bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antonio's sadness in the Stoic theatrum mundi of the Early Modern city
Authors: Vangshardt Rasmus 
Published: April 2019

AbstractAntonio's opening claim in The Merchant of Venice, that he is ‘so sad’ because he has been given a sad role on the world stage, has often been neglected in the history of the play's reception. The present analysis begins with an examination of central passages to clarify the role of sadness in relation to the trope of the theatrum mundi. It shows that the sadness is persistent and earnest, and that this is caused by an understanding of the meaning of the theatrum mundi, which has hitherto been overlooked. The article then considers the historical light in which the theatrum mundi should be seen in the context of the play with respect to the prior textual analysis. The suggestion is that in relation to both the intellectual history of ideas and to Elizabethan audience‐response, the play negotiates a Christian‐Stoic version of the theatrum mundi without breaking away from the genre of comedy and paradoxically not abandoning Antonio's sadness.
The Rise of Public–Private Partnerships in China: An Effective Financing Approach for Infrastructure Investment?
Authors: Tan Jie , Zhao Jerry Zhirong 
Published: April 2019

Abstract
The rise of public‐private partnerships (PPPs) in China has spurred heated debates about their purpose and effectiveness. This article traces the fluctuation of China's PPPs over several decades and finds that PPPs have played a supplementary role in China's infrastructure investment, as a response to the pressures of fiscal shortfalls and government debts. The resurgence of PPPs in recent years aims to bridge the infrastructure gap and alleviate ballooning local debts. These expectations, however, are hard to realize. China's PPPs mainly involve state‐owned enterprises and place increasing financial burdens on the government. The central government has taken measures to attract private sector investment to mitigate the financial risk, but the prospects for PPPs remain unclear.
The dynamics of endothelial changes in vivo following standardized skin injury
Authors: Hanssen Sabina Catharina Andrea , Keijsers Romy Rosa Maria Catharina , Hendriks Anke Gertruda Martina , Seyger Marieke Martha Benedicta , van der Vleuten Catharina Joanna Maria , van de Kerkhof Peter Cornelis Maria 
Published: April 2019

AbstractBackgroundVascular changes, that is, functional and cellular endothelial changes, are of essential importance in healing. Alongside these vascular changes, inflammatory factors and hypoxia may play an important role in recovery.ObjectivesTo investigate the dynamics of functional and cellular endothelial changes and hypoxia in vivo following standardized skin damage caused by tape stripping.MethodsVascular changes (endothelial cell proliferation, vascular network size, vessel diameter) and hypoxia‐inducible factor‐1α were examined immunohistochemically using a CD31/Ki67 double staining and HIF‐1α single staining. Cutaneous perfusion was evaluated using the Twente Optical Perfusion Camera (TOPCam).ResultsThe initial phase is seen to be dominated by endothelial cell proliferation, HIF‐1α expression, and vasodilatation. Cutaneous perfusion intensity is particularly increased in the first 16 hours.The late phase of recovery (after 72 hours) is characterized by a peak of expansion of the vascular network and a second peak of endothelial cell proliferation and HIF‐1α expression.ConclusionEndothelial cell proliferation and HIF‐1α expression appear to be (strongly) related, having maximum levels at 16 hours and 72 hours. Angiogenesis and HIF‐1α expression are not continuous processes, but rather occur intermittently.
Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation
Authors: Brash Breanna M. , Gemensky‐Metzler Anne J. , Wilkie David A. , Miller Eric J. , Chandler Heather L. 
Published: April 2019

