bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased risk for tooth extraction in primary hyperparathyroidism and hypercalcemia: a population study
Authors: Koman A. , Näsman P. , Discacciati A. , Ekbom A. , Nilsson I-L. , Sandborgh-Englund G.
Published: December 2019

The aim of this study was to analyze dental comorbidities in untreated primary hyperparathyroidism (pHPT). Patients with pHPT subjected to parathyroidectomy (PTX) at Karolinska University Hospital, Stockholm, during 2011–2016 (n = 982) were selected from the Scandinavian Quality Register of Thyroid, Parathyroid and Adrenal surgery and compared to a general population cohort (n = 2944), matched for age and gender. Dental data was obtained from the Swedish Dental Health Registry for the 3 years prior to PTX. The incidence rate ratios (IRRs) of tooth loss by extraction, periodontal interventions, and dental visit rate were analyzed by Poisson regression models. In order to analyze the impact of disease severity, the PHPT cohort was sub-grouped based on preoperative serum levels of ionized calcium (S-Ca2+). The total number of tooth extractions, periodontal interventions, and number of visits were similar in the cohorts. PHPT patients belonging to the quartile with the highest S-Ca2+ (≥ 1.51 mmol/L) had increased risk for tooth extraction (IRR 1.85; 95% CI 1.39–2.46). Female gender independently amplified the risk (IRR 1.341, P < 0.027). This study indicates an association between pHPT and oral disorders reflected by increased tooth loss by extraction related to high S-Ca2. Increased awareness of dental comorbidity in primary hyperparathyroidism may benefit a large group of patients with a common disease through earlier detection and prevention.
Longitudinal studies examining the impact of prenatal and subsequent episodes of maternal depression on offspring antisocial behaviour
Authors: Morgan Joanne E. , Channon Sue , Penny Helen , Waters Cerith S.
Published: December 2019

Maternal depression is associated with adverse child outcomes including antisocial behaviour (ASB). Prospective longitudinal studies have focused on the timing and cumulative exposure to maternal depression to further delineate the association and mechanisms of effect. The objective of this systematic review was to synthesise and evaluate the findings of longitudinal studies of maternal depression and offspring antisocial behaviour. Three databases were searched (Psychinfo, Web of Science, and Medline). Twenty of 5936 studies met inclusion criteria. Study quality was assessed using the Critical Appraisal Skills Programme criteria [Critical Appraisal Skills Programme (2017) CASP (cohort observation checklist). https://casp-uk.net/wpcontent/uploads/2018/01/CASP-Cohort-Study-Checklist.pdf]. Results of individual studies were highly varied, using diverse analytical approaches and not all studies explored the independent effects of different episodes. Only three studies examined hypothesised mechanisms. Prenatal, postnatal, and later episodes of depression were all predictive of antisocial outcomes. One particular time period of depression exposure did not emerge as more predictive of offspring ASB than another. However, measures of maternal depression after the perinatal period were limited and typically included a one-off assessment of mothers’ depressive symptoms that was concurrent to the assessment of offspring ASB. When cumulative exposure to maternal depression and specific timing effects were measured within the same study it was cumulative exposure that conferred the greatest risk for offspring ASB—particularly when this exposure began during the perinatal period. Findings are discussed in terms of limitations in the literature and highlight the need for future research to examine the biological and environmental mechanisms that underpin associations between maternal depression and offspring antisocial behaviour during different stages of development.
Study on the prediction of stock price based on the associated network model of LSTM
Authors: Ding Guangyu , Qin Liangxi
Published: December 2019

Stock market has received widespread attention from investors. It has always been a hot spot for investors and investment companies to grasp the change regularity of the stock market and predict its trend. Currently, there are many methods for stock price prediction. The prediction methods can be roughly divided into two categories: statistical methods and artificial intelligence methods. Statistical methods include logistic regression model, ARCH model, etc. Artificial intelligence methods include multi-layer perceptron, convolutional neural network, naive Bayes network, back propagation network, single-layer LSTM, support vector machine, recurrent neural network, etc. But these studies predict only one single value. In order to predict multiple values in one model, it need to design a model which can handle multiple inputs and produces multiple associated output values at the same time. For this purpose, it is proposed an associated deep recurrent neural network model with multiple inputs and multiple outputs based on long short-term memory network. The associated network model can predict the opening price, the lowest price and the highest price of a stock simultaneously. The associated network model was compared with LSTM network model and deep recurrent neural network model. The experiments show that the accuracy of the associated model is superior to the other two models in predicting multiple values at the same time, and its prediction accuracy is over 95%.
Performance bookkeeping for aircraft configurations with fuselage wake-filling propulsion integration
Authors: Habermann A. L. , Bijewitz J. , Seitz A. , Hornung M.
Published: December 2019

The aim of this research is the identification of a unified bookkeeping and evaluation scheme for the integrated performance analysis of a boundary layer ingesting (BLI) concept in the conceptual design phase. A thorough review and classification of existing performance bookkeeping schemes suits as a basis for the derivation of a bookkeeping scheme suitable for the initial sizing as well as detailed design analysis during the conceptual phase of a BLI concept. Figures of merit for the concept performance assessment are evaluated with regard to the requirements of aircraft multidisciplinary conceptual design. Based on the survey, the most practical integral momentum conservation approach is deduced and its application to integrated conceptual sizing and a subsequent design analysis is evaluated. The proposed scheme is universally applicable to coupled airframe–propulsion aircraft concepts, compatible with standard aircraft and propulsion system sizing tools and, under certain assumptions, deployable for low- and high-fidelity evaluation methods. Finally, several figures of merit are selected to cover a range of design aspects in the BLI evaluation.
Triterpenoids from Ainsliaea latifolia and Their Cyclooxyenase-2 (COX-2) Inhibitory Activities
Authors: Yuan Wen-Lin , Dong Xue-Yun , Huang Zheng-Rui , Xiao Si-Jia , Ye Ji , Tian Xin-Hui , Li Hui-Liang , Shen Yun-Heng , Zhang Wei-Dong
Published: December 2019

Eight new triterpenoids were isolated from Ainsliaea latifolia. The structures of these compounds were elucidated by interpretation of spectroscopic data, including HRESIMS and NMR data. Compounds 4–6 are identified as rare trinorcucurbitane or tetranorcucurbitane triterpenoids. The absolute configurations of compounds 1 and 2 were confirmed by Snatzke’s method. All compounds were evaluated for their inhibition against cyclooxyenase-2 (COX-2), in which compound 4 showed significant inhibitory effect against COX-2 with IC50 value of 3.98 ± 0.32 μM, comparable to that of positive control NS-398 (IC50 4.14 ± 0.28 μM).

Graphic Abstract
Performance optimization of polymeric porous membrane-based liquid desiccant air dehumidifier used in air conditioning system
Authors: Jafarpour Ali Mohammad , Fazelpour Farivar , Mousavi Seyyed Abbas
Published: December 2019

In this study an experimental design was developed to optimize the performance and structure of a membrane-based parallel-plate liquid desiccant dehumidifier used in air conditioning regeneration system which operates under high humidity weather conditions. We conducted a series of polymeric porous membranes with different compositions fabricated that were prepared with various weight percentages of polysulfone (PSU), mixed with N-methyl-2-pyrrolidone (NMP) and dimethyl form amide (DMF) solvents. Furthermore, the designed experiments were performed under various operating conditions, indicating that the dehumidification efficiency declines with increasing flow rate, temperature, and humidity. Consequently, a membrane with optimized porosity and moisture permeability was selected which resulted in eliminating the carryover of solution droplets in the air, largely due to separating the flow condition of liquid desiccant (Li Cl) and air. This specific design is also greatly benefited by removing the water vapor from the air stream. The results of mathematical model simulations indicate that the DMF solvent had higher dehumidification capability compared with that of NMP under the optimized operating conditions. Additionally, it can clarify the porosity of the membrane which plays a significant role in the overall performance. Therefore, the fabricated membrane produces fresh cool air, and it can be applied as a guiding sample for designing the membrane-based dehumidifier with improved performance.
The Canons of Fantasy
Authors: Moran Patrick
Published: December 2019

Despite publishing endeavours such as the Ballantine Adult Fantasy Series in the 1970s and Fantasy Masterworks in the early 2000s, the canon of modern fantasy is still very much in flux. This Element examines four key questions raised by the prospect of a fantasy canon: the way in which canon and genre influence each other; the overwhelming presence of Tolkien in any discussion of the classics of fantasy; the multi-media and transmedia nature of the field; and the push for a more inclusive and diverse canon.
Sind Fortbildungsmaßnahmen zu linguistisch fundierter Sprachförderung wirksam?
Authors: Lemmer Rabea , Huschka Sina Simone , Geyer Sabrina , Brandenburg Janin , Ehm Jan-Henning , Lausecker Alina , Schulz Petra , Hasselhorn Marcus
Published: December 2019

Zusammenfassung. Ziel des Beitrags ist es, die Effektivität einer Fortbildungsmaßnahme zu linguistisch fundierter Sprachförderung zu untersuchen. In einem Prätest-Posttest-Kontrollgruppen-Design wurden die Sprachförderkompetenz von Fachkräften ( n = 33) und die produktiven Sprachfähigkeiten der von ihnen geförderten mehrsprachigen Kinder ( n = 78) in den Bereichen Satzstruktur und Kasus erhoben. Die Sprachförderkompetenz der pädagogischen Fachkräfte aus der Experimentalgruppe ( n = 18) war nach Abschluss der Fortbildungsmaßnahme signifikant höher als die Sprachförderkompetenz der pädagogischen Fachkräfte, die keine Fortbildung besucht haben ( n = 15); zudem verbesserten sich die geförderten Kinder im Bereich der Satzstruktur signifikant gegenüber Kindern, deren Fachkräfte keine Fortbildung besuchten. Für den Erwerbsbereich Kasus gab es keine Effekte.
Fachkraft-Kind-Dialoge im Freispiel: Wer hat das Wort?
Authors: Cordes Anne-Kristin , Radan Julia , Wirts Claudia
Published: December 2019

Zusammenfassung. Das Freispiel gilt als eine Situation im Kindergartenalltag, in der die Lernunterstützung eher gering ausfällt. Um das mögliche Potential für sprachliche Lernunterstützung beurteilen zu können, widmet sich die vorliegende Studie der Frage, wie sich Fachkraft-Kind-Dialoge im Freispiel gestalten. Dazu wurden Gesprächsdominanz, -länge und -hauptzweck bestimmt. Die Analyse von 14 Transkripten ergab, dass Kinder zwar mehr Redebeiträge äußerten als Fachkräfte, Fachkräfte jedoch deutlich umfangreichere Redebeiträge produzierten. Die durchschnittliche Gesprächslänge umfasste fünf bis sechs Sprecherwechsel. Bei größerer Gruppengröße sanken die Gesprächsanteile der Kindergruppe. Am häufigsten wurden Gespräche zur sprachlichen Handlungssteuerung und -regulierung, zur emotionalen Anteilnahme und zu organisatorischen Zwecken geführt. Nur 8 % der Gespräche widmeten sich dem kognitiven Austausch von Ideen, Gedanken und Gefühlen. Diese Gespräche umfassten im Mittel zwölf Redebeiträge und waren deutlich länger als Gespräche zu anderen Zwecken. Das Freispiel birgt Gelegenheiten für den Ausbau solcher Dialoge. Eine strukturelle Verringerung der Anzahl der an einer Aktivität teilnehmenden Kinder könnte die kindliche Gesprächsbeteiligung weiter erhöhen.
Gemeinsame Sprachförderung am Übergang Kita-Grundschule: Handlungsorientierungen und Sprachförderkompetenzen von Fach- und Lehrkräften
Authors: Kämpfe Karin , Betz Tanja , Kucharz Diemut , Rezagholinia Sandra
Published: December 2019

Zusammenfassung. Mit dem bildungspolitischen Ziel durchgängiger Sprachförderung sind wachsende Anforderungen an Fach- und Lehrkräfte verbunden. Im Beitrag werden ihre sprachförderbezogenen Handlungsorientierungen und Kompetenzen fokussiert. In der Zusammenführung qualitativer und quantitativer Daten aus der SPRÜNGE-Studie zeigt sich ein Zusammenhang zwischen Orientierungen und Kompetenzen, der Ausgangspunkt für die Gestaltung von (gemeinsamen) Fortbildungen am Übergang sein kann.
Low‐Latitude Whistler‐Wave Spectra and Polarization From VEFI and CINDI Payloads on C/NOFS Satellite
Authors: Jacobson Abram R. , Holzworth Robert H. , Pfaff Robert , Heelis Roderick
Published: December 2019

The Communication/Navigation Outage Forecast System (C/NOFS) satellite's VEFI payload performed frequent recordings of the vector electric field in the band 0–16 kHz during the epoch 2008–2014. The Vector Electric Field Instrument (VEFI) was supported by ion‐composition data from the Coupled Ion Neutral Dynamics Investigation (CINDI) instrument. We focus here on statistics of these “burst‐mode” recordings, of which 6,890 (mostly ~12‐s duration) records meet stringent quality‐control criteria, allowing inference of the wave vector k and its orientation relative to the Earth's magnetic field B0. The 6,890 records occur between ±13° (geographic) latitude and between ~ 400‐ and 850‐km altitude, mostly in the topside ionosphere. The wave activity is dominated by terrestrial lightning. We analyze the whistler‐wave intensity and polarization for each pixel in the time‐frequency spectrogram for each record. We then gather weighted statistics on wave polarization, naturally weighted by wave intensity. In this manner we arrive at statistical results that represent the bulk of the energy flow due to whistler waves. Despite rather nonstationary statistics, we can reach three empirical results.

We see no evidence of a low‐latitude suppression of whistler‐wave activity, in contrast to the predictions of models of transmission through a laminar ionosphere.

The wave vector polar angle is always in the range 40° to 90° from parallel to B0. This indicates that the propagation at low latitudes is dominated by oblique, not ducted, whistlers.

At the lowest magnetic latitudes, the wave vector polar angle with respect to B0 becomes nearly 90°.
Individual prediction of psychotherapy outcome in posttraumatic stress disorder using neuroimaging data
Authors: Zhutovsky Paul , Thomas Rajat M. , Olff Miranda , van Rooij Sanne J. H. , Kennis Mitzy , van Wingen Guido A. , Geuze Elbert
Published: December 2019

Trauma-focused psychotherapy is the first-line treatment for posttraumatic stress disorder (PTSD) but 30–50% of patients do not benefit sufficiently. We investigated whether structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) data could distinguish between treatment responders and non-responders on the group and individual level. Forty-four male veterans with PTSD underwent baseline scanning followed by trauma-focused psychotherapy. Voxel-wise gray matter volumes were extracted from the structural MRI data and resting-state networks (RSNs) were calculated from rs-fMRI data using independent component analysis. Data were used to detect differences between responders and non-responders on the group level using permutation testing, and the single-subject level using Gaussian process classification with cross-validation. A RSN centered on the bilateral superior frontal gyrus differed between responders and non-responder groups (PFWE < 0.05) while a RSN centered on the pre-supplementary motor area distinguished between responders and non-responders on an individual-level with 81.4% accuracy (P < 0.001, 84.8% sensitivity, 78% specificity and AUC of 0.93). No significant single-subject classification or group differences were observed for gray matter volume. This proof-of-concept study demonstrates the feasibility of using rs-fMRI to develop neuroimaging biomarkers for treatment response, which could enable personalized treatment of patients with PTSD.
Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig
Authors: Fjordbakk Cathrine T. , Miranda Jason A. , Sokal David , Donegà Matteo , Viscasillas Jaime , Stathopoulou Thaleia-Rengina , Chew Daniel J. , Perkins Justin D.
Published: December 2019

Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.
Genetics of cognitive trajectory in Brazilians: 15 years of follow-up from the Bambuí-Epigen Cohort Study of Aging
Authors: Gouveia Mateus H. , Cesar Cibele C. , Santolalla Meddly L. , Anna Hanaisa P. Sant , Scliar Marilia O. , Leal Thiago P. , Araújo Nathalia M. , Soares-Souza Giordano B. , Magalhães Wagner C. S. , Mata Ignacio F. , Ferri Cleusa P. , Castro-Costa Erico , Mbulaiteye Sam M. , Tishkoff Sarah A. , Shriner Daniel , Rotimi Charles N. , Tarazona-Santos Eduardo , Lima-Costa Maria Fernanda
Published: December 2019

Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (β = −0.044, SE = 0.01, p = 7.5 × 10−5) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer’s disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.
Peripheral blood mononuclear cell transcriptomes reveal an over-representation of down-regulated genes associated with immunity in HIV-exposed uninfected infants
Authors: Musimbi Zaneta D. , Rono Martin K. , Otieno James R. , Kibinge Nelson , Ochola-Oyier Lynette Isabella , de Villiers Etienne Pierre , Nduati Eunice W.
Published: December 2019

HIV-exposed uninfected (HEU) infants are disproportionately at a higher risk of morbidity and mortality, as compared to HIV-unexposed uninfected (HUU) infants. Here, we used transcriptional profiling of peripheral blood mononuclear cells to determine immunological signatures of in utero HIV exposure. We identified 262 differentially expressed genes (DEGs) in HEU compared to HUU infants. Weighted gene co-expression network analysis (WGCNA) identified six modules that had significant associations with clinical traits. Functional enrichment analysis on both DEGs and the six significantly associated modules revealed an enrichment of G-protein coupled receptors and the immune system, specifically affecting neutrophil function and antibacterial responses. Additionally, malaria pathogenicity genes (thrombospondin 1-(THBS 1), interleukin 6 (IL6), and arginine decarboxylase 2 (ADC2)) were down-regulated. Of interest, the down-regulated immunity genes were positively correlated to the expression of epigenetic factors of the histone family and high-mobility group protein B2 (HMGB2), suggesting their role in the dysregulation of the HEU transcriptional landscape. Overall, we show that genes primarily associated with neutrophil mediated immunity were repressed in the HEU infants. Our results suggest that this could be a contributing factor to the increased susceptibility to bacterial infections associated with higher morbidity and mortality commonly reported in HEU infants.
Phase transitions, collective emotions and decision-making problem in heterogeneous social systems
Authors: Tsarev Dmitriy , Trofimova Anastasiia , Alodjants Alexander , Khrennikov Andrei
Published: December 2019

The paper considers the problem of collective decision-making as a second order phase-transition, which occurs in heterogeneous information-oriented communities possessing frequent information exchange between individuals. We examine the quantum-like model of simplified two-level cognitive systems (TLCS) interacting with a socially important (contextual) information field. The model exploits approaches to the modern social cohesion framework. We refer to some target network community, which is in close interaction (e.g. message exchange) with “reservour” (large network community) possessing infinite degree of freedom. We introduce a new approach for valence and arousal variables, used in cognitive sciences for the description of collective emotion states. We express them via collective polarization and population imbalance respectively. The model predicts a super-radiant phase transition for target network community leading to coherent polarization establishment in the socium. The valence and arousal parameters can be evaluated from actrors behaviour in social network communities as a result of immediate response (decision-making) to some notable news. We introduce Gaussian and Levy distribution functions to reveal the influence of social community inhomogeneity on decision-making features. We show that a critical (social) temperature is determined by the population imbalance (valence), detuning, field coupling strength parameter and relay to conditions of social polarization establishment. We predict coherent social energy release in a community without inversion due to its specific properties close to the superfluid paradigm in quantum physics, or social cohesion in sociology. We establish a connection of our model to the recently presented quantum-like model of the social laser to describe the waves of social protests as the result of collective decision-making process in the system with inversion of population in mental states. Finally, we compare our model with existing social impact models, a.k.a. cellular automata models, in the limit when social community perceives information field in the state induced by large information reservoir (mass-media). Notably, eliminating quantized field we lose important information how collective emotions (arousal) form in social community.
Assessment of TP53 lesions for p53 system functionality and drug resistance in multiple myeloma using an isogenic cell line model
Authors: Munawar Umair , Roth Markus , Barrio Santiago , Wajant Harald , Siegmund Daniela , Bargou Ralf C. , Kortüm K. Martin , Stühmer Thorsten
Published: December 2019

Recent advances in molecular diagnostics have shown that lesions affecting both copies of the gene for tumor suppressor protein 53 (TP53) count among the most powerful predictors for high-risk disease in multiple myeloma (MM). However, the functional relevance and potential therapeutic implications of single hits to TP53 remain less well understood. Here, we have for the first time approximated the different constellations of mono- and bi-allelic TP53 lesions observed in MM patients within the frame of a single MM cell line model and assessed their potential to disrupt p53 system functionality and to impart drug resistance. Both types of common first hit: point mutation with expression of mutant p53 protein or complete loss of contribution from one of two wildtype alleles strongly impaired p53 system functionality and increased resistance to melphalan. Second hits abolished remaining p53 activity and increased resistance to genotoxic drugs even further. These results fit well with the clinical drive to TP53 single- and double-hit disease in MM patients, provide a rationale for the most commonly observed double-hit constellation (del17p+ TP53 point mutation), and underscore the potential increases in MM cell malignancy associated with any type of initial TP53 lesion.
Changes in emm types and superantigen gene content of Streptococcus pyogenes causing invasive infections in Portugal
Authors: Friães A. , Melo-Cristino J. , Ramirez M. ,   Portuguese Group for the Study of Streptococcal Infections, Vaz Teresa , Gião Marília , Ferreira Rui , Fonseca Ana Buschy , Oliveira Henrique , Silva Ana Cristina , Costa Hermínia , Pinto Margarida , Chantre Odete , Marques João , Peres Isabel , Daniel Isabel , Canas Ema , Ferreira Teresa , Marcelo Cristina , Monteiro Lurdes , Lito Luís Marques , Marques Teresa , Martins Filomena , Pessanha Maria Ana , Gonçalves Elsa , Morais Teresa , Lopes Paulo , Felício Luísa , Lameirão Angelina , Vieira Ana Paula Mota , Tomaz Margarida , Bento Rosa , Ramos Maria Helena , Castro Ana Paula , Fonseca Fernando , Castro Ana Paula , Ribeiro Graça , Tomé Rui , Pontes Celeste , Boaventura Luísa , Canhoto Nuno , Afonso Teresa , Pina Teresa , Peres Helena , Fontes Ilse , Martinho Paulo , Domingos Ana , Marrão Gina , Grossinho José , Ribeiro Manuela , Faustino Alberta , Alves Adelaide , Pinheiro Maria Paula , Semedo R. , Coutinho Adriana , Cabral Luísa , Neto Olga , Sancho Luísa , Diogo José , Rodrigues Ana , Nascimento Isabel , Ramalheira Elmano , Bessa Fernanda , Marques I. , Ribeiro José Miguel , Read Maria Antónia , Alves Valquíria , Raposo Engrácia , Magalhães Maria Lurdes , Rochas Helena , Silva Anabela , Rodrigues Margarida , Meneses Maria Favila , de Sousa José Germano , Viana Mariana Bettencourt , Terra Isaura , Rodrigues Vitória , Pereira Patrícia , Duarte Jesuína , Pinto Paula , Moreira Ezequiel , Ferreira João Ataíde , Vicente Adília , Paixão Paulo , Novais Natália
Published: December 2019

Fluctuations in the clonal composition of Group AStreptococcus(GAS) have been associated with the emergence of successful lineages and with upsurges of invasive infections (iGAS). This study aimed at identifying changes in the clones causing iGAS in Portugal. Antimicrobial susceptibility testing,emmtyping and superantigen (SAg) gene profiling were performed for 381 iGAS isolates from 2010–2015. Macrolide resistance decreased to 4%, accompanied by the disappearance of the M phenotype and an increase of the iMLSBphenotype. The dominantemmtypes were:emm1 (28%),emm89 (11%),emm3 (9%),emm12 (8%), andemm6 (7%). There were no significant changes in the prevalence of individualemmtypes,emmclusters, or SAg profiles when comparing to 2006–2009, although an overall increasing trend was recorded during 2000–2015 foremm1,emm75, andemm87. Short-term increases in the prevalence ofemm3,emm6, andemm75 may have been driven by concomitant SAg profile changes observed within theseemmtypes, or reflect the emergence of novel genomic variants of the sameemmtypes carrying different SAgs.
Thawed Mesenchymal Stem Cell Product Shows Comparable Immunomodulatory Potency to Cultured Cells In Vitro and in Polymicrobial Septic Animals
Authors: Tan Yuan , Salkhordeh Mahmoud , Wang Jia-Pey , McRae Andrea , Souza-Moreira Luciana , McIntyre Lauralyn , Stewart Duncan J. , Mei Shirley H. J.
Published: December 2019

Mesenchymal stem cells (MSCs) have been shown to exert immunomodulatory effects in both acute and chronic diseases. In acute inflammatory conditions like sepsis, cell therapy must be administered within hours of diagnosis, requiring “off-the-shelf” cryopreserved allogeneic cell products. However, their immunomodulatory potency, particularly in abilities to modulate innate immune cells, has not been well documented. Herein we compared the stabilities and functionalities of cultured versus thawed, donor-matched MSCs in modulating immune responses in vitro and in vivo. Cultured and thawed MSCs exhibited similar surface marker profiles and viabilities at 0 hr; however, thawed MSCs exhibited higher levels of apoptotic cells beyond 4 hrs. In vitro potency assays showed no significant difference between the abilities of both MSCs (donor-matched) to suppress proliferation of activated T cells, enhance phagocytosis of monocytes, and restore endothelial permeability after injury. Most importantly, in animals with polymicrobial sepsis, both MSCs significantly improved the phagocytic ability of peritoneal lavage cells, and reduced plasma levels of lactate and selected inflammatory cytokines without significant difference between groups. These results show comparable in vitro and in vivo immunomodulatory efficacy of thawed and fresh MSC products, providing further evidence for the utility of a cryopreserved MSC product for acute inflammatory diseases.
Exploring the microbial biotransformation of extraterrestrial material on nanometer scale
Authors: Milojevic Tetyana , Kölbl Denise , Ferrière Ludovic , Albu Mihaela , Kish Adrienne , Flemming Roberta L. , Koeberl Christian , Blazevic Amir , Zebec Ziga , Rittmann Simon K.-M. R. , Schleper Christa , Pignitter Marc , Somoza Veronika , Schimak Mario P. , Rupert Alexandra N.
Published: December 2019

Exploration of microbial-meteorite redox interactions highlights the possibility of bioprocessing of extraterrestrial metal resources and reveals specific microbial fingerprints left on extraterrestrial material. In the present study, we provide our observations on a microbial-meteorite nanoscale interface of the metal respiring thermoacidophile Metallosphaera sedula. M. sedula colonizes the stony meteorite Northwest Africa 1172 (NWA 1172; an H5 ordinary chondrite) and releases free soluble metals, with Ni ions as the most solubilized. We show the redox route of Ni ions, originating from the metallic Ni° of the meteorite grains and leading to released soluble Ni2+. Nanoscale resolution ultrastructural studies of meteorite grown M. sedula coupled to electron energy loss spectroscopy (EELS) points to the redox processing of Fe-bearing meteorite material. Our investigations validate the ability of M. sedula to perform the biotransformation of meteorite minerals, unravel microbial fingerprints left on meteorite material, and provide the next step towards an understanding of meteorite biogeochemistry. Our findings will serve in defining mineralogical and morphological criteria for the identification of metal-containing microfossils.
ZnO nanocrystals derived from organometallic approach: Delineating the role of organic ligand shell on physicochemical properties and nano-specific toxicity
Authors: Wolska-Pietkiewicz Małgorzata , Tokarska Katarzyna , Wojewódzka Anna , Wójcik Katarzyna , Chwojnowska Elżbieta , Grzonka Justyna , Cywiński Piotr J. , Chudy Michał , Lewiński Janusz
Published: December 2019

The surface organic ligands have profound effect on modulation of different physicochemical parameters as well as toxicological profile of semiconductor nanocrystals (NCs). Zinc oxide (ZnO) is one of the most versatile semiconductor material with multifarious potential applications and systematic approach to in-depth understand the interplay between ZnO NCs surface chemistry along with physicochemical properties and their nano-specific toxicity is indispensable for development of ZnO NCs-based devices and biomedical applications. To this end, we have used recently developed the one-pot self-supporting organometallic (OSSOM) approach as a model platform to synthesize a series of ZnO NCs coated with three different alkoxyacetate ligands with varying the ether tail length which simultaneously act as miniPEG prototypes. The ligand coating influence on ZnO NCs physicochemical properties including the inorganic core size, the hydrodynamic diameter, surface charge, photoluminescence (quantum yield and decay time) and ZnO NCs biological activity toward lung cells was thoroughly investigated. The resulting ZnO NCs with average core diameter of 4-5 nm and the hydrodynamic diameter of 8-13 nm exhibit high photoluminescence quantum yield reaching 33% and a dramatic slowing down of charge recombination up to 2.4 µs, which is virtually unaffected by the ligand’s character. Nano-specific ZnO NCs-induced cytotoxicity was tested using MTT assay with normal (MRC-5) and cancer (A549) human lung cell lines. Noticeably, no negative effect has been observed up to the NCs concentration of 10 µg/mL and essentially very low negative toxicological impact could be noticed at higher concentrations. In the latter case, the MTT data analysis indicate that there is a subtle interconnection between inorganic core-organic shell dimensions and toxicological profile of ZnO NCs (strikingly, the NCs coated by the carboxylate bearing a medium ether chain length exhibit the lowest toxicity level). The results demonstrate that, when fully optimized, our organometallic self-supporting approach can be a highly promising method to obtain high-quality and bio-stable ligand-coated ZnO NCs.
Trade-off between motor performance and behavioural flexibility in the action selection of cricket escape behaviour
Authors: Sato Nodoka , Shidara Hisashi , Ogawa Hiroto
Published: December 2019

To survive a predator’s attack successfully, animals choose appropriate actions from multiple escape responses. The motor performance of escape response governs successful survival, which implies that the action selection in escape behaviour is based on the trade-off between competing behavioural benefits. Thus, quantitative assessment of motor performance will shed light on the biological basis of decision-making. To explore the trade-off underlying the action selection, we focused on two distinct wind-elicited escape responses of crickets, running and jumping. We first hypothesized a trade-off between speed and directional accuracy. This hypothesis was rejected because crickets could control the escape direction in jumping as precisely as in running; further, jumping had advantages with regard to escape speed. Next, we assumed behavioural flexibility, including responsiveness to additional predator’s attacks, as a benefit of running. The double stimulus experiment revealed that crickets running in the first response could respond more frequently to a second stimulus and control the movement direction more precisely compared to when they chose jumping for the first response. These data suggest that not only the motor performance but also the future adaptability of subsequent behaviours are considered as behavioural benefits, which may be used for choosing appropriate escape reactions.
Determinants of post-malarial anemia in African children treated with parenteral artesunate
Authors: Scheu Katrin , Adegnika Ayola Akim , Addo Marylyn M. , Ansong Daniel , Cramer Jakob P. , Fürst Svenja , Kremsner Peter G. , Kurth Florian , Jacobs Thomas , May Jürgen , Ramharter Michael , Sylverken Justice , Vinnemeier Christof D. , Agbenyega Tsiri , Rolling Thierry
Published: December 2019

The pathophysiology of malarial anemia is multifactorial and incompletely understood. We assessed mechanistic and risk factors for post-malarial anemia in Ghanaian and Gabonese children with severe P. falciparum malaria treated with parenteral artesunate followed by an oral artemisinin-combination therapy. We analyzed data from two independent studies in which children were followed on Days 7,14, and 28 after treatment with artesunate. Specific hematological parameters included the presence of hemoglobinopathies and erythropoietin. Presence of once-infected erythrocytes was assessed by flow cytometry in a sub-population. Of 143 children with a geometric mean parasitemia of 116,294/µL (95% CI: 95,574–141,505), 91 (88%) had anemia (Hb < 10 g/dL) at presentation. Hemoglobin increased after Day 7 correlating with increased erythropoiesis through adequate erythropoietin stimulation. 22 children (24%) remained anemic until Day 28. Post-artesunate delayed hemolysis was detected in 7 children (5%) with only minor differences in the dynamics of once-infected erythrocytes. Hyperparasitemia and hemoglobin at presentation were associated with anemia on Day 14. On Day 28 only lower hemoglobin at presentation was associated with anemia. Most children showed an adequate erythropoiesis and recovered from anemia within one month. Post-artesunate delayed hemolysis (PADH) and hyperparasitemia are associated with early malarial anemia and pre-existing anemia is the main determinant for prolonged anemia.
Skin fairness is a better predictor for impaired physical and mental health than hair redness
Authors: Flegr Jaroslav , Sýkorová Kateřina
Published: December 2019

About 1–2% of people of European origin have red hair. Especially female redheads are known to suffer higher pain sensitivity and higher incidence of some disorders, including skin cancer, Parkinson’s disease and endometriosis. Recently, an explorative study performed on 7,000 subjects showed that both male and female redheads score worse on many health-related variables and express a higher incidence of cancer. Here, we ran the preregistered study on a population of 4,117 subjects who took part in an anonymous electronic survey. We confirmed that the intensity of hair redness negatively correlated with physical health, mental health, fecundity and sexual desire, and positively with the number of kinds of drugs prescribed by a doctor currently taken, and with reported symptoms of impaired mental health. It also positively correlated with certain neuropsychiatric disorders, most strongly with learning disabilities disorder and phobic disorder in men and general anxiety disorder in women. However, most of these associations disappeared when the darkness of skin was included in the models, suggesting that skin fairness, not hair redness, is responsible for the associations. We discussed two possible explanations for the observed pattern, the first based on vitamin D deficiency due to the avoidance of sunbathing by subjects with sensitive skin, including some redheads, and second based on folic acid depletion in fair skinned subjects, again including some (a different subpopulation of) redheads. It must be emphasized, however, that both of these explanations are only hypothetical as no data on the concentration of vitamin D or folic acid are available for our subjects. Our results, as well as the conclusions of current reviews, suggest that the new empirical studies on the concentration of vitamin D and folic acids in relation to skin and hair pigmentation are urgently needed.
A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk
Authors: Adel Fahmideh Maral , Lavebratt Catharina , Tettamanti Giorgio , Schüz Joachim , Röösli Martin , Kjaerheim Kristina , Grotzer Michael A. , Johansen Christoffer , Kuehni Claudia E. , Lannering Birgitta , Schmidt Lisbeth S. , Darabi Hatef , Feychting Maria
Published: December 2019

Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06–1.49], p = 0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.
Enhanced curcumin solubility and antibacterial activity by encapsulation in PLGA oily core nanocapsules
Authors: Gao Mengqian , Long Xue , Du Jing , Teng Mengting , Zhang Weichen , Wang Yuting , Wang Xingqi , Wang Ziyuan , Zhang Peng , Li Jun
Published: December 2019

PLGA oily core CUR NCs show higher solubility, sustained release and enhanced antibacterial activity.
Photodegradation of Si-doped GaAs nanowire
Authors: Pimenta A. C. S. , Limborço H. , González J. C. , Cifuentes N. , Ramos Sérgio L. L. M. , Matinaga Franklin M.
Published: December 2019

In order to comprehend the photodegradation of GaAs NWs, we investigated their thermal oxidation process in air induced by laser heating in a broad local temperature range.
Drug-likeness of linear pentamidine analogues and their impact on the hERG K+channel – correlation with structural features
Authors: Żołek Teresa , Qile Muge , Kaźmierczak Paweł , Bloothooft Meye , van der Heyden Marcel A. G. , Maciejewska Dorota
Published: December 2019

The pentamidines with S atoms or sulfanilide groups in the linker have favorable drug-likeness parameters and low toxicity.
Microwave-assisted synthesis of 7-azaindoles via iron-catalyzed cyclization of an o-haloaromatic amine with terminal alkynes
Authors: Le Yi , Yang Zhisong , Chen Yumei , Chen Dongmei , Yan Longjia , Wang Zhenchao , Ouyang Guiping
Published: December 2019

An efficient and practical procedure was developed to prepare 7-azaindole, starting from an o-haloaromatic amine and corresponding terminal alkynes under microwave irradiation and the scope was demonstrated with a number of examples.
Solvent-tuned magnetic exchange interactions in Dy2 systems ligated by a μ-phenolato heptadentate Schiff base
Authors: Jiang Zhijie , Sun Lin , Li Min , Wu Haipeng , Xia Zhengqiang , Ke Hongshan , Zhang Yiquan , Xie Gang , Chen Sanping
Published: December 2019

Solvent-tuning changes the magnetic exchange interaction and results in different magnetic relaxation dynamics in Dy2 systems ligated by a μ-phenolato heptadentate Schiff base.
Synthetic antivenoms for snakebites: a slithering road!
Authors: Lohse Brian
Published: December 2019

Since Adam and Eve, humankind has been equally frightened and fascinated by snakes. The ancient Egyptians worshipped the cobra, which decorate sarcophagi and the famous mask of Tutankhamun. Even today, the snake is integral to the Staff of Asclepius, a symbol of medicine. To some extent, medicine has forgotten about the snake, however, bites from venomous snakes still pose a deadly impact on people in low-and middle-income countries. It is estimated that venomous snakes kill between 81,000 and 137,000 people every year, and maim around 400,000, which represents a huge impact both on families and social economics. Around 125 years ago, Calmette began to produce antivenom serum for snakebite victims. Since then, production methods have not changed significantly; then and now, antivenom is made by immunizing animals. Isolated antibodies can neutralize some of the most lethal toxins, thereby saving many lives. However, there is still a need for animals such as horses or sheep, as well as a snake farm, in order to acquire enough venom for immunization procedures. Animal-derived antibodies pose a threat, because they are foreign components injected into the human body, which can give rise to adverse immunogenic reactions. In a worst-case scenario this can lead to anaphylactic shock and death. Synthetic antivenom, is an interesting avenue, which could reduce or entirely remove the need for immunized animals and snake farms. Synthetic antivenoms could be made to high purity and eliminate many current challenges, such as batch-to-batch variations, high costs, limited shelf life and the need for ‘cold-chain’ transportation.
Shock tube‐based calibration installation for dynamic pressure transducers and performance testing
Authors: Yan Laijun , Zhang Xu , Zhang Lihu , Yao Xianghong , Qi Xinhua , Chen Yong , Zhang Long
Published: December 2019

A shock tube‐based calibration installation for dynamic pressure transducers was designed and manufactured. The hardware of the calibration installation contained a shock tube, two pressure transmitters, three transducers for velocity measurement, a temperature transmitter, two data sampling cards and a industrial personal computer, etc. The software of the calibration installation was a data sampling and data processing system. The functions of the software included test conditions monitoring, performance parameters computation, and calibration reports generation, etc. The performance of the calibration installation was tested. The test result showed that the range of the step pressure was 9.60 kPa–1.101 MPa, the maximum rise time of the step pressure was no more than 1μs, the minimum duration of the step pressure plateau was longer than 4 ms, the fluctuation of the step pressure plateau was better than ± 2%, and the maximum 2nd order expand uncertainty of the step pressure was less than 4%. Thus the calibration installation was qualified to be a shock tube‐based dynamic pressure standard because that the performance of the calibration installation was verified to meet the requirements of ‘Verification Regulation of Dynamic Pressure transducers’ and ‘Verification Regulation of Dynamic Pressure standards’.