bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developments of human adrenomedullin-IgG1 Fc fusion proteins
Authors: Nagata Sayaka , Yamasaki Motoo , Kawano Aya , Kitamura Kazuo 
Published: March 2019

Abstract
Human adrenomedullin (hAM) is a hypotensive peptide hormone that exerts powerful anti-inflammatory effects. However, treatment required continuous administration of hAM, as the half-life of native hAM is quite short in blood. To resolve this problem, we designed two kinds of human IgG1 Fc fusion proteins containing either full-length hAM (IgG1-AM) or hAM residues 6–52 [IgG1-AM (6–52)]. A DNA construct was constructed by connecting DNA sequences encoding hAM and the IgG1 Fc region with a DNA sequence encoding a (GGGGS)3 linker. The molecular weights of IgG1-AM and IgG1-AM (6–52) were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography. By protein sequencing, the N-terminal sequence of both recombinant AM-Fc fusions showed the expected human IgG1 sequence. Sufficient concentrations of both AM-Fc fusions were observed in blood 2 days after a single subcutaneous administration. IgG1-AM and IgG1-AM (6–52) stimulated cAMP production in human embryonic kidney-293 cells stably expressing the AM1 receptor. The activity of IgG1-AM (6–52) was higher than that of IgG1-AM. Treatment with IgG1-AM (6–52) inhibited blood pressure increase in spontaneously hypertensive rats. In addition, IgG1-AM (6–52) reduced total inflammation scores in the dextran sulfate sodium colitis model. Therefore, AM-IgG1 Fc fusions represent potential novel therapeutic agents.
First-Line Systemic Treatments for Stage IV Non-Small Cell Lung Cancer in California: Patterns of Care and Outcomes in a Real-World Setting
Authors: Maguire Frances B , Morris Cyllene R , Parikh-Patel Arti , Cress Rosemary D , Keegan Theresa H M , Li Chin-Shang , Lin Patrick S , Kizer Kenneth W 
Published: March 2019

Abstract

Background
Multiple systemic treatments have been developed for stage IV non-small cell lung cancer (NSCLC), but their use and effect on outcomes at the population level are unknown. This study describes the utilization of first-line systemic treatments among stage IV NSCLC patients in California and compares survival among treatment groups.

Methods
Data on 17 254 patients diagnosed with stage IV NSCLC from 2012 to 2014 were obtained from the California Cancer Registry. Systemic treatments were classified into six groups. The Kaplan-Meier method and multivariable Cox proportional hazards models were used to compare survival between treatment groups.

Results
Fifty-one percent of patients were known to have received systemic treatment. For patients with nonsquamous histology, pemetrexed regimens were the most common treatment (14.8%) followed by tyrosine kinase inhibitors (11.9%) and platinum doublets (11.5%). Few patients received pemetrexed/bevacizumab combinations (4.5%), bevacizumab combinations (3.6%), or single agents (1.7%). There was statistically significantly better overall survival for those on pemetrexed regimens (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.80 to 0.92), bevacizumab regimens (HR = 0.73, 95% CI = 0.65 to 0.81), pemetrexed/bevacizumab regimens (HR = 0.68, 95% CI = 0.61 to 0.76), or tyrosine kinase inhibitors (HR = 0.62, 95% CI = 0.57 to 0.67) compared with platinum doublets. The odds of receiving most systemic treatments decreased with decreasing socioeconomic status. For patients with squamous histology, platinum doublets were predominant (33.7%) and were not found to have statistically significantly different overall survival from single agents.

Conclusions
These population-level findings indicate low utilization of systemic treatments, survival differences between treatment groups, and evident treatment disparities by socioeconomic status.
Correlation between mass segregation and structural concentration in relaxed stellar clusters
Authors: de Vita Ruggero , Trenti Michele , MacLeod Morgan 
Published: March 2019

Abstract
The level of mass segregation in the core of globular clusters has been previously proposed as a potential indicator of the dynamical constituents of the system, such as presence of a significant population of stellar-mass black holes (BHs), or even a central intermediate-mass black hole (IMBH). However, its measurement is limited to clusters with high-quality Hubble Space Telescope data. Thanks to a set of state-of-the-art direct N-body simulations with up to 200k particles inclusive of stellar evolution, primordial binaries, and varying BH/neutron stars, we highlight for the first time the existence of a clear and tight linear relation between the degree of mass segregation and the cluster structural concentration index. The latter is defined as the ratio of the radii containing 5 per cent and 50 per cent of the integrated light (R5/R50), making it robustly measurable without the need to individually resolve low-mass stars. Our simulations indicate that given R5/R50, the mass segregation Δm (defined as the difference in main-sequence median mass between centre and half-light radius) is expressed as Δm/M⊙ = −1.166R5/R50 + 0.3246, with a root-mean-square error of 0.0148. In addition, we can explain its physical origin and the values of the fitted parameters through basic analytical modelling. Such correlation is remarkably robust against a variety of initial conditions (including presence of primordial binaries and IMBHs) and cluster ages, with a slight dependence in best-fitting parameters on the prescriptions used to measure the quantities involved. Therefore, this study highlights the potential to develop a new observational tool to gain insight on the dynamical status of globular clusters and on its dark remnants.
Abundant serendipitous emission line sources with JWST/NIRSpec
Authors: Maseda Michael V , Franx Marijn , Chevallard Jacopo , Curtis-Lake Emma 
Published: March 2019

Abstract
The James Webb Space Telescope will provide observational capabilities that far exceed those of current ground- or space-based instrumentation. In particular, the Near-Infrared Spectrograph (NIRSpec) instrument will take highly sensitive spectroscopic data for hundreds of objects simultaneously from 0.6 to 5.3 $\mu$m. Current photometric observations suggest a large and increasing number of faint (MUV &gt; −16) galaxies at high redshift, with increasing evidence that galaxies at these redshifts have optical emission lines with extremely high equivalent widths. A simple model of their emission line fluxes and number density evolution with redshift is used to predict the number of galaxies that NIRSpec will serendipitously observe during normal observations with the microshutter array. At exposure times of ≈20 h in the low-resolution prism mode, the model predicts that, on average, every open 1 × 3 ‘microslit’ will contain an un-targeted galaxy with a detectable [O iii] and/or H α emission line; while most of these detections are predicted to be of [O iii], H α detections alone would still number 0.56 per open ‘microslit’ for this exposure time. Many of these objects are spectroscopically detectable even when they are fainter than current photometric limits and/or their flux centroids lie outside of the open microshutter area. The predicted number counts for such galaxies match z ∼ 2 observations of [O iii] emitters from slitless grism spectroscopic surveys, as well as theoretical predictions based on sophisticated modelling of galaxy spectral energy distributions. These serendipitous detections could provide the largest numbers of z &gt; 6 spectroscopic confirmations in the deepest NIRSpec surveys.
Gene Expression Does Not Support the Developmental Hourglass Model in Three Animals with Spiralian Development
Authors: Wu Longjun , Ferger Kailey E , Lambert J David 
Published: March 2019

Abstract
It has been proposed that animals have a pattern of developmental evolution resembling an hourglass because the most conserved development stage—often called the phylotypic stage—is always in midembryonic development. Although the topic has been debated for decades, recent studies using molecular data such as RNA-seq gene expression data sets have largely supported the existence of periods of relative evolutionary conservation in middevelopment, consistent with the phylotypic stage and the hourglass concepts. However, so far this approach has only been applied to a limited number of taxa across the tree of life. Here, using established phylotranscriptomic approaches, we found a surprising reverse hourglass pattern in two molluscs and a polychaete annelid, representatives of the Spiralia, an understudied group that contains a large fraction of metazoan body plan diversity. These results suggest that spiralians have a divergent midembryonic stage, with more conserved early and late development, which is the inverse of the pattern seen in almost all other organisms where these phylotranscriptomic approaches have been reported. We discuss our findings in light of proposed reasons for the phylotypic stage and hourglass model in other systems.
River Valleys Shaped the Maternal Genetic Landscape of Han Chinese
Authors: Li Yu-Chun , Ye Wei-Jian , Jiang Chuan-Gui , Zeng Zhen , Tian Jiao-Yang , Yang Li-Qin , Liu Kai-Jun , Kong Qing-Peng 
Published: March 2019

AbstractA general south-north genetic divergence has been observed among Han Chinese in previous studies. However, these studies, especially those on mitochondrial DNA (mtDNA), are based either on partial mtDNA sequences or on limited samples. Given that Han Chinese comprise the world’s largest population and reside around the whole China, whether the north-south divergence can be observed after all regional populations are considered remains unknown. Moreover, factors involved in shaping the genetic landscape of Han Chinese need further investigation. In this study, we dissected the matrilineal landscape of Han Chinese by studying 4,004 mtDNA haplogroup-defining variants in 21,668 Han samples from virtually all provinces in China. Our results confirmed the genetic divergence between southern and northern Han populations. However, we found a significant genetic divergence among populations from the three main river systems, that is, the Yangtze, the Yellow, and the Zhujiang (Pearl) rivers, which largely attributed to the prevalent distribution of haplogroups D4, B4, and M7 in these river valleys. Further analyses based on 4,986 mitogenomes, including 218 newly generated sequences, indicated that this divergence was already established during the early Holocene and may have resulted from population expansion facilitated by ancient agricultures along these rivers. These results imply that the maternal gene pools of the contemporary Han populations have retained the genetic imprint of early Neolithic farmers from different river basins, or that river valleys represented relative migration barriers that facilitated genetic differentiation, thus highlighting the importance of the three ancient agricultures in shaping the genetic landscape of the Han Chinese.
Genome-Wide Analysis of Long Intergenic Noncoding RNAs Responding to Low-Nutrient Conditions in Arabidopsis thaliana: Possible Involvement of Trans-Acting siRNA3 in Response to Low Nitrogen
Authors: Fukuda Makiha , Nishida Sho , Kakei Yusuke , Shimada Yukihisa , Fujiwara Toru 
Published: March 2019

AbstractLong intergenic noncoding RNAs (lincRNAs) play critical roles in transcriptional and post-transcriptional regulation of gene expression in a wide variety of organisms. Thousands of lincRNAs have been identified in plant genomes, although their functions remain mostly uncharacterized. Here, we report a genome-wide survey of lincRNAs involved in the response to low-nutrient conditions in Arabidopsis thaliana. We used RNA sequencing data derived from A. thaliana roots exposed to low levels of 12 different nutrients. Using bioinformatics approaches, 60 differentially expressed lincRNAs were identified that were significantly upregulated or downregulated under deficiency of at least one nutrient. To clarify their roles in nutrient response, correlations of expression patterns between lincRNAs and reference genes were examined across the 13 conditions (12 low-nutrient conditions and control). This analysis allowed us to identify lincRNA-RNA pairs with highly positive or negative correlations. In addition, calculating interaction energies of those pairs showed lincRNAs that may act as regulatory interactors; e.g. small interfering RNAs (siRNAs). Among them, trans-acting siRNA3 (TAS3), which is known to promote lateral root development by producing siRNA against Auxin response factor 2, 3, and 4, was revealed as a nitrogen (N)-responsive lincRNA. Furthermore, nitrate transporter 2 was identified as a potential target of TAS3-derived siRNA, suggesting that TAS3 participates in multiple pathways by regulating N transport and root development under low-N conditions. This study provides the first resource for candidate lincRNAs involved in multiple nutrient responses in plants.
Influenza in carehome residents: applying a conceptual framework to describe barriers to the implementation of guidance on treatment and prophylaxis
Authors: Phipps Emily , Watson Conall , Mearkle Rachel , Lock Sarah 
Published: March 2019

AbstractBackgroundThe European Centre for Disease Prevention and Control, National Institute for Health and Care Excellence and Public Health England have all endorsed the use of antivirals for the treatment and prophylaxis of influenza for care home residents. However, implementing these guidelines in practice is often challenging. This article aims to explore what factors impact the management of care home flu outbreaks in England according to national guidelines and highlight opportunities for change.MethodsQualitative data from notified outbreaks between September 2017 to April 2018 in the South East of England were analyzed, applying the Greenhalgh framework for barriers to guideline implementation. Summary statistics on outbreak characteristics were generated. Stakeholders were mapped out using Eden and Ackermann’s grid of interest and influence. A process map was developed to describe operational pathways.ResultsThere was often a delay in notifying potential outbreaks to Public Health England. Clinicians cited a lack of robust evidence for the use of antivirals and the available guidelines being too unwieldy as reasons for not implementing prescribing guidance. Many high interests and high influence stakeholders are involved in the sometimes complex care pathway, requiring coordinated work and agreement before antivirals can be prescribed.ConclusionsOur findings highlight points in the care pathway that stakeholders can target to improve quality of care and increase the likelihood of national guidance being implemented. The principles described in this article can also be applied to other challenges of translating evidence into practice and cross-organisational working.
ESTIMATION OF THE ANISOTROPY EMISSION OF LPN/CIEMAT NEUTRON SOURCES: EFFECT OF HEAVY CAPSULE HOLDERS
Authors: Villafañe Roberto Mendez , de Sousa Lacerda Marco Aurélio , Blanco Xandra Campo , Sánchez Francisco González , Vega-Carrillo Héctor René 
Published: March 2019

Abstract
In order to estimate the anisotropy emission of 241Am-Be and 252Cf neutron sources from the Spanish Neutron Standards Laboratory (LPN/CIEMAT) detailed models of sources capsules and capsule holders were designed with the MCNPX code. Simulations of the sources inside the capsules without the capsule holders were done to validate the MC model by comparison with experimental results provided by other authors. After that, the capsule holders were incorporated to the simulation. In general, a good agreement has been found between measurements and our calculations. Results show the additional encapsulations have significant influence on anisotropy factors, energy spectra and dose rates.
Randomized Trial of an Innovative Electronic Screening and Brief Intervention for Reducing Drinking Among Women of Childbearing Age
Authors: Nayak Madhabika B. , Kaskutas Lee A. , Mericle Amy A. 
Published: March 2019

Objectives:
To evaluate the efficacy of an innovative, self-administered, electronic Screening and Brief Intervention (e-SBI) in English and Spanish, “DrinkWise,” for reducing drinking among nonpregnant women of childbearing age.

Methods:
A parallel design, phase 1 trial included 185 nonpregnant women reporting risky drinking (8 or more drinks in a week or 3 or more drinks in a day) who were recruited from 2 publicly funded Nutritional Assistance for Women, Infants and Children (WIC) program sites in the United States from 2016 to 2017. Participants were 18 to 44 years in age, 75% of Hispanic ethnicity, 44% Spanish speakers, 30% had not completed high school, and 15% were currently breastfeeding. Participants were randomized to receive (intervention condition, n = 99) or not receive (control condition, no intervention, n = 86) DrinkWise and followed at 3 and 6 months.

Results:
Women receiving DrinkWise had greater reductions in the odds of self-reported weekly alcohol use (odds ratio [OR] = 0.22, SE = 0.12, P < 0.01) and heavy alcohol use (OR = 0.23, SE = 0.14, P < 0.05) at 6-month follow-up than controls, with no group differences at 3-month follow-up. Compared with heavy drinking controls, heavy drinkers receiving DrinkWise showed a trend (P = 0.06) for greater reductions in drink (pour) size from 3- to 6-month follow-up.

Conclusions:

DrinkWise may be efficacious in reducing drinking among low-income women of childbearing age and provides a low-cost tool for increasing access to recommended SBI among childbearing-age women. Studies should continue to build DrinkWise's evidence base.

Trial registration: :
ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02337361
The Association of Preoperative Anemia and the Postoperative Course and Oncological Outcome in Patients Undergoing Rectal Cancer Surgery: A Multicenter Snapshot Study
Authors: Bruns Emma R.J. , Borstlap Wernard A. , van Duijvendijk Peter , van der Zaag-Loonen Hester J. , Buskens Christianne J. , van Munster Barbara C. , Bemelman Willem A. , Tanis Pieter J. 
Published: March 2019

BACKGROUND:
There is still controversy about the relationship between preoperative anemia and outcomes after rectal cancer surgery.

OBJECTIVE:
The aim of this study was to analyze the association between preoperative anemia and postoperative complications and the survival of patients undergoing surgery for rectal cancer in the era of laparoscopic surgery and modern perioperative care.

DESIGN:
This was a cohort study.

SETTINGS:
Data were gathered from 71 hospitals in The Netherlands.

PATIENTS:
Patients who underwent resection for rectal cancer in 2011, for whom preoperative hemoglobin level was registered, were included.

INTERVENTIONS(s):
There were no interventions.

MAIN OUTCOME MEASURES:
Short-term outcome parameters were any postoperative complication or mortality within 30 days postoperatively, and pelvic infectious complications defined as anastomotic leakage and presacral abscess. Long-term outcomes were chronic sinus diagnosed at any time during 3-year follow-up, 3-year local and distant recurrence rates, and 3-year overall survival.

RESULTS:
Of 2095 patients, 1857 had a registered preoperative hemoglobin level; 576 (31%) of these patients anemic and 1281 (69%) were nonanemic. Preoperative anemia was not independently associated with postoperative complications (HR, 1.1; 95% CI, 0.9–1.4; p = 0·24) or 30-day mortality (HR, 1.4, 95% CI, 0.7–2.8; p = 0·29). Preoperative anemia was associated with 3-year overall survival (HR, 2.1; 95% CI, 1.7–2.5; p < 0.0001), after multivariable analysis (HR, 1.4; 95% CI, 1.1–1.8; p = 0·008), and with local recurrence rate (HR, 1.6; 95% CI, 1.1–2.4; p = 0.026), but not with distant recurrence rate (HR, 1.2; 95% CI, 1.0–1.5; p = 0.054).

LIMITATIONS:
Preoperative anemia appeared to have only limited association with postoperative and disease-specific outcome after rectal cancer surgery in contrast to published meta-analysis of small historical series.

CONCLUSIONS:
Anemia is associated with overall survival. It might be considered as one of the warning signs in identifying high-risk patients. See Video Abstract at http://links.lww.com/DCR/A913.
Combined Ab Externo Cyclopexy and Cryopexy in Cyclodialysis Cleft Repair
Authors: Liu Xiongfei , Thung Elaine G. , Caprioli Joseph , Law Simon K. 
Published: March 2019

Purpose:
To evaluate outcomes of an ab externo surgical technique combining cyclopexy with partial-thickness scleral flap dissection and suture reattachment of ciliary muscle and cryopexy through partial-scleral bed for cyclodialysis cleft repair.

Materials and Methods:
Consecutive patients in a tertiary academic practice with cyclodialysis cleft confirmed by gonioscopy or ultrasound biomicroscopy and had received the combined procedure were reviewed. Primary outcomes included differences between the preoperative and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP). Secondary outcomes included complications and additional surgeries.

Results:
Six consecutive patients (eyes) from October 2006 to November 2012 (6 y) were enrolled. No patient had received prior laser or surgical treatment for cyclodialysis cleft. Patient’s age ranged from 14 to 81 years (median=37 y). Follow-up ranged from 1 to 72 months (median=12 mo). The cyclodialysis clefts of 3 patients (50%) were caused by blunt injuries and the other 3 (50%) from complicated intraocular surgery. Preoperative BCVA ranged from 20/40 to counting fingers with mean IOP of 2.3±2.1 mm Hg (range, 0 to 6 mm Hg). Final postoperative BCVA ranged from 20/20 to hand motions with mean IOP of 11.3±5.7 mm Hg (range, 3 to 18 mm Hg). Five patients (83%) had an increase in IOP and recovery of vision to 20/50 or better at the final visit (including further surgeries). No complication was noted and no additional cyclopexy was required.

Conclusions:
Combined ab externo cyclopexy with partial-thickness scleral flap dissection and suture reattachment of the ciliary muscle and cryopexy delivered on the partial-thickness scleral bed is safe and effective as primary surgical repair for cyclodialysis cleft.