bluuebunny/crossref_metadata_2025 huggingface dataset:
What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors
Authors: De Leo Antonio , Santini Donatella , Ceccarelli Claudio , Santandrea Giacomo , Palicelli Andrea , Acquaviva Giorgia , Chiarucci Federico , Rosini Francesca , Ravegnini Gloria , Pession Annalisa , Turchetti Daniela , Zamagni Claudio , Perrone Anna Myriam , De Iaco Pierandrea , Tallini Giovanni , de Biase Dario
Published: April 2021

Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.
Facilitations and Hurdles of Genetic Testing in Neuromuscular Disorders
Authors: Barp Andrea , Mosca Lorena , Sansone Valeria Ada
Published: April 2021

Neuromuscular disorders (NMDs) comprise a heterogeneous group of disorders that affect about one in every thousand individuals worldwide. The vast majority of NMDs has a genetic cause, with about 600 genes already identified. Application of genetic testing in NMDs can be useful for several reasons: correct diagnostic definition of a proband, extensive familial counselling to identify subjects at risk, and prenatal diagnosis to prevent the recurrence of the disease; furthermore, identification of specific genetic mutations still remains mandatory in some cases for clinical trial enrollment where new gene therapies are now approaching. Even though genetic analysis is catching on in the neuromuscular field, pitfalls and hurdles still remain and they should be taken into account by clinicians, as for example the use of next generation sequencing (NGS) where many single nucleotide variants of “unknown significance” can emerge, complicating the correct interpretation of genotype-phenotype relationship. Finally, when all efforts in terms of molecular analysis have been carried on, a portion of patients affected by NMDs still remain “not genetically defined”. In the present review we analyze the evolution of genetic techniques, from Sanger sequencing to NGS, and we discuss “facilitations and hurdles” of genetic testing which must always be balanced by clinicians, in order to ensure a correct diagnostic definition, but taking always into account the benefit that the patient could obtain especially in terms of “therapeutic offer”.
Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer
Authors: Szpor Joanna , Streb Joanna , Glajcar Anna , Frączek Paulina , Winiarska Aleksandra , Tyrak Katarzyna E. , Basta Paweł , Okoń Krzysztof , Jach Robert , Hodorowicz-Zaniewska Diana
Published: April 2021

Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN (CD209) in breast cancer. The correlations between DC density and molecular subtype of breast cancer, its hormone receptor status, spatial location and their associations with clinical and pathological prognostic factors were evaluated. We have shown that intratumoural CD1a+ cells were significantly associated with progression-free survival. For LAMP3+ and CD123+ DCs, higher cell densities were associated with non-luminal as compared to luminal cancer phenotype. In contrast, dense CD83+ DC infiltrate was observed in luminal tumours. The number of CD1a+ DCs in both locations was the highest in luminal B/HER2+ cancers. The highest positive cell count of LAMP3+ cells was observed in the triple-negative subtype in both locations. We found higher numbers of LAMP3+ DCs both intratumourally and at the invasive margin, as well as CD123+ DCs intratumourally in tumours with negative expression of oestrogen or progesterone receptors. Our study demonstrates associations between DC subpopulations and histological and clinical characteristics, as well as molecular subtypes in breast carcinoma.
Co-Evolution of Predator-Prey Ecosystems by Reinforcement Learning Agents
Authors: Park Jeongho , Lee Juwon , Kim Taehwan , Ahn Inkyung , Park Jooyoung
Published: April 2021

The problem of finding adequate population models in ecology is important for understanding essential aspects of their dynamic nature. Since analyzing and accurately predicting the intelligent adaptation of multiple species is difficult due to their complex interactions, the study of population dynamics still remains a challenging task in computational biology. In this paper, we use a modern deep reinforcement learning (RL) approach to explore a new avenue for understanding predator-prey ecosystems. Recently, reinforcement learning methods have achieved impressive results in areas, such as games and robotics. RL agents generally focus on building strategies for taking actions in an environment in order to maximize their expected returns. Here we frame the co-evolution of predators and preys in an ecosystem as allowing agents to learn and evolve toward better ones in a manner appropriate for multi-agent reinforcement learning. Recent significant advancements in reinforcement learning allow for new perspectives on these types of ecological issues. Our simulation results show that throughout the scenarios with RL agents, predators can achieve a reasonable level of sustainability, along with their preys.
Toward a Comparison of Classical and New Privacy Mechanism
Authors: Heredia-Ductram Daniel , Nunez-del-Prado Miguel , Alatrista-Salas Hugo
Published: April 2021

In the last decades, the development of interconnectivity, pervasive systems, citizen sensors, and Big Data technologies allowed us to gather many data from different sources worldwide. This phenomenon has raised privacy concerns around the globe, compelling states to enforce data protection laws. In parallel, privacy-enhancing techniques have emerged to meet regulation requirements allowing companies and researchers to exploit individual data in a privacy-aware way. Thus, data curators need to find the most suitable algorithms to meet a required trade-off between utility and privacy. This crucial task could take a lot of time since there is a lack of benchmarks on privacy techniques. To fill this gap, we compare classical approaches of privacy techniques like Statistical Disclosure Control and Differential Privacy techniques to more recent techniques such as Generative Adversarial Networks and Machine Learning Copies using an entire commercial database in the current effort. The obtained results allow us to show the evolution of privacy techniques and depict new uses of the privacy-aware Machine Learning techniques.
Effect of Inter-System Coupling on Heat Transport in a Microscopic Collision Model
Authors: Tian Feng , Zou Jian , Li Lei , Li Hai , Shao Bin
Published: April 2021

In this paper we consider a bipartite system composed of two subsystems each coupled to its own thermal environment. Based on a collision model, we mainly study whether the approximation (i.e., the inter-system coupling is ignored when modeling the system–environment interaction) is valid or not. We also address the problem of heat transport unitedly for both excitation-conserving system–environment interactions and non-excitation-conserving system–environment interactions. For the former interaction, as the inter-system interaction strength increases, at first this approximation gets worse as expected, but then counter-intuitively gets better even for a stronger inter-system coupling. For the latter interaction with asymmetry, this approximation gets progressively worse. In this case we realize a perfect thermal rectification, and we cannot find an apparent rectification effect for the former interaction. Finally and more importantly, our results show that whether this approximation is valid or not is closely related to the quantum correlations between the subsystems, i.e., the weaker the quantum correlations, the more justified the approximation and vice versa.
A Hybrid Constant On-Time Mode for Buck Circuits
Authors: Zhong Shun , Shen Ziqian
Published: April 2021

To achieve a designed and fixed operating frequency for a controller with high dynamic performance and a high load capacity, a hybrid constant on-time (COT) voltage mode for a Buck circuit is proposed and discussed in this paper. The proposed hybrid strategy is a combination of the classical COT method, a dynamic reference voltage technology and a proportional–differential (PD) module. The workflow is demonstrated in brief, simulations of a Buck circuit with the proposed hybrid COT mode are conducted and comparisons with developed pulse-width modulation (PWM) technology and the hysteresis mode are made. The results show that, with the help of the proposed control scheme, impressive performance from the Buck circuit can be expected. The operating frequency can be fixed well by the hybrid technology without losses of performance and robustness in steady state and will not jump much even with the sudden change of the inputs and the load. The proposed control strategy contributes to the foundation of circuit design and optimization.
WMNet: A Lossless Watermarking Technique Using Deep Learning for Medical Image Authentication
Authors: Chen Yueh-Peng , Fan Tzuo-Yau , Chao Her-Chang
Published: April 2021

Traditional watermarking techniques extract the watermark from a suspected image, allowing the copyright information regarding the image owner to be identified by the naked eye or by similarity estimation methods such as bit error rate and normalized correlation. However, this process should be more objective. In this paper, we implemented a model based on deep learning technology that can accurately identify the watermark copyright, known as WMNet. In the past, when establishing deep learning models, a large amount of training data needed to be collected. While constructing WMNet, we implemented a simulated process to generate a large number of distorted watermarks, and then collected them to form a training dataset. However, not all watermarks in the training dataset could properly provide copyright information. Therefore, according to the set restrictions, we divided the watermarks in the training dataset into two categories; consequently, WMNet could learn and identify the copyright information that the watermarks contained, so as to assist in the copyright verification process. Even if the retrieved watermark information was incomplete, the copyright information it contained could still be interpreted objectively and accurately. The results show that the method proposed by this study is relatively effective.
Textile Triboelectric Nanogenerators with Diverse 3D-Spacer Fabrics for Improved Output Voltage
Authors: Kwon Dae-Hyeon , Kwon Jin-Hyuk , Jeong Jaebum , Lee Youngju , Biswas Swarup , Lee Dong-Wook , Lee Sohee , Bae Jin-Hyuk , Kim Hyeok
Published: April 2021

Electrically superior triboelectric nanogenerators (TENG) using 3D fabric and PDMS show great application potential for biokinetic energy harvesting and multifunctional self-power devices. In this study, TENG with fabric-PDMS-fabric structure was produced using various 3D fabrics and PDMS. The peak-to-peak output voltage of various 3D fabrics was compared. The output voltage changes due to structure and vertical fibers. Also, the coefficient of surface friction between the PDMS and the fabric improves the output voltage. TENG using different 3D-spacer polymeric fabrics showed different maximum peak-to-peak output voltage performance. It is attributed to the stiffness, lateral elasticity and 3D morphology of the fabrics. It is considered that those factors including stiffness, lateral elasticity and 3D morphology influence the densities in vertical and lateral fiber to fiber interaction.
SPEAR (Solar Pyrolysis Energy Access Reactor): Theoretical Design and Evaluation of a Small-Scale Low-Cost Pyrolysis Unit for Implementation in Rural Communities
Authors: Caputo Cesare , Mašek Ondřej
Published: April 2021

Energy access and waste management are two of the most pressing developmental and environmental issues on a global level to help mitigate the accelerating impacts of climate change. They are particularly relevant in Sub–Saharan Africa where electrification rates are significantly below global averages and rural areas are lacking a formal waste management sector. This paper explores the potential of integrating solar energy into a biomass pyrolysis unit as a potentially synergetic solution to both issues. The full design of a slow pyrolysis batch reactor targeted at biochar production, following a strict cost minimization approach, is presented in light of the relevant considerations. SPEAR is powered using a Cassegrain optics parabolic dish system, integrated into the reactor via a manual tracking system and optically optimized with a Monte-Carlo ray tracing methodology. The design approach employed has led to the development an overall cost efficient system, with the potential to achieve optical efficiencies up 72% under a 1.5° tracking error. The outputs of the system are biochar and electricity, to be used for soil amendment and energy access purposes, respectively. There is potential to pyrolyze a number of agricultural waste streams for the region, producing at least 5 kg of biochar per unit per day depending on the feedstock employed. Financial assessment of SPEAR yields a positive Net Present Value (NPV) in nearly all scenarios evaluated and a reasonable competitiveness with small scale solar for electrification objectives. Finally, SPEAR presents important positive social and environmental externalities and should be feasibly implementable in the region in the near term.
Regeneration of Riparian and Maritime Pine Forests after a Large Wildfire on the Largest Public Forest of Portugal
Authors: Aguiar Francisca C. , Rodrigues Carolina , Pina João P. , Soares Paula
Published: April 2021

Eighty-six percent of the largest Portuguese public forest, Leiria National Forest (Mata Nacional de Leiria—MNL), central west, was burned in a wildfire in October 2017. Most of the area was covered by maritime pine stands (Pinus pinaster Aiton) crossed by riparian forests along small-sized streams. This work aims to characterize the post-fire vegetation and evaluate its natural regeneration. Sampling was carried out c. 6 months after the fire in 28 plots distributed at pine stands (3.5 × 3.5 m2) and in 24 plots (5 × 20 m2) at stream channels and riverbanks. These latter surveys were repeated in 2019. Data include the floristic composition and cover data of pine stands and streams, and the number of pine seedlings. Six months after the fire, 60% and 93% of the pre-fire species were observed at streams and pine stands, respectively. Fire severity was not related to differences in flora composition, nor with species richness. Pine seedlings were significantly more abundant in pine stands >60 years old compared to younger (<25 y) stands, but no significant differences were observed in the regeneration of understory. On riparian landscapes, the germination and resprouting of invasive exotic species, such as Acacia sp., created dense vegetation formations with decreased native plant diversity and altered the ecosystem structure. Following large wildfires, such as the one in MNL, managers should prioritize preserving the natural regeneration potential in the soil and aerial seed banks.
Fluid Flow of Polar and Less Polar Liquids through Modified Poplar Wood
Authors: Taghiyari Hamid R. , Abbasi Hanieh , Militz Holger , Papadopoulos Antonios N.
Published: April 2021

Fast-growing species often have a low natural durability and can easily be attacked by fungi and insects, and therefore it is often better to preserve them before use. Permeability is a physical property in porous media that significantly affects the penetration of water- and oil-based preservatives into the texture of wood. In the present study, the specific gas permeability and liquid permeability to water and kerosene in poplar wood (Populus nigra var. betulifolia) were measured. The poplar trees were grown in plots with two spacings of 3 × 4 m and 3 × 8 m. Separate sets of specimens were also thermally modified in order to examinethe effects of this modification on gas and liquid permeability values. The results showed higher gas permeability in specimens grown in the plot with wider spacing (3 × 8 m), which was attributed to their larger vessel diameter. Kerosene demonstrated significantly higher permeability in comparison to water. This was attributed to the polar nature of water molecules, which tend to make stronger bonds with wood cell-wall polymers, ultimately delaying the movement of water through vessel elements. Thermal modification had an increasing effect on specific gas permeability. The increase was attributed to cracks that occur in the pits and wood cell wall during thermal modification, making way for the easier flow of fluids. Decreased wettability caused by thermal modification resulted in a significant increase in both water and kerosene permeability values.
Achieving Robust and Socially Acceptable Environmental Policy Recommendations: Lessons from Combining the Choice Experiment Method and Institutional Analysis Focused on Cultural Ecosystem Services
Authors: Louda Jiří , Vojáček Ondřej , Slavíková Lenka
Published: April 2021

The reflection of ecosystem services in environmental policy has recently become a key aspect in solving environmental problems occurring as a consequence of their overburdening. However, decision makers often pay attention predominantly to results of quantitative (monetary valuation) methods. This article explores a new way of combining quantitative and qualitative methods that has proven to be a useful practice for achieving better environmental governance. We combine the (quantitative) choice experiment method and (qualitative) institutional analysis as full and equal complements. In our approach, the goal of qualitative institutional analysis is not to verify the adequacy of willingness-to-pay results but rather to better address cultural and social perspectives of society representatives. Such an approach increases the robustness of policy recommendations and their acceptance in comparison with isolated applications of both methods. To verify this general premise, both methods were applied in the territory of the Eastern Ore Mountains in the Czech Republic to capture preferences and attitudes of local stakeholders as well as tourists towards small-scale ecosystems. The results confirm that preference calculations regarding aesthetic values of ecosystems need to be complemented with facts about institutional settings and barriers in order to better address locally relevant recommendations for decision makers, such as the introduction of new economic instruments (e.g., local taxes or entrance fees). The findings of this study can also be considered for governance of larger local, common-pool resources such as (public) forests or protected areas.
Donor Lymphocyte Infusion to Enhance the Graft-versus-Myeloma Effect
Authors: Gagelmann Nico , Kröger Nicolaus
Published: April 2021

Donor lymphocyte infusion (DLI) has the potential to significantly deepen the response after allogeneic stem cell transplantation (ASCT) in multiple myeloma (MM). Subsequently, DLI offers the opportunity for long-term progression-free and, most importantly, overall survival for patients with MM. DLI application is a complex procedure, whereby many factors need to be considered (e.g., patient-oriented factors prior to application, disease-specific factors, as well as possible combinations with further therapies during and after DLI). There are two settings in which DLI can be given, they are as follows: as a salvage option in progressive disease or in the prophylactic setting for MM patients with resolved disease to further deepen the response. While the first studies used DLI in the salvage setting, results for prophylactic DLI appear to be associated with better and prolonged outcomes. Furthermore, DLI (both prophylactic and salvage) given earlier after ASCT (3–6 months) appear to be associated with better outcomes. The incorporation of novel agents showed similar responses and survival after DLI. However, updated and larger evaluations are urgently needed to determine the specific role of multiple variables in such a complex treatment environment of ASCT in an ever-evolving field of MM. This review underlines the rationale for DLI after ASCT, results in the salvage and prophylactic settings, patterns of disease progression after DLI, as well as avenues to further enhance the graft-versus-myeloma effect exerted by DLI.
An Open Source GIS Application for Spatial Assessment of Health Care Quality Indicators
Authors: Duarte Lia , Teodoro Ana Cláudia , Lobo Mariana , Viana João , Pinheiro Vera , Freitas Alberto
Published: April 2021

Prevention quality indicators (PQIs) constitute a set of measures that can be combined with hospital inpatient data to identify the quality of care for ambulatory care sensitive conditions (ACSC). Geographical information system (GIS) web mapping and applications contribute to a better representation of PQI spatial distribution. Unlike many countries in the world, in Portugal, this type of application remains underdeveloped. The main objective of this work was to facilitate the assessment of geographical patterns and trends of health data in Portugal. Therefore, two innovative open source applications were developed. Leaflet Javascript Library, PostGIS, and GeoServer were used to create a web map application prototype. Python language was used to develop the GIS application. The geospatial assessment of geographical patterns of health data in Portugal can be obtained through a GIS application and a web map application. Both tools proposed allowed for an easy and intuitive assessment of geographical patterns and time trends of PQI values in Portugal, alongside other relevant health data, i.e., the location of health care facilities, which, in turn, showed some association between the location of facilities and quality of health care. However, in the future, more research is still required to map other relevant data, for more in-depth analyses.
Large-Pore Platelet-Rich Fibrin with a Mg Ring to Allow MC3T3-E1 Preosteoblast Migration and to Improve Osteogenic Ability for Bone Defect Repair
Authors: Wong Pei-Chun , Wang Chen-Yun , Jang Jason Shian-Ching , Lee Chian-Her , Wu Jia-Lin
Published: April 2021

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.
The Histone Chaperone HIRA Is a Positive Regulator of Seed Germination
Authors: Layat Elodie , Bourcy Marie , Cotterell Sylviane , Zdzieszyńska Julia , Desset Sophie , Duc Céline , Tatout Christophe , Bailly Christophe , Probst Aline V.
Published: April 2021

Histone chaperones regulate the flow and dynamics of histone variants and ensure their assembly into nucleosomal structures, thereby contributing to the repertoire of histone variants in specialized cells or tissues. To date, not much is known on the distribution of histone variants and their modifications in the dry seed embryo. Here, we bring evidence that genes encoding the replacement histone variant H3.3 are expressed in Arabidopsis dry seeds and that embryo chromatin is characterized by a low H3.1/H3.3 ratio. Loss of HISTONE REGULATOR A (HIRA), a histone chaperone responsible for H3.3 deposition, reduces cellular H3 levels and increases chromatin accessibility in dry seeds. These molecular differences are accompanied by increased seed dormancy in hira-1 mutant seeds. The loss of HIRA negatively affects seed germination even in the absence of HISTONE MONOUBIQUITINATION 1 or TRANSCRIPTION ELONGATION FACTOR II S, known to be required for seed dormancy. Finally, hira-1 mutant seeds show lower germination efficiency when aged under controlled deterioration conditions or when facing unfavorable environmental conditions such as high salinity. Altogether, our results reveal a dependency of dry seed chromatin organization on the replication-independent histone deposition pathway and show that HIRA contributes to modulating seed dormancy and vigor.
Pancreatic Neuroendocrine Neoplasms in Multiple Endocrine Neoplasia Type 1
Authors: Marini Francesca , Giusti Francesca , Tonelli Francesco , Brandi Maria Luisa
Published: April 2021

Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1–2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). pNETs affect 30–80% of MEN1 patients, manifesting prevalently as multiple microadenomas. pNETs in patients with MEN1 are particularly difficult to treat due to differences in their growth potential, their multiplicity, the frequent requirement of extensive surgery, the high rate of post-operative recurrences, and the concomitant development of other tumors. MEN1 syndrome is caused by germinal heterozygote inactivating mutation of the MEN1 gene, encoding the menin tumor suppressor protein. MEN1-related pNETs develop following the complete loss of function of wild-type menin. Menin is a key regulator of endocrine cell plasticity and its loss in these cells is sufficient for tumor initiation. Somatic biallelic loss of wild-type menin in the neuroendocrine pancreas presumably alters the epigenetic control of gene expression, mediated by histone modifications and DNA hypermethylation, as a driver of MEN1-associated pNET tumorigenesis. In this light, epigenetic-based therapies aimed to correct the altered DNA methylation, and/or histone modifications might be a possible therapeutic strategy for MEN1 pNETs, for whom standard treatments fail.
Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency
Authors: Rubio Leticia , Vargas Antonio , Rivera Patricia , López-Gambero Antonio J. , Tovar Rubén , Christians Julian K. , Martín-de-las-Heras Stella , Rodríguez de Fonseca Fernando , Chowen Julie A. , Argente Jesús , Suárez Juan
Published: April 2021

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.
Quantification of Dendritic Spines Remodeling under Physiological Stimuli and in Pathological Conditions
Authors: Bączyńska Ewa , Pels Katarzyna Karolina , Basu Subhadip , Włodarczyk Jakub , Ruszczycki Błażej
Published: April 2021

Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance.
PCSK9 Induces Rat Smooth Muscle Cell Proliferation and Counteracts the Pleiotropic Effects of Simvastatin
Authors: Lupo Maria Giovanna , Marchianò Silvia , Adorni Maria Pia , Zimetti Francesca , Ruscica Massimiliano , Greco Maria Francesca , Corsini Alberto , Ferri Nicola
Published: April 2021

Human atherosclerotic plaque contains smooth muscle cells (SMCs) negative for the contractile phenotype (α-smooth muscle actin) but positive for proprotein convertase subtilisin/kexin type 9 (PCSK9). Thus, we generated rat SMCs which overexpressed human PCSK9 (SMCsPCSK9) with the aim of investigating the role of PCSK9 in the phenotype of SMCs. PCSK9 overexpression in SMCsPCSK9 led to a significant downregulation of the low-density lipoprotein receptor (Ldlr) as well as transgelin (Sm22α), a marker of the contractile phenotype. The cell proliferation rate of SMCsPCSK9 was significantly faster than that of the control SMCs (SMCspuro). Interestingly, overexpression of PCSK9 did not impact the migratory capacity of SMCs in response to 10% FCS, as determined by Boyden’s chamber assay. Expression and activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) was significantly increased in the presence of PCSK9, both in SMCPCSK9 and after treatment with recombinant PCSK9. The transcriptional activity of sterol regulatory element-binding protein (SREBP) was also increased in the presence of PSCK9, suggesting a direct role of PCSK9 in the control of SRE-responsive genes, like HMGCR. We also observed that cholesterol biosynthesis is elevated in SMCPCSK9, potentially explaining the increased proliferation observed in these cells. Finally, concentration-dependent experiments with simvastatin demonstrated that SMCsPCSK9 were partially resistant to the antiproliferative and antimigratory effect of this drug. Taken together, these data further support a direct role of PCSK9 in proliferation, migration, and phenotypic changes in SMCs—pivotal features of atherosclerotic plaque development. We also provide new evidence on the role of PCSK9 in the pharmacological response to statins—gold standard lipid-lowering drugs with pleiotropic action.
The Role of Porphyrinoid Photosensitizers for Skin Wound Healing
Authors: Vallejo Mariana C. S. , Moura Nuno M. M. , Gomes Ana T. P. C. , Joaquinito Ana S. M. , Faustino Maria Amparo F. , Almeida Adelaide , Gonçalves Idalina , Serra Vanda Vaz , Neves Maria Graça P. M. S.
Published: April 2021

Microorganisms, usually bacteria and fungi, grow and spread in skin wounds, causing infections. These infections trigger the immune system and cause inflammation and tissue damage within the skin or wound, slowing down the healing process. The use of photodynamic therapy (PDT) to eradicate microorganisms has been regarded as a promising alternative to anti-infective therapies, such as those based on antibiotics, and more recently, is being considered for skin wound-healing, namely for infected wounds. Among the several molecules exploited as photosensitizers (PS), porphyrinoids exhibit suitable features for achieving those goals efficiently. The capability that these macrocycles display to generate reactive oxygen species (ROS) gives a significant contribution to the regenerative process. ROS are responsible for avoiding the development of infections by inactivating microorganisms such as bacteria but also by promoting cell proliferation through the activation of stem cells which regulates inflammatory factors and collagen remodeling. The PS can act solo or combined with several materials, such as polymers, hydrogels, nanotubes, or metal-organic frameworks (MOF), keeping both the microbial photoinactivation and healing/regenerative processes’ effectiveness. This review highlights the developments on the combination of PDT approach and skin wound healing using natural and synthetic porphyrinoids, such as porphyrins, chlorins and phthalocyanines, as PS, as well as the prodrug 5-aminolevulinic acid (5-ALA), the natural precursor of protoporphyrin-IX (PP-IX).
The Diagnostic Potential of Amyloidogenic Proteins
Authors: Jin Yiyun , Vadukul Devkee Mahesh , Gialama Dimitra , Ge Ying , Thrush Rebecca , White Joe Thomas , Aprile Francesco Antonio
Published: April 2021

Neurodegenerative disorders are a highly prevalent class of diseases, whose pathological mechanisms start before the appearance of any clear symptoms. This fact has prompted scientists to search for biomarkers that could aid early treatment. These currently incurable pathologies share the presence of aberrant aggregates called amyloids in the nervous system, which are composed of specific proteins. In this review, we discuss how these proteins, their conformations and modifications could be exploited as biomarkers for diagnostic purposes. We focus on proteins that are associated with the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and frontotemporal dementia. We also describe current challenges in detection, the most recent techniques with diagnostic potentials and possible future developments in diagnosis.
Cardio- and Neurometabolic Adipobiology: Consequences and Implications for Therapy
Authors: Frohlich Jan , Chaldakov George N. , Vinciguerra Manlio
Published: April 2021

Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), including Alzheimer’s disease (AD), which is viewed herein as a neurometabolic disorder. The pathogenesis and therapy of these diseases are multiplex at basic, clinical and translational levels. Our present goal is to describe new developments in cardiometabolic and neurometabolic adipobiology. Accordingly, we focus on adipose- and/or skeletal muscle-derived signaling proteins (adipsin, adiponectin, nerve growth factor, brain-derived neuroptrophic factor, neurotrophin-3, irisin, sirtuins, Klotho, neprilysin, follistatin-like protein-1, meteorin-like (metrnl), as well as growth differentiation factor 11) as examples of metabotrophic factors (MTFs) implicated in the pathogenesis and therapy of obesity and related CMDs. We argue that these pathologies are MTF-deficient diseases. In 1993 the “vascular hypothesis of AD” was published and in the present review we propose the “vasculometabolic hypothesis of AD.” We discuss how MTFs could bridge CMDs and neurodegenerative diseases, such as AD. Greater insights on how to manage the MTF network would provide benefits to the quality of human life.
Diagnostic of Data Processing by Brazilian Organizations—A Low Compliance Issue
Authors: Ferrão Sâmmara Éllen Renner , Carvalho Artur Potiguara , Canedo Edna Dias , Mota Alana Paula Barbosa , Costa Pedro Henrique Teixeira , Cerqueira Anderson Jefferson
Published: April 2021

In order to guarantee the privacy of users’ data, the Brazilian government created the Brazilian General Data Protection Law (LGPD). This article made a diagnostic of Brazilian organizations in relation to their suitability for LGPD, based on the perception of Information Technology (IT) practitioners who work in these organizations. We used a survey with 41 questions to diagnose different Brazilian organizations, both public and private. The diagnostic questionnaire was answered by 105 IT practitioners. The results show that 27% of organizations process personal data of public access based on good faith and LGPD principles. In addition, our findings also revealed that 16.3% of organizations have not established a procedure or methodology to verify that the LGPD principles are being respected during the development of services that will handle personal data from the product or service design phase to its execution and 20% of the organizations did not establish a communication process to the personal data holders, regarding the possible data breaches. The result of the diagnostic allows organizations and data users to have an overview of how the treatment of personal data of their customers is being treated and which points of attention are in relation to the principles of LGPD.
Unique Duplication of trnN in Odontoptilum angulatum (Lepidoptera: Pyrginae) and Phylogeny within Hesperiidae
Authors: Liu Jiaqi , Xiao Jintian , Hao Xiangyu , Yuan Xiangqun
Published: April 2021

To explore the variation and relationship between gene rearrangement and phylogenetic effectiveness of mitogenomes among lineages of the diversification of the tribe Tagiadini in the subfamily Pyrginae, we sequenced the complete mitogenome of Odontoptilum angulatum. The genome is 15,361 bp with the typical 37 genes, a large AT-rich region and an additional trnN (trnN2), which is completely identical to trnN (sequence similarity: 100%). The gene order differs from the typical Lepidoptera-specific arrangement and is unique to Hesperiidae. The presence of a “pseudo-trnS1” in the non-coding region between trnN1 and trnN2 supports the hypothesis that the presence of an extra trnN can be explained by the tandem duplication-random loss (TDRL) model. Regarding the phylogenetic analyses, we found that the dataset comprising all 37 genes produced the highest node support, as well as a monophyly of Pyrginae, indicating that the inclusion of RNAs improves the phylogenetic signal. Relationships among the subfamilies in Hesperiidae were also in general agreement with the results of previous studies. The monophyly of Tagiadini is strongly supported. Our study provides a new orientation for application of compositional and mutational biases of mitogenomes in phylogenetic analysis of Tagiadini and even all Hesperiidae based on larger taxon sampling in the future.
Influence of Vineyard Inter-Row Groundcover Vegetation Management on Arthropod Assemblages in the Vineyards of North-Eastern Italy
Authors: Zanettin Giulia , Bullo Angela , Pozzebon Alberto , Burgio Giovanni , Duso Carlo
Published: April 2021

In this study, the effects of habitat management practices on both pests and beneficial arthropods were evaluated in vineyards of North-eastern Italy through different field experiments: (1) mowing of inter-row spontaneous grasses in conventional and organic vineyards, (2) different timing of mowing of a green manure mixture, and (3) comparing different green manure mixtures. The first experiment followed a split-plot design, while randomized block design was used in the second and third experiment. In each experiment arthropods were sampled using different methods: leaf sampling, beating and sweep net sampling. Non-mowed spontaneous grasses in inter-rows of vineyards favored the abundance of natural enemies (e.g., predatory mites, parasitic wasps and spiders), and sometimes grapevine leafhoppers. Many arthropod species were recorded in higher numbers in organic vineyards. Late mowing of green manure favored beneficial arthropods (e.g., spiders and parasitic wasps), while it did not influence herbivore density. Groundcover management practices, aimed at increasing plant biodiversity in vineyards, could be a useful tool to enhance beneficial arthropod abundance, although the adoption of this practice should be carefully evaluated when pests occur. Semi-natural areas can contribute to create a more pest-stable agro-ecosystem and should be integrated with appropriate ecological infrastructures surrounding vineyards.
Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study
Authors: Koga Takamitsu , Nakatani Yuya , Ohba Seigo , Hara Masahito , Sumita Yoshinori , Nagai Kazuhiro , Asahina Izumi
Published: April 2021

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size.
Perioperative ABO Blood Group Isoagglutinin Titer and the Risk of Acute Kidney Injury after ABO-Incompatible Living Donor Liver Transplantation
Authors: Cho Hyeyeon , Bae Jinyoung , Yoon Hyun-Kyu , Lee Ho-Jin , Yang Seong-Mi , Choe Suk Hyung , Jung Chul-Woo , Suh Kyung-Suk , Kim Won Ho
Published: April 2021

For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases of ABO-i LT, we collected immunoglobulin (Ig) G and Ig M isoagglutinin titers of baseline, pre-LT, and postoperative peak values. These values were compared between the patients with and without postoperative AKI. Multivariable logistic regression analysis was used to evaluate the association between perioperative isoagglutinin titers and postoperative AKI. Clinical and graft-related outcomes were compared between high and low baseline and postoperative peak isoagglutinin groups. The incidence of AKI was 42.3%. Preoperative baseline and postoperative peak isoagglutinin titers of both Ig M and Ig G were significantly higher in the patients with AKI than those without AKI. Multivariable logistic regression analysis showed that preoperative baseline and postoperative peak Ig M isoagglutinin titers were significantly associated with the risk of AKI (baseline: odds ratio 1.06, 95% confidence interval 1.02 to 1.09; postoperative peak: odds ratio 1.08, 95% confidence interval 1.04 to 1.13). Cubic spline function curves show a positive relationship between the baseline and postoperative peak isoagglutinin titers and the risk of AKI. Clinical outcomes other than AKI were not significantly different according to the baseline and postoperative peak isoagglutinin titers. Preoperative high initial and postoperative peak Ig M isoagglutinin titers were significantly associated with the development of AKI. As the causal relationship between high isoagglutinin titers and risk of AKI is unclear, the high baseline and postoperative isoagglutinin titers could be used simply as a warning sign for the risk of AKI after liver transplantation.
Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality
Authors: Berg Urban , W-Dahl Annette , Nilsdotter Anna , Nauclér Emma , Sundberg Martin , Rolfson Ola
Published: April 2021

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.