bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple Laboratory Test Utilization Interventions to Reduce Inappropriate Specialty Coagulation Testing
Authors: Huang Huiya , Cunningham Ashley M , Harrington Alexandra M 
Published: August 2019

AbstractObjectivesThe naming convention in coagulation may cause confusion in electronic ordering systems, leading to inappropriate test orders. We implemented test utilization efforts and studied utilization before and after interventions for two specialty coagulation assays.MethodsTwo interventions were implemented: test names were changed from factor assay to activity, and residents reviewed all factor V and X requests. A retrospective review of factor V and X activity orders was performed for the period 1 year before and after interventions.ResultsAfter interventions, factor V and X activity orders decreased by approximately 40%. Resulted tests decreased by 53.8% and 47.8%, corresponding to reductions of $2,493.05 and $1,867.80 per year in laboratory charges for factor V and factor X activity, respectively. Abnormal factor V activity results increased from 45% to 59%. Factor V activity orders from outpatient clinics decreased by 21.6%.ConclusionsSimple interventions can reduce inappropriate specialty coagulation test orders and unnecessary costs.
Hybrid modelling of biological systems using fuzzy continuous Petri nets
Authors: Liu Fei , Sun Wujie , Heiner Monika , Gilbert David 
Published: August 2019

Abstract
Integrated modelling of biological systems is challenged by composing components with sufficient kinetic data and components with insufficient kinetic data or components built only using experts’ experience and knowledge. Fuzzy continuous Petri nets (FCPNs) combine continuous Petri nets with fuzzy inference systems, and thus offer an hybrid uncertain/certain approach to integrated modelling of such biological systems with uncertainties. In this paper, we give a formal definition and a corresponding simulation algorithm of FCPNs, and briefly introduce the FCPN tool that we have developed for implementing FCPNs. We then present a methodology and workflow utilizing FCPNs to achieve hybrid (uncertain/certain) modelling of biological systems illustrated with a case study of the Mercaptopurine metabolic pathway. We hope this research will promote the wider application of FCPNs and address the uncertain/certain integrated modelling challenge in the systems biology area.
pWGBSSimla: a profile-based whole-genome bisulfite sequencing data simulator incorporating methylation QTLs, allele-specific methylations and differentially methylated regions
Authors: Chung Ren-Hua , Kang Chen-Yu 
Published: August 2019

AbstractMotivationDNA methylation plays an important role in regulating gene expression. DNA methylation is commonly analyzed using bisulfite sequencing (BS-seq)-based designs, such as whole-genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS) and oxidative bisulfite sequencing (oxBS-seq). Furthermore, there has been growing interest in investigating the roles that genetic variants play in changing the methylation levels (i.e. methylation quantitative trait loci or meQTLs), how methylation regulates the imprinting of gene expression (i.e. allele-specific methylation or ASM) and the differentially methylated regions (DMRs) among different cell types. However, none of the current simulation tools can generate different BS-seq data types (e.g. WGBS, RRBS and oxBS-seq) while modeling meQTLs, ASM and DMRs.ResultsWe developed profile-based whole-genome bisulfite sequencing data simulator (pWGBSSimla), a profile-based bisulfite sequencing data simulator, which simulates WGBS, RRBS and oxBS-seq data for different cell types based on real data. meQTLs and ASM are modeled based on the block structures of the methylation status at CpGs, whereas the simulation of DMRs is based on observations of methylation rates in real data. We demonstrated that pWGBSSimla adequately simulates data and allows performance comparisons among different methylation analysis methods.Availability and implementationpWGBSSimla is available at https://omicssimla.sourceforge.io.Supplementary informationSupplementary data are available at Bioinformatics online.
Latitudinal and altitudinal variation in ecologically important traits in a widespread butterfly
Authors: Günter Franziska , Beaulieu Michaël , Brunetti Massimo , Lange Lena , Schmitz Ornés Angela , Fischer Klaus 
Published: August 2019

AbstractUnderstanding how organisms adapt to complex environments lies at the very heart of evolutionary biology and ecology, and is of particular concern in the current era of anthropogenic global change. Variation in ecologically important traits associated with environmental gradients is considered to be strong evidence for adaptive responses. Here, we study phenotypic variation along a latitudinal and an altitudinal cline in 968 field-collected males of the widespread European butterfly Pieris napi. In contrast to our expectations, body size decreased with increasing latitude and altitude, suggesting that warmer rather than cooler conditions may be more beneficial for individual development in this species. Higher altitudes but not latitudes seemed to be associated with increased flight performance, suggesting stronger challenges for flight activity in high-altitude environments (e.g. due to strong wind). Moreover, wing melanization increased while yellow reflectance decreased towards colder environments in both clines. Thus, increased melanization under thermally challenging conditions seems to compromise investment into a sexually selected trait, resulting in a trade-off. Our study, although exclusively based on field-collected males, revealed indications of adaptive patterns along geographical clines. It documents the usefulness of field-collected specimens, and the strength of comparing latitudinal and altitudinal clines to identify traits being potentially under thermal selection.
Improving the Integration of Restoration and Conservation in Marine and Coastal Ecosystems: Lessons from the Deepwater Horizon Disaster
Authors: Wallace Richard L , Gilbert Sherryl , Reynolds John E 
Published: August 2019

Abstract
In the wake of the Deepwater Horizon disaster, much has been learned about the biological, ecological, physical, and chemical conditions of the Gulf of Mexico. In parallel, the research community has also gained insight about the social and organizational structures and processes necessary for oil spill response and subsequent marine and coastal restoration. However, even with these lessons from both the Deepwater Horizon and previous spills, including 1989’s Exxon Valdez and the Ixtoc 1 in 1979, our understanding of how to avoid future crises has not advanced at the same pace as offshore oil and gas development. We argue that this progress deficit indicates a continued devaluing of marine and coastal resources. We believe that we must, instead, advance a proactive conservation ethic based on the precautionary principle and an appropriately placed burden of proof—strategies that will help reduce our reliance on costly restoration and protect marine and coastal ecosystems.
Prenatal Exposure to Ethanol Alters Synaptic Activity in Layer V/VI Pyramidal Neurons of the Somatosensory Cortex
Authors: Delatour Laurie C , Yeh Pamela W L , Yeh Hermes H 
Published: August 2019

AbstractFetal alcohol spectrum disorder (FASD) encompasses a range of cognitive and behavioral deficits, with aberrances in the function of cerebral cortical pyramidal neurons implicated in its pathology. However, the mechanisms underlying these aberrances, including whether they persist well beyond ethanol exposure in utero, remain to be explored. We addressed these issues by employing a mouse model of FASD in which pregnant mice were exposed to binge-type ethanol from embryonic day 13.5 through 16.5. In both male and female offspring (postnatal day 28–32), whole-cell patch clamp recording of layer V/VI somatosensory cortex pyramidal neurons revealed increases in the frequency of excitatory and inhibitory postsynaptic currents. Furthermore, expressing channelrhodopsin in either GABAergic interneurons (Nkx2.1Cre-Ai32) or glutamatergic pyramidal neurons (Emx1IRES Cre-Ai32) revealed a shift in optically evoked paired-pulse ratio. These findings are consistent with an excitatory-inhibitory imbalance with prenatal ethanol exposure due to diminished inhibitory but enhanced excitatory synaptic strength. Prenatal ethanol exposure also altered the density and morphology of spines along the apical dendrites of pyramidal neurons. Thus, while both presynaptic and postsynaptic mechanisms are affected following prenatal exposure to ethanol, there is a prominent presynaptic component that contributes to altered inhibitory and excitatory synaptic transmission in the somatosensory cortex.
Genomic Characterization of Recent and Historic Meningococcal Serogroup E Invasive Disease in Australia: A Case Series
Authors: Thangarajah Dharshi , Guglielmino Christine J D , Lambert Stephen B , Khandaker Gulam , Vasant Bhakti R , Malo Jonathan A , Smith Helen V , Jennison Amy V 
Published: August 2019

AbstractWe report the recent emergence of invasive meningococcal disease due to serogroup E in Queensland, Australia, in previously healthy patients. Molecular typing revealed the genotype of these strains to be E:P1.21-7,16:F5-36:ST-1157 (cc1157); when analyzed phylogenetically, compared with international cc1157 strains, they were relatively unrelated to each other.
Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9
Authors: Jang Hyun-Duk , Lee Sang Eun , Yang Jimin , Lee Hyun-Chae , Shin Dasom , Lee Hwan , Lee Jaewon , Jin Sooryeonhwa , Kim Soungchan , Lee Seung Ji , You Jihye , Park Hyun-Woo , Nam Ky-Youb , Lee Sang-Hak , Park Sahng Wook , Kim Jin-Soo , Kim Sang-Yeob , Kwon Yoo-Wook , Kwak Soo Heon , Yang Han-Mo , Kim Hyo-Soo 
Published: August 2019

Abstract

Aims
Proprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9. Herein, we investigated the role of CAP1 in PCSK9-mediated lysosomal degradation of LDLR and plasma LDL cholesterol (LDL-C) levels.

Methods and results
The direct binding between PCSK9 and CAP1 was confirmed by immunoprecipitation assay, far-western blot, biomolecular fluorescence complementation, and surface plasmon resonance assay. Fine mapping revealed that the CRD of PCSK9 binds with the Src homology 3 binding domain (SH3BD) of CAP1. Two loss-of-function polymorphisms found in human PCSK9 (S668R and G670E in CRD) were attributed to a defective interaction with CAP1. siRNA against CAP1 reduced the PCSK9-mediated degradation of LDLR in vitro. We generated CAP1 knock-out mice and found that the viable heterozygous CAP1 knock-out mice had higher protein levels of LDLR and lower LDL-C levels in the liver and plasma, respectively, than the control mice. Mechanistic analysis revealed that PCSK9-induced endocytosis and lysosomal degradation of LDLR were mediated by caveolin but not by clathrin, and they were dependent on binding between CAP1 and caveolin-1.

Conclusion
We identified CAP1 as a new binding partner of PCSK9 and a key mediator of caveolae-dependent endocytosis and lysosomal degradation of LDLR.
Validation of self-reported help-seeking, and measurement of the patient interval, for cancer symptoms: an observational study to inform methodological challenges in symptomatic presentation research
Authors: Smith Sarah M , Whitaker Katriina L , Cardy Amanda H , Elliott Alison M , Hannaford Philip C , Murchie Peter 
Published: August 2019

Abstract

Background
To improve earlier presentation with potential symptoms of cancer, accurate data are needed on how people respond to these symptoms. It is currently unclear how self-reported medical help-seeking for symptoms associated with cancer by people from the community correspond to what is recorded in their general practice records, or how well the patient interval (time from symptom onset to first presentation to a health-professional) can be estimated from patient records.

Method
Data from two studies that reviewed general practice electronic records of residents in Scotland, (i) the ‘Useful Study’: respondents to a general population survey who reported experiencing symptoms potentially associated with one of four common cancers (breast, colorectal, lung and upper gastro-intestinal) and (ii) the ‘Detect Cancer Early’ programme: cancer patients with one of the same four cancers. Survey respondents’ self-reported help-seeking (yes/no) was corroborated; Cohen’s Kappa assessed level of agreement. Combined data on the patient interval were evaluated using descriptive analysis.

Results
‘Useful Study’ respondents’ self-report of help-seeking showed exact correspondence with general practice electronic records in 72% of cases (n = 136, kappa 0.453, moderate agreement). Between both studies, 1269 patient records from 35 general practices were reviewed. The patient interval could not be determined in 44% (n = 809) of symptoms presented by these individuals.