AbstractPurposeTo determine whether trypan blue (TB) reduces canine lens epithelial cell (LEC) or corneal endothelial cell (CEC) viability in vitro; if cell death is noted, to subsequently evaluate the molecular mechanism.MethodsCellular viability was determined using a lactate dehydrogenase (LDH) assay. In TB‐treated LECs, caspase 3/7 activity was assessed to evaluate apoptosis; autophagy was evaluated using immunoblotting against LC3 and p62. To evaluate the effects of TB on ex vivo posterior capsule opacification (PCO), following mock cataract surgery, lens capsules were treated with TB and subsequently maintained in culture to determine LEC migration and proliferation.ResultsFollowing acute exposure, TB did not significantly reduce LEC or CEC viability at any of the concentrations tested. Increased caspase 3/7 activity was found in LEC cultures treated with TB for an extended period of time; no change in LC3 or p62 expression was noted. Ex vivo PCO formation was not significantly altered by TB treatment.ConclusionsAcute exposure to TB did not reduce LEC or CEC viability, and only longer exposure to TB was able to initiate apoptosis. Treatment with intraocular TB at the time of cataract surgery is likely safe to the CECs but will not prevent PCO formation.
‘Off pump’ self-expanding injectable tissue valves (IPVR) versus ‘on pump’ conventional tissue valves (PVR) for replacement of the pulmonary valve: trial protocol for a randomised controlled trial (InVITe trial)
Authors: Heys Rachael , Angelini Gianni , Caputo Massimo , Culliford Lucy , Pufulete Maria , Reeves Barnaby C , Rogers Chris A , Stoica Serban , Parry Andrew 
Published: April 2019

IntroductionPatients with congenital heart disease often need repeated operations throughout life to replace the pulmonary valve. Valve replacement with ‘injectable’ self-expanding valves (which is performed ‘off pump’ without the use of cardiopulmonary bypass, CPB) may result in quicker recovery and lower risk of major complications than valve replacement with conventional valves (which is performed ‘on pump’ with the use of CPB).Methods and analysisWe are conducting a multicentre, single-blind randomised controlled trial in patients with congenital heart disease and aged between 12 and 80 years. We will randomise participants in a 1:1 ratio to receive either ‘off pump’ injectable pulmonary valve replacement or ‘on pump’ conventional pulmonary valve replacement. The primary outcome will be the difference between the groups with respect to post-surgery blood loss (as measured by chest drain volume) in the first 24 hours. Secondary outcomes will include in-hospital outcomes (intensive care unit stay, inotropic/vasodilator support, chest drain volume in the first 12 hours post-surgery, time of readiness for extubation, blood products used in the first 24 hours post-surgery, time of fitness for discharge, valve and heart function 6 months post-surgery (assessed using cardiovascular magnetic resonance and ECHOCARDIOGRAPHY) and health-related quality of life 6 weeks and 6 months post-surgery.Ethics and disseminationThis trial has been approved by the South West Exeter Research Ethics Committee. Findings will be shared with participating hospitals and disseminated to the academic community through peer reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and newsletters to participants.Trial registration numberISRCTN23538073
Abdominal aortic calcification, bone mineral density and fractures: a systematic review and meta-analysis protocol
Authors: Rodríguez Alexander J , Leow Kevin , Szulc Pawel , Scott David , Ebeling Peter , Sim Marc , Wong Germaine , Lim Wai H , Schousboe John T , Kiel Douglas P , Prince Richard L , R Lewis Joshua 
Published: April 2019

IntroductionAbdominal aortic calcification (AAC) is associated with low bone mass and increased fracture risk. Two previous meta-analyses have investigated the association between AAC and fracture. However, these meta-analyses only identified articles until December 2016, undertook limited searches and did not explore potential sources of between-study heterogeneity. We aim to undertake a sensitive and comprehensive assessment of the relationship between AAC, bone mineral density (BMD) as well as prevalent and incident fractures.MethodsWe will search MEDLINE, EMBASE, Web of Science core collection and Google Scholar (top 200 articles sorted by relevance) from their inception to 1 June 2018. Reference lists of included studies and previous systematic reviews will be hand searched for additional eligible studies. Retrospective and prospective cohort studies (cross-sectional, case–control and longitudinal) reporting the association between AAC, BMD and fracture at any site will be included. At least two investigators will independently: (A) evaluate study eligibility and extract data, with a third investigator to adjudicate when discrepancies occur, (B) assess study quality by the Newcastle-Ottawa Scale for each cohort/study. The meta-analysis will be reported in adherence to the Meta-analysis of Observational Studies in Epidemiology criteria. AAC will be grouped as either: (1) AAC present or absent, (2) AAC categorised as ‘low’ (referent—lowest reported group) versus ‘high’ (all other groups) or (3) dose–response when AAC was assessed in ≥3 groups. Where primary event data were reported in individual studies, pooled risk differences and risk ratios with 95% CI will be calculated, from which, a summary estimate will be determined using DerSimonian-Laird random effects models. For the AAC and BMD pooled analyses, estimates will be expressed as standardised mean difference with 95% CI. We will examine the likelihood of publication bias and where possible, investigate potential reasons for between-study heterogeneity using subgroup analyses and meta-regression.Ethics and disseminationThe study will be submitted to a peer- reviewed journal and disseminated via research presentations.PROSPERO registration numberCRD42018088019.
How to decide adequately? Qualitative study of GPs’ view on decision-making in self-referred and physician-referred emergency department consultations in Berlin, Germany
Authors: Oslislo Sarah , Heintze Christoph , Schmiedhofer Martina , Möckel Martin , Schenk Liane , Holzinger Felix 
Published: April 2019

ObjectivesPatients with acute symptoms present not only to general practitioners (GPs), but also frequently to emergency departments (EDs). Patients’ decision processes leading up to an ED self-referral are complex and supposed to result from a multitude of determinants. While they are key providers in primary care, little is known about GPs’ perception of such patients. This qualitative study explores the GPs’ view regarding motives and competences of patients self-referring to EDs, and also GPs’ rationale for or against physician-initiated ED referrals.DesignQualitative study with semi-structured, face-to-face interviews; qualitative content analysis.SettingGP practices in Berlin, Germany.Participants15 GPs (female/male: 9/6; mean age 53.6 years).ResultsThe interviewed GPs related a wide spectrum of factors potentially influencing their patients’ decision to visit an ED, and also their own decision-making in potential referrals. Considerations go beyond medical urgency. Statements concerning patients’ surmised rationale corresponded to GPs’ reasoning in a variety of important areas. For one thing, the timely availability of an extended spectrum of diagnostic and therapeutic options may make ED services attractive to both. Access difficulties in the ambulatory setting were mentioned as additional triggers for an ED visit initiated by a patient or a GP. Key patient factors like severity of symptoms and anxiety also play a major role; a desire for reassurance may lead to both self-referred and physician-initiated ED visits. Patients’ health competence was prevailingly depicted as limited, with the internet as an important influencing factor. Counselling efforts by GP were described as crucial for improving health literacy.ConclusionsHealth education could hold promise when aiming to reduce non-urgent ED consultations. Primary care providers are in a key position here. Amelioration of organisational shortages in ambulatory care, for example, limited consultation hours, might also make an important impact, as these trigger both self-referrals and GP-initiated ED referrals.Trial registration numberDRKS00011930.
40
Ar/
39
Ar thermochronology in the Ios basement terrane resolves the tectonic significance of the South Cyclades Shear Zone
Authors: Forster Marnie , Koudashev Oleg , Nie Ruoran , Yeung Sonia , Lister Gordon 
Published: April 2019

Abstract

We conducted
39
Ar diffusion experiments using potassium feldspar from the South Cyclades Shear Zone on Ios, in the Cyclades, Aegean Sea, Greece. Irradiated samples were step-heated in an ultra-high-vacuum resistance furnace attached to a mass spectrometer, thus also allowing
40
Ar/
39
Ar geochronology. Conjoint inversion of these datasets allowed estimation of the relevant diffusion parameters, which were then used to forward model the effect of arbitrary temperature–time histories. Simulations used Monte Carlo methods to improve approximations to the observed age spectra. Two periods of rapid cooling could be inferred. The South Cyclades Shear Zone commenced operation during or shortly after the Eocene–Oligocene transition. Episodes of south-directed movement continued into Early Miocene time, however, with the footwall still hot enough to cause biotite ± garnet metamorphic mineral growth at the base of the overlying, already substantially exhumed, eclogite–blueschist unit. Since its footwall continued to cool, the South Cyclades Shear Zone was an extensional shear zone during both episodes of its operation.
Analysis of excitatory and inhibitory neuron types in the inferior colliculus based on Ih properties
Authors: Naumov Victor , Heyd Julia , de Arnal Fauve , Koch Ursula 
Published: April 2019

The inferior colliculus (IC) is a large midbrain nucleus that integrates inputs from many auditory brainstem and cortical structures. Despite its prominent role in auditory processing, the various cell types and their connections within the IC are not well characterized. To further separate GABAergic and non-GABAergic neuron types according to their physiological properties, we used a mouse model that expresses channelrhodopsin and enhanced yellow fluorescent protein in all GABAergic neurons and allows identification of GABAergic cells by light stimulation. Neuron types were classified upon electrophysiological measurements of the hyperpolarizing-activated current ( Ih) in acute brain slices of young adult mice. All GABAergic neurons from our sample displayed slow-activating Ih with moderate amplitudes, whereas a subset of excitatory neurons showed fast-activating Ih with large amplitudes. This is in agreement with our finding that immunoreactivity against the fast-gating hyperpolarization-activated and cyclic-nucleotide-gated 1 (HCN1) channel was present around excitatory neurons, whereas the slow-gating HCN4 channel was found perisomatically around most inhibitory neurons. Ih properties and neurotransmitter types were correlated with firing patterns to depolarizing current pulses. All GABAergic neurons displayed adapting firing patterns very similar to the majority of glutamatergic neurons. About 15% of the glutamatergic neurons showed an onset spiking pattern, always in combination with large and fast Ih. We conclude that HCN channel subtypes are differentially distributed in IC neuron types and correlate with neurotransmitter type and firing pattern. In contrast to many other brain regions, membrane properties and firing patterns were similar in GABAergic neurons and about one-third of the excitatory neurons. NEW & NOTEWORTHY Neuron types in the central nucleus of the auditory midbrain are not well characterized regarding their transmitter type, ion channel composition, and firing pattern. The present study shows that GABAergic neurons have slowly activating hyperpolarizing-activated current ( Ih) and an adaptive firing pattern whereas at least four types of glutamatergic neurons exist regarding their Ih properties and firing patterns. Many of the glutamatergic neurons were almost indistinguishable from the GABAergic neurons regarding Ih properties and firing pattern.
The Intersection between Tumor Angiogenesis and Immune Suppression
Authors: Rahma Osama E. , Hodi F. Stephen 
Published: April 2019

AbstractBoth immune checkpoint inhibitors (ICI) and antiangiogenesis agents have changed the landscape of cancer treatment in the modern era. While antiangiogenesis agents have demonstrated activities in tumors with high vascularization, including renal cell carcinoma and colorectal cancer, the effect of ICIs has been seen mainly in immunologically recognized tumors, with highly immune-infiltrative lymphocytes. The main challenge in the drug development of ICIs is moving their activities to noninflamed tumors and overcoming resistance that is driven, in part, by the immune-suppressive microenvironment. Angiogenesis factors drive immune suppression by directly suppressing the antigen-presenting cells as well as immune effector cells or through augmenting the effect of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM). Those suppressive immune cells can also drive angiogenesis, creating a vicious cycle of impaired immune activation. The combination of bevacizumab and ipilimumab was the first to show the promising effect of antiangiogenesis and ICIs. A plethora of similar combinations has entered the clinic since then, confirming the promising effects of such approach.
Pancreatic Tumor Microenvironment Modulation by EphB4-ephrinB2 Inhibition and Radiation Combination
Authors: Lennon Shelby , Oweida Ayman , Milner Dallin , Phan Andy V. , Bhatia Shilpa , Van Court Benjamin , Darragh Laurel , Mueller Adam C. , Raben David , Martínez-Torrecuadrada Jorge L. , Pitts Todd M. , Somerset Hilary , Jordan Kimberly R. , Hansen Kirk C. , Williams Jason , Messersmith Wells A. , Schulick Richard D. , Owens Philip , Goodman Karyn A. , Karam Sana D. 
Published: April 2019

Abstract

Purpose:
A driving factor in pancreatic ductal adenocarcinoma (PDAC) treatment resistance is the tumor microenvironment, which is highly immunosuppressive. One potent immunologic adjuvant is radiotherapy. Radiation, however, has also been shown to induce immunosuppressive factors, which can contribute to tumor progression and formation of fibrotic tumor stroma. To capitalize on the immunogenic effects of radiation and obtain a durable tumor response, radiation must be rationally combined with targeted therapies to mitigate the influx of immunosuppressive cells and fibrosis. One such target is ephrinB2, which is overexpressed in PDAC and correlates negatively with prognosis.
Experimental Design: On the basis of previous studies of ephrinB2 ligand-EphB4 receptor signaling, we hypothesized that inhibition of ephrinB2-EphB4 combined with radiation can regulate the microenvironment response postradiation, leading to increased tumor control in PDAC. This hypothesis was explored using both cell lines and in vivo human and mouse tumor models.

