bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomic Diversity Not Associated with Gross Karyotype Differentiation: The Case of Bighead Carps, Genus Hypophthalmichthys (Teleostei, Cypriniformes, Xenocyprididae)
Authors: Sember Alexandr , Pelikánová Šárka , de Bello Cioffi Marcelo , Šlechtová Vendula , Hatanaka Terumi , Do Doan Hiep , Knytl Martin , Ráb Petr
Published: April 2020

The bighead carps of the genus Hypophthalmichthys (H. molitrix and H. nobilis) are important aquaculture species. They were subjected to extensive multidisciplinary research, but with cytogenetics confined to conventional protocols only. Here, we employed Giemsa-/C-/CMA3- stainings and chromosomal mapping of multigene families and telomeric repeats. Both species shared (i) a diploid chromosome number 2n = 48 and the karyotype structure, (ii) low amount of constitutive heterochromatin, (iii) the absence of interstitial telomeric sites (ITSs), (iv) a single pair of 5S rDNA loci adjacent to one major rDNA cluster, and (v) a single pair of co-localized U1/U2 snDNA tandem repeats. Both species, on the other hand, differed in (i) the presence/absence of remarkable interstitial block of constitutive heterochromatin on the largest acrocentric pair 11 and (ii) the number of major (CMA3-positive) rDNA sites. Additionally, we applied here, for the first time, the conventional cytogenetics in H. harmandi, a species considered extinct in the wild and/or extensively cross-hybridized with H. molitrix. Its 2n and karyotype description match those found in the previous two species, while silver staining showed differences in distribution of major rDNA. The bighead carps thus represent another case of taxonomic diversity not associated with gross karyotype differentiation, where 2n and karyotype structure cannot help in distinguishing between genomes of closely related species. On the other hand, we demonstrated that two cytogenetic characters (distribution of constitutive heterochromatin and major rDNA) may be useful for diagnosis of pure species. The universality of these markers must be further verified by analyzing other pure populations of bighead carps.
Comparative Cytogenetic Mapping and Telomere Analysis Provide Evolutionary Predictions for Devil Facial Tumour 2
Authors: Ingles Emory D. , Deakin Janine E.
Published: April 2020

The emergence of a second transmissible tumour in the Tasmanian devil population, devil facial tumour 2 (DFT2), has prompted questions on the origin and evolution of these transmissible tumours. We used a combination of cytogenetic mapping and telomere length measurements to predict the evolutionary trajectory of chromosome rearrangements in DFT2. Gene mapping by fluorescence in situ hybridization (FISH) provided insight into the chromosome rearrangements in DFT2 and identified the evolution of two distinct DFT2 lineages. A comparison of devil facial tumour 1 (DFT1) and DFT2 chromosome rearrangements indicated that both started with the fusion of a chromosome, with potentially critically short telomeres, to chromosome 1 to form dicentric chromosomes. In DFT1, the dicentric chromosome resulted in breakage–fusion–bridge cycles leading to highly rearranged chromosomes. In contrast, the silencing of a centromere on the dicentric chromosome in DFT2 stabilized the chromosome, resulting in a less rearranged karyotype than DFT1. DFT2 retains a bimodal distribution of telomere length dimorphism observed on Tasmanian devil chromosomes, a feature lost in DFT1. Using long term cell culture, we observed homogenization of telomere length over time. We predict a similar homogenization of telomere lengths occurred in DFT1, and that DFT2 is unlikely to undergo further substantial rearrangements due to maintained telomere length.
Transcriptome Analysis of circRNA and mRNA in Theca Cells during Follicular Development in Chickens
Authors: Shen Manman , Wu Ping , Li Tingting , Wu Pengfei , Chen Fuxiang , Chen Lan , Xie Kaizhou , Wang Jinyu , Zhang Genxi
Published: April 2020

Development of ovarian follicles requires interactions between granulosa cells, theca cells, and oocytes. Multiple transcription levels are involved but information about the role of noncoding RNAs, especially circular RNAs (circRNAs), is lacking. Here, we used RNA sequencing to profile circRNAs and mRNAs in theca cells from three types of follicle: small yellow follicles (SYF), the smallest hierarchical follicles (F6), and the largest hierarchical follicles (F1). Using bioinformatics analysis, we identified a total of 14,502 circRNAs in all theca cells, with 5622 widely distributed in all stages of development. Differential expression analysis suggested that some genes display differential isoforms during follicular development. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed enrichment of both differentially expressed circRNAs and mRNAs in pathways associated with reproduction, including the TGF-β signaling pathway, oocyte meiosis, and vascular smooth muscle contraction. Our study provides the first visual information about circRNAs and mRNAs in theca cells during follicle development in chickens and adds to the growing body of knowledge about theca cells.
Insulation and Evaporative Resistance of Clothing for Sugarcane Harvesters and Chemical Sprayers, and Their Application in PHS Model-Based Exposure Predictions
Authors: Kuklane Kalev , Toma Róbert , Lucas Rebekah A.I.
Published: April 2020

