bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Analysis of Salivary Oral Bacteria Associated with Severe Early Childhood Caries and Construction of Caries Assessment Model
Authors: Zhang Lijuan , Sun Tongzheng , Zhu Pengfei , Sun Zheng , Li Shanshan , Li Fan , Zhang Ying , Tan Kaixuan , Lu Jie , Yuan Rongtao , Chen Zhenggang , Guo Dawei , Guo Qingyuan , Teng Fei , Yang Fang
Published: April 2020

To construct a saliva-based caries risk assessment model, saliva samples from 176 severe early childhood caries (S-ECC) children and 178 healthy (H) children were screened by real-time PCR-based quantification of the selected species, includingStreptococcus mutans,Prevotella pallens,Prevotella denticolaandLactobacillus fermentum. Host factors including caries status, dmft indices, age, gender, and geographic origin were assessed in their influence on abundance of the targeted species, which revealed host caries status as the dominant factor, followed by dmft indices (both P < 0.01). Moreover, levels ofS.mutansandP.denticolain the S-ECC group were significantly higher than those in the healthy group (P < 0.001 forS.mutansand P < 0.01 forP.denticola). Interestingly, the co-occurrence network of these targeted species in the S-ECC group differed from that from the healthy group. Finally, based on the combined change pattern ofS.mutansandP.pallens, we constructed an S-ECC diagnosis model with an accuracy of 72%. This saliva-based caries diagnosis model is of potential value for circumstances where sampling dental plague is difficult.
Massive bioconstructions built by Neopycnodonte cochlear (Mollusca, Bivalvia) in a mesophotic environment in the central Mediterranean Sea
Authors: Cardone Frine , Corriero Giuseppe , Longo Caterina , Mercurio Maria , Onen Tarantini Senem , Gravina Maria Flavia , Lisco Stefania , Moretti Massimo , De Giosa Francesco , Giangrande Adriana , Nonnis Marzano Carlotta , Pierri Cataldo
Published: April 2020

The present paper provides a multidisciplinary fine-scale description of a Mediterranean mesophotic new habitat dominated by the bivalve Neopycnodonte cochlear (Poli, 1795), building large and thick pinnacles on vertical cliffs at two study areas along the southern Italian coast. The pinnacles, constituted by a multilayered aggregation of living and dead specimens of N. cochlear, were interconnected with each other to form a framework of high structural complexity, never observed before for this species. The bioconstruction, considerably extended, resulted very complex and diversified in the associated community of structuring organisms. This latter included 165 taxa attributable to different ecological groups occurring in different microhabitats of the bioconstruction. Among the secondary structuring taxa there were scleractinians, serpulids and bryozoans, all contributing to the deposition of calcium carbonate, and poriferans, helping to bind shells together or eroding carbonate by boring species. In comparison with coralligenous sensu stricto and the recently described Mediterranean mesophotic coral reef, the Neopycnodonte bioconstruction showed peculiar features, since it lacked the major contribution of encrusting coralline algae and scleractinians as reef builders, respectively.
Towards a Novel Strategy for Safety, Stability and Driving Dynamics Enhancement During Cornering Manoeuvres in Motorsports Applications
Authors: Roy Aditya , Dasgupta Debabrata
Published: April 2020

With aerodynamics research being primarily focused on drag and lift mitigation strategies till date, engrossed attention has not been received by the event of numerous accidents caused due to negotiation of turns at high speeds by formula and motorsport cars. We present an unexplored and innovative concept of variable side-flap mechanism with a peculiar orientation for introducing three components of forces in the event of turning. Numerical simulations have been performed at two notorious slant angle configurations of the generic ground vehicle body, namely 25° and 35°. In order to analyse the inception of variable forces and flow changes introduced by the flap mechanism, RANS modelling has been performed on nine cases of flap angles from 10° to 90° at six instances of Reynolds numbers between $$1.98\times {10}^{6}$$1.98×106 and $$2.98\times {10}^{6}$$2.98×106. In addition to the introduction of variable drag and downforce components leading to decrement in braking effort and enhancement in overall stability and safety characteristics based on steering input, our proposal holds potential for improving driving dynamics by imparting mild oversteer characteristics due to a flap-induced vortex. To conclude, a safe regime of flap operation in terms of flap angle based on drag, downforce and oversteering dynamics has also been recommended.
Human exploitation of nocturnal felines at Diepkloof Rock Shelter provides further evidence for symbolic behaviours during the Middle Stone Age
Authors: Val Aurore , Porraz Guillaume , Texier Pierre-Jean , Fisher John W. , Parkington John
Published: April 2020

