bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous glucose monitoring in older people with diabetes and memory problems: a mixed-methods feasibility study in the UK
Authors: Mattishent Katharina , Lane Kathleen , Salter Charlotte , Dhatariya Ketan , May Helen M , Neupane Sankalpa , Loke Yoon K
Published: November 2019

Objectives

Older people with diabetes are at increased risk of harm from hypoglycaemia, particularly where there are coexisting memory problems. Continuous glucose monitoring (CGM) offers important benefits in terms of detecting hypoglycaemia, but the feasibility of use and extent of data capture has not been tested in this patient group. Our objective was to investigate the feasibility of trialling a CGM intervention in the community setting in older people with diabetes and memory problems.

Design

Mixed-methods feasibility study.

Setting

Community dwellings in the UK.

Participants

Patients aged ≥65 with diabetes and abbreviated mental test score ≤8 or known dementia.

Intervention

FreeStyle Libre CGM.

Primary and secondary outcome measures

Feasibility criteria were numbers of eligible patients, recruitment, attrition, extent of capture of glucose readings and adverse events. Qualitative interview.

Results

We identified 49 eligible participants; 17 consented, but 5 withdrew before recording of data because they or their carers felt unable to manage study procedures. 12 participants (mean age 85 years) completed the study without adverse events. Data capture across 14 days ranged between 3% and 92% (mean 55%); 6 participants had <60% capture. Hypoglycaemic events were recorded in six out of nine insulin users. Qualitative interviews found: the device does not interfere with daily activities, usability and comfort was positive, and it was helpful for carers in monitoring participants’ glucose concentrations.

Conclusions

The device was acceptable to participants, and carers reported greater ease in monitoring the participant’s glucose concentrations. However, completeness of data capture varied considerably with this device due to the need for users to conduct ≥3 scans per day. Real-time devices with automated data transfer may be more suitable in older people with memory problems.
Mechanical thrombectomy in acute ischemic stroke patients under venoarterial extracorporeal membrane oxygenation
Authors: Le Guennec Loic , Schmidt Matthieu , Clarençon Frédéric , Elhfnawy Ahmed Mohamed , Baronnet Flore , Kalamarides Michel , Lebreton Guillaume , Luyt Charles-Edouard
Published: November 2019

Background

Use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adult patients to treat refractory cardiogenic shock has increased in recent years, and ischemic stroke is the most frequent VA-ECMO-induced cerebrovascular complication. No adult case of mechanical thrombectomy (MT) has been reported.

Methods

Retrospective observational study of hospital medical records of patients who received circulatory support with VA-ECMO with acute ischemic stroke treated with MT, from 2006 to 2018.

Results

Two adult patients on VA-ECMO with acute ischemic stroke treated with MT were found. Both cases were successfully treated.

Conclusion

These cases illustrate the feasibility of performing MT in adult patients on ECMO.
MiR-539 inhibits the malignant behavior of breast cancer cells by targeting SP1
Authors: Cai Fenglin , Chen Luhong , Sun Yuting , He Chunlan , Fu Deyuan , Tang Jinhai
Published: November 2019

The aberrant expression of microRNAs (miRNAs) is involved in the initiation and progression of human cancers. In our study, we found that miR-539 was down-regulated in breast cancer tissues and cell lines. Decreased expression of miR-539 was significantly associated with lymph node metastasis in patients with breast cancer. Overexpression of miR-539 inhibited the proliferation and promoted apoptosis of breast cancer cells. Moreover, highly expressed miR-539 significantly suppressed the epithelial–mesenchymal transition (EMT) and sensitized cells to cisplatin treatment. Mechanistically, miR-539 was found to target the specificity protein 1 (SP1) and down-regulated the expression of SP1 in breast cancer cells. Knockdown of miR-539 consistently increased the expression of SP1. The expression of miR-539 in breast cancer tissues was negatively correlated with the expression of SP1. Restoration of SP1 significantly attenuated the inhibitory effect of miR-539 on the proliferation of breast cancer cells. Taken together, our results indicate that miR-539 has a tumor suppressive role in breast cancer via targeting SP1, suggesting miR-539 as a promising target for the diagnosis of breast cancer.
Alien species stabilize local fisheries catch in a highly invaded ecosystem
Authors: van Rijn Itai , Kiflawi Moshe , Belmaker Jonathan
Published: November 2019

Alien species may be a valuable resource for marine fisheries, yet their contribution to the catch might be balanced by negative effects on indigenous species. In this study, we explored a unique high-resolution time series of catch data from a highly invaded ecosystem in the eastern Mediterranean. We analyzed over 5000 fishing hauls digitalizing from fishers’ logbooks. We found that the catch per unit effort (CPUE) of alien species increased over time, while for indigenous species, CPUE remained relatively stable between 1996 and 2013. This suggests a lack of competitive exclusion of indigenous target species due to the proliferation of alien species. From the perspective of the fishers’ revenues, alien species gradually became a more important part of the catch, while overall fishers’ revenues showed temporal stability. This was the combined result of alien species increasing CPUE and fishers shifting their effort toward shallower water where alien species were dominant. Our findings demonstrate that alien species can become a valuable resource for a local fishing industry with little effect on indigenous species, which is highly relevant to worldwide fisheries experiencing range redistribution of commercial species.
Using portfolio theory in spatial targeting of forest carbon payments: an effective strategy to address spatiotemporal variation in land-use opportunity costs?
Authors: Sharma Bijay P. , Cho Seong-Hoon
Published: November 2019

The objective of our research is to extend current conservation applications of modern portfolio theory (MPT) to develop a framework for the cost-efficient budget distribution for a forest carbon payment program that optimizes risk–reward trade-offs in the presence of economic growth uncertainty over time. We consider correlation across space and time of the fluctuating opportunity costs of restoring forestland under changing future economic conditions using a case study of eight states in the central and southern Appalachian region of the United States. The findings suggest that optimal budget allocation decisions that ignore the covariance component of the spatial variance–covariance structure of forest carbon returns fail to minimize the true risk of conservation investment for any level of expected return. The importance of incorporating the spatial covariance in targeting conservation payments is made explicit through alternative approaches using multi-objective (mean–variance) optimization and an ex post analysis with and without the covariance component of the spatial variance–covariance structure of forest carbon return on investment (ROI). A comparison of these approaches against our MPT-based approach revealed misleading risk–return expectations if the ROI covariance is ignored in the spatial targeting of forest carbon payments under uncertainty.
Study of soil particles containing radioactive cesium in paddy field soil using an energy-dispersive X-ray spectroscopy and autoradiogram method
Authors: Ohnuma Tohru , Ishii Keizo
Published: November 2019

The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011 caused the widespread contamination of Fukushima Prefecture by radioactive cesium. The cesium radioisotopes are considered to have remained in the soil for seven years. We investigated this situation by analyzing soil from paddy fields in the area. We investigated the structure of soil particles using scanning electron microscopy–energy dispersive X-ray spectroscopy (SEM–EDS) and autoradiogram (ARG). We estimated the percentage of clay in the soil based on its composition, and then obtained the radioactivity of the cesium radioisotopes for each soil particle size as a function of penetration. The cesium radioisotopes were exponentially distributed in soil containing a large proportion of clay. Hence, we confirmed that the quantity of clay in the soil is a very important factor with respect to the possibility of the resumption of agriculture in the restricted area.
DFT-focused estimation of mechanical, thermoelectric and thermodynamic properties of ACdF3(A=K, Rb, Cs) fluroperovskites
Authors: Abraham Jisha Annie
Published: November 2019

Structural, electronic, mechanical, thermodynamic and thermoelectric properties of Alkaline fluroperovskites ACdF3(A[Formula: see text]=[Formula: see text]K, Rb, Cs) have been explored using the FP-LAPW method from the perspective of density functional theory (DFT) as employed in the Wien2k package within the generalized gradient approximation (GGA) as well as the local spin density approximation (LSDA). The volume optimization calculations of these materials agree well with experimental as well as available theoretical values. From the energy dispersion curves as well as DOS plots, all the investigated alkali fluroperovskites are found to have an indirect bandgap in [Formula: see text]-M direction using both approximations. The second-order elastic constants as well as mechanical properties such as Young’s modulus, shear modulus, density, anisotropic factor, B/G[Formula: see text] ratio are also computed for these materials. In order to study the thermal and vibrational effects on the studied fluroperovskites, we have employed the quasi-harmonic Debye model that uses a set of energy versus volume calculations. The effects of temperature as well as pressure on the structural parameters are also studied using the non-equilibrium Gibbs function. The transport properties of these perovskites have been investigated using BoltzTrap Code. Comparatively, a good figure of merit of these compounds reveals their possible use in thermoelectric applications.
Thermodynamical properties of bosons and fermions for a lattice motivated dispersion relationship
Authors: Güner Metin , Arik Metin
Published: November 2019

In this paper we calculate the basic thermodynamical quantities for a system of bosonic simple harmonic oscillators (BSHOs) and the corresponding system of fermionic simple harmonic oscillators (FSHOs) using a dispersion relationship similar to cases in general relativity and condensed matter physics. In the FSHO, we see negative temperatures, and in both cases we obtain finally a system of oscillators with only one effective frequency of vibration. Also we see that pressure is less than zero for T[Formula: see text][Formula: see text][Formula: see text]Tc where Tc is the critical temperature for bosons.
Robust Hyperbolic Chaos in Froude Pendulum with Delayed Feedback and Periodic Braking
Authors: Kuznetsov Sergey P. , Sedova Yuliya V.
Published: November 2019

We indicate a possibility of implementing hyperbolic chaos using a Froude pendulum that is able to produce self-oscillations due to the suspension on a shaft rotating at constant angular velocity, in the presence of time-delay feedback and of periodic braking by the application of additional frictional force. We formulate a mathematical model and carry out its numerical research. In the parameter space we reveal areas of chaotic and regular dynamics using the analysis of Lyapunov exponents and some other diagnostic tools. It is shown that there are regions in the parameter space where the Poincaré stroboscopic map has an attractor, which is a kind of Smale–Williams solenoid embedded in the infinite-dimensional state space. We confirm the hyperbolicity of the attractor by numerical calculations including the analysis of angles of intersections of stable and unstable invariant subspaces of vectors of small perturbations for trajectories on the attractor and verify the absence of tangencies between these subspaces.
Hybrid Methods for Studying Stability and Bifurcations in Delayed Feedback Systems
Authors: Itovich Griselda R. , Gentile Franco S. , Moiola Jorge L.
Published: November 2019

The dynamics of two related models of second order delay differential equations with four bifurcating parameters are analyzed. Through a classical technique in the time domain which involves the location of the roots of an exponential polynomial equation, the areas of stability of the equilibrium are set. A frequency-domain methodology is applied to study the Hopf bifurcation phenomena and to describe the behavior of the emerging cycles completely via a feedback system approach. Certain types of singularities, which provoke fold bifurcations of cycles are detected precisely. Also, a complete picture of parameter configurations to produce resonances is established for both models. All results are checked with the software DDE-Biftool.
Effects of Initial Conditions and Circuit Parameters on the SBT-Memristor-Based Chaotic Circuit
Authors: Dou Gang , Duan Huaying , Yang Wenyan , Yang Hai , Guo Mei , Li Yuxia
Published: November 2019

In the paper, a fourth-order SBT-memristor-based chaotic system described by the flux-controlled model is investigated. The stability of the chaotic system is analyzed, and the effects of initial conditions and circuit parameters on the SBT-memristor-based chaotic circuit are discussed by mathematical methods of Lyapunov exponents spectra, bifurcation diagrams, phase orbits and Poincaré maps. Through simulations, it is observed that the dynamical characteristics vary with initial states and circuit parameters. Complex dynamical behaviors such as stable points, period cycles and chaos can be found in the SBT-memristor-based system. It is also found that the system exhibits multistability, which is closely dependent on the initial state of the SBT memristor. This study provides insightful guidance for the design and analysis of memristor-based circuits towards potential real applications.
Undirected Zero-Divisor Graphs and Unique Product Monoid Rings
Authors: Hashemi Ebrahim , Alhevaz Abdollah
Published: November 2019

Let R be an associative ring with identity and Z*(R) be its set of non-zero zero-divisors. The undirected zero-divisor graph of R, denoted by Γ(R), is the graph whose vertices are the non-zero zero-divisors of R, and where two distinct vertices r and s are adjacent if and only if rs = 0 or sr = 0. The distance between vertices a and b is the length of the shortest path connecting them, and the diameter of the graph, diam(Γ(R)), is the superimum of these distances. In this paper, first we prove some results about Γ(R) of a semi-commutative ring R. Then, for a reversible ring R and a unique product monoid M, we prove 0≤ diam(Γ(R))≤ diam(Γ(R[M]))≤3. We describe all the possibilities for the pair diam(Γ(R)) and diam(Γ(R[M])), strictly in terms of the properties of a ring R, where R is a reversible ring and M is a unique product monoid. Moreover, an example showing the necessity of our assumptions is provided.
Pagoda
Authors: Yeh Tsung Tai , Sabne Amit , Sakdhnagool Putt , Eigenmann Rudolf , Rogers Timothy G.
Published: November 2019

Massively multithreaded GPUs achieve high throughput by running thousands of threads in parallel. To fully utilize the their hardware, contemporary workloads spawn work to the GPU in bulk by launching large tasks, where each task is a kernel that contains thousands of threads that occupy the entire GPU.

GPUs face severe underutilization and their performance benefits vanish if the tasks are narrow, i.e., they contain less than 512 threads. Latency-sensitive applications in network, signal, and image processing that generate a large number of tasks with relatively small inputs are examples of such limited parallelism.

This article presents Pagoda, a runtime system that virtualizes GPU resources, using an OS-like daemon kernel called MasterKernel. Tasks are spawned from the CPU onto Pagoda as they become available, and are scheduled by the MasterKernel at the warp granularity. This level of control enables the GPU to keep scheduling and executing tasks as long as free warps are found, dramatically reducing underutilization. Experimental results on real hardware demonstrate that Pagoda achieves a geometric mean speedup of 5.52X over PThreads running on a 20-core CPU, 1.76X over CUDA-HyperQ, and 1.44X over GeMTC, the state-of-the-art runtime GPU task scheduling system.
Grape Seed Procyanidin B2 Protects Porcine Ovarian Granulosa Cells against Oxidative Stress-Induced Apoptosis by Upregulating let-7a Expression
Authors: Zhang Jia-Qing , Wang Xian-Wei , Chen Jun-Feng , Ren Qiao-Ling , Wang Jing , Gao Bin-Wen , Shi Zhi-Hai , Zhang Zi-Jing , Bai Xian-Xiao , Xing Bao-Song
Published: November 2019

Oxidative stress is a causal factor and key promoter of all kinds of reproductive disorders related to granulosa cell (GC) apoptosis that acts by dysregulating the expression of related genes. Various studies have suggested that grape seed procyanidin B2 (GSPB2) may protect GCs from oxidative injury, though the underlying mechanisms are not fully understood. Therefore, whether the beneficial effects of GSPB2 are associated with microRNAs, which have been suggested to play a critical role in GC apoptosis by regulating the expression of protein-coding genes, was investigated in this study. The results showed that GSPB2 treatment protected GCs from a H2O2-induced apoptosis, as detected by an MTT assay and TUNEL staining, and increased let-7a expression in GCs. Furthermore, let-7a overexpression markedly increased cell viability and inhibited H2O2-induced GC apoptosis. Furthermore, the overexpression of let-7a reduced the upregulation of Fas expression in H2O2-treated GCs at the mRNA and protein levels. Dual-luciferase reporter assay results indicated that let-7a directly targets the Fas 3′-UTR. Furthermore, the overexpression of let-7a enhanced the protective effects of GSPB2 against GC apoptosis induced by H2O2. These results indicate that GSPB2 inhibits H2O2-induced apoptosis of GCs, possibly through the upregulation of let-7a.
Frequency and Vibration Characteristics of High‐Speed Gear‐Rotor‐Bearing System with Tooth Root Crack considering Compound Dynamic Backlash
Authors: Liu Jie , Zhao Weiqiang , Liu Weiwei
Published: November 2019

Considering the microstructure of tooth surface and the dynamic characteristics of the vibration responses, a compound dynamic backlash model is employed for the gear transmission system. Based on the fractal theory and dynamic center distance, respectively, the dynamic backlash is presented, and the potential energy method is applied to compute the time‐varying meshing stiffness, including the healthy gear system and the crack fault gear system. Then, a 16‐DOF coupled lateral‐torsional gear‐rotor‐bearing transmission system with the crack fault is established. The fault characteristics in the time‐domain waveform and frequency response and statistics data are described. The effect of crack on the time‐varying meshing stiffness is analyzed. The vibration response of three backlash models is compared. The dynamic response of the system is explored with the increase in crack depth in detail. The results show that the fault features of countershaft are more obvious. Obvious fluctuations are presented in the time‐domain waveform, and sidebands can be found in the frequency domain responses when the tooth root crack appears. The effect of compound dynamic backlash on the system is more obvious than fixed backlash and backlash with changing center distance. The vibration displacement along meshing direction and dynamic meshing force increases with the increase in crack depth. Backlash and variation of center distance show different tendencies with increasing crack depth under different rotational speeds. Amplitude of the sidebands increases with crack depth increasing. The amplitude of multiplication frequency of rotational frequency has an obvious variation with growing crack depth. The sidebands of the multiplication frequency of meshing frequency show more details on the system with complex backlash and crack fault.
Performance Improvement for Two-Lens Panoramic Endoscopic System during Minimally Invasive Surgery
Authors: Kim Dinh Thai , Cheng Ching Hwa , Liu Don Gey , Liu Kai-Che Jack , Huang Shih Wei Wayne , Tran Song Toan
Published: November 2019

One of the major challenges for Minimally Invasive Surgery (MIS) is the limited field of vision (FOV) of the endoscope. A previous study by the authors designed a MIS Panoramic Endoscope (MISPE) that gives the physician a broad field of view, but this approach is still limited, in terms of performance and quality because it encounters difficulty when there is smoke, specular reflections, or a change in viewpoint. This study proposes a novel algorithm that increases the MISPE’s performance. The method calculates the disparity for the region that is overlapped by the two cameras to allow image stitching. An improved evaluation of the homography matrix uses a frame-by-frame calculation, so the stitched videos are more stable for MIS. The experimental results show that the revised MISPE has a FOV that is 55% greater, and the system operates stably in real time. The proposed system allows a frame rate of 26.7 fps on a single CPU computer. The proposed stitching method is 1.55 times faster than the previous method. The stitched image that is obtained using the proposed method is as similar as the ground truth as the SURF-based stitching method that was used in the previous study.
Effect of Induced Membrane Formation Followed by Polymethylmethacrylate Implantation on Diabetic Foot Ulcer Healing When Revascularization Is Not Feasible
Authors: Liu Chao , You Jia-Xing , Chen Yi-Xin , Zhu Wei-Fen , Wang Ying , Lv Pan-Pan , Zhao Feng , Li Hong-Ye , Li Lin
Published: November 2019

No study has investigated the role of induced membrane (IM) formation in treating diabetic foot ulcer (DFU). This retrospective study was aimed (1) at evaluating the potential role of a two-staged surgical approach, comprising polymethylmethacrylate (PMMA) implantation and IM formation, in the treatment of DFU and (2) at comparing the results of those with routine wound debridement in patients with DFUs and nonrevascularized peripheral arterial disease (PAD). Fifty patients with infected DFUs who were not candidates for vascular interventions were enrolled between February 2016 and April 2018 and assigned to the PMMA group (n=28) and conventional group (n=22). The healing rate, major amputation rate, duration of healing, frequency of debridement procedures, patient survival rate, and reulceration of DFUs were determined. The Mann-Whitney U test, independent sample t-test, and χ2 or Fisher exact test were used in statistical analysis. Overall clinical outcomes were statistically different between the groups (Z=−2.495, P=0.013). In the PMMA group, 16 patients (57.1%) with intact IM formation achieved ulceration healing at 13.1±3.7 weeks with a mean number of debridements of 1.3±0.4, which were significantly different compared to those values in 5 patients of the conventional group (22.7%, P=0.014; healing duration: 26.4±7.8 weeks, P=0.016; mean number of debridements: 3.6±0.5, P≤0.001). At a mean 16.8±4.3-month follow-up, patient survival rates were 92.9% and 68.2% in the PMMA and conventional groups, respectively (P=0.032). The major amputation rate and reulceration of DFUs were similar between the groups. The two-staged surgical approach is an available, effective modality for improving healing of DFUs. This study provides preliminary information of IM formation followed by PMMA implantation in the management of DFUs in PAD when revascularization is not feasible.
Bisphosphonates for Secondary Prevention of Osteoporotic Fractures: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Authors: Shi Lei , Min Nan , Wang Fei , Xue Qing-Yun
Published: November 2019

Purpose. To investigate the comparative efficacies of the five most commonly used bisphosphonates for the secondary prevention of osteoporotic fractures in a Bayesian network meta-analysis. Methods. Five databases and the reference lists of all acquired articles from inception to July 2017 were searched. A Bayesian random-effects model was employed, and vertebral, hip and nonvertebral nonhip fractures were assessed by odds ratios (ORs) and 95%credible intervals. Furthermore, with respect to each endpoint, rank probabilities for each bisphosphonate were evaluated using the surface under the cumulative ranking curve (SUCRA) value. Results. Thirteen eligible studies were identified involving 11,822 patients with osteoporotic fractures. Overall in the pairwise meta-analyses, bisphosphonate use significantly reduced the risk of new vertebral, hip, and nonvertebral nonhip fractures, with ORs and 95% confidence intervals of 0.56 (0.49–0.64), 0.69 (0.48–0.98), and 0.82 (0.70–0.97), respectively. In network meta-analyses, significant differences were found between placebo and any one of the five bisphosphonates for new vertebral fractures. The rank probability plot and the SUCRA calculation results suggested that alendronate was the best intervention (14.6%) for secondary prevention of vertebral fractures, followed by zoledronate (15.3%) and etidronate (22.1%). In terms of the incidence of new hip fractures, alendronate was associated with the lowest incidence (18.5%), followed by zoledronate (43.1%) and risedronate (52.5%). However, zoledronate ranked lowest (16.6%) regarding the incidence of new nonvertebral nonhip fractures, followed by risedronate (23.8%) and alendronate (44.1%). Conclusions. Bisphosphonates show significant efficacy for secondary prevention of new vertebral fractures, and alendronate is most likely to be successful at secondary prevention of vertebral and hip fractures compared with the other four bisphosphonates.
Interaction of Screw Dislocation with Edge Interfacial Crack on Fine-Grained Piezoelectric Coating/Substrate
Authors: Hu Shuaishuai , Liu Jiansheng , Li Junlin , Xie Xiufeng
Published: November 2019

The interaction between micro- and macrocracks in a fine-grained piezoelectric coating/substrate under remote antiplane mechanical and in-plane electrical loadings was studied. The principle of superposition and a mapping function method was used to transform the fine-grained coating/substrate structure containing the screw dislocation and the edge interfacial crack into the right semi-infinite plane piezoelectric bimaterial with screw dislocation to simplify the problem. Furthermore, the electric field, displacement field, intensity factors, and image force of these two problems were established. In addition, numerical calculations were then given graphically to study the effects of the elastic modulus of the material, the size of the crack, the thickness of the coating, and the screw dislocation angle on the edge interface crack and dislocation.
Modulus of Elasticity of Two Ceramic Materials and Stress-Inducing Mechanical Deformation following Fabrication Techniques and Adhesive Cementation Procedures of a Dental Ceramic
Authors: Isgrò G. , Rodi D. , Sachs A. , Hashimoto M.
Published: November 2019

Statement of Problem. Fabrication technique, precementation, and cementation operative procedures can induce significant modification of the stressing patterns throughout the thickness of some classes of dental ceramic materials. Objectives. To estimate, by means of the deflection test, residual stress in restorative dental ceramic following fabrication technique, precementation, and resin cement coating procedures and to relate it to the elastic property of the ceramic material tested. Materials and Methods. From IPS e.max® Press, lithium disilicate heat-pressed glass-ceramic (elastic modulus of 95 ± 5 GPa) disc-shaped specimens (n = 10) were made according to the manufacturer’s instructions. One surface of the specimens was polished to provide accurate baseline profilometric measurements (reference surface). Deflection measurements were performed after polishing and annealing alumina air-particle abrasion of the unpolished surface followed by resin cement coating of the alumina air-particle abraded surface. The specimens were reprofiled at 24, 48, and 168 hrs after coating. The Friedman test followed by Dunn’s multiple comparison test was employed to identify significant differences (p<0.05). To compare the difference in mean of maximum mechanical deflection, after cement coating at 0 hr, between two different ceramic materials (IPS e.max Press and Vitadur Alpha (result from another study)), Student’s t-test for unpaired data was performed. Results. Baseline profilometric measurements identified a convex form on the polished surface of the ceramic discs with a mean of maximum mechanical deflection of 4.45 ± 0.87 μm. A significant reduction in convexity of the polished specimens was characterized after alumina air-particle abrasion of the unpolished surface. The mean deflection significantly increased after resin cement coating and did not change over the time investigated. Conclusions. The precementation treatment, namely, alumina air-particle abrasion and cementation procedure of IPS e.max® Press glass-ceramic disc-shaped specimens generates stress that induced mechanical deformation. However, a dental ceramic material with higher elastic modulus (stiffer) would minimize stress-inducing mechanical deformation.
Geriatric Nutritional Risk Index Predicts Adverse Outcomes in Human Malignancy: A Meta-Analysis
Authors: Lv Guo-yue , An Lin , Sun Da-wei
Published: November 2019

Background. Geriatric Nutritional Risk Index (GNRI) has been widely used to assess the nutritional status in a variety of human pathological conditions, but the prognostic value of the GNRI in malignancies has not been evinced. Methods. Relevant studies updated on Jul 27, 2019, were retrieved in available databases, including PubMed, Web of Science, Cochrane library, Chinese CNKI, and Chinese Wan-fang. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled by using STATA 14. Results. A total of 15 studies involving 8,046 subjects were included in this meta-analysis. Meta-analysis results evinced that low GNRI was associated with poor OS (HR=1.95, 95% CI: 1.49-2.56, p≤0.001), poor CSS (HR=1.81, 95% CI: 1.49-2.19, p≤0.001), poor DFS (HR=1.67, 95% CI: 1.28-2.17, p≤0.001), and poor PFS (HR=1.68, 95% CI: 1.28-2.21, p≤0.001), and the correlation of GNRI with OS was not changed when stratified by possible confounding factors, suggesting that malignancy patients with low GNRI would suffer from reduced survival rate and increased recurrence rate. Moreover, low GNRI was also associated with postoperative complications in malignancies. Conclusions. In summary, GNRI is associated poor prognosis in human malignancies, and GNRI should be used as a predictive indicator of adverse outcomes during malignancy treatment.
CD47 Deficiency Attenuates Isoproterenol-Induced Cardiac Remodeling in Mice
Authors: Zuo Zhi , Ji Ming-Yue , Zhao Kun , Su Zhong-Ping , Li Peng , Hou Dao-Rong , Li Yong
Published: November 2019

In this study, we investigated whether CD47 deficiency attenuates isoproterenol- (ISO-) induced cardiac remodeling in mice. Cardiac remodeling was induced by intraperitoneal (i.p.) injection of ISO (60 mg·kg-1·d-1 in 100 μl of sterile normal saline) daily for 14 days and was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased heart weight to body weight (HW/BW) ratios, and visible cardiac fibrosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were found to be significantly higher in the ISO group than in the control group, while superoxide dismutase (SOD) levels were suppressed in the ISO group. However, CD47 knockout significantly limited ISO-induced increases in LDH, CK-MB, and HW/BW ratios, cardiac fibrosis, oxidative stress, and apoptosis in the heart. In addition, CD47 deficiency also increased p-AMPK and LAMP2 expression and decreased HDAC3, cleaved Caspase-3, cleaved Caspase-9, LC3II, and p62 expression in cardiac tissues. In conclusion, CD47 deficiency reduced i.p. ISO-induced cardiac remodeling probably by inhibiting the HDAC3 pathway, improving AMPK signaling and autophagy flux, and rescuing autophagic clearance.
A New Conflict Management in Evidence Theory Based on DEMATEL Method
Authors: Fan Wentao , Xiao Fuyuan
Published: November 2019

D-S evidence theory is widely used in data fusion. However, the result of Dempster’s combination rule is not efficient and in highly conflicting situation. Though the existing methods have been proved efficient to deal with conflict in some applications, the indirect conflict among evidence is neglected to some degree. To solve this problem, a new method is proposed based on decision-making trial and evaluation laboratory (DEMATEL) and the belief correlation coefficient in this paper. The application in target recognition illustrates the efficiency of the proposed method. Compared with Dempster’s rule, averaging method and weighted averaging method, etc., the results obtained by the proposed method have better performance. The main reason is that the indirect conflict is well addressed in the proposed method.
Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis
Authors: Mekuria Abraham Nigussie , Ayele Yohanes , Tola Assefa , Mishore Kirubel Minsamo
Published: November 2019

Background. Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. Objective. A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. Methods. Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. Results. A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR=0.74, 95% CI: 0.55-0.99, I2=97.89%, p<0.00001; adjusted RR=0.76, 95% CI: 0.54–1.07, I2=98.12%, p<0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. Conclusions. According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.
Thermoacoustic Stability Boundaries in the Model Combustion Chamber with a Gas-Centered Swirl Coaxial Injector
Authors: Min Yong Ho , Sohn Chae Hoon , Yoon Youngbin
Published: November 2019

The stability of a combustion chamber with a gas-centered swirl coaxial injector is investigated over a wide range of operating conditions in the aspect of thermoacoustic instabilities. First, flame shapes induced by the injector are analyzed for various recess lengths from experimental results. The spreading angle and flame size are reduced as the recess length increases. And, as a stability criterion, the damping factor is introduced. The operating conditions are divided into 7 sets with 9 tests, and fuel mass flow is fixed in each set. Stability boundaries are identified in terms of damping factor for the 63 tests by experiments without external perturbations. The stability map for the self-excited instability is obtained and it reveals two unstable regions. One is located at low dynamic head ratio and the other one is at high dynamic head ratio. A stable region is found at moderate dynamic head ratios. Relative stability is evaluated by various flow parameters over a wide range of operating conditions in the combustion chamber with a gas-centered swirl coaxial injector.
Molecular Profiles of Matched Primary and Metastatic Tumor Samples Support a Linear Evolutionary Model of Breast Cancer
Authors: Chen Runpu , Goodison Steve , Sun Yijun
Published: November 2019

The interpretation of accumulating genomic data with respect to tumor evolution and cancer progression requires integrated models. We developed a computational approach that enables the construction of disease progression models using static sample data. Application to breast cancer data revealed a linear, branching evolutionary model with two distinct trajectories for malignant progression. Here, we used the progression model as a foundation to investigate the relationships between matched primary and metastasis breast tumor samples. Mapping paired data onto the model confirmed that molecular breast cancer subtypes can shift during progression and supported directional tumor evolution through luminal subtypes to increasingly malignant states. Cancer progression modeling through the analysis of available static samples represents a promising breakthrough. Further refinement of a roadmap of breast cancer progression will facilitate the development of improved cancer diagnostics, prognostics, and targeted therapeutics.

Significance:

Analysis of matched primary and metastatic tumor samples supports a unidirectional, linear cancer evolution process and sheds light on longstanding issues regarding the origins of molecular subtypes and their progression relationships.
Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Nisa Lluís , Francica Paola , Giger Roland , Medo Matúš , Elicin Olgun , Friese-Hamim Manja , Wilm Claudia , Stroh Christopher , Bojaxhiu Beat , Quintin Aurélie , Caversaccio Marco D. , Dettmer Matthias S. , Buchwalder Mélanie , Brodie Tess M. , Aebersold Daniel M. , Zimmer Yitzhak , Carey Thomas E. , Medová Michaela
Published: November 2019

Radiotherapy (RT) along with surgery is the mainstay of treatment in head and neck squamous cell carcinoma (HNSCC). Radioresistance represents a major source of treatment failure, underlining the urgent necessity to explore and implement effective radiosensitization strategies. The MET receptor widely participates in the acquisition and maintenance of an aggressive phenotype in HNSCC and modulates the DNA damage response following ionizing radiation (IR). Here, we assessed MET expression and mutation status in primary and metastatic lesions within a cohort of patients with advanced HNSCC. Moreover, we investigated the radiosensitization potential of the MET inhibitor tepotinib in a panel of cell lines, in vitro and in vivo, as well as in ex vivo patient-derived organotypic tissue cultures (OTC). MET was highly expressed in 62.4% of primary tumors and in 53.6% of lymph node metastases (LNM), and in 6 of 9 evaluated cell lines. MET expression in primaries and LNMs was significantly associated with decreased disease control in univariate survival analyses. Tepotinib abrogated MET phosphorylation and to distinct extent MET downstream signaling. Pretreatment with tepotinib resulted in variable radiosensitization, enhanced DNA damage, cell death, and G2–M-phase arrest. Combination of tepotinib with IR led to significant radiosensitization in one of two tested in vivo models. OTCs revealed differential patterns of response toward tepotinib, irradiation, and combination of both modalities. The molecular basis of tepotinib-mediated radiosensitization was studied by a CyTOF-based single-cell mass cytometry approach, which uncovered that MET inhibition modulated PI3K activity in cells radiosensitized by tepotinib but not in the resistant ones.
ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine
Authors: Bhagwat Shripad V. , McMillen William T. , Cai Shufen , Zhao Baohui , Whitesell Matthew , Shen Weihua , Kindler Lisa , Flack Robert S. , Wu Wenjuan , Anderson Bryan , Zhai Yan , Yuan Xiu-Juan , Pogue Meghann , Van Horn Robert D. , Rao Xi , McCann Denis , Dropsey Andrew J. , Manro Jason , Walgren Jennie , Yuen Eunice , Rodriguez Michael J. , Plowman Gregory D. , Tiu Ramon V. , Joseph Sajan , Peng Sheng-Bin
Published: November 2019

The ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance. Reactivation of ERK signaling is central to the mechanisms of acquired resistance. Therefore, ERK inhibition provides an opportunity to overcome resistance and leads to improved efficacy. In addition, KRAS-mutant cancers remain an unmet medical need in which ERK inhibitors may provide treatment options alone or in combination with other agents. Here, we report identification and activity of LY3214996, a potent, selective, ATP-competitive ERK inhibitor. LY3214996 treatment inhibited the pharmacodynamic biomarker, phospho-p90RSK1, in cells and tumors, and correlated with LY3214996 exposures and antitumor activities. In in vitro cell proliferation assays, sensitivity to LY3214996 correlated with ERK pathway aberrations. LY3214996 showed dose-dependent tumor growth inhibition and regression in xenograft models harboring ERK pathway alterations. Importantly, more than 50% target inhibition for up to 8 to 16 hours was sufficient for significant tumor growth inhibition as single agent in BRAF- and KRAS-mutant models. LY3214996 also exhibited synergistic combination benefit with a pan-RAF inhibitor in a KRAS-mutant colorectal cancer xenograft model. Furthermore, LY3214996 demonstrated antitumor activity in BRAF-mutant models with acquired resistance in vitro and in vivo. Based on these preclinical data, LY3214996 has advanced to an ongoing phase I clinical trial (NCT02857270).
AMPK-Independent LKB1 Activity Is Required for Efficient Epithelial Ovarian Cancer Metastasis
Authors: Buensuceso Adrian , Ramos-Valdes Yudith , DiMattia Gabriel E. , Shepherd Trevor G.
Published: November 2019

Epithelial ovarian cancer (EOC) spreads by direct dissemination of malignant cells and multicellular clusters, known as spheroids, into the peritoneum followed by implantation and growth on abdominal surfaces. Using a spheroid model system of EOC metastasis, we discovered that Liver kinase B1 (LKB1), encoded by the STK11 gene, and its canonical substrate AMP-activated protein kinase (AMPK) are activated in EOC spheroids, yet only LKB1 is required for cell survival. We have now generated STK11-knockout cell lines using normal human FT190 cells and three EOC cell lines, OVCAR8, HeyA8, and iOvCa147. STK11KO did not affect growth and viability in adherent culture, but it decreased anchorage-independent growth of EOC cells. EOC spheroids lacking LKB1 had markedly impaired growth and viability, whereas there was no difference in normal FT190 spheroids. To test whether LKB1 loss affects EOC metastasis, we performed intraperitoneal injections of OVCAR8-, HeyA8-, and iOvCa147-STK11KO cells, and respective controls. LKB1 loss exhibited a dramatic reduction on tumor burden and metastatic potential; in particular, OVCAR8-STK11KO tumors had evidence of extensive necrosis, apoptosis, and hypoxia. Interestingly, LKB1 loss did not affect AMPKα phosphorylation in EOC spheroids and tumor xenografts, indicating that LKB1 signaling to support EOC cell survival in spheroids and metastatic tumor growth occurs via other downstream mediators. We identified the dual-specificity phosphatase DUSP4 as a commonly upregulated protein due to LKB1 loss; indeed, DUSP4 knockdown in HeyA8-STK11KO cells partially restored spheroid formation and viability.

Implications:

LKB1 possesses key tumor-promoting activity independent of downstream AMPK signaling during EOC metastasis.
C-Reactive Protein in the Prediction of Localization of Gastrointestinal Perforation
Authors: Grupp Katharina , Grotelüschen Rainer , Uzunoglu Faik Güntac , Hofmann Bianca , König Alexandra , Perez Daniel , Bockhorn Maximillian , Izbicki Jakob Robert , Bachmann Kai
Published: November 2019

Aim: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. Methods: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. Results: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). Conclusion: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.
Population Survey of Bornean White-Bearded Gibbon, Hylobates albibarbis, in Two Selective Logging Concessions in Central Kalimantan and West Kalimantan
Authors: Yanuar Achmad , Chivers David , Hilman Ian , Saleh Chaerul , Putra Ida Bagus Wiradnyana , Purnomo Susilo , Wasman Khusaeri
Published: November 2019

We surveyed Bornean white-bearded gibbon, Hylobates albibarbis, population densities in lowland and hill dipterocarp forests within the Sari Bumi Kusama and Suka Jaya Makmur logging concessions. These surveys were conducted from 20 to 30 March 2018 in Sari Bumi Kusuma areas and 14 to 24 April 2018 in Suka Jaya Makmur. We used a fixed-point count method to detect and plot morning song bouts of gibbon groups at systematically placed listening posts. At each location in Sari Bumi Kusuma and Suka Jaya Makmur, 18 listening posts were established, and 2 observers noted and plotted gibbon morning great calls. Gibbon group density was higher at Suka Jaya Makmur than at Sari Bumi Kusuma; we estimated that there were 2.29 groups per square kilometre in the former area and 1.86 groups/km2 in the latter. Since Bornean white-bearded gibbons are strictly protected by the Government of Indonesia and listed as an Endangered species by the International Union for Conservation of Nature (IUCN), we need better management practices to protect the populations of this species within production forests (outside protected areas).