bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohort study of medical cannabis authorisation and healthcare utilisation in 2014–2017 in Ontario, Canada
Authors: Eurich Dean , Lee Cerina , Zongo Arsene , Minhas-Sandhu Jasjett K , Hanlon John G , Hyshka Elaine , Dyck Jason 
Published: December 2019

BackgroundThe impact of medical cannabis on healthcare utilisation between 2014 and 2017 in Ontario, Canada. With cannabis legalisation in Canada and some states in the USA, high-quality longitudinal cohort research studies are of urgent need to assess the impact of cannabis use on healthcare utilisation.MethodsA matched cohort study of 9925 medical cannabis authorised adult patients (inhaled (smoked or vaporised) or orally consumed (oils)) at specialised cannabis clinics, and inclusion of 17 732 controls (not authorised) between 24 April 2014 and 31 March 2017 from Ontario, Canada. Interrupted time series and multivariate Poisson regression analyses were conducted. Medical cannabis impact on healthcare utilisation was measured over 6 months: all-cause physician visits, all-cause hospitalisation, ambulatory care sensitive conditions (ACSC)-related hospitalisations, all-cause emergency department (ED) visits and ACSC-related ED visits.ResultsFor medical cannabis patients compared with controls, there was an initial (within the first month) increase in physician visits (additional 4330 visits per 10 000 patients). However, a numerical reduction was noted over the 6-month follow-up, and no statistical difference was observed (p=0.126). Likewise, in hospitalisations and ACSC ED visits, there was an initial increase (44 per 10 000 people, p<0.05) but no statistical difference after follow-up (p=0.34). Conversely, no initial increase in all-cause ED visits was observed with a slight decrease (19 visits per 10 000 patients, p=0.014) in follow-up.ConclusionsAn initial increase (within first month) in healthcare utilisation may be expected among medical cannabis users that appears to wane over time. Proactive follow-up of patients using medical cannabis is warranted to minimise initial risks to patients and actively assess potential benefits/harms of ongoing use.
Simulation of the CBETA 4-pass FFAG ERL using field maps — exclusively
Authors: Méot F. , Berg J. S. , Brooks S. , Trbojevic D. , Tsoupas N. , Crittenden J. 
Published: December 2019

The Cornell-BNL Electron Test Accelerator (CBETA), a four-pass, 150 MeV energy recovery linac (ERL), is now in construction at Cornell. Commissioning commenced on March 2019. A particularity of CBETA is that a single channel loop recirculates the four energies (42, 78, 114 and 150 MeV). The return loop arcs are based on fixed-field alternating gradient (FFAG) optics. The loop is comprised of 107 quadrupole-doublet cells, built using Halbach permanent magnet technology. Spreader and combiner sections (4 independent beam lines each) connect the 36 MeV linac to the FFAG arcs. We introduce here a start-to-end simulation of the 4-pass ERL, based entirely, and exclusively, on the use of magnetic field maps to model the optical components.
Metabolic Imaging Using Hyperpolarized Pyruvate–Lactate Exchange Assesses Response or Resistance to the EGFR Inhibitor Cetuximab in Patient-Derived HNSCC Xenografts
Authors: Mignion Lionel , Acciardo Stefania , Gourgue Florian , Joudiou Nicolas , Caignet Xavier , Goebbels Rose-Marie , Corbet Cyril , Feron Olivier , Bouzin Caroline , Cani Patrice D. , Machiels Jean-Pascal , Schmitz Sandra , Jordan Bénédicte F. 
Published: December 2019

Abstract

Purpose:
Optimal head and neck squamous cell carcinoma (HNSCC) patient selection for anti–EGFR-based therapy remains an unmet need since only a minority of patients derive long-term benefit from cetuximab treatment. We assessed the ability of state-of-the-art noninvasive in vivo metabolic imaging to probe metabolic shift in cetuximab-sensitive and -resistant HNSCC patient-derived tumor xenografts (PDTXs).

Experimental Design:
Three models selected based on their known sensitivity to cetuximab in patients (cetuximab-sensitive or acquired-resistant HNC007 PDTXs, cetuximab-naïve UCLHN4 PDTXs, and cetuximab-resistant HNC010 PDTXs) were inoculated in athymic nude mice.

Results:
Cetuximab induced tumor size stabilization in mice for 4 weeks in cetuximab-sensitive and -naïve models treated with weekly injections (30 mg/kg) of cetuximab. Hyperpolarized 13C-pyruvate–13C-lactate exchange was significantly decreased in vivo in cetuximab-sensitive xenograft models 8 days after treatment initiation, whereas it was not modified in cetuximab-resistant xenografts. Ex vivo analysis of sensitive tumors resected at day 8 after treatment highlighted specific metabolic changes, likely to participate in the decrease in the lactate to pyruvate ratio in vivo. Diffusion MRI showed a decrease in tumor cellularity in the HNC007-sensitive tumors, but failed to show sensitivity to cetuximab in the UCLHN4 model.

Conclusions:
This study constitutes the first in vivo demonstration of cetuximab-induced metabolic changes in cetuximab-sensitive HNSCC PDTXs that were not present in resistant tumors. Using metabolic imaging, we were able to identify hyperpolarized 13C-pyruvate as a potential marker for response and resistance to the EGFR inhibitor in HNSCC.
Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer
Authors: Kvorjak Michael , Ahmed Yasmine , Miller Michelle L. , Sriram Raahul , Coronnello Claudia , Hashash Jana G. , Hartman Douglas J. , Telmer Cheryl A. , Miskov-Zivanov Natasa , Finn Olivera J. , Cascio Sandra 
Published: December 2019

Abstract
Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC). Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression. It is not known what causes changes in glycosylation of MUC1. Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage–associated cytokines compared with normal tissues. We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms. A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells. M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans. Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells. Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17. We demonstrated that IL13 promoted phosphorylation of STAT6 to activate transcription of ST6GALNAC1. A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy. Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.
See related Spotlight on p. 160
Preclinical Evaluation of Pulsed Field Ablation
Authors: Koruth Jacob , Kuroki Kenji , Iwasawa Jin , Enomoto Yoshinari , Viswanathan Raju , Brose Richard , Buck Eric D. , Speltz Molly , Dukkipati Srinivas R. , Reddy Vivek Y. 
Published: December 2019

Background:
Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA’s efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms.

Methods:

A femoral venous approach was used to gain right and left atrial access under general anesthesia in healthy swine. Baseline potentials in right superior pulmonary and inferior common vein and in SVC were assessed. Bipolar PFA was performed with monophasic (PFA
Mono
) and biphasic (PFA
Bi
) waveforms in 7 and 7 swine sequentially and irrigated radiofrequency ablation in 3 swine. Vein potentials were then assessed acutely, and at ≈10 weeks; histology was obtained.

Results:

All targeted veins (n=46) were successfully isolated on the first attempt in all cohorts. The PFA
Bi
waveform induced significantly less skeletal muscle engagement. Pulmonary vein isolation durability was assessed in 28 veins: including the SVC, durability was significantly higher in the PFA
Bi
group (18/18 PFA
Bi
, 10/18 PFA
Mono
, 3/6 radiofrequency,
P
=0.002). Transmurality rates were similar across groups with evidence of nerve damage only with radiofrequency. Pulmonary vein narrowing was noted only in the radiofrequency cohort. The phrenic nerve was spared in all cohorts but at the expense of incomplete SVC encirclement with radiofrequency.

Conclusions:
In this chronic porcine study, PFA-based pulmonary vein and SVC isolation were safe and efficacious with demonstrable sparing of nerves and venous tissue. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.
Myocardial Storage, Inflammation, and Cardiac Phenotype in Fabry Disease After One Year of Enzyme Replacement Therapy
Authors: Nordin Sabrina , Kozor Rebecca , Vijapurapu Ravi , Augusto João B. , Knott Kristopher D. , Captur Gabriella , Treibel Thomas A. , Ramaswami Uma , Tchan Michel , Geberhiwot Tarekegn , Steeds Richard P. , Hughes Derralynn A. , Moon James C. 
Published: December 2019

Background:
Cardiac response to enzyme replacement therapy (ERT) in Fabry disease is typically assessed by measuring left ventricular mass index using echocardiography or cardiovascular magnetic resonance, but neither quantifies myocardial biology. Low native T1 in Fabry disease represents sphingolipid accumulation; late gadolinium enhancement with high T2 and troponin elevation reflects inflammation. We evaluated the effect of ERT on myocardial storage, inflammation, and hypertrophy.

Methods:
Twenty patients starting ERT (60% left ventricular hypertrophy–positive) were compared with 18 patients with early disease and 18 with advanced disease over 1 year at 3 centers. Cardiovascular magnetic resonance (left ventricular mass index, T1, T2, global longitudinal strain, and late gadolinium enhancement) and biomarkers (high-sensitive troponin-T and NT-proBNP [N-terminal Pro-B-type natriuretic peptide]) at baseline (pre-ERT) and 12 months were performed. Early disease controls were stable, treatment-naïve patients (mainly left ventricular hypertrophy–negative); advanced disease controls were stable, established ERT patients (mainly left ventricular hypertrophy–positive).

Results:

Over 1 year, early disease controls increased maximum wall thickness and left ventricular mass index (9.8±2.7 versus 10.2±2.6 mm;
P
=0.010; 65±15 versus 67±16 g/m
2
;
P
=0.005) and native T1 fell (981±58 versus 959±61 ms;
P
=0.002). Advanced disease controls increased T2 in the late gadolinium enhancement area (57±6 versus 60±7 ms;
P
=0.023) with worsening global longitudinal strain (−13.2±3.4 versus −12.1±4.8;
P
=0.039). Newly treated patients had a small reduction in maximum wall thickness (14.8±5.9 versus 14.4±5.7 mm;
P
=0.028), stable left ventricular mass index (93±42 versus 92±40 g/m
2
;
P
=0.186) and a reduction in T1 lowering (917±49 versus 931±54 ms;
P
=0.017).

Conclusions:
Fabry myocardial phenotype development is different at different disease stages. After 1 year of ERT initiation, left ventricular hypertrophy–positive patients have a detectable, small reduction in left ventricular mass and storage.
Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses
Authors: Souza Patricia R. , Marques Raquel M. , Gomez Esteban A. , Colas Romain A. , De Matteis Roberta , Zak Anne , Patel Mital , Collier David J. , Dalli Jesmond 
Published: December 2019

Rationale:
Specialized pro-resolving mediators (SPM—lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood.

Objective:
Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses.

Methods and Results:
Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo.

Conclusions:
Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03347006.
Effect of Statin Therapy on Outcomes of Patients With Acute Ischemic Stroke and Atrial Fibrillation
Authors: Choi Kang‐Ho , Seo Woo‐Keun , Park Man‐Seok , Kim Joon‐Tae , Chung Jong‐Won , Bang Oh Young , Kim Gyeong‐Moon , Song Tae‐Jin , Kim Bum Joon , Heo Sung Hyuk , Jung Jin‐Man , Oh Kyung‐Mi , Kim Chi Kyung , Yu Sungwook , Park Kwang‐Yeol , Kim Jeong‐Min , Park Jong‐Ho , Choi Jay Chol , Hwang Yang‐Ha , Kim Yong‐Jae 
Published: December 2019

Background
There is insufficient evidence on the effect of statins, particularly high‐intensity statins, in patients with acute ischemic stroke and atrial fibrillation. We investigated the impact of statins on the outcomes in these patients, including those who might be vulnerable to statin therapy and those without clinical atherosclerotic cardiovascular diseases.

Methods and Results

A total of 2153 patients with acute ischemic stroke and atrial fibrillation were enrolled in the present nationwide, multicenter, cohort study. The primary composite end point was the occurrence of net adverse clinical and cerebral events (
NACCE
; death from any cause, stroke, acute coronary syndrome, or major bleeding) over a 3‐year period based on statin intensity.
NACCE
rates were lower in patients receiving low‐ to moderate‐intensity (adjusted hazard ratio 0.64; 95%
CI
: 0.52‐0.78) and high‐intensity statins (hazard ratio 0.51; 95%
CI
0.40‐0.66) than in those not receiving statin therapy. High‐intensity statins were associated with a lower risk for
NACCE
than low‐ to moderate‐intensity statins (hazard ratio 0.76; 95%
CI
0.59‐0.96). Subgroup analyses showed that the differences in hazard ratio for 3‐year
NACCE
favored statin use across all subgroups, including older patients, those with low cholesterol levels, patients receiving anticoagulants, and patients without clinical atherosclerotic cardiovascular diseases. Magnified benefits of high‐intensity statins compared with low‐ to moderate‐intensity statins were observed in patients who underwent revascularization therapy and those under 75 years of age.

Conclusions

Statins, particularly high‐intensity statins, could reduce the risk for
NACCE
in patients with acute ischemic stroke and atrial fibrillation; this needs to be further explored in randomized controlled trials.
Substitutions of Oatmeal and Breakfast Food Alternatives and the Rate of Stroke
Authors: Lyskjær Line , Overvad Kim , Tjønneland Anne , Dahm Christina C. 
Published: December 2019

Background and Purpose—
Studies indicate that consuming breakfast every day, and particularly oatmeal, is associated with lower risk of stroke. However, few studies have considered replacement foods when considering foods usually consumed at breakfast. We, therefore, aimed to model substitutions between the breakfast food products oatmeal, eggs, yogurt, or white bread and subsequent risk of stroke.

Methods—
Participants from the Danish cohort study (Diet, Cancer and Health; n=55 095) were followed for 13.4 years, during which 2260 subjects experienced a first-ever stroke. Breakfast foods were assessed using a validated 192-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% CIs for associations between hypothetical substitutions of standard portion sizes of breakfast foods and stroke.

Results—
Modeling replacement of white bread or eggs with oatmeal was associated with a lower rate of total stroke (hazard ratio [HR]=0.96 [95% CI, 0.95–0.98]; HR=0.96 [95% CI, 0.93–0.98], respectively), total ischemic stroke (HR=0.96 [95% CI, 0.94–0.98]; HR=0.96 [95% CI, 0.94–0.99], respectively), and ischemic stroke due to small-artery occlusion (HR=0.95 [95% CI, 0.93–0.98]; HR=0.95 [95% CI, 0.91–0.99], respectively). Furthermore, modeling replacement of eggs with oatmeal was associated with a lower rate of total hemorrhagic stroke (HR=0.94 [95% CI, 0.89–0.99]). Modeling replacement of yogurt with oatmeal was not associated with stroke.

Conclusions—
Our findings suggest that a diet containing oatmeal instead of white bread or eggs may be associated with a lower rate of stroke.
Plato and the Language of Mysteries
Authors: Dinkelaar Bianca M. 
Published: December 2019

Abstract
Despite Plato’s repeated criticism of both µῦθοι and mystery cults, Orphism/Pythagoreanism and the Eleusinian Mysteries feature frequently in his dialogues. This paper uncovers the reason why, and the context in which, Plato employs motifs and language associated with these cults. Prevailing explanations in scholarship are shown to apply in some instances but not others, and to be largely insufficient in providing an underlying reason for Plato’s use of mystery cults in general. Through a detailed examination of various mystery motifs in the dialogues, this paper argues that Plato has simply borrowed from religion what he could not achieve with philosophy alone: emotional appeal.
Morphological and molecular characterisation of Helicotylenchus ciceri n. sp. and H. scoticus Boag & Jairajpuri, 1985 (Nematoda: Hoplolaimidae) from Iran
Authors: Mohammadi Zameleh Fariba , Karegar Akbar , Ghaderi Reza , Mokaram Hesar Abbas 
Published: December 2019

