bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemodynamic outcomes following aortic valve-in-valve procedure
Authors: Zenses Anne-Sophie , Dahou Abdellaziz , Salaun Erwan , Clavel Marie-Annick , Rodés-Cabau Josep , Ong Géraldine , Guzzetti Ezéquiel , Côté Mélanie , De Larochellière Robert , Paradis Jean-Michel , Doyle Daniel , Mohammadi Siamak , Dumont Éric , Chamandi Chekrallah , Rodriguez-Gabella Tania , Rieu Régis , Pibarot Philippe
Published: July 2018

Background and objectives

Transcatheter aortic valve-in-valve implantation (ViV) has emerged as a valuable technique to treat failed surgical bioprostheses (BPs) in patients with high risk for redo surgical aortic valve replacement (SAVR). Small BP size (≤21 mm), stenotic pattern of degeneration and pre-existing prosthesis–patient mismatch (PPM) have been associated with worse clinical outcomes after ViV. However, no study has evaluated the actual haemodynamic benefit associated with ViV. This study aims to compare haemodynamic status observed at post-ViV, pre-ViV and early after initial SAVR and to determine the factors associated with worse haemodynamic outcomes following ViV, including the rates of high residual gradient and ‘haemodynamic futility’.

Methods

Early post-SAVR, pre-ViV and post-ViV echocardiographic data of 79 consecutive patients who underwent aortic ViV at our institution were retrospectively analysed. The primary study endpoint was suboptimal valve haemodynamics (SVH) following ViV defined by the Valve Academic Research Consortium 2 as the presence of high residual aortic mean gradient (≥20 mm Hg) and/or at least moderate aortic regurgitation (AR). Haemodynamic futility of ViV was defined as <10 mm Hg decrease in mean aortic gradient and no improvement in AR compared with pre-ViV.

Results

SVH was found in 61% of patients (57% high residual gradient, 4% moderate AR) after ViV versus 24% early after SAVR. Pre-existing PPM and BP mode of failure by stenosis were independently associated with the primary endpoint (OR: 2.87; 95% CI 1.08 to 7.65; p=0.035 and OR: 3.02; 95% CI 1.08 to 8.42; p=0.035, respectively) and with the presence of high residual gradient (OR: 4.38; 95% CI 1.55 to 12.37; p=0.005 and OR: 5.37; 95% CI 1.77 to 16.30; p=0.003, respectively) following ViV. Criteria of ViV haemodynamic futility were met in 7.6% overall and more frequently in patients with pre-existing PPM and stenotic BP (18.5%) compared with other patients (2.0%). ViV restored haemodynamic function to early post-SAVR level in only 34% of patients.

Conclusion

Although ViV was associated with significant haemodynamic improvement compared with pre-ViV in >90% of patients, more than half harboured SVH outcome. Furthermore, only one-third of patients had a restoration of valve haemodynamic function to the early post-SAVR level. Pre-existing PPM and stenosis pattern of BP degeneration were the main factors associated with SVH and haemodynamic futility following ViV. These findings provide strong support for the prevention of PPM at the time of initial SAVR and careful preprocedural patient screening.
Effects of forest management and harvesting intensity on the timber supply from Finnish forests in a changing climate
Authors: Heinonen Tero , Pukkala Timo , Kellomäki Seppo , Strandman Harri , Asikainen Antti , Venäläinen Ari , Peltola Heli
Published: July 2018

We studied the potential effects of management and harvesting intensity on the timber supply from Finnish forests in a changing climate and, consequently, the possibilities of meeting the increasing wood demand of the growing forest-based bioeconomy. The study employed data from the 11th National Forest Inventory of Finland. Plots located on forest land assigned to timber production were used to develop two even-flow harvesting scenarios with annual timber harvesting targets of 60 and 80 million m3. Calculations were done for a 90-year simulation period under the current and changing climates using recent-generation (Coupled Model Intercomparison Project Phase 5) global climate model projections under three representative concentration pathways forcing scenarios (RCP2.6, RCP4.5, and RCP8.5). Intensified management used improved seed and seedling stock in artificial regeneration. It also used fertilization on subxeric pine-dominated and mesic spruce-dominated stands and ditch maintenance on 40% of drained peatlands, when the growing stock characteristics fulfilled a set of predetermined criteria. Our results showed that, with intensified management, it is possible to harvest 80 million m3·year−1 of timber under mild (RCP2.6) and moderate (RCP4.5) climate change without decreasing the growing stock volume at the country level during the 90-year simulation period. This is not possible under severe climate change (RCP8.5) due to the rapid decline in forest growth, particularly in the south after about 30 years.
A new class of Pöschl–Teller potentials with inverse square singularity and their spectra using the asymptotic iteration method
Authors: Assi I. A. , Sous A. J. , Bahlouli H.
Published: July 2018

The aim of this work is to introduce a new family of potentials with inverse square singularity which we called the Pöschl–Teller family of potentials. We enforced the matrix representation of the wave operator to be symmetric and (2k[Formula: see text]+[Formula: see text]1) band-diagonal with respect to a square integrable basis set. This, in principle, is only satisfied for specific potential functions within the used basis set. The basis functions we used here are written in terms of Jacobi polynomials, which is the same basis used in the Tridiagonal Representation Approach (TRA). This yield a more general form of Pöschl–Teller potential that can have many terms which could be beneficial for modeling different physical systems where this potential applies. As an illustration, we have studied a specific new five-parameter potential that belongs to this new family and calculated the bound states for both s-wave and l-wave cases using the Asymptotic Iteration Method (AIM). Along the way, we have introduced new approximation schemes to deal with the l-wave centrifugal potential within the AIM at different approximation orders.
Mechanical and thermophysical properties of actinide monocarbides
Authors: Singh Devraj , Kumar Amit , Bhalla Vyoma , Thakur Ram Krishna
Published: July 2018

This paper describes the mechanical and thermophysical properties of actinide monocarbides AnCs (An=Np and Cm) as a function of temperature and crystallographic direction. The temperature-dependent second- and third-order elastic constant (SOECs and TOECs) have been computed first using Coulomb and Born–Mayer potential up to second nearest neighbor. SOECs have been applied to find out mechanical constant such as bulk modulus, shear modulus, tetragonal modulus, Poisson’s ratio and Zener anisotropy for the prediction of futuristic performance of the NpC and CmC. We also found the value of G/B [Formula: see text] 0.59 for the chosen materials, which indicates that NpC and CmC have brittle nature. The computed elastic constants are further applied directly to indirectly find out the ultrasonic velocity, Grüneisen parameters, pressure derivative, Debye temperature, micro-hardness, Breazeale’s nonlinearity parameter, thermal relaxation time and thermal conductivity. These evaluated parameters were finally used to compute ultrasonic attenuation of the NpC and CmC along [Formula: see text], [Formula: see text] and [Formula: see text] directions at room temperature. The behavior of the obtained results of this investigation has been compared with similar type of materials.
Fabrication and Characterization of Fluorinated Polyimides (PI) Films with Improved Hydrophobic Property
Authors: Peng Yonghong , Zhang Shuai , Zhu Fanghua , Li Wa , Yi Yong , Du Kai , Yin Qiang
Published: July 2018

There is a demand for composite films with excellent hydrophobic properties in inertial confinement fusion (ICF) physics experiments. In this paper, we prepared fluorinated polyimide hydrophobic films using spinning and plasma etching methods. The experimental results indicate that the water contact angle for the perfluorodecyltrichlorosilane (PFTS) treatment polyimide (PI) film is 112.0[Formula: see text], which is larger than the pure PI film [Formula: see text]. The rap oil contact angle is 84.2[Formula: see text], which is also much larger than the contact angle of PI film [Formula: see text]. Moreover, the surface roughness of the prepared films was measured by white light interferometry (WLI). The surface roughness (Ra) of pure PI is 9.79[Formula: see text]nm, but with the application of FSiO2 particles, the Ra of the films increases to 65.05[Formula: see text]nm. After plasma treatment, the Ra of the PI/FSiO2 composite film increases to 186.71[Formula: see text]nm because plasma treatment can scratch the film surface and increase its roughness. However, treating the PI/FSiO2 composite film with the plasma and PFTS, the Ra is only 88.90[Formula: see text]nm. This decrease in Ra is due to the PFTS, which is able to reduce the surface roughness. The development of composite films, compared to pure PI films, could prove to be an extremely valuable material in ICF experiments.
Mechanisms of sleep deprivation-induced hepatic steatosis and insulin resistance in mice
Authors: Shigiyama Fumika , Kumashiro Naoki , Tsuneoka Yousuke , Igarashi Hiroyuki , Yoshikawa Fukumi , Kakehi Saori , Funato Hiromasa , Hirose Takahisa
Published: July 2018

Sleep deprivation is associated with increased risk for type 2 diabetes mellitus. However, the underlying mechanisms of sleep deprivation-induced glucose intolerance remain elusive. The aim of this study was to investigate the mechanisms of sleep deprivation-induced glucose intolerance in mice with a special focus on the liver. We established a mouse model of sleep deprivation-induced glucose intolerance using C57BL/6J male mice. A single 6-h sleep deprivation by the gentle handling method under fasting condition induced glucose intolerance. Hepatic glucose production assessed by a pyruvate challenge test was significantly increased, as was hepatic triglyceride content (by 67.9%) in the sleep deprivation group, compared with freely sleeping control mice. Metabolome and microarray analyses were used to evaluate hepatic metabolites and gene expression levels and to determine the molecular mechanisms of sleep deprivation-induced hepatic steatosis. Hepatic metabolites, such as acetyl coenzyme A, 3β-hydroxybutyric acid, and certain acylcarnitines, were significantly increased in the sleep deprivation group, suggesting increased lipid oxidation in the liver. In contrast, fasted sleep-deprived mice showed that hepatic gene expression levels of elongation of very long chain fatty acids-like 3, lipin 1, perilipin 4, perilipin 5, and acyl-CoA thioesterase 1, which are known to play lipogenic roles, were 2.7, 4.5, 3.7, 2.9, and 2.8 times, respectively, those of the fasted sleeping control group, as assessed by quantitative RT-PCR. Sleep deprivation-induced hepatic steatosis and hepatic insulin resistance seem to be mediated through upregulation of hepatic lipogenic enzymes.
Expression of miR-206 in human islets and its role in glucokinase regulation
Authors: Joglekar Mugdha V. , Wong Wilson K. M. , Maynard Cody-Lee , Umrani Malati R. , Martin David , Loudovaris Thomas , Thomas Helen E. , Dalgaard Louise T. , Hardikar Anandwardhan A.
Published: July 2018

Inappropriate insulin secretion from β-cells is considered as an early sign of impaired glucose tolerance and type 2 diabetes (T2D). Glucokinase (GCK) is an important enzyme that regulates glucose metabolism and ensures that the normal circulating glucose concentrations are maintained. GCK expression is induced by glucose and regulated via transcription factors and regulatory proteins. Recently, microRNA-206 (miR-206) was reported to regulate GCK and alter glucose tolerance in normal and high-fat diet-fed mice. Although the study findings have implications for human diabetes, studies in human islets are lacking. Here, we analyze human islets from individuals without or with T2D, using TaqMan-based real-time qPCR at the tissue (isolated islet) level as well as at single cell resolution, to assess the relationship between miR-206 and GCK expression in normal and T2D human islets. Our data suggest that, unlike mouse islets, human islets do not exhibit any correlation between miR-206 and GCK transcripts. These data implicate the need for further studies aimed toward exploring its potential role(s) in human islets.
The Impact of Type 2 Diabetes Mellitus on Long-Term Prognosis in Patients of Different Ages with Myocardial Infarction
Authors: Afanasiev S. A. , Garganeeva A. A. , Kuzheleva E. A. , Andriyanova A. V. , Kondratieva D. S. , Popov S. V.
Published: July 2018

The objective of the study was to assess the impact of DM2 at baseline on long-term mortality after acute myocardial infarction (MI) among different age groups. The data were taken from: “Register of Acute Myocardial Infarction.” A total of 862 patients were followed for five years after acute myocardial infarction. The primary endpoint was death from any cause. The patients were categorized into 2 groups based on their ages: group 1—comprised patients older than working age (n=358) and group 2—comprised employable patients (n=504). A total of 208 patients were diagnosed with both cardiovascular disease and DM2. Elderly patients with DM2 had worse prognosis and increased five-year mortality compared with patients of the same age group without DM2. Statistically significant differences in long-term outcomes were found in adult patients (p=0.004) only in group with longer duration of diabetes, unlike the group with DM2 onset. In conclusion, Type 2 DM increased 5-year mortality rate of elderly patients with myocardial infarction. However, younger patients with both myocardial infarction and DM2 had more complications in the early post-MI period compared with patients of the same age group without DM2 but did not show any statistically significant differences in the long-term outcome.
FPGA Implementation of UFMC Based Baseband Transmitter: Case Study for LTE 10MHz Channelization
Authors: Jafri Atif Raza , Majid Javaria , Zhang Lei , Imran Muhammad Ali , Najam-ul-Islam M.
Published: July 2018

Universal filtered multicarrier (UFMC) is a low complexity promising waveform that provides quasi‐orthogonal property among subcarriers. In addition, it can achieve much better out‐of‐band emission performance than orthogonal frequency division multiplexing (OFDM) system. Authors have proposed a hardware platform to implement a UFMC transmitter in this paper. Highly reduced complexity schemes for IFFT, filtering, and spectrum shifting are realized on actual hardware. This helps to achieve overall architecture of the transmitter at the cost of minimal FPGA resource usage. Hence, the overall design uses only 1038 slice registers, 1154 slice LUTs, and 64 multipliers of Xilinx Virtex‐7 XC7VX330t device. A throughput of 773.5 Msamples/sec at an operational frequency of 364 MHz is achieved. This throughput is adequate for processing 50 Physical Resource Blocks (PRB) of LTE 10 MHz channelization in required time. The presented architecture provides a latency of only 2% of one LTE 10MHz channelization symbol due to the implementation of pipelining at different levels. Although the presented hardware design in its current form meets LTE 10MHz channelization throughput requirements, further increase in throughput is possible due to the scalable nature of the architecture. To the best of our knowledge, this work is first ever FPGA solution for UFMC transmitter presented in the literature.
Adaptive Decision of Wireless Access Network for Higher User Satisfaction
Authors: Kim Hyunsoon , Bae Mungyu , Lee Woonghee , Kim Hwangnam
Published: July 2018

Today’s mobile devices mostly contain more than one wireless interface for Internet connection. Smartphones mostly have both LTE and Wi‐Fi for data communication through Internet. Although the availability of Wi‐Fi is incomparable to that of cellular network, its strength lies in the low cost and high data rate due to continuous PHY and MAC advancement of 802.11 protocol extensions. In this paper, we propose a device‐centric system that performs cost‐effective network connectivity to the mobile device by selectively activating Wi‐Fi communication according to the device mobility and corresponding history of Wi‐Fi usage. By analyzing the device mobility using attached sensors, the system selects appropriate Wi‐Fi that has been often used in that mobility state. The system was implemented in actual mobile devices that were used to several experiments we designed to prove high performance of the system.
Characterization of Positional Distribution of Fatty Acids and Triacylglycerol Molecular Compositions of Marine Fish Oils Rich in Omega-3 Polyunsaturated Fatty Acids
Authors: Zhang Huijun , Zhao Hui , Zhang Youwei , Shen Yingbin , Su Hang , Jin Jun , Jin Qingzhe , Wang Xingguo
Published: July 2018

