bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLR network mediates immunity to diverse plant pathogens
Authors: Wu Chih-Hang , Abd-El-Haliem Ahmed , Bozkurt Tolga O. , Belhaj Khaoula , Terauchi Ryohei , Vossen Jack H. , Kamoun Sophien 
Published: July 2017

Significance
Plant and animal nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins often function in pairs to mediate innate immunity to pathogens. However, the degree to which NLR proteins form signaling networks beyond genetically linked pairs is poorly understood. In this study, we discovered that a large NLR immune signaling network with a complex genetic architecture confers immunity to oomycetes, bacteria, viruses, nematodes, and insects. The network emerged over 100 Mya from a linked NLR pair that diversified into up to one-half of the NLRs of asterid plants. We propose that this NLR network increases robustness of immune signaling to counteract rapidly evolving plant pathogens.
Haploid selection within a single ejaculate increases offspring fitness
Authors: Alavioon Ghazal , Hotzy Cosima , Nakhro Khriezhanuo , Rudolf Sandra , Scofield Douglas G. , Zajitschek Susanne , Maklakov Alexei A. , Immler Simone 
Published: July 2017

SignificanceDiploid organisms produce haploid gametes for sexual reproduction, resulting in a biphasic life cycle. Although selection during the diploid phase is well understood, selection during the haploid gametic stage and its consequences are largely ignored despite its potential importance for fundamental evolutionary processes, including the rate of adaptation and inbreeding depression, as well as for applied research into fertilization technology. A current dogma assumes that in animals selection on the haploid gametic genotype is minimal. We examined the importance of haploid selection in the zebrafish and found strong fitness consequences of selection on sperm phenotype in the resulting offspring. Genomic data support the idea that these effects may well be the consequence of selection on the haploid sperm genotype.
proFIA: a data preprocessing workflow for flow injection analysis coupled to high-resolution mass spectrometry
Authors: Delabrière Alexis , Hohenester Ulli M , Colsch Benoit , Junot Christophe , Fenaille François , Thévenot Etienne A 
Published: July 2017

Abstract

Motivation
Flow Injection Analysis coupled to High-Resolution Mass Spectrometry (FIA-HRMS) is a promising approach for high-throughput metabolomics. FIA-HRMS data, however, cannot be preprocessed with current software tools which rely on liquid chromatography separation, or handle low resolution data only.

Results
We thus developed the proFIA package, which implements a suite of innovative algorithms to preprocess FIA-HRMS raw files, and generates the table of peak intensities. The workflow consists of 3 steps: (i) noise estimation, peak detection and quantification, (ii) peak grouping across samples and (iii) missing value imputation. In addition, we have implemented a new indicator to quantify the potential alteration of the feature peak shape due to matrix effect. The preprocessing is fast (less than 15 s per file), and the value of the main parameters (ppm and dmz) can be easily inferred from the mass resolution of the instrument. Application to two metabolomics datasets (including spiked serum samples) showed high precision (96%) and recall (98%) compared with manual integration. These results demonstrate that proFIA achieves very efficient and robust detection and quantification of FIA-HRMS data, and opens new opportunities for high-throughput phenotyping.

Availability and implementation
The proFIA software (as well as the plasFIA dataset) is available as an R package on the Bioconductor repository (http://bioconductor.org/packages/proFIA), and as a Galaxy module on the Main Toolshed (https://toolshed.g2.bx.psu.edu), and on the Workflow4Metabolomics online infrastructure (http://workflow4metabolomics.org).

Supplementary information
Supplementary data are available at Bioinformatics online.
Relationship of American Spinal Injury Association Impairment Scale Grade to Post-injury Hospitalization and Costs in Thoracic Spinal Cord Injury
Authors: Dukes Ellen M , Kirshblum Steven , Aimetti Alex A , Qin Sarah S , Bornheimer Rebecca K , Oster Gerry 
Published: July 2017

Abstract

BACKGROUND
The lifetime economic burden of thoracic spinal cord injury (SCI) is known to be high, but evidence of variability of costs in relation to the American Spinal Injury Association Impairment Scale (AIS) grade is limited.

OBJECTIVE
To estimate lifetime economic costs of hospitalization by AIS grade in thoracic SCI.

