bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geoexpression: A Petri network framework for representing geographic process concurrency
Authors: Davis Austin V. , Wang Shaowen 
Published: September 2018

AbstractWe present a novel framework called geoexpression for representing geographic process concurrency and discuss its implications for geographic dynamic modeling. Unapt representations of geographic process concurrency can lead to non‐deterministic geographic dynamic modeling outcomes, excessive cognitive burdens when reasoning about how concurrent processes interact, and even inconsistent results. After demonstrating the importance of geographic process concurrency, we examine how the characteristics of geographic process concurrency are missing from other state‐of‐the‐art geographic process representations. The geoexpression framework adopts Petri networks to allow researchers to understand how to relate geographic process concurrency to observed modeling patterns. Of interest are the real‐world geographic patterns formed by concurrent geographic processes.
Two‐year follow‐up of donors in a large national study of ferritin testing
Authors: Goldman Mindy , Uzicanin Samra , Osmond Lori , Yi Qi‐Long , Scalia Vito , O'Brien Sheila F. 
Published: September 2018

BACKGROUNDWe assessed donor return rates, donation frequency, and factors related to the evolution of ferritin levels 2 years after entering donors into a large operational study of ferritin testing.STUDY DESIGN AND METHODSFerritin testing was done on donors from representative clinics (n = 12,595). Low‐ferritin donors (<25 μg/L) were informed and not called for 6 months to book a donation. Approximately 37% of donors had ferritin retested on a return donation. Return rate and donation frequency were monitored, and a logistic regression model was constructed.RESULTSThe return rate was lower in low‐ferritin donors (67% vs. 78%), particularly in women who were first‐time donors (36% vs. 61%). Returning low‐ferritin donors made fewer donations in the 2 years after notification compared to the 2 years prenotification (4.5 vs. 7.5 for men, 3.0 vs. 5.0 for women), while donation frequency was lower and increased slightly for normal‐ferritin donors (4.7 vs. 4.4 for men, 3.6 vs. 3.1 for women). An increased number of donations, shorter interdonation intervals, female sex, and younger age are associated with low ferritin levels on initial and repeat testing. Some recovery of ferritin occurred, but most low‐ferritin donors continued to have low or borderline levels on retesting.CONCLUSIONInforming donors of low ferritin results had a long‐lasting impact on return rates and donation frequency, requiring recruitment efforts to maintain adequacy of supply. Increasing the interdonation interval leads to some improvement in ferritin levels; more sustained efforts to encourage donors to improve iron intake are needed to achieve long‐term benefit.
Cumulative effects of Brexit and other UK and EU‐27 bilateral free‐trade agreements on the world’s wine markets
Authors: Anderson Kym , Wittwer Glyn 
Published: September 2018

AbstractSince Britain accounts for a major share of the world’s wine imports, and EU member countries include the world’s major wine exporters, Brexit and subsequent UK and EU‐27 bilateral free‐trade agreements (FTAs) have the potential to disrupt wine markets globally. We use a model of the world’s national wine markets, projected to 2025, to examine potential impacts of Brexit and a series of follow‐on bilateral FTAs. The scenarios assume a UK‐EU‐27 FTA is followed by EU‐27 bilateral FTAs with Australia and New Zealand and then UK bilateral FTAs with those two plus South Africa and Chile (with whom the EU already has FTAs). The new EU‐Japan FTA is also assessed. Brexit’s impact comes more from assumed changes to the UK’s income growth and the pound’s exchange rate than to its tariffs. The bilateral trade consequences of the trade‐diverting and trade‐creating effects of each additional FTA are highlighted. They are then compared with the effects of a multilateral agreement to remove all wine import tariffs globally. Unrealistic though this is, it exposes the far bigger benefits to wine producers and consumers that could emerge from a single multilateral undertaking than from several bilateral or regional FTAs.
A novel form of intracranial coccidioidomycosis is present in dogs and exhibits characteristic clinical and magnetic resonance imaging findings
Authors: Spoor Erich , Stainback Laura , Plummer Scott , Knowles Kim 
Published: September 2018