The regiospecific characteristics of n-3 polyunsaturated fatty acids (PUFAs) in triacylglycerol (TAG) significantly affect the physicochemical and physiological properties of marine fish oils. In this study, the TAG molecular species composition and positional distributions of fatty acids were investigated in three marine fish species rich in omega-3 PUFAs (anchovy, tuna, and salmon). The regiospecific distribution of the fatty acids was measured with the allylmagnesium bromide (AMB) degradation method. The TAG compositions were analyzed with HPLC and the TAG molecular species were identified with APCI/MS. DHA was preferentially distributed at the sn-2 position of TAG, whereas EPA was evenly distributed along the glycerol backbone. The combinations of FAs, DDO, EOP, EPS, DSS, OOS, and PPS were the predominant TAG molecular species, and OOP, DOS, and DPoPo were the characteristic TAG molecules in the anchovy, salmon, and tuna, respectively. These data can be used to distinguish other marine fish species. The TAG composition categorized by TCN and ECN showed well-structured distributions, with double or triple peaks. These findings should greatly extend the use of marine fish oils in food production and may significantly affect the future development of the fish oil industry.
Joint Channel Assignment and Power Allocation Based on Maximum Concurrent Multicommodity Flow in Cognitive Radio Networks
Authors: Salah Ahmed , Abdel-Atty Heba M. , Rizk Rawya Y.
Published: July 2018

Emerging cognitive radio networking technology potentially provides a promising solution to the spectrum underutilization problem in wireless access. In this paper, a cross‐layer routing for secondary multihop is studied in cognitive radio network operating in television white spaces. The framework considers a joint channel, power, and routing assignment under signal to interference noise ratio (SINR) constraints. The problem is formulated as a maximum concurrent multicommodity flow problem. The goal of conducting this research is to develop a new routing protocol for the secondary multihop cognitive radio network. Therefore, the objective of this paper focuses on maximizing a flow rate scaling factor. Moreover, the paper focuses on achieving multipath routing when it is possible under SINR constraints to utilize all possible unused channels efficiently. The numerical results proved the strength of the proposed algorithm in its routing ability under the physical model of SINR, in addition to the ability of using multipath routing if there are available free channels to be used in the cognitive communication paradigm.
CD4hiCD8lowDouble-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation
Authors: Choi Yun Jung , Park Hi-Jung , Park Hye Jin , Jung Kyeong Cheon , Lee Jae-Il
Published: July 2018

Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively. DP T cells expressed high levels of CXCR5 and PD-1 and secreted IFN-γ, IL-4, and IL-21 in amounts equivalent to those secreted by CD4 or CD8 T cells; also, they produced large amounts of granzyme B and perforin. In addition, under steady-state conditions, DP T cells expressed eomesodermin (Eomes) and promyelocytic leukemia zinc finger (PLZF) proteins, both of which act as transcription factors in innate/memory-like T cells. The number of peripheral DP T cells in the islet transplantation model was high in the group that experienced graft rejection; this was not the case in the long-term survival group. Interestingly, numbers of effector memory T cells (TEM) within the DP T cell population increased significantly during islet graft rejection, as did those of TEM within the cytotoxic CD8 T cells. Furthermore, the most conspicuous of which was the increase of CD4hiCD8lowT cell subpopulation at that point. Taken together, the data suggest that peripheral DP T cells showing an innate/memory-like phenotype have both helper and cytotoxic activityin vitroand that they may act as a novel biomarker for graft rejection after islet transplantation.
Ligustilide Ameliorates Memory Deficiency in APP/PS1 Transgenic Mice via Restoring Mitochondrial Dysfunction
Authors: Xu Yi-Jun , Mei Yu , Qu Zi-Ling , Zhang Shi-Jie , Zhao Wei , Fang Jian-Song , Wu Jun , Yang Cong , Liu Si-Jun , Fang Yong-Qi , Wang Qi , Zhang Yong-Bin
Published: July 2018

Ligustilide, the main lipophilic component of Radix angelicae sinensis, has been shown to ameliorate cognitive dysfunction in a few Alzheimer’s disease mouse models, but its mechanism is not fully understood. In this study, we employed 7-month-old APP/PS1 mice to explore whether LIG is able to protect against Alzheimer’s disease progression. The Morris water maze and Y-maze test results showed that eight weeks of intragastric administration of LIG (10 mg/kg, 40 mg/kg) every day improved memory deficit in APP/PS1 mice. The thioflavin-S staining and Western blot results (Aβ1-42monomer/oligomer, APP, ADAM10, SAPPα, and PreP) showed that LIG reduced Aβlevels in the brain of APP/PS1 mice. Transmission electron microscopy analysis showed that LIG reduced the mitochondria number and increased the mitochondrial length in the hippocampal CA1 area of APP/PS1 mice. A reduced level of Drp1 (fission) and increased levels of Mfn1, Mfn2, and Opa1 (fusion) were found in APP/PS1 mice treated with LIG. An increased ATP level in the brain and increased activities of cytochrome c oxidase (CCO) and succinate dehydrogenase (SDH) in mitochondrion separated from the hippocampus and cortex revealed that LIG alleviated mitochondrial dysfunction. LIG exerts an antioxidation effect via reducing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and increasing the activity of Mn-SOD in the brain. Elevated levels of PSD-95, synaptophysin, and synapsin 1 in both the hippocampus and cortex indicated that LIG provided synaptic protection. These findings show that treatment with LIG ameliorates mitochondrial dynamics and morphology issues, improves mitochondrial function, reduces Aβlevels in the brain, restores the synaptic structure, and ameliorates memory deficit in APP/PS1 mice. These results imply that LIG may serve as a potential antidementia drug.
A Mobility Link Service for NDN Consumer Mobility
Authors: Cha Jung-Hwan , Choi Ju-Ho , Kim Ji-Yong , Han Youn-Hee , Min Sung-Gi
Published: July 2018

