bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gasotransmitters in pregnancy: from conception to uterine involution†
Authors: Guerra Damian D , Hurt K Joseph 
Published: March 2019

AbstractGasotransmitters are endogenous small gaseous messengers exemplified by nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S or sulfide). Gasotransmitters are implicated in myriad physiologic functions including many aspects of reproduction. Our objective was to comprehensively review basic mechanisms and functions of gasotransmitters during pregnancy from conception to uterine involution and highlight future research opportunities. We searched PubMed and Web of Science databases using combinations of keywords nitric oxide, carbon monoxide, sulfide, placenta, uterus, labor, and pregnancy. We included English language publications on human and animal studies from any date through August 2018 and retained basic and translational articles with relevant original findings. All gasotransmitters activate cGMP signaling. NO and sulfide also covalently modify target protein cysteines. Protein kinases and ion channels transduce gasotransmitter signals, and co-expressed gasotransmitters can be synergistic or antagonistic depending on cell type. Gasotransmitters influence tubal transit, placentation, cervical remodeling, and myometrial contractility. NO, CO, and sulfide dilate resistance vessels, suppress inflammation, and relax myometrium to promote uterine quiescence and normal placentation. Cervical remodeling and rupture of fetal membranes coincide with enhanced oxidation and altered gasotransmitter metabolism. Mechanisms mediating cellular and organismal changes in pregnancy due to gasotransmitters are largely unknown. Altered gasotransmitter signaling has been reported for preeclampsia, intrauterine growth restriction, premature rupture of membranes, and preterm labor. However, in most cases specific molecular changes are not yet characterized. Nonclassical signaling pathways and the crosstalk among gasotransmitters are emerging investigation topics.
Risk of Malignant Cancers in Inflammatory Bowel Disease
Authors: Loo Simone Y , Vutcovici Maria , Bitton Alain , Lakatos Peter L , Azoulay Laurent , Suissa Samy , Brassard Paul 
Published: March 2019

Abstract

Objectives
To explore the trends and the predictors of incident malignant cancer among patients with inflammatory bowel disease [IBD].

Methods
We identified a cohort of all patients with incident IBD in Quebec, Canada, from 1998 to 2015, using provincial administrative health-care databases [RAMQ and Med-Echo]. Annual incidence rates [IRs] of cancer were calculated using Poisson regression and were compared with those of the Quebec population using standardized incidence ratios [SIRs ]. Temporal trends in these rates were evaluated by fitting generalized linear models. Conditional logistic regression was used to estimate odds ratios [ORs] for predictors associated with cancer development.

Results
The cohort included 35 985 patients with IBD, of which 2275 developed cancers over a mean follow-up of 8 years (IR 785.6 per 100 000 persons per year; 95% confidence interval [CI] 754.0–818.5). The rate of colorectal cancer decreased significantly from 1998 to 2015 [p < 0.05 for linear trend], but the incidence remained higher than expected, compared with the Quebec population [SIR 1.39; 95% CI 1.19–1.60]. Rates of extraintestinal cancers increased non-significantly over time [p = 0.11 for linear trend]. In the IBD cohort, chronic kidney disease [OR 1.29; 95% CI 1.17–1.43], respiratory diseases [OR 1.07; 95% CI 1.02–1.12], and diabetes mellitus [OR 1.06; 95% CI 1.01–1.11] were associated with an increase in the incidence of cancer.

Conclusions
The decreasing rates of colorectal cancer suggest improved management and care in IBD. Further studies are needed to explore the impact of comorbid conditions on the risk of cancer in IBD.
Disparities in treatment of diabetes and hypertension among groups of foreign origin and the general Finnish population
Authors: Etchi Daniel T , Lilja Eero , Koponen Päivikki , Laatikainen Tiina 
Published: March 2019

Abstract

Background
Migrants from low-income countries are more predisposed to diabetes and cardiovascular risks than host European natives, but how treatment targets are met in migrant patients is unclear. We examined health service use and treatment of diabetes and hypertension among selected migrant groups and the general Finnish population and compared prevalence of cardiovascular risk factors between patients and non-patients.

Methods
Cross-sectional data from randomly sampled 30- to 64-year-old participants (387 Russian, 198 Somali and 343 Kurdish origin migrants) of the Migrant Health and Wellbeing Survey (2010–2012) were used. Health 2011 survey data (n = 1086) were used as a comparison group.

Results
Compared with the general population, diabetes-related doctor/nurse visits were more frequent among Russian and Somali, but not the Kurdish group. Use of prescribed antidiabetic and antihypertensive drugs were significantly lower among Russians (78%/56%) and Kurdish (68%/58%), but not in Somalis (85%/62%) compared with the general population (96%/78%). Obesity, elevated blood pressure and elevated glucose levels were more prevalent in patients than non-patients, and over 60% of patients and over 70% of non-patients had elevated plasma low density lipoprotein cholesterol. Differences in cardiovascular disease (CVD) risk profiles between patients and non-patients were not associated with socio-economic factors.

Conclusions
This study indicates disparities in prevalence and management of diabetes and hypertension and their associated risk factors among ethnic groups. Diabetes, CVD risks and treatment outcomes in patients were sub-optimal, especially among foreign origin groups. Comprehensive health promotion strategies are needed to improve cardiometabolic health in vulnerable populations.
Recombinant dermatan sulfate is a potent activator of heparin cofactor II-dependent inhibition of thrombin
Authors: Tykesson Emil , Maccarana Marco , Thorsson Hanna , Liu Jian , Malmström Anders , Ellervik Ulf , Westergren-Thorsson Gunilla 
Published: March 2019

AbstractThe glycosaminoglycan dermatan sulfate (DS) is a well-known activator of heparin cofactor II-dependent inactivation of thrombin. In contrast to heparin, dermatan sulfate has never been prepared recombinantly from material of non-animal origin. Here we report on the enzymatic synthesis of structurally well-defined DS with high anticoagulant activity. Using a microbial K4 polysaccharide and the recombinant enzymes DS-epimerase 1, dermatan 4-O-sulfotransferase 1, uronyl 2-O-sulfotransferase and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase, several new glycostructures have been prepared, such as a homogenously sulfated IdoA-GalNAc-4S polymer and its 2-O-, 6-O- and 2,6-O-sulfated derivatives. Importantly, the recombinant highly 2,4-O-sulfated DS inhibits thrombin via heparin cofactor II, approximately 20 times better than heparin, enabling manipulation of vascular and extravascular coagulation. The potential of this method can be extended to preparation of specific structures that are of importance for binding and activation of cytokines, and control of inflammation and metastasis, involving extravasation and migration.
Legislating for universal access to medicines: a rights-based cross-national comparison of UHC laws in 16 countries
Authors: Perehudoff S Katrina , Alexandrov Nikita V , Hogerzeil Hans V 
Published: March 2019

Abstract
Universal health coverage (UHC) aims to ensure that all people have access to health services including essential medicines without risking financial hardship. Yet, in many low- and middle-income countries (LMICs) inadequate UHC fails to ensure universal access to medicines and protect the poor and vulnerable against catastrophic spending in the event of illness. A human rights approach to essential medicines in national UHC legislation could remedy these inequities. This study identifies and compares legal texts from national UHC legislation that promote universal access to medicines in the legislation of 16 mostly LMICs: Algeria, Chile, Colombia, Ghana, Indonesia, Jordan, Mexico, Morocco, Nigeria, Philippines, Rwanda, South Africa, Tanzania, Turkey, Tunisia and Uruguay. The assessment tool was developed based on WHO’s policy guidelines for essential medicines and international human rights law; it consists of 12 principles in three domains: legal rights and obligations, good governance, and technical implementation. Relevant legislation was identified, mapped, collected and independently assessed by multi-disciplinary, multi-lingual teams. Legal rights and State obligations toward medicines are frequently codified in UHC law, while most good governance principles are less common. Some technical implementation principles are frequently embedded in national UHC law (i.e. pooled user contributions and financial coverage for the vulnerable), while others are infrequent (i.e. sufficient government financing) to almost absent (i.e. seeking international assistance and cooperation). Generally, upper-middle and high-income countries tended to embed explicit rights and obligations with clear boundaries, and universal mechanisms for accountability and redress in domestic law while less affluent countries took different approaches. This research presents national law makers with both a checklist and a wish list for legal reform for access to medicines, as well as examples of legal texts. It may support goal 7 of the WHO Medicines & Health Products Strategic Programme 2016–30 to develop model legislation for medicines reimbursement.
Visual Networks As a Means of Representing Collocational Information in Electronic Dictionaries
Authors: Torner Sergi , Arias-Badia Blanca 
Published: March 2019

AbstractThe digital turn in lexicography has paved the way to new techniques for presenting information in dictionaries. This paper explores the potential of collocational networks (Phillips 1983, Williams 1998) as key lexicographical tools to represent information about lexical combinatorics. Collocational networks, which had initially been used as a means of identifying collocations in large corpora, must now be rethought in order to assist non-expert dictionary users in text production by allowing them to find the exact collocates they are looking for, as well as by offering the grammatical information needed to use collocations accurately. We advocate improving networks by incorporating information visualization techniques (Ware 2008, Pham 2012). Specifically, we suggest a number of measures which may be taken to both simplify access to the information provided by raw output from corpora —much of which may be noise for the dictionary user— and to enrich such collocational data by means of visually-explained relevant grammatical information.
Topological Types of Algebraic Stacks
Authors: Chough Chang-Yeon 
Published: March 2019

AbstractThe main goal of this paper is to set a foundation for homotopy theory of algebraic stacks under model category theory and to show how it can be applied in various contexts. It not only generalizes the étale homotopy theory to algebraic stacks but also provides more suitable framework for the homotopy theory in a broader context. Also, a new result that the profinite completion of pro-simplicial sets admits a right adjoint is provided and integrated with the foundational work to generalize Artin–Mazur’s comparison theorem from schemes to algebraic stacks in a formal way.
A review of measurement practice in studies of clinical decision support systems 1998–2017
Authors: Scott Philip J , Brown Angela W , Adedeji Taiwo , Wyatt Jeremy C , Georgiou Andrew , Eisenstein Eric L , Friedman Charles P 
Published: March 2019

Abstract

Objective
To assess measurement practice in clinical decision support evaluation studies.

Materials and Methods
We identified empirical studies evaluating clinical decision support systems published from 1998 to 2017. We reviewed titles, abstracts, and full paper contents for evidence of attention to measurement validity, reliability, or reuse. We used Friedman and Wyatt’s typology to categorize the studies.

Results
There were 391 studies that met the inclusion criteria. Study types in this cohort were primarily field user effect studies (n = 210) or problem impact studies (n = 150). Of those, 280 studies (72%) had no evidence of attention to measurement methodology, and 111 (28%) had some evidence with 33 (8%) offering validity evidence; 45 (12%) offering reliability evidence; and 61 (16%) reporting measurement artefact reuse.

Discussion
Only 5 studies offered validity assessment within the study. Valid measures were predominantly observed in problem impact studies with the majority of measures being clinical or patient reported outcomes with validity measured elsewhere.

Conclusion
Measurement methodology is frequently ignored in empirical studies of clinical decision support systems and particularly so in field user effect studies. Authors may in fact be attending to measurement considerations and not reporting this or employing methods of unknown validity and reliability in their studies. In the latter case, reported study results may be biased and effect sizes misleading. We argue that replication studies to strengthen the evidence base require greater attention to measurement practice in health informatics research.
Applying machine learning to predict real-world individual treatment effects: insights from a virtual patient cohort
Authors: Fang Gang , Annis Izabela E , Elston-Lafata Jennifer , Cykert Samuel 
Published: March 2019

Abstract

Objective
We aimed to investigate bias in applying machine learning to predict real-world individual treatment effects.

