bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory motion compensation for simultaneous PET/MR based on highly undersampled MR data
Authors: Rank Christopher M. , Heußer Thorsten , Wetscherek Andreas , Freitag Martin T. , Sedlaczek Oliver , Schlemmer Heinz–Peter , Kachelrieß Marc 
Published: November 2016

Purpose:Positron emission tomography (PET) of the thorax region is impaired by respiratory patient motion. To account for motion, the authors propose a new method for PET/magnetic resonance (MR) respiratory motion compensation (MoCo), which uses highly undersampled MR data with acquisition times as short as 1 min/bed.Methods:The proposed PET/MR MoCo method (4D jMoCo PET) uses radial MR data to estimate the respiratory patient motion employing MR joint motion estimation and image reconstruction with temporal median filtering. Resulting motion vector fields are incorporated into the system matrix of the PET reconstruction. The proposed approach is evaluated for the thorax region utilizing a PET/MR simulation with 1 min MR acquisition time and simultaneous PET/MR measurements of six patients with MR acquisition times of 1 and 5 min and radial undersampling factors of 11.2 and 2.2, respectively. Reconstruction results are compared to 3D PET, 4D gated PET and a standard MoCo method (4D sMoCo PET), which performs iterative image reconstruction and motion estimation sequentially. Quantitative analysis comprises the parameters SUVmean, SUVmax, full width at half‐maximum/lesion volume, contrast and signal‐to‐noise ratio.Results:For simulated PET data, our quantitative analysis shows that the proposed 4D jMoCo PET approach with temporal filtering achieves the best quantification accuracy of all tested reconstruction methods with a mean absolute deviation of 2.3% when compared to the ground truth. For measured PET patient data, the mean absolute deviation of 4D jMoCo PET using a 1 min MR acquisition for motion estimation is 2.1% relative to the 5 min MR acquisition. This demonstrates a robust behavior even in case of strong undersampling at MR acquisition times as short as 1 min. In contrast, 4D sMoCo PET shows considerable reduction of quantification accuracy for the 1 min MR acquisition time. Relative to 3D PET, the proposed 4D jMoCo PET approach with temporal filtering yields an average increase of SUVmean, SUVmax, and contrast of 29.9% and 13.8% for simulated and measured PET data, respectively.Conclusions:Employing artifact‐robust motion estimation enables PET/MR respiratory MoCo with MR acquisition times as short as 1 min/bed improving PET image quality and quantification accuracy.
Real‐time electromagnetic seed drop detection for permanent implants brachytherapy: Technology overview and performance assessment
Authors: Racine E. , Hautvast G. , Binnekamp D. , Beaulieu L. 
Published: November 2016

Purpose:To describe the principles and report on the performance of a novel real‐time electromagnetic (EM) seed drop detection technology for permanent implants brachytherapy procedures.Methods:A novel EM hollow needle prototype was recently developed by Philips. It possesses standard 3D tracking capability as well as a seed drop detection mechanism, both performed from a single custom built EM sensor. The detection mechanism is based on the magnetic permeability changes in the sensor as the seeds pass through. Drop position estimates are generated by the tracking information at the dropping instants. Three validation experiments were carried out in this study. First, the robustness of the detection mechanism was tested in free air with four different seed types. Detection waveforms were measured and commented. The accuracy of the seed drop position estimates was then evaluated using both 2D and 3D experiments. The procedures consisted of dropping seeds in phantoms, recording the drop position estimates, and finally registering the resulting spatial distributions on reference ones obtained by accurate modalities. Seeds were dropped on a specially designed plastic support adapted to brachytherapy template dimensions for 2D experiments, and true seed positions (reference distribution) were obtained by optical detection. In 3D experiments, seeds were dropped in edible gelatin and reference distributions were obtained by localizing the implants from CT scans of the phantoms.Results:All four seed types were correctly detected by the needle prototype. In total, 250 seeds were dropped on the plastic support, and 96 were dropped in gelatin phantoms. The detection rate was 100% in both cases. The minimum, maximum, and average drop position errors were, respectively, 0.1(+1.6/ − 0.1), 2.9(+1.4/ − 1.5), and 0.9(+1.4/ − 0.7) mm for 2D, and 0.1(+1.0/ − 0.1), 2.1(+1.1/ − 0.8), and 0.6(+1.2/ − 0.5) mm for 3D experiments.Conclusions:The hollow needle prototype combines both EM tracking and automatic seed drop detection in a compact and convenient form. The EM detection mechanism is robust, and the seed drop position estimates appear sufficiently accurate for potential integration of the technology to current brachytherapy treatment planning systems. In that context, it would serve as a valuable tool for rapid dosimetry validation in real‐time treatment delivery.
The Origin of Mucosal Immunity: Lessons from the Holobiont
Hydra
Authors: Schröder Katja , Bosch Thomas C. G. 
Published: November 2016

ABSTRACT

Historically, mucosal immunity—i.e., the portion of the immune system that protects an organism’s various mucous membranes from invasion by potentially pathogenic microbes—has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as
Hydra
species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont
Hydra
provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in
Hydra
polyps reared under defined short-term gnotobiotic conditions open up the potential of
Hydra
as an animal research model for the study of common mucosal disorders.
Murine Polyomavirus Cell Surface Receptors Activate Distinct Signaling Pathways Required for Infection
Authors: O’Hara Samantha D. , Garcea Robert L. 
Published: November 2016

ABSTRACT
Virus binding to the cell surface triggers an array of host responses, including activation of specific signaling pathways that facilitate steps in virus entry. Using mouse polyomavirus (MuPyV), we identified host signaling pathways activated upon virus binding to mouse embryonic fibroblasts (MEFs). Pathways activated by MuPyV included the phosphatidylinositol 3-kinase (PI3K), FAK/SRC, and mitogen-activated protein kinase (MAPK) pathways. Gangliosides and α4-integrin are required receptors for MuPyV infection. MuPyV binding to both gangliosides and the α4-integrin receptors was required for activation of the PI3K pathway; however, either receptor interaction alone was sufficient for activation of the MAPK pathway. Using small-molecule inhibitors, we confirmed that the PI3K and FAK/SRC pathways were required for MuPyV infection, while the MAPK pathway was dispensable. Mechanistically, the PI3K pathway was required for MuPyV endocytosis, while the FAK/SRC pathway enabled trafficking of MuPyV along microtubules. Thus, MuPyV interactions with specific cell surface receptors facilitate activation of signaling pathways required for virus entry and trafficking. Understanding how different viruses manipulate cell signaling pathways through interactions with host receptors could lead to the identification of new therapeutic targets for viral infection.

IMPORTANCE
Virus binding to cell surface receptors initiates outside-in signaling that leads to virus endocytosis and subsequent virus trafficking. How different viruses manipulate cell signaling through interactions with host receptors remains unclear, and elucidation of the specific receptors and signaling pathways required for virus infection may lead to new therapeutic targets. In this study, we determined that gangliosides and α4-integrin mediate mouse polyomavirus (MuPyV) activation of host signaling pathways. Of these pathways, the PI3K and FAK/SRC pathways were required for MuPyV infection. Both the PI3K and FAK/SRC pathways have been implicated in human diseases, such as heart disease and cancer, and inhibitors directed against these pathways are currently being investigated as therapies. It is possible that these pathways play a role in human PyV infections and could be targeted to inhibit PyV infection in immunosuppressed patients.
Influence of alcohol use on mortality and expenditure during hospital admission: a cross-sectional study
Authors: Peng Shu-Hui , Hsu Shiun-Yuan , Kuo Pao-Jen , Rau Cheng-Shyuan , Cheng Ya-Ai , Hsieh Ching-Hua 
Published: November 2016

ObjectivesThis study was designed to investigate the effect of alcohol intoxication on clinical presentation of hospitalised adult trauma patients at a Level I trauma centre using propensity score matching.DesignCross-sectional study.SettingTaiwan.ParticipantsDetailed data of 929 hospitalised adult trauma patients with alcohol intoxication, aged 20–65 years, and 10 104 corresponding patients without alcohol intoxication were retrieved from the Trauma Registry System between 1 January 2009 and 31 December 2014. Alcohol intoxication was defined as a blood alcohol concentration (BAC) ≥50 mg/dL.Main outcome measuresIn-hospital mortality and expenditure.ResultsPatients with alcohol intoxication presented with significantly higher short-term mortality (OR: 3.0, 95% CI 2.0 to 4.4; p<0.001) than patients without alcohol intoxication. However, on comparison with propensity score-matched patients with respect to sex, age, comorbidity, Glasgow Coma Scale (GCS), injury region based on Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS), alcohol intoxication did not significantly influence mortality (OR: 0.8, 95% CI 0.5 to 1.4; p=0.563). This implied that the higher mortality of alcohol-intoxicated patients was attributable to patient characteristics such as a higher injury severity rather than alcohol intoxication. Even on comparison with sex-matched, age-matched and comorbidity-matched patients without alcohol intoxication, patients with alcohol intoxication still had significantly higher total expenditure (17.4% higher), cost of operation (40.3% higher), cost of examination (52.8% higher) and cost of pharmaceuticals (38.3% higher).ConclusionsThe associated higher mortality of adult trauma patients with alcohol intoxication was completely attributable to other patient characteristics and associated injury severity rather than the effects of alcohol. However, patients with alcohol intoxication incurred significantly higher expenditure than patients without alcohol intoxication, even on comparison with sex-matched, age-matched and comorbidity-matched patients without alcohol intoxication.
Long-term use of secondary prevention medications for heart failure in Western Australia: a protocol for a population-based cohort study
Authors: Qin Xiwen , Teng Tiew-Hwa Katherine , Hung Joseph , Briffa Tom , Sanfilippo Frank M 
Published: November 2016