Named Data Networking (NDN) supports the consumer mobility service by letting a consumer reissue an interest. This method is straightforward, but it may cause several drawbacks, including unnecessary handover overhead and long handover delay. We concentrate on the NDN communication model in which the pair of an interest and a data packet is considered a single communication working set (i.e., transaction unit). In this respect, reissuing an interest means creating a new transaction due to the connection damaged by the movement of a consumer. It makes all states of the current transaction useless, and this is where the drawbacks arise. In order to enhance the consumer mobility service, we propose Mobility Link Service (MLS) operated in NDN face which is responsible for management of a connection for a transaction. MLS reuses the existing states of a transaction by establishing a connection for the transaction instead of creating a new one. In addition, MLS in NDN face makes consumer mobility service transparent to the NDN forwarding plane. Therefore, the consumer mobility service and the NDN architecture can evolve independently. The performance evaluation shows that MLS reduces the amount of retransmitted data and handover latency compared with the existing NDN mobility solution.
Vasorelaxant and Hypotensive Effects of Cheonwangbosimdan in SD and SHR Rats
Authors: Kim Bumjung , Jo Cheolmin , Choi Ho-Young , Lee Kyungjin
Published: July 2018

Historically, traditional herbal medicines (THMs) have been the conventional treatment strategy in the Korean medical system for treating many diseases. However, THMs have rarely been used to treat hypertension, and moreover few studies have investigated the interaction of blood pressure with the coadministration of synthetic antihypertensives. We aimed to evaluate the vasorelaxant and hypotensive effects of the traditional herbal prescription Cheonwangbosimdan (CWBSD; “Tianwangbuxindan” in Chinese) and the combination of CWBSD with amlodipine. CWBSD was extracted with distilled water at 100°C for 2 h. To investigate vasorelaxant activities, CWBSD with amlodipine (10 μg/ml) was added cumulatively (10–1,000 μg/ml) to isolated rat aortic rings precontracted using phenylephrine or potassium chloride in organ chambers. To investigate hypotensive effects, CWBSD (2,476 mg/kg) was orally administered with or without amlodipine (5 mg/kg) to spontaneously hypertensive rats (SHRs). CWBSD increased the relaxation of rat aortic rings induced by amlodipine (P < 0.01). In vivo, CWBSD coadministration with amlodipine also significantly decreased the blood pressure of SHRs compared to the amlodipine‐treated group. These results suggested that CWBSD could be a useful herbal prescription to treat hypertension and we recommend establishing guidelines for the use of herbal medicines in conjunction with antihypertensive drugs, including amlodipine.
The Monitoring-Based Analysis on Deformation-Controlling Factors and Slope Stability of Reservoir Landslide: Hongyanzi Landslide in the Southwest of China
Authors: Han Bing , Tong Bin , Yan Jinkai , Yin Chunrong , Chen Liang , Li Deying
Published: July 2018

Reservoir landslide is a type of commonly seen geological hazards in reservoir area and could potentially cause significant risk to the routine operation of reservoir and hydropower station. It has been accepted that reservoir landslides are mainly induced by periodic variations of reservoir water level during the impoundment and drawdown process. In this study, to better understand the deformation characters and controlling factors of the reservoir landslide, a multiparameter-based monitoring program was conducted on a reservoir landslide—the Hongyanzi landslide located in Pubugou reservoir area in the southwest of China. The results indicated that significant deformation occurred to the landslide during the drawdown period; otherwise, the landslide remained stable. The major reason of reservoir landslide deformation is the generation of seepage water pressure caused by the rapidly growing water level difference inside and outside of the slope. The influences of precipitation and earthquake on the slope deformation of the Hongyanzi landslide were insignificant.
Feasibility of Neurorehabilitation Using a Hybrid Assistive Limb for Patients Who Underwent Spine Surgery
Authors: Yatsugi Aya , Morishita Takashi , Fukuda Hiroyuki , Kotani Naoya , Yagi Kenji , Abe Hiroshi , Shiota Etsuji , Inoue Tooru
Published: July 2018

Recent studies of robotic rehabilitation have demonstrated its efficacy for neurological disorders. However, few studies have used the Hybrid Assistive Limb (HAL) during the early postoperative stage of spine disorders. We aimed to evaluate the safety and efficacy of HAL treatment during the early postoperative period for spine disorder patients. We retrospectively identified patients who underwent spine surgery and who could complete HAL treatment. We evaluated the 10-m walking test (10MWT), the modified Gait Abnormality Rating Scale (GARS-M), Barthel Index (BI), and the walking index for spinal cord injury II (WISCI II) score results before and after robotic rehabilitation. Clinical outcomes were compared after treatment. We included nine patients with various spine problems. After HAL treatment, the speed during the 10MWT significantly improved from 64.1 ± 16.0 to 74.8 ± 10.8 m/min, and the walking cadence decreased from 102.7 ± 17.6 to 92.7 ± 10.9 steps/min. The BI score also improved from 83.3 ± 16.0 to 95.6 ± 5.8, and the WISCI II score improved from 19.7 ± 0.5 to 20.0 ± 0.0. Furthermore, the total GARS-M score improved from 6.0 ± 5.7 to 2.3 ± 3.3. The maximum angles of the trunk swing were improved from 2.2 ± 1.9 to 1.2 ± 0.9 degrees. Neurorehabilitation therapy using HAL for spinal surgery patients was considered feasible following spine surgery.
Hand Detection Using Cascade of Softmax Classifiers
Authors: Zhao Yan-Guo , Zheng Feng , Song Zhan
Published: July 2018

Sliding-window based multiclass hand posture detections are often performed by detecting postures of each predefined category using an independent detector, which makes it lack efficiency and results in high postures confusion rates in real-time applications. To tackle such problems, in this work, an efficient cascade detector that integrates multiple softmax-based binary (SftB) models and a softmax-based multiclass (SftM) model is investigated to perform multiclass posture detection in parallel. The SftB models are used to distinguish the predefined postures from the background regions, and the SftM model is applied to discriminate among all the predefined hand posture categories. Another usage of the cascade structure is that it could effectively decompose the complexity of background pattern space and therefore improve the detection accuracy. In addition, to balance the detection accuracy and efficiency, the HOG features of increasing resolutions will be adopted by classifiers of increasing stage-levels in the cascade structure. The experiments are implemented under various scenarios with complicated background and challenging lightings. Results show the superiority of the proposed SftB classifiers over the traditional binary classifiers such as logistic regression, as well as the accuracy and efficiency improvements brought by the softmax-based cascade architecture compared with the noncascade multiclass softmax detectors.
Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes
Authors: Rodriguez-Vida Alejo , Perez-Gracia Jose Luis , Bellmunt Joaquim
Published: July 2018

Immune checkpoint inhibitors (ICI) have emerged as a novel therapeutic strategy that achieves significant clinical benefit in several tumor types, including urothelial cancer. Overall, these agents have shown objective response rates of around 20% to 23%, which indicates that a significant proportion of patients do not benefit from immunotherapy when given as monotherapy. Moreover, despite an initial response to therapy and an improvement in the median duration of response compared with chemotherapy, still only half of the patients develop long-term maintained remissions. Active research is ongoing in several fields, aiming to increase the number of patients that benefit from ICI, and this research is largely based on the development of biomarkers for personalized immunotherapy and novel combinations of ICI with other agents. This article will review ongoing efforts to develop combinations of ICI with other therapeutic strategies in patients with urothelial cancer, including chemotherapy, targeted agents, other immunotherapy strategies, and radiotherapy.
PERK Regulates Glioblastoma Sensitivity to ER Stress Although Promoting Radiation Resistance
Authors: Dadey David Y.A. , Kapoor Vaishali , Khudanyan Arpine , Thotala Dinesh , Hallahan Dennis E.
Published: July 2018

The aggressive nature and inherent therapeutic resistance of glioblastoma multiforme (GBM) has rendered the median survival of afflicted patients to 14 months. Therefore, it is imperative to understand the molecular biology of GBM to provide new treatment options to overcome this disease. It has been demonstrated that the protein kinase R–like endoplasmic reticulum kinase (PERK) pathway is an important regulator of the endoplasmic reticulum (ER) stress response. PERK signaling has been observed in other model systems after radiation; however, less is known in the context of GBM, which is frequently treated with radiation-based therapies. To investigate the significance of PERK, we studied activation of the PERK–eIF2α–ATF4 pathway in GBM after ionizing radiation (IR). By inhibiting PERK, it was determined that ionizing radiation (IR)-induced PERK activity led to eIF2α phosphorylation. IR enhanced the prodeath component of PERK signaling in cells treated with Sal003, an inhibitor of phospho-eIF2α phosphatase. Mechanistically, ATF4 mediated the prosurvival activity during the radiation response. The data support the notion that induction of ER stress signaling by radiation contributes to adaptive survival mechanisms during radiotherapy. The data also support a potential role for the PERK/eIF2α/ATF4 axis in modulating cell viability in irradiated GBM.

Implications: The dual function of PERK as a mediator of survival and death may be exploited to enhance the efficacy of radiation therapy.

Visual Overview: http://mcr.aacrjournals.org/content/16/10/1447/F1.large.jpg. Mol Cancer Res; 16(10); 1447–53. ©2018 AACR.
Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF–driven Signaling Axis
Authors: Regan Anderson Tarah M. , Ma Shihong , Perez Kerkvliet Carlos , Peng Yan , Helle Taylor M. , Krutilina Raisa I. , Raj Ganesh V. , Cidlowski John A. , Ostrander Julie H. , Schwertfeger Kathryn L. , Seagroves Tiffany N. , Lange Carol A.
Published: July 2018

The metastatic cascade is a complex process that requires cancer cells to survive despite conditions of high physiologic stress. Previously, cooperation between the glucocorticoid receptor (GR) and hypoxia-inducible factors (HIF) was reported as a point of convergence for host and cellular stress signaling. These studies indicated p38 MAPK-dependent phosphorylation of GR on Ser134 and subsequent p-GR/HIF–dependent induction of breast tumor kinase (PTK6/Brk), as a mediator of aggressive cancer phenotypes. Herein, p-Ser134 GR was quantified in human primary breast tumors (n = 281) and the levels of p-GR were increased in triple-negative breast cancer (TNBC) relative to luminal breast cancer. Brk was robustly induced following exposure of TNBC model systems to chemotherapeutic agents (Taxol or 5-fluorouracil) and growth in suspension [ultra-low attachment (ULA)]. Notably, both Taxol and ULA resulted in upregulation of the Aryl hydrocarbon receptor (AhR), a known mediator of cancer prosurvival phenotypes. Mechanistically, AhR and GR copurified and following chemotherapy and ULA, these factors assembled at the Brk promoter and induced Brk expression in an HIF-dependent manner. Furthermore, Brk expression was upregulated in Taxol-resistant breast cancer (MCF-7) models. Ultimately, Brk was critical for TNBC cell proliferation and survival during Taxol treatment and in the context of ULA as well as for basal cancer cell migration, acquired biological phenotypes that enable cancer cells to successfully complete the metastatic cascade. These studies nominate AhR as a p-GR binding partner and reveal ways to target epigenetic events such as adaptive and stress-induced acquisition of cancer skill sets required for metastatic cancer spread.

