bluuebunny/crossref_metadata_2025 huggingface dataset:
Budget impact analysis of pegfilgrastim biosimilar in the treatment of febrile neutropenia in Italy
Authors: Ravasio Roberto , Antonuzzo Lorenzo , Danova Marco , Pronzato Paolo
Published: March 2020

Introduction: Granulocyte-colony stimulating factors (G-CSFs) can significantly reduce the risk of febrile neutropenia (FN) among certain patients receiving chemotherapy. FN is associated with significant clinical and nonclinical complications. At present, the patent protection of pegfilgrastim (Neulasta®) has expired, and a biosimilar (Ziextenzo®) has been approved. Since the biosimilar price is expected to be lower as compared with the originator’s, the present Drug Budget Impact analysis tries to evaluate whether and how much profitable the biosimilar availability will be for the Italian NHS, in terms of cost containment (savings).Methods and Results: The model time horizon extends to five years. The initial overall number of treatments with pegfilgrastim is estimated based on the number of pegfilgrastim packages (assuming a recommended dose of 6 mg is administered after each cytotoxic chemotherapy) and kept constant in time. The model assumes that, year by year, the number of treatments with the originator will partly switch to the biosimilar (according to an uptake rate assumed). The results show that the availability of the biosimilar would provide an €6.4 million cumulated savings to the NHS in the five years.Conclusions: According to the present analysis, the availability of the biosimilar would generate cumulated savings (in five years) as high as €6.4 million for the Italian NHS. 

(HTA & Market Access)
Rhetorical Battles: Jesus as Speaker in the Gospel of Mark
Authors: Ivar Østmoe Tor
Published: March 2020

Building on research relating the New Testament to Greek and Roman literary culture, the article explores the Gospel of Mark's representation of Jesus as speaker. In focus are dialogues in the Gospel's seventh chapter which take place between Jesus and characters with different social background and in different social spaces. The article argues that, in these dialogues, Jesus speaks as a member of the social and cultural elite, as he has access to social spaces and has the necessary skills in rhetoric to adapt his speech to varying circumstances. This representation of Jesus as speaker can have several functions. One is to familiarise readers of the Gospel across the Roman Empire with a distant province, Judaea, as Jesus conforms to expectations for an elite male in Greek and Roman culture. A second is to contribute to Jesus' literary characterisation as subversive or comic, as he engages in ‘rhetorical battles’ with different people and with varying success.
PEMANAFAATAN MEDIA 3 DIMENSI BERBASIS VIRTUAL REALITY UNTUK MENINGKATKAN MINAT DAN HASIL BELAJAR IPA SISWA KELAS V SD
Authors: Dewi Ressi Kartika
Published: March 2020

As professional teachers in 21th century, teachers at all levels of education should be prepared for 4.0 era teaching and learning by utilizing the advancement of  information technology. There is a needs to develop technology based learning media to create creative, inovative, and exciting learning to improve students’s motivation especially in science. This research aims to explain the effectiveness of three dimention (3D) -based virtual reality learning media to improve the fifth grade students’ learning motivation. This research employs ADDIE which inludes analysis, design, development, implementation, and evaluation phases. The research subjects were students from seven elementary schools for try-out, 3 control groups, and 3 experiment groups. The data collecting techniques used  observation, quistionannaire, interview, and performance test. The result shows that virtual reality-based 3D learning media is effective to improve student motivation and achievement of the fifth grade students, indicated by a significant difference in motivation and achievement score of the students before and after using 3D-based virtual reality media.

Sebagai tenaga pengajar profesional guru harus siap  menghadapi era 4.0. yang diindikasikan dengan penggunaan ICT yang intensif dan ekspansif. Guru perlu mampu mengembangkan media pembelajaran berbasis teknologi untuk menciptakan pembelajaran yang kreatif, inovatif, konkrit dan menyenangkan, sehingga dapat membangkitkan minat siswa khususnya pada materi IPA. Penelitian ini bertujuan untuk mendiskripsikan keefektifan media pembelajaran 3 dimensi (3D) berbasis virtual reality dalam peningkatan  minat dan hasil belajar siswa kelas V SD. Penelitian ini termasuk dalam jenis penelitian pengembangan (Research and Development) model ADDIE yang terdiri dari analisis (Analysis), desain (Design), pengembangan (Development), implementasi (Implementation), dan evaluasi (Evaluation). Penelitian dilaksanakan terhadap siswa yang tersebar di 7 sekolah dasar, yaitu 1 sekolah uji coba, 3 sekolah kontrol, dan 3 sekolah eksperimen di Kecamatan Tasikmadu, Surakarta. Teknik pengumpulan data menggunakan metode observasi, angket, wawancara dan tes. Hasil penelitian menunjukkan bahwa media pembelajaran 3 dimensi (3D) berbasis virtual reality efektif untuk meningkatkan minat dan hasil belajar IPA siswa, ditunjukkan oleh  perbedaan yang signifikan minat dan hasil belajar siswa sebelum dan sesudah menggunakan media pembelajaran, dari rata-rata yang semula 52,95 diperoleh capaian rata-rata baru sebesar 82,05.
Lamb Fattening Under Intensive Pasture-Based Systems: A Review
Authors: Fernandez-Turren Gonzalo , Repetto José L. , Arroyo José M. , Pérez-Ruchel Analía , Cajarville Cecilia
Published: March 2020

The benefits of pasture-based systems on the fatty acid composition of sheep meat appear to be achievable despite variability in the quality of the pastures. Lambs fed high levels of temperate pastures have an excess of N-ammonia derived from protein degradation. Furthermore, animal performance is highly variable depending on the quality of the pasture at the time of grazing, and high animal performance in these systems appears to be linked to the use of high-quality pastures with high availability, and is possibly added to by the inclusion of concentrates that allow increasing energy intake and a better use of the N in the pasture. The combination of high-quality pastures and total mixed ration offers a good alternative to the inclusion of concentrates in the diet, improving the use of N, and avoiding acidosis problems. However, information to determine the effect of a number of nutritional strategies on meat quality, and the minimum level of pasture intake necessary to achieve the benefits of pastoral systems is still lacking.
A Global Analysis of Y-STR INRA189 Polymorphism in Chinese Domestic Yak Breeds/Populations
Authors: Ma Zhijie , Xia Xiaoting , Chen Shengmei , Bai Ma , Lei Chuzhao , Han Jianlin
Published: March 2020

The objective of this study was to probe into the polymorphism of Y-STR INRA189 and identify the geographical distribution pattern of its alleles in the Chinese domestic yak gene pool. We examined the variation at INRA189 locus in 682 male yaks representing 15 breeds/populations in China. The results showed that six alleles, including five reported previously (149, 155, 157, 159, and 161 bp) and a new one identified in this study (139 bp), were detected at INRA189 locus based on genotyping analysis. The frequencies of six alleles varied among the 15 yak breeds/populations with a clear phylogeographical pattern, which revealed the paternal genetic difference among Chinese yak breeds/populations. The average polymorphism information content (PIC) among the 15 yak breeds/populations was 0.32, indicating INRA189 to be an intermediate polymorphic Y-STR marker (0.25 < PIC < 0.5) in yak. Sequence alignment revealed that the variations among six alleles at INRA189 were defined by a TG dinucleotide repeat motif, which repeated for 12, 17, 20, 21, 22, and 23 times, corresponding to the alleles of 139, 149, 155, 157, 159, and 161 bp, respectively. Therefore, we believe that the polymorphic yak Y-STR INRA189 can be used to characterize male-mediated genetic events, including paternal genetic origin, diversity, and evolution.
Effects of Management Strategies on Non-Beak-Trimmed Laying Hens in Furnished Cages that Were Reared in a Non-Cage System
Authors: Guinebretière Maryse , Mika Amandine , Michel Virginie , Balaine Loïc , Thomas Rodolphe , Keïta Alassane , Pol Françoise
Published: March 2020

Beak trimming in laying hens limits the negative consequences of injurious pecking, but could be prohibited by future regulations. This study assessed a combination of management strategies during the rearing period (objects, perches, music, human presence) and laying period (scratching mats, objects, feed fiber supplementation) to raise non-beak-trimmed animals. The welfare and laying performances of beak-trimmed (T) and non-beak-trimmed (NT) ISA Brown birds were compared between groups with (E) or without (NE) these strategies, with or without fiber supplementation in the diet during laying period. Fiber supplementation did not provide any benefit on pecking-related problems. In comparison with NT-NE birds, NT-E birds had lower mortality, were less fearful of a novel object, and had a better feather cover, without a negative impact on productivity (same laying rate and egg quality). Although this study showed advantages of beak trimming (T birds had higher body weights, laying rates and lower hen mortality than NT birds), it highlighted related problems (increasing pullet mortality, decreasing early weights and increasing beak defects). This study proposes practical solutions to limit the consequences of injurious pecking in non-beak-trimmed animals.
Effect of Zinc Source and Exogenous Enzymes Supplementation on Zinc Status in Dogs Fed High Phytate Diets
Authors: Pereira Ana Margarida , Guedes Margarida , Matos Elisabete , Pinto Edgar , Almeida Agostinho A. , Segundo Marcela A. , Correia Alexandra , Vilanova Manuel , Fonseca António J. M. , Cabrita Ana Rita J.
Published: March 2020

Zinc is an essential element, a cofactor of many enzymes, and performs catalytic, structural and regulatory functions. Once in the gastrointestinal tract, zinc can interact with food constituents. Phytic acid, the major phosphorus storage in plants, limits zinc availability from animal feeds due to the formation of insoluble complexes with phytates. This study tested the effect of supplemental zinc source (zinc sulfate and a chelate zinc proteinate) and the addition of exogenous enzymes from a solid-state fermentation product of Aspergillus niger to a high phytate diet. The study was designed according to three Latin Squares 4 × 4 with a 2 × 2 factorial arrangement of treatments, with four periods, four diets, and 12 young adult Beagles. Periods lasted 5 weeks each. Diets were supplemented with 75 mg/kg of zinc sulfate (IZ) or zinc proteinate (OZ), and without or with 200 mg/kg of exogenous enzymes (IZ+, OZ+). Results showed that zinc proteinate increased the bioavailability of phosphorus, yet the zinc biomarkers remained unaffected by the zinc source, with the exception of lymphocyte subsets that benefit from zinc proteinate. The use of exogenous enzymes did not affect zinc availability nor nutrient and energy digestibility.
Eco-Virological Preliminary Study of Potentially Emerging Pathogens in Hedgehogs (Erinaceus europaeus) Recovered at a Wildlife Treatment and Rehabilitation Center in Northern Italy
Authors: Delogu Mauro , Cotti Claudia , Lelli Davide , Sozzi Enrica , Trogu Tiziana , Lavazza Antonio , Garuti Giacomo , Castrucci Maria Rita , Vaccari Gabriele , De Marco Maria Alessandra , Moreno Ana
Published: March 2020

The Western European Hedgehog (Erinaceus europaeus) is one of the four hedgehog species belonging to the genus Erinaceus. Among them, E. amurensis is extant in East Asia’s areas only, whereas E. europaeus, E. roumanicus and E. concolor are mainly found in Europe. E. europaeus is endemically distributed from western to central and southern Europe, including Italy. Western European hedgehogs’ ecological and feeding habits, along with their high population densities, notable synanthropic attitudes, frequent contacts with sympatric wild and domestic species, including humans, implicate the possible involvement of E. europaeus in the ecology of potentially emerging viruses, such as coronaviruses, influenza A and influenza D viruses, canine distemper virus, pestiviruses and Aujeszky’s disease virus. We examined 24 E. europaeus individuals found injured in urban and rural areas of Northern Italy. Of the 24 fecal samples collected and tested for the above-mentioned pathogens by both PCR-based and virus isolation methods, 14 were found PCR-positive for betacoronaviruses belonging to lineage C and related to the known Erinaceus coronaviruses (EriCoVs), as determined by partial sequencing of the virus genome. Our findings suggest that hedgehogs could be considered natural reservoirs of CoVs, and also act as chronic shedding carriers of these potentially emerging RNA viruses.
The Influences of Various Housing Systems on Growth, Carcass Traits, Meat Quality, Immunity and Oxidative Stress of Meat-Type Ducks
Authors: Abo Ghanima Mahmoud M. , El-Edel Mohamed A. , Ashour Elwy A. , Abd El-Hack Mohamed E. , Othman Sarah I. , Alwaili Maha A. , Allam Ahmed A. , Khafaga Asmaa F. , Abd El-Aziz Ayman H.
Published: March 2020

The present study aimed to investigate the effect of different housing systems on Pekin ducks. A total of 300-day old Pekin ducklings were randomly divided into four experimental groups; the first housed in a closed house (CH), the second in closed house with open yard (HY), the third group in closed house with swimming pool (CHSP) and the fourth in a closed house with swimming pool and yard (HYSP). Results indicated that the HYSP and CHSP produced higher body weight comparing to the other groups. However, the HYSP gave the highest body weight followed by CHSP then HY and CH. The same trend was observed regarding weight gain and feed-conversion ratio (FCR). Moreover, HYSP, HY and CHSP showed higher dressing percentage, breast muscles and thighs and lower abdominal fat than the CH group. Serum protein was significantly higher in HYSP and HY than that of the closed house. While, lipids, cholesterol and triacylglycerol were significantly lower in groups housed in HY than that of CH. Meat cholesterol and triacylglycerol reduced in groups reared in HY. Housing ducklings in yards and using swimming pools significantly improved the general immunity (phagocytic index and activity and differential leucocytes count), and also improved the oxidative stress parameters. In conclusion, results confirmed that housing ducks in a house supplied with yard and swimming pool can improve its productivity, carcass traits, meat quality, blood lipid profile, immunity and antioxidative status.
Design and Simulation of Electromagnetic Linear Actuators for Jet Dispensers
Authors: Tran Minh-Sang , Hwang Sheng-Jye
Published: March 2020

Three electromagnetic-based linear actuators, namely a solenoid actuator (SA), a moving coil actuator (MCA), and a moving magnet actuator (MMA), are proposed for driving the needle in a jet dispenser. The total resistance force acting on the needle during operation, including the damping force, the friction force, the inertia force, the compression spring force, and the backpressure, are measured by an experimental model. The thrust force required to overcome this resistance force is then predicted for each actuator using finite element analysis (FEA) simulations. Simple two-dimensional models of the SA, MCA, and MMA are constructed using the same coil dimensions in every case in order to facilitate an objective comparison between them. Simulations in ANSYS Maxwell software are then performed to adjust the specific dimensions of each actuator structure in such a way as to generate the thrust force required to drive the needle in the jet dispenser with the minimum excitation current possible. The simulation results show that for a maximum needle driving frequency of 250 Hz and a stroke length of 0.5 mm, the excitation current required to generate the necessary thrust force is equal to 1.8 A and 1.9 A for the MCA and MMA models, respectively, when a return spring is not used, and 2.2 A, 3.8 A, and 4.1 A for the SA, MCA, and MMA models, respectively, when a return spring is employed. It is additionally shown that the thrust force drop of the MCA and MMA models is far less than that of the SA model, about 0.7%, 1.8%, and 61% for three models, respectively. Three preliminary designs for jet dispensers incorporating the proposed actuators are also generated for reference purposes.
Factors in Oncogenesis: Viral Infections in Ovarian Cancer
Authors: Pathak Sudipta , Wilczyński Jacek R. , Paradowska Edyta
Published: March 2020

Ovarian cancer (OC) is one of the leading causes of cancer death in women, with high-grade serous ovarian cancer (HGSOC) being the most lethal gynecologic malignancy among women. This high fatality rate is the result of diagnosis of a high number of new cases when cancer implants have already spread. The poor prognosis is due to our inadequate understanding of the molecular mechanisms preceding ovarian malignancy. Knowledge about the site of origination has been improved recently by the discovery of tube intraepithelial cancer (TIC), but the potential risk factors are still obscure. Due to high tumoral heterogeneity in OC, the establishment of early stage biomarkers is still underway. Microbial infection may induce or result in chronic inflammatory infection and in the pathogenesis of cancers. Microbiome research has shed light on the relationships between the host and microbiota, as well as the direct roles of host pathogens in cancer development, progression, and drug efficacy. While controversial, the detection of viruses within ovarian malignancies and fallopian tube tissues suggests that these pathogens may play a role in the development of OC. Genomic and proteomic approaches have enhanced the methods for identifying candidates in early screening. This article summarizes the existing knowledge related to the molecular mechanisms that lead to tumorigenesis in the ovary, as well as the viruses detected in OC cases and how they may elevate this process.
Hydrodeoxygenation of Benzofuran over Bimetallic Ni-Cu/γ-Al2O3 Catalysts
Authors: Zhu Tianhan , Song Hua , Li Feng , Chen Yanguang
Published: March 2020

Bimetallic NixCu(10−x)/γ-Al2O3 catalysts (where x is the mass fraction of Ni) with different Ni/Cu mass ratios were prepared. The catalysts were characterized by X-ray diffractometry, N2 adsorption–desorption, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, H2-temperature programmed reduction, and transmission electron microscopy. The effect of Ni/Cu mass ratio on benzofuran hydrodeoxygenation was investigated in a fixed-flow reactor. Cu addition improved the NiO reducibility. The strong interaction of Ni and Cu led to the formation of smaller and highly dispersed CuO and NiO species over γ-Al2O3, which favors an improvement in catalytic activity. Among the as-prepared catalysts, the Ni5Cu5/γ-Al2O3 showed the highest deoxygenated product yield (79.9%) with an acceptable benzofuran conversion of 95.2%, which increased by 18.3% and 16.9% compared with that of the monometallic Ni/γ-Al2O3 catalyst. A possible reaction network was proposed, which would provide insight into benzofuran hydrodeoxygenation over the Ni5Cu5/γ-Al2O3 catalyst.
Eco-Friendly Mechanochemical Preparation of Ag2O–MnO2/Graphene Oxide Nanocomposite: An Efficient and Reusable Catalyst for the Base-Free, Aerial Oxidation of Alcohols
Authors: Adil Syed Farooq , Assal Mohamed E. , Khan Mujeeb , Shaik Mohammed Rafi , Kuniyil Mufsir , Sekou Doumbia , Dewidar Ahmed Z. , Al-Warthan Abdulrahman , Siddiqui Mohammed Rafiq H.
Published: March 2020

Recently, the development of eco-friendly mechanochemical approaches for the preparation of novel catalysts with enhanced activity and selectivity has gained considerable attention. Herein, we developed a rapid and solvent-less mechanochemical method for the preparation of mixed metal oxide (Ag2O–MnO2) decorated graphene oxide (GRO)-based nanocomposites (Ag2O–MnO2/(X wt.%)GRO), as the Ag2O–MnO2/(X wt.%)GRO nanocomposite was fabricated by the physical grinding of freshly prepared GRO and pre-annealed (300 °C) mixed metal oxide nanoparticles (NPs) (Ag2O–MnO2) using an eco-friendly milling procedure. The as-prepared nanocatalysts were characterized by using various techniques. Furthermore, the nanocomposites were applied as a heterogeneous catalyst for the oxidation of alcohol by employing gaseous O2 as an eco-friendly oxidant under base-free conditions. The mechanochemically obtained GRO-based composite exhibited noticeable enhancement in the surface area and catalytic performance compared to the pristine Ag2O–MnO2. The results revealed that (1%)Ag2O–MnO2/(5 wt.%)GRO catalyst exhibited higher specific performance (13.3 mmol·g−1·h−1) with a 100% conversion of benzyl alcohol (BnOH) and >99% selectivity towards benzaldehyde (BnH) within 30 min. The enhancement of the activity and selectivity of GRO-based nanocatalyst was attributed to the presence of various oxygen-containing functional groups, a large number of defects, and a high specific surface area of GRO. In addition, the as-prepared nanocatalyst also demonstrated excellent catalytic activity towards the conversion of a variety of other alcohols to respective carbonyls under optimal conditions. Besides, the catalyst ((1%)Ag2O–MnO2/(5 wt.%)GRO) could be efficiently recycled six times with no noticeable loss in its performance and selectivity.
Insights on a Methanation Catalyst Aging Process: Aging Characterization and Kinetic Study
Authors: Morosanu Eduard Alexandru , Salomone Fabio , Pirone Raffaele , Bensaid Samir
Published: March 2020

Power to gas systems is one of the most interesting long-term energy storage solutions. As a result of the high exothermicity of the CO2 methanation reaction, the catalyst in the methanation subsystem is subjected to thermal stress. Therefore, the performance of a commercial Ni/Al2O3 catalyst was investigated over a series of 100 hour-long tests and in-process relevant conditions, i.e. 5 bar from 270 to 500 °C. Different characterization techniques were employed to determine the mechanism of the observed performance loss (N2 physisorption, XRD, TPO). The TPO analysis excluded carbon deposition as a possible cause of catalyst aging. The BET analysis evidenced a severe reduction in the total surface area for the catalyst samples tested at higher temperatures. Furthermore, a direct correlation was found between the catalyst activity decline and the drop of the catalyst specific surface. In order to correctly design a reliable methanation reactor, it is essential to have a kinetic model that includes also the aging kinetics. For this purpose, the second set of experiments was carried out, in order to determine the intrinsic kinetics of the catalyst. The kinetic parameters were identified by using nonlinear regression analysis. Finally, a power-law aging model was proposed to consider the performance loss in time.
Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications
Authors: Chu Dinh-Toi , Nguyen Tiep Tien , Tien Nguyen Le Bao , Tran Dang-Khoa , Jeong Jee-Heon , Anh Pham Gia , Thanh Vo Van , Truong Dang Tien , Dinh Thien Chu
Published: March 2020

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.
Alternative Cell Sources for Liver Parenchyma Repopulation: Where Do We Stand?
Authors: Tricot Tine , De Boeck Jolan , Verfaillie Catherine
Published: March 2020

Acute and chronic liver failure is a highly prevalent medical condition with high morbidity and mortality. Currently, the therapy is orthotopic liver transplantation. However, in some instances, chiefly in the setting of metabolic diseases, transplantation of individual cells, specifically functional hepatocytes, can be an acceptable alternative. The gold standard for this therapy is the use of primary human hepatocytes, isolated from livers that are not suitable for whole organ transplantations. Unfortunately, primary human hepatocytes are scarcely available, which has led to the evaluation of alternative sources of functional hepatocytes. In this review, we will compare the ability of most of these candidate alternative cell sources to engraft and repopulate the liver of preclinical animal models with the repopulation ability found with primary human hepatocytes. We will discuss the current shortcomings of the different cell types, and some of the next steps that we believe need to be taken to create alternative hepatocyte progeny capable of regenerating the failing liver.
At the Crossroads of Apoptosis and Autophagy: Multiple Roles of the Co-Chaperone BAG3 in Stress and Therapy Resistance of Cancer
Authors: Kögel Donat , Linder Benedikt , Brunschweiger Andreas , Chines Silvia , Behl Christian
Published: March 2020

BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.
Sphingolipids and Mitochondrial Dynamic
Authors: Fugio Lais Brigliadori , Coeli-Lacchini Fernanda B. , Leopoldino Andréia Machado
Published: March 2020

For decades, sphingolipids have been related to several biological functions such as immune system regulation, cell survival, and proliferation. Recently, it has been reported that sphingolipids could be biomarkers in cancer and in other human disorders such as metabolic diseases. This is evidenced by the biological complexity of the sphingolipids associated with cell type-specific signaling and diverse sphingolipids molecules. As mitochondria dynamics have serious implications in homeostasis, in the present review, we focused on the relationship between sphingolipids, mainly ceramides and sphingosine-1-phosphate, and mitochondrial dynamics directed by fission, fusion, and mitophagy. There is evidence that the balances of ceramides (C18 and C16) and S1P, as well as the location of specific ceramide synthases in mitochondria, have roles in mitophagy and fission with an impact on cell fate and metabolism. However, signaling pathways controlling the sphingolipids metabolism and their location in mitochondria need to be better understood in order to propose new interventions and therapeutic strategies.
Chondrogenic Differentiation from Induced Pluripotent Stem Cells Using Non-Viral Minicircle Vectors
Authors: Rim Yeri Alice , Nam Yoojun , Park Narae , Jung Hyerin , Lee Kijun , Lee Jennifer , Ju Ji Hyeon
Published: March 2020

Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.
Additive Manufacturing Redesigning of Metallic Parts for High Precision Machines
Authors: Galati Manuela , Calignano Flaviana , Viccica Marco , Iuliano Luca
Published: March 2020

The conventional approach to design and manufacturing often has geometries with an efficient material distribution. For the high-precision machines, that approach involves the design of heavy components that guarantees the stiffness requirements. However, the higher the weight of the part, the higher inertia it has. As a result, when the feed axes are accelerated, the inertial forces deform the machine components and the precision of the machine is reduced. This study investigated the designing for additive manufacturing (DfAM) and designing for assembly (DfA) to increase the material efficiency of components for high-precision applications. A new methodology which considered the design and manufacturing issues and machining as well is given. A comprehensive model for cost evaluation of the part is presented. The case study refers to the rails and the bracket that support and move the flying probe of a testing machine for micro-electromechanical systems (MEMS). The weight of the rails has been decreased by 32% and the components to be assembled have been reduced from 16 to 7. The optimized bracket is more than 50% stiffer than the original one, 10% lighter, and economically competitive.
Novel Mathematical Model of Breast Cancer Diagnostics Using an Associative Pattern Classification
Authors: Santiago-Montero Raúl , Sossa Humberto , Gutiérrez-Hernández David A. , Zamudio Víctor , Hernández-Bautista Ignacio , Valadez-Godínez Sergio
Published: March 2020

Breast cancer is a disease that has emerged as the second leading cause of cancer deaths in women worldwide. The annual mortality rate is estimated to continue growing. Cancer detection at an early stage could significantly reduce breast cancer death rates long-term. Many investigators have studied different breast diagnostic approaches, such as mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have limitations, such as being expensive, time consuming and not suitable for women of all ages. Proposing techniques that support the effective medical diagnosis of this disease has undoubtedly become a priority for the government, for health institutions and for civil society in general. In this paper, an associative pattern classifier (APC) was used for the diagnosis of breast cancer. The rate of efficiency obtained on the Wisconsin breast cancer database was 97.31%. The APC’s performance was compared with the performance of a support vector machine (SVM) model, back-propagation neural networks, C4.5, naive Bayes, k-nearest neighbor (k-NN) and minimum distance classifiers. According to our results, the APC performed best. The algorithm of the APC was written and executed in a JAVA platform, as well as the experimental and comparativeness between algorithms.
Foreword Special Issue Cell Cycle and Regulation
Authors: Zubiaga Ana María
Published: March 2020

The process of cell division is critical to the growth and development of an organism [...]
mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers
Authors: Zhang Yitong , Tseng Joseph Ta-Chien , Lien I-Chia , Li Fenglan , Wu Wei , Li Hui
Published: March 2020

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.
Novel Aspects on The Interaction Between Grapevine and Plasmopara viticola: Dual-RNA-Seq Analysis Highlights Gene Expression Dynamics in The Pathogen and The Plant During The Battle For Infection
Authors: Toffolatti Silvia Laura , De Lorenzis Gabriella , Brilli Matteo , Moser Mirko , Shariati Vahid , Tavakol Elahe , Maddalena Giuliana , Passera Alessandro , Casati Paola , Pindo Massimo , Cestaro Alessandro , Maghradze David , Failla Osvaldo , Bianco Piero Attilio , Quaglino Fabio
Published: March 2020

Mgaloblishvili, a Vitis vinifera cultivar, exhibits unique resistance traits against Plasmopara viticola, the downy mildew agent. This offers the unique opportunity of exploring the molecular responses in compatible and incompatible plant-pathogen interaction. In this study, whole transcriptomes of Mgaloblishvili, Pinot noir (a V. vinifera susceptible cultivar), and Bianca (a resistant hybrid) leaves, inoculated and non-inoculated with the pathogen, were used to identify P. viticola effector-encoding genes and plant susceptibility/resistance genes. Multiple effector-encoding genes were identified in P. viticola transcriptome, with remarkable expression differences in relation to the inoculated grapevine cultivar. Intriguingly, five apoplastic effectors specifically associated with resistance in V. vinifera. Gene coexpression network analysis identified specific modules and metabolic changes occurring during infection in the three grapevine cultivars. Analysis of these data allowed, for the first time, the detection in V. vinifera of a putative P. viticola susceptibility gene, encoding a LOB domain-containing protein. Finally, the de novo assembly of Mgaloblishvili, Pinot noir, and Bianca transcriptomes and their comparison highlighted novel candidate genes that might be at the basis of the resistant phenotype. These results open the way to functional analysis studies and to new perspectives in molecular breeding of grapevine for resistance to P. viticola.
The Metabolization Profile of the CYP2D6 Gene in Amerindian Populations: A Review
Authors: Leitão Luciana P. C. , Souza Tatiane P. , Rodrigues Juliana C. G. , Fernandes Marianne R. , Santos Sidney , Santos Ney P. C.
Published: March 2020

Background: the CYP2D6 gene is clinically important and is known to have a number of variants. This gene has four distinct metabolization profiles that are determined by the different allelic forms present in the individual. The relative frequency of these profiles varies considerably among human populations around the world. Populations from more isolated regions, such as Native Americans, are still relatively poorly studied, however. Even so, recent advances in genotyping techniques and increasing interest in the study of these populations has led to a progressive increase in publication rates. Given this, the review presented here compiled the principal papers published on the CYP2D6 gene in Amerindian populations to determine the metabolic profile of this group. Methods: a systematic literature review was conducted in three scientific publication platforms (Google Scholar, Science Direct, and Pubmed). The search was run using the keywords “CYP2D6 Amerindians” and “CYP2D6 native Americans”. Results: a total of 13 original papers met the inclusion criteria established for this study. All the papers presented frequencies of the different CYP2D6 alleles in Amerindian populations. Seven of the papers focused specifically on Amerindian populations from Mexico, while the others included populations from Argentina, Chile, Costa Rica, Mexico, Paraguay, Peru, and the United States. The results of the papers reviewed here showed that the extensive metabolization profile was the most prevalent in all Amerindian populations studied to date, followed by the intermediate, slow, and ultra-rapid, in that order. Conclusion: the metabolization profiles of the Amerindian populations reviewed in the present study do not diverge in any major way from those of other populations from around the world. Given the paucity of the data available on Amerindian populations, further research is required to better characterize the metabolization profile of these populations to ensure the development of adequate therapeutic strategies.
Computational Cancer Cell Models to Guide Precision Breast Cancer Medicine
Authors: Cheng Lijun , Majumdar Abhishek , Stover Daniel , Wu Shaofeng , Lu Yaoqin , Li Lang
Published: March 2020

Background: Large-scale screening of drug sensitivity on cancer cell models can mimic in vivo cellular behavior providing wider scope for biological research on cancer. Since the therapeutic effect of a single drug or drug combination depends on the individual patient’s genome characteristics and cancer cells integration reaction, the identification of an effective agent in an in vitro model by using large number of cancer cell models is a promising approach for the development of targeted treatments. Precision cancer medicine is to select the most appropriate treatment or treatments for an individual patient. However, it still lacks the tools to bridge the gap between conventional in vitro cancer cell models and clinical patient response to inhibitors. Methods: An optimal two-layer decision system model is developed to identify the cancer cells that most closely resemble an individual tumor for optimum therapeutic interventions in precision cancer medicine. Accordingly, an optimal grid parameters selection is designed to seek the highest accordance for treatment selection to the patient’s preference for drug response and in vitro cancer cell drug screening. The optimal two-layer decision system model overcomes the challenge of heterology data comparison between the tumor and the cancer cells, as well as between the continual variation of drug responses in vitro and the discrete ones in clinical practice. We simulated the model accuracy using 681 cancer cells’ mRNA and associated 481 drug screenings and validated our results on 315 breast cancer patients drug selection across seven drugs (docetaxel, doxorubicin, fluorouracil, paclitaxel, tamoxifen, cyclophosphamide, lapitinib). Results: Comparing with the real response of a drug in clinical patients, the novel model obtained an overall average accordance over 90.8% across the seven drugs. At the same time, the optimal cancer cells and the associated optimal therapeutic efficacy of cancer drugs are recommended. The novel optimal two-layer decision system model was used on 1097 patients with breast cancer in guiding precision medicine for a recommendation of their optimal cancer cells (30 cancer cells) and associated efficacy of certain cancer drugs. Our model can detect the most similar cancer cells for each individual patient. Conclusion: A successful clinical translation model (optimal two-layer decision system model) was developed to bridge in-vitro basic science to clinical practice in a therapeutic intervention application for the first time. The novel tool kills two birds with one stone. It can help basic science to seek optimal cancer cell models for an individual tumor, while prioritizing clinical drugs’ recommendations in practice. Tool associated platform website: We extended the breast cancer research to 32 more types of cancers across 45 therapy predictions.
Mapping of the New Fertility Restorer Gene Rf-PET2 Close to Rf1 on Linkage Group 13 in Sunflower (Helianthus annuus L.)
Authors: Sajer Osama , Schirmak Uta , Hamrit Sonia , Horn Renate
Published: March 2020

The PET2-cytoplasm represents a well characterized new source of cytoplasmic male sterility (CMS) in sunflower. It is distinct from the PET1-cytoplasm, used worldwide for commercial hybrid breeding, although it was, as PET1, derived from an interspecific cross between Helianthus. petiolaris and H. annuus. Fertility restoration is essential for the use of CMS PET2 in sunflower hybrid breeding. Markers closely linked to the fertility restorer gene are needed to build up a pool of restorer lines. Fertility-restored F1-hybrids RHA 265(PET2) × IH-51 showed pollen viability of 98.2% ± 1.2, indicating a sporophytic mode of fertility restoration. Segregation analyses in the F2-population of the cross RHA 265(PET2) × IH-51 revealed that this cross segregated for one major restorer gene Rf-PET2. Bulked-segregant analyses investigating 256 amplified fragment length polymorphism (AFLP) primer combinations revealed a high degree of polymorphism in this cross. Using a subset of 24 AFLP markers, three sequence-tagged site (STS) markers and three microsatellite markers, Rf-PET2 could be mapped to the distal region of linkage group 13 between ORS1030 and ORS630. Three AFLP markers linked to Rf-PET2 were cloned and sequenced. Homology search against the sunflower genome sequence of HanXRQ v1r1 confirmed the physical location of Rf-PET2 close to the restorer gene Rf1 for CMS PET1. STS markers were mapped that can now be used for marker-assisted selection.
Rock Features and Alteration of Stone Materials Used for the Built Environment: A Review of Recent Publications on Ageing Tests
Authors: Alves Carlos , Figueiredo Carlos , Sanjurjo-Sánchez Jorge
Published: March 2020

This work presents a review of recent publications, with publication date between 2017 and 2019, with information on the relation between rock characteristics and the effects of diverse agents associated with alteration of stone materials in the built environment. It considers information obtained from ageing tests performed under laboratory conditions and by exposure to outdoor agents. Several lithological groups were considered, with sedimentary carbonate rocks being the most frequently studied lithotypes and silicate metamorphic rocks being the group with scarcer information. In terms of ageing tests, salt weathering was the most frequent one while there was a noticeable lesser amount of information from tests with biological colonization. The collected data showed the influence of diverse features, from specific minerals to whole-rock properties and the presence of heterogeneities. These information are discussed in the context of formulating a general framework for stone decay.
Morphometric Characteristics, Shapes and Provenance of Holocene Pebbles from the Sava River Gravels (Zagreb, Croatia)
Authors: Barudžija Uroš , Velić Josipa , Malvić Tomislav , Trenc Neven , Matovinović Božinović Nikolina
Published: March 2020

Morphometric analysis of Holocene pebbles from Sava River gravel in NW Croatia revealed shape distributions as observed along a 30 km long watercourse. Limestones, dolomites, and sandstones were identified as the major (>4%) and effusive magmatics in this alluvial aquifer system in Zagreb, with cherts and tuffs as minor pebble lithologies (up to 4%). Their distributions mainly indicate distant Alpine provenance for carbonate pebbles (limestone and dolomite) and local input for sandstones and minor lithotypes, laterally from the Samoborska Gora and Medvednica mountain. Carbonates are predominantly disc- and sphere-shaped, implying distant sources. Scattered distributions of pebble shapes (sphere, disc, blade, and rod) for sandstones and minor lithotypes possibly indicate multiple sources, some of them probably local. The tentatively interpreted “original sedimentary environments” for the main pebble lithotypes (calculated from their flatness ratios) possibly indicate that they are predominantly lake beach pebbles, followed by moraine and riverbed pebbles. However, these results should be strongly questioned.
Climate and the Development of Magma Chambers
Authors: Glazner Allen F.
Published: March 2020

Whether magma accumulating in the crust develops into a persistent, eruptible magma body or an incrementally emplaced pluton depends on the energy balance between heat delivered to the bottom in the form of magma and heat lost out the top. The rate of heat loss to the surface depends critically on whether heat transfer is by conduction or convection. Convection is far more efficient at carrying heat than conduction, but requires both abundant water and sufficient permeability. Thus, all else being equal, both long-term aridity and self-sealing of fractures should promote development of persistent magma bodies and explosive silicic volcanism. This physical link between climate and magmatism may explain why many of the world’s great silicic ignimbrite provinces developed in arid environments, and why extension seems to suppress silicic caldera systems.