Materials and Methods
Using a virtual patient cohort, we simulated real-world healthcare data and applied random forest and gradient boosting classifiers to develop prediction models. Treatment effect was estimated as the difference between the predicted outcomes of a treatment and a control. We evaluated the impact of predictors (ie, treatment predictors [X1], confounders [X2], treatment effects modifiers [X3], and other outcome risk factors [X4]) with known effects on treatment and outcome using real-world data, and outcome imbalance on predicting individual outcome. Using counterfactuals, we evaluated percentage of patients with biased predicted individual treatment effects

Results
The X4 had relatively more impact on model performance than X2 and X3 did. No effects were observed from X1. Moderate-to-severe outcome imbalance had a significantly negative impact on model performance, particularly among subgroups in which an outcome occurred. Bias in predicting individual treatment effects was significant and persisted even when the models had a 100% accuracy in predicting health outcome.

Discussion
Inadequate inclusion of the X2, X3, and X4 and moderate-to-severe outcome imbalance may affect model performance in predicting individual outcome and subsequently bias in predicting individual treatment effects. Machine learning models with all features and high performance for predicting individual outcome still yielded biased individual treatment effects.

Conclusions
Direct application of machine learning might not adequately address bias in predicting individual treatment effects. Further method development is needed to advance machine learning to support individualized treatment selection.
Persistence of a Geographically-Stable Hybrid Zone in Puerto Rican Dwarf Geckos
Authors: Pinto Brendan J , Titus-McQuillan James , Daza Juan D , Gamble Tony 
Published: March 2019

AbstractDetermining the mechanisms that create and maintain biodiversity is a central question in ecology and evolution. Speciation is the process that creates biodiversity. Speciation is mediated by incompatibilities that lead to reproductive isolation between divergent populations and these incompatibilities can be observed in hybrid zones. Gecko lizards are a speciose clade possessing an impressive diversity of behavioral and morphological traits. In geckos, however, our understanding of the speciation process is negligible. To address this gap, we used genetic sequence data (both mitochondrial and nuclear markers) to revisit a putative hybrid zone between Sphaerodactylus nicholsi and Sphaerodactylus townsendi in Puerto Rico, initially described in 1984. First, we addressed discrepancies in the literature on the validity of both species. Second, we sampled a 10-km-wide transect across the putative hybrid zone and tested explicit predictions about its dynamics using cline models. Third, we investigated potential causes for the hybrid zone using species distribution modeling and simulations; namely, whether unique climatic variables within the hybrid zone might elicit selection for intermediate phenotypes. We find strong support for the species-level status of each species and no evidence of movement, or unique climatic variables near the hybrid zone. We suggest that this narrow hybrid zone is geographically stable and is maintained by a combination of dispersal and selection. Thus, this work has identified an extant model system within geckos that that can be used for future investigations detailing genetic mechanisms of reproductive isolation in an understudied vertebrate group.
Isotopic evidence for volatile replenishment of the Moon during the Late Accretion
Authors: Lin Yanhao , van Westrenen Wim 
Published: March 2019

Abstract
The traditional view of a dry, volatile-poor Moon has been challenged by the identification of water and other volatiles in lunar samples, but the volatile budget delivery time(s), source(s) and temporal evolution remain poorly constrained. Here we show that hydrogen and chlorine isotopic ratios in lunar apatite changed significantly during the Late Accretion (LA, 4.1–3.8 billion years ago). During this period, deuterium/hydrogen ratios in the Moon changed from initial carbonaceous-chondrite-like values to values consistent with an influx of ordinary-chondrite-like material and pre-LA elevated δ37Cl values drop towards lower chondrite-like values. Inferred pre-LA lunar interior water contents are significantly lower than pristine values suggesting degassing, followed by an increase during the LA. These trends are consistent with dynamic models of solar-system evolution, suggesting that the Moon's (and Earth's) initial volatiles were replenished ∼0.5 Ga after their formation, with their final budgets reflecting a mixture of sources and delivery times.
Exoscope-Guided (VITOM 3D) Single-Stage Removal of Supratentorial Cavernous Angioma and Hemangioblastoma: 3-Dimensional Operative Video
Authors: Angileri Filippo Flavio , Esposito Felice , Scibilia Antonino , Priola Stefano Maria , Raffa Giovanni , Germanò Antonino 
Published: March 2019

Abstract
This video shows an exoscope-guided single-stage resection with 3-dimensional technology of a supratentorial cavernoma and a supratentorial hemangioblastoma during the same surgical procedure. The patient is a 42-yr-old man with a history of generalized tonico-clonic seizures. Contrast-enhanced magnetic resonance (MR) revealed the presence of a left frontal cavernoma and a left T1 non-enhancing hypointese temporal lesion (hemangioblastoma). The operation was carried out in the lateral position with the sole use of a 3D-exoscope (VITOM-3D, Karl Storz GmbH&Co, Tuttlingen, Germany). The operating room set-up included the surgeons standing at the head of the patients with the operating and navigator screens in the front of them and the exoscope arm entering from the left side.
As recently highlighted, the 3D-exoscope carries several advantages: (1) it allows neurosurgeons to operate in a confortable and stable position; (2) it is less space-occupying in comparison to the microscope; (3) the optics and 3D-screen offer an optimal stereoscopic view in comparison to the 2D-exoscope, important for both surgical and training purposes; (4) although sharing with the endoscope, the image quality and confortable surgeon's position, there is no conflict between the surgical instruments and the scope in the surgical field.
The adopted strategy enabled a complete resection of both lesions. The postoperative course was uneventful and the patient was seizure-free; the antiepileptic drugs were discontinued 3 mo after surgery.
The 3D-exoscope represents a promising surgical tool, which may become part of the neurosurgical armamentarium. Nevertheless, the conceivable capability to improve neurosurgical results will have to be explored.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The patient has consented to the submission of the surgical video for submission to the journal.
Diversity and evolution of the parotoid macrogland in true toads (Anura: Bufonidae)
Authors: O´donohoe M E Ailin , Luna María Celeste , Regueira Eleonora , Brunetti Andres E , Basso Nestor G , Lynch John D , Pereyra Martín O , Hermida Gladys N 
Published: March 2019

AbstractSkin glands in amphibians are either distributed throughout the skin or aggregated in multiglandular structures such as the parotoids typical of most species of Bufonidae. Although many early divergent and derived bufonids lack a discrete parotoid in the postorbital–supratympanic (PoSt) region, they have a great macroscopic diversity in the skin morphology of this region. To understand the origin and evolution of this diversity, in particular of the parotoids, we describe the histomorphology of the skin of the PoSt and dorsal regions in 17 species of bufonids, with or without external evident parotoid, and compare it with previously published descriptions. The survey results in 27 characters that were optimized on a phylogenetic hypothesis of Bufonidae. Our results reveal that the PoSt region has a noteworthy morphological diversity of types of glands, spatial organization and differences in the secretion products. Some morphological characters represent putative synapomorphies of internal clades of Bufonidae and are related to the progressive differentiation towards defined structures (macroglands, parotoids). These morphological results, along with published information on the toxicity of the skin secretions and defensive behaviours in some representative species, allow us to infer possible relationships between these features.
An Analytic Platform for the Rapid and Reproducible Annotation of Ventilator Waveform Data
Authors: Rehm Gregory B. , Kuhn Brooks T. , Lieng Monica K. , Cortes-Puch Irene , Nguyen Jimmy , Guo Edward C. , Delplanque Jean-Pierre , Anderson Nicholas R. , Adams Jason Y. 
Published: March 2019

AbstractAlgorithmic classifiers are crucial components of clinical decision support (CDS) systems needed to advance healthcare delivery. Robust CDS systems must be derived and validated via creation of multi-reviewer adjudicated gold standard datasets. Manual annotation of physiologic data such as mechanical ventilator waveform data (VWD) can be time-consuming, and lacks methodological consistency in dataset development. To address these issues, we have created a system for annotating and adjudicating VWD called the Annotation PipeLine (APL) to optimize VWD annotation by expert reviewers. APL combines visual assessment of waveform characteristics with metadata display, enabling inclusion of quantitative thresholds into annotation decisions by reviewers. APL also includes specific features for resolving multi-reviewer disagreements and generating gold standard data sets. APL’s unique combination of methods and open source framework may accelerate the creation of CDS algorithms for ventilator management, and may serve as a model for future research into physiologic waveform annotation systems.