Implication: Breast cancer cells enlist intracellular stress response pathways that evade chemotherapy by increasing cancer cell survival and promoting migratory phenotypes. Mol Cancer Res; 16(11); 1761–72. ©2018 AACR.
Re-Evaluation of Total CO2 Concentration in Apparently Healthy Younger Adults
Authors: Kraut Jeffrey A. , Lew Vivian , Madias Nicolaos E.
Published: July 2018

The initial assessment of acid-base status is usually based on the measurement of total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3–]. Previously, we posited that the reference limits of serum [TCO2] in current use are too wide. Based on studies on the acid-base composition of normal subjects, we suggested that the reference limits of serum [TCO2] at sea level be set at 23–30 mEq/L. To validate this proposal, we queried the University of California at Los Angeles (UCLA’s) Integrated Clinical and Research Data Repository, a database containing information on 4.5 million patients seen at UCLA from 2006 to the present. Criteria for inclusion included adults (18–40 years of age), who were free of disorders that could affect acid-base balance, were not taking medications that could affect acid-base balance, and were seen for a routine medical examination or immunization in the outpatient setting. The number of individuals who met the inclusion criteria (52% female and 48% male) was 28,480, with a mean age of 28.9 ± 5.1 years. The mean serum [TCO2] level was slightly higher in males than females, 26.6 ± 2.16 mEq/L vs. 25.0 ± 2.11 mEq/L (p < 0.05). Ninety-one percent of patient values were within the proposed 23–30 mEq/L range and 61.7% were within the 24–27 mEq/L range. These findings validate our proposal that the reference range of serum [TCO2] in venous blood at sea level be narrowed to 23–30 mEq/L. Subjects with serum [TCO2] outside this range might require assessment with a venous blood gas to exclude the presence of clinically important acid-base disorders.
Is HERV-K and HERV-W Expression Regulated by miR-155 in Kidney Transplant Patients with Human Cytomegalovirus Infection?
Authors: Bergallo Massimiliano , Daprà Valentina , Calvi Cristina , Montanari Paola , Galliano Ilaria , Ravanini Paolo
Published: July 2018

According to the latest update, 2,578 unique mature micro­RNAs (miRNAs) are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. A previous study analyzing global miRNA expression patterns in GH cells (high human endogenous retrovirus, HERV, K vs. low) showed that 2 miRNAs (miR-663 and miR-638) are differentially regulated and exhibit expression parallel to that of HERV-K. The aim of this study was to evaluate HERV-K and -W pol gene and miR-155 expression in kidney transplant recipients and the possible relationship between them. The comparison between kidney transplant patients negative for human cytomegalovirus (HCMV) infection and positive patients showed a significant difference in terms of miR-155 expression (p = 0.0111). We demonstrated that HERV-K and -W pol gene expression was significantly higher in CMV-infected kidney transplant recipients versus those not infected as previously reported by our groups. Our correlation data suggest that miR-155 are not directly involved in regulating the HERV notwithstanding that we together observed increased expression of HERV-K and -W and diminished expression of miR-155 in HCMV-infected human kidney transplant recipients.
Interferon Lambda Family along with HTLV-1 Proviral Load, Tax, and HBZ Implicated in the Pathogenesis of Myelopathy/Tropical Spastic Paraparesis
Authors: Mozhgani Sayed-Hamidreza , Jahantigh Hamid Reza , Rafatpanah Houshang , Valizadeh Narges , Mohammadi Asadollah , Basharkhah Samira , Rezaee Seyed Abdolrahim
Published: July 2018

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease related to human T lymphotropic virus type 1 (HTLV-1) infection. Interferon type III (IFN-λ), which includes IL28, IL29, and IL28R, and affects the outcome of viral infections, might be complicated in the progression of HAM/TSP. Here, we investigated the host-virus interactions in the manifestation of HAM/TSP, using IL28B, IL29, IL28R, HTLV-1 Tax, HTLV-1 basic leucine zipper factor (HBZ), and proviral load (PVL). The study groups consisted of 20 patients with HAM/TSP, 20 asymptomatic HTLV-1 carriers (ACs), and 20 healthy controls (HCs). The means of PVL, Tax, and HBZ gene expressions in the HAM/TSP group (p = 0.004, 0.006, and < 0.0001, respectively) were significantly higher than in the AC group. The comparison of IL28B, IL29, and IL28R expression in the HAM/TSP, AC, and HC groups revealed no significant difference between the first 2, but lower concentrations in the HCs (IL28B: p = 0.03, 0.01; IL29: p = 0.07, 0.01; and IL28R: p < 0.0001, respectively). In the HAM/TSP group, correlations were seen between Tax and HBZ (R = 0.61, p = 0.004) and between Tax and IL29 (R = 0.45, p = 0.04). Negative correlations were observed between Tax and IL28B (R = –0.49, p = 0.02) and between HBZ and IL28R (R = –0.43, p = 0.06). In the ACs, an inverse correlation was found between Tax and IL28B (R = –0.42, p = 0.06). These findings suggest that IL29, IL28B, and IL28R interfere in the infection of HAM/TSP, mainly via Tax activation.
Carvedilol-Induced Liver Injury, a Rare Cause of Mixed Hepatitis: A Clinical Case
Authors: Rua João , Prata Ana Rita , Marques Ricardo , Silva Rafael , Gomes Bráulio , Fraga João , Fortuna Jorge
Published: July 2018