AbstractThe neurological examination findings, clinical pathology (includingCoccidioides immitisIgG/IgM serology) and magnetic resonance imaging (MRI) findings in 13 dogs with a novel form of intracranial coccidioidomycosis are described in a retrospective case series, with long‐term clinical resolution documented in 11/13 dogs (84.6% of cases) with oral fluconazole therapy. The medical records of the Veterinary Neurological Center in Phoenix, Arizona from the years 2000 to 2017 were utilized to search for dogs with appropriate inclusion criteria. Magnetic resonance imaging findings were highly consistent across all cases and characteristically demonstrated bilaterally symmetric T2 hyperintensity throughout the frontal lobes, caudate nuclei, and rostral internal capsule, ±faint, wispy contrast enhancement on T1‐postcontrast images. These findings were in stark contrast to previously reported MRI findings in dogs with intracranial coccidioidomycosis, which were typically characterized by a focal, strongly contrast enhancing granuloma and extensive vasogenic edema, typically unilateral. Schnauzer breeds represented eight of 13 (61.5%) cases, possibly suggesting a breed predilection. Three cases underwent repeat MRI after resolution of neurological signs and documentation of a decreasedCoccidioidestiter in response to fluconazole therapy. All demonstrated complete resolution of previously identified lesions, but with marked, severe atrophy of the caudate nuclei and frontal lobes bilaterally. Findings from this study document a variant appearance for intracranial coccidioidomycosis that, to the author's knowledge, has not been previously described in dogs. Authors propose that, although this variant demonstrates extensive pathological changes within the forebrain, the clinical outcome and response to treatment is favorable in a majority of cases.
Academic trajectories of very preterm born children at school age
Authors: Twilhaar E Sabrina , de Kieviet Jorrit F , van Elburg Ruurd M , Oosterlaan Jaap 
Published: September 2018

ObjectivesTo characterise the developmental trajectories of arithmetic, reading comprehension and spelling abilities of very preterm and full-term born children during primary school.DesignA longitudinal analysis of academic performance data of very preterm and full-term born children was performed. Academic performance was assessed in grade 1–6 of primary school using a pupil monitoring system, with 11 measurements of arithmetic and spelling performance and 7 measurements of reading comprehension. Data were analysed using mixed-effects models.PatientsA Dutch cohort of 52 very preterm children born between 2001–2003 and 58 full-term controls participated.ResultsNo group-by-time interactions were found for any of the academic domains, indicating no differences in progress between groups. Through the course of primary school, very preterm born children scored on average 0.53 SD lower on arithmetic (95% CI −0.71 to –0.35, p<0.001), 0.31 SD on reading comprehension (95% CI −0.48 to –0.14, p<0.001) and 0.21 SD on spelling (95% CI −0.37 to –0.05, p=0.01) compared with full-term peers.ConclusionsThis is the first longitudinal study to show that the academic difficulties of very preterm born children persisted during primary school. Their progression was similar to full-term born peers, suggesting intact learning abilities. This provides opportunities for interventions to improve the academic outcomes of very preterm born children.
Heart rate assessment using NeoTapAdvancedSupport: a simulation study
Authors: Binotti Marco , Cavallin Francesco , Ingrassia Pier Luigi , Pejovic Nicolas J , Monzani Alice , Genoni Giulia , Trevisanuto Daniele 
Published: September 2018

BackgroundNeoTapAdvancedSupport (NeoTapAS) is a mobile application, based on a screen tapping method that calculates the heart rate (HR). We aimed to evaluate the accuracy of NeoTapAS in reliably determining HR from auscultation in a high-fidelity simulated newborn resuscitation scenario.MethodsPaediatric residents assessed HR by auscultation plus NeoTapAS in an asphyxiated term infant scenario and orally communicated the estimated HR. An external observer simultaneously documented the actual HR set in the manikin and the communicated HR.ResultsOne hundred and sixty HR measurements were recorded. The agreement between communicated and set HR was good (Cohen’s kappa 0.80, 95% CI 0.72 to 0.87; Bangdiwala’s weighted agreement strength statistic 0.93). Bland-Altman plot showed a mean difference between communicated and set HR values of 1 beats per minute (bpm) (95% agreement limits −9 to 11 bpm).ConclusionNeoTapAS showed a good accuracy in estimating HR and it could be an important resource in settings with limited availability of ECG monitor.
Cilioretinal artery hypoperfusion and its association with paracentral acute middle maculopathy
Authors: Pichi Francesco , Fragiotta Serena , Freund K Bailey , Au Adrian , Lembo Andrea , Nucci Paolo , Sebastiani Stefano , Gutierrez Hernandez Juan Carlos , Interlandi Emanuela , Pellegrini Francesco , Dolz-Marco Rosa , Gallego-Pinazo Roberto , Orellana-Rios Jorge , Adatia Feisal A , Munro Monique , Abboud Emad B , Ghazi Nicola , Cunha Souza Eduardo , Amer Radgonde , Neri Piergiorgio , Sarraf David 
Published: September 2018

Background/aimsTo study the multimodal imaging findings of a large series of eyes with cilioretinal artery obstruction (CILRAO) and describe the systemic associations.MethodsMulticentre, retrospective chart review from 12 different retina clinics worldwide of eyes with CILRAO, defined as acute retinal whitening in the distribution of the cilioretinal artery, were identified. The clinical, systemic information and multimodal retinal imaging findings were collected and analysed.ResultsA total of 53 eyes of 53 patients with CILRAO were included in the study. In 100% of eyes, fundus photography illustrated deep retinal whitening corresponding to the course of the cilioretinal artery. Twenty-eight patients (52.8%) presented with isolated CILRAO (baseline best-corrected visual acuity (BCVA) 20/50, final BCVA 20/25) associated with nocturnal hypotension, 23 patients (43.4%) with CILRAO secondary to central retinal vein occlusion (CRVO) (baseline BCVA 20/40, final BCVA 20/20) and two patients with CILRAO due to biopsy-proven giant cell arteritis (GCA) (baseline BCVA 20/175, final BCVA 20/75). With spectral domain optical coherence tomography (SD-OCT), a hyper-reflective band involving the inner nuclear layer (ie, paracentral acute middle maculopathy or PAMM) was noted in 51 eyes (28/28 eyes with isolated CILRAO and 23/23 eyes with CILRAO+CRVO) corresponding to the retinal whitening. In the two eyes with CILRAO+GCA, SD-OCT illustrated hyper-reflective ischaemia of both the middle and inner retina.ConclusionsIsolated CILRAO and CILRAO secondary to CRVO are the result of hypoperfusion or insufficiency, rather than occlusion, of the cilioretinal artery and are associated with PAMM or selective infarction of the the inner nuclear layer. With GCA, there is complete occlusion of the cilioretinal artery producing ischaemia involving both the middle and inner retina associated with worse visual outcomes.
Story of the ALS-FTD continuum retold: rather two distinct entities
Authors: Lulé Dorothée E , Aho-Özhan Helena E A , Vázquez Cynthia , Weiland Ulrike , Weishaupt Jochen H , Otto Markus , Anderl-Straub Sarah , Semler Elisa , Uttner Ingo , Ludolph Albert C 
Published: September 2018

ObjectiveTo determine the evolution and profile of cognitive and behavioural deficits in amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) to disentangle the development of FTD in ALS and vice versa.MethodsIn a prospective design, cognitive and behavioural profiles of 762 patients with motor predominant ALS (flail arm/leg syndrome, primary lateral sclerosis, pseudobulbar palsy, ALS) and behavioural predominant FTD (bvFTD, ALS-FTD) were determined and caregivers of patients with ALS were asked on the evolution of behavioural symptoms. Data were compared with 49 healthy controls. Cognition was measured with the Edinburgh Cognitive and Behavioral ALS Screen.ResultsEvolution and features of cognitive profile of patients with motor predominant ALS were distinctly different from patients with behavioural FTD with regard to number and degree of affected cognitive domains. Also, in ALS mostly minus symptoms evolved after physical symptom onset whereas in ALS-FTD plus and minus symptoms were reported with an onset before physical degradation.ConclusionEvolution of cognitive and behavioural profile in patients with motor predominant ALS is distinctly different from those psychocognitive findings in patients with behavioural variant dementia. This may support the hypothesis that (possibly genetic) triggers decide in the preclinical phase on either motor or psychocognitive phenotypes.
Fabrication of sandwich-like microfluidic chip with circular cross-section micro-channels
Authors: Wang Hong Cheng , Zhao Miao Miao , Wu Li Qun 
Published: September 2018

In microfluidic chips, most micro-channel cross-section shapes are rectangular or triangular in existing chip fabricating technologies, including hot embossing, lithography, etching, injection molding, etc. However, compared with the above micro-channel shapes, a circular shape has advantages in aspects of fluid flow, droplet generation, heat transfer and blood vessel replication. This paper presents a sandwich-like microfluidic chip with circular cross-section micro-channels. The sandwich-like structure includes three layers. The top and bottom layers are PDMS material while the middle layer is composed of micron glass capillaries (used as micro-channels) with circular cross-sections. The glass capillaries are made of borosilicate tube by a glass heating process. Sphere shaped paraffin wax is used as a sacrificial material to form micro-channel junctions. To test the functions of the fabricated micro sandwich-like microfluidic chip, a droplet generating experiment was conducted in the T-junction chip. The droplet size can be controlled in the range of 20–400 [Formula: see text]m by varying the water and oil flow rates. This proposed microfluidic chip structure has the advantages of short processing cycle, low cost and small flow resistance.
The mean first-passage time in simplified FitzHugh–Nagumo neural model driven by correlated non-Gaussian noise and Gaussian noise
Authors: Guo Yong-Feng , Xi Bei , Wei Fang , Tan Jian-Guo 
Published: September 2018

In this paper, the mean first-passage time (MFPT) in simplified FitzHugh–Nagumo (FHN) neural model driven by correlated multiplicative non-Gaussian noise and additive Gaussian white noise is studied. Firstly, using the path integral approach and the unified colored-noise approximation (UCNA), the analytical expression of the stationary probability distribution (SPD) is derived, and the validity of the approximation method employed in the derivation is checked by performing numerical simulation. Secondly, the expression of the MFPT of the system is obtained by applying the definition and the steepest-descent method. Finally, the effects of the multiplicative noise intensity D, the additive noise intensity Q, the noise correlation time [Formula: see text], the cross-correlation strength [Formula: see text] and the non-Gaussian noise deviation parameter q on the MFPT are discussed.
Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer
Authors: Aarestrup Julie , Trabert Britton , Ulrich Lian G. , Wentzensen Nicolas , Sørensen Thorkild I.A. , Baker Jennifer L. 
Published: September 2018

Abstract

Background:
Adult body size is related to ovarian cancer risks, but size in childhood may also influence risks. We investigated if childhood body mass index (kg/m2), height, and growth patterns were associated with ovarian cancer overall and by histologic subtypes, including effects of birthweight.

Methods:
A cohort of 155,958 girls from the Copenhagen School Health Records Register, born 1930 to 1989 with measured weights and heights from 7 to 13 years, were included. During follow-up, 1,041 ovarian cancers were recorded. Overweight was defined using International Obesity Task Force criteria. Cox regressions were performed.

Results:
Compared with non-overweight girls, at most ages girls with overweight had increased risks of ovarian cancer overall (HR range: 1.24–1.34), mucinous, endometrioid, and clear cell ovarian cancers, but not serous and other ovarian cancers. Childhood height had positive and significant associations with ovarian cancer overall (HR range: 1.07–1.10 per z-score) and the endometrioid subtype but not with the other subtypes. Adjusting for birthweight minimally altered the associations with childhood body size. In growth analyses, girls with overweight or who were tall at 7 and 13 years had increased risks of ovarian cancer overall compared with average-sized girls at both ages.

Conclusions:
Ovarian carcinogenesis is linked to childhood overweight, tallness, and growth, with variations across histological subtypes, suggesting that early life plays a role in the origins of this disease.

Impact:
These findings emphasize that healthy body size and growth during childhood are important as they may contribute to reducing ovarian cancer risks.
A Designer Cross-reactive DNA Immunotherapeutic Vaccine that Targets Multiple MAGE-A Family Members Simultaneously for Cancer Therapy
Authors: Duperret Elizabeth K. , Liu Shujing , Paik Megan , Trautz Aspen , Stoltz Regina , Liu Xiaoming , Ze Kan , Perales-Puchalt Alfredo , Reed Charles , Yan Jian , Xu Xiaowei , Weiner David B. 
Published: September 2018

