bluuebunny/crossref_metadata_2025 huggingface dataset:
Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study
Authors: Liu Zhong-Yu , Au Man-Ting , He Tian-Wei , Yang Bu , Liu Bin , Zhang Liang-Ming , Luo Chun-Xiao , Rong Li-Min , Wen Chun-Yi
Published: February 2019

Purpose. Blood vessels and skeleton interact together. Endothelin-1 is a potent vasoconstrictor and also has an effect on bone metabolism. The dual antagonist to both endothelin-1 type A and B receptors, Macitentan, has been approved for clinical management of pulmonary arterial hypertension while little is known about the secondary effect of the drug on spine. We aimed to answer how vertebral bone mass responded to Macitentan treatment in mice. Methods. Sixteen male balb/c mice at 6 months were randomly assigned into 2 groups. Vehicle and Macitentan were administrated via intraperitoneal injection to Control group and Treatment group, respectively, for 4 months. At sacrifice, plasma endothelin-1 was evaluated with ELISA and vertebral bone mass was evaluated with Microcomputed Tomography and histological analysis. Results. We found higher plasma endothelin-1 level (p<0.01) and less vertebral bone mass (p<0.05) in Treatment group compared to controls. Moreover, less osteoblasts and more osteoclasts were observed in the vertebral trabecular bone in the Treatment group compared to controls, by immunohistochemistry of the cell-specific markers. Conclusions. Treatment with Macitentan is associated with significant lower vertebral bone mass and therefore the secondary effect of dual antagonists to endothelin-1 receptors on the skeleton should be monitored and investigated in clinical practice. Both osteoblasts and osteoclasts may be involved while the molecular mechanism needs to be further explored.
Evaluating the Cost-Effective Use of Follow-Up Colonoscopy Based on Screening Findings and Age
Authors: Joseph Grace N. , Heidarnejad Farid , Sherer Eric A.
Published: February 2019

Introduction. Colorectal cancer (CRC), if not detected early, can be costly and detrimental to one’s health. Colonoscopy can identify CRC early as well as prevent the disease. The benefit of screening colonoscopy has been established, but the optimal frequency of follow-up colonoscopy is unknown and may vary based on findings from colonoscopy screening and patient age. Methods. A partially observed Markov process (POMP) was used to simulate the effects of follow-up colonoscopy on the development of CRC. The POMP uses adenoma and CRC growth models to calculate the probability of a patient having colorectal adenomas and CRC. Then, based on mortality, quality of life, and the costs associated with diagnosis, treatment, and surveillance of colorectal cancer, the overall costs and increase in quality-adjusted life years (QALYs) are calculated for follow-up colonoscopy scenarios. Results. At the $100,000/QALY gained threshold, only one follow-up colonoscopy is cost-effective only after screening at age 50 years. The optimal follow-up is 8.5 years, which gives 84.0 QALYs gained/10,000 persons. No follow-up colonoscopy was cost-effective at the $50,000 and $75,000/QALY gained thresholds. The intervals were insensitive to the findings at screening colonoscopy. Conclusion. Follow-up colonoscopy is cost-effective following screening at age 50 years but not if screening occurs later. Following screening at age 50 years, the optimal follow-up interval is close to the currently recommended 10 years for an average risk screening but does not vary by colonoscopy result.
Review of the Problems of Diagnosis of Endopelvic Haemorrhage, Its Intensity, Volume, and Duration, and Treatment Methods of Circulatory Injuries and Surgical Hemostasis after Pelvic Fractures
Authors: Lazarev Anatoly , Golokhvast Kirill , Borozda Ivan
Published: February 2019

Objective.The development of pelvic surgeries is now making new evolutionary jump for us to witness; this would be unimaginable without significant achievements in anesthesiology and new technologies of blood replacement.Methods.This overview presents analysis of 41 domestic and 20 foreign references sources that are devoted to the problematics of treating patients with fluid injuries of pelvis accompanied by retroperitoneal haemorrhage.Results.The following considers details on determination of endopelvic haemorrhage nature, its intensity, volume, and duration, as well as the treatment methods for circulatory injuries and surgical haemostasis.Conclusions.Energy of mechanical influence of traumatizing agent determines the damage levels (system disintegration) for pelvic ring, the bone core, and soft tissue mass. Diagnosis tactics and treatment of patients with disintegrating pelvic damage in the end are determined with volumes and intensity of haemorrhage as well as the character of related damage.
Obturator Bypass with Bovine Carotid Artery Graft: A Novel Twist to a Traditional Technique
Authors: Brown Sarah , Esper Christopher , Henwood Jon
Published: February 2019

When managing an infected groin, though rarely performed, a transobturator bypass remains an important alternative in the armament of a vascular surgeon. Autologous vein and synthetic PTFE are known conduit options for obturator bypasses, although the advantage of utilizing an autologous biological conduit when dealing with infection may not be an option for every patient. On literature review, bovine carotid grafts have been used in infrainguinal revascularizations with comparable results to autologous vein; however, no cases can be found for its use in obturator bypass thus far.
Optimum Configuration of Solar PV Topologies for DC Microgrid Connected to the Longhouse Communities in Sarawak, Malaysia
Authors: Sharip Mohd R. M. , Haidar Ahmed M. A. , Jimel Aaron C.
Published: February 2019

In the past few years, the prime focus of supplying electricity to the longhouse communities in the rural areas of Sarawak has been initiated based on the utilization of a single-source microgrid configuration. The existing AC power supply-based solar photovoltaic (PV) systems in these areas pose many problems, mainly owing to the stages of conversion, energy losses, and the quality of power transfer. As the solar PV system is a DC source and most of the appliances in longhouse communities could be operated using DC source, an opportunity to design a microgrid with high reliability and efficiency would be achieved by the implementation of an optimal DC microgrid configuration. With this aim, the paper proposes a multiple-source DC microgrid configuration for the longhouse communities in Sarawak. Initially, a framework has been developed to design simulation models for both microgrid configurations (single and multiple sources) using MATLAB Simulink. The configuration of each system consists of a solar PV and energy storage to form a standalone microgrid. Due to the change in system configuration of DC microgrid, in the modeling approach, the standard power flow equations are modified to include solely the DC parameters. To validate the proposed configuration with the associated modeling approach in terms of the power flow reliability, system efficiency, and power-voltage curve, an experimental setup representing the Simulink model has been designed for each standalone microgrid configuration. The configurations have been assessed in the same location with different daily weather conditions. The obtained simulation and experimental results confirm that the proposed configuration of multiple sources is more reliable and efficient than the existing single-source configuration.
A Review of Danshen Combined with Clopidogrel in the Treatment of Coronary Heart Disease
Authors: Zhang Zhaojian , Wang Yu , Tan Wangxiao , Wang Siwei , Liu Jinghua , Liu Xiao , Wang Xiaoying , Gao Xiumei
Published: February 2019

Objective. Danshen, the root ofSalvia miltiorrhizaBunge, is a traditional herbal medicine in China, which has been used to treat irregular menstruation, cold hernia, and abdominal pain for thousands of years. Danshen is frequently used in combination with drugs to treat cardiovascular diseases. Clopidogrel is a commonly used drug for treating coronary heart disease, but clopidogrel resistance restricts its development. Therefore, the clinical efficacy of Danshen combined with clopidogrel treats coronary heart disease and the relationship between Danshen and clopidogrel metabolism enzymes is suggested for future investigations.Materials and Methods. The information was collected by searching online databases, and the RevMan 5.3 software was used to perform meta-analysis.Results. Twenty-two articles, including 2587 patients, were enrolled after the evaluation. Meta-analysis showed that Danshen combined with clopidogrel was more effective than clopidogrel alone in treating coronary heart disease by improving clinical curative effect, reducing the frequency of angina pectoris, improving electrocardiogram results, shortening the duration of angina pectoris, and easing adverse reactions. Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel.Conclusion. Danshen combined with clopidogrel may compensate for individual differences of clopidogrel resistance among individuals in the treatment of coronary heart disease. Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel.
Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy
Authors: Xiang Qin , Yuan Lamei , Cao Yanna , Xu Hongbo , Li Yunfeiyang , Deng Hao
Published: February 2019

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.
Specific Autoantibodies and Clinical Phenotypes Correlate with the Aberrant Expression of Immune-Related MicroRNAs in Dermatomyositis
Authors: Ye Lifang , Zuo Yu , Yang Hanbo , Li Wenli , Peng Qinglin , Lu Xin , Wang Guochun , Shu Xiaoming
Published: February 2019

Aims. The serum concentrations of miRNAs, miR-23a-3p, miR-23b-3p, miR-146a-5p, miR-146b-5p, and miR-150-5p, were shown to be associated with the immune and inflammatory progressions. We assessed the expressions of these five miRNAs in association with clinical phenotypes and myositis-specific autoantibody-defined subgroups of dermatomyositis (DM). Methods. The present study included 49 patients with DM and 30 healthy controls. The serum concentrations of miR-23a-3p, miR-23b-3p, miR-146a-5p, miR-146b-5p, and miR-150-5p were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Associations between the serum concentrations of miRNAs and DM clinical immune phenotypes were examined as well. Results. The serum concentrations of miR-23b-3p, miR-146a-5p, and miR-150-5p were significantly downregulated in DM patients (P<0.001, P<0.001, and P=0.002, respectively), while miR-146b-5p was remarkably upregulated in DM patients compared with healthy controls (P=0.039). Similarly, the expressions of miR-23b-3p, miR-146a-5p, and miR-150-5p were significantly downregulated in the peripheral blood mononuclear cells (PBMCs) from DM patients. Further study indicated that the serum level of miR-23b-3p was significantly correlated with creatine kinase (CK) (r=−0.286, P=0.046) and the serum level of miR-146a-5p was evidently correlated with C-reactive protein (CRP) (r=−0.358, P=0.012). Significant correlations were also observed between the serum levels of miR-146b-5p and CRP (r=−0.347, P=0.014) and the erythrocyte sedimentation rate (ESR) (r=−0.287, P=0.046). In addition, the expression level of miR-146b-5p was upregulated in DM complicated by tumors compared with those without tumors (P=0.001 and P<0.001, respectively). Especially, miR-150-5p was significantly downregulated in DM patients with anti-MDA5 antibodies and anti-NXP2 antibodies compared with those without (P=0.017 and P=0.047, respectively). No significant differences were observed between the four serum microRNAs in patients with and without interstitial lung diseases (all P>0.05). Conclusion. The results suggest an association between the four immune-related microRNAs and different clinical immune-phenotypes, and this association may regulate the complexity of disease processes through multipathways in DM patients.
Novel Resource Allocation Algorithms for the Social Internet of Things Based Fog Computing Paradigm
Authors: Kim Sungwook
Published: February 2019

Social Internet of Things (SIoT) is a control paradigm by the integration of social networking concepts into the Internet of Things, and Fog Computing (FC) is an emerging technology that is aimed at moving the cloud computing facilities to the access network. Recently, the SIoT and FC models are combined by using complementary features, and a new Social Fog IoT (SFIoT) paradigm has been developed. In this paper, we design novel resource allocation algorithms for the SFIoT system. Considering the social relationship and each preference, mobile devices in the SFIoT effectively share the limited computation and communication resources of FC operators. To formulate the interaction among mobile devices and FC operator, we adopt the basic concept of two game models: voting and bargaining games. Bicooperative voting approach can make control decisions for the resource allocation method, and Nash bargaining solution is used to effectively distribute the computation resource to different application tasks. Based on the two-phase game model, the proposed scheme takes various benefits in a fair-efficient way. Through the extensive simulation experiments, we can validate the superiority of our proposed approach by the fact that it produces a mutually acceptable agreement among game players and significantly outperforms the existing protocols. Last, we point out the further challenges and future research issues about the SFIoT paradigm opportunities.
Remodelling and Improvements in Organoid Technology to Study Liver Carcinogenesis in a Dish
Authors: Tharehalli Umesh , Svinarenko Michael , Lechel André
Published: February 2019

Primary liver cancer (PLC) is the sixth most common tumour disease and one of the leading causes of cancer-related death worldwide. The two most common types of PLC are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Diverse subgroups are described and a manifold number of gene mutations are known. Asymptomatic disease progression and limited therapeutic options are the reasons for the high mortality rate in PLC. Up to date, the multikinase inhibitors sorafenib and lenvatinib are the only FDA-approved first-line treatments for advanced HCC. One of the major drawbacks in the preclinical drug development is the lack of suitable model systems. In recent years, 3D organoid cultures were established from several organs and tumour subtypes, thereby opening new avenues in tumour research. 3D organoid cultures are used to describe the tumour diversity, for cancer modelling in a dish and for therapy responsiveness. The establishment of living biobanks and the development of next-generation matrices are promising approaches to overcome drug resistance and to improve the quality of personalised anticancer strategies for patients with PLC. In this review, we summarise the current knowledge of 3D cultures generated from healthy liver and primary liver cancer.
Mucormycosis as the Elusive Cause of an Aortic Thrombus and Tissue-Obliterating Abscess
Authors: Paul Shira R. , Gable Preston S.
Published: February 2019

Invasive mucormycosis is an increasingly common cause of morbidity and mortality in hematologic malignancy patients. Early consideration of the diagnosis is essential in at-risk patients, exhibiting suggestive signs and symptoms. A 56-year-old female with acute myeloid leukemia initially presented with neutropenic fever before subsequently developing dense hemiplegia due to septic emboli to the spine and multifocal abscesses. These findings were later determined to be a result of a disseminated mucor infection and represented a rare manifestation of the disease. Despite the disseminated nature of the infection, identification of the causative organism was initially impeded by limitations in obtaining a tissue sample in a severely thrombocytopenic patient, as is common among hematologic malignancy patients. As a result of this limitation, diagnosis was ultimately made via PCR on bronchiolar lavage fluid. Early consideration of the diagnosis with prompt initiation of treatment is of utmost importance in this invasive infection. Further research is needed to identify and validate rapid, minimally invasive strategies for early diagnosis of mucormycosis.
Chronic Q Fever with Vascular Involvement: Progressive Abdominal Pain in a Patient with Aortic Aneurysm Repair in the United States
Authors: Wiley Zanthia , Reddy Sujan , Jacobs Slifka Kara M. , Brandon David C. , Jernigan John , Kersh Gilbert J. , Armstrong Paige A.
Published: February 2019

