bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role, mechanism and potentially novel biomarker of microRNA-17-92 cluster in macrosomia
Authors: Li Jing , Chen Liping , Qiuqin Tang  , Wu Wei , Hao Gu  , Lou Liu  , Jie Wu  , Hua Jiang  , Hongjuan Ding  , Xia Yankai , Chen Daozhen , Hu Yali , Wang Xinru 
Published: November 2015

AbstractMacrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.
Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody
Authors: Wuerth Michelle E. , Cragerud Rebecca K. , Clint Spiegel P. 
Published: November 2015

AbstractBlood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.
Off-Pump Conversion: In-hospital Mortality and Long-Term Survival
Authors: Pullan Mark , Oo Aung , Poullis Michael 
Published: November 2015

Background There is an ongoing debate on the benefits and risks of off-pump coronary artery bypass grafting (CABG) surgery. The fate of patients who start with their procedure being an off-pump one and then have to undergo conversion to an on-pump procedure is debated with regard to in-hospital mortality and unknown with regard to long-term survival. We investigated the in-hospital mortality and long-term survival of patients who underwent conversion from off- to on-pump surgery.
Methods We performed a multivariate and propensity analysis on in-hospital mortality and long-term survival of postisolated CABG patients in a single institution having 15,704 patients of which 5,353 who underwent off-pump CABG were analyzed.
Results In-hospital mortality was 2.15% for the study cohort, and 73 (1.4%) off-pump cases were converted. Univariate analysis demonstrated that patients undergoing conversion had a significantly increased in-hospital mortality (p < 0.001) and reduced long-term survival (p = 0.002). Logistic regression (receiver operating curve 0.77, Hosmer-Lemeshow test 0.46) and Cox analysis demonstrated that in-hospital mortality and long-term survival were not significantly affected by conversion. Propensity analysis (one:many match) demonstrated that in-hospital mortality was not significantly affected (p = 0.7), and long-term survival - univariate, and multivariate were also not significantly reduced in patients undergoing conversion.
Conclusion Conversion from off- to on-pump by a team of surgeons and anesthetists who are dedicated off-pump specialists does not have an impact on in-hospital mortality or long-term survival.
A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity
Authors: Heijink Anne Margriet , Blomen Vincent A. , Bisteau Xavier , Degener Fabian , Matsushita Felipe Yu , Kaldis Philipp , Foijer Floris , van Vugt Marcel A. T. M. 
Published: November 2015

SignificanceInhibition of Wee1 is considered an attractive anticancer therapy forTP53mutant tumors. However, additional factors besides p53 inactivation may determine Wee1 inhibitor sensitivity, which we searched for using unbiased functional genetic screening. We discovered that the mutational status of several S-phase genes, includingCDK2, determines the cytotoxicity induced by Wee1 inhibition. Notably, we found that Wee1 inhibition induces two distinct phenotypes: accumulation of DNA damage in S phase and karyokinesis/cytokinesis failure during mitosis. Stable depletion of S-phase genes only reversed the formation of DNA damage, but did not rescue karyokinesis/cytokinesis failure upon Wee1 inhibition. Thus, inactivation of nonessential S-phase genes can overcome Wee1 inhibitor resistance, while allowing the survival of genomically instable cancer cells.
Corporate funding and ideological polarization about climate change
Authors: Farrell Justin 
Published: November 2015

Significance
Ideological polarization around environmental issues—especially climate change—have increased in the last 20 years. This polarization has led to public uncertainty, and in some cases, policy stalemate. Much attention has been given to understanding individual attitudes, but much less to the larger organizational and financial roots of polarization. This gap is due to prior difficulties in gathering and analyzing quantitative data about these complex and furtive processes. This paper uses comprehensive text and network data to show how corporate funding influences the production and actual thematic content of polarization efforts. It highlights the important influence of private funding in public knowledge and politics, and provides researchers a methodological model for future studies that blend large-scale textual discourse with social networks.
Animal origin of 13th-century uterine vellum revealed using noninvasive peptide fingerprinting
Authors: Fiddyment Sarah , Holsinger Bruce , Ruzzier Chiara , Devine Alexander , Binois Annelise , Albarella Umberto , Fischer Roman , Nichols Emma , Curtis Antoinette , Cheese Edward , Teasdale Matthew D. , Checkley-Scott Caroline , Milner Stephen J. , Rudy Kathryn M. , Johnson Eric J. , Vnouček Jiří , Garrison Mary , McGrory Simon , Bradley Daniel G. , Collins Matthew J. 
Published: November 2015

SignificanceThis study reports the first use, to our knowledge, of triboelectric extraction of protein from parchment. The method is noninvasive and requires no specialist equipment or storage. Samples can be collected without the need to transport the artifacts; instead, researchers can sample when and where possible and analyze when required. The level of access we have achieved highlights the importance of this technique. For this study, we have extracted proteins from 513 parchment samples, used to resolve the long-standing question of the origin of “uterine vellum.” We find no evidence of unexpected species, such as rabbit or squirrel. We suggest that uterine vellum was often an achievement of technological production using available resources, and would not have demanded unsustainable agricultural practices.
Mid-Pleistocene climate transition drives net mass loss from rapidly uplifting St. Elias Mountains, Alaska
Authors: Gulick Sean P. S. , Jaeger John M. , Mix Alan C. , Asahi Hirofumi , Bahlburg Heinrich , Belanger Christina L. , Berbel Glaucia B. B. , Childress Laurel , Cowan Ellen , Drab Laureen , Forwick Matthias , Fukumura Akemi , Ge Shulan , Gupta Shyam , Kioka Arata , Konno Susumu , LeVay Leah J. , März Christian , Matsuzaki Kenji M. , McClymont Erin L. , Moy Chris , Müller Juliane , Nakamura Atsunori , Ojima Takanori , Ribeiro Fabiana R. , Ridgway Kenneth D. , Romero Oscar E. , Slagle Angela L. , Stoner Joseph S. , St-Onge Guillaume , Suto Itsuki , Walczak Maureen D. , Worthington Lindsay L. , Bailey Ian , Enkelmann Eva , Reece Robert , Swartz John M. 
Published: November 2015

Significance
In coastal Alaska and the St. Elias orogen, over the past 1.2 million years, mass flux leaving the mountains due to glacial erosion exceeds the plate tectonic input. This finding underscores the power of climate in driving erosion rates, potential feedback mechanisms linking climate, erosion, and tectonics, and the complex nature of climate−tectonic coupling in transient responses toward longer-term dynamic equilibration of landscapes with ever-changing environments.
The structure of tropical forests and sphere packings
Authors: Taubert Franziska , Jahn Markus Wilhelm , Dobner Hans-Jürgen , Wiegand Thorsten , Huth Andreas 
Published: November 2015

SignificanceExplaining the tree size structure of tropical forests is of crucial importance because other important forest attributes can be derived from this. The tree diameter distribution, for example, determines the amount of carbon stored in a forest. Here we present a simple and powerful approach based on stochastic geometry and tree allometries that can be used to predict tree diameter distributions.
Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies
Authors: Zheng Zhengui , Armfield Brooke A. , Cohn Martin J. 
Published: November 2015

Significance
Birth defects of external genitalia occur at a striking frequency, affecting ∼1:250 live births. Congenital penile anomalies (CPAs) encompass a range of malformations, including failure of urethral tube closure (hypospadias), penile curvature (chordee), micropenis, and feminization of male genitalia. Both genetic anomalies and exposures to endocrine disrupting chemicals (EDCs) are suspected to be involved; however, little is known about the underlying causes or the developmental window(s) of sensitivity to antiandrogenic or estrogenic signals. This study shows that disruption of androgen signaling at different stages of genital development can induce different types of CPA. We identify a cell type in which the androgen receptor (AR) is essential for genital masculinization and uncover previously unknown mechanisms through which antiandrogenic and estrogenic signals induce penile malformations.
Evolution in leaps: The punctuated accumulation and loss of cultural innovations
Authors: Kolodny Oren , Creanza Nicole , Feldman Marcus W. 
Published: November 2015

Significance
The archaeological record suggests that cultural traits, as manifested in the tool repertoire, can accumulate exponentially, that technology can appear in bursts after long periods of stasis, and that dramatic cultural losses can occur. We introduce a model that accounts for this range of observations by considering a multifaceted creative process of innovation, accounting for the possibility that certain traits facilitate the invention of related traits. Further, we determine that differential distribution of tool-related knowledge, typically ignored in models, can dramatically affect the dynamics of cultural evolution, suggesting the concept of an effective cultural population size. Finally, we demonstrate that a fluctuating environment can lead to large-scale cultural losses and select for generalist tools that are useful in multiple conditions.
ER trapping reveals Golgi enzymes continually revisit the ER through a recycling pathway that controls Golgi organization
Authors: Sengupta Prabuddha , Satpute-Krishnan Prasanna , Seo Arnold Y. , Burnette Dylan T. , Patterson George H. , Lippincott-Schwartz Jennifer 
Published: November 2015

Significance
Using a rapamycin-based, endoplasmic reticulum (ER) trapping scheme, modified to avoid the problem of an endogenous ER-localized FKBP-binding protein, we demonstrate that Golgi enzymes constitutively recycle back to the ER and that such recycling plays a central role in the maintenance, biogenesis, and inheritance of the Golgi apparatus in mammalian cells. We describe morphological characteristics of the retrograde carriers that ferry Golgi enzymes back to the ER and identify key molecular machinery regulating carrier formation. The study helps resolve the long-standing debate regarding the extent of Golgi enzyme trafficking back to the ER, paving the way for further investigations into the mechanistic details and functional implications of the Golgi's steady-state existence and relationship to the ER.
Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic
Authors: Zhang Hai-nan , Yang Lina , Ling Jian-ya , Czajkowsky Daniel M. , Wang Jing-Fang , Zhang Xiao-Wei , Zhou Yi-Ming , Ge Feng , Yang Ming-kun , Xiong Qian , Guo Shu-Juan , Le Huang-Ying , Wu Song-Fang , Yan Wei , Liu Bingya , Zhu Heng , Chen Zhu , Tao Sheng-ce 
Published: November 2015

Significance
Arsenic holds promise for treating a wide range of tumors. To understand arsenic's antitumor mechanism further, we identified 360 arsenic-binding proteins using a human proteome microarray and found proteins of glycolysis to be highly enriched. In-depth in vitro and in vivo analysis revealed that glycolysis in general and the rate-limiting enzyme hexokinase-2 of the glycolytic pathway in particular play a key role in mediating the anticancer activity of arsenic. These findings shed light on the mode of action of arsenic, and the newly identified arsenic-binding proteins may serve as a rich resource for future studies.
Sieve estimation in a Markov illness-death process under dual censoring
Authors: Boruvka Audrey , Cook Richard J. 
Published: November 2015

AbstractSemiparametric methods are well established for the analysis of a progressive Markov illness-death process observed up to a noninformative right censoring time. However, often the intermediate and terminal events are censored in different ways, leading to a dual censoring scheme. In such settings, unbiased estimation of the cumulative transition intensity functions cannot be achieved without some degree of smoothing. To overcome this problem, we develop a sieve maximum likelihood approach for inference on the hazard ratio. A simulation study shows that the sieve estimator offers improved finite-sample performance over common imputation-based alternatives and is robust to some forms of dependent censoring. The proposed method is illustrated using data from cancer trials.
Simulating feedback from nuclear clusters: the impact of multiple sources
Authors: Bourne Martin A. , Power Chris 
Published: November 2015

Abstract
Nuclear star clusters (NCs) are found to exist in the centres of many galaxies and appear to follow scaling relations similar to those of supermassive black holes. Previous analytical work has suggested that such relations are a consequence of feedback-regulated growth. We explore this idea using high-resolution hydrodynamical simulations, focusing on the validity of the simplifying assumptions made in analytical models. In particular, we investigate feedback emanating from multiple stellar sources rather than from a single source, as is usually assumed, and show that collisions between shells of gas swept up by feedback leads to momentum cancellation and the formation of high-density clumps and filaments. This high-density material is resistant both to expulsion from the galaxy potential and to disruption by feedback; if it falls back on to the NC, we expect the gas to be available for further star formation or for feeding a central black hole. We also note that our results may have implications for the evolution of globular clusters and stellar clusters in high-redshift dark matter haloes.
Response of metastatic glioma to vemurafenib
Authors: Leaver Katie Emily , Zhang Niushen , Ziskin Jennifer L. , Vogel Hannes , Recht Lawrence , Thomas Reena P. 
Published: November 2015

Abstract
Extraneural metastatic disease of glioma is rare and poses unique therapeutic challenges. Increasingly, the ability to sequence genetic alterations in tumors has allowed for the identification of common oncogenic signatures such as the activating BRAFV600E mutation and may be useful in therapeutic decision making. We report two patients with widespread aggressive gliomas whose tumors were found to express the BRAFV600E mutation and then responded robustly albeit transiently when exposed to vemurafenib. Although both patients succumbed to their disease, our results suggest that targeting BRAF might be appropriate for patients with aggressive gliomas that express this mutation.
Assessing behavioral syndromes in patients with brain tumors using the
frontal systems behavior scale (FrSBe)
Authors: Cabrera Sergio , Edelstein Kim , Mason Warren P. , Tartaglia Maria Carmela 
Published: November 2015

Abstract

Background
Personality changes following brain tumors may be due to disruption of frontal-subcortical networks. The relation between personality changes and tumor parameters such as volumes of the surgical cavity, residual tumor, or nonspecific white matter abnormalities is unknown. In this study we examined the relation between these tumor parameters and abnormal behaviors typically associated with frontal lobe dysfunction.

Methods
Thirty-one patients with intracranial tumors who completed the Frontal Systems Behavior Scale (FrSBe) during clinical neuropsychological assessment and had a solitary, well-delimited brain lesion on MRI within 3 months of that assessment were included. Tumor parameters were manually segmented using OsiriX. Nonparametric statistics were used to determine the relationship between tumor parameters and frontal behavioral dysfunction as measured by FrSBe scores.

Results
Patients reported significantly more behavior problems after tumor diagnosis. Tumor cavity volume was correlated with self-reported Executive Dysfunction (rho = 0.450, P = .047), and there was a trend in the relationship with self-reported Apathy (rho = 0.438, P = .053). Nonspecific white matter abnormality volume was also correlated with self-reported Apathy (rho = 0.810, P = .01). There were no correlations between FrSBe scores and residual tumor volume or summed volumes of tumor-related parameters.

Conclusion
Our results suggest that tumor parameters have differential effects on behaviors associated with frontal-subcortical networks and corroborate the high frequency of behavioral dysfunction in brain tumor patients. Examination of these relationships in a prospective trial is warranted to establish incidence, prevalence, risk factors, and consequences of behavioral disturbances in brain tumor patients.
Classification of Early Onset Scoliosis has Excellent Interobserver and Intraobserver Reliability
Authors: Cyr Micaela , Hilaire Tricia St. , Pan Zhaoxing , Thompson George H. , Vitale Michael G. , Garg Sumeet 
Published: November 2015

Background:
Classification systems can be useful tools for clinical care and research but must be proven as reliable. The purpose of this study was to evaluate the interobserver and intraobserver reliability of the Classification of Early Onset Scoliosis (C-EOS) scheme.

Methods:
After IRB approval, 50 cases were drawn from a prospectively collected database of patients with EOS. Cases were selected using a stratified randomization scheme based on etiology. These cases were used to create an internet survey that was sent to pediatric orthopaedic faculty, research coordinators, and fellows involved in EOS care and research. Participants were asked to classify each case and were provided with a written C-EOS scheme that could be referenced while they completed the survey. Surveys were sent to participants twice, 3 weeks apart, to assess both intraobserver and interobserver reliability. Fleiss κ and Cohen κ were used to assess interobserver and intraobserver reliability, respectively.

Results:
There were 36 total participants, 29 who completed the survey twice (21 faculty, 13 research coordinators, and 2 fellows). Overall Fleiss κ coefficient for interobserver reliability was excellent across the major categories of etiology (0.84), major curve (0.93), and kyphosis (0.96). Overall intraobserver reliability was excellent with Cohen κ values for etiology (0.92), major curve (0.96), and kyphosis (0.98). Faculty members had excellent agreement for etiology (0.90), major curve (0.91), and kyphosis (0.96). Research coordinators had high levels of agreement for etiology (0.78), and excellent for major curve (0.95) and kyphosis (0.96). Intraobserver reliability was excellent across all major categories for all groups: faculty, research coordinators, and fellows.

Conclusions:
The study shows high levels of interobserver and intraobserver agreement of the C-EOS scheme. The C-EOS scheme can be used as a reliable tool for classifying EOS patients for clinical communication and research.

Level of Evidence:
Level II—diagnostic study.
Advanced Low-Cost Ultrasound-Guided Vascular Access Simulation
Authors: Sanchez-de-Toledo Joan , Villaverde Ivan 
Published: November 2015

Abstract
There is a growing body of literature that supports the use of ultrasound for vascular access. Advanced simulation has become a widely applied technique for training medical staff in vascular access. Nevertheless, advanced simulators are expensive and of limited usage. We describe both a step-wise systematic approach and an experimental cadaveric model of vascular access using a simple piece of chicken that can be easily used for trainees.
Predicting the Rate of Cognitive Decline in Alzheimer Disease
Authors: Canevelli Marco , Kelaiditi Eirini , del Campo Natalia , Bruno Giuseppe , Vellas Bruno , Cesari Matteo 
Published: November 2015

Background:
Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors.

Methods:
Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) “slow” progression, as indicated by a decrease in the MMSE score ≤1 point; (2) “intermediate” progression, decrease in the MMSE score between 2 and 5 points; and (3) “rapid” progression, decrease in the MMSE score ≥6 points.

Results:
A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both “intermediate” and “rapid” decline. Conversely, increasing age was negatively associated with “rapid” cognitive worsening.

Conclusions:
A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations.