bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical Innovation in the Era of Global Surgery
Authors: Garas George , Cingolani Isabella , Patel Vanash , Panzarasa Pietro , Alderson Derek , Darzi Ara , Athanasiou Thanos 
Published: January 2019

Objective:
To present a novel network-based framework for the study of collaboration in surgery and demonstrate how this can be used in practice to help build and nurture collaborations that foster innovation.

Background:
Surgical innovation is a social process that originates from complex interactions among diverse participants. This has led to the emergence of numerous surgical collaboration networks. What is still needed is a rigorous investigation of these networks and of the relative benefits of various collaboration structures for research and innovation.

Methods:
Network analysis of the real-world innovation network in robotic surgery. Hierarchical mixed-effect models were estimated to assess associations between network measures, research impact and innovation, controlling for the geographical diversity of collaborators, institutional categories, and whether collaborators belonged to industry or academia.

Results:
The network comprised of 1700 organizations and 6000 links. The ability to reach many others along few steps in the network (closeness centrality), forging a geographically diverse international profile (network entropy), and collaboration with industry were all shown to be positively associated with research impact and innovation. Closed structures (clustering coefficient), in which collaborators also collaborate with each other, were found to have a negative association with innovation (P < 0.05 for all associations).

Conclusions:
In the era of global surgery and increasing complexity of surgical innovation, this study highlights the importance of establishing open networks spanning geographical boundaries. Network analysis offers a valuable framework for assisting surgeons in their efforts to forge and sustain collaborations with the highest potential of maximizing innovation and patient care.
Association of Primary Ventral Hernia and Pregnancy
Authors: Oma Erling , Jensen Kristian K. , Bisgaard Thue , Jorgensen Lars N. 
Published: January 2019

Objective:
To determine the optimal timing of elective repair, the primary objective of this study was to assess if parity at the time of repair and subsequent pregnancy were associated with reoperation for recurrence. The secondary objective was to examine if parity was associated with hernia formation requiring surgical repair.

Summary Background Data:
Women of childbearing age constitute 18% of patients operated on for a primary ventral hernia, but consensus is lacking on the management in women who might subsequently become pregnant.

Methods:
In this nationwide retrospective cohort-study, all women born in Denmark from 1962 to 1971 were eligible for inclusion and followed from age 15 to 45 years. The follow-up rate was 100%. Data on pregnancies and surgical procedures were obtained from the Danish Medical Birth Registry and National Patient Registry. Extended Cox regression and Poisson regression were used for statistical analysis.

Results:
In total, 470,646 women were included, of whom 2113 underwent repair of a primary ventral hernia. The 10-year cumulative incidence of reoperation for recurrence was 14.1% (95% CI 12.3%–16.0%). Parity at the time of repair was not associated with reoperation for recurrence, while a subsequent pregnancy was associated with a 1.6-fold increased risk (hazard ratio 1.58, 95% CI 1.08–2.31). Parous women had a 7-fold increased risk of undergoing hernia repair compared with nulliparous, in an age-adjusted model (incidence rate ratio 7.04, 95% CI 5.87–8.43).

Conclusion:
To reduce the risk of hernia recurrence, the optimal timing of elective repair is after the last pregnancy.
Ion counting demonstrates a high electrostatic potential of the nucleosome
Authors: Gebala Magdalena , Johnson Stephanie , Narlikar Geeta , Herschlag Daniel 
Published: January 2019

AbstractThe fundamental unit of chromatin is the nucleosome, which comprises of DNA wrapped around a histone protein octamer. The association of positively charged histone proteins with negatively charged DNA is intuitively thought to attenuate the electrostatic repulsion of DNA, resulting in a weakly charged nucleosome complex. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing models have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Further, our results show that the wrapping of DNA around a histone octamer increases the propensity of the DNA to make interactions with multivalent cations like Mg2+. These findings indicate that presentation of DNA on a nucleosome may more strongly attract positively-charged DNA binding proteins. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.
An evolutionary recent IFN-IL-6-CEBP axis is linked to monocyte expansion and tuberculosis severity in humans
Authors: Delgobo Murilo , Mendes Daniel A. G. B. , Kozlova Edgar , Rocha Edroaldo Lummertz , Rodrigues-Luiz Gabriela F. , Mascarin Lucas , Dias Greicy , Patrício Daniel O. , Dierckx Tim , Bicca Maíra A. , Breton Gaëlle , de Menezes Yonne Karoline Tenório , Starick Márick R. , Rovaris Darcita , Del Moral Joanita , Mansur Daniel S. , Van Weyenbergh Johan , Báfica André 
Published: January 2019

AbstractMonocyte counts are increased during human tuberculosis (TB) but it has not been determined whetherMycobacterium tuberculosis(Mtb) directly regulates myeloid commitment. We demonstrated that exposure toMtbdirects primary human CD34+cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast,Mtbenhanced IL-6 responses by CD34+cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloidIL-6/IL6R/CEBPgene module associated with disease severity. Furthermore, genetic and functional analysis revealed theIL6/IL6R/CEBPgene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggestMtbco-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans.
Comprehensive Substrate Specificity Profiling of the Human Nek Kinome Reveals Unexpected Signaling Outputs
Authors: van de Kooij Bert , Creixell Pau , van Vlimmeren Anne , Joughin Brian A. , Miller Chad J. , Haider Nasir , Linding Rune , Stambolic Vuk , Turk Benjamin E. , Yaffe Michael B. 
Published: January 2019

AbstractHuman NimA-related kinases (Neks) have multiple mitotic and non-mitotic functions, but few substrates are known. We systematically determined the phosphorylation-site motifs for the entire Nek kinase family, except for Nek11. While all Nek kinases strongly select for hydrophobic residues in the −3 position, the family separates into four distinct groups based on specificity for a serine versus threonine phospho-acceptor, and preference for basic or acidic residues in other positions. Unlike Nek1-Nek9, Nek10 is a dual-specificity kinase that efficiently phosphorylates itself and peptide substrates on serine and tyrosine, and its activity is enhanced by tyrosine auto-phosphorylation. Nek10 dual-specificity depends on residues in the HRD+2 and APE-4 positions that are uncommon in either serine/threonine or tyrosine kinases. Finally, we show that the phosphorylation-site motifs for the mitotic kinases Nek6, Nek7 and Nek9 are essentially identical to that of their upstream activator Plk1, suggesting that Nek6/7/9 function as phospho-motif amplifiers of Plk1 signaling.
Reversible silencing of endogenous receptors in intact brain tissue using two-photon pharmacology
Authors: Pittolo Silvia , Lee Hyojung , Lladó Anna , Tosi Sébastien , Bosch Miquel , Bardia Lídia , Gómez-Santacana Xavier , Llebaria Amadeu , Soriano Eduardo , Colombelli Julien , Poskanzer Kira E. , Perea Gertrudis , Gorostiza Pau 
Published: January 2019

AbstractThe physiological activity of proteins is often studied with loss-of-function genetic approaches, but the corresponding phenotypes develop slowly and can be confounding. Photopharmacology allows direct, fast and reversible control of endogenous protein activity, with spatiotemporal resolution set by the illumination method. Here, we combine a photoswitchable allosteric modulator (alloswitch) and two-photon excitation (2PE) using pulsed near-infrared lasers to reversibly silence mGlu5 receptor activity in intact brain tissue. Endogenous receptors can be photoactivated in neurons and astrocytes with pharmacological selectivity and with an axial resolution between 5 and 10 μm. Thus, two-photon pharmacology (2PP) using alloswitch allows investigating mGlu5-dependent processes in wild type animals, including synaptic formation and plasticity, and signaling pathways from intracellular organelles.
Anterior Cleft Palate due to Cbfb deficiency and its rescue by folic acid
Authors: Sarper Safiye E. , Inubushi Toshihiro , Kurosaka Hiroshi , Minagi Hitomi Ono , Murata Yuka , Kuremoto Koh-ichi , Sakai Takayoshi , Taniuchi Ichiro , Yamashiro Takashi 
Published: January 2019

AbstractCore binding factor β (Cbfb) is a cofactor of Runx transcription factors. Among Runx transcription factors, Runx1 is a prerequisite for anterior-specific palatal fusion. However, whether Cbfb serves as a modulator or obligatory factor in Runx signaling that regulates palatogenesis is unclear. We herein report that Cbfb is essential and indispensable in anterior palatogenesis. Palatal fusion inCbfbmutants is disturbed due to failed disintegration of the fusing epithelium specifically at the anterior portion, as is observed inRunx1mutants. In this mutants, theTgfb3expression is disturbed at the corresponding area of the failed palatal fusion, where phosphorylation of Stat3 is also disturbed. TGFB3 protein rescues the palatal fusionin vitro.Strikingly, the anterior cleft palate inCbfbmutants is further rescued by pharmaceutical application of folic acid that activates suppressed Stat3 phosphorylation andTgfb3expressionin vitro.With these findings, we provide the first evidence that Cbfb is a prerequisite for anterior palatogenesis as an obligatory cofactor in the Runx1/Cbfb-Stat3-Tgfb3 signaling axis. Furthermore, the rescue of the mutant cleft palate using folic acid may elucidate potential therapeutic targets by Stat3 modification for the prevention and pharmaceutical intervention of cleft palate.Summary StatementEpithelial deletion of Cbfb results in an anterior cleft palate with impaired fusion of the palatal process and folic acid application rescues the mutant phenotype with Stat3 activationin vitro.
Performance in a novel environment subject to ghost competition
Authors: Bisschop Karen , Mortier Frederik , Bonte Dries , Etienne Rampal S. 
Published: January 2019

ABSTRACTBackgroundA central tenet of the evolutionary theory of communities is that competition impacts evolutionary processes such as local adaptation. Species in a community exert a selection pressure on other species and may drive them to extinction. We know, however, very little about the influence of unsuccessful or ghost species on the evolutionary dynamics within the community.MethodsHere, we studied the long-term influence of a ghost competitor on the performance of a more successful species using experimental evolution. We transferred the spider mite Tetranychus urticae onto a novel host plant under initial presence or absence of a competing species, the congeneric mite T. ludeni.ResultsThe latter species unintentionally went extinct soon after the start of the experiment, but we nevertheless completed the experiment and found that the initial density of this ghost competitor positively affected the performance (i.e. fecundity) of the more successful species.This effect on T. urticae even lasted for at least 25 generations.DiscussionOur study supports the hypothesis that early experienced selection pressures can exert a persistent evolutionary signal on species’ performance in novel environments.
Epithelial invagination by vertical telescoping
Authors: Li Jingjing , Economou Andrew D. , Green Jeremy B.A. 
Published: January 2019

AbstractEpithelial bending is a fundamental process that shapes organs during development. All currently known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Often this shape change occurs by cytoskeletal contraction at cell apices (“apical constriction”) but mechanisms such as basal nuclear positioning (“basal wedging”) or extrinsic compression are also known. Here we demonstrate a completely different mechanism which occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement. Specifically, we show that cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards to create the invagination. We further show that this occurs by active cell-on-cell migration: outer cells migrate with an apical leading edge protrusion, depressing the central cells to “telescope” the epithelium downwards into the underlaying mesenchyme. Cells remain basally attached to the underlying lamina while their apical protrusions are dynamic and planar polarised centripetally. These protrusions depend on the actin cytoskeleton, and inhibition of the branching molecule Arp2/3 inhibits them and the invagination. FGF and Hedgehog morphogen signals are also required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by novel morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes.
The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation
Authors: Hildebrandt Andrea , Brüggemann Mirko , Boerner Susan , Rücklé Cornelia , Heidelberger Jan Bernhard , Dold Annabelle , Busch Anke , Hänel Heike , Voigt Andrea , Ebersberger Stefanie , Ebersberger Ingo , Roignant Jean-Yves , Zarnack Kathi , König Julian , Beli Petra 
Published: January 2019

AbstractCells have evolved quality control mechanisms to ensure protein homeostasis by detecting and degrading aberrant mRNAs and proteins. A common source of aberrant mRNAs is premature polyadenylation, which can result in non-functional protein products. Translating ribosomes that encounter poly(A) sequences are terminally stalled, followed by ribosome recycling and decay of the truncated nascent polypeptide via the ribosome-associated quality control (RQC). Here, we demonstrate that the conserved RNA-binding E3 ubiquitin ligase Makorin Ring Finger Protein 1 (MKRN1) promotes ribosome stalling at poly(A) sequences during RQC. We show that MKRN1 interacts with the cytoplasmic poly(A)-binding protein (PABP) and is positioned upstream of poly(A) tails in mRNAs. Ubiquitin remnant profiling uncovers PABP and ribosomal protein RPS10, as well as additional translational regulators as main ubiquitylation substrates of MKRN1. We propose that MKRN1 serves as a first line of poly(A) recognition at the mRNA level to prevent production of erroneous proteins, thus maintaining proteome integrity.
Out-migration of university enrolment: the mobility behaviour of Italian students
Authors: D’Agostino Antonella , Ghellini Giulio , Longobardi Sergio 
Published: January 2019

PurposeStudent mobility from the south to the north/centre of Italy is an increasingly crucial topic because the most important consequence is the continual depletion of universities situated in the southern regions. Using micro-data from the Italian Ministry of Education, University and Research (MIUR), the purpose of this paper is to investigate how contextual factors affect this mobility.Design/methodology/approachEmpirical evidence is provided by developing a multilevel logit model of student decisions to move at university enrolment that allows us to identify the unique effects that student and province characteristics have on out-migration. Multilevel analysis is appropriate because the research questions focus on the role of province characteristics, variables that are measured at the macro level, on student-level outcome (out-migration) while controlling for student-level characteristics, variables that are measured at the micro level.FindingsThe present paper intends to contribute to the literature by quantifying the way in which contextual factors affect student mobility from the south to the north/centre of Italy. Findings show that province differences remain significant even after controlling for individual characteristics stressing the importance of the geographical dimension for student mobility. These findings have important policy implications for the future of university system in Italy.Originality/valueThis paper is relevant to the literature concerning this issue because most of the empirical applications are based on spatial models that do not take into account individual characteristics of the students. In addition, the multilevel methodology proposed can be easily generalise to other countries.
Non-performing loans and financial development: new evidence
Authors: Ozili Peterson K. 
Published: January 2019

Purpose
This paper aims to investigate the influence of financial development on non-performing loans (NPL).

Design/methodology/approach
The model used in this study follows the NPL model of Louzis et al. (2012), Ozili (2015) and Beck et al. (2015).

Findings
The findings indicate that financial development, measured as foreign bank presence and financial intermediation, are positively associated with NPLs. Also, bank efficiency, loan loss coverage ratio, competition and banking system stability are inversely associated with NPLs, while NPLs are positively associated with banking crises and bank concentration. In the regional analysis, NPLs are negatively associated with regulatory capital and bank liquidity, implying that banking sectors with greater regulatory capital and liquidity experience fewer NPLs.

Practical implications
National bank regulators/supervisor should not only consider the role that financial development structures play in influencing aggregate NPLs but also ensure that thorough supervision of the lending practices of banks is in place as well as the active monitoring of the financial intermediation process in the country.

Originality/value
The study is the first to use a global sample to examine the direct relationship between NPL and financial development.
Detecting spatial-temporal clusters of violent behavior in South Korea with space-time permutation scan statistics
Authors: Yeom Yunho 
Published: January 2019

Purpose
The purpose of this paper is to detect spatial-temporal clusters of violence in Gwanak-gu, Seoul with space-time permutation scan statistics (STPSS) and identifies the temporal threshold for such detection to alert law enforcement officers quickly.

Design/methodology/approach
The case study was the Gwanak Police Station Call Database 2017 where civilian calls reporting violence were georeferenced with coordinated points. In analyzing the database, this study used the STPSS requiring only individual case data, such as time and location, to detect clusters of investigated phenomena. This study executed a series of experiments using different minimum and maximum temporal thresholds in detecting clusters of violence.

Findings
Results of the STPSS analyses with different temporal thresholds detected spatial-temporal clusters in Gwanak-gu. Number, location and duration of clusters depended on the temporal settings of the scanning window. Among four models, a model allowing the possible clusters to be detected within a 7-day minimum and 30-day maximum temporal threshold was more representative of reality than other models.

Originality/value
This study illustrates the clustering of violence with the STPSS by detecting spatial-temporal clusters of violence and identifying the appropriate temporal threshold in detecting such clusters. Identification of such a threshold is useful to alert law enforcement officers quickly and enables them to allocate their resources optimally.
How to assess Drosophila heat tolerance: Unifying static and dynamic tolerance assays to predict heat distribution limits
Authors: Jørgensen Lisa Bjerregaard , Malte Hans , Overgaard Johannes 
Published: January 2019

Abstract

Thermal tolerance is a critical determinant of ectotherm distribution, which is likely to be influenced by future climate change. To predict such distributional changes, simple and comparable measures of heat tolerance are needed and these measures should ideally correlate with the characteristics of the species current thermal environments.

A recent model (thermal tolerance landscapes—TTLs) uses the exponential relation between temperature and knockdown time to describe the thermal tolerance of ectotherms across time/temperature scales. Here, we established TTLs for 11 Drosophila species representing different thermal ecotypes by measuring knockdown time at 9–17 stressful temperatures (0.5°C intervals). These temperatures caused knockdown times ranging from <10 min to >12 hrs and all species displayed the expected exponential relation between temperature and knockdown time (average R2 = 0.98).

Previous studies using TTLs have reported a trade‐off between tolerance to acute and chronic heat stress in ectotherms. The present study did not find evidence to support this trade‐off in drosophilids. Instead, we show how this “trade‐off” can arise as an analytical artefact caused by insufficient data collection and excessive data extrapolation.

Dynamic assays represent an alternative method to describe heat tolerance of ectotherms, where animals are exposed to gradually increasing temperatures until knockdown. The comparability of static and dynamic assays has previously been questioned, but here we show that static and dynamic assays give comparable information on heat tolerance. Using the constants derived from static TTLs, we mathematically model the expected dynamic knockdown temperature and subsequently confirm this model by comparison to empirically obtained knockdown temperatures from all 11 species.

Characterisation of heat tolerance in laboratory settings is an important tool in thermal biology, but more so if the measures correlate with the environmental gradients that characterise the fundamental niche of species. Here, we show that both static and dynamic assays were characterised by strong correlations to precipitation of the driest month and maximum temperature of the warmest month combined (R2 = 0.68–0.71). This demonstrates that both assay types offer simple measures of heat tolerance that are ecologically relevant for the tested drosophilids.

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