bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic effects of somatic mutations in ER-positive breast cancer
Authors: Griffith Obi L. , Spies Nicholas C. , Anurag Meenakshi , Griffith Malachi , Luo Jingqin , Tu Dongsheng , Yeo Belinda , Kunisaki Jason , Miller Christopher A , Krysiak Kilannin , Hundal Jasreet , Ainscough Benjamin J , Skidmore Zachary L. , Campbell Katie , Kumar Runjun , Fronick Catrina , Cook Lisa , Snider Jacqueline E. , Davies Sherri , Kavuri Shyam M. , Chang Eric C. , Magrini Vincent , Larson David E. , Fulton Robert S , Liu Shuzhen , Leung Samuel , Voduc David , Bose Ron , Dowsett Mitch , Wilson Richard K. , Nielsen Torsten O. , Mardis Elaine R , Ellis Matthew J. 
Published: August 2018

AbstractHere we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.
Structural homogeneity and mass density of bulk metallic glasses revealed by their rough surfaces and ultra-small angle neutron scattering (USANS)
Authors: Kim Man-Ho , Suh Jin-Yoo , Fleury Eric , Han Su Gyeong , Hong Kyung Tae 
Published: August 2018

AbstractThe ultra-small angle neutron scattering (USANS) measures the microscale structure of heterogeneity and the scattering from rough surfaces with small scattering volumes can be neglected. But this is not true in amorphous alloys. The small angle scattering from such surfaces is not negligible, regardless of scattering volume. However, we demonstrate that the unwanted rough surfaces can be utilized to determine the homogeneity and mass density of amorphous metallic glasses using the USANS and surface neutron contrast matching technique. The power law scattering of the homogeneous Cu50Zr50 amorphous alloy disappeared under the surface contrast-matched environment, a mixture of hydrogenated/deuterated ethanol having low surface tension against the metallic alloys, indicating that the scattering originated not from its internal structure but from the rough surface. This confirms the structural homogeneity not only at the atomic level but also on a larger scale of micrometer. On the other hand, the crystallized Cu50Zr50 alloy showed strong power-law scattering under the matching environment due to the structural heterogeneity inside the alloy. This technique can apply to the bulk samples when the transmission is high enough not causing multiple scattering that is easily detected with USANS and when the surface roughness is dominant source of scattering.
The 2015 landslide and tsunami in Taan Fiord, Alaska
Authors: Higman Bretwood , Shugar Dan H. , Stark Colin P. , Ekström Göran , Koppes Michele N. , Lynett Patrick , Dufresne Anja , Haeussler Peter J. , Geertsema Marten , Gulick Sean , Mattox Andrew , Venditti Jeremy G. , Walton Maureen A. L. , McCall Naoma , Mckittrick Erin , MacInnes Breanyn , Bilderback Eric L. , Tang Hui , Willis Michael J. , Richmond Bruce , Reece Robert S. , Larsen Chris , Olson Bjorn , Capra James , Ayca Aykut , Bloom Colin , Williams Haley , Bonno Doug , Weiss Robert , Keen Adam , Skanavis Vassilios , Loso Michael 
Published: August 2018

AbstractGlacial retreat in recent decades has exposed unstable slopes and allowed deep water to extend beneath some of those slopes. Slope failure at the terminus of Tyndall Glacier on 17 October 2015 sent 180 million tons of rock into Taan Fiord, Alaska. The resulting tsunami reached elevations as high as 193 m, one of the highest tsunami runups ever documented worldwide. Precursory deformation began decades before failure, and the event left a distinct sedimentary record, showing that geologic evidence can help understand past occurrences of similar events, and might provide forewarning. The event was detected within hours through automated seismological techniques, which also estimated the mass and direction of the slide - all of which were later confirmed by remote sensing. Our field observations provide a benchmark for modeling landslide and tsunami hazards. Inverse and forward modeling can provide the framework of a detailed understanding of the geologic and hazards implications of similar events. Our results call attention to an indirect effect of climate change that is increasing the frequency and magnitude of natural hazards near glaciated mountains.
Unaltered intrinsic functional brain architecture in young women with primary dysmenorrhea
Authors: Lee Lin-Chien , Chen Yueh-Hua , Lin Chia-Shu , Li Wei-Chi , Low Intan , Tu Cheng-Hao , Chou Chih-Che , Cheng Chou-Ming , Yeh Tzu-Chen , Chen Li-Fen , Chao Hsiang-Tai , Hsieh Jen-Chuen 
Published: August 2018

AbstractPrimary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.
Self-report data as a tool for subtype identification in genetically-defined Parkinson’s Disease
Authors: Winslow Ashley R. , Hyde Craig L. , Wilk Jemma B. , Eriksson Nicholas , Cannon Paul , Miller Melissa R. , Hirst Warren D. 
Published: August 2018

AbstractThrough a targeted recruitment 23andMe has collected DNA and patient-reported symptoms from more than 10,000 subjects reporting a physician-verified diagnosis of PD. This study evaluated the potential of self-report, web-based questionnaires to rapidly assess disease natural history and symptomology in genetically-defined PD populations. While average age-at-diagnosis was significantly lower in GBA mutation carriers compared to idiopathic PD, or iPD (idiopathic PD, defined as no GBA mutations and no LRRK2 G2019S mutation), there were no significant differences in symptoms. Conversely, LRRK2 G2019S carrier status significantly associated with reporting of milder daily symptoms of lightheadedness and several differences were observed at a false discovery rate < 0.1, including increased reporting of changes in walking as an initial symptom of disease, decreased reporting of lightheadedness upon standing, and milder symptoms related to daily functioning. The subclinical differences in symptoms reported by LRRK2 G2019S carriers suggest differences in underlying pathophysiology and/or disease progression in LRRK2 carriers compared to iPD. Importantly, we confirm previous findings in PD genetic subsets where disease characteristics were ascertained through clinical exam. Overall, these data support the effective use of self-report and genetic data to rapidly analyze information from a large disease population or difficult to identify genetic subgroups.
Acoustic Tweezing Cytometry Induces Rapid Initiation of Human Embryonic Stem Cell Differentiation
Authors: Topal Tuğba , Hong Xiaowei , Xue Xufeng , Fan Zhenzhen , Kanetkar Ninad , Nguyen Joe T. , Fu Jianping , Deng Cheri X. , Krebsbach Paul H. 
Published: August 2018

AbstractMechanical forces play critical roles in influencing human embryonic stem cell (hESC) fate. However, it remains largely uncharacterized how local mechanical forces influence hESC behavior in vitro. Here, we used an ultrasound (US) technique, acoustic tweezing cytometry (ATC), to apply targeted cyclic subcellular forces to hESCs via integrin-bound microbubbles (MBs). We found that ATC-mediated cyclic forces applied for 30 min to hESCs near the edge of a colony induced immediate global responses throughout the colony, suggesting the importance of cell-cell connection in the mechanoresponsiveness of hESCs to ATC-applied forces. ATC application generated increased contractile force, enhanced calcium activity, as well as decreased expression of pluripotency transcription factors Oct4 and Nanog, leading to rapid initiation of hESC differentiation and characteristic epithelial-mesenchymal transition (EMT) events that depend on focal adhesion kinase (FAK) activation and cytoskeleton (CSK) tension. These results reveal a unique, rapid mechanoresponsiveness and community behavior of hESCs to integrin-targeted cyclic forces.
Outer membrane lipoprotein RlpA is a novel periplasmic interaction partner of the cell division protein FtsK in Escherichia coli
Authors: Berezuk Alison M. , Glavota Sabrina , Roach Elyse J. , Goodyear Mara C. , Krieger Jonathan R. , Khursigara Cezar M. 
Published: August 2018

AbstractIn Escherichia coli, formation of new cells is mediated by the elongasome and divisome that govern cell elongation and septation, respectively. Proper transition between these events is essential to ensure viable progeny are produced; however, the components of each complex responsible for transmission of the cell signal to shift from elongation to septation are unclear. Recently, a region within the N-terminal domain of the essential divisome protein FtsK (FtsKN) was identified that points to a key role for FtsK as a checkpoint of cell envelope remodeling during division. Here, we used site-specific in vivo UV cross-linking to probe the periplasmic loops of FtsKN for protein interaction partners critical for FtsKN function. Mass spectrometry analysis of five unique FtsKN periplasmic cross-links revealed a network of potential FtsKN interactors, one of which included the septal peptidoglycan binding protein rare lipoprotein A (RlpA). This protein was further verified as a novel interaction partner of FtsKN by an in vitro pull-down assay. Deletion of rlpA from an FtsK temperature-sensitive E. coli strain partially restored cell growth and largely suppressed cellular filamentation compared to the wild-type strain. This suggests that interaction with RlpA may be critical in suppressing septation until proper assembly of the divisome.
Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
Authors: Barbé Laure , Le Moullac-Vaidye Béatrice , Echasserieau Klara , Bernardeau Karine , Carton Thomas , Bovin Nicolai , Nordgren Johan , Svensson Lennart , Ruvoën-Clouet Nathalie , Le Pendu Jacques 
Published: August 2018

AbstractHuman strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of theFUT2wild type allele in sera from young healthy adults. Nonetheless,in vitroinfection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
Sonication of heart valves detects more bacteria in infective endocarditis
Authors: Gomes Anna , van Oosten Marleen , Bijker Kasper L. B. , Boiten Kathleen E. , Salomon Elisa N. , Rosema Sigrid , Rossen John W. A. , Natour Ehsan , Douglas Yvonne L. , Kampinga Greetje A. , van Assen Sander , Sinha Bhanu 
Published: August 2018

AbstractOptimal antimicrobial treatment of infective endocarditis requires identification and susceptibility patterns of pathogens. Sonication of explanted heart valves could increase the identification and culture of pathogens, as shown in prosthetic joint and pacemaker/ICD infections. We tested 26 explanted heart valves from 20 patients with active definite endocarditis for added diagnostic value of sonication to the standard microbiological workup in a prospective diagnostic proof of concept study. Two sonication protocols (broth enrichment vs. centrifugation) were compared in an additional 35 negative control valves for contamination rates. We selected sonication/centrifugation based on acceptable false positive rates (11.4%; 4/35). Sonication/enrichment yielded many false positive results in negative controls (28.6%; 10/35), mainly Propionibacterium acnes (next-generation sequencing excluded technical problems). Compared to direct culture only, adding sonication/centrifugation (including molecular testing) significantly increased the diagnostic yield from 6/26 to 17/26 valves (p = 0.003). Most importantly, culture positives almost doubled (from 6 to 10), providing unique quantitative information about antimicrobial susceptibility. Even if direct molecular testing was added to the standard workup, sonication/centrifugation provided additional diagnostic information in a significant number of valves (8/26; 31%; p = 0.013). We concluded that sonication/centrifugation added relevant diagnostic information in the workup of heart valves with infective endocarditis, with acceptable contamination rates.
Scenario analysis of ecosystem service changes and interactions in a mountain-oasis-desert system: a case study in Altay Prefecture, China
Authors: Fu Qi , Hou Ying , Wang Bo , Bi Xu , Li Bo , Zhang Xinshi 
Published: August 2018

AbstractScenario analysis of ecosystem services (ES) can provide a scientific basis for ecosystem management. The objective of this study was to reveal the effects of future land use scenarios on ES in a mountain-oasis-desert system (MODS). We first simulated land use changes for the period of 2015–2035 in Altay Prefecture under three different scenarios: business as usual (BAU), economic development (ED), and ecological conservation (EC). We then evaluated water yield (WY), crop production (CP), soil conservation (SC), sand fixation (SF), carbon sequestration (CS), and aesthetic value (AV) and investigated the multiple interactions among ES at the regional and grid scales. The results showed that SC, CS, and AV continually increased, WY continually decreased under the three scenarios. Our study revealed that the multiple interactions among ES were spatially heterogeneous in the MODS and the spatial heterogeneities changed across scenarios. The locations of and causes for the formation of the multiple interactions among ES were identified based on spatial analysis. This information can help decision-makers develop targeted and differentiated ecosystem management strategies. This study can increase the understanding of the multiple interactions among ES. Our findings can provide a reference for studies of other regions with the MODS structure.
Evaluation of modified Interferon alpha mRNA constructs for the treatment of non-melanoma skin cancer
Authors: Hochmann Sarah , Mittermeir Michaela , Santic Radmila , Koszik Frieder , Griessner Lanay , Sonderegger Alina Sarah , Hoffmann Thomas , Russe Elisabeth , Scheiblhofer Sandra , Weiss Richard , Mandler Markus , Schneeberger Achim , Strunk Dirk 
Published: August 2018

AbstractApplication of in vitro transcribed (IVT) messenger ribonucleic acid (mRNA) is an increasingly popular strategy to transiently produce proteins as therapeutics in a tissue or organ of choice. Here, we focused on the skin and aimed to test if whole human skin tissue explant technology can be used to evaluate the expression efficacy of different IVT Interferon alpha (IFN-α) mRNA constructs in situ, after biolistic delivery. Skin explants were viable and intact for at least five days based on histologic analysis and TUNEL staining. Using GFP reporter mRNA formulations, we found mostly epidermal expression after biolistic delivery. Two out of five sequence-optimized IFN-α mRNA variants resulted in significantly improved IFN-α protein expression in human skin compared to native IFN-α mRNA transfection. IFN-α secretion analysis of the surrounding culture media confirmed these results. We provide a proof-of-concept that IFN-α mRNA delivery into intact human full thickness skin explants can be utilized to test mRNA sequence modifications ex vivo. This approach could be used to develop novel mRNA-based treatments of common epidermal skin conditions including non-melanoma skin cancer, where IFN-α protein therapy has previously shown a strong therapeutic effect.
Visualizing Degradation of Black Phosphorus Using Liquid Crystals
Authors: Naqvi Bilal Abbas , Shehzad Muhammad Arslan , Cha Janghwan , Min Kyung-Ah , Khan M. Farooq , Hussain Sajjad , Seo Yongho , Hong Suklyun , Eom Jonghwa , Jung Jongwan 
Published: August 2018

AbstractBlack Phosphorus (BP) is an excellent material from the post graphene era due to its layer dependent band gap, high mobility and high Ion/Ioff. However, its poor stability in ambient poses a great challenge for its practical and long-term usage. The optical visualization of the oxidized BP is the key and the foremost step for its successful passivation from the ambience. Here, we have conducted a systematic study of the oxidation of the BP and developed a technique to optically identify the oxidation of the BP using Liquid Crystal (LC). It is interesting to note that we found that the rapid oxidation of the thin layers of the BP makes them disappear and can be envisaged by using the alignment of the LC. The molecular dynamics simulations also proved the preferential alignment of the LC on the oxidized BP. We believe that this simple technique will be effective in passivation efforts of the BP, and will enable it for exploitation of its properties in the field of electronics.
The Hepcidin/Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells
Authors: Ramakrishnan Latha , Pedersen Sofia L. , Toe Quezia K. , West Laura E. , Mumby Sharon , Casbolt Helen , Issitt Theo , Garfield Benjamin , Lawrie Allan , Wort S. John , Quinlan Gregory J. 
Published: August 2018

AbstractStudies were undertaken to examine any role for the hepcidin/ferroportin axis in proliferative responses of human pulmonary artery smooth muscle cells (hPASMCs). Entirely novel findings have demonstrated the presence of ferroportin in hPASMCs. Hepcidin treatment caused increased proliferation of these cells most likely by binding ferroportin resulting in internalisation and cellular iron retention. Cellular iron content increased with hepcidin treatment. Stabilisation of ferroportin expression and activity via intervention with the therapeutic monoclonal antibody LY2928057 reversed proliferation and cellular iron accumulation. Additionally, IL-6 treatment was found to enhance proliferation and iron accumulation in hPASMCs; intervention with LY2928057 prevented this response. IL-6 was also found to increase hepcidin transcription and release from hPASMCs suggesting a potential autocrine response. Hepcidin or IL-6 mediated iron accumulation contributes to proliferation in hPASMCs; ferroportin mediated cellular iron excretion limits proliferation. Haemoglobin also caused proliferation of hPASMCs; in other novel findings, CD163, the haemoglobin/haptoglobin receptor, was found on these cells and offers a means for cellular uptake of iron via haemoglobin. Il-6 was also found to modulate CD163 on these cells. These data contribute to a better understanding of how disrupted iron homeostasis may induce vascular remodelling, such as in pulmonary arterial hypertension.
Computational characterization and identification of human polycystic ovary syndrome genes
Authors: Zhang Xing-Zhong , Pang Yan-Li , Wang Xian , Li Yan-Hui 
Published: August 2018

AbstractHuman polycystic ovary syndrome (PCOS) is a highly heritable disease regulated by genetic and environmental factors. Identifying PCOS genes is time consuming and costly in wet-lab. Developing an algorithm to predict PCOS candidates will be helpful. In this study, for the first time, we systematically analyzed properties of human PCOS genes. Compared with genes not yet known to be involved in PCOS regulation, known PCOS genes display distinguishing characteristics: (i) they tend to be located at network center; (ii) they tend to interact with each other; (iii) they tend to enrich in certain biological processes. Based on these features, we developed a machine-learning algorithm to predict new PCOS genes. 233 PCOS candidates were predicted with a posterior probability >0.9. Evidence supporting 7 of the top 10 predictions has been found.
Germinated soy germ with increased soyasaponin Ab improves BMP-2-induced bone formation and protects against in vivo bone loss in osteoporosis
Authors: Choi Chan-Woong , Choi Sik-Won , Kim Han-Jun , Lee Kwang-Sik , Kim Shin-Hye , Kim Sun-Lim , Do Sun Hee , Seo Woo-Duck 
Published: August 2018

AbstractOsteoporosis is frequently induced following menopause, and bone fractures result in serious problems including skeletal deformity, pain, and increased mortality. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aimed to clarify the bone protecting effects of germinated soy germ extracts (GSGE) and their mode of action. GSGE increased expression of alkaline phosphatase (ALP) and osteocalcin (OCL) by stimulating the expression of runt-related transcription factor 2 (Runx2) and osterix (Osx) through activation of Smad signaling molecules. Furthermore, germination of soy germ increased levels of nutritional components, especially soyasaponin Ab. The anabolic activity of soyasaponin Ab in GSGE was also evaluated. GSGE and soyasaponin Ab significantly protected against ovariectomy (OVX)-induced bone loss and improved bone-specific alkaline phosphatase (BALP) level in mouse serum. These in vitro and in vivo study results demonstrated that GSGE and soyasaponin Ab have potential as therapeutic candidate agents for bone protection in postmenopausal osteoporosis.