bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowing Your Beans in Parkinson’s Disease: A Critical Assessment of Current Knowledge about Different Beans and Their Compounds in the Treatment of Parkinson’s Disease and in Animal Models
Authors: Rijntjes Michel
Published: October 2019

This review contains a critical appraisal of current knowledge about the use of beans in both animal models and patients with Parkinson’s disease (PD). The potential beneficial effects of beans in PD are increasingly being touted, not only in scientific journals but also by the lay media. While there is a long tradition in Ayurvedic medicine of prescribing extracts from Mucuna pruriens (MP), whose seeds contain 5% L-3,4-dihydroxyphenylalanin (L-DOPA), many other beans also contain L-DOPA (broad beans, common beans, and soybeans) or have other ingredients (coffee and cocoa) that may benefit PD patients. Indeed, bean-derived compounds can elicit neuroprotective effects in animal models of PD, while several studies in human PD patients have shown that motor performance can improve after ingestion of bean extracts. However, there are several arguments countering the view that beans serve as a natural therapy for PD: (i) the results from animal PD models are not necessarily directly applicable to humans; (ii) beans have many bioactive ingredients, some of which can be harmful in large doses; (iii) studies in human PD patients are scarce and only report on the effects of single doses or the administration of bean extract over short periods of time; and (iv) no data on long-term efficacy or side effects of bean therapy are available. Therefore, reservations about the use of beans as a “natural” therapy for PD seem to be justified.
Removal of the Rhodamine B Dye at Ti/Ru0.3Ti0.7O2 Anode Using Flow Cell System
Authors: Baddouh Ali , El Ibrahimi Brahim , Amaterz Elhassan , Rguiti M. Mohamed , Bazzi Lahcen , Hilali Mustapha
Published: October 2019

The electrochemical oxidation of the Rhodamine B dye (Rh-B) was carried out using dimensionally stable type anode (DSA, Ti/Ru0.3Ti0.7O2). The work was performed using the electrochemical flow cell system. The effect of several operating factors, such as supporting electrolytes, current density, electrolysis time, temperature, and initial concentration of Rh-B dye, were investigated. The UV-visible spectroscopy and chemical oxygen demand (COD) measurements were conducted to monitor the removal and degradation of Rh-B. The best color removal achieved was found to be 98.3% after 10 min applying 3.9 mA·cm−2 as a current density using 0.07 mol·L−1 of NaCl. Meanwhile, the highest COD removal rate (93.0%) was obtained for an applied current density of 3.9 mA·cm−2 as the optimal operating condition after 180 min reaction time, with 2.98 kW h·m−3 as energy consumption. This shows that the best conditions for color removal are not certainly the same as those for the COD removal. The rises in the concentration of NaCl, and applied current increased the Rh-B color removal rate. The decline in Rh-B dye concentration followed pseudo-first-order kinetics. The obtained values of apparent rate constant were increased by increasing chloride ion concentration. It is concluded that the electro-oxidation on DSA electrode using a flow cell is a suitable process for the removal of Rh-B dye in aqueous solutions.
Drivers of Food Choice among Pastoral/Agro-Pastoral Community in Somali Regional State, Eastern Ethiopia
Authors: Gebremichael Berhe , Asfaw Abiyot
Published: October 2019

Background. Although nutritional problems are among the Ethiopian government’s priorities, the progress of nutritional indicators in the pastoral/agro-pastoral community is below the national figure. This could be because of poor food choice decisions, which remains poorly understood. Therefore, this study aimed to explore the drivers of food choice among the pastoral/agro-pastoral community of Somali Regional State, Eastern Ethiopia. Materials and Methods. A qualitative study was conducted among 16 Focused Group Discussions (FGDs) and six Key Informant Interviews (KIIs) from May 7 to 27, 2018. Participants were selected purposefully. Native speakers of Somali language, who had previous qualitative data collection experience, collected the data. The overall collected data were cleaned, coded, sorted, categorized, and analyzed line-by-line. Content analysis was used to drive the key themes and sub-themes. Results. The study found that the commonest food item usually consumed by the community was porridge (“Shurow”), which is made from wheat or corn flour. The porridge is sometimes mixed with milk or butter. Besides, they consume boiled bean, wheat or sorghum (“Garaw”) that is mixed with oil or sugar. However, the consumption of fruits and vegetables was rare and seasonal. These all indicate that their feeding habit was monotonous with poor food choice decisions. The reported driving factors of food choice included drought, income, cost, availability and quality of foods, market access, familiarity with new foods, knowledge of nutritious foods, and health status of individuals. Conclusions. The food choice of the community was poor in the study area. Therefore, the health and agricultural sectors should work together to improve the feeding habits of this community by improving their knowledge and the availability of nutritious foods.
Genetic Polymorphisms of Toll-like receptors 2 and 9 as Susceptibility Factors for the Development of Ankylosing Spondylitis and Psoriatic Arthritis
Authors: Oliveira-Toré Camila F. , Moraes Amarilis G. , Martinez Gabriela F. , Neves Janisleya S. F. , Macedo Luciana C. , Rocha-Loures Marco A. , Quirino Marília G. , Alves Hugo V. , Sell Ana M. , Visentainer Jeane E. L.
Published: October 2019

Introduction. Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are classified as spondyloarthritis (SpA), a group of inflammatory rheumatic diseases with complex genetic etiology. Toll-like receptors (TLRs) have an important role in the mechanism of innate immunity and may influence inflammatory responses. Polymorphisms in TLR genes that lead to changes in these receptors or that interfere with the transcription rates of mRNA TLR may be involved in the chronic inflammatory immune response observed in SpA. Currently, there is a lack of studies associating genetic polymorphisms in TLRs and SpA. Objective. Therefore, this case-control study is aimed at analyzing the influence of the respective SNPs on TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084 in the immunopathogenesis of SpA. Methods. The polymorphisms genotyped by PCR-RFLP were TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084. The HLA-B∗27 was performed by PCR-SSP. Results. Logistic regression analysis showed a strong association between SNPs in TLR2 and TLR9 and susceptibility to SpA (OR=12.56; CI=6.5-25.9 and OR=1.62; CI=1.20-2.21, respectively). No association was observed among HLA-B∗27 and TLR polymorphisms (p=0.72), nor among BASDAI and TLR polymorphisms (p=0.85). Discussion. Our findings suggest that polymorphisms in TLR2 and TLR9 genes may contribute to the immunopathogenesis of the SpA. The rs187084, rs5743836, and rs5743708 polymorphisms were associated with the risk of SpA development, in this study, and lead to significant changes in the innate and adaptive immune response profile, as well as the maintenance of the regulation of immunological mechanisms. Conclusion. The polymorphism rs5743708 for the TLR2 and the rs187084_rs5743836 TLR9 haplotypes appear to be involved in the development of clinical forms of SpA and can be a possible therapeutic target for the spondyloarthritis.
Study on Bending Damage Constitutive Model and Mechanical Properties of Limestone Based on Acoustic Emission
Authors: Zhang Yuanshuai , Zuo Shuangying , Yu Bo , Chen Shiwan , Jia Jienan
Published: October 2019

To reveal the mechanical characteristics and damage evolution mechanism of limestone in the bending process, the cumulative acoustic emission (AE) hits were used to define the damage variable, and the rock microbody hypothesis and the Weibull distribution function were applied to further improve the damage variable. Meanwhile, the bending damage constitutive model of limestone under three‐point bending was developed based on the Lemaitre strain equivalence principle and the continuum damage theory. Then, the three‐point bending test with acoustic emission monitoring was carried out to verify the rationality and validity of the model. Results showed that the modified damage variable D had an exponential distribution with the strain ε, and the damage was mainly concentrated in the macrocrack propagation stage. Moreover, the bending neutral layer moved towards the compressive zone in the bending damage process. The bending neutral layer, furthermore, moved slowly a small distance at the initial stage of bending fracture but moved fast a long distance at the end stage of bending fracture. In addition, the bending damage constitutive model could be quantitatively expressed by the cumulative AE hits Np, the stress σ, the strain ε, and Young’s modulus E. The theoretical stress‐strain model curves agreed well with experimental results, which demonstrated that the proposed model could capture the damage evolution of limestone reasonably in the bending process.
MicroRNA-150 Modulates Adipogenic Differentiation of Adipose-Derived Stem Cells by Targeting Notch3
Authors: Li Xiang , Zhao Yu , Li Xiuquan , Wang Qiao , Ao Qiang , Wang Xiaohong , Tian Xiaohong , Tong Hao , Kong Deyu , Chang Shijie , Bai Shuling , Fan Jun
Published: October 2019

MicroRNAs (miRNAs) influence stem cell functions, including mobilization, proliferation, and differentiation. miR-150 is abundantly expressed in monocytes. Knockdown of miR-150 promotes bone marrow stem cell migration. The role of miR-150 in adipose-derived stem cells (ADSCs) is unclear. In this study, the effects of miR-150 on adipogenic differentiation and proliferation of ADSCs were investigated. ADSCs were isolated from the inguinal adipose tissue of wild-type (WT) and miR-150 knockout (KO) mice and were induced for adipogenic differentiation. The miR-150 level was detected by real-time PCR. ADSCs were transfected by miR-150 or small-interfering RNA (siRNA) of Notch3. MTT assay and colony formation assay were performed in miR-150 knockdown and control ADSCs. Real-time PCR showed that miR-150 was expressed in ADSCs. miR-150 knockdown significantly decreased the capacity of adipogenic differentiation of ADSCs, as compared with their counterparts from WT mice. It is intriguing that the overexpression of miR-150 significantly increased C/EBPα and PPAR-γ expression and lipid formation in ADSCs with adipogenic induction. Overexpression of miR-150 significantly decreased Notch3 expression in ADSCs compared with the control groups. Furthermore, Notch3 inhibition promoted the adipogenic differentiation in ADSCs. miR-150 also suppressed proliferation potential and the expression of Nanog in ADSCs. In summary, this study demonstrates, for the first time, that miR-150 promotes adipogenic differentiation and inhibits proliferation of ADSCs. miR-150 regulates adipogenic differentiation of ADSCs, likely mediated by the downregulation of Notch3.
Cytotoxicity Evaluation of Endodontic Pins on L929 Cell Line
Authors: Cannella Vincenza , Altomare Roberta , Chiaramonte Gabriele , Di Bella Santina , Mira Francesco , Russotto Laura , Pisano Patrizia , Guercio Annalisa
Published: October 2019

Objective. The aim of this study was to evaluate the cytotoxic potential of a type of endodontic pin on L929 cell line according to the UNI EN ISO 10993/2009 rule. Methods. L929 cells were used for the assays; extracts were prepared from three different-diameter endodontic pins, made of epoxy resin and fiberglass matrix and from Reference Materials (ZDEC, ZDBC, and HDP films). MTS assay was performed after 24 h, 48 h, and 72 h of exposure of L929 cells to pin and Reference Material extracts, 5% phenol solution, and control reagent. Cells cultured with different media containing extracts were monitored for up to 72 h and stained with haematoxylin/eosin. Results. Pins of different diameters had no cytotoxic effects on L929 cells at 24 h, 48 h, and 72 h (all values >70%). Cells cultured in medium containing pin extracts grew without any differences compared to the control cells. Conclusion. The endodontic pins tested showed no cytotoxic effects and did not induce changes in morphology for up to 72 h.
Nigella sativa Oil Mouth Rinse Improves Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia
Authors: Hussain Saad Abdulrahman , Mohammed Ameen Hazha Abdulah , Mohammed Mohammed Omer , Ahmed Khadija Muhamed , Hama-Gareb Ali Rebaz , Safar Banaz Mubarak , Saeed Kamal Ahmed
Published: October 2019

Objective. The present study aims at evaluating the beneficial effect of Nigella sativa (NS) oil mouth rinse in the management of chemotherapy- (CT-) induced oral mucositis (OM) in patients with acute myeloid leukemia (AML). Methods. Fifty-four AML patients were participated in this study and randomly allocated to either the test group or a control group. The patients of the test group received NS oil mouth rinse during 28-day CT, while the participants of the control group received a “magic mouthwash” formula. The primary outcome of this study was the incidence and severity of CT-induced OM in terms of erythema and ulcer. The secondary outcomes were the pain severity score, swallowing function, and the salivary concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Results. NS oil mouth rinse attenuated the progression of CT-induced OM compared with the control formula (AUC = 5.9 vs. 38.4, P<0.05) and significantly decreased the erythema and ulceration scores (AUC of total OMAS = 11.4 vs. 85.9, P<0.001) compared with the magic mouthwash formula. It also reduced the pain score and enabled all the participants of this group to consume normal food during treatment. It significantly decreased salivary IL-6 (AUC = 7376 vs. 16599, P<0.001), while the changes of TNF-α levels were not significant (AUC = 676.9 vs. 885.2, P>0.05). Conclusions. NS oil mouth rinse is effective in attenuating the severity of CT-induced OM and improves the pain and swallowing function in AML patients.
Sarcoidosis and Multiple Myeloma: A Case Report and Literature Review
Authors: Tiago Serra Joao , Martinho Aurelia , Paixao Duarte Fernanda , Aldomiro Fernando
Published: October 2019

The existence of a sarcoidosis-lymphoma syndrome has been previously proposed since the relation between sarcoidosis and an increased risk of lymphoproliferative disorders is well established. Multiple myeloma is a malignant multifocal proliferation of clonal plasma cells within the bone marrow, and its association with sarcoidosis has been rarely described. We present a concurrent diagnosis of sarcoidosis and multiple myeloma and make a brief analysis of the reported cases in the literature. A 65-year-old woman underwent surgery for the excision of a wrist mass that presented 3 years before. Histological analysis showed sarcoid-type epithelioid granulomas without necrosis, establishing soft tissue sarcoidosis. Further evaluation revealed marked interstitial lung parenchyma lesions and large intrathoracic adenopathies. Bronchofibroscopy with transbronchial biopsy confirmed lung sarcoidosis. In addition, blood analysis showed monoclonal IgG kappa gammopathy. A bone marrow biopsy confirmed hypercellularity with 60% plasma cells and plasmocyte infiltration. Thus, the diagnosis of systemic sarcoidosis and multiple myeloma was established simultaneously. In a brief review of the literature, we identified 33 reports of cases with both sarcoidosis and multiple myeloma. We point out the importance of a high level of suspicion for the association of sarcoidosis with malignant haematological diseases such as multiple myeloma.
Investigation of the Clinical Significance and Prognostic Value of the lncRNA ACVR2B-As1 in Liver Cancer
Authors: Nie Yuanyuan , Jiao Yan , Li Yanqing , Li Wei
Published: October 2019

A refined liver cancer staging system and effective prognostic prediction can help clinicians make optimized treatment decisions, which is essential in our fight against cancer and for improving the unsatisfying survival rate of liver cancer globally. The prognosis of liver cancer is not only related to tumor status, it is also affected by the patients’ liver functions and the chosen treatment. Currently, several staging systems are being tested. Herein, we analyzed RNA-seq data from the TCGA database and identified a newly annotated lncRNA, ACVR2B-AS1, whose expression is upregulated in liver cancer. Higher ACVR2B-AS1 expression is an independent adverse prognostic factor for overall survival (OS) and relapse-free survival (RFS) in liver cancer patients. Our work suggests that the lncRNA ACVR2B-AS1 could be a candidate biomarker for liver cancer prognosis. Furthermore, ACVR2B-AS1 might serve as a potential therapeutic target, which is a possibility that is worthy of further study.
A Fast RFID Tag Anticollision Algorithm for Dynamic Arrival Scenarios Based on First-Come-First-Serve
Authors: Zhang Guofeng , Tao Sha , Yu Lina , Xiao Wan’ang , Cai Qiang , Gao Wanlin , Jia Jingdun , Wen Juan
Published: October 2019

Radio-frequency identification (RFID) tag anticollision algorithm is a key technology that affects the performance of RFID systems. In dynamic arrival scenarios, when the tags arrive the reader’s interrogation zone, they cannot participate in the ongoing identification immediately, resulting in longer waiting time and tag miss. Focusing on solving this problem, based on blocking technology, dynamic frame-slotted ALOHA (DFSA) algorithm, and the first-come-first-serve (FCFS) idea, a fast RFID tag anticollision algorithm for dynamic arrival scenarios is proposed, named as “DAS-DFSA algorithm”. By optimizing the instruction structure and identification process, the DAS-DFSA allows the new arrival tag to immediately participate in the ongoing identification process, the tag’s waiting time is shortened, and the miss rate is reduced. DAS-DFSA not only adopts blocking technology to prevent the collision between the arrival tag and waiting tag but also uses unequal-length slots to reduce the communication time overhead. Simulation results show that the identification speed of the algorithm is significantly improved and high system efficiency is guaranteed. Under the same operating conditions, compared with similar algorithms, the waiting time is shortened by more than 44.548% and the identification speed is improved by at least 39.053%. More importantly, it can provide the instant-on-service for dynamic arrival tags and can fully meet the requirements of fast identification of tags in different dynamic arrival scenarios.
Optimistic Fair Exchange in Cloud-Assisted Cyber-Physical Systems
Authors: Wang Jun , Luo Feixiang , Zhou Zequan , Luo Xiling , Wang Zhen
Published: October 2019

Recently, optimistic fair exchange in electronic commerce (e-commerce) or mobile commerce (m-commerce) has made great progress. However, new technologies create large amounts of data and it is difficult to handle them. Fortunately, with the assistance of cloud computing and big data, optimistic fair exchange of digital items in cyber-physical systems (CPSes) can be efficiently managed. Optimistic fair exchange in cloud-assisted CPSes mainly focuses on online data exchange in e-commerce or online contracts signing. However, there exist new forms of risks in the uncertain network environment. To solve the above problems, we use a new technique called verifiably encrypted identity-based signature (VEIS) to construct optimistic fair exchange in cloud-assisted CPSes. VEIS is an encrypted signature, and we can check the validity of the underlying signature without decrypting it. We introduce a robust arbitration mechanism to guarantee fairness of the exchange, and even the trusted third party (TTP) cannot get the original signatures of the exchange parties. And the TTP in our protocol is offline, which greatly improves the efficiency. Besides, we show that our protocol is secure, fair, and practical.
Presence of Virulence Genes inEnterococcusSpecies Isolated from Meat Turkeys in Germany Does Not Correlate with Chicken Embryo Lethality
Authors: Maasjost Julia , Lüschow Dörte , Kleine Anne , Hafez Hafez M. , Mühldorfer Kristin
Published: October 2019

Virulence-associated traits have frequently been studied in enterococci and are considered to contribute towards the pathogenicity of infections. In the present study,Enterococcusisolates were collected during diagnostic investigations from meat turkeys in Germany. Twenty-eight isolates of three differentEnterococcusspecies were analyzed for five selected putative virulence traits to understand their potential role in the pathogenicity using the chicken embryo lethality assay. TenE. faecalis, tenE. faecium, and eightE. gallinarumisolates were examined for the presence of common virulence genes and their phenotypic expression, namely, the cytolysin operon, five individualcylgenes (cylLL,cylLS,cylM,cylB, andcylA), gelatinase (gelE), hyaluronidase (hylEfm), aggregation substance (asa1), and enterococcal surface protein (esp). TheEnterococcusisolates showed significant species-dependent differences in the presence of genotypic traits (p<0.001by Fisher’s exact test; Cramer’sV = 0.68). At least one gene and up to three virulence traits were found inE. faecalis, while sixE. faeciumisolates and oneE. gallinarumisolate did not display any virulence-associated pheno- or genotype. More than half of theEnterococcusisolates (n = 15) harbored thegelEgene, but onlyE. faecalis(n = 10) expressed the gelatinase activityin vitro. ThehylEfmgene was found in fiveE. gallinarumisolates only, while seven isolates showed the hyaluronidase activity in the phenotypic assay. In Cramer’sVstatistic, a moderate association was indicated for species (V ≤ 0.35) or genotype (V < 0.43) and the results from the embryo lethality assay, but the differences were not significant. AllE. gallinarumisolates were less virulent with mortality rates ranging between 0 and 30%. TwoE. faecalisisolates were highly virulent, harboring the wholecyl-operon as well asgelEandasa1genes. Likewise, oneE. faeciumisolate caused high embryo mortality but did not harbor any of the investigated virulence genes. For the first time,Enterococcusisolates of three different species collected from diseased turkeys were investigated for their virulence properties in comparison. The results differed markedly between theEnterococcusspecies, withE. faecalisharboring the majority of investigated genes and virulence traits. However, the genotype did not entirely correlate with the phenotype or the isolates’ virulence potential and pathogenicity for chicken embryos.
Seismic Performance Evaluation of Modern Bare and Masonry‐Infilled RC SMRF Structures
Authors: Ahmad M. E. , Ahmad N. , Pervez S. , Iqbal A. , Khan A. Z. , Rahim M. E. , Hassan W. , Umer K. , Khan K.
Published: October 2019

Improper execution of modern code‐designed structures in many developing countries have resulted in significant deficient building stock; low strength of concrete, reduced reinforcement, inappropriate detailing of beam‐column members, and lack of lateral ties in joint panels. Observations based on earthquake‐induced damages and experimental studies conducted on such buildings have revealed significant vulnerability of beam‐column joints of bare moment‐resisting frame structures. Shake table tests were conducted on selected three 1 : 4 reduced‐scale three‐story reinforced concrete (RC) moment‐resisting frames, including one bare RC frame and two masonry‐infilled RC frames, having relatively lower bay width‐to‐height ratio. The models were tested under multilevels of seismic excitations using natural acceleration time history of 1994 Northridge and also free vibration tests, to acquire the models’ dynamic characteristics, i.e., frequencies and elastic viscous damping, and seismic response parameters, i.e., roof displacement, interstory drift and interstory shear, and seismic response curves, in order to understand the role of masonry infill in the selected frames under moderate seismic actions. The inclusion of masonry infill avoided joint shear hinging of the frame. Additionally, the infill provided energy dissipation to the structure through masonry sliding over multiple cracks. This enabled the structure to control seismic displacement demand and resist relatively higher ground motions, yet limiting structural damages.
Dynamic Changes of DNA Methylation and Transcriptome Expression in Porcine Ovaries during Aging
Authors: Xi Xiaoyu , Zou Qin , Wei Yingying , Chen Yan , Wang Xue , Lv Daojun , Li Peilin , Wen Anxiang , Zhu Li , Tang Guoqing , Ma Jideng , Li Mingzhou , Li Xuewei , Jiang Yanzhi
Published: October 2019

The biological function of human ovaries declines along with aging. To identify the underlying molecular changes during ovarian aging, pigs were used as model animals. Genome-wide DNA methylation and transcriptome-wide RNA expression analyses were performed via high-throughput sequencing of ovaries from young pigs (180 days, puberty stage of first ovulation) and old pigs (eight years, reproductive exhaustion stage). The results identified 422 different methylation regions between old and young pigs; furthermore, a total of 2,243 mRNAs, 95 microRNAs, 248 long noncoding RNAs (lncRNAs), and 116 circular RNAs (circRNAs) were differentially expressed during both developmental stages. Gene ontology analysis showed that these genes related to different methylation and expression are involved in the ovarian aging cycle. Specifically, these are involved in cell apoptosis, death effector domain binding, embryonic development, reproduction and fertilization process, ovarian cumulus expansion, and the ovulation cycle. Multigroup cooperative control relationships were also assessed, and competing endogenous RNA (ceRNA) networks were constructed in the ovarian aging cycle. These data will help to clarify ovary age-associated potential molecular changes in DNA methylation and transcriptional patterns over time.
Data Mining of Prognostic Microenvironment-Related Genes in Clear Cell Renal Cell Carcinoma: A Study with TCGA Database
Authors: Chen Bin , Chen Wei , Jin Jing , Wang Xueping , Cao Yifang , He Yi
Published: October 2019

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent kidney malignancies. The tumor microenvironment (TME) is highly related to the oncogenesis, progress, and prognosis of ccRCC. The aim of this study was to infer the level of infiltrating stromal and immune cells and assess the prognostic value of them. The gene expression profile was obtained from TCGA and used for calculating the stromal and immune scores. Based on a cut-off value, patients were divided into low- and high-stromal/immune score groups. Survival analysis was performed to evaluate the prognostic value of stromal and immune scores. Moreover, differentially expressed genes (DEGs) that are highly related to TME were determined and applied for functional enrichment analysis and protein-protein interaction (PPI) network. The Kaplan-Meier plot demonstrated that patients with high-immune scores and stromal scores had poorer clinical outcome. In addition, a total of 89 DEGs were identified and mainly involved in 5 pathways. The top 5 degree genes were extracted from the PPI network; among them, IL10 and XCR1 were highly associated with prognosis of ccRCC. The results of the present study demonstrated that ESTIMATE algorithm-based stromal and immune scores may be a credible indicator of cancer prognosis and IL10 along with XCR1 may be a potential key regulator for the TME of ccRCC.
Physical Modeling and Numerical Simulation of the Seismic Responses of Metro Tunnel near Active Ground Fissures
Authors: Liu Nina , Lu Quanzhong , Li Jun , Peng Jianbing , Fan Wen , Liu Weiliang
Published: October 2019

Ground fissures pose serious hazards to underground, as well as aboveground, structures. In underground railways, which are near ground fissures, the potential for disasters is even higher since tunnels face threats from fissure activities. To determine the interaction between a tunnel and ground fissure in the event of an earthquake, field surveys and data analysis were applied to study the activity and damage caused by the fissure. Shaking table tests and a numerical simulation model were used to understand the dynamic response of the fissure site and tunnel. The fissure site had a clear hanging wall effect, where the acceleration amplification was larger in the hanging wall than that in the footwall both on the surface and at the middle of the fissure site. The zone of influence was also wider in the hanging wall. The acceleration magnification factor increased with the burial depth and peak acceleration of the input earthquake. The peak ground acceleration (PGA) decreased with the burial depth on both sides of the fissure. The greatest PGA coefficient was obtained at the surface of the site. The vertical soil pressure was influenced by the metro tunnel and fissure. The vertical soil pressure was larger in the hanging wall, especially in the zone near the fissure, but was less near the tunnel. The horizontal soil pressure above the tunnel was less than that near the fissure. The results of this study are essential for the safe design of underground railway systems.
Pneumonia, an Unusual Initial Presentation of Neonatal Herpes Infection
Authors: Kouadio Franck , Klinger Gil
Published: October 2019

Neonatal herpes simplex virus (HSV) infection is a life-threatening infection with high morbidity and mortality rates. Neonatal herpes, most commonly due to HSV type 2, is a multi-system disease; however, initial pulmonary presentation is extremely unusual. We describe an infant presenting with progressive respiratory distress, which was the dominant clinical feature of HSV infection during the first days of life. Sepsis work-up and antibiotic treatment were immediately initiated; however, antiviral treatment was not given until the infant’s death. HSV type 1 was isolated in nasopharyngeal and endotracheal aspirates. HSV pneumonia should be considered in a newborn with respiratory deterioration not compatible with common neonatal respiratory diseases.
Static Low-Angle Squatting Reduces the Intra-Articular Inflammatory Cytokines and Improves the Performance of Patients with Knee Osteoarthritis
Authors: Zhao Zhihong , Wang Rui , Guo Yu , Chen Lianxu , Wang Kai , Zhou Haibo , Li Hongwei , Zhou Jingbin
Published: October 2019

Osteoarthritis (OA) is one of the major diseases leading to disability, and inflammation plays an important role in the pathogenesis of OA. However, inflammation of OA is multifactorial, chronic, and in low intensity, which makes drug-based immunotherapy difficult. Here, we have designed a novel method of exercise—static low angle squat (SLAS), which reduces the intra-articular inflammation of OA knee as well as strengthens the vastus medialis of quadriceps. A two-year follow-up trial of current exercise methods demonstrated long-term, significant improvement in pain relief, range of motion, muscle strength, and knee stability.
Emulsion Electrospun Fiber Mats of PCL/PVA/Chitosan and Eugenol for Wound Dressing Applications
Authors: Mouro Cláudia , Simões Manuel , Gouveia Isabel C.
Published: October 2019

In recent years, the damaging effects of antimicrobial resistance relating to wound management and infections have driven the ongoing development of composite wound dressing mats containing natural compounds, such as plant extracts and their derivatives. The present research reports the fabrication of novel electrospun Polycaprolactone (PCL)/Polyvinyl Alcohol (PVA)/Chitosan (CS) fiber mats loaded with Eugenol (EUG), an essential oil, known for its therapeutic properties. The electrospun fiber mats were prepared via electrospinning from either water-in-oil (W/O) or oil-in-water (O/W) emulsions and characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), total porosity measurements, and water contact angle. The in vitro EUG release profile and antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa were also evaluated. The obtained results proved that the EUG was loaded efficiently into electrospun PCL/PVA/CS fiber mats and the two W/O and O/W emulsions prepared from the PCL/PVA/CS (7 : 3 : 1) and PCL/PVA/CS (3 : 7 : 1) revealed porosity within the ideal range of 60–90%, even when EUG was loaded. The measured contact angle values showed that the O/W emulsion exhibited a more hydrophilic character and the wettability noticeably decreased after adding EUG in both emulsion blends. Furthermore, the electrospun PCL/PVA/CS fiber mats demonstrated a rapid release of EUG during the first 8 hours, which enhanced gradually afterward (up to 120 hours). Moreover, an efficient antibacterial activity against S. aureus (inhibition ratios of 92.43% and 83.08%) and P. aeruginosa (inhibition ratios of 94.68% and 87.85%) was displayed and the in vitro cytotoxic assay demonstrated that the normal human dermal fibroblasts (NHDF) remained viable for at least 7 days, after direct contact with the produced electrospun fiber mats. Therefore, such findings support the biocompatibility and suitability of using these EUG-loaded electrospun PCL/PVA/CS fiber mats as a new innovative wound dressing material with potential for preventing and treating microbial wound infections.
Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia
Authors: Lopez Cécile K. , Noguera Esteve , Stavropoulou Vaia , Robert Elie , Aid Zakia , Ballerini Paola , Bilhou-Nabera Chrystèle , Lapillonne Hélène , Boudia Fabien , Thirant Cécile , Fagnan Alexandre , Arcangeli Marie-Laure , Kinston Sarah J. , Diop M'Boyba , Job Bastien , Lecluse Yann , Brunet Erika , Babin Loélia , Villeval Jean Luc , Delabesse Eric , Peters Antoine H.F.M. , Vainchenker William , Gaudry Muriel , Masetti Riccardo , Locatelli Franco , Malinge Sébastien , Nerlov Claus , Droin Nathalie , Lobry Camille , Godin Isabelle , Bernard Olivier A. , Göttgens Berthold , Petit Arnaud , Pflumio Françoise , Schwaller Juerg , Mercher Thomas
Published: October 2019

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2–GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2–GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2–GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes.

Significance:

This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.

See related commentary by Cruz Hernandez and Vyas, p. 1653.

This article is highlighted in the In This Issue feature, p. 1631
Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape
Authors: Ahmetlić Fatima , Riedel Tanja , Hömberg Nadine , Bauer Vera , Trautwein Nico , Geishauser Albert , Sparwasser Tim , Stevanović Stefan , Röcken Martin , Mocikat Ralph
Published: October 2019

Foxp3+ regulatory T cells (Tregs) sustain immune homeostasis and may contribute to immune escape in malignant disease. As a prerequisite for developing immunologic approaches in cancer therapy, it is necessary to understand the ontogeny and the antigenic specificities of tumor-infiltrating Tregs. We addressed this question by using a λ-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3+ Tregs suppress antitumor responses in endogenous lymphoma. Ablation of Foxp3+ Tregs significantly delayed tumor development. The ratio of Treg to effector T cells was elevated in growing tumors, which could be ascribed to differential proliferation. The Tregs detected were mainly natural Tregs that apparently recognized self-antigens. We identified MHC class II–restricted nonmutated self-epitopes, which were more prevalent in lymphoma than in normal B cells and could be recognized by Tregs. These epitopes were derived from proteins that are associated with cellular processes related to malignancy and may be overexpressed in the tumor.
Long-Term Mortality in Patients with Positive Lymph Nodes at the Time of Radical Prostatectomy
Authors: Froehner Michael , Koch Rainer , Farahzadi Samaneh , Heberling Ulrike , Borkowetz Angelika , Twelker Lars , Baretton Gustavo B. , Wirth Manfred P. , Thomas Christian
Published: October 2019

Background: The aim of this study was to determine prognostic factors and to provide long-term mortality data in patients with positive lymph nodes at the time of radical prostatectomy in a sample with long-term follow-up. Methods: A total of 527 patients with complete data sets treated in the years 1992–2014 were studied. The median follow-up was 7.2 years. The median number of removed lymph nodes was 15. Age, year of surgery, Gleason score, local tumor stage, prostate-specific antigen level, lymph node density, lymph node count and the number of positive lymph nodes were included in multivariable competing risk analyses with prostate cancer mortality as endpoint. Results: After 20 years, 28% of patients (95% CI 20–36%) died from non-prostate cancer (competing) causes, whereas 29% (95% CI 23–36%) died from prostate cancer. Only lymph node density (stratified by the median of 11.1%; hazard ratio [HR] 1.66, 95% CI 1.04–2.64, p = 0.0340) and Gleason score (8–10 vs. <8: HR 5.97, 95% CI 3.18–11.23, p < 0.0001) were independent predictors of prostate cancer mortality. Patients with a Gleason score <8 and a lymph node density < median had a 20-year prostate cancer mortality of only 5% (95% CI 0–10%), whereas this rate in patients with Gleason score 8–10 and a lymph node density ≥ median was 44% (95% CI 32–56%), p < 0.0001. Conclusions: Mortality in patients with positive lymph nodes was determined by tumor aggressiveness and the relative extent of spread; neither the year of surgery nor the number of removed lymph nodes was associated with outcome. Patients with a lymph node density of <11.1% and a Gleason score <8 had an excellent long-term outcome.
Effect of Group Size on Time Budgets and Ranging Behavior of White-Headed Langurs in Limestone Forest, Southwest China
Authors: Zhang Kechu , Zhou Qihai , Xu Huailiang , Huang Zhonghao
Published: October 2019

The ecological constraints model is well supported by data from most frugivorous primates; however, the prediction power of the model is weak for folivorous primates. From September 2016 to August 2017, we collected comparative data on time budgets, daily path lengths and diets of four groups of white-headed langurs (Trachypithecus leucocephalus), including two large groups (G-DS and G-ZWY) and two small groups (G-LZ and G-NN) in Chongzuo White-Headed Langur National Nature Reserve, Guangxi Province, Southwest China. The aim was to obtain evidence of foraging competition and to test the ecological constraints model on this highly folivorous primate in its karst habitat. The results showed that langurs in the larger groups spent more time traveling, less time resting, and had a longer average daily path length than those in the small groups. Diet composition and dietary diversity were not significantly different between the large and small groups. Our study demonstrates that langurs from large groups suffer scramble competition in limestone forests and supports the validity of the ecological constraints model for folivores.
Tofacitinib in Pediatric Psoriasis: An Open-Label Trial to Study Its Safety and Efficacy in Children
Authors: AlMutairi Nawaf , Nour Tarek
Published: October 2019

Introduction: Psoriasis is a chronic, multifactorial, inflammatory disorder, with an estimated prevalence of 0.71% in children. The commonly used therapeutic agents target the underlying inflammation. Tofacitinib has demonstrated efficacy in adult psoriasis. Aim: To study the efficacy, safety, and tolerability of tofacitinib in pediatric patients with moderate to severe chronic plaque psoriasis. Methods: The study included children aged between 8 and 17 years, with moderate to severe psoriasis, given tofacitinib 5 mg orally twice daily for at least 36 weeks. The clinical response was estimated using the Psoriasis Area and Severity Index (PASI) score, Physician’s Global Assessment (PGA), and the Children’s Dermatology Life Quality Index (CDLQI). The incidence and severity of adverse events (AEs) were meticulously recorded in each case. Results: A total of 47 patients, with a median age of 12.3 years, completed the study. At week 12, 55.32% achieved PASI 75, and 70.21% at week 36. PGA of clear or almost clear responses at week 12 were 59.57 and 65.96%, ­respectfully, at week 36. Relatively few and mostly minor ­adverse effects were noted. No severe AEs were reported. ­Conclusion: The treatment with tofacitinib was safe and well tolerated, and led to significant improvement of their disease and quality of life as reflected in CDLQI scores. However, the results need to be validated in larger multicenter trials.
Comparison of Six Different Allergen Extracts for Subcutaneous Specific Immunotherapy in Children: An Open-Labelled, Prospective, Controlled Observational Trial
Authors: Kopp Matthias Volkmar , König Inke R. , Friedrichs Frank , Umpfenbach Hans Ulrich , Niggemann Bodo , Millner-Uhlemann Martina
Published: October 2019

Background: Numerous products are available for subcutaneous (SCIT) and sublingual allergen-specific immunotherapy, but there are no information about the direct comparability regarding efficacy, safety, and tolerability of the different extracts. Aims: The aim of this open-labelled, prospective, controlled observational trial was to test the feasibility of a comparison of different products for SCIT in children. Methods: Pediatrician practices recruited patients with a confirmed diagnosis of a seasonal allergic rhinoconjunctivitis (AR) with or without asthma and an allergic sensitization against grass pollen allergen. Every patient was offered SCIT with one out of six allergen extracts: ALK SQ Depot, ALK Avanz, Allergovit, Depigoid, Purethal, Pollinex Quattro. Scores for symptoms and medications were calculated and the difference between treatment years and baseline were recorded. Results: In total, 284 were recruited and 255 children (89.8%; mean age 10.4, SD 3.54 years; 65% males) participated in this trial. Overall, 49,649 patient days were recorded in the electronic database (mean 183.2 days/patient). There was no significant difference in the AR and asthma symptom score or the medication score between the six different SCIT preparations. Similarly, no differences were observed in terms of safety and tolerability. Conclusion: The comparison of different SCIT products using an online tool is feasible. Based on our preliminary data, all extracts indicated efficacy; however, larger groups would be necessary to demonstrate superiority or non-inferiority of one specific SCIT product.
Pneumocephalus in a Pediatric Patient with Glioma Receiving Trametinib
Authors: Gorsi Hamza , Marupudi Neena I. , Sood Sandeep , Altinok Deniz , Yankelevich Maxim
Published: October 2019

The mitogen-activated protein kinase (MAPK) pathway consists of the Ras/Raf/MEK/ERK signaling cascade, and its upregulation plays a major role in the pathogenesis of pediatric astrocytomas and molecular inhibitors of this pathway including trametinib and dabrafenib have been tested in early-phase clinical trials and used by pediatric oncologists in children with BRAF-mutated gliomas. We report a clinical case where a child with progressive BRAF-mutated glioma developed an uncommon and difficult to manage complication – pneumocephalus from intracranial air entry and trapping through dehisced surgical wounds and preexisting skull burr holes. The patient’s wound breakdown coincided with skin toxicity from MEK inhibitor therapy. With increasing use of targeted molecular inhibitors in pediatric neuro-oncology, this case illustrates the potentially complicated course of MEK inhibitor therapy in patients with scalp surgical wounds and burr holes that were placed within few weeks from initiation of drug therapy, especially if patients have additional factors that can contribute to poor wound healing such as use of steroids and malnutrition.
Restoring the High-Frequency Dynamic Visual Acuity with a Vestibular Implant Prototype in Humans
Authors: Starkov Dmitrii , Guinand Nils , Lucieer Florence , Ranieri Maurizio , Cavuscens Samuel , Pleshkov Maksim , Guyot Jean-Philippe , Kingma Herman , Ramat Stefano , Perez-Fornos Angelica , van de Berg Raymond
Published: October 2019

Introduction: The vestibular implant could become a clinically useful device in the near future. This study investigated the feasibility of restoring the high-frequency dynamic visual acuity (DVA) with a vestibular implant, using the functional Head Impulse Test (fHIT). Methods: A 72-year-old female, with bilateral vestibulopathy and fitted with a modified cochlear implant incorporating three vestibular electrodes (MED-EL, Innsbruck, Austria), was available for this study. Electrical stimulation was delivered with the electrode close to the lateral ampullary nerve in the left ear. The high-frequency DVA in the horizontal plane was tested with the fHIT. After training, the patient underwent six trials of fHIT, each with a different setting of the vestibular implant: (1) System OFF before stimulation; (2) System ON, baseline stimulation; (3) System ON, reversed stimulation; (4) System ON, positive stimulation; (5) System OFF, without delay after stimulation offset; and (6) System OFF, 25 min delay after stimulation offset. The percentage of correct fHIT scores for right and left head impulses were compared between trials. Results: Vestibular implant stimulation improved the high-frequency DVA compared to no stimulation. This improvement was significant for “System ON, baseline stimulation” (p = 0.02) and “System ON, positive stimulation” (p < 0.001). fHIT scores changed from 19 to 44% (no stimulation) to maximum 75–94% (System ON, positive stimulation). Conclusion: The vestibular implant seems capable of improving the high-frequency DVA. This functional benefit of the vestibular implant illustrates again the feasibility of this device for clinical use in the near future.