bluuebunny/crossref_metadata_2025_split huggingface dataset:
Several microRNAs could predict survival in patients with hepatitis B-related liver cancer
Authors: Zhen Ye , Xinghui Zhao , Chao Wu , Yi Zhao , Jinwen Chen , Ruifang Gao , Chao Zhang , Min Zhao , Chunlei Guo , Yan Fang , Lingfang Du , Long Shen , Wenzhi Shen , Xiaohe Luo , Rong Xiang 
Published: March 2017

AbstractMicroRNAs as biomarkers play an important role in the tumorigenesis process, including hepatocellular carcinomas (HCCs). In this paper, we used The Cancer Genome Atlas (TCGA) database to mine hepatitis B-related liver cancer microRNAs that could predict survival in patients with hepatitis B-related liver cancer. There were 93 cases of HBV-HCC and 49 cases of adjacent normal controls included in the study. Kaplan–Meier survival analysis of a liver cancer group versus a normal control group of differentially expressed genes identified eight genes with statistical significance. Compared with the normal liver cell line, hepatocellular carcinoma cell lines had high expression of 8 microRNAs, albeit at different levels. A Cox proportional hazards regression model for multivariate analysis showed that four genes had a significant difference. We established classification models to distinguish short survival time and long survival time of liver cancers. Eight genes (mir9-3, mir10b, mir31, mir519c, mir522, mir3660, mir4784, and mir6883) were identified could predict survival in patients with HBV-HCC. There was a significant correlation between mir10b and mir31 and clinical stages (p < 0.05). A random forests model effectively estimated patient survival times.
Reduced graphene oxide@TiO2 nanorod@reduced graphene oxide hybrid nanostructures for photoelectrochemical hydrogen production
Authors: Wang Longlu , Li Yue , Liu Yutang 
Published: March 2017

The optimised geometrical configuration between TiO2 nanorods (NRs) arrays and reduced graphene oxide (RGO) is essential for their application in catalysis of photoelectrochemical hydrogen production system. The scrupulous design of hierarchical nanoarchitectures by integration of multiple active materials can reinforce the light harvesting efficiency, enhance photocarrier generation and provide fast electron transport and efficient charge collection. Graphene film formed on the top surface and at the bottom of titanium dioxide nanorod (TiO2NRs) arrays were scrupulously fabricated in this paper. More importantly, the hydrogen production rate of RGO@TiO2NR@RGO hybrid nanostructures was up to 800 μmol/h−1 m2 (radiation intensity: 160 mW/cm2) which is over 2.5 times compared with bare TiO2NR.
An Extrapericardial Minimally Invasive Approach for Implantable Cardioverter Defibrillator
Authors: Madjarov Jeko , Poole Brad , Madzharov Svetozar , Fedor John , Robicsek Francis , Katz Michael 
Published: March 2017

AbstractThe indications for placement of an implantable cardioverter defibrillators (ICDs) have greatly expanded over the last years. However, standard transvenous approach is not suitable for a subset of patients who cannot benefit from ICD therapy. Here, we have demonstrated the feasibility and efficacy of extrapericardial ICD placement through a minimally invasive access in intact hearts as well as in postmyocardial infarction large animal models. Based on our data, we conclude that extrapericardial ICD placement is a feasible approach that may be a valuable alternative or adjunct to current defibrillator lead systems.
Role of Neuroimaging in Guiding Treatment Decisions on Endovascular Thrombectomy
Authors: Kaiser Daniel , Gerber Johannes , Puetz Volker 
Published: March 2017

AbstractSix recent randomized controlled trials showed a significant benefit of endovascular therapy on patient outcome in acute ischemic stroke due to anterior cerebral artery occlusion. The positive results of these trials need to be implemented in clinical routine. Suitable patients should be evaluated for thrombectomy reliably and fast. All trials confirmed the role of pretherapeutic neuroimaging as crucial in selecting patients who can benefit from endovascular therapy. However, different approaches have been used, including imaging of the target vascular occlusion, infarct core, arterial collateral supply or the penumbra. In this review we discuss, in the context of the recent trials, the different methods of non-invasive neuroimaging and their role in decision-making for thrombectomy in acute ischemic stroke.
The future of research assessment in the humanities: bottom-up assessment procedures
Authors: Ochsner Michael , Hug Sven , Galleron Ioana 
Published: March 2017

AbstractResearch assessment in the social sciences and humanities (SSH) is delicate. Assessment procedures meet strong criticisms from SSH scholars and bibliometric research shows that the methods that are usually applied are ill-adapted to SSH research. While until recently research on assessment in the SSH disciplines focused on the deficiencies of the current assessment methods, we present some European initiatives that take a bottom-up approach. They focus on research practices in SSH and reflect on how to assess SSH research with its own approaches instead of applying and adjusting the methods developed for and in the natural and life sciences. This is an important development because we can learn from previous evaluation exercises that whenever scholars felt that assessment procedures were imposed in a top-down manner without proper adjustments to SSH research, it resulted in boycotts or resistance. Applying adequate evaluation methods not only helps foster a better valorization of SSH research within the research community, among policymakers and colleagues from the natural sciences, but it will also help society to better understand SSH’s contributions to solving major societal challenges. Therefore, taking the time to encourage bottom-up evaluation initiatives should result in being able to better confront the main challenges facing modern society. This article is published as part of a collection on the future of research assessment.
Sensing relative signal in the Tgf-β/Smad pathway
Authors: Frick Christopher L. , Yarka Clare , Nunns Harry , Goentoro Lea 
Published: March 2017

Significance
It is not fully understood how cells process information in the face of noise. We posed this question in the transforming growth factor-β (Tgf-β) pathway, a major intercellular signaling pathway in animal cells. We found evidence that rather than sensing the signaling state of the Tgf-β pathway, cells sense the signaling state relative to background. Finding that signaling dynamics are interpreted in a relative manner may have implications for how we understand the pathway’s context-dependent outcomes and roles in diseases. Our work reinforces an emerging principle that individual cells process signal in a relative manner.
Allele-specific non-CG DNA methylation marks domains of active chromatin in female mouse brain
Authors: Keown Christopher L. , Berletch Joel B. , Castanon Rosa , Nery Joseph R. , Disteche Christine M. , Ecker Joseph R. , Mukamel Eran A. 
Published: March 2017

Significance
Mammalian cells contain two copies of the genome inherited from the two parents. Although most genes are expressed using both, a small but critical part of the genome has different levels of expression from each copy. These parts include the X chromosome in females and imprinted genes in both genders, which play key roles in brain development and cognition. We measured gene expression and DNA methylation, an epigenetic modification of the genome, in the brains of mice using a technique that allowed us to analyze the maternal and paternal copies of the genome separately. Our findings show that a brain-specific form of DNA methylation called non-CG methylation marks regions of active transcription within the inactive X chromosome.
Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer’s pathology
Authors: Zhang Zui , Takeda-Uchimura Yoshiko , Foyez Tahmina , Ohtake-Niimi Shiori , Narentuya  , Akatsu Hiroyasu , Nishitsuji Kazuchika , Michikawa Makoto , Wyss-Coray Tony , Kadomatsu Kenji , Uchimura Kenji 
Published: March 2017

Significance
Keratan sulfate (KS) is an extracellular sulfated glycan covalently attached to core proteins in the brain. Here, we show that a type of KS with a certain molecular mass in microglia and its synthetic enzyme GlcNAc6ST1, previously known as a sulfotransferase for ligands of L-selectin, are upregulated in model mice and patients with Alzheimer’s disease. GlcNAc6ST1 deficiency resulted in increased amyloid-β phagocytosis and hyperresponsiveness to an antiinflammatory cytokine in primary microglia. Moreover, amyloid-β pathology was mitigated in GlcNAc6ST1-deficient Alzheimer’s model mice. These data support a model in which GlcNAc6ST1 regulates microglial functions via synthesizing sialic acid-modified KS, a potential ligand for microglial carbohydrate-recognizing receptors, in Alzheimer’s pathology.
Highly oriented photosynthetic reaction centers generate a proton gradient in synthetic protocells
Authors: Altamura Emiliano , Milano Francesco , Tangorra Roberto R. , Trotta Massimo , Omar Omar Hassan , Stano Pasquale , Mavelli Fabio 
Published: March 2017

Significance
The photosynthetic reaction center (RC), an integral membrane protein at the core of bioenergetics of all autotrophic organisms, has been reconstituted in the membrane of giant unilamellar vesicles (RC@GUV) by retaining the physiological orientation at a very high percentage (90 ± 1%). Owing to this uniform orientation, it has been possible to demonstrate that, under red-light illumination, photosynthetic RCs operate as nanoscopic machines that convert light energy into chemical energy, in the form of a proton gradient across the vesicle membrane. This result is of great relevance in the field of synthetic cell construction, proving that such systems can easily transduce light energy into chemical energy eventually exploitable for the synthesis of ATP.
EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms
Authors: van Lengerich Bettina , Agnew Christopher , Puchner Elias M. , Huang Bo , Jura Natalia 
Published: March 2017

Significance
Signaling by human epidermal growth factor receptor (HER) receptors relies on heteromeric interactions between four members of the family: EGF receptor, HER2, HER3, and HER4. These interactions remain remarkably poorly understood. Using super-resolution microscopy imaging and signaling assays, we demonstrate a rich scope of HER receptor organization patterns that are differentially influenced by ligands and coreceptor expression, resulting in unique phosphorylation signatures of HER receptors. We also show that there are fundamental differences in molecular mechanisms that govern HER receptor cross-activation, which do not always follow the canonical kinase dimerization mechanism. Our data underscore an emerging concept in the field that HER receptor signaling needs to be interpreted in the context of higher-order receptor oligomers, redefining the basic signaling unit relevant for receptor function.
Experimental evidence that parasites drive eco-evolutionary feedbacks
Authors: Brunner Franziska S. , Anaya-Rojas Jaime M. , Matthews Blake , Eizaguirre Christophe 
Published: March 2017

SignificanceAnthropogenic effects on the environment are ubiquitous and have enormous impacts on individual and ecosystem health. It is widely accepted that environmental change affects disease distribution, but how it may affect parasite-driven evolution remains elusive. Our results provide experimental evidence that parasites play a major role in ecosystem dynamics and, as a result, can affect selection in subsequent host generations. This role is further modified by the prevailing environmental conditions that affect disease dynamics in two ways: through altered ecological opportunities for disease and through altered evolutionary effects on the host.
Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating
Authors: Vullo Sabrina , Bonifacio Gaetano , Roy Sophie , Johner Niklaus , Bernèche Simon , Kellenberger Stephan 
Published: March 2017

Significance
Many physiological processes are regulated by pH. The acid-sensing ion channels (ASICs) are neuronal pH sensors involved in learning, fear behavior, neurodegeneration after ischemic stroke, and pain sensation. The mechanism by which acidic pH activates ASICs is still poorly understood. We show here that the “acidic pocket,” the binding site of several toxins, is not essential for channel function but has, rather, a modulatory role. Furthermore, we describe the structural rearrangements occurring in this domain during ASIC activity, and highlight the importance of the “palm” domain in channel opening and current decay. In this study, we provide insights on the molecular mechanisms controlling ASIC activity together with a rational basis for the development of ASIC-targeting drugs.
Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles
Authors: Schulz Robert , Yamamoto Kenji , Klossek André , Flesch Roman , Hönzke Stefan , Rancan Fiorenza , Vogt Annika , Blume-Peytavi Ulrike , Hedtrich Sarah , Schäfer-Korting Monika , Rühl Eckart , Netz Roland R. 
Published: March 2017

Significance
Human skin consists of distinct layers and is designed to prevent water loss and to keep harmful materials out, which makes transcutaneous drug delivery challenging. A model for drug diffusion within skin is introduced that as the only input requires experimental concentration profiles measured at three distinct penetration times. For the specific example of the antiinflammatory drug dexamethasone, the modeling shows that both free-energy and diffusivity profiles are highly inhomogeneous, which reveals the basic mechanism of epidermal barrier function: slow diffusion in the outer stratum corneum hinders fast penetration into the skin, whereas a pronounced free-energy step from the epidermis to the dermis underneath reduces long-time permeation. Targeted drug delivery strategies through skin must reflect these properties.
Decoupling local mechanics from large-scale structure in modular metamaterials
Authors: Yang Nan , Silverberg Jesse L. 
Published: March 2017

Significance
The forward-design approach to mechanical metamaterials determines a structure’s properties after it is designed. In contrast, the inverse-design approach specifies parameter domains then optimizes a cost function to achieve a desired property. The former approach guarantees a structure will exist but lacks the ability to prescribe function. The latter approach has prescribed function, but existence is not guaranteed. Here, we trivialize these design challenges for metamaterials by decoupling local mechanical properties from the bulk structure, allowing both to be specified independently. This work introduces a design strategy that substantially advances the capacity to engineer mechanical metamaterials by specifically using modular units with more free design parameters than constraints. The fundamental strategy is explicitly demonstrated with an origami- and kirigami-inspired structure.
Structural basis for specific ligation of the peroxisome proliferator-activated receptor δ
Authors: Wu Chyuan-Chuan , Baiga Thomas J. , Downes Michael , La Clair James J. , Atkins Annette R. , Richard Stephane B. , Fan Weiwei , Stockley-Noel Theresa A. , Bowman Marianne E. , Noel Joseph P. , Evans Ronald M. 
Published: March 2017

Significance
Clinical treatments for metabolic diseases rely on agents with high selectivity to specific targets often within a class of structurally and functionally related proteins. In this paper, we uncover physical and chemical features governing selective small-molecule binding to peroxisome proliferator-activated receptor (PPAR) δ concomitant with distinct conformational changes in the receptor, key to therapeutic modulation of lipid catabolism, transport, and storage. These studies reveal the subtle interplay between ligand configuration and chemistry coupled to modulation of PPARδ structural dynamics. This set of structure–activity relationships (SARs) guide synthetic ligand designs necessary to refine therapeutic leads for temporally and spatially regulating PPARδ during the course of metabolic disease onset and progression.
p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates
Authors: Nguyen Thang Van , Li Jing , Lu Chin-Chun (Jean) , Mamrosh Jennifer L. , Lu Gang , Cathers Brian E. , Deshaies Raymond J. 
Published: March 2017

SignificanceWe have recently reported that glutamine synthetase (GS) is negatively regulated by glutamine through a feedback loop involving the E3 ubiquitin ligase CRL4CRBN. However, the molecular events that take place at each step of the pathway are not well understood. Here, we show that valosin-containing protein (VCP)/p97, is required for GS degradation. It acts downstream of CRL4CRBN. p97 extracts ubiquitylated GS subunits from the decamer so that they can be degraded by the proteasome. Interestingly, p97 is also required for immunomodulatory drug-induced degradation of all four known CRL4CRBNneosubstrates, including Ikaros family zinc finger proteins 1 (IKZF1) and 3 (IKZF3), casein kinase 1α (CK1α), and the translation termination factor GSPT1, which accounts for antitumor activity of these drugs. Our findings could have important implications for patient responsiveness to cancer therapy with immunomodulatory drugs.
‘English a foreign tongue’
Authors: Sebba Mark 
Published: March 2017

Abstract
The 2011 UK Census was the first ever to ask a question about language in England. The period during which the census was planned coincided with a period of intense politicisation of the language issue, which had previously not been a major point of controversy.
The census results showed that 98.3% of the adult population either spoke English as their ‘main language’, or could speak it well or very well. In 4% of households no adults spoke English as a main language. These statistics produced an intense media reaction focussed on the number of people who supposedly could not speak English, with some high-level misunderstandings about what the figures meant.
This paper discusses the pervasiveness in the census process of ideologies about language, and how an apparently honest attempt to collect information for service providers was used to justify anti-immigration discourse and the reduction of services for non-speakers of English.
Blood, Soil, and Tears
Authors: Santa Ana Otto , Waitkuweit Kevin Hans , Hernandez Mishna Erana 
Published: March 2017

Abstract
The Fourteenth Amendment to the US Constitution grants citizenship to every child born on US soil. While most Americans think this 150 year old formulation is permanent, it is actually open to change. We explore the legal debate over the current formulation of US citizenship. Using the research design of the exemplar case study, we undertake a conceptual metaphor-based critical discourse analysis of three contending contemporary legal stances regarding US citizenship. In the light of four current court cases, some legal theorists argue that the formulation is both undemocratic and inadequate, and should be amended to address 21st century national concerns. Others argue to retain the current formulation in spite of these concerns. Our study reveals that the rival stances are argued in terms of irreconcilable conceptual metaphors, and each legal stance in itself is deficient to address these current concerns.
Association Between Cardiovascular Health and Endothelial Function With Future Erectile Dysfunction: The Multi-Ethnic Study of Atherosclerosis
Authors: Lane-Cordova Abbi D. , Kershaw Kiarri , Liu Kiang , Herrington David , Lloyd-Jones Donald M. 
Published: March 2017

Abstract

BACKGROUND
The association of Cardiovascular Health (CVH; defined by the American Heart Association by assigning points for health-related behavioral and clinical factors) with endothelial and erectile dysfunction has not been reported, although endothelial and erectile dysfunction have been associated with components of CVH.

METHODS
Data were collected in 1,136 men in the Multi-Ethnic Study of Atherosclerosis at baseline and erectile dysfunction status (measured by survey or medication use) at exam 5. CVH was determined with 7 health metrics. Endothelial function was measured with brachial artery flow-mediated dilation (FMD). Poisson regression was used to determine associations between CVH and erectile dysfunction across categories of CVH (low, moderate, and high).

RESULTS
Age and proportion of Black or Latino participants decreased while proportion of Chinese-American participants increased with higher CVH category. FMD was higher in men without erectile dysfunction and higher in men with high vs. low CVH. Erectile dysfunction prevalence was lower with better CVH; 58% in men with low CVH, 41% with moderate CVH, and 33% with high CVH (P &lt; 0.001). CVH was associated with erectile dysfunction; prevalence ratio = 0.75 (95% confidence interval (CI) = 0.66, 0.84) with moderate CVH and 0.68 (95% CI = 0.49, 0.94) with high CVH (vs. men with low CVH) and 0.93 (95% CI = 0.91, 0.96) for every 1-point higher CVH score in a fully adjusted model, including FMD, age, education, depression score, use of antidepressant or beta-blocker medications, chronic disease, heavy drinking, and race.

CONCLUSION
CVH is associated with future erectile dysfunction, even after adjustment for baseline FMD. Maintaining high CVH may improve quality of life for men.
Rapid Sequentialin SituMultiplexing With DNA-Exchange-Imaging
Authors: Wang Yu , Woehrstein Johannes B. , Donoghue Noah , Dai Mingjie , Avendaño Maier S. , Schackmann Ron C.J. , Zoeller Jason J. , Wang Shan Shan H. , Tillberg Paul W. , Park Demian , Lapan Sylvain W. , Boyden Edward S. , Brugge Joan S. , Kaeser Pascal S. , Church George M. , Agasti Sarit S. , Jungmann Ralf , Yin Peng 
Published: March 2017

AbstractTo decipher the molecular mechanism of biological function, it is critical to map the molecular composition of individual cells in the context of their biological environmentin situ. Immunofluorescence (IF) provides specific labeling for molecular profiling. However, conventional IF methods have finite multiplexing capabilities due to spectral overlap of the fluorophores. Various sequential imaging methods have been developed to circumvent this spectral limit, but are not widely adopted due to the common limitation of requiring multi-rounds of slow (typically over 2 hours at room temperature to overnight at 4 °C in practice) immunostaining. DNA-Exchange-Imaging is a practical platform for rapidin situspectrally-unlimited multiplexing. This technique overcomes speed restrictions by allowing for single-step immunostaining with DNA-barcoded antibodies, followed by rapid (less than 10 minutes) buffer exchange of fluorophore-bearing DNA imager strands. By eliminating the need for multiple rounds of immunostaining, DEI enables rapid spectrally unlimited sequential imaging. The programmability of DNA-Exchange-Imaging allows us to further adapt it to diverse microscopy platforms (with Exchange-Confocal, Exchange-SIM, Exchange-STED, and Exchange-PAINT demonstrated here), achieving highly multiplexedin situprotein visualization in diverse samples (including neuronal and tumor cells as well as fresh-frozen or paraffin-embedded tissue sections) and at multiple desired resolution scales (from ~300 nm down to sub-20-nm). Validation highlights include 8-target imaging using single-channel Exchange-Confocal in tens of micron thick retina tissue sections in 2-3 hours (as compared to days required in principle by previous methods using comparable equipment), and 8-target super-resolution imaging with ~20 nm resolution using Exchange-PAINT in primary neurons. These results collectively suggest DNA-Exchange as a versatile, practical platform for rapid, highly multiplexedin situimaging, potentially enabling new applications ranging from basic science, to drug discovery, and to clinical pathology.