METHODS
Using SCI Model Systems data from January 2000 to March 2016 from the National Spinal Cord Injury Statistical Center, we estimated mean total annual days of all-cause hospitalization by AIS grade among persons with thoracic SCI, based on assessments 1, 5, and 10 yr post-injury. We combined this information with secondary cost data and projections of life expectancy to estimate lifetime economic costs of hospitalization by AIS grade in persons aged 35 yr at time of thoracic SCI. Future costs were discounted to present value at 3% annually.

RESULTS
One year post-injury, mean total annual days of hospitalization ranged from 2.1 for persons with AIS-D injuries to 5.9 for those who were AIS-A. Similar differences were noted 5 and 10 yr post-SCI. The estimated net present value of expected lifetime costs of hospitalization following thoracic SCI at age 35 yr was $321 534, $249 514, $188 989, and $68 120 (2015 US$) for AIS-A, AIS-B, AIS-C, and AIS-D injuries, respectively.

CONCLUSION
Persons with less severe thoracic SCI, as reflected in AIS grade, spend fewer days in hospital over their lifetimes, leading to lower costs of inpatient care. Therapies improving AIS grade following thoracic SCI may provide cost savings in addition to addressing substantial unmet need.
Single-Fraction Radiosurgery Using Conservative Doses for Brain Metastases: Durable Responses in Select Primaries With Limited Toxicity
Authors: Cummings Michael , Youn Paul , Bergsma Derek P , Usuki Kenneth Y , Walter Kevin , Sharma Manju , Okunieff Paul , Schell Michael C , Milano Michael T 
Published: July 2017

Abstract

BACKGROUND
Optimal doses for single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases are not well established. Our institution utilized conservative dosing compared to maximum-tolerated doses from the Radiation Therapy Oncology Group 90-05 Phase I study.

OBJECTIVE
To report individual lesion control (LC) from conservative single-fraction doses and determine factors affecting LC.

METHODS
From 2003 to 2015, patients who underwent linear accelerator-based single-fraction SRS for cerebral/cerebellar metastases and receiving at least 1 follow-up magnetic resonance imaging (MRI) were identified. Lesion response was assessed by a size-based rating system and modified “Response Assessment in Neuro-Oncology Brain Metastases” (RANO-BM) criteria.

RESULTS
Among 188 patients with 519 lesions, median survival was 13.1 mo; median follow-up time with MRI was 9.6 mo per course. Median tumor-periphery dose was 15 Gy (range: 7.5-20.7). Median lesion volume was 0.5 cc and diameter was 9 mm (range: 2-45). Concordance between RANO-BM and size-based system was 93%. Crude 1-yr LC was 80%, 73%, 56%, and 38% for lesions 1 to 10, 11 to 20, 21 to 30, >31 mm, respectively. On multivariate analysis, increased size, melanoma and colorectal histology, and progression after whole brain radiation therapy predicted worse LC. When excluding lesions treated as a boost, dose was a significant predictor of LC in multivariate models (hazard ratio 0.89, P = .01). Symptomatic radiation necrosis occurred in 10 lesions in 10 patients.

CONCLUSION
Histology predicts LC after conservative SRS doses with evidence of a dose–response relationship. Conservative single-fraction SRS doses confer minimal toxicity and acceptable control in certain subgroups (breast cancer, <5 mm), with suboptimal control in larger lesions and in combination with whole brain radiation therapy.
Validity of Level of Supervision Scales for Assessing Pediatric Fellows on the Common Pediatric Subspecialty Entrustable Professional Activities
Authors: Mink Richard B. , Schwartz Alan , Herman Bruce E. , Turner David A. , Curran Megan L. , Myers Angela , Hsu Deborah C. , Kesselheim Jennifer C. , Carraccio Carol L. 
Published: July 2017

Purpose
Entrustable professional activities (EPAs) represent the routine and essential activities that physicians perform in practice. Although some level of supervision scales have been proposed, they have not been validated. In this study, the investigators created level of supervision scales for EPAs common to the pediatric subspecialties and then examined their validity in a study conducted by the Subspecialty Pediatrics Investigator Network (SPIN).

Method
SPIN Steering Committee members used a modified Delphi process to develop unique scales for six of the seven common EPAs. The investigators sought validity evidence in a multisubspecialty study in which pediatric fellowship program directors and Clinical Competency Committees used the scales to evaluate fellows in fall 2014 and spring 2015.

