bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay
Authors: Hou Helei , Yang Xiaonan , Zhang Jinping , Zhang Zhe , Xu Xiaomei , Zhang Xiaoping , Zhang Chuantao , Liu Dong , Yan Weihua , Zhou Na , Zhu Hongmei , Qian Zhaoyang , Li Zhuokun , Zhang Xiaochun 
Published: October 2017

AbstractNext-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes. Somatic ctDNA mutations were detected in 82.8% (111/134) of patients in the total cohort. Of the 119 patients with advanced NSCLC, 27.7% (33/119) were suitable for treatment with National Comprehensive Cancer Network (NCCN) guideline-approved targeted drugs. Actionable genetic alterations included 25 EGFR mutations, 5 BRAF mutations, and 1 MET mutation, as well as 1 EML4-ALK gene fusion and 1 KIF5B-RET gene fusion. In 19.3% (23/119) of the patients, we also identified genomic alterations with that could be targeted by agents that are in clinical trials, such as mTOR inhibitors, PARP inhibitors, and CDK4/6 inhibitors. Additionally, the EGFR T790M mutation was found in 46.7% (7/15) of the patients with EGFR-TKI-resistant NSCLC, suggesting that the NGS-based ctDNA assay might be an optional method to monitor EGFR-TKI resistance and to discover mechanisms of drug resistance.
A fossil species of the enigmatic early polypod fern genus Cystodium (Cystodiaceae) in Cretaceous amber from Myanmar
Authors: Regalado Ledis , Schmidt Alexander R. , Appelhans Marc S. , Ilsemann Bork , Schneider Harald , Krings Michael , Heinrichs Jochen 
Published: October 2017

AbstractThe monospecific fern genus Cystodium (Cystodiaceae; Polypodiales) occurs exclusively in the tropical forests of the Malay Archipelago, the Admiralty Islands, the Louisiade Archipelago, and the Solomon Islands. Divergence time estimates suggest that the genus originated in the Mesozoic; however, fossil evidence to validate this suggestion has been lacking. Amber from Myanmar (Burmese amber) is an important source of new information on the diversity of vascular cryptogams in the Cretaceous. This paper describes the fossil taxon Cystodium sorbifolioides nov. sp. based on a fragment of a fertile leaf preserved in Burmese amber that represents the first fossil evidence of the family Cystodiaceae. Cystodium sorbifolioides is used to obtain a minimum age estimate for the Cystodiaceae and the closely related, monogeneric Lonchitidaceae and Lindsaeaceae. The fossil strengthens the hypothesis that the forest ecosystems of Malesia and Melanesia represent refugia for many tropical plant lineages that originated in the Cretaceous.
Signatures of adaptation and symbiosis in genomes and transcriptomes of Symbiodinium
Authors: González-Pech Raúl A. , Ragan Mark A. , Chan Cheong Xin 
Published: October 2017

AbstractSymbiodiniumis best-known as the photosynthetic symbiont of corals, but some clades are symbiotic in other organisms or include free-living forms. Identifying similarities and differences among these clades can help us understand their relationship with corals, and thereby inform on measures to manage coral reefs in a changing environment. Here, using sequences from 24 publicly available transcriptomes and genomes ofSymbiodinium, we assessed 78,389 gene families inSymbiodiniumclades and the immediate outgroupPolarella glacialis, and identified putative overrepresented functions in gene families that (1) distinguishSymbiodiniumfrom other members of Order Suessiales, (2) are shared by all of theSymbiodiniumclades for which we have data, and (3) based on available information, are specific to each clade. Our findings indicate that transmembrane transport, mechanisms of response to reactive oxygen species, and protection against UV radiation are functions enriched in allSymbiodiniumclades but not inP. glacialis. Enrichment of these functions indicates the capability ofSymbiodiniumto establish and maintain symbiosis, and to respond and adapt to its environment. The observed differences in lineage-specific gene families imply extensive genetic divergence among clades. Our results provide a platform for future investigation of lineage- or clade-specific adaptation ofSymbiodiniumto their environment.
Ambipolar field role in formation of electron distribution function in gas discharge plasma
Authors: Yuan Chengxun , Bogdanov E. A. , Kudryavtsev A. A. , Rabadanov K. M. , Zhou Zhongxiang 
Published: October 2017

AbstractIt is shown that the local approximation for electron distribution function (EDF) determination at plasma periphery, where the ambipolar field is dominant, is not applicable even at high pressures when the characteristic plasma size exceeds the energy relaxation length of the electrons R > λ
ε
. Therefore, consistent results can be obtained only when solving the complete kinetic equation in both energy and spatial variables (i.e. it is necessary to solve nonlocal kinetic equation).
Rotational Diffusion of Soft Vesicles Filled by Chiral Active Particles
Authors: Chen Jiamin , Hua Yunfeng , Jiang Yangwei , Zhou Xiaolin , Zhang Linxi 
Published: October 2017

AbstractWe investigate the dynamics of two-dimensional soft vesicles filled with chiral active particles by employing the overdamped Langevin dynamics simulation. The unidirectional rotation is observed for soft vesicles, and the rotational angular velocity of vesicles depends mainly on the area fraction (ρ) and angular velocity (ω) of chiral active particles. There exists an optimal parameter for ω at which the rotational angular velocity of vesicle takes its maximal value. Meanwhile, at low concentration the continuity of curvature is destroyed seriously by chiral active particles, especially for large ω, and at high concentration the chiral active particles cover the vesicle almost uniformly. In addition, the center-of-mass mean square displacement for vesicles is accompanied by oscillations at short timescales, and the oscillation period of diffusion for vesicles is consistent with the rotation period of chiral active particles. The diffusion coefficient of vesicle decreases monotonously with increasing the angular velocity ω of chiral active particles. Our investigation can provide a few designs for nanofabricated devices that can be driven in a unidirectional rotation by chiral active particles or could be used as drug-delivery agent.
A teleost CD46 is involved in the regulation of complement activation and pathogen infection
Authors: Li Mo-fei , Sui Zhi-hai , Sun Li 
Published: October 2017

AbstractIn mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that responsible for the FI interaction, involving different rCsCD46 sites. Cellular study showed that CsCD46 was expressed on peripheral blood leukocytes (PBL) and protected the cells against the killing effect of complement. When the CsCD46 on PBL was blocked by antibody before incubation of the cells with bacterial pathogens, cellular infection was significantly reduced. Consistently, when tongue sole were infected with bacterial pathogens in the presence of rCsCD46, tissue dissemination and survival of the pathogens were significantly inhibited. These results provide the first evidence to indicate that CD46 in teleosts negatively regulates complement activation via FI and protects host cells from complement-induced damage, and that CD46 is required for optimal bacterial infection probably by serving as a receptor for the bacteria.
Identification of novel cis-regulatory elements of Eya1 in Xenopus laevis using BAC recombineering
Authors: Maharana Santosh Kumar , Pollet Nicolas , Schlosser Gerhard 
Published: October 2017

AbstractThe multifunctional Eya1 protein plays important roles during the development of cranial sensory organs and ganglia, kidneys, hypaxial muscles and several other organs in vertebrates. Eya1 is encoded by a complex locus with candidate cis-regulatory elements distributed over a 329 kbp wide genomic region in Xenopus. Consequently, very little is currently known about how expression of Eya1 is controlled by upstream regulators. Here we use a library of Xenopus tropicalis genomic sequences in bacterial artificial chromosomes (BAC) to analyze the genomic region surrounding the Eya1 locus for enhancer activity. We used BAC recombineering to first create GFP reporter constructs, which were analysed for enhancer activity by injection into Xenopus laevis embryos. We then used a second round of BAC recombineering to create deletion constructs of these BAC reporters to localize enhancer activity more precisely. This double recombineering approach allowed us to probe a large genomic region for enhancer activity without assumptions on sequence conservation. Using this approach we were able to identify two novel cis-regulatory regions, which direct Eya1 expression to the somites, pharyngeal pouches, the preplacodal ectoderm (the common precursor region of many cranial sensory organs and ganglia), and other ectodermal domains.
Trichostatin A ameliorates renal tubulointerstitial fibrosis through modulation of the JNK-dependent Notch-2 signaling pathway
Authors: Tung Chun-Wu , Hsu Yung-Chien , Cai Chang-Jhih , Shih Ya-Hsueh , Wang Ching-Jen , Chang Pey-Jium , Lin Chun-Liang 
Published: October 2017

AbstractRenal fibrosis is the final common pathological feature in a variety of chronic kidney disease. Trichostatin A (TSA), a histone deacetylase inhibitor, reportedly attenuates renal fibrosis in various kidney disease models. However, the detailed molecular action of TSA in ameliorating renal fibrotic injury is not yet fully understood. In a cultured renal fibroblastic cell model, we showed that TGF-β1 triggers upregulation of α-SMA and fibronectin, two hallmarks of myofibroblastic activation. During the course of TGF-β1 treatment, activation of Smad2/3, p38, ERK, JNK and Notch-2 was also detected. Under the conditions, administration of TSA significantly decreased TGF-β1-stimulated expression of α-SMA, fibronectin, phospho-JNK, and cleaved Notch-2; however, the levels of phospho-Smad2/3, phospho-p38 and phospho-ERK remained unchanged. Pharmacological inhibition of different signaling pathways and genetic knockdown of Notch-2 further revealed JNK as an upstream effector of Notch-2 in TGF-β1-mediated renal fibrosis. Consistently, we also demonstrated that administration of TSA or a γ-secretase inhibitor RO4929097 in the mouse model of unilateral ureteral obstruction significantly ameliorated renal fibrosis through suppression of the JNK/Notch-2 signaling activation. Taken together, our findings provide further insights into the crosstalk among different signaling pathways in renal fibrosis, and elucidate the molecular action of TSA in attenuating fibrogenesis.
Microbial network of the carbonate precipitation process induced by microbial consortia and the potential application to crack healing in concrete
Authors: Zhang Jiaguang , Zhou Aijuan , Liu Yuanzhen , Zhao Bowei , Luan Yunbo , Wang Sufang , Yue Xiuping , Li Zhu 
Published: October 2017

AbstractCurrent studies have employed various pure-cultures for improving concrete durability based on microbially induced carbonate precipitation (MICP). However, there have been very few reports concerned with microbial consortia, which could perform more complex tasks and be more robust in their resistance to environmental fluctuations. In this study, we constructed three microbial consortia that are capable of MICP under aerobic (AE), anaerobic (AN) and facultative anaerobic (FA) conditions. The results showed that AE consortia showed more positive effects on inorganic carbon conversion than AN and FA consortia. Pyrosequencing analysis showed that clear distinctions appeared in the community structure between different microbial consortia systems. Further investigation on microbial community networks revealed that the species in the three microbial consortia built thorough energetic and metabolic interaction networks regarding MICP, nitrate-reduction, bacterial endospores and fermentation communities. Crack-healing experiments showed that the selected cracks of the three consortia-based concrete specimens were almost completely healed in 28 days, which was consistent with the studies using pure cultures. Although the economic advantage might not be clear yet, this study highlights the potential implementation of microbial consortia on crack healing in concrete.
Phosphodiester backbone of the CpG motif within immunostimulatory oligodeoxynucleotides augments activation of Toll-like receptor 9
Authors: Pohar Jelka , Lainšček Duško , Kunšek Ana , Cajnko Miša-Mojca , Jerala Roman , Benčina Mojca 
Published: October 2017

AbstractToll-like receptor 9 (TLR9) stimulatory CpG-containing oligodeoxynucleotides (ODNs) with phosphorothioate backbones have successfully replaced the naturally occurring agonists of TLR9 in drug development due to their increased stability. Replacing the nonbridging oxygen with a sulfur atom in the phosphate linkage of ODNs has been accepted as having a minor impact on the chemical and physical properties of the agonists. Here, we report that the TLR9 binding site exhibits a strong bias in favor of a phosphodiester backbone over the phosphorothioate backbone of the CpG motif. Furthermore, we show that while single point mutations of W47, W96 and K690 within the TLR9 binding site retains full TLR9 activation by phosphodiester-based ODNs, activation by phosphorothioate-based ODNs is strongly impaired. The substitution of a phosphorothioate linkage for a phosphodiester linkage of just the CpG motif considerably improves the activation potency of a phosphorothioate-based oligonucleotide for human B-cells and plasmacytoid dendritic cells, as well as for mouse bone marrow-derived dendritic cells and macrophages. Our results highlight the functional significance of the phosphodiester linkage of a CpG dinucleotide for binding, which is important in designing improved immunostimulatory TLR9 agonists.
EFHD2 promotes epithelial-to-mesenchymal transition and correlates with postsurgical recurrence of stage I lung adenocarcinoma
Authors: Fan Chi-Chen , Cheng Wei-Chung , Huang Yu-Chuen , Sher Yuh-Pyng , Liou Nia-Jhen , Chien Yu-Chuan , Lin Pei-Shan , Lin Pei-Syuan , Chen Chung-Hsuan , Chang Wei-Chao 
Published: October 2017

AbstractSurgery is the only curative treatment for early-stage non-small cell lung cancer (NSCLC) patients. However, approximately one-third of these patients develop recurrence, which remains the main cause of mortality in the postsurgical treatment of NSCLC. Many molecular markers have been proposed to predict recurrence of early-stage disease, but no marker has demonstrated sufficient reliability for clinical application. In the present study, the novel protein EF-hand domain-containing protein D2 (EFHD2) was identified as expressed in highly metastatic tumor cells. EFHD2 increased the formation of protrusive invadopodia structures and cell migration and invasion abilities and promoted the epithelial-to-mesenchymal transition (EMT) character of lung adenocarcinoma cells. We demonstrated that the mechanism of EFHD2 in enhancing EMT occurs partly through inhibition of caveolin-1 (CAV1) for cancer progression. The expression of EFHD2 was significantly correlated with postsurgical recurrence of patients with stage I lung adenocarcinoma in the Kaplan-Meier-plotter cancer database search and our retrospective cohort study (HR, 6.14; 95% CI, 2.40–15.74; P < 0.001). Multivariate Cox regression analysis revealed that EFHD2 expression was an independent clinical predictor for this disease. We conclude that EFHD2 expression is associated with increased metastasis and EMT and could serve as an independent marker to predict postsurgical recurrence of patients with stage I lung adenocarcinoma.
Paracrine interactions between mesenchymal stem cells and macrophages are regulated by 1,25-dihydroxyvitamin D3
Authors: Saldaña Laura , Vallés Gema , Bensiamar Fátima , Mancebo Francisco José , García-Rey Eduardo , Vilaboa Nuria 
Published: October 2017

AbstractMesenchymal stem cells (MSC) modulate the macrophage-mediated inflammatory response through the secretion of soluble factors. In addition to its classical effects on calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25D3) has emerged as an important regulator of the immune system. The present study investigates whether 1,25D3 modulates the paracrine interactions between MSC and macrophages. 1,25D3 stimulated MSC to produce PGE2and VEGF and regulated the interplay between macrophages and MSC toward reduced pro-inflammatory cytokine production. Conditioned media (CM) from co-cultures of macrophages and MSC impaired MSC osteogenesis. However, MSC cultured in CM from 1,25D3-treated co-cultures showed increased matrix maturation and mineralization. Co-culturing MSC with macrophages prevented the 1,25D3-induced increase in RANKL levels, which correlated with up-regulation of OPG secretion. MSC seeding in three-dimensional (3D) substrates potentiated their immunomodulatory effects on macrophages. Exposure of 3D co-cultures to 1,25D3 further reduced the levels of soluble factors related to inflammation and chemotaxis. As a consequence of 1,25D3 treatment, the recruitment of monocytes toward CM of 3D co-cultures decreased, while the osteogenic maturation of MSC increased. These data add new insights into the pleiotropic effects of 1,25D3 on the crosstalk between MSC and macrophages and highlight the role of the hormone in bone regeneration.
Morphology transition of the primary silicon particles in a hypereutectic A390 alloy in high pressure die casting
Authors: Wang J. , Guo Z. , Song J. L. , Hu W. X. , Li J. C. , Xiong S. M. 
Published: October 2017

AbstractThe microstructure of a high-pressure die-cast hypereutectic A390 alloy, including PSPs, pores, α-Al grains and Cu-rich phases, was characterized using synchrotron X-ray tomography, together with SEM, TEM and EBSD. The Cu-rich phases exhibited a net morphology and distributed at the boundaries of the α-Al grains, which in turn surrounded the PSPs. Statistical analysis of the reconstructed 1000 PSPs showed that both equivalent diameter and shape factor of the PSPs exhibited a unimodal distribution with peaks corresponding to 25 μm and 0.78, respectively.) PSPs morphology with multiple twinning were observed and morphological or growth transition of the PSPs from regular octahedral shape (with a shape factor of 0.85 was mainly caused by the constraint of the Cu-rich phases. In particular, the presence of the Cu-rich phases restricted the growth of the α-Al grains, inducing stress on the internal silicon particles, which caused multiple twinning occurrence with higher growth potential and consequently led to growth transitions of the PSPs.
Impact of Performance Feedback in Family-Centered and Culturally Responsive Interview Instruction
Authors: Brown Jennifer A. 
Published: October 2017

Purpose
Conducting culturally responsive and family-centered diagnostic interviews is an important part of speech and language services. However, there is limited information on the effective ways to teach speech-language pathology graduate students to acquire these skills. The purpose of this study was to examine the effect of performance feedback on graduate students' use of ethnographic principles, open-ended questions, and restating and summarizing comments in caregiver interviews.

Method

A randomized controlled crossover design (
n
= 26) was used to examine the differential effects of students receiving performance feedback or general feedback on role-play interviews. Ethnographic principles, open-ended questions, and restating and summarizing comments were measured at 3 time points: after class instruction (Groups 1 and 2), after the first feedback type allocation (Group 1: performance feedback; Group 2: general feedback), and after the second feedback type allocation (Group 1: general feedback; Group 2: performance feedback).

Results
Statistically significant increases, with large effect sizes, were found in students' use of ethnographic principles, open-ended questions, and restating and summarizing comments following the performance feedback conditions.

Conclusion
These findings suggest that performance feedback is an effective and efficient instructional procedure to increase culturally responsive and family-centered interview skills through an ethnographic interview approach in preservice speech-language pathology students.
Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs
Authors: Fathi Ibrahim , Eltawila Ahmed , Elsherif Ahmad , Elkerm Yasser , Harhaus Leila , Kneser Ulrich , Sakr Mahmoud , Eweida Ahmad 
Published: October 2017

Background Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.
Methods We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.
Results The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.
Conclusion The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation.