bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac remodeling in aortic and mitral valve disease: a simulation study with clinical validation
Authors: Maksuti Elira , Westerhof Berend E. , Ugander Martin , Donker Dirk W. , Carlsson Marcus , Broomé Michael
Published: February 2019

Remodeling is an important long-term determinant of cardiac function throughout the progression of heart disease. Numerous biomolecular pathways for mechanosensing and transduction are involved. However, we hypothesize that biomechanical factors alone can explain changes in myocardial volume and chamber size in valve disease. A validated model of the human vasculature and the four cardiac chambers was used to simulate aortic stenosis, mitral regurgitation, and aortic regurgitation. Remodeling was simulated with adaptive feedback preserving myocardial fiber stress and wall shear stress in all four cardiac chambers. Briefly, the model used myocardial fiber stress to determine wall thickness and cardiac chamber wall shear stress to determine chamber volume. Aortic stenosis resulted in the development of concentric left ventricular hypertrophy. Aortic and mitral regurgitation resulted in eccentric remodeling and eccentric hypertrophy, with more pronounced hypertrophy for aortic regurgitation. Comparisons with published clinical data showed the same direction and similar magnitudes of changes in end-diastolic volume index and left ventricular diameters. Changes in myocardial wall volume and wall thickness were within a realistic range in both stenotic and regurgitant valvular disease. Simulations of remodeling in left-sided valvular disease support, in both a qualitative and quantitative manner, that left ventricular chamber size and hypertrophy are primarily determined by preservation of wall shear stress and myocardial fiber stress.

NEW & NOTEWORTHY Cardiovascular simulations with adaptive feedback that normalizes wall shear stress and fiber stress in the cardiac chambers could predict, in a quantitative and qualitative manner, remodeling patterns seen in patients with left-sided valvular disease. This highlights how mechanical stress remains a fundamental aspect of cardiac remodeling. This in silico study validated with clinical data paves the way for future patient-specific predictions of remodeling in valvular disease.
Oxygenation during general anesthesia and thoracic surgery in a patient with Titusville low-oxygen affinity hemoglobin
Authors: Scaravilli Vittorio , Polli Federico , Mendogni Paolo , Zanella Alberto , Graziadei Giovanna , Pesenti Antonio , Taccone Paolo
Published: February 2019

The purpose of this case study is to describe the physiological characteristics of a patient with the low-oxygen affinity Titusville hemoglobin variant. A 46-yr-old man with exertional dyspnea was diagnosed with a mediastinal lymphadenopathy of unknown origin and, to obtain definitive diagnosis by biopsy, underwent endobronchial ultrasound-guided transbronchial needle aspirate under sedation and video-assisted thoracoscopy under general anesthesia. High inspired fraction of oxygen ([Formula: see text]) was used to guarantee adequate oxygenation even during the one-lung ventilation needed for thoracoscopy. Following radial and pulmonary arterial catheterization, continuous mixed-venous oxygen saturation ([Formula: see text]), cardiac output, oxygen delivery (DO2), oxygen consumption (V̇o2), and oxygen extraction ratio (ERO2) were measured. Serial blood gas analyses were obtained at different [Formula: see text]. Anesthesia and surgery were carried out safely. Data obtained during the clinical case were utilized to 1) construct an in vivo Titusville hemoglobin dissociation curve and 2) describe oxygen delivery and consumption of a human with Titusville mutation. Titusville hemoglobin showed relatively high P50 (i.e., 30 vs. normal of 27) and very low cooperativity (Hill coefficient of 1.45 vs. normal 2.27), which was compensated in our patient by increases in cardiac output, rather than by augmenting oxygen extraction.
DV-Hop Node Location Algorithm Based on GSO in Wireless Sensor Networks
Authors: Song Ling , Zhao Liqin , Ye Jin
Published: February 2019

Node location is one of the most important problems to be solved in practical application of WSN. As a typical location algorithm without ranging, DV-Hop is widely used in node localization of wireless sensor networks. However, in the third phase of DV-Hop, a least square method is used to solve the nonlinear equations. Using this method to locate the unknown nodes will produce large coordinate errors, poor stability of positioning accuracy, low location coverage, and high energy consumption. An improved localization algorithm based on hybrid chaotic strategy (MGDV-Hop) is proposed in this paper. Firstly, a glowworm swarm optimization of hybrid chaotic strategy based on chaotic mutation and chaotic inertial weight updating (MC-GSO) is proposed. The MC-GSO algorithm is used to control the moving distance of each firefly by chaos mutation and chaotic inertial weight when the firefly falls into a local optimum. The experimental results show that MC-GSO has better convergence and higher accuracy and avoids the premature convergence. Then, MC-GSO is used to replace the least square method in estimating node coordinates to solve the problem that the localization accuracy of the DV-Hop algorithm is not high. By establishing the error fitness function, the linear solution of coordinates is transformed into a two-dimensional combinatorial optimization problem. The simulation results and analysis confirm that the improved algorithm (MGDV-Hop) reduces the average location error, increases the location coverage, and decreases and balances the energy consumption as compared to DV-Hop and the location algorithm based on classical GSO (GSDV-Hop).
Speed Simulation of Pig Restarting from Stoppage in Gas Pipeline
Authors: He Honggang , Liang Zheng
Published: February 2019

