bluuebunny/crossref_metadata_2025 huggingface dataset:
An Improved Collaborative Filtering Recommendation Algorithm and Recommendation Strategy
Authors: Li Xiaofeng , Li Dong
Published: May 2019

The e-commerce recommendation system mainly includes content recommendation technology, collaborative filtering recommendation technology, and hybrid recommendation technology. The collaborative filtering recommendation technology is a successful application of personalized recommendation technology. However, due to the sparse data and cold start problems of the collaborative recommendation technology and the continuous expansion of data scale in e-commerce, the e-commerce recommendation system also faces many challenges. This paper has conducted useful exploration and research on the collaborative recommendation technology. Firstly, this paper proposed an improved collaborative filtering algorithm. Secondly, the community detection algorithm is investigated, and two overlapping community detection algorithms based on the central node and k-based faction are proposed, which effectively mine the community in the network. Finally, we select a part of user communities from the user network projected by the user-item network as the candidate neighboring user set for the target user, thereby reducing calculation time and increasing recommendation speed and accuracy of the recommendation system. This paper has a perfect combination of social network technology and collaborative filtering technology, which can greatly increase recommendation system performance. This paper used the MovieLens dataset to test two performance indexes which include MAE and RMSE. The experimental results show that the improved collaborative filtering algorithm is superior to other two collaborative recommendation algorithms for MAE and RMSE performance.
HPV-16 Infection Is Associated with a High Content of CD39 and CD73 Ectonucleotidases in Cervical Samples from Patients with CIN-1
Authors: de Lourdes Mora-García María , López-Cisneros Sofía , Gutiérrez-Serrano Vianey , García-Rocha Rosario , Weiss-Steider Benny , Hernández-Montes Jorge , Sánchez-Peña Héctor I. , Ávila-Ibarra Luis Roberto , Don-López Christian Azucena , Muñóz-Godínez Ricardo , Pineda Daniela Berenice Torres , Chacón-Salinas Rommel , Vallejo-Castillo Luis , Pérez-Tapia Sonia Mayra , Monroy-García Alberto
Published: May 2019

The development of cervical cancer (CeCa) is associated with high-risk human papilloma virus (HR-HPV) infections, mainly HPV-16, which is present in more than 50% of cases. The presence of immunosuppressive factors in the early stages of the disease is also strongly linked to CeCa progression. In this context, it is unknown whether ectonucleotidases CD39 and CD73, which are involved in the production of adenosine (Ado) that suppresses the specific antitumor immune response, are present in precursor lesions of CeCa. In this pilot study, we analyzed the presence of CD39 and CD73 and their capacity to generate Ado in 25 cervical samples from patients with grade 1 cervical intraepithelial neoplasms (CIN-1) and 25 samples from normal donors (NDs) free of HPV infection. Cells obtained from cervical samples of CIN-1 patients positive for HPV-16 showed higher CD39 and CD73 contents compared to samples obtained from CIN-1 patients negative for HPV-16 and NDs. Interestingly, solubilized cervical mucus from these patients also showed higher contents of soluble CD39 and CD73, which were associated with a greater capacity to produce Ado from the hydrolysis of adenosine triphosphate (ATP) and adenosine monophosphate (AMP). In addition, serum samples of these patients showed higher levels of TGF-βthan those of CIN-1 patients negative for HPV-16 and ND. These results suggest that persistent infection with HR-HPV, mostly HPV-16, in CIN-1 patients may promote the expression of CD39 and CD73 through the production of TGF-βin precursor lesions to generate an immunosuppressive microenvironment and allow its progression to CeCa.
Granulicatella adiacens and Abiotrophia defectiva Native Vertebral Osteomyelitis: Three Cases and Literature Review of Clinical Characteristics and Treatment Approach
Authors: Puzzolante Cinzia , Cuomo Gianluca , Meschiari Marianna , Bedini Andrea , Bonazza Aurora , Venturelli Claudia , Sarti Mario , Mussini Cristina
Published: May 2019

Granulicatella adiacens and Abiotrophia defectiva are an increasingly recognized cause of osteoarticular infections. We describe two cases of G. adiacens and one case of A. defectiva native vertebral osteomyelitis (NVO) and review all published cases. Nine cases of G. adiacens NVO and two cases of A. defectiva NVO were previously described. Patients were usually middle-aged men, and classical risk factors for NVO were present in half of the cases. Concomitant bacteremia was reported in 78.6% of cases, and concurrent infective endocarditis occurred in 36.4% of this sub-group of patients. Many different antibiotic schemes were recorded, with median treatment duration of 6 weeks. In the most recent reports, glycopeptides represented the most frequent empirical therapy, possibly due to the increasing emergence of G. adiacens and A. defectiva penicillin-resistant strains. Stabilization surgery was rarely required (14.3% of cases), and clinical cure was generally achieved. In conclusion, Granulicatella spp. and Abiotrophia spp. NVO is rare but increasingly described. A total antibiotic course of six weeks seems to be appropriate for noncomplicated cases, and clinical outcome is generally favorable.
Differences in Leukocyte Telomere Length between Coronary Heart Disease and Normal Population: A Multipopulation Meta-Analysis
Authors: Xu Xiaofeng , Hu Haochang , Lin Ying , Huang Fangzhong , Ji Huihui , Li Yin , Lin Shaoyi , Chen Xiaomin , Duan Shiwei
Published: May 2019

Coronary heart disease (CHD) is one of the most common causes of death in the world. Numerous studies have shown that as the degree of atherosclerotic disease increases, leukocyte telomere length gradually decreases. Short telomeres increase the risk of all-cause death and cardiovascular death. However, the reported results are not consistent, since the experimental design method, the measurement method, and the disease outcome are different. Therefore, we searched five major literature databases (Pubmed, Web of science, Embase, CNKI, and Wangfang) and finally included 18 eligible articles (including 5,150 patients with CHD and 9341 controls). We found that telomere length in patients with CHD was significantly shorter than that in controls, and the telomere length was inversely correlated with the severity of CHD. Subgroup analysis showed that telomere shortening was the most significant in Asian patients with CHD, in CHD patients with an average age <65 years, and in men with CHD. The mechanism of shortening the telomere length leading to the occurrence and development of CHD is worthy of further study.
A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells
Authors: Pollock Tanner B. , Mack Jacob M. , Day Ryan J. , Isho Noail F. , Brown Raquel J. , Oxford Alexandra E. , Morrison Brad E. , Hayden Eric J. , Rohn Troy T.
Published: May 2019

Despite the fact that harboring the apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer’s disease (AD), the exact mechanism by which apoE4 contributes to disease progression remains unknown. Recently, we demonstrated that a 151 amino-terminal fragment of apoE4 (nApoE41-151) localizes within the nucleus of microglia in the human AD brain, suggesting a potential role in gene expression. In the present study, we investigated this possibility utilizing BV2 microglia cells treated exogenously with nApoE41-151. The results indicated that nApoE41-151leads to morphological activation of microglia cells through, at least in part, the downregulation of a novel ER-associated protein, CXorf56. Moreover, treatment of BV2 cells with nApoE41-151resulted in a 68-fold increase in the expression of the inflammatory cytokine, TNFα, a key trigger of microglia activation. In this regard, we also observed a specific binding interaction of nApoE41-151with the TNFαpromoter region. Collectively, these data identify a novel gene-regulatory pathway involving CXorf56 that may link apoE4 to microglia activation and inflammation associated with AD.
A New Approach for the Approximate Analytical Solution of Space-Time Fractional Differential Equations by the Homotopy Analysis Method
Authors: Demir Ali , Bayrak Mine Aylin , Ozbilge Ebru
Published: May 2019

The motivation of this study is to construct the truncated solution of space-time fractional differential equations by the homotopy analysis method (HAM). The first space-time fractional differential equation is transformed into a space fractional differential equation or a time fractional differential equation before the HAM. Then the power series solution is constructed by the HAM. Finally, taking the illustrative examples into consideration we reach the conclusion that the HAM is applicable and powerful technique to construct the solution of space-time fractional differential equations.
DNA Methylation Profiles and Their Diagnostic Utility in BC
Authors: Shan Ming , Zhang Lei , Liu Yang , Gao Chunyang , Kang Wenli , Yang Weiwei , He Yan , Zhang Guoqiang
Published: May 2019

Biomarkers, including DNA methylation, have shown a great potential for use in personalized medicine for BC and especially for the diagnosis of BC in developing countries. According to the bisulfite sequencing PCR in twelve specimens (BC and matched normal tissues), nine genetic probes were designed to detect the frequency of methylation of the promoters in a total of 302 paired cases of BC and matched normal breast tissues. Finally, a total of 900 serum samples were used to validate the use of these methylation biomarkers for clinical diagnosis of BC. A high frequency of promoter methylation of SFN, HOXA11, P16, RARβ, PCDHGB7, hMLH1, WNT5a, HOXD13, and RASSF1a was observed in BC tissues. The methylation frequencies of HOXD13 and hMLH1 increased with the progression of BC. The methylation frequencies of HOXD13 and WNT5a were significantly higher in BC. We found that methylation modification-positive samples were most consistently associated with luminal BC. Finally, we confirmed that RASSF1a, P16, and PCDHGB7 displayed a significant sensitivity and specificity as diagnostic biomarkers for BC (P<0.001), and a panel that combined these three genes displayed increased significance (AUC, 0.781; P<0.001). These data suggest that epigenetic markers in serum can potentially be used to diagnose BC. The identification of additional BC-specific methylated genes would improve the sensitivity and specificity of this approach. This study could also indicate that different molecular subtypes of BC are caused by distinct genetic and epigenetic mechanisms.
Partial Characterization of Novel Bacteriocin SF1 Produced by Shigella flexneri and Their Lethal Activity on Members of Gut Microbiota
Authors: Padilla Carlos , Carrasco-Sánchez Verónica , Padilla Andrés , Lobos Olga
Published: May 2019

A strain of Shigella flexneri producing bacteriocin was isolated from a patient with diarrhea. The main objective of this study was to isolate and partially characterize the bacteriocin. The producing microorganism was identified using biochemical, serological, and molecular methods. The lethal activity of the S. flexneri strain was studied using the drop method. This bacterial strain showed activity against different strains of E. coli and B. fragilis. Using immunological techniques, it was determined that S. flexneri belongs to serotype 2a, and by PCR, the presence of the ipaH plasmid was determined. By chromatographic techniques, it was determined that the bacteriocin is a peptide of high purity with a molecular weight of 66294.094 Da. The amino acid composition and sequence were determined by the Edman reaction, and a sequence of 619 amino acid residues was obtained. Only in five positions of this sequence, the amino acid glutamine changed to glutamic acid with respect to colicin U produced by S. boydii. From an ecological point of view, it could be assumed that SF1 bacteriocin contributes to eliminate some members of the normal microbiota of the human intestine, facilitating colonization and then producing the invasion process that characterizes the pathogenicity of Shigella.
The Efficacy of Intravitreal Conbercept for Chronic Central Serous Chorioretinopathy
Authors: Mao Jianbo , Zhang Caiyun , Liu Chenyi , Shen Lijun , Lao Jimeng , Shao Yirun , Chen Yiqi , Tao Jiwei
Published: May 2019