Results:
Our data show this treatment regimen significantly reduces regulatory T-cell, macrophage, and neutrophil infiltration and stromal fibrosis, enhances effector T-cell activation, and decreases tumor growth. Furthermore, our data show that depletion of regulatory T cells in combination with radiation reduces tumor growth and fibrosis.

Conclusions:
These are the first findings to suggest that in PDAC, ephrinB2–EphB4 interaction has a profibrotic, protumorigenic role, presenting a novel and promising therapeutic target.
Association of ACE gene polymorphism with cardiovascular determinants of trained and untrained Iranian men
Authors: Falahati Akram , Arazi Hamid 
Published: April 2019

Abstract
Background
The insertion (I) rather than deletion (D) of human angiotensin converting enzyme gene (ACE) is associated with lower circulating ACE activity and with endurance performance among Caucasians. The frequency of the ACE gene I/D allele in Iranian sample seems to be more similar to the Caucasians. To assess the possible relationship between I/D polymorphism of ACE gene with athletic status and selected cardiovascular indices and VO2max in an Iranian population, DNA samples were obtained from 57 trained and untrained men, with soccer as their main training modality. Genotyping for ACE I/D polymorphism was performed using polymerase chain reaction. VO2max was determined by an incremental test to volitional exhaustion on a motorized treadmill.

Results
I/D genotype was neither associated with elite athlete status nor with VO2max, resting heart rate, systolic and diastolic blood pressure. There was no interaction effect of training statue x ACE genotype for each of the examined indices.

Conclusions
ACE gene variation was not a determinant of cardiovascular function and VO2max in either trained or untrained Iranian participating in soccer. The absence of an association between either I/D genotype and elite Iranian athlete status and better cardiovascular function also suggests that the ACE gene does not contribute significantly to the phenomenal success of Iranian soccer players.
Deep onshore reflection seismic imaging of the chalk group strata using a 45 kg accelerated weight-drop and combined recording systems with dense receiver spacing
Authors: Kammann Janina , Malehmir Alireza , Brodic Bojan , Tagliavento Mattia , Stemmerik Lars , Nørmark Egon , Lykke-Andersen Holger , Nielsen Lars 
Published: April 2019

The Chalk Group forms important hydrocarbon reservoirs offshore and water aquifers onshore Denmark. Within a day of fieldwork, a 450 m long reflection seismic profile was acquired onshore in an area in southeast Denmark, where the Chalk Group extends almost to the surface and is approximately 900 m thick. The main objective of the study was to image the complete Chalk Group in high resolution and to study the origin of reflectivity within the different chalk units. A 45 kg accelerated weight-drop source, in combination with dense receiver spacing using microelectromechanical sensors mounted on a streamer and 48 planted geophones, was used for data acquisition. The profile runs subparallel to the cliffs of Stevns, and the recorded signal reaches the base of the Chalk Group at approximately 600 ms. The fully cored 443 m-deep Stevns-1 borehole, which is located at the recorded seismic line, provides excellent control on lithologic and facies changes. Comparison with the borehole data demonstrates that our seismic data set provides a high-resolution image of the internal layering of the Chalk Group. We find that the internal reflection coefficients of the Chalk Group are, in general, small based on wireline-log data. However, the reflected amplitudes are just big enough to be recorded with the receiver setup used, even from the pure chalk beds of the Chalk Group. The reflectivity seen on the high-resolution seismic profile is influenced by occurrences of clay-enriched chalk layers. Flint bands consisting of numerous flint nodules are a characteristic of the uppermost part of the Chalk Group at Stevns. The flint nodules appear to produce significant scattering of the seismic signals, and flint-rich layers appear with diffuse internal reflectivity characteristics. Outcrop-scale mound structures in Danian and Upper Cretaceous outcrops are for the first time seismically resolved.