Introduction: Drug-induced liver injury is an increasingly prevalent consequence of the diversification of available therapeutic weapons, mostly idiosyncratic and with several possible mechanisms and patterns of specific damage for each drug. Carvedilol, a widely used non-selective alpha and beta blocker leads, in very rare cases, to injury of the bile ducts by toxic metabolites, resulting in a mixed-pattern hepatitis with possible progression to chronic cholestatic syndrome and cirrhosis. The authors report the second known case of this important toxicity. Clinical Case: An 83-year-old woman was admitted to the Internal Medicine ward for etiological clarification of a mixed-pattern hepatitis. Clinical history was unremarkable and structural, infectious, and autoimmune causes were excluded by blood tests and imaging exams, ultimately leading to the diagnosis of toxic hepatitis that was further confirmed by liver biopsy with morphologic findings of mixed-pattern liver injury. Carvedilol, started 6 months before, was deemed the causal agent since it was the only drug with a clinically, temporally, analytically, and histologically compatible pattern. The withdrawal of the drug resulted in slow reversal of the referred abnormalities. Conclusion: In very rare cases, carvedilol can cause important liver toxicity as a chronic cholestatic syndrome which can evolve to cirrhosis. It should be taken in consideration as causal agent in similar cases and stopped immediately upon suspicion, as the timely withdrawal results in reversion of the pathological findings.
Contrasting Rates of LINE-1 Amplification among New World Primates of the Atelidae Family
Authors: Sookdeo Akash , Ruiz-García Manuel , Schneider Horacio , Boissinot Stéphane
Published: July 2018

LINE-1 (L1) retrotransposons constitute the dominant category of transposons in mammalian genomes. L1 elements are active in the vast majority of mammals, and only a few cases of L1 extinction have been documented. The only possible case of extinction in primates was suggested for South American spider monkeys. However, these previous studies were based on a single species. We revisited this question with a larger phylogenetic sample, covering all 4 genera of Atelidae and 3 species of spider monkeys. We used an enrichment method to clone recently inserted L1 elements and performed an evolutionary analysis of the sequences. We were able to identify young L1 elements in all taxa, suggesting that L1 is probably still active in all Atelidae examined. However, we also detected considerable variations in the proportion of recent elements indicating that the rate of L1 amplification varies among Atelidae by a 3-fold factor. The extent of L1 amplification in Atelidae remains overall lower than in other New World monkeys. Multiple factors can affect the amplification of L1, such as the demography of the host and the control of transposition. These factors are discussed in the context of host life history.
Ultralow Anterior Resection and Coloanal Anastomosis for Low-Lying Rectal Cancer: An Appraisal Based on Bowel Function
Authors: Cheong Chinock , Oh Seung Yeop , Choi Soo Jeong , Suh Kwang Wook
Published: July 2018

Backgrounds/Aims: On the basis of acceptable oncologic results, ultralow anterior resection (ULAR) and colo-anal anastomosis plus hand-sewn coloanal anastomosis have been performed for treating very low-lying rectal cancer. However, many patients experience bowel dysfunction after ULAR. Studies have provided inadequate data on bowel dysfunctions and only a few functional studies have focused on low rectal cancer. Therefore, we aimed to elucidate the severity of bowel dysfunction after ULAR in a single-surgeon cohort. Methods: In this prospective observational study, we analyzed data of 203 patients who underwent sphincter-preserving surgery for low-lying rectal cancer (tumor located within 5 cm from the anus) between January 2011 and December 2014. During routine follow-up, examinations (3–6 months interval) after ileostomy closure, patients were asked about their bowel functions based on the Wexner incontinence and LAR syndrome (LARS) scores. Patients were divided into 2 groups: LAR group (LAR with double-stapled anastomosis) and ULAR group (ULAR with coloanal anastomosis), and functional scores were compared between 6 and 36 months. Seven risk factors for major LARS were analyzed. Results: At 36 months after surgery, 94.2 and 70.6% of patients in the ULAR group still had moderate to severe incontinence and major LARS respectively. Fecal incontinence improved significantly over time (ULAR group, 14.4 vs. 7.2, p = 0.045; LAR group, 13.9 vs. 5.4, p < 0.05). However, improvement in LARS over time was observed in the LAR group only (26.5 vs. 19.7, p = 0.045). In the ULAR group, the difference did not reach a statistical significance (33.6 vs. 26.0, p = 0.10). Major LARS and moderate incontinence were significantly higher in the ULAR group than in the LAR group (70.6 vs. 47.6%, p = 0.001; 82.4 vs. 32.0%, p = 0.012 respectively). Among the 7 factors evaluated in multivariable analysis, old age (> 70), male sex, ULAR per se, and chemoradiation therapy were found to be meaningful risk factors for major LARS. Conclusion: In patients with low rectal cancers undergoing ULAR plus coloanal anastomosis, bowel dysfunctions were severe. Bowel dysfunctions improved over time, but most patients still experienced major bowel dysfunctions even 36 months after surgery. Risk factors for bowel dysfunctions were old age, male sex, adjuvant chemoradiation therapy, and ULAR. Therefore, ULAR should be performed in carefully selected patients with low-lying rectal cancer.