AbstractPurpose:Cancer/testis antigens have emerged as attractive targets for cancer immunotherapy. Clinical studies have targeted MAGE-A3, a prototype antigen that is a member of the MAGE-A family of antigens, in melanoma and lung carcinoma. However, these studies have not yet had a significant impact due to poor CD8+ T-cell immunogenicity, platform toxicity, or perhaps limited target antigen availability. In this study, we develop an improved MAGE-A immunogen with cross-reactivity to multiple family members.Experimental Design:In this study, we analyzed MAGE-A expression in The Cancer Genome Atlas and observed that many patients express multiple MAGE-A isoforms, not limited to MAGE-A3, simultaneously in diverse tumors. On the basis of this, we designed an optimized consensus MAGE-A DNA vaccine capable of cross-reacting with many MAGE-A isoforms, and tested immunogenicity and antitumor activity of this vaccine in a relevant autochthonous melanoma model.Results:Immunization of this MAGE-A vaccine by electroporation in C57Bl/6 mice generated robust IFNγ and TNFα CD8+ T-cell responses as well as cytotoxic CD107a/IFNγ/T-bet triple-positive responses against multiple isoforms. Furthermore, this MAGE-A DNA immunogen generated a cross-reactive immune response in 14 of 15 genetically diverse, outbred mice. We tested the antitumor activity of this MAGE-A DNA vaccine in Tyr::CreER;BRAFCa/+;Ptenlox/lox transgenic mice that develop melanoma upon tamoxifen induction. The MAGE-A DNA therapeutic vaccine significantly slowed tumor growth and doubled median mouse survival.Conclusions:These results support the clinical use of consensus MAGE-A immunogens with the capacity to target multiple MAGE-A family members to prevent tumor immune escape.
MORAb-202, an Antibody–Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity
Authors: Cheng Xin , Li Jing , Tanaka Keigo , Majumder Utpal , Milinichik Andrew Z. , Verdi Arielle C. , Maddage Christopher J. , Rybinski Katherine A. , Fernando Shawn , Fernando Danielle , Kuc Megan , Furuuchi Keiji , Fang Frank , Uenaka Toshimitsu , Grasso Luigi , Albone Earl F. 
Published: September 2018

Abstract
Microtubule-targeting agents (MTA) have been investigated for many years as payloads for antibody–drug conjugates (ADC). In many cases, these ADCs have shown limited benefits due to lack of efficacy or significant toxicity, which has spurred continued investigation into novel MTA payloads for next-generation ADCs. In this study, we have developed ADCs using the MTA eribulin, a derivative of the macrocyclic polyether natural product halichondrin B, as a payload. Eribulin ADCs demonstrated in vitro potency and specificity using various linkers and two different conjugation approaches. MORAb-202 is an investigational agent that consists of the humanized anti-human folate receptor alpha (FRA) antibody farletuzumab conjugated via reduced interchain disulfide bonds to maleimido-PEG2-valine-citrulline-p-aminobenzylcarbamyl-eribulin at a drug-to-antibody ratio of 4.0. MORAb-202 displayed preferable biophysical properties and broad potency across a number of FRA-positive tumor cell lines as well as demonstrated improved specificity in vitro compared with farletuzumab conjugated with a number of other MTA payloads, including MMAE, MMAF, and the reducible maytansine linker-payload sulfo-SPDB-DM4. A single-dose administration of MORAb-202 in FRA-positive human tumor cell line xenograft and patient-derived tumor xenograft models elicited a robust and durable antitumor response. These data support further investigation of MORAb-202 as a potential new treatment modality for FRA-positive cancers, using the novel MTA eribulin as a payload.
Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer
Authors: Todenhöfer Tilman , Seiler Roland , Stewart Craig , Moskalev Igor , Gao Jian , Ladhar Simroop , Kamjabi Alireza , Al Nakouzi Nader , Hayashi Tetsuharo , Choi Stephen , Wang Yuzhuo , Frees Sebastian , Daugaard Mads , Oo Htoo Zarni , Fisel Pascale , Schwab Matthias , Schaeffeler Elke , Douglas James , Hennenlotter Jörg , Bedke Jens , Gibb Ewan A. , Fazli Ladan , Stenzl Arnulf , Black Peter C. 
Published: September 2018

Abstract
The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo. Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.