Many workers are exposed to heat stress that can be exacerbated by the type of clothing they wear. The resulted heat strain can lead to short or long-term heat-related disorders. This study aimed to measure clothing properties of sugarcane field workers and evaluate the heat strain by an international standard, predicted heat strain model (PHS). The clothing thermal insulation and evaporative resistance values of sugarcane cutter and chemical sprayer outfits were acquired for the whole body, body regions and specific body parts via thermal manikin measurements. The detailed clothing insulation values of body parts can be utilized in advanced thermo-physiological models, while in this study, the values for the whole body together with weather data were used in PHS. Estimated duration limited exposure times (DLE) for an hour-by-hour prediction over a workday and for a range of high humidity scenarios were calculated. Such evaluation tools can be used for risk assessment and management to support organizational measures and prepare equipment and materials in the case of hot weather events in order to avoid dehydration and other heat-related disorders.
Racial Disparities in Associations between Neighborhood Demographic Polarization and Birth Weight
Authors: Fong Kelvin C. , Yitshak-Sade Maayan , Lane Kevin J. , Fabian M. Patricia , Kloog Itai , Schwartz Joel D. , Coull Brent A. , Koutrakis Petros , Hart Jaime E. , Laden Francine , Zanobetti Antonella
Published: April 2020

Neighborhood demographic polarization, or the extent to which a privileged population group outnumbers a deprived group, can affect health by influencing social dynamics. While using birth records from 2001 to 2013 in Massachusetts (n = 629,675), we estimated the effect of two demographic indices, racial residential polarization (RRP) and economic residential polarization (ERP), on birth weight outcomes, which are established predictors of the newborn’s future morbidity and mortality risk. Higher RRP and ERP was each associated with higher continuous birth weight and lower odds for low birth weight and small for gestational age, with evidence for effect modification by maternal race. On average, per interquartile range increase in RRP, the birth weight was 10.0 g (95% confidence interval: 8.0, 12.0) higher among babies born to white mothers versus 6.9 g (95% CI: 4.8, 9.0) higher among those born to black mothers. For ERP, it was 18.6 g (95% CI: 15.7, 21.5) higher among those that were born to white mothers versus 1.8 g (95% CI: −4.2, 7.8) higher among those born to black mothers. Racial and economic polarization towards more privileged groups was associated with healthier birth weight outcomes, with greater estimated effects in babies that were born to white mothers than those born to black mothers.
To Comply or Not to Comply: Roma Approach to Health Laws
Authors: Pavlikova Barbara , Freel Lenka , van Dijk Jitse P.
Published: April 2020

According to the general public in Slovakia, compliance with the law is problematic when it comes to Roma and health. Roma compliance with laws has not yet been studied. The aim of this is study was to explore the determinants of Roma behavior in the field of health laws. We used the concept of a semi-autonomous field proposed by Moore (1973) and the theory of planned behavior by Ajzen (1985). We found that Roma (non-)compliance with health laws was influenced by many different factors, such as beliefs, traditions, living conditions and culture. Group beliefs overrule national laws and also individual preferences, which tend to be subordinate to the group view. The less contact Roma from settlements have with non-Roma, the stronger their own rules are in the field of health. Roma health status is influenced by many factors: group beliefs and community traditions are stronger and overrule individual and state behavioral influence. A community-based participatory approach together with improvement of living conditions in cooperation with Roma is desirable.
The Gut Microbiota of the Egyptian Mongoose as an Early Warning Indicator of Ecosystem Health in Portugal
Authors: Cunha Mónica V. , Albuquerque Teresa , Themudo Patrícia , Fonseca Carlos , Bandeira Victor , Rosalino Luís M.
Published: April 2020

The Egyptian mongoose is a carnivore mammal species that in the last decades experienced a tremendous expansion in Iberia, particularly in Portugal, mainly due to its remarkable ecological plasticity in response to land-use changes. However, this species may have a disruptive role on native communities in areas where it has recently arrived due to predation and the potential introduction of novel pathogens. We report reference information on the cultivable gut microbial landscape of widely distributed Egyptian mongoose populations (Herpestes ichneumon, n = 53) and related antimicrobial tolerance across environmental gradients. The panel of isolated species is consistent with the typical protein-based diet of a carnivore: Firmicutes predominate (89% of individuals), while Clostridiales, Enterobacteriales, and Lactobacillales are the major classes. Forty-one individuals (77.4%) harbour Clostridium spp. A spatial influence on mongooses’ microbiota is confirmed by nonmetric multidimensional scaling analysis, with a significant contribution of municipality to their microbiota composition. Antimicrobial susceptibility testing of mongoose commensal bacteria to 28 compounds evidences xenobiotic tolerance of Escherichia coli (E. coli), enterococci, Salmonella Spartel and Mbandaka serotypes and Pseudomonas bacteria, among others. The common isolation of antimicrobial tolerant microbiota from the mongoose’s gut suggests this species is exposed to anthropogenic influence and is affected by forestry and agricultural-related practices, reflecting its easy adaptation to ecological gradients across agroecosystems. We thus propose regular microbial and phenotypic resistance profiling of widely distributed mongooses as a sentinel tool for xenobiotics’ lifecycle and ecosystem health in Portugal.
A Multilevel Model Approach for Investigating Individual Accident Characteristics and Neighborhood Environment Characteristics Affecting Pedestrian-Vehicle Crashes
Authors: Park Seunghoon , Ko Dongwon
Published: April 2020

Walking is the most basic movement of humans and the most fundamental mode of transportation. To promote walking, it is necessary to create a safe environment for pedestrians. However, pedestrian-vehicle crashes still remain relatively high in South Korea. This study employs a multilevel model to examine the differences between the lower-level individual characteristics of pedestrian crashes and the upper-level neighborhood environmental characteristics in Seoul, South Korea. The main results of this study are as follows. The individual characteristics of pedestrian-vehicle crashes are better at explaining pedestrian injury severity than built environment characteristics at the neighborhood level. Older pedestrians and drivers suffer more severe pedestrian injuries. Larger vehicles such as trucks and vans are more likely to result in a high severity of pedestrian injuries. Pedestrian injuries increase during inclement weather and at night. The severity of pedestrian injuries is lower at intersections and crosswalks without traffic signals than at crosswalks and intersections with traffic signals. Finally, school zones and silver zones, which are representative policies for pedestrian safety in South Korea, fail to play a significant role in reducing the severity of pedestrian injuries. The results of this study can guide policymakers and planners when making decisions on how to build neighborhoods that are safer for pedestrians.
Estimation of the Excess COVID-19 Cases in Seoul, South Korea by the Students Arriving from China
Authors: Ryu Sukhyun , Ali Sheikh Taslim , Lim Jun-Sik , Chun Byung Chul
Published: April 2020

Background: In March 2020, overall, 37,000 international students from China, a country at risk of the 2019-novel coronavirus (COVID-19) infection has arrived in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in the Korean home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students from China, we used a deterministic compartmental model for epidemic and performed a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the number of the infected individuals would reach 40–72 from 12 March–24 March with the arrival of 0.2% of pre-infectious individuals. Furthermore, the number of isolated individuals would peak at 40–64 from 13 March–27 March in Seoul, South Korea. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics by the international student from China were less likely to occur in Seoul, South Korea. Conclusions: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine of the individuals from countries with the virus risk are warranted along with other containment policies.
Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study
Authors: Abe Arata , Tanaka Mayui , Yasuoka Akihito , Saito Yoshikazu , Okada Shinji , Mishina Masahiro , Abe Keiko , Kimura Kazumi , Asakura Tomiko
Published: April 2020

Circulating miRNA species are promising symptom markers for various diseases, including cardiovascular disease. However, studies regarding their role in the treatment process are limited, especially concerning cerebral infarction. This study aimed to extract miRNA markers to investigate whether they reflect both onset and treatment process of cerebral infarction. A total of 22 patients (P-group) and 22 control subjects (C-group) were examined for their whole-blood miRNA profiles using DNA GeneChip™ miRNA 4.0 Array, with six patients examined after treatment (T-group). A total of 64 miRNAs were found to be differentially expressed between the C- and P-groups. Out of 64 miRNAs, the expression levels of two miRNAs correlated with hypertension. A total of 155 miRNAs were differentially expressed between the P- and T-groups. Five common miRNAs were found among the 64 and 155 miRNAs identified. Importantly, these common miRNAs were inversely regulated in each comparison (e.g., C < P > T), including miR-505-5p, which was previously reported to be upregulated in aortic stenosis patients. Our previous study using rat cerebral infarction models detected the downregulation of an apoptosis repressor, WDR26, which was repressed by one of the five miRNAs. Our results provide novel information regarding the miRNA-based diagnosis of cerebral infarction in humans. In particular, the five common miRNAs could be useful makers for the onset and the treatment process. Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN000038321).
Functional Role of N-Terminal Extension of Human AP Endonuclease 1 In Coordination of Base Excision DNA Repair via Protein–Protein Interactions
Authors: Moor Nina , Vasil’eva Inna , Lavrik Olga
Published: April 2020

Human apurinic/apyrimidinic endonuclease 1 (APE1) has multiple functions in base excision DNA repair (BER) and other cellular processes. Its eukaryote-specific N-terminal extension plays diverse regulatory roles in interaction with different partners. Here, we explored its involvement in interaction with canonical BER proteins. Using fluorescence based-techniques, we compared binding affinities of the full-length and N-terminally truncated forms of APE1 (APE1NΔ35 and APE1NΔ61) for functionally and structurally different DNA polymerase β (Polβ), X-ray repair cross-complementing protein 1 (XRCC1), and poly(adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP1), in the absence and presence of model DNA intermediates. Influence of the N-terminal truncation on binding the AP site-containing DNA was additionally explored. These data suggest that the interaction domain for proteins is basically formed by the conserved catalytic core of APE1. The N-terminal extension being capable of dynamically interacting with the protein and DNA partners is mostly responsible for DNA-dependent modulation of protein–protein interactions. Polβ, XRCC1, and PARP1 were shown to more efficiently regulate the endonuclease activity of the full-length protein than that of APE1NΔ61, further suggesting contribution of the N-terminal extension to BER coordination. Our results advance the understanding of functional roles of eukaryote-specific protein extensions in highly coordinated BER processes.
RNA Signaling in Pulmonary Arterial Hypertension—A Double-Stranded Sword
Authors: Turton Helena A. , Thompson A. A. Roger , Farkas Laszlo
Published: April 2020

Recognition of and response to pathogens and tissue injury is driven by the innate immune system via activation of pattern recognition receptors. One of the many patterns recognized is RNA and, while several receptors bind RNA, Toll-like receptor 3 (TLR3) is well placed for initial recognition of RNA molecules due to its localization within the endosome. There is a growing body of work describing a role for TLR3 in maintenance of vascular homeostasis. For example, TLR3 deficiency has been shown to play repair and remodeling roles in the systemic vasculature and in lung parenchyma. A hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, yet drivers and triggers of this remodeling remain incompletely understood. Based on its role in the systemic vasculature, our group discovered reduced endothelial TLR3 expression in PAH and revealed a protective role for a TLR3 agonist in rodent models of pulmonary hypertension. This review will provide an overview of RNA signaling in the vasculature and how it relates to PAH pathobiology, including whether targeting double-stranded RNA signaling is a potential treatment option for PAH.
The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors
Authors: Baci Denisa , Bosi Annalisa , Gallazzi Matteo , Rizzi Manuela , Noonan Douglas M. , Poggi Alessandro , Bruno Antonino , Mortara Lorenzo
Published: April 2020

Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME has gained greater attention in the design of specific therapies within the new era of immunotherapy. It is now clear that the immune contexture in OvCA, here referred as tumor immune microenvironment (TIME), acts as a crucial orchestrator of OvCA progression, thus representing a necessary target for combined therapies. Currently, several advancements of antitumor immune responses in OvCA are based on the characterization of tumor-infiltrating lymphocytes, which have been shown to correlate with a significantly improved clinical outcome. Here, we reviewed the literature on selected TIME components of OvCA, such as macrophages, neutrophils, γδ T lymphocytes, and natural killer (NK) cells; these cells can have a role in either supporting or limiting OvCA, depending on the TIME stimuli. We also reviewed and discussed the major (immune)-therapeutic approaches currently employed to target and/or potentiate macrophages, neutrophils, γδ T lymphocytes, and NK cells in the OvCA context.
Bisphenol A Exposure in utero Disrupts Hypothalamic Gene Expression Particularly Genes Suspected in Autism Spectrum Disorders and Neuron and Hormone Signaling
Authors: Henriksen Anne D. , Andrade Alejandro , Harris Erin P. , Rissman Emilie F. , Wolstenholme Jennifer T.
Published: April 2020

Bisphenol A (BPA) is an endocrine-disrupting compound detected in the urine of more than 92% of humans, easily crosses the placental barrier, and has been shown to influence gene expression during fetal brain development. The purpose of this study was to investigate the effect of in utero BPA exposure on gene expression in the anterior hypothalamus, the basal nucleus of the stria terminalis (BNST), and hippocampus in C57BL/6 mice. Mice were exposed in utero to human-relevant doses of BPA, and then RNA sequencing was performed on male PND 28 tissue from whole hypothalamus (n = 3/group) that included the medial preoptic area (mPOA) and BNST to determine whether any genes were differentially expressed between BPA-exposed and control mice. A subset of genes was selected for further study using RT-qPCR on adult tissue from hippocampus to determine whether any differentially expressed genes (DEGs) persisted into adulthood. Two different RNA-Seq workflows indicated a total of 259 genes that were differentially expressed between BPA-exposed and control mice. Gene ontology analysis indicated that those DEGs were overrepresented in categories relating to mating, cell–cell signaling, behavior, neurodevelopment, neurogenesis, synapse formation, cognition, learning behaviors, hormone activity, and signaling receptor activity, among others. Ingenuity Pathway Analysis was used to interrogate novel gene networks and upstream regulators, indicating the top five upstream regulators as huntingtin, beta-estradiol, alpha-synuclein, Creb1, and estrogen receptor (ER)-alpha. In addition, 15 DE genes were identified that are suspected in autism spectrum disorders.
Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery
Authors: Gorzkiewicz Michał , Kopeć Olga , Janaszewska Anna , Konopka Małgorzata , Pędziwiatr-Werbicka Elżbieta , Tarasenko Irina I. , Bezrodnyi Valeriy V. , Neelov Igor M. , Klajnert-Maculewicz Barbara
Published: April 2020