IntroductionHeart failure (HF) is a chronic, debilitating and progressive disease associated with high morbidity and mortality. Evidence-based medications (EBMs) are the cornerstone of management of patients with HF. In Australia, these EBMs are subsidised by the Commonwealth Government under the Pharmaceutical Benefits Scheme. Suboptimal dispensing and non-adherence to these EBMs have been observed in patients with HF. Our study will investigate trends in dispensing patterns, as well as adherence and persistence of EBMs for HF. We will also identify factors influencing these patterns and their impact on long-term clinical outcomes.Methods and analysisThis whole population-based cohort study will use longitudinal data for people aged 65–84 years who were hospitalised for HF in Western Australia between 2003 and 2008. Linked state-wide and national data will provide patient-level information on medication dispensing, medical visits, hospitalisations and death. Drug dispensing trends will be described, drug adherence and persistence estimated and the association with all-cause/cardiovascular death and hospitalisations reported.Ethics and disseminationThis project has received approvals from the Western Australian Department of Health Human Research Ethics Committee and the Western Australian Aboriginal Health Ethics Committee. Results will be published in relevant cardiology journals and presented at national and international conferences.
Vertical stiffness is not related to anterior cruciate ligament elongation in professional rugby union players
Authors: Serpell Benjamin G , Scarvell Jennie M , Pickering Mark R , Ball Nick B , Perriman Diana , Warmenhoven John , Smith Paul N 
Published: November 2016

BackgroundNovel research surrounding anterior cruciate ligament (ACL) injury is necessary because ACL injury rates have remained unchanged for several decades. An area of ACL risk mitigation which has not been well researched relates to vertical stiffness. The relationship between increased vertical stiffness and increased ground reaction force suggests that vertical stiffness may be related to ACL injury risk. However, given that increased dynamic knee joint stability has been shown to be associated with vertical stiffness, it is possible that modification of vertical stiffness could help to protect against injury. We aimed to determine whether vertical stiffness is related to measures known to load, or which represent loading of, the ACL.MethodsThis was a cross-sectional observational study of 11 professional Australian rugby players. Knee kinematics and ACL elongation were measured from a 4-dimensional model of a hopping task which simulated the change of direction manoeuvre typically observed when non-contact ACL injury occurs. The model was generated from a CT scan of the participant's knee registered frame by frame to fluoroscopy images of the hopping task. Vertical stiffness was calculated from force plate data.ResultsThere was no association found between vertical stiffness and anterior tibial translation (ATT) or ACL elongation (r=−0.05; p=0.89, and r=−0.07; p=0.83, respectively). ATT was related to ACL elongation (r=0.93; p=0.0001).ConclusionsVertical stiffness was not associated with ACL loading in this cohort of elite rugby players but a novel method for measuring ACL elongation in vivo was found to have good construct validity.
Neuromuscular responses differ between slip-induced falls and recoveries in older adults
Authors: Sawers Andrew , Pai Yi-Chung (Clive) , Bhatt Tanvi , Ting Lena H. 
Published: November 2016

How does the robust control of walking and balance break down during a fall? Here, as a first step in identifying the neuromuscular determinants of falls, we tested the hypothesis that falls and recoveries are characterized by differences in neuromuscular responses. Using muscle synergy analysis, conventional onset latencies, and peak activity, we identified differences in muscle coordination between older adults who fell and those who recovered from a laboratory-induced slip. We found that subjects who fell recruited fewer muscle synergies than those who recovered, suggesting a smaller motor repertoire. During slip trials, compared with subjects who recovered, subjects who fell had delayed knee flexor and extensor onset times in the leading/slip leg, as well as different muscle synergy structure involving those muscles. Therefore, the ability to coordinate muscle activity around the knee in a timely manner may be critical to avoiding falls from slips. Unique to subjects who fell during slip trials were greater bilateral (interlimb) muscle activation and the recruitment of a muscle synergy with excessive coactivation. These differences in muscle coordination between subjects who fell and those who recovered could not be explained by differences in gait-related variables at slip onset (i.e., initial motion state) or variations in slip difficulty, suggesting that differences in muscle coordination may reflect differences in neural control of movement rather than biomechanical constraints imposed by perturbation or initial walking mechanics. These results are the first step in determining the causation of falls from the perspective of muscle coordination. They suggest that there may be a neuromuscular basis for falls that could provide new insights into treatment and prevention. Further research comparing the muscle coordination and mechanics of falls and recoveries within subjects is necessary to establish the neuromuscular causation of falls. NEW & NOTEWORTHY A central question relevant to the prevention of falls is: How does the robust control of walking and balance break down during a fall? Previous work has focused on muscle coordination during successful balance recoveries or the kinematics and kinetics of falls. Here, for the first time, we identified differences in the spatial and temporal coordination of muscles among older adults who fell and those who recovered from an unexpected slip.
Molecular Signature to Risk-Stratify Prostate Cancer of Intermediate Risk
Authors: Yin Yu , Zhang Qingfu , Zhang Hong , He Yiping , Huang Jiaoti 
Published: November 2016

Abstract
A new 30-gene signature has been described that separates prostate cancers of Gleason score ≤6 from those of Gleason score ≥8. It provides independent prognostic information for prostate cancers of intermediate risk (Gleason score of 7), which has the potential to stratify these patients into different risk groups. Clin Cancer Res; 23(1); 6–8. ©2016 AACR.
See related article by Sinnott et al., p. 81
Successful Treatment of a Patient with Glioblastoma and a Germline POLE Mutation: Where Next?
Authors: Snyder Alexandra , Wolchok Jedd D. 
Published: November 2016

Abstract
Summary: Hypermutation and elevated neoantigen count in glioblastoma occurred in a patient harboring a germline POLE mutation and are associated with a clinical and antitumor immune response to PD-1 blockade. Cancer Discov; 6(11); 1210–11. ©2016 AACR.
See related article by Johanns et al., p. 1230.
Association Between Duration of Dual Antiplatelet Therapy and Angiographic Multivessel Disease on Outcomes in Patients Treated With Newer-Generation Drug-Eluting Stents
Authors: Lee Seung-Yul , Hong Myeong-Ki , Shin Dong-Ho , Kim Jung-Sun , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Kim Hyo-Soo , Valgimigli Marco , Colombo Antonio , Gilard Martine , Palmerini Tullio , Stone Gregg W. 
Published: November 2016

Background—
There is general agreement that the optimal duration of dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents should be individualized. We hypothesized that the extent of coronary artery disease may affect the clinical outcomes of DAPT.

Methods and Results—

We pooled patient-level data from 5 large, randomized trials comparing short-term DAPT with prolonged therapy. From the data, we identified 5476 patients who received newer-generation drug-eluting stents. Net adverse clinical event (NACE) was defined as a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding. At 1 year, NACE had occurred in 171 patients (3.1%). Independent predictors of NACE were older age (>65 years), sex, presence of diabetes mellitus, left ventricular dysfunction (ejection fraction <40%), and angiographic multivessel disease. Multivessel disease and DAPT duration were significantly associated with NACE (
P
for interaction=0.002); the association was driven by the greater occurrence of myocardial infarction in patients with multivessel disease. In patients with multivessel disease, 6-month DAPT (versus 12-month DAPT) was associated with a higher incidence of myocardial infarction (adjusted hazard ratio=2.748; 95% confidence interval=1.375–5.491;
P
=0.004), compared with patients with single-vessel disease (
P
for interaction=0.001).

Conclusions—
In patients treated with newer-generation drug-eluting stents, a significant interaction between DAPT strategy and multivessel disease was found regarding the occurrence of NACE at 1 year. Among adverse events, myocardial infarction was more frequent in 6-month DAPT than in 12-month DAPT in patients with multivessel disease.
Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke
Authors: von Kummer Rüdiger , Mori Etsuro , Truelsen Thomas , Jensen Jens-Kristian S. , Grønning Bjørn A. , Fiebach Jochen B. , Lovblad Karl-Olof , Pedraza Salvador , Romero Javier M. , Chabriat Hugues , Chang Ku-Chou , Dávalos Antoni , Ford Gary A. , Grotta James , Kaste Markku , Schwamm Lee H. , Shuaib Ashfaq , Albers Gregory W. 
Published: November 2016

Background and Purpose—
The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window.

Methods—
Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events.

Results—

In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64;
P
=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85;
P
=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08–2.35;
P
=0.019). Recanalization was associated with favorable outcomes (mRS 0–2) at day 90 in both the treatment arms.

Conclusions—
Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00856661.