Summary
Helicotylenchus ciceri n. sp. and H. scoticus are described and illustrated based on morphological, morphometric and molecular characters. The new species is characterised by a conical and truncated lip region with five or six distinct annuli, stylet 32-37 μm long with anteriorly concave knobs, secretory-excretory pore posterior to the pharyngo-intestinal valve, dorsally convex-conoid tail with a terminal projection, phasmids 14 (7-20) annuli anterior to the level of anus, empty spermatheca and absence of males. Intraspecific variation of 16 populations of H. scoticus, collected from chickpea and lentil fields in Kermanshah province, western Iran, is discussed. The results of the phylogenetic analyses based on the sequences of the partial 18S rRNA, D2-D3 expansion segments of 28S rRNA and ITS rRNA genes are provided for the studied species, confirming their differences from each other and determining the position of them and their relationships with closely related species.
Ficophagus (Nematoda: Aphelenchoididae) from sycones of Ficus subgenus Urostigma, sections Malvanthera and Urostigma, in eastern Australia
Authors: Davies Kerrie A. , Bartholomaeus Faerlie , Mei Li Dong , Zhao Zeng Qi , Ye Weimin , Giblin-Davis Robin M. 
Published: December 2019

Summary
Ficophagus from collecting trips in eastern Australia, made over 15 years, are summarised and show that species of the genus occurred widely in sycones of Ficus, subgenus Urostigma, section Malvanthera. Two new species (based on morphological differences and molecular sequencing) are described: Ficophagus elizabethae sp. n. from Ficus macrophylla, F. rubiginosa and F. obliqua, and Ficophagus richardi sp. n. from Ficus obliqua; and a morphospecies, Ficophagus Morphospecies malandicus from Ficus obliqua. Ficophagus elizabethae sp. n. is characterised by having the excretory pore (EP) opening from the level of the junction of the conus and shaft of the stylet to that of the knobs, a relatively long procorpus (1.0-2.5 times length of stylet), female tail with an obliquely truncate tail with a hyaline area and a finely to broadly rounded tip which may be mucronate; post-vulval uterine sac (PUS) ca one vulval body diam. (VBD) in length; rose-thorn-shaped spicule with distinct rostrum and prominent condylus; and genital papillae arranged as largest pair adcloacal, second pair posterior to mid-tail length, and third small pair near tail tip; and was collected from Sydney in New South Wales, to Bundaberg in Queensland (QLD). Ficophagus richardi sp. n. is characterised by having the EP opening at the level of the junction of the stylet shaft and conus, a labial cap which is raised around the opening for the stylet; procorpus 0.8-1.7 times length of the stylet, PUS <1 VBD in length, long uterus, and female tail with a V-shaped hyaline area at the bluntly rounded tip; rose-thorn-shaped spicule with a small rostrum and prominent condylus, three pairs genital papillae, first and largest on anterior cloacal lip, second at 70% of tail length measured from cloacal aperture, and third near tip, and was collected from Ban Ban Springs in the south to the Bundaberg region in the mid-north of QLD. In addition, in the absence of pertinent molecular sequences, a morphospecies is described. Ficophagus Morphospecies malandicus is characterised by having the EP opening anterior to the junction of the stylet conus and shaft, procorpus 0.9-2 times length of stylet, a short PUS usually <1 VBD long, short uterus, rose-thorn-shaped spicule with a raised condylus and prominent rostrum, and three pairs of subventral papillae on the tail (one adcloacal, one posterior to mid-tail and one near tail tip); and was collected from the Atherton Tableland, QLD. A table comparing morphological characteristics is provided to help with identification of Ficophagus nematodes from figs of the section Malvanthera in eastern Australia.