bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic accuracy of a pH stick, modified to detect gastric lipase, to confirm the correct placement of nasogastric tubes
Authors: Rowat Anne M , Graham Catriona , Dennis Martin 
Published: July 2018

ObjectiveThe correct placement of a nasogastric feeding tube is usually confirmed by establishing that an aspirate is acidic using a pH stick. However, antacid medication and achlorhydria can cause false negative pH tests that may delay feeding and increase resource use. The purpose of this study was to evaluate a modified pH stick designed to detect gastric lipase and therefore reduce false negative tests.MethodsIn this prospective observational study, a convenience sample of adult patients who had either gastric and oesophageal samples taken during routine diagnostic gastroscopy (n=97) or bronchial and saliva samples taken during a bronchoscopy (n=106). The samples were tested by blinded observers using the modified and standard pH sticks. The sensitivities and specificities of the two pH sticks in identifying gastric and non-gastric aspirates were compared using the pH cut-off ≤5.5.ResultsThe sensitivities of a pH≤5.5 to correctly identify gastric samples were 66% (95% CI 56 to 75) and 68% (95% CI 57 to 77) for the modified and the standard pH, respectively. The specificities were 81% (95% CI 76 to 85) and 79% (95% CI 74 to 84). There were no significant differences in the distribution of the discordant results between the paired gastric and non-gastric samples for both the modified and standard pH sticks at pH≤5.5 (both McNemar’s tests, p≥0.05).ConclusionsThere were no significant differences between the paired modified and standard pH tests for the gastric samples. Due to the limited accuracy of pH sticks, further research is required to identify accurate and cost-effective bedside methods to confirm the correct placement of nasogastric tubes.
Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice
Authors: Anhê Fernando F , Nachbar Renato T , Varin Thibault V , Trottier Jocelyn , Dudonné Stéphanie , Le Barz Mélanie , Feutry Perrine , Pilon Geneviève , Barbier Olivier , Desjardins Yves , Roy Denis , Marette André 
Published: July 2018

ObjectiveThe consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential.DesignBy using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice.ResultsTreatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls.ConclusionOur results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.
Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis
Authors: Pinder Emma M , Rostron Anthony J , Hellyer Thomas P , Ruchaud-Sparagano Marie-Helene , Scott Jonathan , Macfarlane James G , Wiscombe Sarah , Widdrington John D , Roy Alistair I , Linnett Vanessa C , Baudouin Simon V , Wright Stephen E , Chadwick Thomas , Fouweather Tony , Juss Jatinder K , Chilvers Edwin R , Bowett Susan A , Parker Jennie , McAuley Daniel F , Conway Morris Andrew , Simpson A John 
Published: July 2018

BackgroundCritically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired.MethodsThis was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 μg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety.ResultsThirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever.ConclusionsGM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.
Zealand hard red spring wheat
Authors: Spaner D. , Iqbal M. , Navabi A. , Strenzke K. , Beres B. 
Published: July 2018

Zealand hard red spring wheat (Triticum aestivum L.) was developed using a modified bulk breeding method at the University of Alberta in Edmonton, AB. Zealand is an apically awn-letted, hollow-stemmed cultivar with a combination of high yield potential, tall plant type, large leaves, and early maturity. In three years of testing in the Western Bread Wheat Cooperative Registration Test during 2013–2015, Zealand exhibited grain yield similar to Glenn and Carberry and 5%–6% lower than Unity and AAC Viewfield, though this difference was not significant (p > 0.05). Zealand yielded 37% greater than the highest-yielding Canada Western Red Spring (CWRS) check, CDC Osler, in A-level testing at a certified organic farm. Zealand matured 1–4 d earlier and was taller than all the check cultivars, but exhibited lodging resistance better than Unity and similar to the other checks. The test weight of Zealand (79.1 kg hL−1) was lower than Glenn and similar to the other checks, while its seed mass was in the range of the check cultivars. Overall, Zealand was rated as resistant (R) to the prevalent races of leaf rust, moderately resistant (MR) to stripe rust and loose smut, intermediate (I) to stem rust and leaf spot, and moderately susceptible (MS) to common bunt and Fusarium head blight. Three years of end-use quality evaluation indicated that Zealand is acceptable for the CWRS class, with relatively few weaknesses. The tall plant type, large leaves, and early maturity render Zealand suitable for organic/high weed environments.
Point convolutional neural networks by extension operators
Authors: Atzmon Matan , Maron Haggai , Lipman Yaron 
Published: July 2018

This paper presents Point Convolutional Neural Networks (PCNN): a novel framework for applying convolutional neural networks to point clouds. The framework consists of two operators: extension and restriction, mapping point cloud functions to volumetric functions and vise-versa. A point cloud convolution is defined by pull-back of the Euclidean volumetric convolution via an extension-restriction mechanism.
The point cloud convolution is computationally efficient, invariant to the order of points in the point cloud, robust to different samplings and varying densities, and translation invariant, that is the same convolution kernel is used at all points. PCNN generalizes image CNNs and allows readily adapting their architectures to the point cloud setting.
Evaluation of PCNN on three central point cloud learning benchmarks convincingly outperform competing point cloud learning methods, and the vast majority of methods working with more informative shape representations such as surfaces and/or normals.
Generic deriving of generic traversals
Authors: Kiss Csongor , Pickering Matthew , Wu Nicolas 
Published: July 2018

Functional programmers have an established tradition of using traversals as a design pattern to work with recursive data structures. The technique is so prolific that a whole host of libraries have been designed to help in the task of automatically providing traversals by analysing the generic structure of data types. More recently, lenses have entered the functional scene and have proved themselves to be a simple and versatile mechanism for working with product types. They make it easy to focus on the salient parts of a data structure in a composable and reusable manner.
This paper uses the combination of lenses and traversals to give rise to a library with unprecedented expressivity and flexibility for querying and modifying complex data structures. Furthermore, since lenses and traversals are based on the generic shape of data, this information is used to generate code that is as efficient as hand-optimised versions. The technique leverages the structure of data to produce generic abstractions that are then eliminated by the standard workhorses of modern functional compilers: inlining and specialisation.
Contextual equivalence for a probabilistic language with continuous random variables and recursion
Authors: Wand Mitchell , Culpepper Ryan , Giannakopoulos Theophilos , Cobb Andrew 
Published: July 2018

We present a complete reasoning principle for contextual equivalence in an untyped probabilistic language. The language includes continuous (real-valued) random variables, conditionals, and scoring. It also includes recursion, since the standard call-by-value fixpoint combinator is expressible.
We demonstrate the usability of our characterization by proving several equivalence schemas, including familiar facts from lambda calculus as well as results specific to probabilistic programming. In particular, we use it to prove that reordering the random draws in a probabilistic program preserves contextual equivalence. This allows us to show, for example, that

(let x =
e
1
in let y =
e
2
in
e
0
) =

ctx

(let y =
e
2
in let x =
e
1
in
e
0
)

(provided
x
does not occur free in
e
2
and
y
does not occur free in
e
1
) despite the fact that
e
1
and
e
2
may have sampling and scoring effects.
Merlin: a language server for OCaml (experience report)
Authors: Bour Frédéric , Refis Thomas , Scherer Gabriel 
Published: July 2018

We report on the experience of developing Merlin, a language server for the OCaml programming language in development since 2013. Merlin is a daemon that connects to your favourite text editor and provides services that require a fine-grained understanding of the programming language syntax and static semantics: instant feedback on warnings and errors, autocompletion, "type of the code under the cursor", "go to definition", etc.
Language servers need to handle incomplete and partially-incorrect programs, and try to be incremental to minimize recomputation after small editing actions. Merlin was built by carefully adapting the existing tools (the OCamllex lexer and Menhir parser generators) to better support incrementality, incompleteness and error handling. These extensions are elegant and general, as demonstrated by the interesting, unplanned uses that the OCaml community found for them. They could be adapted to other frontends -- in any language.
Besides incrementality, we discuss the way Merlin communicates with editors, describe the design decisions that went into some demanding features and report on some of the non-apparent difficulties in building good editor support, emerging from expressive programming languages or frustrating tooling ecosystems.
We expect this experience report to be of interest to authors of interactive language tooling for any programming language; many design choices may be reused, and some hard-won lessons can serve as warnings.
Generic zero-cost reuse for dependent types
Authors: Diehl Larry , Firsov Denis , Stump Aaron 
Published: July 2018

Dependently typed languages are well known for having a problem with code reuse. Traditional non-indexed algebraic datatypes (e.g. lists) appear alongside a plethora of indexed variations (e.g. vectors). Functions are often rewritten for both non-indexed and indexed versions of essentially the same datatype, which is a source of code duplication.
We work in a Curry-style dependent type theory, where the same untyped term may be classified as both the non-indexed and indexed versions of a datatype. Many solutions have been proposed for the problem of dependently typed reuse, but we exploit Curry-style type theory in our solution to not only reuse data and programs, but do so at zero-cost (without a runtime penalty). Our work is an exercise in dependently typed generic programming, and internalizes the process of zero-cost reuse as the identity function in a Curry-style theory.
Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Bone Metastasis in Breast Cancer
Authors: Ubellacker Jessalyn M. , Baryawno Ninib , Severe Nicolas , DeCristo Molly J. , Sceneay Jaclyn , Hutchinson John N. , Haider Marie-Therese , Rhee Catherine S. , Qin Yuanbo , Gregory Walter M. , Garrido-Castro Ana C. , Holen Ingunn , Brown Janet E. , Coleman Robert E. , Scadden David T. , McAllister Sandra S. 
Published: July 2018

AbstractThe presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiologic, pathologic, and therapeutic conditions impact hematopoiesis, it remains unclear whether targeting hematopoiesis presents opportunities for limiting bone metastasis. Using preclinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive. Specifically, ZA modulated hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to activate metastasis-suppressive activity. Granulocyte-colony stimulating factor (G-CSF) promoted ZA resistance by redirecting M/OCP differentiation. We identified M/OCP and bone marrow transcriptional programs associated with metastasis suppression and ZA resistance. Analysis of patient blood samples taken at randomization revealed that women with high-plasma G-CSF experienced significantly worse outcome with adjuvant ZA than those with lower G-CSF levels. Our findings support discovery of therapeutic strategies to direct M/OCP lineage potential and biomarkers that stratify responses in patients at risk of recurrence.Significance: Bone marrow myeloid/osteoclast progenitor cell lineage potential has a profound impact on breast cancer bone metastasis and can be modulated by G-CSF and bone-targeting agents. Cancer Res; 78(18); 5300–14. ©2018 AACR.
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma
Authors: Toker Aras , Nguyen Linh T. , Stone Simone C. , Yang S.Y. Cindy , Katz Sarah Rachel , Shaw Patricia A. , Clarke Blaise A. , Ghazarian Danny , Al-Habeeb Ayman , Easson Alexandra , Leong Wey L. , McCready David R. , Reedijk Michael , Guidos Cynthia J. , Pugh Trevor J. , Bernardini Marcus Q. , Ohashi Pamela S. 
Published: July 2018

Abstract
Purpose: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell–associated molecules that can be targeted by tumor immunotherapies.
Experimental Design: The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays.
Results: Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation.
Conclusions: The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. Clin Cancer Res; 24(22); 5685–96. ©2018 AACR.
Concurrent HER or PI3K Inhibition Potentiates the Antitumor Effect of the ERK Inhibitor Ulixertinib in Preclinical Pancreatic Cancer Models
Authors: Jiang Hongmei , Xu Mai , Li Lin , Grierson Patrick , Dodhiawala Paarth , Highkin Maureen , Zhang Daoxiang , Li Qiong , Wang-Gillam Andrea , Lim Kian-Huat 
Published: July 2018

Abstract
Effective treatment for pancreatic ductal adenocarcinoma (PDAC) is an urgent, unmet medical need. Targeting KRAS, the oncogene that is present in &gt;95% of PDAC, is a heavily pursued strategy, but remains unsuccessful in the clinic. Therefore, targeting key effector cascades of KRAS oncoprotein, particularly the mitogenic RAF–MEK–ERK pathway, represents the next best strategy. However, RAF or MEK inhibitors have failed to show clinical efficacy in PDAC. Several studies have shown that cancer cells treated with RAF or MEK inhibitors adopt multiple mechanisms to reactivate ERK signaling. Therefore, development of ERK-specific inhibitors carries the promise to effectively abrogate this pathway. Ulixertinib (or BVD-523) is a first-in-class ERK-specific inhibitor that has demonstrated promising antitumor activity in a phase I clinical trial for advanced solid tumors with NRAS and BRAF mutations, providing a strong rationale to test this inhibitor in PDAC. In this study, we show that ulixertinib effectively inhibits in vitro growth of multiple PDAC lines and potentiates the cytotoxic effect of gemcitabine. Moreover, we found that PDAC cells treated with ulixertinib upregulates the parallel PI3K–AKT pathway through activating the HER/ErbB family proteins. Concurrent inhibition of PI3K or HER proteins synergizes with ulixertinib in suppressing PDAC cell growth in vitro and in vivo. Overall, our study provides the preclinical rationale for testing combinations of ulixertinib with chemotherapy or PI3K and HER inhibitors in PDAC patients. Mol Cancer Ther; 17(10); 2144–55. ©2018 AACR.
Auranofin Enhances Ibrutinib's Anticancer Activity in EGFR-Mutant Lung Adenocarcinoma
Authors: Hu Jing , Zhang Huijuan , Cao Mengru , Wang Li , Wu Shuhong , Fang Bingliang 
Published: July 2018

Abstract
We previously found that ibrutinib has anticancer activity in EGFR-mutant non–small cell lung cancer (NSCLC). One of our recent studies showed that auranofin, a gold complex that has been used to treat rheumatoid arthritis, inhibited the PI3K/AKT/mTOR pathway and promoted apoptosis in some NSCLC cells. Because the PI3K/AKT/mTOR pathway is one of the major downstream pathways of EGFR, we hypothesized that ibrutinib's activity might be enhanced by combination therapy with auranofin in NSCLC cells. To this end, we examined ibrutinib's dose responses in EGFR-mutant H1975, PC9, and H1650 cells and in EGFR wild-type Calu3 and H460 cells in the presence or absence of auranofin. Although low concentrations of auranofin alone demonstrated mild anticancer activities, its presence dramatically enhanced ibrutinib's activity in H1975, PC9, and H1650 cells (IC50 value reduced 10- to 100-fold), but had only mild effect on Calu3 and H460 cells, demonstrating that ibrutinib's anti-EGFR activity is enhanced when it is combined with auranofin. A mechanistic analysis revealed that ibrutinib alone induced dramatic inhibition of the MEK/ERK pathway in both H1975 and H1650 cells, whereas auranofin alone inhibited the AKT/mTOR pathway. The combination of ibrutinib and auranofin led to a dramatically enhanced inhibition of the expression or phosphorylation of multiple key nodes in the AKT/mTOR and MEK/ERK pathways in both cell lines. In mice, the combination of ibrutinib and auranofin significantly suppressed the growth of H1975 xenografted tumors without inducing obvious toxic effects. Our results demonstrate the feasibility of improving ibrutinib's anti-EGFR activity for NSCLC using combination therapy with auranofin. Mol Cancer Ther; 17(10); 2156–63. ©2018 AACR.
Cancer-Associated Hypercoagulation Increases the Risk of Early Recurrent Stroke in Patients with Active Cancer
Authors: Fujinami Jun , Ohara Tomoyuki , Kitani-Morii Fukiko , Tomii Yasuhiro , Makita Naoki , Yamada Takehiro , Kasai Takashi , Nagakane Yoshinari , Nakagawa Masanori , Mizuno Toshiki 
Published: July 2018

<b><i>Background:</i></b> This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. <b><i>Methods:</i></b> We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. <b><i>Results:</i></b> One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher ­D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42–30.7, <i>p</i> = 0.015). <b><i>Conclusions:</i></b> Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.