Results
Separate scales for the six EPAs, each with five levels of progressive entrustment, were created. In both fall and spring, more than 300 fellows in each year of training from over 200 programs were assessed. In both periods and for each EPA, there was a progressive increase in entrustment levels, with second-year fellows rated higher than first-year fellows (P < .001) and third-year fellows rated higher than second-year fellows (P < .001). For each EPA, spring ratings were higher (P < .001) than those in the fall. Interrater reliability was high (Janson and Olsson’s iota = 0.73).

Conclusions
The supervision scales developed for these six common pediatric subspecialty EPAs demonstrated strong validity evidence for use in EPA-based assessment of pediatric fellows. They may also inform the development of scales in other specialties.
Linguistic Context Versus Semantic Competition in Word Recognition by Younger and Older Adults With Cochlear Implants
Authors: Amichetti Nicole M. , Atagi Eriko , Kong Ying-Yee , Wingfield Arthur 
Published: July 2017

Objectives:
The increasing numbers of older adults now receiving cochlear implants raises the question of how the novel signal produced by cochlear implants may interact with cognitive aging in the recognition of words heard spoken within a linguistic context. The objective of this study was to pit the facilitative effects of a constraining linguistic context against a potential age-sensitive negative effect of response competition on effectiveness of word recognition.

Design:
Younger (n = 8; mean age = 22.5 years) and older (n = 8; mean age = 67.5 years) adult implant recipients heard 20 target words as the final words in sentences that manipulated the target word’s probability of occurrence within the sentence context. Data from published norms were also used to measure response entropy, calculated as the total number of different responses and the probability distribution of the responses suggested by the sentence context. Sentence-final words were presented to participants using a word-onset gating paradigm, in which a target word was presented with increasing amounts of its onset duration in 50 msec increments until the word was correctly identified.

Results:
Results showed that for both younger and older adult implant users, the amount of word-onset information needed for correct recognition of sentence-final words was inversely proportional to their likelihood of occurrence within the sentence context, with older adults gaining differential advantage from the contextual constraints offered by a sentence context. On the negative side, older adults’ word recognition was differentially hampered by high response entropy, with this effect being driven primarily by the number of competing responses that might also fit the sentence context.

Conclusions:
Consistent with previous research with normal-hearing younger and older adults, the present results showed older adult implant users’ recognition of spoken words to be highly sensitive to linguistic context. This sensitivity, however, also resulted in a greater degree of interference from other words that might also be activated by the context, with negative effects on ease of word recognition. These results are consistent with an age-related inhibition deficit extending to the domain of semantic constraints on word recognition.
Risks Versus Benefits of Anticoagulation for Atrial Fibrillation in Cirrhotic Patients
Authors: Choi Jonggi , Kim Junhwan , Shim Ju Hyun , Kim Minsu , Nam Gi-Byoung 
Published: July 2017

Background & Aims:
To evaluate the clinical benefits and risks of anticoagulation with warfarin in cirrhotic patients with atrial fibrillation (AF).

Methods:
A total of 465 cirrhotic patients diagnosed with nonvalvular AF were retrospectively analyzed. We compared incidences of ischemic stroke and major bleeding events between the 2 groups and examined the factors predicting ischemic stroke or major bleeding events.

Results:
Of 465 patients with AF, 113 (24.3%) received warfarin. Warfarin users had a lower mean Child–Pugh score (6.1 ± 1.5 vs. 7.6 ± 2.6) and a higher mean CHA2DS2VASc score (2.0 ± 2.5 vs. 1.7 ± 1.3) than nonusers (P's < 0.05). Overall, the incidence of ischemic stroke was low in cirrhotic patients with AF. It was not dependent on the CHA2DS2VASc score (hazard ratio, 1.40; 95% confidence interval, 0.96–2.05; P = 0.081), and was comparable in warfarin users (0.9%/person-year) and nonusers (1.2%/person-year). However, the incidence of major bleeding events was significantly higher in warfarin users (5.9% vs. 2.6%; P < 0.05). A multivariate analysis identified warfarin use (2.60; 95% confidence interval, 1.32–5.12) and Child–Pugh score (1.25; 1.04–1.49) as independently associated with bleeding events in these cirrhotic patients (P's < 0.05). There was no correlation between HAS-BLED score and risk of major bleeding (1.20; 0.95–1.52; P = 0.123).

Conclusions:
Anticoagulation with warfarin in cirrhotic patients with AF may not significantly reduce the risk of ischemic stroke, whereas it increases hemorrhagic complications.
Diagnostic Accuracy of Lymphoscintigraphy for Lymphedema and Analysis of False-Negative Tests
Authors: Hassanein Aladdin H. , Maclellan Reid A. , Grant Frederick D. , Greene Arin K. 
Published: July 2017

Background:
Lymphedema is the chronic enlargement of tissue due to inadequate lymphatic function. Diagnosis is made by history and physical examination and confirmed with lymphoscintigraphy. The purpose of this study was to assess the accuracy of lymphoscintigraphy for the diagnosis of lymphedema and to determine characteristics of patients with false-negative tests.

Methods:
Individuals referred to our lymphedema program with “lymphedema” between 2009 and 2016 were analyzed. Subjects were assessed by history, physical examination, and lymphoscintigraphy. Patient age at presentation, duration of lymphedema, location of disease, gender, previous infections, and lymphedema type were analyzed.

Results:
The study included 227 patients (454 limbs); lymphedema was diagnosed clinically in 169 subjects and confirmed by lymphoscintigraphy in 162 (117 primary, 45 secondary; 96% sensitivity). Fifty-eight patients were thought to have a condition other than lymphedema, and all had negative lymphoscintigrams (100% specificity). A subgroup analysis of the 7 individuals with lymphedema clinically, but normal lymphoscintigrams, showed that all had primary lymphedema; duration of disease and infection history were not different between true-positive and false-negative lymphoscintigram results (P = 0.5). Two patients with a false-negative test underwent repeat lymphoscintigraphy, which then showed lymphatic dysfunction consistent with lymphedema.

Conclusion:
Lymphoscintigraphy is very sensitive and specific for lymphedema. All patients with false-negative studies had primary lymphedema. A patient with a high clinical suspicion of lymphedema and a normal lymphoscintigram should be treated conservatively for the disease and undergo repeat lymphoscintigraphy.
EFFICACY AND SAFETY OF RANIBIZUMAB FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION DUE TO UNCOMMON CAUSE
Authors: Lai Timothy Y. Y. , Staurenghi Giovanni , Lanzetta Paolo , Holz Frank G. , Melissa Liew Shiao Hui , Desset-Brethes Sabine , Staines Harry , Hykin Philip G. ,   on behalf of the MINERVA study group
Published: July 2017

Purpose:To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with choroidal neovascularization because of an uncommon cause enrolled in the 12-month MINERVA study.Methods:In this Phase III, double-masked study, adult (≥18 years) patients (N = 178) were randomized 2:1 to receive either ranibizumab (n = 119) or sham (n = 59) at baseline and, if needed, at Month 1 and open-label individualized ranibizumab from Month 2. Best-corrected visual acuity change from baseline to Month 2 (primary endpoint) and Month 12, treatment exposure, and safety over 12 months were reported. Subgroup analysis was conducted on five predefined choroidal neovascularization etiologies (angioid streak, postinflammatory, central serous chorioretinopathy, idiopathic, and miscellaneous).Results:Ranibizumab showed superior efficacy versus sham from baseline to Month 2 (adjusted least-squares mean best-corrected visual acuity: +9.5 vs. −0.4 letters;P< 0.001). At Month 12, the mean best-corrected visual acuity change was +11.0 letters (ranibizumab) and +9.3 letters (sham). Across the 5 subgroups, the treatment effect ranged from +5.0 to +14.6 letters. The mean number of ranibizumab injections was 5.8 (ranibizumab arm) with no new ocular or nonocular adverse events.Conclusion:Ranibizumab 0.5 mg resulted in clinically significant treatment effect versus sham at Month 2. Overall, ranibizumab was effective in treating choroidal neovascularization of various etiologies with no new safety findings.
CHOROIDAL VASCULAR HYPERPERMEABILITY AS A PREDICTOR OF TREATMENT RESPONSE FOR POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Yanagi Yasuo , Ting Daniel S. W. , Ng Wei Yan , Lee Shu Yen , Mathur Ranjana , Chan Choi Mun , Yeo Ian , Wong Tien Yin , Cheung Gemmy Chui Ming 
Published: July 2017

Purpose:
To investigate the influence of choroidal vascular hyperpermeability (CVH) and choroidal thickness on treatment outcomes in eyes with polypoidal choroidal vasculopathy (PCV) undergoing anti–vascular endothelial growth factor monotherapy or combination therapy of photodynamic therapy and anti–vascular endothelial growth factor injections.

