bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuning Structure and Dynamics of Blue Copper Azurin Junctions via Single Amino-Acid Mutations
Authors: Ortega Maria , Vilhena J. G. , Zotti Linda A. , Díez-Pérez Ismael , Cuevas Juan Carlos , Pérez Rubén
Published: October 2019

In the growing field of biomolecular electronics, blue-copper Azurin stands out as one of the most widely studied protein in single-molecule contacts. Interestingly, despite the paramount importance of the structure/dynamics of molecular contacts in their transport properties, these factors remain largely unexplored from the theoretical point of view in the context of single Azurin junctions. Here we address this issue using all-atom Molecular Dynamics (MD) of Pseudomonas Aeruginosa Azurin adsorbed to a Au(111) substrate. In particular, we focus on the structure and dynamics of the free/adsorbed protein and how these properties are altered upon single-point mutations. The results revealed that wild-type Azurin adsorbs on Au(111) along two well defined configurations: one tethered via cysteine groups and the other via the hydrophobic pocket surrounding the Cu 2 + . Surprisingly, our simulations revealed that single amino-acid mutations gave rise to a quenching of protein vibrations ultimately resulting in its overall stiffening. Given the role of amino-acid vibrations and reorientation in the dehydration process at the protein-water-substrate interface, we suggest that this might have an effect on the adsorption process of the mutant, giving rise to new adsorption configurations.
A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning
Authors: Polano Maurizio , Chierici Marco , Dal Bo Michele , Gentilini Davide , Di Cintio Federica , Baboci Lorena , Gibbs David L. , Furlanello Cesare , Toffoli Giuseppe
Published: October 2019

Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we set up and validated a machine learning approach to predict the potential for positive response to ICI. Support vector machines (SVM) and extreme gradient boosting (XGboost) models were developed with a 10×5-fold cross-validation schema on 80% of TCGA cases to predict ICI responsiveness defined by a score combining tumor mutational burden and TGF- β signaling. On the remaining 20% validation subset, our SVM model scored 0.88 accuracy and 0.27 Matthews Correlation Coefficient. The proposed machine learning approach could be useful to predict the putative response to ICI treatment by expression data of primary tumors.
Genetic and Lineage Classification of Glioma-Initiating Cells Identifies a Clinically Relevant Glioblastoma Model
Authors: Saito Norihiko , Hirai Nozomi , Aoki Kazuya , Sato Sho , Suzuki Ryo , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Sakurai Takatoshi , Iwabuchi Satoshi
Published: October 2019

The Cancer Genome Atlas (TCGA) project described a robust gene expression-based molecular classification of glioblastoma (GBM), but the functional and biological significance of the subclasses has not been determined. The present comprehensive analysis of 25 glioma-initiating cell (GIC) lines classifies GIC lines into four subtypes (classical, mesenchymal, proneural, and neural) that are closely related to the TCGA GBM subclasses and display distinct lineage characteristics and differentiation behavior that recapitulate neural development. More importantly, the GIC subtypes exhibit distinct biological phenotypes in relation to self-renewal capacity, proliferation, invasiveness, and angiogenic potential in vitro and in vivo. In addition, the GIC subtypes exhibit divergent patterns of signaling pathway activation and deactivation of the Wnt, Notch, and TGF-β pathways. These results will improve drug discovery targeting certain genetic mutation in glioblastoma and improve the development of precision medicine.
PD-1-Associated Gene Expression Signature of Neoadjuvant Trastuzumab-Treated Tumors Correlates with Patient Survival in HER2-Positive Breast Cancer
Authors: Hendricks William P. D. , Briones Natalia , Halperin Rebecca F. , Facista Salvatore , Heaton Paul R. , Mahadevan Daruka , Kim Suwon
Published: October 2019

The therapeutic HER2-targeting antibody trastuzumab has been shown to elicit tumor immune response in a subset of HER2-positive (HER2+) breast cancer. We performed genomic and immunohistochemical profiling of tumors from eight patients who have completed multiple rounds of neoadjuvant trastuzumabb to identify predictive biomarkers for trastuzumab-elicited tumor immune responses. Immunohistochemistry showed that all tumors had an activated tumor immune microenvironment positive for nuclear NF-κB/p65RelA, CD4, and CD8 T cell markers, but only four out of eight tumors were positive for the PD-1 immune checkpoint molecule, which is indicative of an exhausted immune environment. Exome sequencing showed no specific driver mutations correlating with PD-1 positivity. Hierarchical clustering of the RNA sequencing data revealed two distinct groups, of which Group 2 represented the PD-1 positive tumors. A gene expression signature that was derived from this clustering composed of 89 genes stratified HER2+ breast cancer patients in the TCGA dataset and it was named PD-1-Associated Gene Expression Signature in HER2+ Breast Cancer (PAGES-HBC). Patients with the Group 2 PAGES-HBC composition had significantly more favorable survival outcomes with mortality reduced by 83% (hazard ratio 0.17; 95% CI, 0.05 to 0.60; p = 0.011). Analysis of three longitudinal samples from a single patient showed that PAGES-HBC might be transiently induced by trastuzumab, independent of clonal tumor expansion over time. We conclude that PAGES-HBC could be further developed as a prognostic predictor of trastuzumab response in HER2+ breast cancer patients and be potentially used as an alternative biomarker for anti-PD-1 therapy trials.
Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics
Authors: Lai Quirino , Vitale Alessandro , Manzia Tommaso , Foschi Francesco , Levi Sandri Giovanni , Gambato Martina , Melandro Fabio , Russo Francesco , Miele Luca , Viganò Luca , Burra Patrizia , Giannini Edoardo ,   on behalf of the Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group
Published: October 2019

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells’ extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet–tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC.
Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer
Authors: Lum Caroline , Alamgeer Muhammad
Published: October 2019

Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.
Process and Carbon Footprint Analyses of the Allam Cycle Power Plant Integrated with an Air Separation Unit
Authors: Fernandes Dan , Wang Song , Xu Qiang , Buss Russel , Chen Daniel
Published: October 2019

The Allam cycle is the latest advancement in power generation technologies with a high cycle efficiency, zero NOx emission, and carbon dioxide available at pipeline specification for sequestration and utilization. The Allam cycle plant is a semi-closed, direct-fired, oxy-fuel Brayton cycle that uses high pressure supercritical carbon dioxide as a working fluid with sophisticated heat recuperation. This paper conducted process analyses including exergy analysis, sensitivity analysis, air separation unit (ASU) oxygen pump/compressor option analysis, and carbon footprint analysis for the integrated Allam power plant (natural gas)/ASU complex with a high degree of heat and work integration. Earlier works on exergy analysis were done on the Allam cycle and ASU independently. Exergy analysis on the integrated plants helps identify the equipment with the largest loss of thermodynamic efficiency. Sensitivity analysis investigated the effects of important ASU operational parameters along with equipment constraint limits on the downstream Allam cycle. Energy efficiency and carbon footprint are compared among the state-of-the-art fossil-fuel power generation cycles.
Trinodal Self-Penetrating Nets from Reactions of 1,4-Bis(alkoxy)-2,5-bis(3,2’:6’,3’’-terpyridin-4’-yl)benzene Ligands with Cobalt(II) Thiocyanate
Authors: Manfroni Giacomo , Prescimone Alessandro , Batten Stuart R. , Klein Y. Maximilian , Gawryluk Dariusz J. , Constable Edwin C. , Housecroft Catherine E.
Published: October 2019

The tetratopic ligands 1,4-bis(2-ethylbutoxy)-2,5-bis(3,2’:6’,3’’-terpyridin-4’-yl)benzene (1) and 1,4-bis(3-methylbutoxy)-2,5-bis(3,2’:6’,3’’-terpyridin-4’-yl)benzene (2) have been prepared and characterized by 1H and 13C{1H} NMR, IR, and absorption spectroscopies and mass spectrometry. Reactions of 1 and 2 with cobalt(II) thiocyanate under conditions of crystal growth at room temperature result in the formation of [{Co(1)(NCS)2}·MeOH·3CHCl3]n and [{Co(2)(NCS)2}·0.8MeOH·1.8CHCl3]n. Single-crystal X-ray diffraction reveals that each crystal lattice consists of a trinodal self-penetrating (62.84)(64.82)(65.8)2 net. The nodes are defined by two independent cobalt centres and the centroids of two crystallographically independent ligands which are topologically equivalent.
Bacteria with Different Assemblages in the Soil Profile Drive the Diverse Nutrient Cycles in the Sugarcane Straw Retention Ecosystem
Authors: Zhang Caifang , Tayyab Muhammad , Abubakar Ahmad Yusuf , Yang Ziqi , Pang Ziqin , Islam Waqar , Lin Zhaoli , Li Shiyan , Luo Jun , Fan Xiaoliang , Fallah Nyumah , Zhang Hua
Published: October 2019

Straw retention, an alternative to artificial fertilization, commonly mitigates soil degradation and positively affects soil fertility. In this study, we investigated the succession of soil bacteria during two sugarcane straw retention treatments (control (CK) and sugarcane straw retention (SR)) and at four depths (0–10, 10–20, 20–30, and 30–40 cm) in fallow soil in a sugarcane cropping system. Using an Illumina MiSeq (16S rRNA) and soil enzyme activity, we explored the SR influence on soil bacterial communities and enzyme activities and its inclusive impact on soil fertility, with an emphasis on topsoil (0–10 cm) and subsoil (10–40 cm). Our results show that SR effectively improved soil fertility indicators (C, N, and P), including enzyme activities (C and N cycling), throughout the soil profile: these soil parameters greatly improved in the topsoil compared to the control. Sugarcane straw retention and soil depth (0–10 cm vs. 10–40 cm) were associated with little variation in bacterial species richness and alpha diversity throughout the soil profile. Subsoil and topsoil bacterial communities differed in composition. Compared to the CK treatment, SR enriched the topsoil with Proteobacteria, Verrucomicrobia, Actinobacteria, Chloroflexi, and Nitrospirae, while the subsoil was depleted in Nitrospirae and Acidobacteria. Similarly, SR enriched the subsoil with Proteobacteria, Verrucomicrobia, Actinobacteria, Chloroflexi, Gemmatimonadetes, and Bacteroidetes, while the topsoil was depleted in Acidobacteria, Gemmatimonadetes, and Planctomycetes compared to the CK. At the genus level, SR enriched the topsoil with Gp1, Gp2, Gp5, Gp7, Gemmatimonas, Kofleria, Sphingomonas, and Gaiella, which decompose lignocellulose and contribute to nutrient cycling. In summary, SR not only improved soil physicochemical properties and enzyme activities but also enriched bacterial taxa involved in lignocellulosic decomposition and nutrient cycling (C and N) throughout the soil profile. However, these effects were stronger in topsoil than in subsoil, suggesting that SR enhanced fertility more in topsoil than in subsoil in fallow land.
Accuracy Assessment of 3D Photogrammetric Models from an Unmanned Aerial Vehicle
Authors: Barba Salvatore , Barbarella Maurizio , Di Benedetto Alessandro , Fiani Margherita , Gujski Lucas , Limongiello Marco
Published: October 2019

The unmanned aerial vehicle (UAV) photogrammetric survey of an archaeological site has proved itself to be particularly efficient. In order to obtain highly accurate and reliable results, it is necessary to design carefully the flight plan and the geo-referencing, while also evaluating the indicators of the accuracy rate. Using as a test case a UAV photogrammetric survey conducted on the archaeological site of the Roman Amphitheatre of Avella (Italy), in this paper, we propose a pipeline to assess the accuracy of the results according to some quality indicators. The flight configuration and the georeferencing chosen is then be checked via the residuals on the ground control points (GCPs), evenly distributed on the edges and over the entire area. With the aim of appraising the accuracy of the final model, we will suggest a method for the outlier detection, taking into account the statistical distribution (both global and of portion of the study object) of the reprojection errors. A filter to reduce the noise within the model will then be implemented through the detection of the angle formed by homologous rays, in order to reach a compromise between the number of the usable points and the reduction of the noise linked to the definition of the 3D model.
Assessment of Green Investments’ Impact on Sustainable Development: Linking Gross Domestic Product Per Capita, Greenhouse Gas Emissions and Renewable Energy
Authors: Lyeonov Serhiy , Pimonenko Tetyana , Bilan Yuriy , Štreimikienė Dalia , Mentel Grzegorz
Published: October 2019

The paper analyses the linkages between GDP per capita, greenhouse gas (GHG) emissions, and renewable energy (RE) in the total final energy consumption and green investments (PICE) which are measured as private investments, jobs, and gross value added related to circular economy sectors. The object of the analysis is the EU countries during the 2008-2016 period (crisis and post-crisis period). In the paper, data from the following databases was used: the Eurostat, the World Data Bank, and the European Environmental Agency. For addressing the linkages between the aforementioned indicators, the following methods were applied: panel unit root test, Pedroni panel cointegration tests, and the fully modified ordinary least squares (FMOLS) and dynamic ordinary least squares (DOLS) panel cointegration techniques. The findings show that FMOLS and DOLS demonstrate the same results as GHG, PICE, RE influence on GDP of the EU countries. The findings prove there is linking between gross domestic product per capita, greenhouse gas emissions, renewable energy in the total final energy consumption and green investments. The findings also show that green investment (PICE) could provoke the growth of GDP per capita by 6.4%, the decline of GHG by 3.08%, and the increase of renewable energy in the total final energy consumption by 5.6%.
Analysis and Modeling of the Wear-Out Process of a Lithium-Nickel-Manganese-Cobalt Cell during Cycling Operation under Constant Load Conditions
Authors: Burzyński Damian , Pietracho Robert , Kasprzyk Leszek , Tomczewski Andrzej
Published: October 2019

This article describes the analyses of modeling the wear process of lithium-nickel-manganese-cobalt cells operating cyclically under constant load conditions. The main aging processes taking place in cells and the methodology of the modeling are discussed. The process of cell wear is examined, taking into account the influence of cyclic operating parameters (temperature, discharge current, and discharge depth). On the basis of the analyses carried out, a new function reflecting the influence of ambient temperature on the durability of the cell is proposed. A new fuzzy model of the wear process of the NMC 18650 type cell, depending on the parameters of the discharge half cycle, has been developed. The results of the model have been verified by experimental research.
Will Human-Induced Vegetation Regreening Continually Decrease Runoff in the Loess Plateau of China?
Authors: Li Yanzhong , Mao Dehua , Feng Aiqing , Schillerberg Tayler
Published: October 2019

China has become the largest contributing country to global vegetation regreening. However, the regreening pattern and subsequent impact on arid areas have not been comprehensively evaluated. Therefore, we selected the Loess Plateau, a representative arid region that has undergone evident vegetation restoration, to investigate the spatial patterns and temporal trends, as well as the drivers of vegetation change. This study primarily focused on 12 afforested watersheds during 2000–2018. Furthermore, both the impacts of vegetation regreening on runoff for the past two decades and the future projections were quantified based on the fraction of photosynthetically active radiation (fPAR), the Budyko model, and the global climate models (GCMs). fPAR for the last two decades indicates that vegetation in the Loess Plateau has experienced a continuous increasing trend during the growing season, primarily in response to the implementation of the Grain for Green Project (GFGP). Of the 12 watersheds, 9 experienced significant fPAR change with a change rate above 50%, and 11 exhibited a significant increase (p < 0.05) in runoff sensitivity to vegetation regreening, which indicates that vegetation regreening plays an increasingly important role in controlling runoff variation. The decline in runoff caused by vegetation regreening was particularly noticeable before 2011 or 2012; afterwards, runoff tended to vary with precipitation. In the future (2020–2049 and 2050–2099), decrease in runoff by regreening will be limited, as runoff is anticipated to decrease by 3.5% in 2020–2049 and 4.1% in 2050–2099 with a 20% increase in fPAR. These results indicate that runoff tends to be stable even with continuous vegetation regreening. While the reduction of runoff by regreening will be limited in the future, rapid human-induced vegetation regreening may aggravate water scarcity when flash droughts occur and may result in disasters in water-limited regions to the socio-economic stability and agriculture. Our study will provide an applicable theoretical foundation for water resources decision-making and ecological restoration.
Dipole and Convergent Single-Well Thermal Tracer Tests for Characterizing the Effect of Flow Configuration on Thermal Recovery
Authors: de La Bernardie Jérôme , Bour Olivier , Guihéneuf Nicolas , Chatton Eliot , Longuevergne Laurent , Le Borgne Tanguy
Published: October 2019

Experimental characterization of thermal transport in fractured media through thermal tracer tests is crucial for environmental and industrial applications such as the prediction of geothermal system efficiency. However, such experiments have been poorly achieved in fractured rock due to the low permeability and complexity of these media. We have thus little knowledge about the effect of flow configuration on thermal recovery during thermal tracer tests in such systems. We present here the experimental set up and results of several single-well thermal tracer tests for different flow configurations, from fully convergent to perfect dipole, achieved in a fractured crystalline rock aquifer at the experimental site of Plœmeur (H+ observatory network). The monitoring of temperature using Fiber-Optic Distributed Temperature Sensing (FO-DTS) associated with appropriate data processing allowed to properly highlight the heat inflow in the borehole and to estimate temperature breakthroughs for the different tests. Results show that thermal recovery is mainly controlled by advection processes in convergent flow configuration while in perfect dipole flow field, thermal exchanges with the rock matrix are more important, inducing lower thermal recovery.
Implementation of the European School Fruit and Vegetables Scheme in Spain (2009–2017)
Authors: Soares Panmela , Comino Iris , Martínez-Milán María Asunción , Davó-Blanes M. Carmen , Altavilla Cesare , Caballero Pablo
Published: October 2019

The School Fruit and Vegetables Scheme (SFVS) implemented by the European Union in 2009/2010 aims to improve the diet of students and to support agricultural markets and environmental sustainability. The objective of this study was to identify the characteristics of the School Fruit and Vegetables Scheme implementation from 2009 to 2017 in Spain and its autonomous communities. A descriptive, longitudinal, observational, and retrospective study was carried out on the basis of document analysis of SFVS reports. We studied the average budget for Spain and its autonomous communities (AC), the number of students enrolled, the cost of the SFVS by student and by day, the duration of the SFVS, the quantity of fruits and vegetables (FV) per student and day (g), the variety of FV, the recommendation to include local, seasonal, and organic foods, and the educational activities (EA). The results were studied by the AC which are territorial entities of Spain. The budget almost doubled during the study, thanks mainly to EU funds. However, the number of students increased only from 18% in 2009 to 20% in 2016. The quantity of FV increased from 2579 to 4000 tons, and the duration of the SFVS increased from 9.8 to 19.6 days. In the AC, there were variations in EA, in the number of enrolled students (7.4% to 45.6%), in the cost per student (from €2.3 to €28), and in the duration in days (5.6 to 70 days). The recommendation to include local, seasonal, and organic foods was implemented in five of the eight years studied. The development and scope of the SFVS in Spain are still insufficient to generate an equitable healthy dietary pattern in the school population. However, the SFVS has generated an economic market for agricultural production due to the amount of FV distributed in each academic course.
Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models
Authors: Fujii Yuta , Inoue Hiroaki , Arai Yuji , Shimomura Seiji , Nakagawa Shuji , Kishida Tsunao , Tsuchida Shinji , Kamada Yoichiro , Kaihara Kenta , Shirai Toshiharu , Terauchi Ryu , Toyama Shogo , Ikoma Kazuya , Mazda Osam , Mikami Yasuo
Published: October 2019

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.
Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease
Authors: Di Vincenzo Angelo , Tana Claudio , El Hadi Hamza , Pagano Claudio , Vettor Roberto , Rossato Marco
Published: October 2019

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.
Tackling Missing Heritability by Use of an Optimum Curve: A Systematic Review and Meta-Analysis
Authors: Wegener Sleeswijk Anneke , Heijungs Reinout , Durston Sarah
Published: October 2019

Missing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept study uses a systematic review and meta-analysis of the association between variants of the serotonin transporter promoter (5-HTTLPR) and autism to explore the hypothesis that some missing heritability can be explained using an optimum curve. A systematic literature search was performed to identify transmission disequilibrium tests on the short/long (S/L) 5-HTTLPR polymorphism in relation to autism. We analysed five American, seven European, four Asian and two American/European samples. We found no transmission preference in the joint samples and in Europe, preferential transmission of S in America and preferential transmission of L in Asia. Heritability will be underestimated or missed in genetic association studies if two alternative genetic variants are associated with the same disorder in different subsets of a sample. An optimum curve, relating a multifactorial biological variable that incorporates genes and environment to a score for a human trait, such as social competence, can explain this. We suggest that variants of functionally related genes will sometimes appear in fixed combinations at both sides of an optimum curve and propose that future association studies should account for such combinations.
Naturally Prefabricated Marine Biomaterials: Isolation and Applications of Flat Chitinous 3D Scaffolds from Ianthella labyrinthus (Demospongiae: Verongiida)
Authors: Schubert Mario , Binnewerg Björn , Voronkina Alona , Muzychka Lyubov , Wysokowski Marcin , Petrenko Iaroslav , Kovalchuk Valentine , Tsurkan Mikhail , Martinovic Rajko , Bechmann Nicole , Ivanenko Viatcheslav N. , Fursov Andriy , Smolii Oleg B. , Fromont Jane , Joseph Yvonne , Bornstein Stefan R. , Giovine Marco , Erpenbeck Dirk , Guan Kaomei , Ehrlich Hermann
Published: October 2019

Marine sponges remain representative of a unique source of renewable biological materials. The demosponges of the family Ianthellidae possess chitin-based skeletons with high biomimetic potential. These three-dimensional (3D) constructs can potentially be used in tissue engineering and regenerative medicine. In this study, we focus our attention, for the first time, on the marine sponge Ianthella labyrinthus Bergquist & Kelly-Borges, 1995 (Demospongiae: Verongida: Ianthellidae) as a novel potential source of naturally prestructured bandage-like 3D scaffolds which can be isolated simultaneously with biologically active bromotyrosines. Specifically, translucent and elastic flat chitinous scaffolds have been obtained after bromotyrosine extraction and chemical treatments of the sponge skeleton with alternate alkaline and acidic solutions. For the first time, cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) have been used to test the suitability of I. labyrinthus chitinous skeleton as ready-to-use scaffold for their cell culture. Results reveal a comparable attachment and growth on isolated chitin-skeleton, compared to scaffolds coated with extracellular matrix mimetic Geltrex®. Thus, the natural, unmodified I. labyrinthus cleaned sponge skeleton can be used to culture iPSC-CMs and 3D tissue engineering. In addition, I. labyrinthus chitin-based scaffolds demonstrate strong and efficient capability to absorb blood deep into the microtubes due to their excellent capillary effect. These findings are suggestive of the future development of new sponge chitin-based absorbable hemostats as alternatives to already well recognized cellulose-based fabrics.
Differential Susceptibility of Catheter Biomaterials to Biofilm-Associated Infections and Their Remedy by Drug-Encapsulated Eudragit RL100 Nanoparticles
Authors: Pandey Vivek Kumar , Srivastava Kumar Rohit , Ajmal Gufran , Thakur Vijay Kumar , Gupta Vijai Kumar , Upadhyay Siddh Nath , Mishra Pradeep Kumar
Published: October 2019

Biofilms are the cause of major bacteriological infections in patients. The complex architecture of Escherichia coli (E. coli) biofilm attached to the surface of catheters has been studied and found to depend on the biomaterial’s surface properties. The SEM micrographs and water contact angle analysis have revealed that the nature of the surface affects the growth and extent of E. coli biofilm formation. In vitro studies have revealed that the Gram-negative E. coli adherence to implanted biomaterials takes place in accordance with hydrophobicity, i.e., latex > silicone > polyurethane > stainless steel. Permanent removal of E. coli biofilm requires 50 to 200 times more gentamicin sulfate (G-S) than the minimum inhibitory concentration (MIC) to remove 90% of E. coli biofilm (MBIC90). Here, in vitro eradication of biofilm-associated infection on biomaterials has been done by Eudragit RL100 encapsulated gentamicin sulfate (E-G-S) nanoparticle of range 140 nm. It is 10–20 times more effective against E. coli biofilm-associated infections eradication than normal unentrapped G-S. Thus, Eudragit RL100 mediated drug delivery system provides a promising way to reduce the cost of treatment with a higher drug therapeutic index.
Evolution of the Proto Sex-Chromosome in Solea senegalensis
Authors: Rodríguez María , Molina Belén , Merlo Manuel , Arias-Pérez Alberto , Portela-Bens Silvia , García-Angulo Aglaya , Cross Ismael , Liehr Thomas , Rebordinos Laureana
Published: October 2019

Solea senegalensis is a flatfish belonging to the Soleidae family within the Pleuronectiformes order. It has a karyotype of 2n = 42 (FN = 60; 6M + 4 SM + 8 St + 24 T) and a XX/XY system. The first pair of metacentric chromosomes has been proposed as a proto sex-chromosome originated by a Robertsonian fusion between acrocentric chromosomes. In order to elucidate a possible evolutionary origin of this chromosome 1, studies of genomic synteny were carried out with eight fish species. A total of 88 genes annotated within of 14 BACs located in the chromosome 1 of S. senegalensis were used to elaborate syntenic maps. Six BACs (BAC5K5, BAC52C17, BAC53B20, BAC84K7, BAC56H24, and BAC48P7) were distributed in, at least, 5 chromosomes in the species studied, and a group of four genes from BAC53B20 (grsf1, rufy3, slc4a4 and npffr2) and genes from BAC48K7 (dmrt2, dmrt3, dmrt1, c9orf117, kank1 and fbp1) formed a conserved cluster in all species. The analysis of repetitive sequences showed that the number of retroelements and simple repeat per BAC showed its highest value in the subcentromeric region where 53B20, 16E16 and 48K7 BACs were localized. This region contains all the dmrt genes, which are associated with sex determination in some species. In addition, the presence of a satellite “chromosome Y” (motif length: 860 bp) was detected in this region. These findings allowed to trace an evolutionary trend for the large metacentric chromosome of S. senegalensis, throughout different rearrangements, which could be at an initial phase of differentiation as sex chromosome.
A Review of Computational Methods for Cervical Cells Segmentation and Abnormality Classification
Authors: Conceição Teresa , Braga Cristiana , Rosado Luís , Vasconcelos Maria João M.
Published: October 2019

Cervical cancer is the one of the most common cancers in women worldwide, affecting around 570,000 new patients each year. Although there have been great improvements over the years, current screening procedures can still suffer from long and tedious workflows and ambiguities. The increasing interest in the development of computer-aided solutions for cervical cancer screening is to aid with these common practical difficulties, which are especially frequent in the low-income countries where most deaths caused by cervical cancer occur. In this review, an overview of the disease and its current screening procedures is firstly introduced. Furthermore, an in-depth analysis of the most relevant computational methods available on the literature for cervical cells analysis is presented. Particularly, this work focuses on topics related to automated quality assessment, segmentation and classification, including an extensive literature review and respective critical discussion. Since the major goal of this timely review is to support the development of new automated tools that can facilitate cervical screening procedures, this work also provides some considerations regarding the next generation of computer-aided diagnosis systems and future research directions.
Temperature and Sugar Feeding Effects on the Activity of a Laboratory Strain of Aedes aegypti
Authors: Upshur Irvin Forde , Bose Elizabeth Annadel , Hart Cameron , Lahondère Chloé
Published: October 2019

Aedes aegypti is an invasive mosquito species that is expected to expand its global distribution through climate change. As poikilotherms, mosquitoes are greatly affected by the temperature of the environment which can impact host-seeking, blood-feeding, and flight activity as well as survival and ability to transmit pathogens. However, an important aspect of mosquito biology on which the effect of temperature has not been investigated is water and sugar-feeding and how access to a sugar source might affect the insect’s activity and survival under different thermal conditions. To close this knowledge gap, we relied on actometer experiments to study the activity of both female and male Ae. aegypti at 20 °C, 25 °C, and 30 °C, providing either water or 10% sucrose to the insects. We then measured the total carbohydrate contents of alive mosquitoes using the anthrone protocol. Survival was assessed and compared between all groups. Results from this study will inform on the thermal biology of Ae. aegypti mosquitoes and how access to sugar affects their activity.
Minimally Invasive AC Joint Reconstruction System (MINAR®) in Modified Triple-Button Technique for the Treatment of Acute AC Joint Dislocation
Authors: Breuer Robert , Unterrainer Alexandra , Komjati Micha , Tiefenboeck Thomas M. , Trieb Klemens , Pirkl Christof
Published: October 2019

Acute acromioclavicular (AC) joint dislocation is a frequent sports injury with more than 100 different operation methods described. A total of 65 patients with an acute AC joint dislocation were treated with the modified MINAR® system between 2009 and 2013. Clinical outcome, horizontal and vertical instability, as well as concomitant intraarticular injuries were assessed. We used Zanca, stress and axial X-rays for radiological assessment. A Constant score of 95 (±8.8), University of California Los Angeles Shoulder score (UCLA) of 31 (±4.9), Disabilities of Arm, Shoulder and Hand (DASH) of 9.1 (±14.3), and Visual Analogue Scale (VAS) of 0.9 (±0.126) was found. A total of 30 patients (59%) had no signs of reduction loss, nine patients (18%) a slight loss, 11 patients (22%) a partial loss, and one patient (2%) a total loss. No significant influence on the clinical scores could be shown. The postoperative coracoclavicular (CC) distance negatively affected the Constant (p = 0.007) and UCLA scores (p = 0.035). A longer time interval to surgery had a negative influence on all scores (p ≤ 0.001). We could not find any signs of persistent horizontal instability or intraarticular injuries at follow-up. The MINAR® system promises satisfactory functional and radiological results. When setting the correct indication, patients benefit from an early operation. No persisting horizontal instability was observed following suturing of the AC capsule and the delta fascia.
Comments from the Editors on the Special Issue “Assessment and Treatment of Addictions: New Tools for Old Problems”
Authors: Barrio Pablo , Miquel Laia , Gual Antoni
Published: October 2019

New conceptual and technological solutions have been proposed to solve addictive disorders and will be presented in the future. In this Special Issue, we present some of the new assessment tools and treatment options for internet addiction, alcohol, cannabis, cocaine, and gambling disorders.
Axin Family of Scaffolding Proteins in Development: Lessons from C. elegans
Authors: Mallick Avijit , Taylor Shane K. B. , Ranawade Ayush , Gupta Bhagwati P.
Published: October 2019

Scaffold proteins serve important roles in cellular signaling by integrating inputs from multiple signaling molecules to regulate downstream effectors that, in turn, carry out specific biological functions. One such protein, Axin, represents a major evolutionarily conserved scaffold protein in metazoans that participates in the WNT pathway and other pathways to regulate diverse cellular processes. This review summarizes the vast amount of literature on the regulation and functions of the Axin family of genes in eukaryotes, with a specific focus on Caenorhabditis elegans development. By combining early studies with recent findings, the review is aimed to serve as an updated reference for the roles of Axin in C. elegans and other model systems.
Diagnostic Pathway and Clinical Significance of Premature Ventricular Beats (PVBs) in Trained Bicuspid Aortic Valve (BAV) Athletes
Authors: Donadei Matteo , Casatori Lorenzo , Bini Vittorio , Galanti Giorgio , Stefani Laura
Published: October 2019

Purpose: Bicuspid aortic valve (BAV) represents a common congenital cardiac disease (1–2%) normally compatible with sports activity. In the case of competitive sports, eligibility can be barred by the presence of symptoms, aortic valve dysfunction, or arrhythmias. This investigation of a large cohort of BAV athletes aims to verify the prevalence of premature ventricular beats (PVBs) found in the exercise test (ET) at the first sports medicine clinical evaluation. Methods: A sample of 356 BAV athletes, regularly examined over a period of 10 years at the Sports Medicine Center of the University of Florence, was retrospectively evaluated for arrhythmic events found in the first sports medicine check-up carried out. The athletes (321 M and 79 F), aged between 8–50 years (mean age 21.8 ± 11.6), practised sports at high dynamic cardiovascular intensity (mainly soccer, basketball, and athletics). Criteria for participation included a 2D echocardiography and ET conducted at 85% of maximal effort. Ventricular arrhythmic events were reported if found to be ≥3 at rest and/or during the exercise test and for subjects with any other cardiac or systemic structural diseases. Individuals aged >50 were excluded from the study. The selected participants were matched with a control group of 400 athletes with similar levels of training (age 20.0 ± 9.9) without BAV. Results: Only 25 (7.02%) of BAV athletes showed PVBs at the ET. A total of 403 single PVBs and four monomorphic couples were observed; a polymorphic pattern was present in only three athletes, and only five had exercise-induced PVBs at peak. None had acute events or major arrhythmias. The difference in PVBs prevalence in BAV athletes vs. controls (PVBs 6.25%) was not significant (p > 0.05). Conclusions: The prevalence of PVBs is low in BAV athletes and appears not to differ from athletes without BAV. Despite this, the behaviour of PVBs at the ET should be considered for the major suspicion for arrhythmic events. More data in this field could optimize the cost/effectiveness ratio for eventual ECG Holter indications.
Reduction of Ejection Forces in Injection Molding by Applying Mechanically Post-Treated CrN and CrAlN PVD Films
Authors: Tillmann Wolfgang , Stangier Dominic , Lopes Dias Nelson Filipe , Gelinski Nikolai , Stanko Michael , Stommel Markus , Krebs Eugen , Biermann Dirk
Published: October 2019

In injection molding, the reduction of ejection forces is a process relevant aspect to improve the production rates. For this purpose, CrN and CrAlN films were sputtered on cylindrical and quadratic AISI H11 cores of an injection mold in order to investigate their influence on the resulting ejection forces to demold polypropylene test components. Within this context, the ejection forces of the PVD coated cores were compared to those of uncoated cores made of AISI H11. For both the cylindrical and quadratic cores, the as-deposited CrN and CrAlN films exhibit higher ejection forces than the uncoated cores due to the increase of the roughness profile after sputtering. It is known that the ejection forces are directly related to the surface roughness. In order to ensure comparable surface conditions to the uncoated surfaces, and to demonstrate the potential of PVD coated mold surfaces when reducing the ejection forces, the coated surfaces were mechanically post-treated to obtain a similar roughness profile as the uncoated cores. The combination of a PVD deposition and post-treatment ensures a significant reduction of the ejection forces by 22.6% and 23.7% for both core geometries.
The Treaty Claims Settlement Process in New Zealand and Its Impact on Māori
Authors: Mutu Margaret
Published: October 2019

This article considers research conducted on the impact of the Crown’s treaty claims settlement policy on Māori in New Zealand. It provides a brief background to the Treaty of Waitangi and the subsequent British colonisation process that relied on the Doctrine of Discovery in breach of the treaty. It outlines how colonisation dispossessed Māori of 95 percent of their lands and resources, usurped Māori power and authority and left them in a state of poverty, deprivation and marginalisation while procuring considerable wealth, prosperity and privilege for British settlers. The work of the Waitangi Tribunal, the commission of inquiry set up to investigate those breaches, is considered, as is the Crown’s reaction to the 1987 Lands case in developing its treaty claims settlement policy. The Crown unilaterally imposed the policy despite vehement opposition from Māori. Since 1992, it has legislated more than seventy ‘settlements’. The research shows that overall, the process has traumatised claimants, divided their communities, and returned on average less than one percent of their stolen lands. Proposals for constitutional transformation have drawn widespread support from Māori as a solution to British colonisation. United Nations treaty-monitoring bodies have recommended that the government discuss this with Māori.
New Microbe Killers: Self-Assembled Silver(I) Coordination Polymers Driven by a Cagelike Aminophosphine
Authors: Jaros Sabina W. , Haukka Matti , Florek Magdalena , Guedes da Silva M. Fátima C. , Pombeiro Armando J. L. , Kirillov Alexander M. , Smoleński Piotr
Published: October 2019

New Ag(I) coordination polymers, formulated as [Ag(µ-PTAH)(NO3)2]n (1) and [Ag(µ-PTA)(NO2)]n (2), were self-assembled as light- and air-stable microcrystalline solids and fully characterized by NMR and IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS(±), elemental analysis, powder (PXRD) and single-crystal X-ray diffraction. Their crystal structures reveal resembling 1D metal-ligand chains that are driven by the 1,3,5-triaza-7-phospaadamantane (PTA) linkers and supported by terminal nitrate or nitrite ligands; these chains were classified within a 2C1 topological type. Additionally, the structure of 1 features a 1D→2D network extension through intermolecular hydrogen bonds, forming a two-dimensional hydrogen-bonded network with fes topology. Furthermore, both products 1 and 2 exhibit remarkable antimicrobial activity against different human pathogen bacteria (S. aureus, E. coli, and P. aeruginosa) and yeast (C. albicans), which is significantly superior to the activity of silver(I) nitrate as a reference topical antimicrobial.