Conclusions
Patient self-report of help-seeking for symptoms potentially associated with cancer offer a reasonably accurate method to research responses to these symptoms. Incomplete patient interval data suggest routine general practice records are unreliable for measuring this important part of the patient’s symptom journey.
Effects of module truncation on biochemical characteristics and products distribution of a new alginate lyase with two catalytic modules
Authors: Hu Fu , Li Qian , Zhu Benwei , Ni Fang , Sun Yun , Yao Zhong 
Published: August 2019

Abstract
In this work, we investigated the functions of structural modules within alginate lyase by truncating an endo-type alginate lyase into two successive catalytic modules. The effects of module deletion on biochemical characteristics and product distributions were further investigated. The N-terminal module (Aly7B-CDI) exhibited no activity toward alginate, polyM or polyG, but the C-terminal module (Aly7B-CDII) retained its activity. The full-length enzyme (Aly7B) and its truncated counterpart (Aly7B-CDII) had similar substrate specificities, but Aly7B-CDII had lower activity. Moreover, the activity of Aly7B was much higher than Aly7B-CDII at 30°C. Aly7B-CDII, however, possessed higher optimal pH and better pH stability than the full-length enzyme. The final degradation products for Aly7B were unsaturated di-, tri- and tetra-oligosaccharides, and those for Aly7B-CDII were unsaturated mono-, di-, tri-, tetra- and penta-oligosaccharides. Therefore, the potential impact of the noncatalytic module Aly7B-CDI on the catalytic module Aly7B-CDII was further elucidated by characterizing Aly7B and its truncations. These data contribute to the functional understanding of these differing modules.
The Causes and Effects of Leaks in International Negotiations
Authors: Castle Matthew , Pelc Krzysztof J 
Published: August 2019

AbstractInternational negotiations are founded on secrecy. Yet, unauthorized leaks of negotiating documents have grown common. What are the incentives behind leaks, and what are their effects on bargaining between states? Specifically, are leaks offensive or defensive: are they intended to spur parties to make more ambitious commitments, or are they more often intended to claw back commitments made? We examine these questions in the context of trade negotiations, the recurring form of which affords us rare empirical traction on an otherwise elusive issue. We assemble the first dataset of its kind, covering 120 discrete leaks from 2006 to 2015. We find that leaks are indeed rising in number. Leaks are clustered around novel legal provisions and appear to be disproportionately defensive: they serve those actors intent on limiting commitments made. The European Union (EU) appears responsible for the majority of leaks occurring worldwide. Using party manifesto data to track changing ideological positions within the EU, we find that the occurrence of leaks correlates with opposition to economic liberalization within the average EU political party. Moreover, leaks appear effective in shifting public debate. We examine trade officials’ internal communications and media coverage in the wake of a specific leak of negotiations between Canada and the EU. A given negotiating text attracts more negative coverage when it is leaked than when the same text is officially released. In sum, political actors leak information strategically to mobilize domestic audiences toward their preferred negotiating outcome.
Tubulin detyrosination promotes human trophoblast syncytium formation
Authors: Wang Rui , Yu Ruoxuan , Zhu Cheng , Lin Hai-Yan , Lu Xiaoyin , Wang Hongmei 
Published: August 2019

AbstractHuman trophoblast syncytialization is one of the most important yet least understood events during placental development. In this study, we found that detyrosinated α-tubulin (detyr-α-tub), which is negatively regulated by tubulin tyrosine ligase (TTL), was elevated during human placental cytotrophoblast fusion. Correspondingly, relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells, but fusing trophoblast cells exhibited much lower levels of TTL. Notably, fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL levels. Mechanistically, chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of detyr-α-tub. Restoration of detyr-α-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43 (Cx43), which in turn promoted successful fusion between trophoblast cells. Taken together, the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and syncytialization. Insufficient tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.
Microbiological and clinical characteristics of cryptococcemia: a retrospective analysis of 85 cases in a Chinese hospital
Authors: Fu Yiqi , Xu Min , Zhou Hua , Yao Yake , Zhou Jianying , Pan Zhijie 
Published: August 2019

Abstract
Cryptococcemia is a life-threatening fungal infection. Sometimes, it is hard to diagnose. The studies to describe the characteristics of cryptococcemia specifically were limited. We performed this retrospective analysis in a Chinese hospital during 2002–2015, including 85 cryptococcemia cases and 52 Cryptococcus spp. isolates. The species, mating type, antifungal susceptibility and multilocus sequence typing of Cryptococcus spp. were determined. C. neoformans var. grubii MATα of sequence type (ST) 5 is the representative strain of cryptococcemia, accounting for 51 isolates. The MIC50/90 values were 0.5/0.5, 1.0/1.0, 2.0/4.0, ≤0.06/0.25, and ≤0.06/≤0.06 μg/ml for amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole, respectively. Cryptococcemia was the first diagnostic proof of cryptococcosis in 37 patients (43.5%, 37/85). Compared with the patients initially diagnosed of cryptococcosis in other sites (mainly cerebrospinal fluid), the patients firstly diagnosed by blood culture had prolonged time from admission to diagnosis of cryptococcosis (9 days vs. 2 days, P &lt; .001) and higher 30-day mortality (54.1% vs. 20.8%, P = .003), while fewer symptoms of meningitis (45.9% vs. 100%, P &lt; .001). For the patients receiving lumbar puncture, the occurrence of meningitis was similar between the patients firstly diagnosed by blood culture and those firstly diagnosed in other sites (94.1% vs. 100%, P = .26). However, the patients first diagnosed by blood culture had lower baseline intracranial pressure (250 mm H2O vs. 342.5 mm H2O, P = .001). In conclusion, patients with cryptococcemia as the first diagnostic proof of cryptococcosis usually had neglected subtle symptoms of meningitis, which may result in delayed diagnosis and catastrophic outcome.
Broad-lined type Ic supernova iPTF16asu: A challenge to all popular models
Authors: Wang L J , Wang X F , Cano Z , Wang S Q , Liu L D , Dai Z G , Deng J S , Yu H , Li B , Song L M , Qiu Y L , Wei J Y 
Published: August 2019

ABSTRACT
It is well known that ordinary supernovae (SNe) are powered by 56Ni cascade decay. Broad-lined type Ic SNe (SNe Ic-BL) are a subclass of SNe that are not all exclusively powered by 56Ni decay. It was suggested that some SNe Ic-BL are powered by magnetar spin-down. iPTF16asu is a peculiar broad-lined type Ic supernova discovered by the intermediate Palomar Transient Factory. With a rest-frame rise time of only 4 d, iPTF16asu challenges the existing popular models, for example, the radioactive heating (56Ni-only) and the magnetar +56Ni models. Here we show that this rapid rise could be attributed to interaction between the SN ejecta and a pre-existing circumstellar medium ejected by the progenitor during its final stages of evolution, while the late-time light curve can be better explained by energy input from a rapidly spinning magnetar. This model is a natural extension to the previous magnetar model. The mass-loss rate of the progenitor and ejecta mass are consistent with a progenitor that experienced a common envelope evolution in a binary. An alternative model for the early rapid rise of the light curve is the cooling of a shock propagating into an extended envelope of the progenitor. It is difficult at this stage to tell which model (interaction+magnetar + 56Ni or cooling+magnetar + 56Ni) is better for iPTF16asu. However, it is worth noting that the inferred envelope mass in the cooling+magnetar + 56Ni is very high.
Cosmological filaments in the light of excursion set of saddle points
Authors: Fard Mohammad Ansari , Taamoli Sina , Baghram Shant 
Published: August 2019

ABSTRACT
The universe in large scales is structured as a network known as cosmic web. Filaments are one of the structural components of this web, which can be introduced as a novel probe to study the formation and evolution of structures and as a probe to study the cosmological models and to address the missing baryon problem. The aim of this work is to introduce an analytical framework to study the statistics of filaments such as number density of them and also to obtain the length-mass relation. For this objective, we model filaments as collapsed objects which have an extension in one direction, accordingly we use the ellipsoidal collapse to study the evolution of an over-dense region via gravitational instability. We find that the non-linear density of filaments in the epoch of formation is almost mass independent and is in order of ∼30. By introducing filament’s extended condition, we find a fitting function for length-mass relation. For the statistics of filaments, we propose a novel framework named excursion set of saddle points. In this approach, we count the saddle points of the density field Hessian matrix, and relate it to the count of filaments. In addition, we addressed the filament in filament problem with up-crossing approximation.