Methods:
The authors performed a prospective, observational cohort study involving 72 eyes of 72 patients with polypoidal choroidal vasculopathy (mean age 68.6 years, 51% men) treated with either monotherapy (n = 41) or combination therapy (n = 31). Each eye was imaged with color fundus photography, fluorescent angiography, indocyanine green angiography, and spectral domain optical coherence tomography. Indocyanine green angiography images were used to evaluate CVH, and spectral domain optical coherence tomography was used to measure central choroidal thickness. Changes in visual acuity over 12 months, and number of anti–vascular endothelial growth factor injections were investigated.

Results:
Choroidal vascular hyperpermeability was present in 31 eyes (43.1%). Visual acuity change over 12 months was numerically better in the CVH group compared with the CVH (−) group (−0.099 and −0.366 logarithm of the minimal angle of resolution unit in the CVH (−) and CVH (+) groups, respectively, multivariate P = 0.063) and significantly better in a matched pair analysis (P = 0.033). Furthermore, in the combination therapy group, the number of injection was significantly lower in the CVH (+) group compared with the CVH (−) group (4.68 vs. 2.58 injections/year in the CVH (−) and CVH (+) groups; P = 0.0044). There was no significant relationship between treatment response and choroidal thickening.

Conclusion:
The presence of CVH is associated with better visual outcome in eyes with polypoidal choroidal vasculopathy and lower injection number in combination therapy. Thus, CVH, but not choroidal thickness, should be further evaluated as a potential biomarker for selecting patients for combination therapy.
Recurrence Rate and Graft Stability With Fibrin Glue Compared With Suture and Autologous Blood Coagulum for Conjunctival Autograft Adherence in Pterygium Surgery: A Meta-Analysis
Authors: Maiti Rituparna , Mukherjee Somnath , Hota Debasish 
Published: July 2017

Purpose:
To minimize recurrence and improve graft stability after pterygium surgery, conjunctival autograft adherence is done using fibrin glue (FG) or autologous blood coagulum (ABC). But there are studies that have reported conflicting or inconclusive results. This meta-analysis was conducted to evaluate the postoperative recurrence rate and graft stability after using FG, sutures, and ABC.

Methods:
MEDLINE, Cochrane databases, and ICTRP were searched and PRISMA guidelines as well as recommended meta-analysis practices were followed. The odds ratio was calculated to estimate the effect size to assess the difference in recurrence and graft stability between the groups. Heterogeneity across the studies was explored using subgroup analyses and quality assessment using the Cochrane risk of bias tool and sensitivity analysis.

Results:
After screening, 30 studies were included for meta-analysis. The random model analysis for recurrence revealed an effect size of 0.44 [95% confidence interval (CI), 0.32–0.60], and subgroup analysis for studies comparing FG and sutures showed an effect size of 0.38 (95% CI, 0.27–0.53). In case of studies comparing FG and ABC, the random model analysis revealed an effect size of 1.01 (95% CI, 0.45–2.26). The random model analysis for graft stability revealed an effect size of 0.87 (95% CI, 0.57–1.31). In subgroup analysis, the random model revealed an effect size of 0.39 (95% CI, 0.17–0.88) indicating significant better graft stability with FG over ABC.

Conclusions:
This meta-analysis reveals the superiority of FG over sutures as the use of FG can significantly reduce the recurrence rate, but no significant difference in graft stability was found between FG and sutures. No significant difference was found in the recurrence rate between FG and ABC, but graft stability was found to be better with FG compared with ABC.
Total pancreatectomy for recurrent acute and chronic pancreatitis: a critical review of patient selection criteria
Authors: Faghih Mahya , Garcia Gonzalez Francisco , Makary Martin A. , Singh Vikesh K. 
Published: July 2017

Purpose of review
Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis.

Recent findings
The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy.

Summary
The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery.