bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer
Authors: Leighl Natasha B. , Page Ray D. , Raymond Victoria M. , Daniel Davey B. , Divers Stephen G. , Reckamp Karen L. , Villalona-Calero Miguel A. , Dix Daniel , Odegaard Justin I. , Lanman Richard B. , Papadimitrakopoulou Vassiliki A. 
Published: April 2019

AbstractPurpose:Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non–small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC.Patients and Methods:Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360).Results:Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%; P &lt; 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets (EGFR, ALK, ROS1, BRAF) concordance was &gt;98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 EGFR-, ALK-, or BRAF-positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days; P &lt; 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; P &lt; 0.0001).Conclusions:In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.See related commentary by Meador and Oxnard, p. 4583
Engineering Multidimensional Evolutionary Forces to Combat Cancer
Authors: McCoach Caroline E. , Bivona Trever G. 
Published: April 2019

AbstractWith advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fitness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fitness relationships to improve outcomes of patients with cancer.Significance:Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance.
Incidence and Mortality of Parkinson’s Disease in Estonia
Authors: Kadastik-Eerme Liis , Taba Nele , Asser Toomas , Taba Pille 
Published: April 2019

<b><i>Background:</i></b> There is lack of data on the incidence of Parkinson’s disease (PD) based on repeat studies. Mortality rates of PD in Estonia have never been studied before. <b><i>Objectives:</i></b> To estimate the incidence and mortality rates of PD in ­Estonia, to compare current incidence rates with those of the prior epidemiological study in Estonia, and to examine the reported causes of death of the study population. <b><i>Methods:</i></b> Eligible subjects were identified from multiple case-finding sources. Subjects were subsequently tracked on the Electronic-Health Record until either the end of the study, or their death. Incidence rates and standardized mortality ratios (SMR) were calculated. Causes of death were identified, based on the data from death certificates. <b><i>Results:</i></b> In the current study, the overall age-adjusted incidence rate was 28.0/100,000 person-years (95% CI 25.2–30.8). Compared with the previous study, the age-adjusted incidence rate inEstonia has not significantly changed (rate ratio 1.11; <i>p </i>= 0.19). Overall SMR for the inception cohort of PD cases with a median follow-up time of 5 years was 1.12 (95% CI 0.88–1.36; <i>p</i> = 0.3). For those deceased subjects known to have had clinically diagnosed PD, this was mentioned on 46.8% of death certificates. <b><i>Conclusions:</i></b> Over the last 20 years, the overall incidence of PD in Estonia has remained comparatively stable. The data did not show an excess mortality in PD patients (vs. general population) in the first 5 years of the disease.
Circulating Markers of Inflammation Persist in Children and Adults With Giant Aneurysms After Kawasaki Disease
Authors: Lech Miroslaw , Guess Jamey , Duffner Jay , Oyamada Jun , Shimizu Chisato , Hoshino Shinsuke , Farutin Victor , Bulik Dorota A. , Gutierrez Bryan , Sarvaiya Hetal , Kapoor Bulbul , Koppes Laura , Saldova Radka , Stockmann Henning , Albrecht Simone , McManus Ciara , Rudd Pauline M. , Kaundinya Ganesh V. , Manning Anthony M. , Bosques Carlos J. , Kahn Andrew M. , Daniels Lori B. , Gordon John B. , Tremoulet Adriana H. , Capila Ishan , Gunay Nur Sibel , Ling Leona E. , Burns Jane C. 
Published: April 2019

Background:
The sequelae of Kawasaki disease (KD) vary widely with the greatest risk for future cardiovascular events among those who develop giant coronary artery aneurysms (CAA). We sought to define the molecular signature associated with different outcomes in pediatric and adult KD patients.

Methods:
Molecular profiling was conducted using mass spectrometry–based shotgun proteomics, transcriptomics, and glycomics methods on 8 pediatric KD patients at the acute, subacute, and convalescent time points. Shotgun proteomics was performed on 9 KD adults with giant CAA and matched healthy controls. Plasma calprotectin was measured by ELISA in 28 pediatric KD patients 1 year post-KD, 70 adult KD patients, and 86 healthy adult volunteers.

Results:
A characteristic molecular profile was seen in pediatric patients during the acute disease, which resolved at the subacute and convalescent periods in patients with no coronary artery sequelae but persisted in 2 patients who developed giant CAA. We, therefore, investigated persistence of inflammation in KD adults with giant CAA by shotgun proteomics that revealed a signature of active inflammation, immune regulation, and cell trafficking. Correlating results obtained using shotgun proteomics in the pediatric and adult KD cohorts identified elevated calprotectin levels in the plasma of patients with CAA. Investigation of expanded pediatric and adult KD cohorts revealed elevated levels of calprotectin in pediatric patients with giant CAA 1 year post-KD and in adult KD patients who developed giant CAA in childhood.

Conclusions:
Complex patterns of biomarkers of inflammation and cell trafficking can persist long after the acute phase of KD in patients with giant CAA. Elevated levels of plasma calprotectin months to decades after acute KD and infiltration of cells expressing S100A8 and A9 in vascular tissues suggest ongoing, subclinical inflammation. Calprotectin may serve as a biomarker to inform the management of KD patients following the acute illness.
Synchronous Bidirectional Neural Machine Translation
Authors: Zhou Long , Zhang Jiajun , Zong Chengqing 
Published: April 2019

AbstractExisting approaches to neural machine translation (NMT) generate the target language sequence token-by-token from left to right. However, this kind of unidirectional decoding framework cannot make full use of the target-side future contexts which can be produced in a right-to-left decoding direction, and thus suffers from the issue of unbalanced outputs. In this paper, we introduce a synchronous bidirectional–neural machine translation (SB-NMT) that predicts its outputs using left-to-right and right-to-left decoding simultaneously and interactively, in order to leverage both of the history and future information at the same time. Specifically, we first propose a new algorithm that enables synchronous bidirectional decoding in a single model. Then, we present an interactive decoding model in which left-to-right (right-to-left) generation does not only depend on its previously generated outputs, but also relies on future contexts predicted by right-to-left (left-to-right) decoding. We extensively evaluate the proposed SB-NMT model on large-scale NIST Chinese-English, WMT14 English-German, and WMT18 Russian-English translation tasks. Experimental results demonstrate that our model achieves significant improvements over the strong Transformer model by 3.92, 1.49, and 1.04 BLEU points, respectively, and obtains the state-of-the-art per- formance on Chinese-English and English- German translation tasks.1
Reply to ““Taxonomic certification versus the scientific method”: a rebuttal of Rogers (2012)” by Stribling et al., 2012
Authors: ROGERS D. CHRISTOPHER 
Published: April 2019

I am grateful to Stribling et al., (2012) for pointing out two errors I made in my original opinion piece (Rogers, 2012), namely citing Stribling et al., 2003 as Stribling et al., 2002, and stating that that same reference used the term “bench taxonomist” when in reality it was “production taxonomist”.
A new species of Pseudophryne (Anura: Myobatrachidae) from the central Australian ranges
Authors: DONNELLAN S. C. , MAHONY M. J. , BERTOZZI T. 
Published: April 2019

The myobatrachid frog genus Pseudophryne is highly variable in color pattern in eastern Australia where many species are distinguished by distinctive dorsal patterns. In contrast Pseudophryne from the western half of the continent are morphologically conservative. Two nominal species are widespread in south-western Australia and north-western South Australia, with one, P. occidentalis, being found in semi-arid and arid regions. Using mitochondrial DNA and morphological characters we establish that populations in the ranges of north-western South Australia assigned to P. occidentalis are a separate species. The new species comprises one of four major lineages of Pseudophryne while P. occidentalis falls within another lineage confined to south-western Australia.
The Influences of Urban Building Complexes on the Ambient Flows over the Washington–Reston Region
Authors: Zhang Da-Lin , Jin Menglin S. , Shou Yixuan , Dong Chunqing 
Published: April 2019

AbstractThis paper examines the collective impacts of urban building complexes on the planetary boundary layer (PBL) winds using both observations and a mesoscale model. Horizontal winds measured on the rooftops of federal buildings over the regions of Washington, D.C., and a small city nearby (i.e., Reston, Virginia) show the blocking effects of urban building complexes on the downstream winds during the daytime of 9 July 2007. A modeling study of the case using a coupled version of the Weather Research and Forecasting (WRF)–multilayer urban canopy model in which the observed building height and density information is implemented to advance the calculations of momentum and heat, reproduces the rooftop-observed wind patterns and the related urban heat island effects, especially the wake flows on the downstream sides of the above-mentioned two cities. Results show that under daytime conditions the building complexes can collectively form a mesoscale wake on the downwind side of each city, about 2–10 km away, horizontally from the edge of the building complexes. The wake flow may extend to much higher levels than the building tops, depending on the incoming flow strength, the static stability in the PBL, the height of the building complexes, and the time of the day because of the strength of surface insolation.
The Outflow–Rainband Relationship Induced by Environmental Flow around Tropical Cyclones
Authors: Dai Yi , Majumdar Sharanya J. , Nolan David S. 
Published: April 2019

Abstract
This study investigates the role of the asymmetric interaction between the tropical cyclone (TC) and the environmental flow in governing the TC inner-core asymmetric structure. Motivated by the limitations of bulk measures of vertical wind shear in representing the complete environmental flow, the TC outflow is used as a focus for the asymmetric interaction. By analyzing an idealized numerical simulation, it is demonstrated that parcels can go directly from the asymmetric rainband to the upper-level outflow. The relatively large vertical mass flux in the rainband region also suggests that the asymmetric rainband is an important source of the outflow. In a simulation that suppresses convection by reducing the water vapor within the rainband region, the upper-level outflow is weakened, further supporting the hypothesis that the rainband and outflow are directly connected. Finally, it is demonstrated that the asymmetric outflow and the outer rainband are coupled through the descending inflow below the outflow. Some of the main characteristics of the outflow–rainband relationship are also supported by a real-case numerical simulation of Hurricane Bill (2009). The relationship is potentially useful for understanding and predicting the evolution of the TC inner-core structure during the interaction with the large-scale environmental flow.
An Episodic Weakening in the Boreal Spring SST–Precipitation Relationship in the Western Tropical Pacific since the Late 1990s
Authors: Jo Hyun-Su , Yeh Sang-Wook , Cai Wenju 
Published: April 2019

Abstract
We found that a positive sea surface temperature (SST)–precipitation relationship in the western tropical Pacific (WTP) during boreal spring, in which higher SSTs are associated with higher precipitation, episodically weakens from the late 1990s to the early 2010s. During 1980–98, warm SSTs induce positive precipitation and low pressure in the WTP. The associated enhanced convection dampens the initial warm SSTs by reflecting incoming solar radiation. The reduced incoming solar radiation into the ocean leads to a SST cooling tendency. In contrast, the associated southwesterly wind anomalies reduce oceanic mixing by decreasing the mean wind, contributing to an SST warming tendency, though relatively small. Therefore, the cloud–radiation effect is a dominant process of the negative SST tendency. By contrast, during 1999–2014, although an SST cooling tendency is similarly induced by warm SST anomalies, the cooling tendency is enhanced by anomalous ocean advection, as a result of enhanced easterly wind anomalies in the southern part of the WTP. This results in a weakening of a positive relationship of the SST and precipitation during 1999–2014. As such, the associated anomalous convective heating in the WTP during 1999–2014 is weak, changing the atmospheric teleconnection patterns in the midlatitude and surface air temperature anomalies in western North America and northeastern Eurasia.
Getting Rid of Risky Foreigners: Promoting Community Protection at the Expense of Administrative Justice?
Authors: Billings Peter 
Published: April 2019

AbstractThis article offers a critical analysis of the norms, policy, procedures and outcomes associated with contemporary decision-making under the ‘character test’ per Migration Act 1958 (Cth) s 501. Of late there has been a steep increase in the number of visa refusals and cancellations on adverse character grounds due to the convergence of a reformulated character test and single-minded, authoritarian, administration by ministerial office-holders. This article teases out the significant and, arguably, adverse consequences for the quality of administrative justice of ministerial control over visa decisions absent independent administrative review. It is argued that the integrity of ministerial decision-making and the legitimacy of outcomes are dubious. This is because the process of identifying and balancing the important countervailing community interests and individual (human) rights, in the course of reaching the preferable decision, does not appear to be carried out in a detached, proper and genuine manner, pursuant to rational and intelligible reasoning processes. In conclusion, when viewed holistically, the judicial decisions analysed in this article suggest that the unwavering pursuit of community protection has come at a significant adverse cost to administrative justice and, necessarily, to individuals/families who bear the harsh consequences.
Effect of Water Precautions on Otorrhea Incidence after Pediatric Tympanostomy Tube: Randomized Controlled Trial Evidence
Authors: Subtil Joao , Jardim Ana , Araujo João , Moreira Carla , Eça Tiago , McMillan Merlin , Simoes Dias Sara , Vera Cruz Paulo , Voegels Richard , Paço Joao , Rosenfeld Richard 
Published: April 2019

ObjectivesTympanostomy with ventilation tube insertion is the most common otologic surgery. Many surgeons recommend water precautions, although its utility is questioned. We aimed to investigate if water precautions reduce the rate of otorrhea after transtympanic tube insertion.Study DesignMulticenter randomized controlled trial.Subjects and MethodsA total of 244 children aged 2 to 10 years undergoing their first set of Shepard tubes for otitis media with effusion and concomitant adenoidectomy were randomized to 2 groups: 1 with ear protection during water exposure (ear plugs and headbands, n = 130) and 1 without (n = 114). Bathing or swimming with unprotected ears was considered the exposure event and incidence of otorrhea, the primary outcome. Outcomes were assessed during the 6‐month follow‐up period.ResultsIn the water precaution group, 32% had at least 1 episode of otorrhea as compared with 22% in the unprotected group, which was not statistically significant (P =. 09). Only 37% of the episodes of otorrhea in the protected group and 36% in the unprotected group had a temporal relation to water exposure (no difference, P =. 81). Respectively, 56% and 52% of the episodes of otorrhea were in the context of upper respiratory tract infection. Global quality of life improved significantly, irrespective of whether water protection was prescribed.ConclusionThe incidence of otorrhea was not different with or without prescription of ear protection during water exposure among children with tympanostomy tubes, which supports current guideline recommendations that routine water precautions are unnecessary in this population.
The role of implied volatility in liquidity provision
Authors: Cahill Daniel , Fong Kingsley , Wee Marvin , Yang Joey Wenling 
Published: April 2019

This article examines the informational volatility – the permanent component of volatility that is driven by information – and its effect on stock liquidity provision. Using option-implied volatility as a proxy for informational volatility, our results show it has a significant negative influence on liquidity provision prior to earnings announcement even after controlling for trade-related market conditions. We find the effect of informational volatility only exists on the bid-side but not the ask-side of the order book. Further analysis suggests that the information contained in implied volatility concerns the future uncertainty of the underlying stock. JEL Classification: G12, G14, G30
Exploring health-care providers’ experiences in the care of clients on opioid agonist treatment in two western Canadian clinics
Authors: Maina Geoffrey , Tahir Hira , Docabo Angelica , Kahia Nyambura , Brunelle Caroline 
Published: April 2019

IntroductionPrescribing methadone as part of opioid agonist therapy is a common treatment approach to manage opioid use disorder. Unfortunately, many clients prematurely discontinue opioid agonist therapy because of restrictions attached to the therapy.PurposeThe purpose of this study was to explore health-care provider experiences as they worked with clients on opioid agonist therapy in a western Canadian city.MethodsIn this descriptive, qualitative study, we interviewed 18 health-care providers working in an opioid agonist therapy setting. The focus of the interviews was on the organization of opioid agonist therapy care at their clinic, their personal experiences and challenges faced when providing care to their clients. Interviews were recorded electronically and transcribed verbatim and thematic analysis was completed using NVIVO software.ResultsThe following three themes emerged from the data relate to the care organization and health care provider (HCP)-clients dynamics. These are: (1) fragmentation of care for a complex problem, (2) enforcing compliance to treatment, and (3) the importance of a therapeutic alliance to improve overall care.ConclusionThe opioid agonist therapy model is biocentric and emphasizes abstinence which can create tension between providers and clients. Making the model of care more patient centred might help to improve client retention rates and successful treatment outcomes.
Fathers’ Involvement in Their Wives’/Partners’ Breastfeeding: A Descriptive Correlational Study
Authors: Leng Regina Ng Wan , Shorey Shefaly , Yin Sharon Lee Kit , Chan Cynthia Pang Pui , He Hong-Gu 
Published: April 2019

Background: Fathers’ involvement has been identified as a significant predictor in maternal breastfeeding outcomes. Its benefits have been well-documented, but limited studies have examined its influencing factors. Research aim: To investigate factors influencing fathers’ involvement in their partners’ breastfeeding. Methods: A descriptive correlational design was used. Data were collected from 151 fathers from four obstetrics wards of a public hospital in Singapore from October 2016 to December 2016. Self-administered questionnaires were used to examine factors such as fathers’ knowledge and involvement in breastfeeding, attitudes towards breastfeeding, and perceived improvements of knowledge and attitudes for fathers’ involvement in breastfeeding on the discharge day of their partners’ and 2 weeks post-birth. Data were analyzed using IBMSPSS24.0. Results: Fathers’ involvement in their partners’ breastfeeding yielded a moderate to high mean score. The multiple linear regression analysis showed that five independent factors significantly influenced fathers’ involvement in their partners’ breastfeeding: (1) perceived approval of family members and friends in fathers’ breastfeeding involvement; (2) knowledge regarding breastfeeding and their involvement; (3) perceived behavioral control for fathers’ breastfeeding involvement; (4)marital relationship; and (5) perceived improvements of knowledge and attitudes 2 weeks post-birth. Conclusions: The study provided evidence on the significant factors that influenced fathers’ involvement in their partners’ breastfeeding, which can be used to guide healthcare professionals when providing appropriate support to facilitate fathers’ involvement. Future studies should continue to evaluate fathers’ involvement in breastfeeding longitudinally so that relevant support can be rendered.