bluuebunny/crossref_metadata_2025 huggingface dataset:
066 Impact of long-term teriflunomide treatment on lymphocyte counts and infections in pooled temso and tower studies
Authors: Comi Giancarlo , Macdonell Richard , Benamor Myriam , Truffinet Philippe , Thangavelu Karthinathan , Mandel Matt , Freedman Mark S
Published: May 2018

Introduction

In TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide was associated with early reductions in mean lymphocyte counts, which remained within the normal range. Here, we analyse long-term effects of teriflunomide on lymphocyte counts and infections in pooled TEMSO/TOWER core and extension data (TEMSO extension, NCT00803049).

Methods

Pooled data from core studies are reported for patients receiving placebo or teriflunomide 14 mg. In the extensions, placebo-treated patients received active treatment; results from pooled core and extension studies are reported for the teriflunomide 14 mg group. Lymphocyte counts were obtained every 2 weeks until Week 24, and every 6 weeks thereafter. Lymphopenia was identified from 2 consecutive lymphocyte counts below LLN and graded by Common Terminology Criteria for Adverse Events.

Results

In the core studies, placebo/teriflunomide-treated patients rarely experienced Grade 1 (0.7%/2.1%) or 2 (0.5%/1.4%) lymphopenia. Infections were reported in placebo-treated (40.0%/75.0%) and teriflunomide-treated (73.3%/20.0%) patients with Grade 1 or 2 lymphopenia, respectively. No patients with Grade 1 lymphopenia and 1 placebo-treated patient with Grade 2 lymphopenia developed a serious infection. In the combined core and extension studies, teriflunomide-treated patients (n=1354) experienced few Grade 1 (3.0%) or 2 (2.4%) lymphopenias; infections were reported in 25/40 (62.5%) and 19/33 (57.6%) patients, respectively, vs 718/1281 (56.0%) patients without lymphopenia. Serious infections occurred in patients without lymphopenia (47 patients [3.7%]) and in those with Grade 1 (1 [2.5%]) or Grade 2 (3 [9.1%]) lymphopenia. No Grade 3/4 lymphopenias were recorded. Despite the overall low rate of lymphopenia, occurrence and severity of lymphopenia will also be reported in subgroups of Asian and white patients.

Conclusion

In long-term TEMSO and TOWER trials, low-grade lymphopenia was uncommon, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia, consistent with an immunomodulatory mechanism of action of teriflunomide with limited impact on protective immunity.
068 Evaluation of the long-term treatment effect of teriflunomide on cognitive outcomes and association with brain volume change: data from temso and its extension study
Authors: Sprenger Till , Lechner-Scott Jeannette , Sormani Maria P , Wolinsky Jerry S , Wuerfel Jens , Thangavelu Karthinathan , Cavalier Steven , Mandel Matt , Kappos Ludwig
Published: May 2018

Introduction

In a blinded SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis of TEMSO (NCT00134563), teriflunomide significantly reduced brain volume loss (BVL) over 2 years vs placebo. Further analysis indicated a strong correlation between 2 year BVL and disability worsening, showing better disability outcomes for patients with lower rates of BVL. Here, we explore the relationship between BVL and long-term changes in cognitive function in TEMSO and its extension (NCT00803049).

Methods

The effect of teriflunomide on cognitive function was assessed by change from baseline in Paced Auditory Serial Addition Test (PASAT)−3 scores in the TEMSO core (n=1086) and extension (n=740) studies. To evaluate change in PASAT-3 scores over 5 years, the TEMSO population was categorised into groups defined by percentage brain volume change from baseline to Year 2 (assessed by SIENA).

Results

Adjusted mean changes from baseline to Week 96 in PASAT-3 raw/Z-scores were –0.265/–0.022 and 0.870/0.073 for placebo and teriflunomide 14 mg, respectively (difference vs placebo, p=0.0435 in both instances). Long-term improvements in PASAT-3 Z-scores were observed with teriflunomide 14 mg treatment: mean (SD) changes from baseline at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. Mean (SD) units of change from baseline in raw PASAT-3 scores for teriflunomide 14 mg–treated patients at Weeks 156 and 276 were 2.36 (7.73) and 2.43 (8.24), respectively. In an association analysis, the group with least BVL from baseline to Year 2 demonstrated a significant improvement in PASAT-3 score with teriflunomide treatment over 5 years vs the group with most BVL.

Conclusion

Teriflunomide significantly improved PASAT-3 performance vs placebo over 5 years in the TEMSO core and extension studies. Slower rates of BVL over 2 years correlated with better long-term PASAT-3 improvement. This study suggests that BVL earlier in the disease course predicts longer-term cognitive function.

Study support

Sanofi.
069 Peginterferon beta-1a improves clinical and radiological disease outcomes in patients who are newly diagnosed with relapsing-remitting multiple sclerosis (RRMS): subgroup analysis of advance
Authors: Newsome Scott D , Arnold Douglas L , Yun Jang , Meergans Matthias , Naylor Maria L
Published: May 2018

Introduction

The pivotal phase 3 ADVANCE study evaluated the efficacy of subcutaneous peginterferon beta-1a 125 mcg every 2 weeks in RRMS patients, approximately 45% of whom were newly diagnosed and had no prior disease-modifying therapy (DMT) use. We evaluated peginterferon beta-1a’s effect on clinical and radiological disease activity in newly diagnosed, treatment-naive patients from ADVANCE.

Methods

ADVANCE was a 2 year double-blinded study. In year 1, patients were randomised to receive peginterferon beta-1a every 2 or 4 weeks or placebo. In year 2, placebo patients were re-randomised to receive peginterferon beta-1a every 2 or 4 weeks (delayed-treatment group). Here, the subgroup of patients diagnosed ≤1 year prior to enrolment who had no prior DMT use was analysed. Annualised relapse rate (ARR), time to first relapse, 24 week confirmed disability worsening (CDW), MRI endpoints, and safety were compared between the every-2-weeks group and the delayed-treatment group.

Results

Over 2 years, the adjusted ARR in newly diagnosed patients was 32.3% lower for the peginterferon beta-1a every-2-weeks group (n=231) than for the delayed-treatment group (n=229; p=0.0352). Time to first relapse was longer in the every-2-weeks group than in the delayed-treatment group (p=0.0101), and the rate of 24 week CDW was numerically lower in the every-2-weeks group than in the delayed-treatment group. At year 2, the number of new/newly-enhancing T2 lesions was lower in the every-2-weeks than in the delayed-treatment group (p<0.0001), although no difference in the number of gadolinium-enhancing lesions was observed. The safety profile in newly diagnosed patients was similar to that of the overall patient population.

Conclusion

Newly diagnosed, treatment-naive patients had significantly reduced disease activity when administered peginterferon beta-1a every 2 weeks compared with delayed-treatment patients. These results are generally consistent with results from the ADVANCE overall population and highlight the benefits of initiating therapy early in the RRMS disease course.

Study support

Biogen
087 Cerebral fat embolism in a case of endoscopic oesophageal dilatation
Authors: Clarke Andrew , Vallat Wilson , Kleinig Timothy
Published: May 2018

Introduction

Fat Embolism Syndrome (FES) is rare, usually occurring in the setting of long bone fractures or trauma. Furthermore, isolated neurological form or pure cerebral fat embolism (CFE) is an atypical presentation. The authors are not aware of any previously documented cases of endoscopy related CFE without accompanying trauma.

Case

A 61 year old male presented for an elective endoscopy with dilatation for known oesophageal ulcer with stricturing. In post-operative recovery one hour post dilatation, he was found to have left sided weakness, aphasia and right fixed lateral gaze, NIHSS score of 18. He subsequently developed generalised tonic clonic seizures with reduced sensorium requiring intubation. CT brain was normal. MRI brain the following day showed bi-hemispheric punctate scattered white matter diffusion weighted restrictions (starfield pattern) characteristic for CFE. There were no signs of respiratory distress or petechial skin rash. Cardiac monitoring and transthoracic echocardiography with bubble test were normal.

Conclusion

This case highlights a rare presentation of an uncommon syndrome, in a previously unidentified patient cohort, and the most appropriate investigation required to diagnose CFE.
094 Vascular targeting of phosphatidylserine causing thrombotic occlusion in an arteriovenous malformation animal model
Authors: Stoodley Marcus , Gauden Andrew , Lee Vivienne , Subramanian Sinduja , Moutrie Vaughan , Zhao Zhenjun , McRobb Lucinda
Published: May 2018

Introduction

One third of brain arteriovenous malformations (AVMs) are untreatable with current methods. Previous work has identified phosphatidylserine externalised in the endothelial plasma membrane after treatment with radiosurgery as a potential target for biological pro-thrombotic therapy. We hypothesise that treatment of AVMs with Gamma knife radiosurgery (GKS) and a vascular targeting agent with a thrombotic compound will cause localised thrombosis within the AVM vessels.

Methods

A rat animal model was used by performing an end-to-side anastomosis of the external jugular vein (EJV) to the common carotid artery. The model AVM was treated with radiosurgery (20 Gy) using a Leksell Gamma Knife. At 3 weeks following GKS a dose of a conjugate of annexin V and thrombin was administered intravenously. Groups injected with saline or thrombin alone were used as controls. At 4 weeks, an angiogram was performed with tissue harvested for histology.

Results

There was angiographic evidence of AVM occlusion in 69% of conjugate-treated animals and none of the control animals (p=0.002). AVM occlusion occurred in 63% of the GKS group treated with conjugate (p=0.03), and in 75% of the sham-GKS conjugate treated group (p=0.009). Histological evidence of thrombus was present within the EJV and nidus of 62.5% of animals in the GKS with conjugate group and <25% of the control groups (p=0.026).

Conclusion

This study demonstrates that targeting of PS with an annexin V-thrombin conjugate is effective in causing thrombotic occlusion in a model AVM. These results are the first of their kind and indicate that ligand vascular targeting with radiation sensitisation may become a potential future treatment in brain AVMs.
097 A rare case of recurrent transient global amnesia
Authors: Saleem Sameer , Patel Ronak , Gawarikar Yash
Published: May 2018

Introduction

Transient global amnesia (TGA) is a clinical syndrome characterised by the sudden onset of anterograde amnesia accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, without compromise of other neurologic functions.

Case

A 71 year old male presented to the neurology clinic with history of recurrent episodes of reversible anterograde amnesia with repetitive questioning. His first two episodes were in May 2016 and clinically very typical of TGA. After that he had recurrent episodes and he noted that they were happening on a monthly basis. He had an episode on 24 March 2017 at Yangon airport as he was returning from a trip to Myanmar. He had had three episodes in February 2017 and two in March and April 2017 and one episode on 20 May 2017. Initial MRI brain showed frontotemporal atrophy suggestive of Alzheimer’s disease and there was hypo-perfusion on the nuclear medicine study. EEG did not show any epileptic activity. His partner described a typical episode where the patient lost his memory for the preceding 24 hours and he had repetitive questioning such as ”what day is it” repeatedly. During the entire episode, he was conscious and able to converse appropriately. He had another episode of amnesia on 19 August and was admitted and underwent an MRI of brain, which showed characteristic punctate abnormalities in the bilateral hippocampi on B2000 DWI.

Conclusion

The estimated annual rate of recurrence of TGA is 5.8%. Diagnosis is made from typical clinical features and typical MRI DWI findings of punctate lesions in the hippocampal with a DWI resolution of B=2000, and a thin slice thickness of 2 to 3 mm. Our patient had 11 documented episodes of transient amnesia and was a diagnostic dilemma until the characteristic hippocampal abnormalities were demonstrated on MRI.
Anatomy of the deep venous system in vein of Galen malformation and its changes after endovascular treatment depicted by magnetic resonance venography
Authors: Winkler Olivia , Brinjikji Waleed , Lanfermann Heinrich , Brassel Friedhelm , Meila Dan
Published: May 2018

Background and purpose

It is classically thought that the internal cerebral veins (ICV) do not communicate with the venous pouch of vein of Galen malformations (VGM). We report on the anatomy of the deep venous system in VGM with special emphasis on the drainage of the ICV and possible changes after endovascular treatment.

Materials and methods

We retrospectively analyzed DSA and 2D time-of-flight MR venograms of 55 children with VGM. We evaluated all pre- and post-operative images for the presence of the ICVs and determined their route of venous drainage.

Results

Of 55 children, pre-operative 2D MRV detected the ICVs in 19 cases (35%) compared with one case (2%) for pre-embolization DSA (2%) (P<0.0001). Of the cases in which the ICVs were seen preoperatively, in 15 cases (78.9%) the ICV drained directly into the VGM while in the other four cases, the ICV used alternative venous drainage routes. On post-operative MRV, the ICVs were seen in 17 cases (31%) on MRV and 10 cases (18.2%) on DSA with drainage into an adult-like vein of Galen in 13 cases (76%), respectively (P=0.08). In four cases normal ICV drainage into the vein of Galen was seen even when the venous sac was closed. In two cases there was a change in ICV drainage from the vein of Galen to the lateral mesencephalic vein.

Conclusion

The communication of the ICV with the VGM is a common phenomenon. Different changes of venous drainage routes do occur after treatment and are best seen on MRV.
Prevalence of human papillomavirus by geographical regions, sexual orientation and HIV status in China: a systematic review and meta-analysis
Authors: Ma Xiaomeng , Wang Qian , Ong Jason J , Fairley Christopher K , Su Shu , Peng Peng , Jing Jun , Wang Linhong , Soe Nyi Nyi , Cheng Feng , Zhang Lei
Published: May 2018

Objective

Human papillomavirus (HPV) infection causes multiple cancers in both women and men. In China, both HPV vaccination and cervical cancer screening coverages are low. We aim to investigate the temporal and geographical trends of HPV DNA prevalence in heterosexual men, women, men who have sex with men (MSM) and people living with HIV (PLHIV) in China.

Methods

We conducted a systematic review, collecting publications in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Data from January 2000 to May 2017. A total of 247 studies were selected for this meta-analysis to estimate pooled HPV prevalence, incidence of cervical cancer and risk of infection for subgroups. Meta-regression was applied to identify contributing factors to prevalence heterogeneities.

Results

The national HPV prevalence was 15.6% (95% CI (14.4% to 16.9%)) in women with normal cervical cytology, and Central China had the highest prevalence (20.5% (15.2% to 25.8%)). HPV prevalence in heterosexual men (14.5% (11.3% to 17.7%)) was comparable with that of women (OR=1.09 (0.98 to 1.17)), but HPV prevalence in MSM (59.9% (52.2% to 67.6%)) was significantly higher than that in heterosexual men (OR=8.81 (8.01 to 9.69)). HIV-positive women (45.0% (38.4% to 51.6%)) and HIV-positive MSM (87.5% (82.3% to 90.9%)) had 4.67 (3.61 to 6.03) and 6.46 (5.20 to 8.02) times higher risk of HPV infection than their HIV negative counterparts.