Within the animal kingdom, carnivores occupied a unique place in prehistoric societies. At times predators or competitors for resources and shelters, anthropogenic traces of their exploitation, often for non-nutritional purposes, permeate the archaeological record. Scarce but spectacular depictions in Palaeolithic art confirm peoples’ fascination with carnivores. In contrast with the European record, research on hominin/carnivore interactions in Africa has primarily revolved around the hunting or scavenging debate amongst early hominins. As such, the available information on the role of carnivores in Anatomically Modern Humans’ economic and cultural systems is limited. Here, we illustrate a particular relationship between humans and carnivores during the MIS5-4 Still Bay and Howiesons Poort techno-complexes at Diepkloof Rock Shelter, South Africa. The recovery of numerous felid remains, including cut-marked phalanges, tarsals and metapodials, constitutes direct evidence for carnivore skinning and, presumably, pelt use in the southern African Middle Stone Age. Carnivore exploitation at the site seems to have focused specifically on nocturnal, solitary and dangerous felines. The lines of evidence presented here suggest the capture and fur use of those felines in the context of highly codified and symbolically loaded cultural traditions.
Weaning Immunosuppressant in Patients with Failing Kidney Grafts and The Outcomes: A Single-Center Retrospective Cohort Study
Authors: Ryu Hyunjin , Kim Yong Chul , Moon Jong Joo , Song Eun Young , Min Sang-il , Ha Jongwon , Joo Kwon Wook , Kim Yon Su , Ahn Curie , Lee Hajeong
Published: April 2020

An immunosuppressant weaning protocol in failing allografts has not yet been established. Maintaining immunosuppressants would preserve residual renal function (RRF) and prevent graft intolerance syndrome and sensitization but would increase the risks of infection and malignancy. In this study, graft failure cases after kidney transplantation in a single center were reviewed retrospectively. The outcome differences in all-cause mortality, infection-related hospitalization, cancer, graft intolerance syndrome, re-transplantation, and RRF duration between the immunosuppressant maintaining and weaning groups 6 months after graft failure were compared. Among the weaning group, the outcome differences according to low-dose steroid use were also compared at 6 and 12 months. In a total of 131 graft failure cases, 18 mortalities, 42 infection-related hospitalizations, 22 cancer cases, 11 graft intolerance syndrome cases, and 28 re-transplantations occurred during the 94-month follow-up. Immunosuppressant maintenance significantly decreased the patient survival rate 6 months after graft failure compared with weaning (log-rank P = 0.008) and was an independent risk factor for mortality, even after adjustments (hazard ratio, 3.01; P = 0.025). Infection-related hospitalization, graft intolerance syndrome development, and re-transplantation were not affected by the immunosuppressant weaning protocol. Among the immunosuppressant weaning group, low-dose steroid maintenance at 6 and 12 months helped preserved RRF (P = 0.008 and P = 0.003, respectively).
Association of prenatal psychological distress and postpartum depression with varying physical activity intensity: Japan Environment and Children’s Study (JECS)
Authors: Susukida Ryoko , Usuda Kentaro , Hamazaki Kei , Tsuchida Akiko , Matsumura Kenta , Nishi Daisuke , Inadera Hidekuni ,   Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: April 2020

Evidence is mixed on the associations between physical activity during pregnancy and perinatal depression, and it is limited for different physical activity intensities. Data for 92,743 pregnant women from the Japan Environment and Children’s Study were analyzed in this study. Psychological distress during pregnancy was assessed as moderate or severe using the Kessler Psychological Distress Scale (K6 5–12 and ≥13, respectively). Postpartum depression was assessed using the Edinburgh Postpartum Depression Scale (EPDS; cut-off score 9). Women with only light physical activity had significantly lower odds of psychological distress during pregnancy than those with no physical activity (K6 5–12: adjusted odds ratio [AOR] 0.86, 95% confidence interval [95%CI] 0.82, 0.90; K6 ≥ 13: AOR 0.64, 95%CI 0.58, 0.72). Women with a combination of light, moderate and vigorous physical activity had significantly higher odds of psychological distress during pregnancy (K6 5–12: AOR 1.32, 95%CI 1.18, 1.48; K6 ≥ 13: AOR 1.45, 95%CI 1.16, 1.81) and depression after childbirth (EPDS ≥ 9: AOR 1.42, 95%CI 1.24, 1.61). Physical activity intensity should be considered when assessing psychological distress risk during pregnancy and depression risk after delivery. Future research should evaluate specific physical activity programs with optimal intensity for pregnant women to prevent and treat their psychological distress and depression.
Estimation and correction of bias in network simulations based on respondent-driven sampling data
Authors: Zhu Lin , Menzies Nicolas A. , Wang Jianing , Linas Benjamin P. , Goodreau Steven M. , Salomon Joshua A.
Published: April 2020

Respondent-driven sampling (RDS) is widely used for collecting data on hard-to-reach populations, including information about the structure of the networks connecting the individuals. Characterizing network features can be important for designing and evaluating health programs, particularly those that involve infectious disease transmission. While the validity of population proportions estimated from RDS-based datasets has been well studied, little is known about potential biases in inference about network structure from RDS. We developed a mathematical and statistical platform to simulate network structures with exponential random graph models, and to mimic the data generation mechanisms produced by RDS. We used this framework to characterize biases in three important network statistics – density/mean degree, homophily, and transitivity. Generalized linear models were used to predict the network statistics of the original network from the network statistics of the sample network and observable sample design features. We found that RDS may introduce significant biases in the estimation of density/mean degree and transitivity, and may exaggerate homophily when preferential recruitment occurs. Adjustments to network-generating statistics derived from the prediction models could substantially improve validity of simulated networks in terms of density, and could reduce bias in replicating mean degree, homophily, and transitivity from the original network.
Characterization and Pharmacological Evaluation of Anti-Cellulite Herbal Product(s) Encapsulated in 3D-Fabricated Polymeric Microneedles
Authors: Amer Reham I. , El-Osaily Ghada H. , Bakr Riham O. , El Dine Riham Salah , Fayez Ahmed M.
Published: April 2020