Pigging is a common operation in the oil and gas industry. Because of the compressibility of the gas, starting up a pipeline inspection gauge (pig) from a stoppage can generate a very high speed of the pig, which is dangerous to the pipe and the pig itself. Understanding the maximum speed a pig achieves in the restarting process would contribute to pig design and safe pigging. This paper presents the modeling of a pig restarting from a stoppage in gas pipeline. In the model, the transient equations of gas flow are solved by method of characteristics (MOC). Runge‐Kutta method is used for solving the pig speed equation. The process of a pig restarting from a stoppage in a horizontal gas pipe is simulated. The results indicate that the maximum speed a pig achieves from a stoppage is primarily determined by the pressure of the pipe and the pressure change caused by the obstructions. Furthermore, response surface methodology (RSM) is used to study the maximum speed of pig. An empirical formula is present to predict the maximum speed of a pig restarting from a stoppage in gas pipeline.
Coronary Artery Disease Is Associated with an Increased Amount of T Lymphocytes in Human Epicardial Adipose Tissue
Authors: Mráz Miloš , Cinkajzlová Anna , Kloučková Jana , Lacinová Zdeňka , Kratochvílová Helena , Lipš Michal , Pořízka Michal , Kopecký Petr , Pierzynová Aneta , Kučera Tomáš , Melenovský Vojtěch , Stříž Ilja , Lindner Jaroslav , Haluzík Martin
Published: February 2019

Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24±7.45 vs. 11.22±1.34%, p=0.025) with a similar trend observed in non-CAD subjects (29.68±7.61 vs. 10.13±2.01%, p=0.067). T (CD3+) cells were increased (75.33±2.18 vs. 65.24±4.49%, p=0.032) and CD3- cells decreased (21.17±2.26 vs. 31.64±4.40%, p=0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22±2.43 vs. 0.96±0.21%, p=0.039 for CAD and 12.49±5.83 vs. 1.16±0.19%, p=0.016 for non-CAD) and reduced natural killer (NK) cells (5.96±1.32 vs. 13.22±2.10%, p=0.012 for CAD and 5.32±1.97 vs. 13.81±2.72%, p=0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.
Wear Mechanism of Abrasive Gas Jet Erosion on a Rock and the Effect of Abrasive Hardness on It
Authors: Liu Yong , Zhang Huidong , Ranjith Pathegama Gamage , Wei Jianping , Liu Xiaotian
Published: February 2019

The existing erosion models of abrasive gas jet tend to neglect the effects of the rebounding abrasive. To address this shortcoming, abrasive wear tests were conducted on limestone by using an abrasive gas jet containing different types of particles and with different standoff distances. The results indicate that erosion pits have the shape of an inverted cone and a hemispherical bottom. An annular platform above the hemispherical bottom connects the bottom with the side of the pit. The primary cause of the peculiar pit shape is the flow field geometry of the gas jet with its entrained particles. There is an annular region between the axis and boundary of the abrasive gas jet, and it contains no abrasive. Particles swirling around the axis form a hemispherical bottom. After rebounding, the abrasive with the highest velocity enlarges the diameters of both the hemispherical bottom and erosion pit and induces the formation of an annular platform. The surface features of different areas of the erosion pit are characterized using a scanning electron microscope (SEM). It can be concluded that the failure modes for different locations are different. The failure is caused by an impact stress wave of the incident abrasive at the bottom. Plastic deformation is the primary failure mode induced by rebounding particles at the sides of the hemispherical bottom. The plastic deformation induced by the incident abrasive and fatigue failure induced by the rebounding abrasive are the primary failure modes on the annular platform. Fatigue failure induced by rebounding particles is the primary mode at the sides of the erosion pits. The rock failure mechanism that occurs for particles with different hardness is the same, but the rock damaged by the hard abrasive has a rougher surface.
Time Characteristics of the Influence Radius by Injecting N2 to Displace Coalbed Methane: A Case Study
Authors: Li-wei Chen , Tian-hong Yang , Hong-min Yang , Li-guo Wang
Published: February 2019

Injecting N2 to displace methane is an effective way to enhance coalbed methane drainage, and the influence radius of this process is an important factor in borehole arrangement. To determine reasonable spacing between injection boreholes and discharge boreholes, experimental and theoretical studies were carried out. The change of rule for the influence radius was determined based on the flow rate changes at the discharge boreholes when injecting gas into a coal seam in the field. Based on gas seepage-diffusion theory, a model for injecting N2 to displace coalbed methane was established. Through numerical simulation, the time characteristics of the influence radius were analyzed. The results show the following: Under different gas injection pressure conditions, the influence radius increases exponentially as injection time increases, but the rate of increase of the influence radius decreases gradually. For the same injection time, the higher the injection pressure, the wider the influence radius will be. After obtaining field results, regression analysis was applied to analyze the numerical results of gas injection at different pressures, and then, the quantitative relationship between the injection influence radius r, the injection time t, and the injection pressure p was found. According to the results calculated using this formula at an injection pressure of 0.5 MPa, the optimum spacing between boreholes was determined to be 1.5 m at the Shigang Coal Mine. The analysis of reasonable spacing between injection and extraction boreholes at different injection pressures shows that the reasonable spacing between boreholes was linearly correlated with gas injection pressures. This study has important theoretical and practical significance for the spacing between boreholes in a reasonable arrangement when injecting N2 to displace methane.
Persistent Idiopathic Facial Pain Associated with Somatoform Disorder in an 11-Year-Old Boy
Authors: Sakurai Yoshihiko , Fujii Asami , Kato Fumie
Published: February 2019

Persistent idiopathic facial pain (PIFP) is a poorly understood chronic disorder that rarely occurs in children. An 11-year-old boy initially presented with right cheek pain and a streptococcal infection 6 weeks previously. Facial cellulitis was suspected, which was resolved by antibiotic treatment. The right cheek pain recurred within 4 weeks of this initial visit. Because the antibiotic treatment did not relieve the pain, the patient visited our outpatient clinic. Physical examination revealed facial tenderness in an area that corresponded with the region supplied by the second branch of the trigeminal nerve (maxillary nerve), suggesting trigeminal neuralgia (TN). However, brain magnetic resonance imaging revealed no vascular compression. Furthermore, the continuous nagging and dull nature of the pain experienced by the patient differed from the sudden and severe nature of pain associated with TN. Subsequently, PIFP was diagnosed. The patient was unable to attend school because of prolonged lassitude, nausea, headache, and anorexia. Psychological counseling revealed psychological stress related to his out-of-school life. Upon learning stress management through psychotherapy, his general malaise gradually improved, and he was able to attend school with more facial expressions. This case indicates the psychogenic aspect of PIFP as well as the value of psychological counseling.
Crack Initiation Characteristics of Gas-Containing Coal under Gas Pressures
Authors: Yin Zhiqiang , Chen Zhiyu , Chang Jucai , Hu Zuxiang , Ma Haifeng , Feng Ruimin
Published: February 2019

In deep coal mines, coal before the working face is subjected to coupled high mining-induced stress and gas pressure. Such condition may facilitate crack formation and propagation in the coal seam, leading to serious coal and gas disasters. In this study, the mechanical properties (i.e., uniaxial compressive strength, tensile strength, and fracture toughness) of gas-containing coal with four levels of initial gas pressure (i.e., 0.0, 0.5, 1.0, and 1.5 MPa) were investigated by uniaxial compression, Brazilian disc, and notched semicircular bending loading test. A newly developed gas-sealing device and an RMT-150 rock mechanics testing machine were used. Fracture modes under different initial gas pressures were also determined. A theoretical method of fracture mechanics was used to analyze crack initiation characteristics under gas adsorption state. Results show that the uniaxial compressive strength, tensile strength, and fracture toughness of gas-containing coal decreased with increasing initial gas pressure. The tensional fracture occurred in gas-containing coal under uniaxial compressive loading with high gas pressure. Cracks in gas-containing coal propagated under small external loads due to the increase in effective stress of crack tip and decrease in cracking strength. This study provided evidence for modifications of the support design of working face in deep coal mines. Furthermore, the correlations between fracture toughness, compressive strength, and tensile strength of gas-containing coal were investigated.
Coenzyme Q10 Ameliorates Pancreatic Fibrosis via the ROS-Triggered mTOR Signaling Pathway
Authors: Xue Ran , Wang Jianxin , Yang Lixin , Liu Xinjuan , Gao Yan , Pang Yanhua , Wang Yanbin , Hao Jianyu
Published: February 2019

Aim. Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis. Any remedies that inhibit the activation of PSCs can be potential candidates for therapeutic strategies in pancreatic fibrosis-related pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Our study is aimed at exploring the protective effect of coenzyme Q10 (CoQ10) against pancreatic fibrosis. Methods. Pancreatic fibrosis was induced by 20% L-arginine (250 mg/100 g) at 1 h intervals twice per week for 8 weeks in C57BL/6 mice. CoQ10 was administered for 4 weeks. Isolated primary PSCs from C57BL/6 mice were treated with 100 μM CoQ10 for 72 h, as well as Rosup and specific inhibitors. The effects of CoQ10 on the activation of PSCs, autophagy, collagen deposition, histological changes, and oxidative stress were analyzed by western blotting, biochemical estimations, immunofluorescence staining, and hematoxylin-eosin, Masson, and Sirius red staining, as well as with a reactive oxygen species (ROS) assay. Results. Pretreatment and posttreatment of CoQ10 decreased autophagy, activation of PSCs, oxidative stress, histological changes, and collagen deposition in the CP mouse model. In primary PSCs, expression levels of p-PI3K, p-AKT, and p-mTOR were upregulated with CoQ10. A rescue experiment using specific inhibitors of the PI3K-AKT-mTOR pathway demonstrated that the PI3K-AKT-mTOR signaling pathway was the underlying mechanism by which CoQ10 ameliorated fibrosis. With the addition of Rosup, expression levels of the autophagy biomarkers LC3 and Atg5 were elevated. Meanwhile, the levels of p-PI3K, p-AKT, and p-mTOR were lower. Conclusions. Our findings demonstrated that CoQ10 alleviates pancreatic fibrosis by the ROS-triggered PI3K/AKT/mTOR signaling pathway. CoQ10 may be a therapeutic candidate for antifibrotic methods.
Uniaxial Compression Creep Relaxation and Grading of Coal Samples via Tests on the Progressive Failure Characteristics
Authors: Xiong Zuqiang , Song Changsheng , Su Chengdong , Wang Xiaolei , Wang Cheng , Hao Yu
Published: February 2019

An RMT-150B electrohydraulic servo testing system was used to perform uniaxial compression and uniaxial grading relaxation (creep) tests. The deformation, strength, and failure characteristics of the progressive failure process of coal samples under three loading modes were analyzed. The analysis results show that the prepeak stress-strain curve of the coal samples and the load relationships are not clear and that the whole compression process of coal still showed compression, elastic, yielding, and failure stages. The local stress drop characteristics during our relaxation creep grading tests showed no clear peak value and showed a yield curve with the shape of a conventional single plateau. The values of the mechanical parameters of axial compression were significantly higher than those obtained in the grade relaxation (creep) tests, which showed the mechanical parameters of coal samples with aging characteristics. In the relaxation (creep) tests, when the stress ratio was less than 70%, the relaxation (creep) characteristics of the sample were not clear. When the ratio of stress relaxation (creep) was more than 70% in the relaxation (creep) tests during displacement (stress) with a constant relaxation (creep) over the duration of the test, the evolution, development, and convergence of microcracks in the coal samples were observed. Relaxation (creep) stress was higher, failure duration was shorter, and the duration of failure was longer. For fully mechanized coal faces, increasing the support resistance and timely moving the support after coal cutting may prevent rib spalling accidents by reducing coal stress and exposure time in the front of the working face. Additionally, routine uniaxial compressive failures showed a simple form, having a clear tension-shear dual rupture surface. The staged relaxation creep failure testing of coal is more complex. The entire coal samples were divided into many thin-sheet debris via gradual collapse and shedding, and the number of cracks increased significantly, showing evident lateral expansion characteristics that are similar to the rib spalling characteristics in high coal mining working faces.
Noncommutativity in Effective Loop Quantum Cosmology
Authors: Espinoza-García Abraham , Torres-Lomas Efraín , Pérez-Payán Sinuhé , Díaz-Barrón Luis Rey
Published: February 2019

We construct a noncommutative extension of the Loop Quantum Cosmology effective scheme for the flat FLRW model with a free scalar field via a theta deformation. Firstly, a deformation is implemented in the configuration sector, among the holonomy variable and the matter degree of freedom. We show that this type of noncommutativity retains, to some degree, key features of the Loop Quantum Cosmology paradigm for a free field. Secondly, a deformation is implemented in the momentum sector, among the momentum associated with the holonomy variable and the momentum associated with the matter field. We show that in this latter case the scalar field energy density is the same as the one in standard Loop Quantum Cosmology.
Anodic Titanium Oxide Layers Modified with Gold, Silver, and Copper Nanoparticles
Authors: Syrek Karolina , Grudzień Joanna , Sennik-Kubiec Aneta , Brudzisz Anna , Sulka Grzegorz D.
Published: February 2019

Titanium(IV) oxide is commonly used in photocatalysis. However, it has some drawbacks, e.g., a high rate of electron-hole recombination and a wide bandgap. In here, the surface of anodic titanium(IV) oxide (ATO) was modified with metal nanoparticles (gold, silver, and copper) in order to enhance its photoelectrochemical (PEC) and photocatalytic (PC) properties. SEM analysis revealed that Au, Ag, and Cu nanoparticles obtained on an ATO surface by chemical methods had an average diameter of 50 ± 10 nm, 30 ± 6 nm, and 25 ± 3 nm, respectively. Enhancement of photoelectrochemical water-splitting current efficiency in the wavelength range of 300–400 nm was observed due to the occurrence of the Schottky barriers. However, the nanoparticles had no effect on the current efficiency in the range of 400–600 nm which meant that the surface plasmon resonance (SPR) effect was not observed. A rate of methyl red photodecomposition was improved after the modification of the ATO surface. The best results were obtained for ATO decorated with gold nanoparticles.
Spatiotemporal Distributions and Dynamics of Human Infections with the A H7N9 Avian Influenza Virus
Authors: Chen Yongxue , Wen Yongxian
Published: February 2019

In 2013 in mainland China, a novel avian influenza virus H7N9 began to infect humans and had aroused severe fatality in the infected humans, followed by the annual outbreaks. By methods of GIS and kriging interpolation, we get the geographical distributions. We obtain the longitudinal characteristics of these outbreaks based on statistics and diagrams. After these spatiotemporal distributions, an eco-epidemiological model is established and analyzed. In this model, the general incidence functions, the factor of fully killed infected poultry, and the virus in environment are taken into account. Theoretical analysis shows that the endemic will be formed to a large extent once the H7N9 avian influenza virus exists in poultry. On the basis of dynamics, we explore the possible disease control measures by numerical simulations. Simulations indicate that measures of vaccination in poultry and stopping live poultry transactions are the primary choices for disease control in humans, and strengthened inhibition effects and environmental disinfections can effectively control the outbreak.
The Impact of Early Neuroimaging and Developmental Assessment in a Preterm Infant Diagnosed with Cerebral Palsy
Authors: Gullion Lily , Stansell Jennifer , Moss Hunter , Jenkins Dorothea , Aljuhani Turki , Coker-Bolt Patty
Published: February 2019

Premature infants are at risk for cerebral palsy (CP) that is typically diagnosed between 18–24 months. We present a case study of an infant who was discharged from the neonatal intensive care unit (NICU) without obvious neurological deficits but was later diagnosed with hemiplegic CP. The infant was enrolled in an infant motor study, which included neuroimaging and developmental motor assessments. At term, anatomical MRI showed bilateral periventricular leukomalacia, abnormal brain metabolites in frontal white matter via MR spectroscopy (MRS), and low fractional anisotropy (FA) values obtained from diffusional kurtosis imaging (DKI) in several cortical white matter tracts compared to a group of typically developing infants without neuroimaging abnormalities. In addition, the infant scored below average on a developmental assessment administered at term and three months as well as on the standard Bayley III assessment at 12 months. Abnormal neuroimaging and low scores on the early developmental assessment prompted referral for intervention services at two months. With intensive therapy, by 45 months, the infant was average in self-care, mobility, and communication skills, although below average in visual motor and gross motor coordination. This case highlights the clinical impact of early detection and referral using combined neuroimaging and developmental testing.
Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC
Authors: Wu Lianpin , Yi Baozhu , Wei Shi , Rao Dapeng , He Youhua , Naik Gurudatta , Bae Sejong , Liu Xiaoguang M. , Yang Wei-Hsiung , Sonpavde Guru , Liu Runhua , Wang Lizhong
Published: February 2019

Although c-MYC and mTOR are frequently activated proteins in prostate cancer, any interaction between the two is largely untested. Here, we characterize the functional cross-talk between FOXP3–c-MYC and TSC1–mTOR signaling during tumor progression. Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells. Conversely, inhibition of mTOR increased pT58 but decreased pS62. Loss of both FOXP3 and TSC1 in prostate cancer cells synergistically enhanced c-MYC expression via regulation of c-Myc transcription and protein phosphorylation. This crosstalk between FOXP3 and TSC1 appeared to be mediated by both the mTOR–4EBP1–c-MYC and FOXP3–c-MYC pathways. In mice, Tsc1 and Foxp3 double deletions in the prostate led to prostate carcinomas at an early age; this did not occur in these mice with an added c-Myc deletion. In addition, we observed synergistic antitumor effects of cotreating mice with inhibitors of mTOR and c-MYC in prostate cancer cells and in Foxp3 and Tsc1 double-mutant mice. In human prostate cancer, loss of nuclear FOXP3 is often accompanied by low expression of TSC1. Because loss of FOXP3 transcriptionally induces c-Myc expression and loss of TSC1 activates mTOR signaling, these data suggest cross-talk between FOXP3–c-MYC and TSC1–mTOR signaling that converges on c-MYC to regulate tumor progression. Coadministration of c-MYC and mTOR inhibitors may overcome the resistance to mTOR inhibition commonly observed in prostate cancer cells.

Significance:

These results establish the principle of a synergistic action of TSC1 and FOXP3 during prostate cancer progression and provide new therapeutic targets for patients who have prostate cancer with two signaling defects.
Spleen Tyrosine Kinase–Mediated Autophagy Is Required for Epithelial–Mesenchymal Plasticity and Metastasis in Breast Cancer
Authors: Shinde Aparna , Hardy Shana D. , Kim Dongwook , Akhand Saeed Salehin , Jolly Mohit Kumar , Wang Wen-Hung , Anderson Joshua C. , Khodadadi Ryan B. , Brown Wells S. , George Jason T. , Liu Sheng , Wan Jun , Levine Herbert , Willey Christopher D. , Krusemark Casey J. , Geahlen Robert L. , Wendt Michael K.
Published: February 2019

The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states contributes to their metastatic potential. Therefore, driving tumor cells into a stable mesenchymal state, as opposed to complete tumor cell eradication, presents an opportunity to pharmacologically limit disease progression by promoting an asymptomatic state of dormancy. Here, we compare a reversible model of epithelial–mesenchymal transition (EMT) induced by TGFβ to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor lapatinib. Only cells capable of returning to an epithelial phenotype resulted in skeletal metastasis. Gene expression analyses of the two mesenchymal states indicated similar transition expression profiles. A potently downregulated gene in both datasets was spleen tyrosine kinase (SYK). In contrast to this similar diminution in mRNA, kinome analyses using a peptide array and DNA-conjugated peptide substrates showed a robust increase in SYK activity upon TGFβ-induced EMT only. SYK was present in cytoplasmic RNA processing depots known as P-bodies formed during the onset of EMT, and SYK activity was required for autophagy-mediated clearance of P-bodies during mesenchymal–epithelial transition (MET). Genetic knockout of autophagy-related 7 (ATG7) or pharmacologic inhibition of SYK activity with fostamatinib, a clinically approved inhibitor of SYK, prevented P-body clearance and MET, inhibiting metastatic tumor outgrowth. Overall, this study suggests assessment of SYK activity as a biomarker for metastatic disease and the use of fostamatinib as a means to stabilize the latency of disseminated tumor cells.

Significance:

These findings present inhibition of spleen tyrosine kinase as a therapeutic option to limit breast cancer metastasis by promoting systemic tumor dormancy.

See related commentary by Farrington and Narla, p. 1756
Cancer Health Impact Program (CHIP): Identifying Social and Demographic Associations of mHealth Access and Cancer Screening Behaviors Among Brooklyn, New York, Residents
Authors: Camacho-Rivera Marlene , Rice Samuel L. , Oh Sehyun , Paris Manuel , Akpara Ezinne , Molina Justen , Obadina Michael , Mcmillan Shireene , Aracena Joshua L. Mendez , Morency Jason , Muniz Rosario Costas , Gany Francesca , Brown Carol L. , Gonsky Jason , Osborne Joseph R.
Published: February 2019

Background:

The Bedford-Stuyvesant (BS) and Bushwick (BW) communities of central Brooklyn, New York, are located within the 50-mile core radius of Memorial Sloan Kettering's main catchment area. Cancer is the second leading cause of death among the predominantly African American and Hispanic neighborhoods, with BS and BW having higher prostate cancer and colorectal mortality rates than New York City as a whole. There is significant opportunity to design cancer interventions that leverage the accessibility and acceptability of mobile health (mHealth) tools among the BS and BW communities.

Methods:

The Cancer Health Impact Program (CHIP) is a collaborative that was formed for this purpose. Through CHIP, we used a tablet-based, Health Information National Trends (HINTS)-based multimodality survey to collect and analyze social and demographic patterns of prostate cancer and colorectal cancer screening, as well as mHealth access, among BS and BW residents.

Results:

Among 783 participants, 77% reported having a smartphone, 40% reported access to a mobile health application, 17% reported blood stool kit testing, and 26% of men reported PSA test screening. Multivariable logistic regression models results demonstrated that participants who reported owning smartphones, but were unsure whether they had access to a health app, were also significantly more likely to report blood stool kit testing compared with participants without smartphones. In fully adjusted models, access to a health app was not significantly associated with PSA testing. Non-Hispanic white participants were 86% less likely to report blood stool kit testing when compared with non-Hispanic black participants [OR = 0.15; 95% confidence interval (CI) 0.02–0.49]. Participants with a prior history of cancer were three times more likely to report blood stool kit testing when compared with those without cancer history (OR = 3.18; 95% CI, 1.55–6.63).

Conclusions:

For blood stool kit testing, significant differences were observed by race/ethnicity, cancer history, age, and smartphone use; for PSA screening, only age was significant in fully adjusted models.

Impact:

Our results demonstrate that while access to smartphones and mobile health apps may be prevalent among minority communities, other social and demographic characteristics are more likely to influence screening behaviors.
The Microbiome in Lung Cancer Tissue and Recurrence-Free Survival
Authors: Peters Brandilyn A. , Hayes Richard B. , Goparaju Chandra , Reid Christopher , Pass Harvey I. , Ahn Jiyoung
Published: February 2019

Background:

Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been studied.

Methods:

In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 patients with non–small cell lung cancer (NSCLC). We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free (RFS) and disease-free survival (DFS), and compared microbiome diversity and composition between paired tumor and normal samples.

Results:

Higher richness and diversity in normal tissue were associated with reduced RFS (richness P = 0.08, Shannon index P = 0.03) and DFS (richness P = 0.03, Shannon index P = 0.02), as was normal tissue overall microbiome composition (Bray–Curtis P = 0.09 for RFS and P = 0.02 for DFS). In normal tissue, greater abundance of family Koribacteraceae was associated with increased RFS and DFS, whereas greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced RFS or DFS (P < 0.05). Tumor tissue diversity and overall composition were not associated with RFS or DFS. Tumor tissue had lower richness and diversity (P ≤ 0.0001) than paired normal tissue, though overall microbiome composition did not differ between the paired samples.

Conclusions:

We demonstrate, for the first time, a potential relationship between the normal lung microbiota and lung cancer prognosis, which requires confirmation in a larger study.

Impact:

Definition of bacterial biomarkers of prognosis may lead to improved survival outcomes for patients with lung cancer.
C8orf76 Promotes Gastric Tumorigenicity and Metastasis by Directly Inducing lncRNA DUSP5P1 and Associates with Patient Outcomes
Authors: Wang Xiaohong , Liang Qiaoyi , Zhang Lianhai , Gou Hongyan , Li Ziyu , Chen Huarong , Dong Yujuan , Ji Jiafu , Yu Jun
Published: February 2019

Purpose:

We identified for the first time that C8orf76 (chromosome 8 open reading frame 76) is preferentially amplified in gastric cancer. We elucidated its role and clinical significance in gastric carcinogenesis.

Experimental Design:

The clinical impact of C8orf76 was assessed in 592 patients with gastric cancer. The biological function of C8orf76 was studied in vitro, in vivo, and in gastric cancer patient-derived organoid models. C8orf76 downstream effector and pathways were identified by RNA sequencing, chromatin immunoprecipitation sequencing, luciferase reporter, and electrophoretic mobility shift assay.

Results:

C8orf76 was upregulated in 69.74% and 65.71% of two independent cohorts of gastric cancers and was positively associated with C8orf76 amplification. Multivariate analysis showed that gastric cancer patients with C8orf76 amplification (cohort I, n = 129; cohort II, n = 107) or overexpression (n = 356) had a significantly shortened survival. C8orf76 significantly promoted gastric cancer cell proliferation, cell-cycle transformation, and migration/invasion, but suppressed cell apoptosis. Silencing C8orf76 expression exerted opposite effects in vitro and significantly inhibited xenograft tumor growth, lung metastasis, and liver metastasis in nude mice. Silencing C8orf76 also significantly suppressed the growth of patient-derived organoids. Mechanically, C8orf76 activated MAPK/ERK signaling cascade. C8orf76 directly bound to the promoter region of lncRNA dual specificity phosphatase 5 pseudogene 1 (DUSP5P1) with a binding motif of AGGCTG and activated DUSP5P1 transcription. DUSP5P1 induced MAPK/ERK signaling and promoted gastric tumorigenesis. Knockdown DUSP5P1 abrogated the effect of C8orf76 in activating MAPK/ERK cascade and the tumor-promoting function.

Conclusions:

C8orf76 directly binds to oncogenic lncRNA DUSP5P1 to induce its expression and activates MAPK signaling. C8orf76 plays a pivotal oncogenic role in gastric carcinogenesis and is an independent prognostic factor for gastric cancer patients.
A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2–Positive Metastatic Breast Cancer
Authors: Lok Sheau W. , Whittle James R. , Vaillant François , Teh Charis E. , Lo Louisa L. , Policheni Antonia N. , Bergin Alice R.T. , Desai Jayesh , Ftouni Sarah , Gandolfo Luke C. , Liew Danny , Liu He K. , Mann G. Bruce , Moodie Kate , Murugasu Anand , Pal Bhupinder , Roberts Andrew W. , Rosenthal Mark A. , Shackleton Kylie , Silva Maria João , Siow Zhen R. , Smyth Gordon K. , Taylor Leanne , Travers Avraham , Yeo Belinda , Yeung Miriam M. , Bujak Andjelija Zivanovic , Dawson Sarah-Jane , Gray Daniel H.D. , Visvader Jane E. , Lindeman Geoffrey J.
Published: February 2019

Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0–8) were treated with daily tamoxifen (20 mg) and venetoclax (200–800 mg). Apart from uncomplicated “on-target” lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and the clinical benefit rate was 75%. Treatment responses were preempted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations.

Significance:

In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors.

See related commentary by Drago et al., p. 323.

This article is highlighted in the In This Issue feature, p. 305
Comparison of the Efficacy of Holmium Laser Enucleation of the Prostate in Treating Prostate Volumes of ≤80 and > 80 mL
Authors: Gazel Eymen , Kaya Engin , Yalcin Serdar , Aybal Halil Çagri , Aydogan Tahsin Batuhan , Tunc Lutfi
Published: February 2019

Introduction: Holmium laser enucleation of the prostate (HoLEP) is becoming the new standard procedure for treating benign prostatic hyperplasia (BPH), a common condition in aging men. Most studies have focused on proving its efficacy in treating large prostates. In this study, we compared its efficacy in treating small (< 80 mL) and large (> 80 mL) prostates. Methods: This prospective study included 119 patients with BPH who underwent HoLEP by the same surgeon between June 2015 and December 2017. They were divided into 2 groups according to their prostate volumes (≤80 mL: Group 1; > 80 mL: Group 2). Various pre- and postoperative parameters were compared within and between the groups. Results: International Prostate Symptom Score (IPSS), postvoid residual (PVR) volume, and voiding time (VT) significantly decreased, and the peak urinary flow rate (Qmax), average urinary flow rate (Qave), and quality of life (QoL) score significantly increased postoperatively in both groups. The postoperative changes in IPSS, QoL score, Qmax, Qave, VT, PVR volume, and hemoglobin levels were not significantly different between the groups. In addition, no significant difference was observed in postoperative complications between the groups. Conclusions: Our results indicate that HoLEP is an effective procedure for treating both small and large prostates.
An Evaluation of the Effect of Vision on Standing Stability in the Early Stage of Parkinson’s Disease
Authors: Mirahmadi Mina , Karimi Mohammad Taghi , Esrafilian Amir
Published: February 2019

Background: Postural instability is a common disorder in Parkinson’s disease (PD). The aim of this study was to evaluate stance stability of the subjects at the early stage of PD with both linear and nonlinear approaches. Moreover, this study aimed to find the effect of visual control on quiet stance postural control in these patients. Method: Seventeen PD patients (Hoehn/Yahr scale: 1) and 17 healthy control subjects were instructed to maintain quiet postural stance in 2 conditions (opened eyes and closed eyes). Four linear (excursion, path length, velocity, root mean square) and 1 nonlinear (approximate entropy) center of pressure (COP) parameters were calculated. A 2 × 2 mixed ANOVA was used for the final analysis. Results: Although there was no difference between the stability of PD patients and healthy control subjects based on excursion of COP in both mediolateral (ML) and anteroposterior (AP) directions, other linear parameters (path length of COP sways, velocity of COP sways, and root mean square in both ML and AP planes) showed that PD patients were significantly unstable compared to normal subjects (p value < 0.05). Vision influenced the stability of both groups significantly. The interaction of vision and group was not significant based on linear and nonlinear stability parameters. Conclusion: Although patients in the early stage of PD seem to be unstable based on COP linear measures, their postural control system is still flexible to adapt to environmental perturbations in quiet stance and they are not more visually dependent than healthy subjects to control stability in this position.
Association Between Fatty Acids of Blood Cell Membranes and Incidence of Coronary Heart Disease
Authors: Papandreou Christopher , Sala-Vila Aleix , Galié Serena , Muralidharan Jananee , Estruch Ramón , Fitó Montserrat , Razquin Cristina , Corella Dolores , Ros Emilio , Timiraos Juan , Lapetra Jose , Serra-Majem Lluis , Carlos Silvia , Castañer Olga , Asensio Eva M. , Salas-Salvadó Jordi , Bulló Mònica
Published: February 2019

Objective—

To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk.

Approach and Results—

This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. After adjustment for classical CHD risk factors and multiple testing, 1 SD increase in baseline levels of C22:0, C24:0 and the sum of individual very long chain saturated fatty acids was associated with 56% (OR, 0.44 [95% CI, 0.28–0.69]), 59% (OR, 0.41 [95% CI, 0.25–0.65]), and 55% (OR, 0.45 [95% CI, 0.29–0.70]) a decreased odds of developing CHD, respectively. Baseline C20:1n9 was associated with higher odds of CHD (OR, 1.58 [95% CI, 1.25–2.00]).

Conclusions—

Higher levels of C22:0 and C24:0 were associated with a lower CHD incidence, whereas higher levels of C20:1n9 were associated with a higher risk. This study adds to the growing body of evidence suggesting potential differences in the cardiovascular disease effects of different types of circulating saturated fatty acids.
Aplysina Nardo (Porifera, Verongida, Aplysinidae) from the Brazilian coast with description of eight new species
Authors: PINHEIRO ULISSES DOS S. , HAJDU EDUARDO , CUSTÓDIO MÁRCIO R.
Published: February 2019

A revision of Brazilian Aplysina was conducted based on morphological study of species alive as well as preserved in the collections of Museu Nacional. In total, 190 specimens were studied in the lab. Identification was achieved by analysis of the external morphology, in combination with skeletal architecture and its components. Our analyses revealed marked within individual variation for most species in characters associated to the spongin fibres, suggesting a low diagnostic strength for this set of characters in Aplysina. External morphology, on the other hand, permitted clearcut diagnoses for most species. Fifteen species were identified and are fully described below. Eight of these are new to science. A neotype for A. fulva is proposed here. The amended list of Aplysina species for the Brazilian coast is: A. alcicornis sp.n., A. caissara, A. cauliformis, A. cristagallus sp.n, A. fistularis, A. fulva, A. insularis, A. lacunosa, A. lactuca sp.n., A. lingua sp.n., A. muricyana sp.n., A. orthoreticulata sp.n., A. pergamentacea, A. pseudolacunosa sp.n. and A. solangeae sp.n. A tentative identification key for these species is provided.