Q fever is a zoonotic bacterial infection caused by Coxiella burnetii. Chronic Q fever comprises less than five percent of all Q fever cases and, of those, endocarditis is the most common presentation (up to 78% of cases), followed by vascular involvement. Risk factors for chronic Q fever with vascular involvement include previous vascular surgery, preexisting valvular defects, aneurysms, and vascular prostheses. The most common symptoms of chronic Q fever with vascular involvement are nonspecific, including weight loss, fatigue, and abdominal pain. Criteria for diagnosis of chronic Q fever include clinical evidence of infection and laboratory criteria (antibody detection, detection of Coxiella burnetii DNA, or growth in culture). Treatment of chronic Q fever with vascular involvement includes a prolonged course of doxycycline and hydroxychloroquine (≥18 months) as well as early surgical intervention, which has been shown to improve survival. Mortality is high in untreated chronic Q fever. We report a case of chronic Q fever with vascular involvement in a 77-year-old man with prior infrarenal aortic aneurysm repair, who lived near a livestock farm in the southeastern United States.
Potential Factors Affected Safety and Efficacy of Transcatheter Plug Closure for Pediatric Hemoptysis with Anomalous Bronchial Arteries
Authors: Kuang Hong-Yu , Li Qiang , Xiang Ping , Feng Chuan , Yi Qi-Jian , Lu Tie-Wei
Published: February 2019

Objective. To evaluate the safety and efficacy of interventional care in pediatric hemoptysis for anomalous bronchial arteries (BAs) and to identify the potential factors resulting in hemoptysis recurrence. Methods. 20 children complained of hemoptysis were diagnosed with anomalous BAs. All patients received transcatheter plug occlusion in Department of Cardiology, Children’s Hospital of Chongqing Medical University. The safety and efficacy were evaluated according to clinical symptoms and images monitoring of enrolled subjects grouped as recurrence group and nonrecurrence group. The potential factors causing hemoptysis recurrence were reviewed and summarized. Results. No deaths were recorded in a follow-up. Otherwise, hemoptysis recurrence was found in 8 subjects for 14 times, accounting for about 40%. Compared with nonrecurrence group, it indicated a statistical significance in hemoglobin levels (P=0.049), mycoplasma pneumonia particle assays (MP-PA) titers (P=0.030), and number of anomalous BAs (P=0.020). Meanwhile, 50% recurrent scenarios were associated with a respiratory infection by microbiological assessment before transcatheter plug occlusion. The repeat occlusion was applied for unclosed BAs leading to visual recurrent hemoptysis, the average interval time of which was 5.4 ± 3.6 mon. Conclusion. The data from this retrospective study have shown that transcatheter plug occlusion is a relatively safe procedure with a low mortality. The number of abnormal BAs has been identified as a highly significant predictor of recurrence, and the role of MP and other potential factors should be verified in a multicenter, larger sample size, and randomized controlled trial.
One-Sided and Two-Sided w-of-w Runs-Rules Schemes: An Overall Performance Perspective and the Unified Run-Length Derivations
Authors: Shongwe S. C. , Malela-Majika J.-C. , Rapoo E. M.
Published: February 2019

The one-sided and two-sided Shewhart w-of-w standard and improved runs-rules monitoring schemes to monitor the mean of normally distributed observations from independent and identically distributed (iid) samples are investigated from an overall performance perspective, i.e., the expected weighted run-length (EWRL), for every possible positive integer value of w. The main objective of this work is to use the Markov chain methodology to formulate a theoretical unified approach of designing and evaluating Shewhart w-of-w standard and improved runs-rules for one-sided and two-sided X- schemes in both the zero-state and steady-state modes. Consequently, the main findings of this paper are as follows: (i) the zero-state and steady-state ARL and initial probability vectors of some of the one-sided and two-sided Shewhart w-of-w standard and improved runs-rules schemes are theoretically similar in design; however, their empirical performances are different and (ii) unlike previous studies that use ARL only, we base our recommendations using the zero-state and steady-state EWRL metrics and we observe that the steady-state improved runs-rules schemes tend to yield better performance than the other considered competing schemes, separately, for one-sided and two-sided schemes. Finally, the zero-state and steady-state unified approach run-length equations derived here can easily be used to evaluate other monitoring schemes based on a variety of parametric and nonparametric distributions.
Do Systemic Factors Influence the Fate of Nonunions to Become Atrophic? A Retrospective Analysis of 162 Cases
Authors: Rupp Markus , Kern Stefanie , El Khassawna Thaqif , Ismat Abdullah , Malhan Deeksha , Alt Volker , Heiss Christian , Raschke Michael J.
Published: February 2019

