bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes
Authors: Küssel Lorenz , Herkner Harald , Wahrmann Markus , Eskandary Farsad , Doberer Konstantin , Binder Julia , Pateisky Petra , Zeisler Harald , Böhmig Georg A. , Bond Gregor 
Published: October 2017

AbstractThe significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193–7938 vs. 1093, IQR 395–5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67–0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.
Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors
Authors: Numao Shin , Hasler Franziska , Laguerre Claire , Srinivas Honnappa , Wack Nathalie , Jäger Petra , Schmid Andres , Osmont Arnaud , Röthlisberger Patrik , Houguenade Jeremy , Bergsdorf Christian , Dawson Janet , Carte Nathalie , Hofmann Andreas , Markert Christian , Hardaker Liz , Billich Andreas , Wolf Romain M. , Penno Carlos A. , Bollbuck Birgit , Miltz Wolfgang , Röhn Till A. 
Published: October 2017

AbstractLeukotriene A4 Hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that comprises both epoxide hydrolase and aminopeptidase activity, exerted by two overlapping catalytic sites. The epoxide hydrolase function of the enzyme catalyzes the biosynthesis of the pro-inflammatory lipid mediator leukotriene (LT) B4. Recent literature suggests that the aminopeptidase function of LTA4H is responsible for degradation of the tripeptide Pro-Gly-Pro (PGP) for which neutrophil chemotactic activity has been postulated. It has been speculated that the design of epoxide hydrolase selective LTA4H inhibitors that spare the aminopeptidase pocket may therefore lead to more efficacious anti-inflammatory drugs. In this study, we conducted a high throughput screen (HTS) for LTA4H inhibitors and attempted to rationally design compounds that would spare the PGP degrading function. While we were able to identify compounds with preference for the epoxide hydrolase function, absolute selectivity was not achievable for highly potent compounds. In order to assess the relevance of designing such aminopeptidase-sparing LTA4H inhibitors, we studied the role of PGP in inducing inflammation in different settings in wild type and LTA4H deficient (LTA4H KO) animals but could not confirm its chemotactic potential. Attempting to design highly potent epoxide hydrolase selective LTA4H inhibitors, therefore seems to be neither feasible nor relevant.
Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains from Patients with Necrotizing Skin and Soft Tissue Infections
Authors: Krapp Fiorella , Morris Andrew R. , Ozer Egon A. , Hauser Alan R. 
Published: October 2017

AbstractTwo types of Klebsiella pneumoniae (KP) strains are currently emerging: hypervirulent (hvKP) strains and carbapenem-resistant (CR-KP) strains. To date, these two strain types rarely overlap. Recent reports, however, suggest that CR-KP strains are increasing in virulence. hvKP strains frequently present as highly invasive infections, such as necrotizing skin and soft tissue infections (NSSTI). To examine whether CR-KP strains with features of hvKP were present in our U.S. hospital, we retrospectively identified four cases of CR-KP NSSTI diagnosed between January 2012 and January 2016. Whole-genome sequencing was used to perform multilocus sequence typing, capsular typing, and identification of virulence and antimicrobial resistance genes. Additionally, the virulence of each isolate was determined in vitro and using murine pneumonia and subcutaneous infection models. We identified one CR-KP isolate that possessed features of hypervirulent KP, including a hypermucoviscous phenotype, K2 capsule, and resistance to phagocytosis. Of the four CR-KP isolates, two had no evidence of enhanced pathogenicity in either mouse model, demonstrating that low-virulence strains can cause NSSTI in immunosuppressed patients. The remaining two isolates exhibited low virulence in the pneumonia model but high virulence in the subcutaneous infection model, suggesting that the virulence attributes of these isolates are adapted to causing NSSTI.
Microarray gene expression of periosteum in spontaneous bone regeneration of mandibular segmental defects
Authors: Li Zheyi , Pan Juli , Ma Jinling , Zhang Zhen , Bai Yuxing 
Published: October 2017

AbstractSpontaneous bone regeneration could occur to reestablish mandibular bony continuity in patients who underwent partial or total mandibulectomy for tumors with periosteum-preserving. However, scarce data is available related to the precise role of periosteum in this bone regeneration. Therefore we aimed to investigate the gene expression of periosteum that were involved in the mandibular bone regeneration. Mandibular segmental defects were created in six mini-pigs with periosteum preserved. The periosteum of defects and control site were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the mechanisms concerning immature wound healing were clearly up-regulated at week 1. In contrast, by week-2, the GO categories of skeletal development, ossification and bone mineralization were significantly over-represented at week-2 with several genes encoding cell differentiation, extracellular matrix formation, and anatomical structure development. Furthermore, Tgfβ/Bmp, Wnt and Notch signaling were all related to the osteogenic process in this study. Besides osteogenesis, genes related to angiogenesis and neurogenesis were also prominent at week-2. These findings revealed that the gene expression profile of the periosteum’s cells participating in bone regeneration varied in different time points, and numbers of candidate genes that differentially expressed during early healing stages of intramembranous bone regeneration were suggested.
Gut microbiome alterations in Alzheimer’s disease
Authors: Vogt Nicholas M. , Kerby Robert L. , Dill-McFarland Kimberly A. , Harding Sandra J. , Merluzzi Andrew P. , Johnson Sterling C. , Carlsson Cynthia M. , Asthana Sanjay , Zetterberg Henrik , Blennow Kaj , Bendlin Barbara B. , Rey Federico E. 
Published: October 2017

AbstractAlzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis
Authors: Li Changlong , Ren Hui , Chen Hong , Song Junxian , Li Sufang , Lee Chongyou , Liu Jun , Cui Yuxia 
Published: October 2017

AbstractG20210A polymorphism (rs1799963) within the prothrombin gene is associated with a higher circulation level of prothrombin, thus increasing the likelihood of developing myocardial infarction (MI). Opinions differ regarding the correlation between prothrombin G20210A genotype and MI risk, which prompted us to conduct a meta-analysis to determine this association. PubMed, EMBASE, Web of Science and CNKI were searched for pertinent reports. A total of 34 studies involving 14 611 MI cases and 84 358 controls were analyzed in this quantitative analysis. We found a statistically significant association between prothrombin G20210A polymorphism and MI in the allele model (A vs. G, OR = 1.43, 95%CI: 1.18–1.72), heterozygote model (GA vs. GG, OR = 1.41, 95%CI: 1.16–1.72) and dominant model (GA + AA vs. GG, OR = 1.41, 95%CI: 1.15–1.72). The association remains significant in Caucasians but not in non-Caucasians. Moreover, prothrombin G20210A polymorphism increases MI risk in an age-related manner. A further significant association was found in a subpopulation younger than 55 years (allele model, OR = 1.76, 95%CI: 1.32–2.35; heterozygote model, OR = 1.70, 95%CI: 1.24–2.33; dominant model, OR = 1.70, 95%CI: 1.24–2.34). Sensitivity analysis and publication bias analysis revealed stable and statistically robust results. Our meta-analysis demonstrated that prothrombin G20210A polymorphism may represent a risk factor for MI.
Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models
Authors: Gao Hao , Mangion Kenneth , Carrick David , Husmeier Dirk , Luo Xiaoyu , Berry Colin 
Published: October 2017

AbstractBiomechanical computational models have potential prognostic utility in patients after an acute ST-segment–elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg). Cardiac MRI was performed in the patients (2 days & 6 months post-STEMI) and the volunteers, and biomechanical heart models were synthesized for each subject. The candidate parameters included normalized active tension (ATnorm) and active tension at the resting sarcomere length (Treq, reflecting required contractility). Myocardial contractility was inversely determined from personalized heart models by matching CMR-imaged LV dynamics. Compared with controls, patients with recent STEMI exhibited increased LV wall active tension when normalized by SBP. We observed a linear relationship between Treq 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p = 0.03). Treq may be associated with changes in LV function in the longer term in STEMI patients complicated by LV dysfunction. Further studies seem warranted.
Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing In Vitro Fertilization
Authors: Abu-Halima Masood , Häusler Sebastian , Backes Christina , Fehlmann Tobias , Staib Claudia , Nestel Sigrun , Nazarenko Irina , Meese Eckart , Keller Andreas 
Published: October 2017

AbstractMicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 109/mL EVs), as compared to a negative outcome (7.35 × 109/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.
Rainbow-trapping absorbers: Broadband, perfect and asymmetric sound absorption by subwavelength panels for transmission problems
Authors: Jiménez Noé , Romero-García Vicent , Pagneux Vincent , Groby Jean-Philippe 
Published: October 2017

AbstractPerfect, broadband and asymmetric sound absorption is theoretically, numerically and experimentally reported by using subwavelength thickness panels in a transmission problem. The panels are composed of a periodic array of varying crosssection waveguides, each of them being loaded by Helmholtz resonators (HRs) with graded dimensions. The low cut-off frequency of the absorption band is fixed by the resonance frequency of the deepest HR, that reduces drastically the transmission. The preceding HR is designed with a slightly higher resonance frequency with a geometry that allows the impedance matching to the surrounding medium. Therefore, reflection vanishes and the structure is critically coupled. This results in perfect sound absorption at a single frequency. We report perfect absorption at 300 Hz for a structure whose thickness is 40 times smaller than the wavelength. Moreover, this process is repeated by adding HRs to the waveguide, each of them with a higher resonance frequency than the preceding one. Using this frequency cascade effect, we report quasi-perfect sound absorption over almost two frequency octaves ranging from 300 to 1000 Hz for a panel composed of 9 resonators with a total thickness of 11 cm, i.e., 10 times smaller than the wavelength at 300 Hz.
2D Raman band splitting in graphene: Charge screening and lifting of the K-point Kohn anomaly
Authors: Wang Xuanye , Christopher Jason W. , Swan Anna K. 
Published: October 2017

AbstractPristine graphene encapsulated in hexagonal boron nitride has transport properties rivalling suspended graphene, while being protected from contamination and mechanical damage. For high quality devices, it is important to avoid and monitor accidental doping and charge fluctuations. The 2D Raman double peak in intrinsic graphene can be used to optically determine charge density, with decreasing peak split corresponding to increasing charge density. We find strong correlations between the 2D1 and 2D2 split vs 2D line widths, intensities, and peak positions. Charge density fluctuations can be measured with orders of magnitude higher precision than previously accomplished using the G-band shift with charge. The two 2D intrinsic peaks can be associated with the “inner” and “outer” Raman scattering processes, with the counterintuitive assignment of the phonon closer to the K point in the KM direction (outer process) as the higher energy peak. Even low charge screening lifts the phonon Kohn anomaly near the K point for graphene encapsulated in hBN, and shifts the dominant intensity from the lower to the higher energy peak.
Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images
Authors: Wang Xiangxue , Janowczyk Andrew , Zhou Yu , Thawani Rajat , Fu Pingfu , Schalper Kurt , Velcheti Vamsidhar , Madabhushi Anant 
Published: October 2017

AbstractIdentification of patients with early stage non-small cell lung cancer (NSCLC) with high risk of recurrence could help identify patients who would receive additional benefit from adjuvant therapy. In this work, we present a computational histomorphometric image classifier using nuclear orientation, texture, shape, and tumor architecture to predict disease recurrence in early stage NSCLC from digitized H&E tissue microarray (TMA) slides. Using a retrospective cohort of early stage NSCLC patients (Cohort #1, n = 70), we constructed a supervised classification model involving the most predictive features associated with disease recurrence. This model was then validated on two independent sets of early stage NSCLC patients, Cohort #2 (n = 119) and Cohort #3 (n = 116). The model yielded an accuracy of 81% for prediction of recurrence in the training Cohort #1, 82% and 75% in the validation Cohorts #2 and #3 respectively. A multivariable Cox proportional hazard model of Cohort #2, incorporating gender and traditional prognostic variables such as nodal status and stage indicated that the computer extracted histomorphometric score was an independent prognostic factor (hazard ratio = 20.81, 95% CI: 6.42–67.52, P < 0.001).
Studying the role of axon fasciculation during development in a computational model of the Xenopus tadpole spinal cord
Authors: Davis Oliver , Merrison-Hort Robert , Soffe Stephen R. , Borisyuk Roman 
Published: October 2017

AbstractDuring nervous system development growing axons can interact with each other, for example by adhering together in order to produce bundles (fasciculation). How does such axon-axon interaction affect the resulting axonal trajectories, and what are the possible benefits of this process in terms of network function? In this paper we study these questions by adapting an existing computational model of the development of neurons in the Xenopus tadpole spinal cord to include interactions between axons. We demonstrate that even relatively weak attraction causes bundles to appear, while if axons weakly repulse each other their trajectories diverge such that they fill the available space. We show how fasciculation can help to ensure axons grow in the correct location for proper network formation when normal growth barriers contain gaps, and use a functional spiking model to show that fasciculation allows the network to generate reliable swimming behaviour even when overall synapse counts are artificially lowered. Although we study fasciculation in one particular organism, our approach to modelling axon growth is general and can be widely applied to study other nervous systems.
Pinned domain wall oscillator as a tuneable direct current spin wave emitter
Authors: Voto Michele , Lopez-Diaz Luis , Martinez Eduardo 
Published: October 2017

AbstractLocal perturbations in the relative orientation of the magnetic moments in a continuous magnetic system can propagate in the form of waves. These so-called spin waves represent a promising candidate as an information carrier for spin-based low-power applications. A localized, energy-efficient excitation of coherent and short-wavelength spin waves is a crucial technological requirement, and alternatives to excitation via the Oersted field of an alternating current must be explored. Here, we show how a domain wall pinned at a geometrical constriction in a perpendicularly magnetized thin nanowire emits spin waves when forced to rotate by the application of a low direct current flowing along the wire. Spin waves are excited by the in-plane stray field of the rotating domain wall and propagate at an odd harmonic of the domain wall rotation frequency in the direction of the electron’s flow. The application of an external field, opposing domain wall depinning induced by the current, breaks the symmetry for spin wave propagation in the two domains, allowing emission in both directions but at different frequencies. The results presented define a new approach to manufacture tuneable high-frequency spin wave emitters of easy fabrication and low power consumption.
Direct estimation of de novo mutation rates in a chimpanzee parent-offspring trio by ultra-deep whole genome sequencing
Authors: Tatsumoto Shoji , Go Yasuhiro , Fukuta Kentaro , Noguchi Hideki , Hayakawa Takashi , Tomonaga Masaki , Hirai Hirohisa , Matsuzawa Tetsuro , Agata Kiyokazu , Fujiyama Asao 
Published: October 2017

AbstractMutations generate genetic variation and are a major driving force of evolution. Therefore, examining mutation rates and modes are essential for understanding the genetic basis of the physiology and evolution of organisms. Here, we aim to identify germlinede novomutations through the whole-genome surveyance of Mendelian inheritance error sites (MIEs), those not inherited through the Mendelian inheritance manner from either of the parents, using ultra-deep whole genome sequences (>150-fold) from a chimpanzee parent-offspring trio. We identified such 889 MIEs and classified them into four categories based on the pattern of inheritance and the sequence read depth: [i]de novosingle nucleotide variants (SNVs), [ii] copy number neutral inherited variants, [iii] hemizygous deletion inherited variants, and [iv]de novocopy number variants (CNVs). Fromde novoSNV candidates, we estimated a germlinede novoSNV mutation rate as 1.48 × 10−8per site per generation or 0.62 × 10−9per site per year. In summary, this study demonstrates the significance of ultra-deep whole genome sequencing not only for the direct estimation of mutation rates but also for discerning various mutation modes includingde novoallelic conversion andde novoCNVs by identifying MIEs through the transmission of genomes from parents to offspring.
Marine self-potential survey for exploring seafloor hydrothermal ore deposits
Authors: Kawada Yoshifumi , Kasaya Takafumi 
Published: October 2017

AbstractWe conducted a self-potential survey at an active hydrothermal field, the Izena hole in the mid-Okinawa Trough, southern Japan. This field is known to contain Kuroko-type massive sulphide deposits. This survey measured the self-potential continuously in ambient seawater using a deep-tow array, which comprises an electrode array with a 30-m-long elastic rod and a stand-alone data acquisition unit. We observed negative self-potential signals not only above active hydrothermal vents and visible sulphide mounds but also above the flat seafloor without such structures. Some signals were detectable >50 m above the seafloor. Analysis of the acquired data revealed these signals’ source as below the seafloor, which suggests that the self-potential method can detect hydrothermal ore deposits effectively. The self-potential survey, an easily performed method for initial surveys, can identify individual sulphide deposits from a vast hydrothermal area.