Purpose. To evaluate the efficacy and safety of conbercept for patients with chronic central serous chorioretinopathy (CSC). Methods. A retrospective clinical study. Thirty-one patients (35 eyes) with chronic CSC were given intravitreal injections of conbercept and followed up for at least 6 months. Observed indicators included best-corrected visual acuity (BCVA), central macular thickness (CMT), and resolution of subretinal fluid (SRF). Serial changes in BCVA and CMT were analyzed by using repeated measures analysis of variance. Results. During the 6-month follow-up, the mean number of injections required and performed was 1.77 ± 0.60. The logMAR BCVA was 0.48 ± 0.26 at the baseline, 0.34 ± 0.26, 0.30 ± 0.26, 0.27 ± 0.26, 0.24 ± 0.26, and 0.23 ± 0.26 at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 27.173, P<0.05). CMT was 313.74 ± 144.51 μm at the baseline and decreased to 263.49 ± 120.44 μm, 225.91 ± 91.98 μm, 195.77 ± 66.69 μm, 189.74 ± 65.41 μm, and 199.49 ± 81.50 μm at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 18.093, P<0.05). Full resolution of SRF was achieved in 8 (22.9%) eyes at 1 month, 16 (45.7%) eyes at 2 months, 22 (62.9%) eyes at 3 months, and 27 (77.1%) eyes at 6 months after the initial treatment of anti-VEGF injection. No severe adverse event was noted relevant to the therapy. Conclusions. Intravitreal injection of conbercept may effectively reduce the CMT and improve the BCVA in chronic CSC in a short term of 6 months.
Initial Effects of Electroacupuncture for Chronic Severe Functional Constipation and the Potential Underlying Factors: Secondary Analysis of a Randomized Controlled Trial
Authors: Zeng Yuxiao , Liu Yan , Liu Sixing , Liu Zhishun
Published: May 2019

Background. Electroacupuncture (EA) has been found to be effective for treating chronic severe functional constipation (CSFC). However, the initial effects of treatment usually affect the acceptability and compliance of patients with chronic disease in particular. Which class of CSFC patients will have a better initial response to EA remains uncertain and requires investigation. Methods. This was a secondary analysis of an original multicenter randomized controlled trial in which patients with CSFC were randomly assigned to receive 28 sessions of EA or sham electroacupuncture (SA) over 8 weeks with 12 weeks of follow-up. The primary outcome, namely, response with complete spontaneous bowel movements (CSBMs), required participants to have ≥ 3 CSBMs and an increase of ≥ 1 CSBM from the baseline over the first week of treatment. Logistic regression analysis with bootstrapping techniques was performed to determine independent factors related to the response. Results. A total of 1051 eligible patients were included in this study of whom 161 patients were classified as responders at week 1. The CSBM response rate was higher in the EA group (17.5%) than in the SA group (13.2%). And the proportion of these 1-week early responders remained to have higher clinical response at the end of 8-week treatment and 12 weeks after treatment. Age and higher baseline CSBMs were related to CSBM response within the first week: with every 1-year increase in age, the likelihood of clinical response was reduced by 1.7% (odds ratio [OR] 0.983, 95% confidence interval [CI] 0.972 to 0.993; P=0.001). The odds of a CSBM response in patients with 1< CSBMs ≤ 2 at baseline were 4.64 times higher than that in patients with CSBMs ≤ 1 (OR 4.64, 95%CI 4.01 to 5.27). Conclusions. EA produced its initial effects within the first week of treatment. And the effects could last until week 8 and week 20. A younger age and higher number of CSBMs at baseline may increase likelihood of a response.
Integrated Management Software for Factory Production of Modular Buildings
Authors: Nam SungHoon , Lee DooYong , Cho BongHo , Kim KyungRai
Published: May 2019

After the first modular construction project in Korea in 2003, the scope and demand for modular systems have gradually increased. However, modular producers in Korea utilize spreadsheets to manage the process, manpower, and materials required for modular construction. This is inadequate compared to other countries that are more advanced in modular construction such as Japan and the United Kingdom. The management system in Korea decreases the effectiveness of modular construction in reducing construction time and cost. There is no formal system for managing modular production in Korea. Although some construction management programs utilized in the traditional construction industry are available, they do not reflect the flow of modular production, that is, to simultaneously produce several types of modules in accordance with demand in a factory. This research develops a modular‐construction‐specific production management system that has three overall functions: factory setup, project creation, and result analysis. These functions can link all the relevant data for managing modular production and can help manage several types of modules. The production management system is verified through simulation of the existing processes observed for a completed project and comparing the results to an alternative process. Through such comparisons, an optimized process design can be achieved.
Use of Healthcare Services Two Years before Diagnosis in Danish Sarcoma Patients, 2000–2013
Authors: Rædkjær Mathias , Maretty-Kongstad Katja , Baad-Hansen Thomas , Safwat Akmal , Petersen Michael M. , Keller Johnny , Vedsted Peter
Published: May 2019

Background. Sarcoma is a rare type of cancer with nonspecific symptoms and uncertain aetiology. Thus, timely diagnosis of sarcomas is a clinical challenge. The aim of this study was to investigate the use of healthcare services 24 months preceding a sarcoma diagnosis compared to a matched cohort. Materials and Methods. The study was a retrospective, population-based, matched cohort registry-study. Patients with sarcoma in Denmark in 2000–2013 were identified in the Danish Sarcoma Registry (n = 2167) and matched 1 : 10 on gender, age, and listed general practice. Using a binomial regression model, incidence rate ratios were calculated for face-to-face contacts in general practice, inpatient and outpatient visits, surgery, paraclinical examinations, and diagnostic imaging. Analyses were stratified for sarcoma subtypes, grade, stage, gender, and presence of comorbidity. Results. The sarcoma patients had significantly increased incidence rate ratios in use of healthcare services compared to the matched cohort a year before their diagnoses. An increase in consultation rates was seen 11 months before diagnosis for inpatient visits, 9 months before diagnosis in general practice and outpatient visits, 8 months before diagnosis for paraclinical examinations, and 4 and 3 months before diagnosis for diagnostic imaging and surgery, respectively. There were no clinical significant differences in length of increased consultation rates between sarcoma type, stage, and grade. Sarcoma patients with comorbidity had persistently higher consultation rates compared to patients without comorbidity. Conclusions. The use of healthcare services among sarcoma patients increased several months before diagnosis in all healthcare sectors. The results reveal a diagnostic time window and a potential to refer, diagnose, and treat sarcoma patients in a timelier manner.
Power Efficiency of Energy Harvester Driven by Harmonic Excitation with Amplitude Perturbation
Authors: Kucab Krzysztof , Górski Grzegorz
Published: May 2019

In this paper, we examine the influence of the background’s stochastic excitations on an output power generated by using an energy harvester. The harvester is composed of two magnets attached to a piezoelastic oscillators separated by a distance Δ from the static magnets fastened directly to the device. We also introduce the parameter α which describes the mass ratio of moving magnets. We examine the output power for different excitation frequencies, different values of α, and different amplitudes δ0 of the stochastic force. We also analyze the influence of δ0 and Δ on the effective output power (EOP), the mean value of output power averaged over the considered frequencies, produced by using the harvester. We have observed that increasing δ0 causes the growth of generated mean power, especially in the low-frequency regime, while the maximum power near the resonance frequency remains unchanged. The EOP also grows with increasing δ0 for all examined values of α. The environment’s stochastic behavior improves slightly the harvester’s efficiency as compared to the purely harmonic case. Analyzing the dependence of EOP on Δ, we observed the maximum which appears at values of Δ corresponding to the situation when the system starts to work in the unsynchronized regime.
A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation
Authors: Ye Zhishuai , Zhang Shanfeng , Liu Yubo , Wang Shujing , Zhang Jianing , Huang Rongchong
Published: May 2019

Background. Circulating monocytes play a critical role in the pathogenesis of atherosclerosis. Monocyte homing to sites of atherosclerosis is primarily initiated by selectin. Thus, blockade of the interaction of selectins and their ligands holds a significant role in monocyte homing which might be a potential approach to treat atherosclerosis. Here, we investigated the efficacy of a novel peptide analogue of selectin ligands IELLQAR in atherosclerosis. Methods and Results. In this study, we firstly measured the effect of the IELLQAR selectin-binding peptide on the inhibition of binding of selectins to monocytes by flow cytometry, which exhibited a dose-dependent inhibitory effect on the binding of the P-, E-, and L-selectins to monocytes, especially the inhibition of P-selectin binding to human peripheral blood monocytes (PBMCs) (half maximal inhibitory concentration (IC50~5 μM)) and THP-1 cells (IC50~10 μM). Furthermore, IELLQAR inhibited P-selectin-induced activation of CD11b on the surface of monocytes and decreased adhesion of monocytes to the endothelium. ApoE-/- mice with or without IELLQAR (1 or 3 mg/kg) fed a Western-type diet (WTD) or which had disturbed blood flow-induced shear stress underwent partial left carotid artery ligation (PLCA) to induce atherosclerosis. In the WTD- and PLCA-induced atherosclerosis models, atherosclerotic plaque formation and monocyte/macrophage infiltration of the arterial wall both decreased in ApoE-/- mice treated with the IELLQAR peptide. Our results also revealed that IELLQAR inhibited the differentiation of monocytes into macrophages through P-selectin-dependent activation of the nuclear factor- (NF-) κB and mammalian target of rapamycin (mTOR) pathways. Conclusion. Collectively, our results demonstrated that IELLQAR, a peptide analogue of selectin ligands, inhibited selectin binding to monocytes, which led to subsequent attenuation of atherosclerosis via inhibition of monocyte activation. Hence, use of the IELLQAR peptide provides a new approach and represents a promising candidate for the treatment of atherosclerosis in the early stage of disease.
Lightweight Privacy Preservation for Securing Large-Scale Database-Driven Cognitive Radio Networks with Location Verification
Authors: Zhu Rui , Xu Li , Zeng Yali , Yi Xun
Published: May 2019

The database-driven cognitive radio networks (CRNs) are regarded as a promising approach to utilizing limited spectrum resources in large-scale Internet of Things (IoT). However, database-driven CRNs face some security and privacy threats. Firstly, secondary users (SUs) should send identity and location information to the database (DB) to obtain a list of available channels, such that the curious DB might easily misuse and threaten the privacy of SUs. Secondly, malicious SUs might send fake location information to the DB in order to occupy channels with better quantity in advance and so gain benefits. This might also cause serious interference to primary users (PUs). In this paper, we propose a lightweight privacy-preserving location verification protocol to protect the identity and location privacy of each SU and to verify the location of SUs. In the proposed protocol, the SU does not need to provide location information to request an available channel from the DB. Therefore, the DB cannot get the location information of any SU. In the proposed protocol, the base station (BS) selects some SUs as witnesses to generate location proofs for each other in a distributed fashion. This new witness selection mechanism makes the proposed protocol reliable when a malicious SU generates fake location information to cheat the BS and also prevents SU-Witness collusion attacks. The results also show that the proposed protocol can provide strong privacy preservation for SUs and can effectively verify the location of the SUs. The security analysis shows that the proposed protocol can resist various types of attacks. Moreover, compared with previous protocols, the proposed protocol is lightweight because it relies on symmetric cryptography and it is unaffected by the area covered by the DB.
Effect of Calcium Carbonate Whisker and Fly Ash on Mechanical Properties of Cement Mortar under High Temperatures
Authors: Wang Li , Zhang Hongliang , Zhao Bendong , Gao Yang
Published: May 2019

Calcium carbonate (CaCO3) whisker, as a new type of microfibrous material, has been extensively used in the reinforcement of cementitious materials. However, the combined effect of CaCO3 whisker and fly ash on mechanical properties of cementitious materials under high temperatures was still unknown. In this study, the coupling effect of CaCO3 whisker, and fly ash on mechanical properties of the cement was investigated. Two sets of cement mortars were fabricated, including CaCO3 whisker-based mortar which contained 0 wt.%, 5 wt.%, 10 wt.%, 15 wt.%, and 20 wt.% CaCO3 whisker as cement substitution and CaCO3 whisker-based fly ash mortar which contained 30 wt.% fly ash in addition to 0 wt.%, 5 wt.%, 10 wt.%, 15 wt.%, and 20 wt.% CaCO3 whisker as cement substitution. Mass loss, compressive strength, and flexural strength of these two sets of specimens before and after being subjected to high temperatures of 200°C, 400°C, 600°C, 800°C, and 1000°C were measured. Based on the results of the aforementioned tests, load-deflection test was performed on the specimen which exhibited the superior performance to further study its mechanical behavior after exposure to high temperatures. Moreover, microstructural analysis, such as mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM), was conducted to reveal the damage mechanism of high temperature and to illustrate the combined effect of CaCO3 whisker and fly ash on high-temperature resistance of the cement. Results showed that fly ash could improve the high-temperature performance of CaCO3 whisker-based mortar before 600°C and limit the loss of strength after 600°C.
Research Needs for Implementing Cancer Prevention and Early Detection in Developing Countries: From Scientists’ to Implementers’ Perspectives
Authors: Murillo Raúl , Robles Claudia
Published: May 2019

Implementation of evidence-based cancer prevention and early detection in low- and middle-income countries (LMIC) is challenging. Limited and inappropriate introduction of novel alternatives results in an equity gap whereby low-income populations receive a lower benefit. Implementation research represents an opportunity to foster the adoption and expansion of evidence-based cancer control strategies; however, scientific development in high-income countries does not necessarily fulfill the particular needs of LMIC in the field. A review on the link between implementation research and practice, the tension between theory and pragmatism, the conflict around implementation research methods, and determinants of research priority definition was carried out by considering the perspective of cancer prevention and early detection implementers in LMIC. Basic principles and alternatives to overcome implementation research challenges in these settings are discussed.
Increased Insular Connectivity and Enhanced Empathic Ability Associated with Dance/Music Training
Authors: Gujing Li , Hui He , Xin Li , Lirong Zhang , Yutong Yao , Guofeng Ye , Jing Lu , Shulin Zhou , Lei Yang , Cheng Luo , Dezhong Yao
Published: May 2019

Dance and music are expressive art forms. Previous behavioural studies have reported that dancers/musicians show a better sensorimotor ability and emotional representation of others. However, the neural mechanism behind this phenomenon is not completely understood. Recently, intensive researches have identified that the insula is highly enrolled in the empathic process. Thus, to expand the knowledge of insular function associated with empathy under the dance/music training background, we mapped the insular network and its associated brain regions in 21 dancers, 20 musicians, and 24 healthy controls using resting-state functional connectivity (FC) analysis. Whole brain voxel-based analysis was performed using seeds from the posterior insula (PI), the ventral anterior insula (vAI), and the dorsal anterior insula (dAI). The training effects of dance and music on insular subnetworks were then evaluated using one-way analysis of variance ANOVA. Increased insular FC with those seeds was found in dancers/musicians, including PI and anterior cingulated cortex (ACC), vAI and middle temporal gyrus (MTG) and middle cingulated cortex (MCC), and dAI and ACC and MTG. In addition, significant associations were found between discrepant insular FC patterns and empathy scores in dancers and musicians. These results indicated that dance/music training might enhance insular subnetwork function, which would facilitate integration of intero/exteroceptive information and result in better affective sensitivity. Those changes might finally facilitate the subjects’ empathic ability.
Numerical Treatment for the Three-Dimensional Eyring-Powell Fluid Flow over a Stretching Sheet with Velocity Slip and Activation Energy
Authors: Umar Muhammad , Akhtar Rizwan , Sabir Zulqurnain , Wahab Hafiz Abdul , Zhiyu Zhu , Imran Ali , Shoaib Muhammad , Raja Muhammad Asif Zahoor
Published: May 2019

In this manuscript, a computational paradigm of technique shooting is exploited for investigation of the three-dimensional Eyring-Powell fluid with activation energy over a stretching sheet with slip arising in the field of fluid dynamics. The problem is modeled and resulting nonlinear system of PDEs is transformed into nonlinear system of ODEs using well-known similarity transformations. The strength of shooting based computing approach is employed to analyze the dynamics of the system. The proposed technique is well-designed for different scenarios of the system based on three-dimensional non-Newtonian fluid with activation energy over a stretching sheet. Slip condition is also incorporated to enhance the physical and dynamical analysis of the system. The proposed results are compared with the bvp4C method for the correctness of the solver. Graphical and numerical illustrations are used to envisage the behavior of different proficient physical parameters of interest including magnetic parameter, stretching rate parameter, velocity slip parameter, Biot number on velocity, and Lewis number on temperature and concentration.
Intracellular Delivery of an Antibody Targeting Gasdermin-B Reduces HER2 Breast Cancer Aggressiveness
Authors: Molina-Crespo Ángela , Cadete Ana , Sarrio David , Gámez-Chiachio Manuel , Martinez Lidia , Chao Kinlin , Olivera Ana , Gonella Andrea , Díaz Eva , Palacios José , Dhal Pradeep K. , Besev Magnus , Rodríguez-Serrano Macarena , García Bermejo María Laura , Triviño Juan Carlos , Cano Amparo , García-Fuentes Marcos , Herzberg Osnat , Torres Dolores , Alonso Maria José , Moreno-Bueno Gema
Published: May 2019

Purpose:

Gasdermin B (GSDMB) overexpression/amplification occurs in about 60% of HER2 breast cancers, where it promotes cell migration, resistance to anti-HER2 therapies, and poor clinical outcome. Thus, we tackle GSDMB cytoplasmic overexpression as a new therapeutic target in HER2 breast cancers.

Experimental Design:

We have developed a new targeted nanomedicine based on hyaluronic acid–biocompatible nanocapsules, which allow the intracellular delivery of a specific anti-GSDMB antibody into HER2 breast cancer cells both in vitro and in vivo.

Results:

Using different models of HER2 breast cancer cells, we show that anti-GSDMB antibody loaded to nanocapsules has significant and specific effects on GSDMB-overexpressing cancer cells' behavior in ways such as (i) lowering the in vitro cell migration induced by GSDMB; (ii) enhancing the sensitivity to trastuzumab; (iii) reducing tumor growth by increasing apoptotic rate in orthotopic breast cancer xenografts; and (iv) diminishing lung metastasis in MDA-MB-231-HER2 cells in vivo. Moreover, at a mechanistic level, we have shown that AbGB increases GSDMB binding to sulfatides and consequently decreases migratory cell behavior and may upregulate the potential intrinsic procell death activity of GSDMB.

Conclusions:

Our findings portray the first evidence of the effectiveness and specificity of an antibody-based nanomedicine that targets an intracellular oncoprotein. We have proved that intracellular-delivered anti-GSDMB reduces diverse protumor GSDMB functions (migration, metastasis, and resistance to therapy) in an efficient and specific way, thus providing a new targeted therapeutic strategy in aggressive HER2 cancers with poor prognosis.
Potential of Parameters of Iron Metabolism for the Diagnosis of Anemia of Inflammation in the Critically Ill
Authors: Boshuizen Margit , Binnekade Jan M. , Nota Benjamin , van de Groep Kirsten , Cremer Olaf L. , Horn Janneke , Schultz Marcus J. , van Bruggen Robin , Juffermans Nicole P. ,   Molecular Diagnosis and Risk Stratification of Sepsis (MARS) Consortium
Published: May 2019

Background: Anemia of inflammation (AI) is the most common cause of anemia in the critically ill, but its diagnosis is a challenge. New therapies specific to AI are in development, and they require accurate detection of AI. This study explores the potential of parameters of iron metabolism for the diagnosis of AI during an ICU stay. Methods: In a nested case-control study, 30 patients developing AI were matched to 60 controls. The iron parameters were determined in plasma samples during an ICU stay. Receiver operating characteristic curves were used to determine the iron parameter threshold with the highest sensitivity and specificity to predict AI. Likelihood ratios as well as positive and negative predictive values were calculated as well. Results: The sensitivity of iron parameters for diagnosing AI ranges between 62 and 76%, and the specificity between 57 and 72%. Iron and transferrin show the greatest area under the curve. Iron shows the highest sensitivity, and transferrin and transferrin saturation display the highest specificity. Hepcidin and ferritin show the lowest specificity. At an actual anemia prevalence of 53%, the diagnostic accuracy of iron, transferrin, and transferrin saturation was fair, with a positive predictive value between 71 and 73%. Combining iron, transferrin, transferrin saturation, hepcidin, and/or ferritin levels did not increase the accuracy of the AI diagnosis. Conclusions: In this explorative study on the use of different parameters of iron metabolism for diagnosing AI during an ICU stay, low levels of commonly measured markers such as plasma iron, transferrin, and transferrin saturation have the highest sensitivity and specificity and outperform ferritin and hepcidin.
Cigarette Smoke Extract Activates Tartrate-Resistant Acid Phosphatase-Positive Macrophage
Authors: Igari Kimihiro , Kelly Matthew J. , Yamanouchi Dai
Published: May 2019