Conclusion

HPV infection is prevalent in China, particularly in Central China, in comparison with the global level and neighbouring countries. Targeted HPV vaccination for women, MSM and PLHIV and scale-up of cervical screening for women are priorities in curbing the HPV epidemic in China.
A systematic understanding of signaling by ErbB2 in cancer using phosphoproteomics
Authors: Sidhanth C. , Manasa P. , Krishnapriya S. , Sneha S. , Bindhya S. , Nagare R.P. , Garg M. , Ganesan T.S.
Published: May 2018

ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%–30%) and gastric cancer (10%–20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins. It also focuses on the techniques that are currently available to evaluate the entire phosphoproteome following activation of ErbB2. Identification of new and relevant phosphoproteins can not only serve as new therapeutic targets but also as a surrogate marker in patients to assess the activity of compounds that inhibit ErbB2. Overall, such analysis will improve understanding of signaling by ErbB2.
Use of alkylated, amphiphilic zinc porphyrins to disperse individualized SWCNTs
Authors: Münich Peter W. , Wagner Pawel , Officer David L. , Guldi Dirk M.
Published: May 2018

A series of zinc porphyrins, namely ZnPa and ZnPb, which exist predominantly as aggregates, are utilized in a top-down preparation of individualized and stabilized single wall carbon nanotubes (SWCNTs). Sizable interactions in the ground state of the corresponding SWCNT/ZnPa and SWCNT/ZnPb electron donor–acceptor systems lead to charge transfer in the excited state. The product includes the simultaneous reduction of the electron-accepting SWCNTs and the oxidation of the electron-donating ZnPa and ZnPb.
Prediction of half-metallicity in the NaS, NaSe and NaTe alkali-metal chalcogenides using first principles
Authors: Sadouki H. , Belkadi A. , Zaoui Y. , Amari S. , Obodo K. O. , Beldi L. , Bouhafs B.
Published: May 2018

First-principles full-potential linearized augmented plane-wave method based on density functional theory is used to investigate the structural, electronic and magnetic properties of NaS, NaSe and NaTe alkali-metal chalcogenides binary compounds. These compounds in different crystalline phases: NaCl (B1), CsCl (B2), ZB (B3), NiAs (B81), WZ (B4) and Pnma were calculated within the generalized gradient approximation (GGA-PBE) and the modified Becke–Johnson approach (mBJ-GGA-PBE) for the exchange-correlation energy and potential. We found that the most stable phase for the NaX binary compounds is the nonmagnetic Pnma phase. The calculated lattice parameters, bulk moduli, their first-pressure derivatives and internal parameters are in good agreement with the other theoretical data. The electronic band structure and density of states show that half-metallic and magnetic character arises, which can be attributed to the presence of spin-polarized [Formula: see text] orbitals in the group VI elements. The NaS, NaSe and NaTe binary compounds show half-metallic character in ZB and WZ phases, with an integer magnetic moment of 1 [Formula: see text] per formula unit and half-metallic gaps.
Symmetric and antisymmetric vibration in elastic plate with voids immersed in a liquid
Authors: Lianngenga R. , Duhawma L. P. , Thangmawia L.
Published: May 2018

The problem of the symmetric and antisymmetric vibrations are attempted for the elastic plate with voids immersed in a liquid. The frequency equations are derived and deduced for the cases of plate wave, flexural and Rayleigh waves. It is also derived the cases when the liquid is replaced by vacuum/air. The two modes of vibration for the modified symmetric, antisymmetric, plate, flexural and Rayleigh waves in the considered medium are discussed. Numerically and analytically, the phase speeds and attenuations of symmetric and antisymmetric vibration, plate wave, flexural and Rayleigh waves are computed for a particular model. The effects of voids parameters on the phase speeds are also discussed.
Open-slope, translational submarine landslide in a tectonically active volcanic continental margin (Licosa submarine landslide, southern Tyrrhenian Sea)
Authors: Sammartini M. , Camerlenghi A. , Budillon F. , Insinga D. D. , Zgur F. , Conforti A. , Iorio M. , Romeo R. , Tonielli R.
Published: May 2018

The southern Tyrrhenian continental margin is the product of Pliocene–Recent back-arc extension. An area of approximately 30 km
2
of gentle (about 1.5°) lower slope of the last glacial outer shelf sedimentary wedge in water depths of between 200 and 300 m failed between 14 and 11 ka BP. We approached the landslide by multibeam and sub-bottom profiler surveying, high-resolution multichannel seismics, and coring for stratigraphic and geotechnical purposes. With regard to a slope-stability analysis, we carried out an assessment of the stratigraphic and structural setting of the area of the Licosa landslide. This analysis revealed that the landslide detached along a marker bed that was composed of the tephra layer Y-5 (
c.
39 ka). Several previously unknown geological characteristics of the area are likely to have affected the slope stability. These are the basal erosion of the slope in the Licosa Channel, a high sedimentation rate in the sedimentary wedge, earthquake shaking, the volcanic ash nature of the detachment surface, subsurface gas/fluid migration, and lateral porewater flow from the depocentre of wedge to the base of the slope along the high-permeability ash layers. A newly discovered prominent structural discontinuity is identified as the fault whose activity may have triggered the landslide.
From Tissues to Cell Types and Back: Single-Cell Gene Expression Analysis of Tissue Architecture
Authors: Chen Xi , Teichmann Sarah A. , Meyer Kerstin B.
Published: May 2018