The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra- and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA. The aim of the present work was to evaluate the formation of dendriplexes using novel poly(lysine) dendrimers (containing lysine and arginine or histidine residues in their structure), and to verify the hypothesis that the use of these polymers may allow an efficient method of siRNA transfer into the cells in vitro to be obtained. The fluorescence polarization studies, as well as zeta potential and hydrodynamic diameter measurements were used to characterize the dendrimer:siRNA complexes. The cytotoxicity of dendrimers and dendriplexes was evaluated with the resazurin-based assay. Using the flow cytometry technique, the efficiency of siRNA transport to the myeloid cells was determined. This approach allowed us to determine the properties and optimal molar ratios of dendrimer:siRNA complexes, as well as to demonstrate that poly(lysine) dendrimers may serve as efficient carriers of genetic material, being much more effective than the commercially available transfection agent Lipofectamine 2000. This outcome provides the basis for further research on the application of poly(lysine) dendrimers as carriers for nucleic acids in the field of gene therapy.
Induction of CEMIP in Chondrocytes by Inflammatory Cytokines: Underlying Mechanisms and Potential Involvement in Osteoarthritis
Authors: Ohtsuki Takashi , Hatipoglu Omer F. , Asano Keiichi , Inagaki Junko , Nishida Keiichiro , Hirohata Satoshi
Published: April 2020

In patients with osteoarthritis (OA), there is a decrease in both the concentration and molecular size of hyaluronan (HA) in the synovial fluid and cartilage. Cell migration-inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), was recently reported as an HA depolymerization-related molecule expressed in the cartilage of patients with OA. However, the underlying mechanism of CEMIP regulation is not well understood. We found that CEMIP expression was transiently increased by interleukine-1β (IL-1β) stimulation in chondrocytic cells. We also observed that ERK activation and NF-κB nuclear translocation were involved in the induction of CEMIP by IL-1β. In addition, both administration of HA and mechanical strain attenuated the CEMIP induction in IL-1β-stimulated chondrocytes. In conclusion, we clarified the regulatory mechanism of CEMIP in chondrocytes by inflammatory cytokines and suggested the potential involvement in osteoarthritis development.
Digital PCR: A Reliable Tool for Analyzing and Monitoring Hematologic Malignancies
Authors: Coccaro Nicoletta , Tota Giuseppina , Anelli Luisa , Zagaria Antonella , Specchia Giorgina , Albano Francesco
Published: April 2020

The digital polymerase chain reaction (dPCR) is considered to be the third-generation polymerase chain reaction (PCR), as it yields direct, absolute and precise measures of target sequences. dPCR has proven particularly useful for the accurate detection and quantification of low-abundance nucleic acids, highlighting its advantages in cancer diagnosis and in predicting recurrence and monitoring minimal residual disease, mostly coupled with next generation sequencing. In the last few years, a series of studies have employed dPCR for the analysis of hematologic malignancies. In this review, we will summarize these findings, attempting to focus on the potential future perspectives of the application of this promising technology.
Twin Research in the Post-Genomic Era: Dissecting the Pathophysiological Effects of Adversity and the Social Environment
Authors: Turner Jonathan D. , D’Ambrosio Conchita , Vögele Claus , Diewald Martin
Published: April 2020

The role of twins in research is evolving as we move further into the post-genomic era. With the re-definition of what a gene is, it is becoming clear that biological family members who share a specific genetic variant may well not have a similar risk for future disease. This has somewhat invalidated the prior rationale for twin studies. Case co-twin study designs, however, are slowly emerging as the ideal tool to identify both environmentally induced epigenetic marks and epigenetic disease-associated processes. Here, we propose that twin lives are not as identical as commonly assumed and that the case co-twin study design can be used to investigate the effects of the adult social environment. We present the elements in the (social) environment that are likely to affect the epigenome and measures in which twins may diverge. Using data from the German TwinLife registry, we confirm divergence in both the events that occur and the salience for the individual start as early as age 11. Case co-twin studies allow for the exploitation of these divergences, permitting the investigation of the role of not only the adult social environment, but also the salience of an event or environment for the individual, in determining lifelong health trajectories. In cases like social adversity where it is clearly not possible to perform a randomised-controlled trial, we propose that the case co-twin study design is the most rigorous manner with which to investigate epigenetic mechanisms encoding environmental exposure. The role of the case co-twin design will continue to evolve, as we argue that it will permit causal inference from observational data.
CO2 Derivatives of Molecular Tin Compounds. Part 1: Hemicarbonato and Carbonato Complexes
Authors: Plasseraud Laurent
Published: April 2020

This review focuses on organotin compounds bearing hemicarbonate and carbonate ligands, and whose molecular structures have been previously resolved by single-crystal X-ray diffraction analysis. Most of them were isolated within the framework of studies devoted to the reactivity of tin precursors with carbon dioxide at atmospheric or elevated pressure. Alternatively, and essentially for the preparation of some carbonato derivatives, inorganic carbonate salts such as K2CO3, Cs2CO3, Na2CO3 and NaHCO3 were also used as coreagents. In terms of the number of X-ray structures, carbonate compounds are the most widely represented (to date, there are 23 depositions in the Cambridge Structural Database), while hemicarbonate derivatives are rarer; only three have so far been characterized in the solid-state, and exclusively for diorganotin complexes. For each compound, the synthesis conditions are first specified. Structural aspects involving, in particular, the modes of coordination of the hemicarbonato and carbonato moieties and the coordination geometry around tin are then described and illustrated (for most cases) by showing molecular representations. Moreover, when they were available in the original reports, some characteristic spectroscopic data are also given for comparison (in table form). Carbonato complexes are arbitrarily listed according to their decreasing number of hydrocarbon substituents linked to tin atoms, namely tri-, di-, and mono-organotins. Four additional examples, involving three CO2 derivatives of C,N-chelated stannoxanes and one of a trinuclear nickel cluster Sn-capped, are also included in the last part of the chapter.
Aerodynamic Simulations for Floating Darrieus-Type Wind Turbines with Three-Stage Rotors
Authors: Dabachi Mohamed Amine , Rahmouni Abdellatif , Rusu Eugen , Bouksour Otmane
Published: April 2020

Growing energy demand is causing a significant decrease in the world’s hydrocarbon stock in addition to the pollution of our ecosystem. Based on this observation, the search for alternative sorts of energy to fossil fuels is being increasingly explored and exploited. Wind energy is experiencing a very important development, and it offers a very profitable opportunity for exploitation since the wind is always available and inexhaustible. Several technical solutions exist to exploit wind energy, such as floating vertical axis wind turbines (F-VAWTs), which provide an attractive and cost-effective solution for exploiting higher resources of offshore wind in deep water areas. Recently, the use of the Darrieus vertical axis wind turbine (VAWT) offshore has attracted increased interest because it offers significant advantages over horizontal axis wind turbines (HAWTs). In this context, this article presents a new concept of floating Darrieus-type straight-bladed turbine with three-stage rotors. A double-multiple stream tube (DMST) model is used for aerodynamic simulations to examine several critical parameters, including, solidity turbine, number of blades, rotor radius, aspect ratio, wind velocity, and rotor height. This study also allows to identify a low solidity turbine (σ = 0.3), offering the best aerodynamic performance, while a two-bladed design is recommended. Moreover, the results also indicate the interest of a variable radius rotor, as well as the variation of the height as a function of the wind speed on the aerodynamic efficiency.
Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives
Authors: Galvez-Sánchez Carmen M. , Reyes del Paso Gustavo A.
Published: April 2020

Fibromyalgia syndrome (FMS) is a chronic illness characterized by widespread pain and other clinical and emotional symptoms. The lack of objective markers of the illness has been a persistent problem in FMS research, clinical management, and social recognition of the disease. A critical historical revision of diagnostic criteria for FMS, especially those formulated by the American College of Rheumatology (ACR), was performed. This narrative review has been structured as follows: Introduction; historical background of FMS, including studies proposing and revising the diagnostic criteria; the process of development of the ACR FMS diagnostic criteria (1990 and 2010 versions); revisions of the 2010 ACR FMS diagnostic criteria; the development of scales based on the 2010 and 2011 criteria, which could help with diagnosis and evaluation of the clinical severity of the disease, such as the Polysymptomatic Distress Scale and the FMS Survey Questionnaire; relationships of prevalence and sex ratio with the different diagnostic criteria; validity and diagnostic accuracy of the ACR FMS criteria; the issues of differential diagnosis and comorbidity; the strength and main limitations of the ACR FMS criteria; new perspectives regarding FMS diagnosis; and the impact of the novel findings in the diagnosis of FMS. It is concluded that despite the official 2010 FMS diagnostic criteria and the diagnostic proposal of 2011 and 2016, complaints from health professionals and patients continue.
Incident Comorbidities, Aging and the Risk of Stroke in 608,108 Patients with Atrial Fibrillation: A Nationwide Analysis
Authors: Fauchier Laurent , Bodin Alexandre , Bisson Arnaud , Herbert Julien , Spiesser Pascal , Clementy Nicolas , Babuty Dominique , Chao Tze-Fan , Lip Gregory Y. H.
Published: April 2020

Background: We hypothesized that the change in stroke risk profile between baseline and follow-up may be a better predictor of ischemic stroke than the baseline stroke risk determination using the CHA2DS2-VASc score ((congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65–75 years, sex category (female))). Methods: We collected information for all patients treated with atrial fibrillation (AF) in French hospitals between 2010 and 2019. We studied 608,108 patients with AF who did not have risk factors of the CHA2DS2-VASc score (except for age and sex). The predictive accuracies of baseline and follow-up CHA2DS2-VASc scores, as well as the ‘Delta CHA2DS2-VASc’ (i.e., change/difference between the baseline and follow-up CHA2DS2-VASc scores) for prediction of ischemic stroke were studied. Results: The mean CHA2DS2-VASc score at baseline was 1.7, and increased to 2.4 during follow-up of 2.2 ± 2.4 years, (median (interquartile range: IQR) 1.2 (0.1–3.8) years), resulting in a mean Delta CHA2DS2-VASc score of 0.7. Among 20,082 patients suffering ischemic stroke during follow-up, 67.1% had a Delta CHA2DS2-VASc score ≥1 while they were only 40.4% in patients without ischemic stroke. The follow-up CHA2DS2-VASc score and Delta CHA2DS2-VASc score were predictors of ischemic stroke (C-index 0.670, 95% confidence interval (CI) 0.666–0.673 and 0.637, 95%CI 0.633–0.640) and they performed better than baseline CHA2DS2-VASc score (C-index 0.612, 95%CI 0.608–0.615, p < 0.0001). Conclusions: Stroke risk was non-static, and many AF patients had ≥1 new stroke risk factor(s) before ischemic stroke occurred. The follow-up CHA2DS2-VASc score and its change (i.e., ‘Delta CHA2DS2-VASc’) were better predictors of ischemic stroke than relying on the baseline CHA2DS2-VASc score.
Effect of Subcutaneous Insulin on Spirometric Maneuvers in Patients with Type 1 Diabetes: A Case-Control Study
Authors: Sánchez Enric , Mizab Chadia , Sauret Ariadna , Barbé Ferran , Martí Raquel , López-Cano Carolina , Hernández Marta , Gutiérrez-Carrasquilla Liliana , Carmona Paola , González Jessica , Dalmases Mireia , Hernández Cristina , Simó Rafael , Lecube Albert
Published: April 2020

In order to compare spirometric maneuvers in adults according to the presence of type 1 diabetes, a case-control study including 75 patients with type 1 diabetes and 75 controls matched by sex, age, and body mass index were designed. In addition, 75 patients with type 1 diabetes were added to examine the potential the impact of subcutaneous insulin therapy on pulmonary function. Lung function measurements were assessed according to the global initiative for chronic obstructive lung disease guidelines. Basal insulin included long-acting insulin analogues and the delivered background insulin in patients with pump therapy. Bolus insulin included rapid-acting insulin analogues and the delivered insulin to cover postprandial hyperglycemias. Patients with type 1 diabetes showed lower spirometric values in comparison to the control group, together with a higher prevalence of forced expiratory volume in the first second (FEV1) <80% (10.7% vs. 2.7%, p = 0.044) and restrictive ventilatory pattern (10.7% vs. 0%, p = 0.006) The dose of basal insulin (U/kg/day) showed a negative correlation with forced vital capacity (FVC) (r = −0.205, p = 0.012) and FEV1 (r = −0.182, p = 0.026). The optimal cut-off value for identifying patients with a restrictive spirometric pattern was 0.5 U/kg/day of basal insulin. Additionally, basal insulin (U/kg/day) independently predicted the presence of both a restrictive spirometric pattern (OR = 77.1 (3.2 to 1816.6), p = 0.007) and an abnormal FEV1 (OR = 29.9 (1.5 to 562.8), p = 0.023). In patients with type 1 diabetes, higher basal insulin dosage seems to be related with an impairment of pulmonary function.
Multiparametric Modelling of Survival in Pancreatic Ductal Adenocarcinoma Using Clinical, Histomorphological, Genetic and Image-Derived Parameters
Authors: Kaissis Georgios A. , Jungmann Friederike , Ziegelmayer Sebastian , Lohöfer Fabian K. , Harder Felix N. , Schlitter Anna Melissa , Muckenhuber Alexander , Steiger Katja , Schirren Rebekka , Friess Helmut , Schmid Roland , Weichert Wilko , Makowski Marcus R. , Braren Rickmer F.
Published: April 2020

Rationale: Pancreatic ductal adenocarcinoma (PDAC) remains a tumor entity of exceptionally poor prognosis, and several biomarkers are under current investigation for the prediction of patient prognosis. Many studies focus on promoting newly developed imaging biomarkers without a rigorous comparison to other established parameters. To assess the true value and leverage the potential of all efforts in this field, a multi-parametric evaluation of the available biomarkers for PDAC survival prediction is warranted. Here we present a multiparametric analysis to assess the predictive value of established parameters and the added contribution of newly developed imaging features such as biomarkers for overall PDAC patient survival. Methods: 103 patients with resectable PDAC were retrospectively enrolled. Clinical and histopathological data (age, sex, chemotherapy regimens, tumor size, lymph node status, grading and resection status), morpho-molecular and genetic data (tumor morphology, molecular subtype, tp53, kras, smad4 and p16 genetics), image-derived features and the combination of all parameters were tested for their prognostic strength based on the concordance index (CI) of multivariate Cox proportional hazards survival modelling after unsupervised machine learning preprocessing. Results: The average CIs of the out-of-sample data were: 0.63 for the clinical and histopathological features, 0.53 for the morpho-molecular and genetic features, 0.65 for the imaging features and 0.65 for the combined model including all parameters. Conclusions: Imaging-derived features represent an independent survival predictor in PDAC and enable the multiparametric, machine learning-assisted modelling of postoperative overall survival with a high performance compared to clinical and morpho-molecular/genetic parameters. We propose that future studies systematically include imaging-derived features to benchmark their additive value when evaluating biomarker-based model performance.
Lower Activity and Function Scores Are Associated with a Higher Risk of Preoperative Deep Venous Thrombosis in Patients Undergoing Total Hip Arthroplasty
Authors: Kawai Toshiyuki , Goto Koji , Kuroda Yutaka , Matsuda Shuichi
Published: April 2020

This study was performed to investigate the relationship between patients’ activity and function levels and the incidence of preoperative deep venous thrombosis (DVT) prior to total hip arthroplasty (THA). We retrospectively reviewed 500 patients admitted for primary or revision THA from July 2014 to October 2018. The diagnosis of DVT was confirmed using Doppler ultrasonography 1 month before THA. The patients’ activity and hip function were evaluated using several clinical scores: the Harris Hip Score (HHS), Oxford Hip Score (OHS), University of California Los Angeles (UCLA) activity score, and visual analog scale (VAS) score. Those scores and the medical history were examined for correlations with preoperative DVT using univariate and multivariate models. Univariate regression analysis showed that older age, current steroid use, anticoagulant use, a history of DVT, collagen disease, a lower UCLA activity score, and a lower OHS were associated with an elevated risk of preoperative DVT. The multivariate analyses showed that a higher UCLA activity score (odds ratio (OR): 0.0049–0.012) and higher OHS (OR: 0.0012–0.0088) were associated with a lower risk of preoperative DVT in each model. Age (OR: 1.07 in both models), current steroid use (OR: 9.32–10.45), and a history of DVT (OR: 27.15–74.98) were associated with a higher risk of preoperative DVT in both models. Older age, current steroid use, a history of DVT, a lower UCLA activity score, and a lower OHS were risk factors for preoperative DVT before THA, even when controlling for potential confounders. Patients exhibiting low activity and low function levels were more likely to have DVT, even before surgery.
COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy!
Authors: Pomara Cristoforo , Li Volti Giovanni , Cappello Francesco
Published: April 2020

The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community’s efforts, there is an increasing body of published studies describing the virus’ biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.
Salivary Levels of Titanium, Nickel, Vanadium, and Arsenic in Patients Treated with Dental Implants: A Case-Control Study
Authors: Papi Piero , Raco Andrea , Pranno Nicola , Di Murro Bianca , Passarelli Pier Carmine , D’Addona Antonio , Pompa Giorgio , Barbieri Maurizio
Published: April 2020

Background: Recent articles have hypothesized a possible correlation between dental implants dissolution products and peri-implantitis. The null hypothesis tested in this case-control study was that there would be no differences in salivary concentrations of titanium (Ti), vanadium (V), nickel (Ni) and arsenic (As) ions among patients with dental implants, healthy (Group A) or affected by peri-implantitis (Group B), compared to subjects without implants and/or metallic prosthetic restorations (Group C). Methods: Inductively coupled plasma mass spectrometry was used to analyze saliva samples. One-way repeated-measure analysis of variance (ANOVA) was used to identify statistically significant differences in the salivary level of Ti, V, Ni and As between the three groups. Results: A total of 100 patients were enrolled in the study (42 males and 58 females), distributed in three groups: 50 patients in Group C, 26 patients in Group B and 24 patients Group B. In our study, concentrations of metallic ions were higher in Group A and B, compared to the control group, with the exception of vanadium. However, there were no statistically significant differences (p > 0.05) for metallic ions concentrations between Group A and Group B. Conclusions: Based on our results, there are no differences in titanium or other metals concentrations in saliva of patients with healthy or diseased implants.
Topical VEGF-C/D Inhibition Prevents Lymphatic Vessel Ingrowth into Cornea but Does Not Improve Corneal Graft Survival
Authors: Salabarria Ann-Charlott , Koch Manuel , Schönberg Alfrun , Zinser Elisabeth , Hos Deniz , Hamdorf Matthias , Imhof Thomas , Braun Gabriele , Cursiefen Claus , Bock Felix
Published: April 2020

Vascular endothelial growth factor-C/D (VEGF-C/D) regulates lymphangiogenesis. Ingrowth of lymphatic vessels is negatively associated with corneal transplantation success. In this study, we therefore analyzed the effect local blockade of VEGF-C/D has on inflamed corneas. We used the murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation. Mice were treated with a VEGF-C/D trap prior to transplantation. Topical inhibition of VEGF-C/D significantly reduced lymphatic vessel ingrowth, but increased Macrophage numbers in the cornea. Furthermore, corneal transplantation success was not improved by the topical application of the compound. This study demonstrates that local VEGF-C/D inhibition is insufficient to increases corneal transplantation success, likely due to interaction with immune cells.