9% versus 4.8%;
P
<0.001). Both the presence of at least one of these parameters (HR, 3.69;
P
=0.002) and the residual intrastent plaque/thrombus protrusion (HR, 2.83;
P
=0.008) were confirmed as independent predictors of device-oriented cardiovascular events.

Conclusions—

In this retrospective study of acute coronary syndrome patients undergoing percutaneous coronary intervention, a composite of OCT-defined suboptimal stent implantation characteristics at the culprit lesion and residual intrastent plaque/thrombus protrusion was associated with adverse outcome.