With the recent transformative developments in single-cell genomics and, in particular, single-cell gene expression analysis, it is now possible to study tissues at the single-cell level, rather than having to rely on data from bulk measurements. Here we review the rapid developments in single-cell RNA sequencing (scRNA-seq) protocols that have the potential for unbiased identification and profiling of all cell types within a tissue or organism. In addition, novel approaches for spatial profiling of gene expression allow us to map individual cells and cell types back into the three-dimensional context of organs. The combination of in-depth single-cell and spatial gene expression data will reveal tissue architecture in unprecedented detail, generating a wealth of biological knowledge and a better understanding of many diseases.
Molecular Mechanisms of Fast Neurotransmitter Release
Authors: Brunger Axel T. , Choi Ucheor B. , Lai Ying , Leitz Jeremy , Zhou Qiangjun
Published: May 2018

This review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca2+-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity.
Efficacy and Safety of Traditional Chinese Medicine on Nonerosive Reflux Disease: A Meta‐Analysis of Randomized Controlled Trials
Authors: Xiao Jiao , Yang Yunfeng , Zhu Yuanrong , Qin Yan , Li Yifan , Fu Mengjie , Zhai Zhengdong , Zhu Lingyun
Published: May 2018

Objectives. Traditional Chinese medicine (TCM) therapy for nonerosive reflux disease (NERD) remains controversial. The aim of this study was to evaluate the efficacy and safety of TCM regimens in NERD treatment. Methods. Randomized controlled trials (RCTs) of TCM treatment for NERD through September 31, 2017, were systematically identified in PubMed, Wanfang Data, CNKI, VIP, CBM, Ovid, Web of Science, and Cochrane Library databases. Quality assessment was performed by employing the Cochrane Risk of Bias assessment tool. Results. A total of 725 and 719 patients in 14 RCTs were randomly divided into TCM alone and conventional Western medicine groups, respectively. The clinical total effective rate of the TCM group was markedly higher than that of the single proton pump inhibitors (PPIs) or Prokinetics therapy group (RR = 1.19, 95% CI = 1.07–1.31, and P = 0.0008), while it was comparable to that of the combination of PPIs and Prokinetics therapy group (RR = 1.14, 95% CI = 1.00–1.29, and P = 0.05). Compared with Western medicine group, the TCM group showed improved symptom relief through a reduced RDQ score (SMD = −0.91; 95% CI = −1.68–−0.15; and P = 0.02). Additionally, TCM clearly decreased the recurrence rate (RR = 0.38, 95% CI = 0.28–0.52, and P < 0.00001). Adverse events, such as constipation, sickness, fever, abdominal distension, and stomach noise, were slight for both the TCM and Western medicine groups and disappeared after the easement of pharmacological intervention; in particular, TCM possessed fewer side effects. Conclusion. Compared with PPIs or Prokinetics therapy alone, TCM single therapy can better improve the clinical total effective rate and symptom relief and decrease the recurrence rate and adverse events in the treatment of NERD. Our results suggest that TCM will be a promising alternative therapy for NERD patients in the future.
Medical Image Fusion Based on Sparse Representation and PCNN in NSCT Domain
Authors: Xia Jingming , Chen Yiming , Chen Aiyue , Chen Yicai
Published: May 2018

The clinical assistant diagnosis has a high requirement for the visual effect of medical images. However, the low frequency subband coefficients obtained by the NSCT decomposition are not sparse, which is not conducive to maintaining the details of the source image. To solve these problems, a medical image fusion algorithm combined with sparse representation and pulse coupling neural network is proposed. First, the source image is decomposed into low and high frequency subband coefficients by NSCT transform. Secondly, the K singular value decomposition (K-SVD) method is used to train the low frequency subband coefficients to get the overcomplete dictionary D, and the orthogonal matching pursuit (OMP) algorithm is used to sparse the low frequency subband coefficients to complete the fusion of the low frequency subband sparse coefficients. Then, the pulse coupling neural network (PCNN) is excited by the spatial frequency of the high frequency subband coefficients, and the fusion coefficients of the high frequency subband coefficients are selected according to the number of ignition times. Finally, the fusion medical image is reconstructed by NSCT inverter. The experimental results and analysis show that the algorithm of gray and color image fusion is about 34% and 10% higher than the contrast algorithm in the edge information transfer factor QAB/F index, and the performance of the fusion result is better than the existing algorithm.
Transient Elastography for Significant Liver Fibrosis and Cirrhosis in Chronic Hepatitis B: A Meta-Analysis
Authors: Qi Xiaolong , An Min , Wu Tongwei , Jiang Deke , Peng Mengyun , Wang Weidong , Wang Jing , Zhang Chunqing , CHESS Study Group on behalf of the
Published: May 2018

