bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pediatric Sepsis Biomarker Risk Model (PERSEVERE) Biomarkers Predict Clinical Deterioration and Mortality in Immunocompromised Children Evaluated for Infection
Authors: Jacobs L. , Berrens Z. , Stenson E. K. , Zackoff M. W. , Danziger L. A. , Lahni P. , Wong H. R. 
Published: January 2019

AbstractPediatric sepsis and bacterial infection cause significant morbidity and mortality worldwide, with immunocompromised patients being at particularly high risk of rapid deterioration and death. This study evaluated if PERSEVERE, PERSEVERE-II, or the PERSEVERE biomarkers, can reliably estimate the risk of clinical deterioration and 28-day mortality among immunocompromised pediatric patients. This is a single-center prospective cohort study conducted from July 2016 through September 2017 incorporating 400 episodes of suspected bacterial infection from the inpatient units at Cincinnati Children’s Hospital Medical Center, a large, tertiary care children’s hospital. The primary analysis assessed clinical deterioration within 72 hours of evaluation for infection. Secondarily, we assessed 28-day mortality. Clinical deterioration was seen in 15% of subjects. Twenty-eight day mortality was 5%, but significantly higher among critically ill patients. Neither PERSEVERE nor PERSEVERE-II performed well to predict clinical deterioration or 28-day mortality, thus we derived new stratification models using the PERSEVERE biomarkers with both high sensitivity and negative predictive value. In conclusion, we evaluated previously validated biomarker risk models in a novel population of largely non-critically ill immunocompromised pediatric patients, and attempted to stratify patients based on a new outcome metric, clinical deterioration. The new highly predictive models indicate common physiologic pathways to clinical deterioration or death from bacterial infection.
Frequency and Phase Characteristics of Candle Flame Oscillation
Authors: Chen Ting , Guo Xiao , Jia Ji , Xiao Jinghua 
Published: January 2019

AbstractThe combustion of candles exhibits a variety of dynamical behaviors. Binding several candles together will result in flickering of candle flames, which is generally described as a nonlinear oscillator. The impact on the frequency of the flame by several factors, such as the arrangement, the number and the asymmetry of the oscillators, is discussed. Experimental results show that the frequency gradually decreases as the number of candles increases in the case of an isolated oscillator, while alternation between the in-phase and the anti-phase synchronization appears in a coupled system of two oscillators. Moreover, envelopes in the amplitude of the oscillatory luminance are displayed when candles are coupled asymmetrically. Since the coupling between oscillators is dominated by thermal radiation, a “overlapped peaks model” is proposed to phenomenologically explain the relationship between temperature distribution, coupling strength and the collective behavior in coupled system of candle oscillators in both symmetric and asymmetric cases.
Extricating New Physics Scenarios at DUNE with Higher Energy Beams
Authors: Masud Mehedi , Bishai Mary , Mehta Poonam 
Published: January 2019

AbstractThe proposed Deep Underground Neutrino Experiment (DUNE) utilizes a wide-band on-axis tunable muon-(anti)neutrino beam with a baseline of 1300 km to search for CP violation with high precision. Given the long baseline, DUNE is also sensitive to effects due to matter induced non-standard neutrino interactions (NSI) which can interfere with the standard three-flavor oscillation paradigm. Hence it is desirable to design strategies to disentangle effects due to NSI from standard oscillations. In this article, we exploit the tunability of the DUNE neutrino beam over a wide-range of energies to devise an experimental strategy for separating oscillation effects due to NSI from the standard three-flavor oscillation scenario. Using χ2 analysis, we obtain an optimal combination of beam tunes and distribution of run times in neutrino and anti-neutrino modes that would enable DUNE to isolate new physics scenarios from the standard. We can distinguish scenarios at 3σ (5σ) level for almost all (~50%) values of δ. To the best of our knowledge, our strategy is entirely new and has not been reported elsewhere.
Macaque monkeys learn by observation in the ghost display condition in the object-in-place task with differential reward to the observer
Authors: Ferrucci Lorenzo , Nougaret Simon , Genovesio Aldo 
Published: January 2019

AbstractObservational learning has been investigated in monkeys mainly using conspecifics or humans as models to observe. Some studies attempted to clarify the social agent’s role and to test whether non-human primates could learn from observation of a non-social agent, usually mentioned as a ‘ghost display’ condition, but they reported conflicting results. To address this question, we trained three rhesus monkeys in an object-in-place task consisting of the presentation of five subsequent problems composed of two objects, one rewarded and one unrewarded, for six times, or runs. Three types of learning conditions were tested. In the individual learning condition, the monkeys performed the first run, learned from it and improved their performance in the following runs. In the social and non-social learning conditions, they observed respectively a human model and a computer performing the first run and learned by the observation of their successes or errors. In all three conditions, the monkeys themselves received the reward after correct choices only. One-trial learning occurred in all three conditions. The monkeys performed over chance in the second run in all conditions, providing evidence of non-social observational learning with differential reward in macaque monkeys using a “ghost display” condition in a cognitive task.
The E3 ubiquitin ligase Itch is required for B-cell development
Authors: Liu Xiaoling , Zhang Yu , Wei Yinxiang , Wang Zhiding , Zhu Gaizhi , Fang Ying , Zhai Bing , Xu Ruonan , Han Gencheng , Chen Guojiang , Xiao He , Hou Chunmei , Shen Beifen , Li Yan , Ma Ning , Wang Renxi 
Published: January 2019

AbstractThe E3 ubiquitin ligase Itch interacts with Foxo1 and targets it for ubiquitination and degradation during follicular helper T-cell differentiation, whereas the transcription factor Foxo1 plays a critical role in B-cell development. Thus, we proposed that Itch mediates B-cell differentiation. Unexpectedly, we found that Itch deficiency downregulated Foxo1 expression in B cells. Itch cKO (conditional knock out in B cells) mice had fewer pro-B cells in the bone marrow, more small resting IgM−IgD−B cells in the periphery, and lower B-cell numbers in the lymph nodes through decreased Foxo1-mediated IL-7Rα, RAG, and CD62L expression, respectively. Importantly, Itch deficiency reduced Foxo1 mRNA expression by up-regulating JunB-mediated miR-182. Finally, Foxo1 negatively regulated JunB expression by up-regulating Itch. Thus, we have identified a novel regulatory axis between Itch and Foxo1 in B cells, suggesting that Itch is essential for B-cell development.
Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis
Authors: Oyanagi Toshihito , Takeshita Nobuo , Hara Mamiko , Ikeda Etsuko , Chida Toko , Seki Daisuke , Yoshida Michiko , Seiryu Masahiro , Takano Ikuko , Kimura Seiji , Oshima Masamitsu , Tsuji Takashi , Takano-Yamamoto Teruko 
Published: January 2019

AbstractRegenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.
Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale
Authors: Cho Chulmin , Michailidis Vassilia , Lecker Irene , Collymore Chereen , Hanwell David , Loka Mary , Danesh Matthew , Pham Christine , Urban Paige , Bonin Robert P. , Martin Loren J. 
Published: January 2019

AbstractMost research laboratories abide by guidelines and mandates set by their research institution regarding the administration of analgesics to control pain during the postoperative period. Unfortunately, measuring pain originating from the head is difficult, making adequate decisions regarding pain control following stereotaxic surgery problematic. In addition, most postsurgical analgesia protocols require multiple injections over several days, which may cause stress and distress during a critical recovery period. Here we sought to (1) assess the degree of postoperative pain following craniotomy in mice, (2) compare the efficacy of three common rodent analgesics (carprofen, meloxicam and buprenorphine) for reducing this pain and (3) determine whether the route of administration (injected or self-administered through the drinking supply) influenced pain relief post-craniotomy. Using the mouse grimace scale (MGS), we found that injectable analgesics were significantly more effective at relieving post-craniotomy pain, however, both routes of administration decreased pain scores in the first 24 h postsurgery. Specifically, buprenorphine administered independently of administration route was the most effective at reducing MGS scores, however, female mice showed greater sensitivity to carprofen when administered through the water supply. Although it is necessary to provide laboratory animals with analgesics after an invasive procedure, there remains a gap in the literature regarding the degree of craniotomy-related pain in rodents and the efficacy of alternative routes of administration. Our study highlights the limitations of administering drugs through the drinking supply, even at doses that are considered to be higher than those currently recommended by most research institutions for treating pain of mild to moderate severity.
Astragaloside IV inhibits glucose-induced epithelial-mesenchymal transition of podocytes through autophagy enhancement via the SIRT–NF-κB p65 axis
Authors: Wang Xiaolei , Gao Yanbin , Tian Nianxiu , Wang Tao , Shi Yimin , Xu Jiayi , Wu Bingjie 
Published: January 2019

AbstractBoth autophagy and podocyte epithelial-mesenchymal transition (EMT) are critical factors in glomerular diseases that involve proteinuria and fibrosis. Here, we sought to determine whether plant-derived saponin astragaloside IV (AS-IV) was able to reverse renal fibrosis and improve renal function through regulation of autophagy and podocyte EMT. Cultured immortalized mouse podocytes and KK-Ay mice models of diabetes were exposed to AS-IV. Western blotting, real-time PCR, immunofluorescence and histochemistry were used to analyze markers of autophagy and podocyte EMT. We observed that AS-IV inhibited glucose-induced podocyte EMT and enhanced autophagy by decreasing NF-κB subunit p65 acetylation as well as increasing Sirtuin1 (SIRT1) expression. Treatment of the cells and animal models with a SIRT1 inhibitor EX527 was able to reverse these effects. The SIRT1 activator SRT1720 was also found to decrease p65 acetylation and enhance autophagy in glucose-induced podocyte EMT. Additionally, further treatment with autophagy inhibitor 3-methyladenine was able to reverse the effects of AS-IV on podocyte EMT, while the autophagy activator rapamycin or the NF-κB pathway inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) were able to reverse glucose-induced podocyte EMT. Notably, both renal fibrosis and renal function in diabetic KK-Ay mice were improved after treatment with AS-IV. These findings support AS-IV as a renoprotective agent that likely exerts its effects on podocyte EMT through modulation of the SIRT1–NF-κB pathway and autophagy activation. Further studies are required to clarify the role of AS-IV as a potential therapeutic agent in glomerular diseases.
Ultrasonic versus conventional gap arthroplasty for the release of ankylosis of temporomandibular joint: a prospective cohort study
Authors: Jia Tingting , Wang Li , Chen Youbai , Zhao Rui , Zhu Liang , Xing Lejun , Rao Naman , Zhang Jie , Zhang Qixu , August Meredith , Han Yan , Zhang Haizhong 
Published: January 2019

AbstractThe purpose of this study was to compare the clinical outcomes of ultrasonic surgery to the conventional bone cutting technique using bur and saw for the release of ankylosis of temporomandibular joint. We conducted a prospective cohort study on 25 patients with 38 ankylotic joints at Chinese PLA General Hospital from March 01, 2012 to March 01, 2016. Patients were followed up at least 2 years postoperatively. The primary outcome was the intraoperative blood loss per joint. The secondary outcome was the long-term (≥2 years) improvement of maximum mouth opening. The blood loss was significantly reduced in the ultrasonic group compared to the conventional group (107.3 ± 62.3 ml vs. 186.3 ± 92.6 ml, P = 0.019). The long-term improvements of maximum mouth opening were substantial and stable in both groups (33.5 ± 4.8 mm in the ultrasonic group vs. 29.2 ± 6 mm in the conventional group, P = 0.06). Multivariate linear regression analysis showed a significant association between blood loss and technique used (coefficient: 66.3, 95% confidence interval: 22.1,110.4, P = 0.006). The ultrasonic surgery was associated with less intraoperative blood loss when compared to the conventional method for the release of ankylosis of temporomandibular joint while providing a stable and comparable long-term improvement of maximum mouth opening.
Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo
Authors: Prati Bruna , da Silva Abjaude Walason , Termini Lara , Morale Mirian , Herbster Suellen , Longatto-Filho Adhemar , Nunes Rafaella Almeida Lima , Córdoba Camacho Lizeth Carolina , Rabelo-Santos Silvia Helena , Zeferino Luiz Carlos , Aguayo Francisco , Boccardo Enrique 
Published: January 2019

AbstractAlterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.
The Three Dimensional Spatial Structure of Antarctic Krill Schools in the Laboratory
Authors: Murphy David W. , Olsen Daniel , Kanagawa Marleen , King Rob , Kawaguchi So , Osborn Jon , Webster Donald R. , Yen Jeannette 
Published: January 2019

AbstractAnimal positions within moving groups may reflect multiple motivations including saving energy and sensing neighbors. These motivations have been proposed for schools of Antarctic krill, but little is known about their three-dimensional structure. Stereophotogrammetric images of Antarctic krill schooling in the laboratory are used to determine statistical distributions of swimming speed, nearest neighbor distance, and three-dimensional nearest neighbor positions. The krill schools swim at speeds of two body lengths per second at nearest neighbor distances of one body length and reach similarly high levels of organization as fish schools. The nearest neighbor position distribution is highly anisotropic and shows that Antarctic krill prefer to swim in the propulsion jet of their anterior neighbor. This position promotes communication and coordination among schoolmates via hydrodynamic signals within the pulsed jet created by the metachronal stroking of the neighboring krill’s pleopods. The hydrodynamic communication channel therefore plays a large role in structuring the school. Further, Antarctic krill avoid having a nearest neighbor directly overhead, possibly to avoid blockage of overhead light needed for orientation. Other factors, including the elongated body shape of Antarctic krill and potential energy savings, also may help determine the three dimensional spatial structure of tightly packed krill schools.
Field-free Magnetization Switching by Utilizing the Spin Hall Effect and Interlayer Exchange Coupling of Iridium
Authors: Liu Yang , Zhou Bing , Zhu Jian-Gang 
Published: January 2019

AbstractMagnetization switching by spin-orbit torque (SOT) via spin Hall effect represents as a competitive alternative to that by spin-transfer torque (STT) used for magnetoresistive random access memory (MRAM), as it doesn’t require high-density current to go through the tunnel junction. For perpendicular MRAM, however, SOT driven switching of the free layer requires an external in-plane field, which poses limitation for viability in practical applications. Here we demonstrate field-free magnetization switching of a perpendicular magnet by utilizing an Iridium (Ir) layer. The Ir layer not only provides SOTs via spin Hall effect, but also induce interlayer exchange coupling with an in-plane magnetic layer that eliminates the need for the external field. Such dual functions of the Ir layer allows future build-up of magnetoresistive stacks for memory and logic applications. Experimental observations show that the SOT driven field-free magnetization reversal is characterized as domain nucleation and expansion. Micromagnetic modeling is carried out to provide in-depth understanding of the perpendicular magnetization reversal process in the presence of an in-plane exchange coupling field.
Cell migration on microposts with surface coating and confinement
Authors: Hui Jianan , Pang Stella W. 
Published: January 2019

Abstract
Understanding cell migration in a 3D microenvironment is essential as most cells encounter complex 3D extracellular matrix (ECM) in vivo. Although interactions between cells and ECM have been studied previously on 2D surfaces, cell migration studies in 3D environment are still limited. To investigate cell migration under various degrees of confinements and coating conditions, 3D platforms with micropost arrays and controlled fibronectin (FN) protein coating were developed. MC3T3-E1 cells spread and contacted the top surface of microposts if FN was coated on top. When FN was coated all over the microposts, cells were trapped between microposts with 3 μm spacing and barely moved. As the spacing between microposts increased from 3 to 5 μm, cells became elongated with limited cell movement of 0.18 μm/min, slower than the cell migration speed of 0.40 μm/min when cells moved on top. When cells were trapped in between the microposts, cell nuclei were distorted and actin filaments formed along the sidewalls of microposts. With the addition of a top cover to introduce cell confinement, the cell migration speed was 0.23 and 0.84 μm/min when the channel height was reduced from 20 to 10 μm, respectively. Cell traction force was monitored at on the top and bottom microposts with 10 μm channel height. These results show that the MC3T3-E1 cell morphology, migration speed, and movement position were affected by surface coating and physical confinement, which will provide significant insights for in vivo cell migration within a 3D ECM.
Les lois françaises de bioéthique
Authors: Thouvenin Dominique 
Published: January 2019

médecine/sciences (m/s) a, tout au long de son existence, accompagné les nombreux débats qui ont agité la communauté scientifique et médicale concernant les questions de bioéthique posées par les bouleversements majeurs que les avancées de la recherche biomédicale ont introduits dans les pratiques thérapeutiques. La révision des lois de bioéthique est désormais proche et notre revue a voulu éclairer nos lectrices et nos lecteurs en leur proposant des regards multiples et croisés sur différents thèmes que cette révision aborde. Regard d’une juriste sur l’histoire de ces lois, leur genèse et les débats qui ont présidé à leur évolution jusqu’à ce jour, regard d’une sociologue sur certains des débats qui ont animé les États généraux de 2018, regard d’un philosophe penseur du « moment » et s’interrogeant sur ce que signifie la bioéthique, et, enfin, regards comparatifs de collègues étrangers mais francophones (un grand merci à ces auteur[e]s !) qui nous éclairent sur la façon dont certaines des thématiques faisant l’objet de ces lois dans notre pays sont abordées dans d’autres pays. Enfin, nous essaierons, autant que faire se peut, d’accompagner ces manuscrits de Nouvelles et de Synthèses portant sur les dernières avancées des sciences biologiques et médicales susceptibles d’éclairer les débats en leur apportant des données scientifiques et cliniques.
Marie Gaille et la Rédaction
Notfallversorgung und Erstbehandlung epileptischer Anfälle im Erwachsenenalter
Authors: Schiefer Johannes , Surges Rainer 
Published: January 2019

AbstractSuspected epileptic seizures are a frequent cause of emergency hospital care. After single seizures, the emergency management includes safety measures and diagnostic efforts to distinguish epileptic seizures from its manifold mimics and to possibly detect acute causes of epileptic seizures. Convulsive status epilepticus requires rapid anticonvulsant treatment according to established protocols and diagnostics to rule out underlying acute brain diseases. After a first seizure, typical EEG- and MRI findings may indicate an elevated recurrence risk, thereby justifying the ultimate diagnosis of epilepsy and initiation of anticonvulsant therapy. This article reviews the recent definition of epilepsy, summarizes clinical characteristics of epileptic seizures and its mimics and provides an overview of established therapies of single convulsive seizures, convulsive status epilepticus and early care of adults after first unprovoked seizures.