Skin health is vital for a healthy body. Herbal remedies have long been used for skin care, and their global use has tremendously increased over the past three decades. Although cellulite is seen as a normal condition by the medical community, it is considered a serious cosmetic concern for most affected women. Many topical anti-cellulite creams are available on the market, but unfortunately, their efficacy has not been proven scientifically. Microneedles (MNs) represent a new approach to enhance the permeation of loaded medication through the skin. In this study, the anti-cellulite effects of Vitex agnus-castus and Tamarindus indica extracts were compared using safe and effective polymeric MNs. This delivery system offers a painless alternative to the combined treatment strategy of microneedling devices and anti-cellulite products. The selected standardized extracts were evaluated for their mineral, phenolic and flavonoid contents, which are correlated to a promising antioxidant effect, as demonstrated by an in vitro radical scavenging activity assay. 3D-printing techniques were chosen for fabrication of a micromold, which is inexpensive for mass production. To ensure that MNs were sufficiently strong to perforate the skin without breaking, axial failure force was measured using a micro-mechanical test machine. The anticellulite effects of MNs were assessed using an in vivo diet-induced obesity guinea pig model. Skin properties, histopathology and inflammatory markers were examined. MNs loaded with plant extracts were statistically comparable in normalizing the oxidative state and reducing inflammation, while myeloperoxidase levels were more significantly reduced by T. indica than by V. agnus-castus. This novel delivery system opens the door for new transdermal strategies for cellulite management.
Neural basis of interindividual variability in social perception in typically developing children and adolescents using diffusion tensor imaging
Authors: Vinçon-Leite A. , Saitovitch A. , Lemaitre H. , Rechtman E. , Fillon L. , Grevent D. , Calmon R. , Brunelle F. , Boddaert N. , Zilbovicius M.
Published: April 2020

Humans show great interindividual variability in the degree they engage in social relationship. The neural basis of this variability is still poorly understood, particularly in children. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is social perception, in typically developing children. For that purpose, we first used eye-tracking to objectively measure eye-gaze processing during passive visualization of social movie clips in 24 children and adolescents (10.5 ± 2.9 y). Secondly, we correlated eye-tracking data with measures of fractional anisotropy, an index of white matter microstructure, obtained using diffusion tensor imaging MRI. The results showed a large interindividual variability in the number of fixations to the eyes of characters during visualization of social scenes. In addition, whole-brain analysis showed a significant positive correlation between FA and number of fixations to the eyes,mainly in the temporal part of the superior longitudinal fasciculi bilaterally, adjacent to the posterior superior temporal cortex. Our results indicate the existence of a neural signature associated with the interindividual variability in social perception in children, contributing for better understanding the neural basis of typical and atypical development of a broader social expertise.
Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model
Authors: Lichtenstein Flavio , Iqbal Asif , de Lima Will Sonia Elisabete Alves , Bosch Rosemary Viola , DeOcesano-Pereira Carlos , Goldfeder Mauricio Barbugiani , Chammas Roger , Trufen Carlos Eduardo Madureira , Morais Katia Luciano Pereira , de Souza Jean Gabriel , Natalino Renato Jose Mendonça , de Azevedo Inacio Junqueira , Nishiyama Junior Milton Yutaka , Oliveira Ursula , Alves Francisco Ivanio Arruda , Araujo Jaqueline Mayara , Lobba Aline Ramos Maia , Chudzinski-Tavassi Ana Marisa
Published: April 2020

We have investigated Amblyomin-X-treated horse melanomas to better understand its mode of action through transcriptome analysis and the in vivo model. Amblyomin-X is a Kunitz-type homologous protein that selectively leads to the death of tumor cells via ER stress and apoptosis, currently under investigation as a new drug candidate for cancer treatment. Melanomas are immunogenic tumors, and a better understanding of the immune responses is warranted. Equine melanomas are spontaneous and not so aggressive as human melanomas are, as this study shows that the in vivo treatment of encapsulated horse melanoma tumors led to a significant reduction in the tumor size or even the complete disappearance of the tumor mass through intratumoral injections of Amblyomin-X. Transcriptome analysis identified ER- and mitochondria-stress, modulation of the innate immune system, apoptosis, and possibly immunogenic cell death activation. Interactome analysis showed that Amblyomin-X potentially interacts with key elements found in transcriptomics. Taken together, Amblyomin-X modulated the tumor immune microenvironment in different ways, at least contributing to induce tumor cell death.
Phylogenetic Inference of H3N2 Canine Influenza A Outbreak in Ontario, Canada in 2018
Authors: Xu Wanhong , Weese J. Scott , Ojkic Davor , Lung Oliver , Handel Katherine , Berhane Yohannes
Published: April 2020

The first Canadian H3N2 canine influenza A outbreak involving an Asian-origin H3N2 canine influenza virus (CIV) began in southwestern Ontario, Canada, in late December 2017. More H3N2 CIV cases were identified in central and eastern Ontario between March and October 2018. Based on epidemiological investigation, 5 clusters were identified (C1, C2, C3a, C3b, and C4); however, the origin of infection has only been revealed for epidemiological cluster C1. Here, we use phylogenetic analyses to unravel the links of virus transmission between the 5 epidemiological clusters and the origin of infection for all epidemiological clusters. Our results demonstrate that the Canadian H3N2 CIV sequences were grouped into four distinct phylogenetic clusters with minimal genetic diversity between these clusters. Large scale phylogenetic analysis of H3N2 CIV from around the globe showed that the Canadian CIVs formed a distinct new clade along with CIVs that have been circulating in the USA since 2017–2018 and in China since 2017. This clade shares a common ancestor of Asian origin. This study concludes that the H3N2 CIV outbreak in Ontario was driven by multiple introductions of South Korean/Chinese-origin H3N2 CIVs over 10 months.
Cardiolipin is required in vivo for the stability of bacterial translocon and optimal membrane protein translocation and insertion
Authors: Ryabichko Sergey , Ferreira Vilena de Melo , Vitrac Heidi , Kiyamova Ramziya , Dowhan William , Bogdanov Mikhail
Published: April 2020

Translocation of preproteins across the Escherichia coli inner membrane requires anionic lipids by virtue of their negative head-group charge either in vivo or in situ. However, available results do not differentiate between the roles of monoanionic phosphatidylglycerol and dianionic cardiolipin (CL) in this essential membrane-related process. To define in vivo the molecular steps affected by the absence of CL in protein translocation and insertion, we analyzed translocon activity, SecYEG stability and its interaction with SecA in an E. coli mutant devoid of CL. Although no growth defects were observed, co- and post-translational translocation of α-helical proteins across inner membrane and the assembly of outer membrane β-barrel precursors were severely compromised in CL-lacking cells. Components of proton-motive force which could impair protein insertion into and translocation across the inner membrane, were unaffected. However, stability of the dimeric SecYEG complex and oligomerization properties of SecA were strongly compromised while the levels of individual SecYEG translocon components, SecA and insertase YidC were largely unaffected. These results demonstrate that CL is required in vivo for the stability of the bacterial translocon and its efficient function in co-translational insertion into and translocation across the inner membrane of E. coli.
Author Correction: Radiological Investigation of High Background Radiation Areas
Authors: Mubarak Fawzia , Fayez-Hassan M. , Mansour N. A. , Salah Ahmed Talaat , Ali Abdallah
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
New Insights into Mechanical, Metabolic and Muscle Oxygenation Signals During and After High-Intensity Tethered Running
Authors: Manchado-Gobatto F. B. , Marostegan A. B. , Rasteiro F. M. , Cirino C. , Cruz J. P. , Moreno M. A. , Gobatto C. A
Published: April 2020

High-intensity exercises including tethered efforts are commonly used in training programs for athletes, active and even sedentary individuals. Despite this, the knowledge about the external and internal load during and after this effort is scarce. Our study aimed to characterize the kinetics of mechanical and physiological responses in all-out 30 seconds (AO30) tethered running and up to 18 minutes of passive recovery. Additionally, in an innovative way, we investigated the muscle oxygenation in more or less active muscles (vastus lateralis and biceps brachii, respectively) during and after high-intensity tethered running by near-infrared spectroscopy – NIRS. Twelve physically active young men were submitted to AO30 on a non-motorized treadmill to determine the running force, velocity and power. We used wearable technologies to monitor the muscle oxygenation and heart rate responses during rest, exercise and passive recovery. Blood lactate concentration and arterial oxygen saturation were also measured. In a synchronized analysis by high capture frequency of mechanical and physiological signals, we advance the understanding of AO30 tethered running. Muscle oxygenation responses showed rapid adjustments (both, during and after AO30) in a tissue-dependence manner, with very low tissue saturation index observed in biceps brachii during exercise when compared to vastus lateralis. Significant correlations between peak and mean blood lactate with biceps brachii oxygenation indicate an important participation of less active muscle during and after high-intensity AO30 tethered running.
Co-targeting EGFR and mTOR with gefitinib and everolimus in triple-negative breast cancer cells
Authors: El Guerrab Abderrahim , Bamdad Mahchid , Bignon Yves-Jean , Penault-Llorca Frédérique , Aubel Corinne
Published: April 2020

Triple-negative breast cancers (TNBC) are unlikely to respond to hormonal therapies and anti-HER2-targeted therapies. TNBCs overexpress EGFR and exhibit constitutive activation of the PI3K/AKT/mTOR signalling pathway. We hypothesized that simultaneously blocking EGFR and mTOR could be a potential therapeutic strategy for the treatment of TNBC. We examined the antitumour activity of the mTOR inhibitor everolimus combined with the EGFR tyrosine kinase inhibitor gefitinib in TNBC cell with or without activating mutations in the PI3K/AKT/mTOR signalling pathway. We demonstrated that everolimus and gefitinib induced synergistic growth inhibition in the PI3K and PTEN-mutant CAL-51 cell line but not in the PTEN-null HCC-1937 cell line. The antiproliferative effect was associated with synergistic inhibition of mTOR and P70S6K phosphorylation, as well as a significant reduction in 4E-BP1 activation in the CAL-51 cell line. We also showed that combination therapy significantly inhibited cell cycle progression and increased apoptosis in this cell line. Gene and protein expression analysis revealed significant downregulation of cell cycle regulators after exposure to combined treatment. Collectively, these results suggested that dual inhibition of mTOR and EGFR may be an effective treatment for TNBC with activating mutations of PI3K.
Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals
Authors: Oluwagbemigun Kolade , Anesi Andrea , Ulaszewska Maria , Clarke Gerard , Alexy Ute , Schmid Matthias , Roden Michael , Herder Christian , Mattivi Fulvio , Nöthlings Ute
Published: April 2020

Amino acid metabolites in biofluids are associated with high body mass index (BMI) and cardiometabolic abnormalities. However, prospective investigations regarding these associations are few, particularly among young individuals. Moreover, little is presently known about the impact of long-term high BMI. Using data from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study (111 males and 107 females), we prospectively investigated relations between repeatedly measured urinary levels of 33 metabolites and (1) previously identified long-term BMI trajectory groups from childhood into late adolescence and (2) cardiometabolic risk markers in late adolescence–young adulthood, in sex-specific linear mixed regression models. Males with long-term overweight had lower indole-3-acetic acid when compared to others. Further, methionine, isoleucine, tryptophan, xanthurenic acid, and indole-3-carboxaldehyde were negatively associated with C-reactive protein (CRP), but 5-hydroxyindole-3-acetic acid was positively associated with CRP. No associations were observed in females. Long-term overweight from childhood into late adolescence is associated with decreased urinary levels of gut bacteria-derived indole-3-acetic acid, and several urinary amino acids, including gut bacteria-derived indole-3-carboxaldehyde are associated with elevated CRP later on in life. Taken together, our data suggest that indole metabolites, and their gut bacteria producers play potentially important roles in overweight-related inflammation.
Fluid shear stress coupled with narrow constrictions induce cell type-dependent morphological and molecular changes in SK-BR-3 and MDA-MB-231 cells
Authors: Cognart Hamizah Ahmad , Viovy Jean-Louis , Villard Catherine
Published: April 2020

Cancer mortality mainly arises from metastases, due to cells that escape from a primary tumor, circulate in the blood as circulating tumor cells (CTCs), permeate across blood vessels and nest in distant organs. It is still unclear how CTCs overcome the harsh conditions of fluid shear stress and mechanical constraints within the microcirculation. Here, a minimal model of the blood microcirculation was established through the fabrication of microfluidic channels comprising constrictions. Metastatic breast cancer cells of epithelial-like and mesenchymal-like phenotypes were flowed into the microfluidic device. These cells were visualized during circulation and analyzed for their dynamical behavior, revealing long-lived plastic deformations and significant differences in biomechanics between cell types. γ-H2AX staining of cells retrieved post-circulation showed significant increase of DNA damage response in epithelial-like SK-BR-3 cells, while gene expression analysis of key regulators of epithelial-to-mesenchymal transition revealed significant changes upon circulation. This work thus documents first results of the changes at the cellular, subcellular and molecular scales induced by the two main mechanical stimuli arising from circulatory conditions, and suggest a significant role of this still elusive step of the metastatic cascade in cancer cells heterogeneity and aggressiveness.
Detection and imaging of gadolinium accumulation in human bone tissue by micro- and submicro-XRF
Authors: Turyanskaya Anna , Rauwolf Mirjam , Pichler Vanessa , Simon Rolf , Burghammer Manfred , Fox Oliver J. L. , Sawhney Kawal , Hofstaetter Jochen G. , Roschger Andreas , Roschger Paul , Wobrauschek Peter , Streli Christina
Published: April 2020

Gadolinium-based contrast agents (GBCAs) are frequently used in patients undergoing magnetic resonance imaging. In GBCAs gadolinium (Gd) is present in a bound chelated form. Gadolinium is a rare-earth element, which is normally not present in human body. Though the blood elimination half-life of contrast agents is about 90 minutes, recent studies demonstrated that some tissues retain gadolinium, which might further pose a health threat due to toxic effects of free gadolinium. It is known that the bone tissue can serve as a gadolinium depot, but so far only bulk measurements were performed. Here we present a summary of experiments in which for the first time we mapped gadolinium in bone biopsy from a male patient with idiopathic osteoporosis (without indication of renal impairment), who received MRI 8 months prior to biopsy. In our studies performed by means of synchrotron radiation induced micro- and submicro-X-ray fluorescence spectroscopy (SR-XRF), gadolinium was detected in human cortical bone tissue. The distribution of gadolinium displays a specific accumulation pattern. Correlation of elemental maps obtained at ANKA synchrotron with qBEI images (quantitative backscattered electron imaging) allowed assignment of Gd structures to the histological bone structures. Follow-up beamtimes at ESRF and Diamond Light Source using submicro-SR-XRF allowed resolving thin Gd structures in cortical bone, as well as correlating them with calcium and zinc.
The establishment of neuron-specific enolase reference interval for the healthy population in southwest China
Authors: Miao Qiang , Cai Bei , Gao Xuedan , Su Zhenzhen , Zhang Junlong
Published: April 2020

To investigate and establish a reference interval (RI) of neuron-specific enolase (NSE) in southwest China’s healthy population by using the laboratory information system database. A total of 86957 periodic health examination individuals of the medical examination center in West China Hospital from 2016 to 2018 were included in the study. We used the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate the outliers, and the normal distribution method and the nonparametric method to estimate the 95% distribution RI. The NSE 95% distribution RI we established in healthy populations in southwest China through normal distribution and nonparametric method were 0–19.64 ng/ml and 0–20.46 ng/ml, respectively. The obtained RIs verification conformed to the standard and was significantly different from the reagent instruction(P < 0.05). The RI established by the nonparametric method was superior to the RI of the normal distribution method and reagent instruction(P < 0.05). We initially established an NSE RI that was suitable for the healthy southwest China population. The Box-Cox conversion combined with the Tukey method and nonparametric method is a reliable and straightforward indirect method for reference interval acquisition, which is suitable for the promotion and application of clinical laboratory.
Analysis of the inhibiting activity of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) on matrix metalloproteinases
Authors: Mendes Soraia R. , Amo-Maestro Laura del , Marino-Puertas Laura , Diego Iñaki de , Goulas Theodoros , Gomis-Rüth F. Xavier
Published: April 2020

Matrix metalloproteinases (MMPs) occur in 23 human paralogues with key functions in physiology, and their activity is controlled by protein inhibitors. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which is essential for embryogenesis and tumour suppression, has been reported to inhibit MMPs. Here, we developed eukaryotic and bacterial expression systems for different RECK variants and analysed their inhibitory capacity against representative MMPs in vitro. We could not detect any significant inhibition. Instead, we found that partially purified RECK from the conditioned medium of transfected Expi293F cells but not that of ExpiCHO-S or Drosophila Schneider cells contained a contaminant with proteolytic activity. The contaminant was removed through treatment with a small-molecule serine peptidase inhibitor and additional chromatographic purification. A tantamount contaminant was further detected in an equivalent expression system of the N-terminal fragment of the proteoglycan testican 3, but not in those of two other proteins. These results indicate that previous reports of inhibitory activity of recombinant RECK on MMPs, which were performed with partially purified samples, were probably masked by a coeluting contaminant present in the supernatant of HEK293-derived cells. Thus, RECK is probably not a direct inhibitor of MMP catalytic activity but may still regulate MMPs through other mechanisms.
Epicardial adipose tissue thickness is not associated with adverse cardiovascular events in patients undergoing haemodialysis
Authors: Chen Ying-Chih , Lee Wen-Hsien , Lee Meng-Kuang , Hsu Po-Chao , Tsai Wei-Chung , Chu Chun-Yuan , Lee Chee-Siong , Yen Hsueh-Wei , Lin Tsung-Hsien , Voon Wen-Chol , Lai Wen-Ter , Sheu Sheng-Hsiung , Su Ho-Ming
Published: April 2020

In non-haemodialysis (HD) patients, increased epicardial adipose tissue (EAT) thickness was significantly associated with adverse cardiovascular (CV) events. This study was designed to investigate whether EAT thickness was a useful parameter in the prediction of adverse CV events in HD patients. In addition, we also evaluated the major correlates of EAT thickness in these patients. In 189 routine HD patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV death, non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease, and hospitalization for heart failure. The follow-up period for CV events was 2.5 ± 0.7 years. Thirty-one CV events were documented. The multivariable analysis demonstrated that older age, smoking status, the presence of diabetes mellitus and coronary artery disease, and low albumin levels were independently correlated with adverse CV events. However, increased EAT thickness was not associated with adverse CV events (P = 0.631). Additionally, older age, female sex, low haemoglobin, and low early diastolic mitral annular velocity were correlated with high EAT thickness in the univariable analysis. In the multivariable analysis, older age and female sex were still correlated with high EAT thickness. In conclusion, high EAT thickness was associated with older age and female sex in the multivariable analysis in our HD patients. However, EAT thickness was not helpful in predicting adverse CV events in such patients. Further large-scale studies are necessary to verify this finding.
Age-adjusted global glomerulosclerosis predicts renal progression more accurately in patients with IgA nephropathy
Authors: Chung Chan-Sung , Lee Ji-Hye , Jang Si-Hyong , Cho Nam-Jun , Kim Wook-Joon , Heo Nam Hun , Gil Hyo-Wook , Lee Eun Young , Moon Jong-Seok , Park Samel
Published: April 2020

The Oxford classification was developed to predict the outcome of IgA nephropathy (IgAN). Based on the upper reference limit (95th percentile) for the number of globally sclerotic glomeruli (GSG) expected on biopsy according to age, we evaluated whether the prognosis of IgAN was affected by the age-calibrated numbers of GSG independent of the Oxford classification. Patients diagnosed with IgAN on renal biopsy in a single center from January 2011 to December 2018 were analyzed retrospectively. Patients with more GSG number than the upper reference limit expected on biopsy according to age were categorized in a group of GSG abnormal for age. We analyzed in two ways, calculating the median rate of decline in estimated glomerular filtration rate (eGFR) and time-to-event defined as a decline of eGFR level to 40% lower than the baseline. There were 111 patients in the group of GSG abnormal for age. In this group, the rate of eGFR decline was faster by 1.85 (3.68–0.03) ml/min/1.73 m2 per year in the fully-adjusted robust regression model. The adjusted hazard ratio for eGFR decline for renal outcome was 29.10 (2.18–388.49). The cumulative incidence of CKD progression was significantly higher, especially for those with T score of 0 in the Oxford classification. We suggest that GSG abnormal for age is an independent risk factor in predicting the renal outcome of IgAN.
The difference of burden of ectopic beats in different types of atrial fibrillation and the effect of atrial fibrillation type on stroke risk in a prospective cohort of patients with atrial fibrillation (CODE-AF registry)
Authors: Cho Seunghoon , Kim Jun , Kim Jin-Bae , Park Junbeom , Park Jin-Kyu , Kang Ki-Woon , Shim Jaemin , Choi Eue-Keun , Lee Young Soo , Park Hyung Wook , Joung Boyoung
Published: April 2020

The relationship between atrial fibrillation (AF) type and stroke risk is still controversial. We investigated the difference of burden of atrial ectopic beats in different types of AF and the effect of the AF type on stroke risk in patients with non-valvular AF. In the prospective, multicenter observational registry with more than about 10,000 AF patients, 8883 non-valvular AF patients (mean age, 67.0 years; 36% were women) with eligible follow-up visits participated. We compared the burden of ectopic beats and stroke risk between patients with paroxysmal AF (n = 5,808) and non-paroxysmal AF (n = 3,075). The patients with a non-paroxysmal type of AF were older, male-predominant and had a higher prevalence of comorbidities and had more anticoagulation and rhythm control treatment than those with paroxysmal AF. In terms of the difference in burden of ectopic beats, patients with non-paroxysmal AF had a higher proportion of atrial premature beats (APBs) (paroxysmal vs. non-paroxysmal, median 3% vs. 5%; p = 0.001) in 24 hours Holter monitoring. During a median follow-up period of 16.8 months (Interquartile range [IQR], 11.67–20.52), a total of 82 (0.92%) patients experienced ischemic stroke with incidence rates of 0.50 and 1.09 events per 100 person-year for paroxysmal and non-paroxysmal AF, respectively. The cumulative incidence of stroke events was significantly higher in non-paroxysmal AF than in paroxysmal AF (p < 0.001). The risk of ischemic stroke was higher in non-paroxysmal AF with an adjusted hazard ratio (HR) of 2.08 (95% confidence interval [CI], 1.33–3.25; p = 0.001) than in paroxysmal AF. The type of AF was associated with an increased risk of stroke, along with the difference of burden of ectopic beats (specially in APBs) in different types of AF. These results suggest that the type of AF should be considered in stroke prevention and decision-making for oral anticoagulation in AF patients.
Dyke intrusion and stress-induced collapse of volcano flanks: The example of the 2018 event at Mt. Etna (Sicily, Italy)
Authors: Giampiccolo E. , Cocina O. , De Gori P. , Chiarabba C.
Published: April 2020

Magmatic intrusions, eruptions and flank collapses are frequent processes of volcano dynamics, inter-connected at different space and time scales. The December 2018 recrudescent episode at Mt. Etna is an exemplary case where a sudden intrusive event culminated with a short eruption, intense seismicity and a shallow large strike-slip earthquake at the edge of the eastern sliding flank. Here, we show that high resolution velocity models and transient changes of VP and VP/VS resolve the magma intrusion through a dyke and local stress increase at the base of the unstable flank, inducing the collapse. Episodic brittle faulting occurs at the edge of the sliding sector, locally contributed by high fluid pressure. The feedback between magma ascent, stress changes and flank collapse is driving the volcano dynamics, with processes ranging from long term to transient episodes.
Deep Learning Predicts Total Knee Replacement from Magnetic Resonance Images
Authors: Tolpadi Aniket A. , Lee Jinhee J. , Pedoia Valentina , Majumdar Sharmila
Published: April 2020

Knee Osteoarthritis (OA) is a common musculoskeletal disorder in the United States. When diagnosed at early stages, lifestyle interventions such as exercise and weight loss can slow OA progression, but at later stages, only an invasive option is available: total knee replacement (TKR). Though a generally successful procedure, only 2/3 of patients who undergo the procedure report their knees feeling “normal” post-operation, and complications can arise that require revision. This necessitates a model to identify a population at higher risk of TKR, particularly at less advanced stages of OA, such that appropriate treatments can be implemented that slow OA progression and delay TKR. Here, we present a deep learning pipeline that leverages MRI images and clinical and demographic information to predict TKR with AUC 0.834 ± 0.036 (p < 0.05). Most notably, the pipeline predicts TKR with AUC 0.943 ± 0.057 (p < 0.05) for patients without OA. Furthermore, we develop occlusion maps for case-control pairs in test data and compare regions used by the model in both, thereby identifying TKR imaging biomarkers. As such, this work takes strides towards a pipeline with clinical utility, and the biomarkers identified further our understanding of OA progression and eventual TKR onset.
Ultradian and Infradian Rhythms in the Dynamic of Testosterone Concentration in the Serum of the White-Breasted Hedgehog Erinaceus roumanicus
Authors: Rutovskaya Marina  ;V. , Kosyreva Anna M. , Diatroptov Mikhail E.
Published: April 2020

The aim of the study was to identify ultradian (intraday) and infradian (multi-day) rhythms in the dynamics of testosterone concentration in the blood serum of white-breasted hedgehogs. Blood sampling was performed from the femoral veins of 12 male hedgehogs. We found ultradian rhythms of testosterone on both sampling dates—March 7–8 (a day length of 11 hours and 15 minutes) and May 10–11 (a day length of 16 hours). An 8-hour rhythm of testosterone concentration has been established. The acrophases were at the same times in both photoperiods and thus independent of sunset times. The study of the infradian rhythms of testosterone was daily carried out on May 22—June 3, at 07:40 to 08:50 and from June 27 to July 7, at 16:15–16:50. It revealed an infradian rhythm of the testosterone concentration with a period of 4-days in both the morning and the evening sampling. According to our previous investigation, the infradian rhythms of testosterone among individual hedgehogs, rodents and primates have the same period. That indicates the common mechanisms for their formation. In case of experimental studies, the phase of ultradian and infradian biorhythms will need to be taken into account because the testosterone concentration in acrophase is 2–4 times higher than in bathyphase.
Sex differences in auditory fear discrimination are associated with altered medial prefrontal cortex function
Authors: Day Harriet L. L. , Suwansawang Sopapun , Halliday David M. , Stevenson Carl W.
Published: April 2020

The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex (mPFC) function. PTSD is characterized by fear overgeneralization involving impaired fear regulation by safety signals. We recently found that males show fear discrimination and females show fear generalization involving reduced safety signalling after extended fear discrimination training. Here we determined if these sex differences involve altered mPFC function. Male and female rats underwent three days of auditory fear discrimination training, where one tone (CS+) was paired with footshock and another tone (CS−) was presented alone. Local field potentials were recorded from prelimbic (PL) and infralimbic (IL) mPFC during retrieval. We found that males discriminated and females generalized based on cue-induced freezing at retrieval. This was accompanied by sex differences in basal theta and gamma oscillations in PL and IL. Importantly, males also showed PL/IL theta activation during safety signalling by the CS− and IL gamma activation in response to the threat-related CS+, both of which were absent in females. These results add to growing evidence indicating that sex differences in learned fear inhibition are associated with altered mPFC function.
Association between olfactory function and inhibition of emotional competing distractors in major depressive disorder
Authors: Wang Fang , Jin Jin , Wang Jun , He Ruoqiao , Li Kaiyun , Hu Xiaonan , Li Yongchao , Zhu Yuncheng
Published: April 2020

We aimed to investigate the changes of olfaction of major depressive disorder (MDD) before and after medical treatment, and to preliminarily scrutinize the association between the olfactory function and the severity of depressive symptoms, response inhibition, and emotional responding. Forty-eight medicine-naïve MDD patients plus 33 healthy controls (HC) matched on gender, ages, and level of education, were recruited in the test group. The Chinese Smell Identification Test (CSIT), Self-reported Olfactory Scale (SROS), 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and mean reaction time/accuracy rate (ΔMRT) of emotional Stroop test were measured. The patients were assessed before the treatment (baseline) and 3 months after the treatment (follow-up). The data at the baseline level were measured then associated using multiple linear regression stepwise analysis. The MDD patients had lower scores of the CSIT and SROS and longer ΔMRT at baseline level compared to HC while the ΔMRT of MDD patients remained longer after 3-month treatment (p’s < 0.05). At the baseline level, the regression equation including age and ΔMRT of negative word-color congruent (NEG-C), was finally observed as follows: y(CSIT) = 10.676–0.063 × 1–0.002 × 2, [x1 = the age(y), x2 = the NEG-C (ms)]. The olfactory function of MDD appears to be correlated negatively with the age and the ΔMRT of negative stimuli before treatment. After the remission of MDD, the olfactory dysfunction was improved, which might be regarded as a responding phenotype of brain function of MDD rather than the emotional responding.
Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells
Authors: Calahorra Jesús , Martínez-Lara Esther , Granadino-Roldán José M. , Martí Juan M. , Cañuelo Ana , Blanco Santos , Oliver F. Javier , Siles Eva
Published: April 2020

Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.