Background. The hepatitis B virus infection is a global health issue and the stage of liver fibrosis affects the prognosis in patients with chronic hepatitis B (CHB). We performed the meta-analysis describing diagnostic accuracy of transient elastography (TE) for predicting CHB-related fibrosis. Methods. We performed an adequate literature search to identify studies that assessed the diagnostic accuracy of TE in CHB patients using biopsy as reference standard. Hierarchical summary receiver-operating curves model and the bivariate mixed-effects binary regression model were applied to generate summary receiver-operating characteristic curves and pooled estimates of sensitivity and specificity. Results. The area under the summary receiver-operating curve for significant fibrosis and cirrhosis was 0.86 (95% confidence interval (CI): 0.83–0.89) and 0.92 (95% CI: 0.90–0.94), respectively. The sensitivity, specificity, and diagnostic odds ratio of TE for significant fibrosis were 0.78 (95% CI: 0.73–0.81, p<0.01; I2=85.59%), 0.81 (95% CI: 0.77–0.84, p<0.01; I2=88.20%), and 14.44 (95% CI: 10.80–19.31, p<0.01; I2=100%) and for cirrhosis were 0.84 (95% CI: 0.80–0.88, p<0.01; I2=76.67%), 0.87 (95% CI: 0.84–0.90, p<0.01; I2=90.89%), and 36.63 (95% CI: 25.38–52.87, p<0.01; I2=100%), respectively. The optimal cut-off values of TE were 7.25 kPa for diagnosing significant fibrosis and 12.4 kPa for diagnosing cirrhosis, respectively. Conclusion. TE is of great value in the detection of patients with CHB-related cirrhosis but has a suboptimal accuracy in the detection of significant fibrosis.
Valorisation of GRP Dust Waste in Fired Clay Bricks
Authors: Mobili Alessandra , Giosuè Chiara , Tittarelli Francesca
Published: May 2018

In Europe, the total amount of Glass Reinforced Plastic (GRP) waste is increasing. In order to valorise GRP dust (GRPd) waste and to reduce the consumption of nonrenewable resources in building materials, GRPd has been already investigated in cementitious materials where it gives even an improvement in some performances of the final products. Valorisation of GRPd waste in the production of bricks can be considered as a further alternative. In this paper, GRPd waste was substituted to the clay volume at 5% and 10% for the manufacturing of fired clay bricks. All specimens were subjected to a firing temperature of 850°C for 6 hours, then tested and compared in terms of porosity, compressive and flexural strengths, density, and water absorption. Despite a decrease in compressive strength up to 46% with 10% of GRPd substitution and an increase of water absorption from 14% to 29% with 5% and 10% of GRPd substitution, respectively, an increase in terms of lightness (about 10%), maximum flexural strength (up to 31%), and deflections at the maximum load (up to 130%) has been registered by specimens with 10% of GRPd substitution.
Stability Analysis of an Advanced Persistent Distributed Denial-of-Service Attack Dynamical Model
Authors: Zhang Chunming , Xiao Jingwei
Published: May 2018

The advanced persistent distributed denial-of-service (APDDoS) attack is a fairly significant threat to cybersecurity. Formulating a mathematical model for accurate prediction of APDDoS attack is important. However, the dynamical model of APDDoS attack has barely been reported. This paper first proposes a novel dynamical model of APDDoS attack to understand the mechanisms of APDDoS attack. Then, the attacked threshold of this model is calculated. The global stability of attack-free and attacked equilibrium are both proved. The influences of the model’s parameters on attacked equilibrium are discussed. Eventually, the main conclusions of the theoretical analysis are examined through computer simulations.
A New Linear Difference Scheme for Generalized Rosenau-Kawahara Equation
Authors: Chen Tao , Xiang Kaili , Chen Peimin , Luo Xumei
Published: May 2018

We introduce in this paper a new technique, a semiexplicit linearized Crank-Nicolson finite difference method, for solving the generalized Rosenau-Kawahara equation. We first prove the second-order convergence in L∞-norm of the difference scheme by an induction argument and the discrete energy method, and then we obtain the prior estimate in L∞-norm of the numerical solutions. Moreover, the existence, uniqueness, and satiability of the numerical solution are also shown. Finally, numerical examples show that the new scheme is more efficient in terms of not only accuracy but also CPU time in implementation.
Introducción del Editor
Authors: Prat A. Gabriel
Published: May 2018

Sin resumen
Hemorragia Subaracnoidea y Malformaciones Vasculares Encefálicas
Authors: Méndez S, Jorge
Published: May 2018

Sin resumen
Infección urinaria: diagnóstico y tratamiento.
Authors: Guzmán Durán Ana María , Valdivieso Dávila Andrés
Published: May 2018

Sin resumen
Aporte del médico en atención primaria al cuidado de los ancianos en la comunidad.
Authors: Marín Larraín Pedro Paulo
Published: May 2018

Sin resumen
Visita de acreditadores de la Association of American Medical Colleges.
Authors: Escuela de Medicina Boletín
Published: May 2018

Sin resumen
Lactancia materna
Authors: Juez Garcia Gabriela
Published: May 2018

Sin resumen
Proteínas glicosiladas en la fisiopatología de la nefropatía diabetica.
Authors: Olmos Coelho Pablo , Gatica Gattamelati María Pía , Arriagada Oyarzo Pablo
Published: May 2018

Sin resumen
KLF4 Mediates the Effect of 5-ASA on the β-Catenin Pathway in Colon Cancer Cells
Authors: Parenti Sandra , Montorsi Lucia , Fantini Sebastian , Mammoli Fabiana , Gemelli Claudia , Atene Claudio Giacinto , Losi Lorena , Frassineti Chiara , Calabretta Bruno , Tagliafico Enrico , Ferrari Sergio , Zanocco-Marani Tommaso , Grande Alexis
Published: May 2018

Mesalazine (5-ASA) is an aminosalicylate anti-inflammatory drug capable of inducing μ-protocadherin, a protein expressed by colorectal epithelial cells that is downregulated upon malignant transformation. Treatment with 5-ASA restores μ-protocadherin expression and promotes the sequestration of β-catenin to the plasma membrane. Here, we show that 5-ASA–induced μ-protocadherin expression is directly regulated by the KLF4 transcription factor. In addition, we suggest the existence of a dual mechanism whereby 5-ASA–mediated β-catenin inhibition is caused by μ-protocadherin–dependent sequestration of β-catenin to the plasma membrane and by the direct binding of KLF4 to β-catenin. In addition, we found that 5-ASA treatment suppresses the expression of miR-130a and miR-135b, which target KLF4 mRNA, raising the possibility that this mechanism is involved in the increased expression of KLF4 induced by 5-ASA. Cancer Prev Res; 11(8); 503–10. ©2018 AACR.
Endogenous Hydrogen Sulfide Ameliorates NOX4 Induced Oxidative Stress in LPS-Stimulated Macrophages and Mice
Authors: Wang Xi-Ling , Pan Li-Long , Long Fen , Wu Wei-Jun , Yan Di , Xu Peng , Liu Si-Yu , Qin Ming , Jia Wan-Wan , Liu Xin-Hua , Zu Yi Zhun
Published: May 2018

Background/Aims: Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure. Cystathionine-γ-lyase (CSE)/ hydrogen sulfide (H2S) has potential anti-inflammatory activities in a variety of inflammatory diseases. NADPH oxidase 4 (Nox4), a member of the NADPH oxidases, is the major source of reactive oxygen species (ROS) and its expression is increased in sepsis, but its function in CSE-mediated anti-inflammatory activities remains unknown. Methods: Macrophages were either transfected with CSE, Nox4 siRNA or transduced with lentiviral vector encoding CSE or Nox4, and then stimulated with lipopolysaccharide (LPS). The expression of inflammatory mediators and signaling pathway activation were measured by quantitative PCR (qPCR), ELISA, and immunoblotting. LPS-induced shock severity in WT, Nox4 knockdown and CSE knockout (CSE-/-) mice was assessed. Results: Here we showed that CSE and Nox4 were upregulated in macrophage and mouse in response to LPS. After LPS stimulation, the inflammatory responses were significantly ameliorated by lentiviral Nox4 shRNA knockdown, but were exacerbated by lentiviral overexpressing Nox4. Furthermore, Nox4 mediated inflammation through PI3K/Akt and p-p38 mitogen-activated protein kinase signal pathway. Notably, CSE knockout served to amplify the inflammatory cascade by increasing Nox4-ROS signaling activation in septic mice and macrophage. Similarly, the enhanced production of inflammatory mediators by macrophages was reduced by CSE overexpression. Conclusion: Thus, we demonstrated that CSE/H2S attenuated LPS-induced sepsis against oxidative stress and inflammation damage probably largely through mediated Nox4 pathway.
Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients
Authors: Hu Xiang , Li Ya-Qi , Li Qing-Guo , Ma Yan-Lei , Peng Jun-Jie , Cai Sanjun
Published: May 2018

Background/Aims: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Methods: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. Results: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. Conclusion: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.
Development and validation of the WebAd-Q Questionnaire to monitor adherence to HIV therapy
Authors: Vale Felipe Campos , Santa-Helena Ernani Tiaraju de , Santos Maria Altenfelder , Carvalho Wania Maria do Espirito Santo , Menezes Paulo Rossi , Basso Caritas Relva , Silva Mariliza Henrique , Alves Ana Maroso , Nemes Maria Ines Battistella
Published: May 2018

OBJECTIVE: To present the development and validation of the WebAd-Q Questionnaire, a self-report instrument to monitor adherence to antiretroviral therapy in HIV/AIDS centers in Brazil. METHODS: The WebAd-Q is an electronic questionnaire that has three questions about the use of antiretrovirals in the last week. It was constructed from interviews and focus groups with 38 patients. Its validity was tested in a study with a sample of 90 adult patients on antiretroviral therapy for at least three months. We used electronic monitoring bottles, pill counting, and self-report interview to compare adherence. The WebAd-Q was answered on the sixtieth day, twice, with at least one hour of interval. The viral load of the patients was obtained from the service records. We have analyzed the agreement between the answers to the WebAd-Q, the associations, and the correlations with viral load and performance compared to other measures of adherence. RESULTS: Among the invited patients, 74 (82.2%) answered the WebAd-Q. No difficulties were reported to answer the questionnaire. The average answer time was 5 min 47 sec. The set of three questions of the WebAd-Q obtained agreement of 89.8%, with Kappa of 0.77 (95%CI 0.61–0.94). The non-adherence answers of the WebAd-Q were associated with detectable viral load. We obtained moderate viral load correlations with the non-adherence scale according to the WebAd-Q. For the three questions of the WebAd-Q, patients with non-adherence answers were also reported as less adherent according to the other measures of adherence. CONCLUSIONS: The WebAd-Q answered all the issues considered relevant in the validation of questionnaires, was well understood by patients, was associated with viral load, and obtained good agreement and good performance compared to the other measures. The feasibility analysis of its implementation still depends on a national study on its applicability.
Epigenomes in Cardiovascular Disease
Authors: Rosa-Garrido Manuel , Chapski Douglas J. , Vondriska Thomas M.
Published: May 2018

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies.
Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages
Authors: Mueller Paul A. , Zhu Lin , Tavori Hagai , Huynh Katherine , Giunzioni Ilaria , Stafford John M. , Linton MacRae F. , Fazio Sergio
Published: May 2018

Background:

We previously showed that mice lacking MΦLRP1
-/-
(low-density lipoprotein receptor–related protein 1 in macrophages) undergo accelerated atherosclerotic plaque formation due to changes in macrophages including increased apoptosis, decreased efferocytosis, and exaggerated transition to the inflammatory M1 phenotype. Here we sought to explore the role of macrophage low-density lipoprotein receptor–related protein 1 during regression of atherosclerosis since regressing plaques are characterized by transitioning of macrophages to M2 status as inflammation resolves.

Methods:

Apolipoprotein E
-/-
mice on a high-fat diet for 12 weeks were reconstituted with bone marrow from apolipoprotein E–producing wild-type or MΦLRP1
-/-
mice, and then placed on a chow diet for 10 weeks (n=9 to 11 mice/group). A cohort of apolipoprotein E
-/-
mice reconstituted with apolipoprotein E
-/-
bone marrow served as baseline controls (n=9).

Results:

Plaques of both wild-type and MΦLRP1
-/-
bone marrow recipients regressed compared with controls (11% and 22%, respectively;
P
<0.05), and plaques of MΦLRP1
-/-
recipients were 13% smaller than those of wild-type recipients (
P
<0.05). Recipients of MΦLRP1
-/-
marrow had 36% fewer M1 macrophages (
P
<0.01) and 2.5-fold more CCR7 (C-C chemokine receptor type 7)–positive macrophages in the plaque relative to wild-type mice (
P
<0.01). Additionally, in vivo studies of cellular egress showed a 4.6-fold increase in 5-ethynyl-2´-deoxyuridine–labeled CCR7
+
macrophages in mediastinal lymph nodes. Finally, in vivo studies of reverse cholesterol transport showed a 1.4-fold higher reverse cholesterol transport in MΦLRP1
-/-
recipient mice (
P
<0.01).

Conclusions:

Absence of macrophage low-density lipoprotein receptor–related protein 1 unexpectedly accelerates atherosclerosis regression, enhances reverse cholesterol transport, and increases expression of the motility receptor CCR7, which drives macrophage egress from lesions.
Does the mass of sample loaded affect faecal haemoglobin concentration using the faecal immunochemical test?
Authors: Piggott Carolyn , John Cerin , Bruce Helen , Benton Sally C
Published: May 2018

Background

Quantitative faecal immunochemical tests (FIT) for haemoglobin are being used for colorectal cancer (CRC) screening for asymptomatic populations and are being indicated as a suitable test to rule out CRC in symptomatic populations. Faecal samples are typically collected by patients using a probe attached to the cap of a device which is inserted into a collection device into the preservative buffer, passing through a collar to remove excess sample: this process has potential for pre-analytical error. This study investigates whether faecal haemoglobin concentration (f-Hb) results are affected by the mass and method of sample collection.

Methods

Faecal samples with detectable f-Hb were loaded into collection devices from four manufacturers using increasing masses of sample. The f-Hb in the device buffer was measured using the relevant analyser. The results from the minimum recommended load were compared with results of ‘sample overloading’.

Results

The variation in the faecal mass added to the probe (overall CVs: EXTEL HEMO AUTO-MC Collection Picker 300%, OC-Auto Sampling Bottle 3 237%, SENTiFIT pierceTube 264%, Specimen Collection Container A 250%), was more than the variation in f-Hb (respective overall CVs: 62%, 35%, 47%, 39%). The mass of faeces added to the probes increased significantly ( P < 0.0001 for all four devices), but the f-Hb did not increase significantly (EXTEL HEMO AUTO-MC Collection Picker P = 0.6820, OC-Auto Sampling Bottle 3 P = 0.9368, SENTiFIT pierceTube P = 0.7551, Specimen Collection Container A P = 0.6864).

Conclusion

The mass of sample loaded onto the probe did not impact the f-Hb significantly using all four tested devices.
The effect of loneliness on depression: A meta-analysis
Authors: Erzen Evren , Çikrikci Özkan
Published: May 2018

Background:

Negative emotions, which have a common, chronic and recurrent structure, play a vital role in the development and maintenance of psychopathology. In this study, loneliness as a negative emotion was considered to be a predisposing factor in depression.

Aim:

The aim of this meta-analysis is to determine the effect of loneliness on depression.

Method:

Initially, a literature scan was performed and all related literature was pooled together ( n = 531). Based on scales determined by the researchers, it was decided to include 88 studies in the analysis. This study obtained a sampling group of 40,068 individuals.

Results:

The results of using a random effects model for analysis showed that loneliness had a moderately significant effect on depression. None of the variables of study sampling group, type of publication and publication year were found to be moderator variables.

Conclusion:

According to the results of the research, loneliness may be said to be a significant variable affecting depression. The findings obtained are discussed in light of the literature.