Introduction. Nonunions are a challenge for orthopedic surgeons. In hypertrophic nonunions, improvement of mechanical stability usually is the satisfactory treatment, whereas in atrophic nonunions improvement of the biological environment is most important. However, scientific evidence revealed that “avital” nonunions are not avascular and fibrous tissue contains cells with osteogenic potential. To find out if systemic factors suppress this intrinsic potential in atrophic nonunions, this study compares characteristics of hypertrophic with atrophic nonunion patients. Methods. We analyzed medical records of 162 surgically treated patients suffering from aseptic long bone nonunions. Atrophic and hypertrophic nonunions were distinguished by absence or presence of callus and calcification in the fracture gap. Mechanical implant loosening and patient characteristics such as age, gender, and body mass index were assessed. Fracture classification according to AO/OTA, open and closed fractures, and osteosynthesis were recorded. In addition, comorbidities and allergies between both groups were compared. Results. A higher number of hypertrophic nonunion patients were male with often allergies. Hypertrophic nonunion occurred more often after intramedullary nailing compared to atrophic nonunions. Atrophic nonunion patients being nonallergic were significantly older than nonallergic patients suffering from hypertrophic nonunions. In both atrophic and hypertrophic nonunion patients, age was lower in patients with accompanying injuries compared with age of patients with isolated fractures. Conclusion. Systemic factors influence development of nonunion types. In nonallergic patients, atrophic nonunions occur more often in the elderly. This manuscript is a first step to identify different factors which might influence the nature of nonunion. To enable nonunion treatment which is tailored to individual patient characteristics, further prospective studies with more sophisticated research methods are necessary.
Molecular Mechanisms Underpinning Microparticle-Mediated Cellular Injury in Cardiovascular Complications Associated with Diabetes
Authors: Benameur Tarek , Osman Aisha , Parray Aijaz , Ait Hssain Ali , Munusamy Shankar , Agouni Abdelali
Published: February 2019

Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100–1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues. Of interest and because of their easy detection using a variety of techniques, circulating MPs were recognized as biomarkers for cell activation. MPs were also found to mediate critical actions in intercellular communication and transmitting biological messages by acting as paracrine vehicles. High plasma numbers of MPs were reported in many cardiovascular and metabolic disturbances that are closely associated with insulin resistance and low-grade inflammation and have been linked to adverse actions on cardiovascular function. This review highlights the involvement of MPs in cardiovascular complications associated with diabetes and discusses the molecular mechanisms that underpin the pathophysiological role of MPs in the onset and progression of cellular injury in diabetes.
The Finite Element Modulation of Thermostressed State of Coating Formation at Electric Contact Surfacing of “Shaft” Type Parts
Authors: Berezshnaya Olena V. , Gribkov Eduard P. , Borovik Pavlo V. , Kassov Valeriy D.
Published: February 2019

The finite element modulation of forming of coating at electric contact surfacing is provided. This model considers distribution of thermal properties and geometric parameters along the thermal deformation zone during the process of electric contact surfacing by tapes. It is found that the change of the value of the speed asymmetry factor leads to increasing of the friction coefficient in the zone of surfacing which is caused by the increasing of the tangential contact stresses in the zone of contact of the electrode tape with the surface of the part. This leads to the forming of the coating with higher adhesion strength, and thereby the higher quality of the restored part under the lower operating regimes such as current pulse, force of the roller electrode, and duration of the current pulse is achieved. Mentioned above allows to decrease the thermal influence on the structure of the material.
Pneumocephalus and Meningitis as Complications of Mastoiditis
Authors: Barry Conor , Rahmani George , Bergin Diane
Published: February 2019

Pneumocephalus in the absence of trauma, tumour, or surgery is a rare entity. We report a case of a 73-year-old lady who presented with sepsis leading to confusion and unresponsiveness. A CT of brain revealed mastoiditis, sinusitis, and associated pneumocephalus. Further investigations led to an eventual diagnosis of pneumococcal meningitis. The combination of pneumocephalus and meningitis as complications of mastoiditis is rare with very few cases published in the literature. We describe one such case.
Preparation and In Vivo Expression of CS-PEI/pCGRP Complex for Promoting Fracture Healing
Authors: Li Chun-Liang , Qin Feng , Li Rong-rong , Zhuan Jia , Zhu Hai-Yong , Wang Yu , Wang Kai
Published: February 2019

Background/Objective. CGRP is a calcitonin gene-related peptide that is capable of promoting bone development and bone regeneration. Chitosan is a nontoxic and degradable biomaterial. However, the gene transfection efficiency of chitosan is low, whereas PEI (polyethyleneimine) has higher capability of transfection efficiency. In this paper, PEI was covalently linked to chitosan, and the rat CGRP plasmid was encapsulated in a CS-PEI complex to construct CS-PEI/pCGRP nanoparticles. The characterization and biological effects of CS-PEI/pCGRP nanoparticles were investigated in vivo. Methods. CS-PEI/pCGRP nanoparticles were prepared by a complex coacervation method. The PEI distribution degree on chitosan was measured with a dialysis method and 1H-NMR analysis. The particle size and zeta potential of CS-PEI/pCGRP nanoparticles were detected by dynamic light scattering. The binding of CS-PEI to pCGRP was detected by gel retardation assay. The transfection effect was evaluated by RT-qPCR. A rat femoral fracture model was established and treated with PBS, pCGRP, CS-PEI, and CS-PEI/pCGRP to detect the expression of CGRP and downstream genes in early healing of fractures by RT-qPCR, western blot, and immunohistochemistry (IHC). Results. The particle size and zeta potential of CS-PEI/pCGRP nanoparticles were stable when the mass ratio of CS-PEI and pCGRP was higher than 5 : 1, the ratio which could also effectively protect pCGRP from DNase I degradation. CS-PEI/pCGRP could obviously increase CGRP expression in rat bone marrow stromal cells. In vivo fracture healing experiments demonstrated that CGRP could be delivered to the body via the CS-PEI and expressed in situ after a 3-week treatment. Moreover, CS-PEI/pCGRP significantly enhanced the mRNA and protein levels of downstream RUNX2 and ALP. Conclusion. CS-PEI/pCGRP nanoparticles were an effective nonviral gene transfection system that could upregulate CGRP expression in vivo and accelerate the expression of key biomarkers for early healing of fractures.
Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis
Authors: Vasyliev Roman G. , Gubar Olga S. , Gordiienko Inna M. , Litvinova Larisa S. , Rodnichenko Anzhela E. , Shupletsova Valeria V. , Zlatska Alona V. , Yurova Kristina A. , Todosenko Natalia M. , Khadzhynova Veronika E. , Shulha Mariia V. , Novikova Svitlana N. , Zubov Dmytro O.
Published: February 2019

Introduction. The adult neural crest-derived stem cells (NCSCs) have significant perspectives for use in regenerative medicine. The most attractive sources for adult NCSC isolation are the hair follicles (HF) and skin dermis (SD) because of easy access and minimally invasive biopsy. The aim of this study was to compare the biological properties of HF- and SD-derived NCSCs after their large-scale expansion. Methods. The conventional explant method was used to obtain HF NCSCs. For the isolation of SD NCSCs, a new combined technique consisting of preplating and subsequent culturing in 3D blood plasma-derived fibrin hydrogel was applied. The studied cells were characterized by flow cytometry, ICC, qPCR, Bio-Plex multiplex assay, and directed multilineage differentiation assays. Results. We have obtained both adult SD and HF NCSCs from each skin sample (n=5). Adult SD and HF NCSCs were positive for key neural crest markers: SOX10, P75 (CD271), NESTIN, SOX2, and CD349. SD NCSCs showed a higher growth rate during the large-scale expansion compared to HF NCSCs (p<0.01). Final population of SD NCSCs also contained more clonogenic cells (p<0.01) and SOX10+, CD271+, CD105+, CD140a+, CD146+, CD349+ cells (p<0.01). Both HF and SD NCSCs had similar gene expression profiling and produced growth factors, but some quantitative differences were detected. Adult HF and SD NCSCs were able to undergo directed differentiation into neurons, Schwann cells, adipocytes, and osteoblasts. Conclusion. The HF and SD are suitable sources for large-scale manufacturing of adult NCSCs with similar biological properties. We demonstrated that the NCSC population from SD was homogenous and displayed significantly higher growth rate than HF NCSCs. Moreover, SD NCSC isolation is cheaper, easier, and minimally time-consuming method.
Additive Manufacturing Technologies: An Overview about 3D Printing Methods and Future Prospects
Authors: Jiménez Mariano , Romero Luis , Domínguez Iris A. , Espinosa María del Mar , Domínguez Manuel
Published: February 2019

The use of conventional manufacturing methods is mainly limited by the size of the production run and the geometrical complexity of the component, and as a result we are occasionally forced to use processes and tools that increase the final cost of the element being produced. Additive manufacturing techniques provide major competitive advantages due to the fact that they adapt to the geometrical complexity and customised design of the part to be manufactured. The following may also be achieved according to field of application: lighter weight products, multimaterial products, ergonomic products, efficient short production runs, fewer assembly errors and, therefore, lower associated costs, lower tool investment costs, a combination of different manufacturing processes, an optimised use of materials, and a more sustainable manufacturing process. Additive manufacturing is seen as being one of the major revolutionary industrial processes of the next few years. Additive manufacturing has several alternatives ranging from simple RepRap machines to complex fused metal deposition systems. This paper will expand upon the structural design of the machines, their history, classification, the alternatives existing today, materials used and their characteristics, the technology limitations, and also the prospects that are opening up for different technologies both in the professional field of innovation and the academic field of research. It is important to say that the choice of technology is directly dependent on the particular application being planned: first the application and then the technology.
Application of Variational Mode Decomposition and k‐Nearest Neighbor Algorithm in the Quantitative Nondestructive Testing of Wire Ropes
Authors: Zheng Pengbo , Zhang Juwei
Published: February 2019

In this paper, we present a nondestructive testing device for wire rope by unsaturated magnetic excitation as an alternative to existing magnetic flux leakage (MFL) detection devices. The existing devices are heavy and inconvenient and offer somewhat lower accuracy and low signal‐to‐noise ratios (SNRs). Our design implements variational mode decomposition (VMD) and a wavelet transformation to remove noise from the raw MFL signals. Grayscale images representing the denoised MFL data simplify visual interpretation of the results and location of defects in both axial and circumferential directions. Quantification of defects is enabled using a k‐nearest neighbor (KNN) algorithm to classify broken wires. Experimental results show that our design offers lighter weight, better convenience, and high sensitivity along with better removal of noise and more accurate classification of defects.
Analysis of Mucosal Melanoma Whole-Genome Landscapes Reveals Clinically Relevant Genomic Aberrations
Authors: Zhou Rong , Shi Chaoji , Tao Wenjie , Li Jiang , Wu Jing , Han Yong , Yang Guizhu , Gu Ziyue , Xu Shengming , Wang Yujue , Wang Lizhen , Wang Yanan , Zhou Guoyu , Zhang Chenping , Zhang Zhiyuan , Sun Shuyang
Published: February 2019

Purpose:

Unlike advances in the genomics-driven precision treatment of cutaneous melanomas, the current poor understanding of the molecular basis of mucosal melanomas (MM) has hindered such progress for MM patients. Thus, we sought to characterize the genomic landscape of MM to identify genomic alterations with prognostic and/or therapeutic implications.

Experimental Design:

Whole-genome sequencing (WGS) was performed on 65 MM samples, including 63 paired tumor blood samples and 2 matched lymph node metastases, with a further droplet digital PCR–based validation study of an independent MM cohort (n = 80). Guided by these molecular insights, the FDA-approved CDK4/6 inhibitor palbociclib was tested in an MM patient-derived xenograft (PDX) trial.

Results:

Besides the identification of well-recognized driver mutations of BRAF (3.1%), RAS family (6.2%), NF1 (7.8%), and KIT (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene POM121 (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (CDK4, MDM2, and AGAP2) at 12q13-15, and this co-occurred significantly with amplification of TERT at 5p15, which was verified in the validation cohort; (iv) the PDX trial demonstrated robust antitumor effects of palbociclib in MMs harboring CDK4 amplification.

Conclusions:

Our largest-to-date cohort WGS analysis of MMs defines the genomic landscape of this deadly cancer at unprecedented resolution and identifies genomic aberrations that could facilitate the delivery of precision cancer treatments.

See related commentary by Shoushtari, p. 3473
Radiotherapy and Cisplatin Increase Immunotherapy Efficacy by Enabling Local and Systemic Intratumoral T-cell Activity
Authors: Kroon Paula , Frijlink Elselien , Iglesias-Guimarais Victoria , Volkov Andriy , van Buuren Marit M. , Schumacher Ton N. , Verheij Marcel , Borst Jannie , Verbrugge Inge
Published: February 2019

To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast cancer model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate with anti–PD-1 treatment. One requirement to improve anti-PD-1–mediated tumor control was to promote tumor-specific cytotoxic T-cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1–unrelated mechanisms of CTL suppression in the tumor microenvironment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1–targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T-cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.
Desafíos para la paz en un mundo globalizado
Authors: Mingol Irene Comins
Published: February 2019

Este artigo aborda as contribuições de uma filosofia do cuidado para a construção de uma cidadania cosmopolita no mundo globalizado. A capacidade do ser humano para a empatia com o outro, ser sensível às suas necessidades e responder adequadamente a essas demandas são elementos fundamentais no mundo globalizado de interdependências crescentes. Para isso, este texto aborda a importância de uma filosofia do cuidado para ressignificar algumas suposições dominantes sobre a natureza humana e indica o potencial da ética do cuidado para tratar temas morais em contextos globais.
Uma breve introdução à pesquisa sobre paz transracional e transformação elicitiva de conflito
Authors: Dietrich Wolfgang , Vollet Neuza L. R.
Published: February 2019

Este artigo é uma síntese da trilogia Muitas pazes do autor. Este trabalho aprofunda a filosofia das muitas pazes e de paz transracional e deriva da famosa pirâmide de conflito de Lederach, com um entendimento sistêmico mais amplo do conflito como um fenômeno relacional. Além disso, oferece ferramenta para a análise desses processos complexos que ocorrem nas “fronteiras de contato em movimento” humanas. Por fim, introduz ressonância, correspondência e homeostase como princípios de mapeamento elicitivo de conflito.
Teorias da comunicação, transferência do conhecimento e implicações na subserviência dos sujeitos nas organizações
Authors: Lima Fábia Pereira
Published: February 2019

Este artigo reflete sobre estudos de transferência de conhecimento nas organizações, denunciando como certas concepções podem encobrir postulados que coisificam o homem e abrem caminho para a naturalização de correntes teóricas e práticas de subserviência ao modelo produtivo capitalista, que são reproduzidas e integram a cultura organizacional. O artigo defende que os estudos de comunicação organizacional podem e devem contribuir para desconstruir premissas que integrem a sutil rede de violências simbólicas que pautam relações sociais, objetos de pesquisa e práticas organizacionais.
Os espaços e as vozes de informação em ambientes hospitalares
Authors: Mortari Elisângela Carlosso Machado
Published: February 2019

Este texto busca compreender as etapas de circulação dos sentidos relacionados à agenda de notícias no campo da saúde pública, especialmente as produzidas nas assessorias de comunicação dos hospitais-escola localizados na região Sul do Brasil. Para a pesquisa realizada, as práticas de comunicação exigem avaliação quando ocorrem em ambientes de alta complexidade e circulação de sentidos. Foram analisadas notícias publicadas pelas assessorias dos hospitais de Santa Maria, Pelotas, Rio Grande, Florianópolis e Curitiba de janeiro a agosto de 2017.
Involucramiento de las organizaciones en la construcción de paz
Authors: Fuentes Martinez Sandra I.
Published: February 2019

A realidade da América Latina e do Caribe exige o envolvimento ativo das organizações na construção da paz, processo que é complexo, de longo prazo e requer a participação de todos os atores da sociedade. De maneira particular, as empresas que têm a capacidade, o dever, o poder e os recursos para promover essa transformação. Esse envolvimento implica a compreensão e a adoção de diretrizes globais que orientem o trabalho pela paz, com reflexos no respeito aos direitos humanos e ao desenvolvimento sustentável. Da mesma forma, requer gestão estratégica da comunicação para reconstruir o tecido social, fortalecendo a interrelação da organização com a sociedade ao construir vínculos baseados na confiança e ao desarmar a palavra para construir uma nova narrativa de paz que consolide uma sociedade harmoniosa e pacífica.
Violência organizacional
Authors: Gonçalves Gisela , Cabral Raquel , Salhani Jorge
Published: February 2019

The objective of this article is to discuss the notion of organizational violence from the critical Peace Studies perspective – particularly concerning Johan Galtung’s violence typology – and to relate it to the principles that guide responsible ethics and conducts in organizations in the private, public and non-profit sectors. As main results, this article presents the fundamentals of the legitimation mechanisms of organizational violence based on specific examples in organizations. It also aimed to question the discourses and practices that legitimize organizational violence.
Diálogos entre o Norte e o Sul Global sobre violência e comunicação para a paz
Authors: Vicente Maximiliano Martin , Aldás Eloísa Nos
Published: February 2019

Entrevista com Eloísa Nos Aldás e Maximiliano Martin Vicente
Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes
Authors: Hemerich Daiane , Pei Jiayi , Harakalova Magdalena , van Setten Jessica , Boymans Sander , Boukens Bas J. , Efimov Igor R. , Michels Michelle , van der Velden Jolanda , Vink Aryan , Cheng Caroline , van der Harst Pim , Moore Jason H. , Mokry Michal , Tragante Vinicius , Asselbergs Folkert W.
Published: February 2019

Background:

Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context.

Methods:

We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements.

Results:

Regions differentially affected in disease showed a stronger enrichment (
P
=8.6×10
−5
) for QRS-associated variants than those not showing differential activity (
P
=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment (
P
=0.001) than differentially acetylated enhancers (
P
=0.8) and super-enhancers (
P
=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped.

Conclusions:

Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.