Background: It has been reported that smoking is one of the strongest positive risk factors for abdominal aortic aneurysms (AAAs). Although many studies have been directed to decipher the effect of smoking on AAA, its effect on macrophage activation has not yet been explored. Objectives: We have reported the importance of osteoclastogenesis (OCG) in aneurysm formation. Therefore, we examined the effect of cigarette smoking on OCG and arterial aneurysmal formation by using cigarette smoke extract (CSE) in this study. Methods: Macrophage cell lines were stimulated with CSE, and their activation and differentiation were examined in vitro. Since macrophages activated through the OCG pathway are identified by tartrate-resistant acid phosphatase (TRAP) expression, these cells are referred to as TRAP-positive macrophages (TPMs) in this study. We also applied CSE-contained PBS in the calcium chloride-induced mouse carotid aneurysm model in vivo. Results: Macrophages stimulated with CSE expressed significantly higher levels of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), TRAP, cathepsin K, matrix metalloproteinase-9 and membrane-type metalloproteinase (MT1-MMP). CSE-treated mouse aneurysms showed increased aneurysm size with increased TPM infiltration and protease expression compared to non-CSE-treated mouse aneurysms. Conclusions: These results suggest that CSE intensifies OCG in macrophages and promotes arterial aneurysmal progression.
A Review of Urine Ancillary Tests in the Era of the Paris System
Authors: Allison Derek B. , VandenBussche Christopher J.
Published: May 2019

Aside from its diagnostic importance, urinary tract endoscopy is an uncomfortable, expensive, and time-consuming procedure. Patients with a history of urothelial carcinoma remain at an increased risk for recurrence and the development of de novo disease; most have had exposure to carcinogenic risk factors for decades prior to their first diagnosis that have bathed the entire urothelial tract. Consequently, monitoring these patients over their lifetime has made urothelial carcinoma one of the most expensive cancers for the US healthcare system. This expense has provided a financial incentive for academic and commercial groups to develop a test with a sufficient negative predictive value to reduce the frequency of surveillance procedures. Slide-based tests require a separate slide prepared from a split urine sample or from an additional urinary tract specimen. This process can place an additional burden on the laboratory due to changes in the workflow, especially if the split specimens need to be stored until a cytologic diagnosis is rendered (i.e., when used as a reflex test). Importantly, slide-based tests allow for the result to be directly correlated with cytomorphologic findings; however, these tests require the cells of interest to be present. Thus, slide-based tests suffer from the same sensitivity issues as urinary tract cytology. In contrast, slide-free tests do not require an additional slide to be prepared, and laboratory testing may be centralized to a core facility or performed on-site. Some tests detect the expression of altered or abnormally expressed subcellular material (proteins, DNA, etc.) in urothelial neoplasms, which are found in tumor cells and/or in the urine specimen when the proteins are either excreted or leaked from degenerating tumor cells. Slide-free tests may also be developed into point-of-care tests, meaning that the result may be available to the urologist but not to the cytopathologist. Since these proteins are often disassociated from the tumor cells that produce them, such tests may have a positive result even if tumor cells are absent in the tested specimen. Here we review critical concepts as well as several ancillary tests that have been developed for urinary tract specimens.
Finger-Like Projections in Lobar Haemorrhage on Early Magnetic Resonance Imaging Is Associated with Probable Cerebral Amyloid Angiopathy
Authors: Renard Dimitri , Parvu Teodora , Thouvenot Eric
Published: May 2019

Background: Recently, finger-like projections (FLP) and subarachnoid haemorrhage extension (SAHE) of lobar intracerebral haemorrhage (LH) on acute CT together with ApoE4 genotype have been used in a prediction model for histopathologically proven cerebral amyloid angiopathy (CAA). Our aim was to analyse FLP and SAHE on acute/early subacute magnetic resonance imaging (MRI) and to assess the association with probable CAA diagnosis according to modified Boston criteria. Methods: We retrospectively studied MRI scans (and CT if available) performed <7 days in a cohort of consecutive acute LH patients >55 years. Results: Forty-six patients (24 men and 22 women; mean age 73; 28 probable and 18 possible CAA patients) were analysed. Mean symptom onset-MRI delay was 1.3 days (including 26 patients with MRI <24 h). Both probable and possible CAA groups were comparable regarding age, sex, time MRI and CT performance, MRI field strength, and LH volume. On MRI, both FLP and SAHE were observed more frequently in probable than in possible CAA (FLP 43 vs. 6%, p = 0.0073; SAHE 79 vs. 44%, p = 0.027), and associated with larger LH volumes (FLP, p = 0.011; SAHE, p = 0.047). FLP was associated with earlier performed MRI (mean 0.3 vs. 1.75 days, p = 0.025). In the subgroup of 35 patients with available CT (performed a mean of 2.2 days before or after MRI), FLP presence on CT was observed more frequently in probable than in possible CAA (57 vs. 7%, p = 0.0039). Concordance of MRI and CT for FLP presence/absence was 89%. Conclusions: In acute LH patients, FLP and SAHE on acute/early subacute phase MRI are associated with probable CAA diagnosis. Larger LH volumes are associated with FLP and SAHE on MRI, and early performed MRI with FLP.
Quantitative Multiparametric MRI May Augment the Response to Radiotherapy in Mid-Treatment Assessment of Patients with Esophageal Carcinoma
Authors: Xie Tieming , Ye Zhimin , Pang Peipei , Shao Guoliang
Published: May 2019

Objective: The purpose of this study was to assess the mid-treatment response to radiotherapy (RT) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with esophageal cancer (EC). Methods: 42 patients with squamous EC were prepared for DCE-MRI and DWI scans both before treatment (NRT) and after the fifth radiotherapy (5th RT). The patients were classified into two groups (complete response [CR] and partial response [PR]) according to tumor regression after treatment. The quantitative parameters of DCE-MRI (Ktrans, Kep, Ve, and ADC) were measured. A receiver operating characteristic curve (ROC) was used to detect the efficiency of the above parameters. Results: After 1 month of RT, 29 patients were classified as CR and 11 patients were classified as PR. In the NRT group, the p values of Ktrans, Kep, Ve, and ADC were 0.004, 0.078, 0.0008, and <0.0001, respectively. After the 5th RT, the p values of the above parameters were <0.001, 0.005, 0.108, and 0.365, respectively. In the NRT group, the areas under the ROC curves of Ktrans, Ve, and ADC were 0.790, 0.617, and 0.737; the sensitivity values were 89.3, 92.5, and 90.0%; the specificity values were 69.4, 27.5, and 50.0%. In the 5th RT group, the areas under the ROC curves of Ktrans and Kep were 0.816 and 0.804; the sensitivity values were 71.2 and 95.0%; the specificity values were 81.6 and 50.0%. Conclusion: DCE-MRI combined with DWI is effective in the early prediction of radiotherapeutic response of EC after the 5th RT other than after the traditional final treatment.
Augmentation of Urinary Lactoferrin Enhances Host Innate Immune Clearance of Uropathogenic Escherichia coli
Authors: Patras Kathryn A. , Ha Albert D. , Rooholfada Emma , Olson Joshua , Ramachandra Rao Satish P. , Lin Ann E. , Nizet Victor
Published: May 2019

Urinary tract infection (UTI) is a prominent global health care burden. Although UTI is readily treated with antibiotics in healthy adults, complicated cases in immune-compromised individuals and the emerging antibiotic resistance of several uropathogens have accelerated the need for new treatment strategies. Here, we surveyed the composition of urinary exosomes in a mouse model of uropathgenic Escherichia coli (UPEC) UTI to identify specific urinary tract defense constituents for therapeutic development. We found an enrichment of the iron-binding glycoprotein lactoferrin in the urinary exosomes of infected mice. In subsequent in vitro studies, we identified human bladder epithelial cells as a source of lactoferrin during UPEC infection. We further established that exogenous treatment with human lactoferrin (hLf) reduces UPEC epithelial adherence and enhances neutrophil antimicrobial functions including bacterial killing and extracellular trap production. Notably, a single intravesicular dose of hLf drastically reduced bladder bacterial burden and neutrophil infiltration in our murine UTI model. We propose that lactoferrin is an important modulator of innate immune responses in the urinary tract and has potential application in novel therapeutic design for UTI.
Challenging the Current Risk Factors of Appendiceal Neuroendocrine Neoplasms: Can They Accurately Predict Local Lymph Nodal Invasion? Results from a Large Case Series
Authors: Galanopoulos Michail , McFadyen Rory , Drami Ioanna , Naik Rishi , Evans Nicholas , Luong Tu Vinh , Watkins Jennifer , Caplin Martyn , Toumpanakis Christos
Published: May 2019

Background: Appendiceal neuroendocrine neoplasms (ANEN) are uncommon entities, which run mostly an indolent course. Appendicectomy alone is usually curative, except for in a selected group of patients that are deemed to be at risk of loco-regional metastases, in whom a completion right hemicolectomy (RHC) is recommended. The current “Guidelines” criteria for the latter have been controversial, and may result in overtreatment, which is concerning for a young patient population. Objective: The aim of this study is to evaluate the prognostic value of the current criteria in identifying more accurately those at-risk patients. Methods: This was a retrospective study of the 263 cases of ANEN referred for advice or management to a tertiary referral unit over a 10-year period. Seventy-two patients underwent RHC, based on criteria, suggested by International Guidelines. Each one of those was assessed to identify whether it correlated with lymph node invasion (LNI) at the RHC surgical specimen. Results: Tumour grade (p < 0.001), vascular (p = 0.044) and lymph vessel invasion (p < 0.001) were all found to be statistically significant independent risk factors for LNI identified following RHC, whilst tumour size (p = 0.375) and mesoappendiceal invasion (MAI) (p = 0.317) were not statistically significant. However, deep MAI and tumour size >2 cm showed a correlation with each other on LNI positive subgroup analysis. Location in appendiceal base made LNI more likely but again was not significant (p = 0.133). Conclusions: Higher tumour grade and lymphovascular invasion should be considered as the most important risk prognosticators. Surprisingly, tumour size was not found to be significant in our cohort. Further international multicentre studies with large numbers of patients are needed to fully validate those data.