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Παρασκευή, 15 Δεκεμβρίου 2017

Post-mortem computed tomography compared to medico-legal autopsy – pathologies in the torso and limbs

Publication date: Available online 15 December 2017
Source:Journal of Forensic Radiology and Imaging
Author(s): Adi Adelman, Margarita Vasserman, Gil Graziani, Chen Kugel, Karen Meir, Tali Bdolah-Abram, Alon Krispin
IntroductionPost-mortem computed tomography (PMCT) has become a routine part of post-mortem forensic evaluation in many institutes worldwide. Its added benefit to the traditional autopsy is indisputable, but its ability to detect different findings compared to those found in an autopsy has only been evaluated in a limited number of large scale studies.MethodsIn this retrospective study, we assessed the agreement between autopsy and PMCT, and their ability to detect pathological findings (by "Kappa" and "McNemar" scores, respectively), using all finding of both methods as reference standard. We included findings in the torso and the limbs extracted from autopsy and PMCT reports of 105 consecutive cases.ResultsThe level of agreement between autopsy and PMCT depends on the tissues, locations, and type of pathologies examined. Autopsy much better demonstrates bullet tracks (68/76 vs. 18/76, p<0.01) and stab wounds (22/25 vs. 11/25, p=0.013), while PMCT is more sensitive to shrapnel (86/121 vs. 37/121, p<0.001). PMCT better demonstrates fractures (259/344 vs. 222/344, p=0.012), especially in bones that are hard to access in autopsy, but is less sensitive to rib fractures (137/177 vs. 115/177, p=0.037). Parenchymal organ pathologies are not well demonstrated by PMCT (194/257 vs. 117/257, p=<0.001).ConclusionsShrapnel, foreign bodies, gas-related pathologies, pelvic fluid and fractures, excluding rib fractures, are detected more often by post-mortem CT. It is important to consider PMCT as a tool in the evaluation of specific tissues and organs, possibly providing solid answers, or at least directing the team in the performance of the autopsy.



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Low Tube Voltage and Iterative Model Reconstruction in Follow-up CT Angiography After Thoracic Endovascular Aortic Repair

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Publication date: Available online 14 December 2017
Source:Academic Radiology
Author(s): Ping Hou, Xiangnan Feng, Jie Liu, Xiaopeng Wang, Yaojun Jiang, Leigang Dong, Jianbo Gao
Rationale and ObjectivesThis study aimed to investigate the feasibility of reducing radiation exposure and contrast medium (CM) dose in follow-up computed tomography angiography (CTA) after thoracic endovascular aortic repair (TEVAR) using low tube voltage and knowledge-based iterative model reconstruction (IMR).Materials and MethodsThirty-six patients that required follow-up CTA after TEVAR were included in this intra-individual study. The conventional protocol with standard tube voltage of 120 kVp and CM volume of 70 mL was applied in the first follow-up CTA of all the patients (control group A). The ultra-low CM dose protocol with low tube voltage of 80 kVp and weight-adapted CM volume of 0.4 mL/kg was utilized in the second follow-up CTA (study group B). Set A.FBP (group A filtered back-projection) contained images for group A that were reconstructed through FBP method. Three sets (B.FBP, B.HIR, and B.IMR) for group B were reconstructed using three methods, FBP, hybrid iterative reconstruction (HIR), and IMR, respectively. Objective measurements including aortic attenuations, image noise, contrast-to-noise ratios (CNRs), and figure of merit of CNR (FOMCNR), and subjective rating scores of the four image sets were compared.ResultsCompared to the images in set A.FBP, the images in set B.IMR had better quality in terms of equivalent attenuation values, equivalent subjective scores, lower noise, higher or equivalent CNRs, and higher FOMCNR. The quality of images in sets B.FBP and B.HIR was unacceptable. The radiation exposure and CM dose in group B were 1.94 mGy and 28 ± 5 mL, respectively, representing reductions of 77.6% (P < .001) and 60% (P < .001) as compared to those in group A.ConclusionsIn follow-up examinations after TEVAR, CTA with ultra-low radiation exposure and CM dose is feasible using low tube voltage and IMR for nonobese patients.



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Volumetric MRI in Neurofibromatosis Type 1 (NF1) Comes of Age to Help Determine Initiation and Monitoring of Targeted Therapies for Plexiform Neurofibromas

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Publication date: Available online 13 December 2017
Source:Academic Radiology
Author(s): David Viskochil, Luke L. Linscott




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Essentials of Statistical Methods for Assessing Reliability and Agreement in Quantitative Imaging

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Publication date: Available online 11 December 2017
Source:Academic Radiology
Author(s): Arash Anvari, Elkan F. Halpern, Anthony E. Samir
Quantitative imaging is increasing in almost all fields of radiological science. Modern quantitative imaging biomarkers measure complex parameters including metabolism, tissue microenvironment, tissue chemical properties or physical properties. In this paper, we focus on measurement reliability assessment in quantitative imaging. We review essential concepts related to measurement such as measurement variability and measurement error. We also discuss reliability study methods for intraobserver and interobserver variability, and the applicable statistical tests including: intraclass correlation coefficient, Pearson correlation coefficient, and Bland-Altman graphs and limits of agreement, standard error of measurement, and coefficient of variation.



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Understanding Patient Preference in Female Pelvic Imaging

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Publication date: Available online 11 December 2017
Source:Academic Radiology
Author(s): Michelle D. Sakala, Ruth C. Carlos, Mishal Mendiratta-Lala, Elisabeth H. Quint, Katherine E. Maturen
Rationale and ObjectivesWomen with pelvic pain or abnormal uterine bleeding may undergo diagnostic imaging. This study evaluates patient experience in transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) and explores correlations between preference and symptom severity.Materials and MethodsInstitutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant prospective study. Fifty premenopausal women with pelvic symptoms evaluated by recent TVUS and MRI and without history of gynecologic cancer or hysterectomy were included. A phone questionnaire used validated survey instruments including Uterine Fibroid Symptoms Quality of Life index, Testing Morbidities Index, and Wait Trade Off for TVUS and MRI examinations.ResultsUsing Wait Trade Off, patients preferred TVUS over MRI (3.58 vs 2.80 weeks, 95% confidence interval [CI] −1.63, 0.12; P = .08). Summary test utility of Testing Morbidities Index for MRI was worse than for TVUS (81.64 vs 87.42, 95%CI 0.41, 11.15; P = .03). Patients reported greater embarrassment during TVUS than during MRI (P < .0001), but greater fear and anxiety both before (P < .0001) and during (P < .001) MRI, and greater mental (P = .02) and physical (P = .02) problems after MRI versus TVUS. Subscale correlations showed physically inactive women rated TVUS more negatively (R = −0.32, P = .03), whereas women with more severe symptoms of loss of control of health (R = −0.28, P = .04) and sexual dysfunction (R = −0.30, P = .03) rated MRI more negatively.ConclusionWomen with pelvic symptoms had a slight but significant preference for TVUS over MRI. Identifying specific distressing aspects of each test and patient factors contributing to negative perceptions can direct improvement in both test environment and patient preparation. Improved patient experience may increase imaging value.



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Smoking-related lung abnormalities on computed tomography images: comparison with pathological findings

Abstract

Smoking-related lung abnormalities are now an increasing public health concern. According to the findings of large-cohort studies, approximately 8% of smokers have interstitial lung abnormalities, which are associated with a relatively high risk of all-cause mortality. We reviewed the radiological and pathological findings of smoking-related interstitial lung diseases, such as respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, and airspace enlargement with fibrosis. We have also discussed the histological basis of unclassifiable interstitial pneumonia in smokers, which exhibits airway-centered cystic lesions with fibrosis. A variety of radiological findings coexist in the lungs of a smoker. This overlapping of multiple pathological conditions might cause the radiological patterns of diseases to become unclassifiable. Therefore, diagnosis should be performed not on the basis of a single radiological finding, but in a comprehensive manner, by including clinical symptoms and disease behavior. Among interstitial abnormalities in smokers, the usual interstitial pneumonia (UIP) pattern is correlated with a worse prognosis than others. Basal-predominant subpleural reticulation is a clue for accurate diagnosis of UIP, which can be achieved by computer-aided quantitative analysis.



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Comment on “Epidermal growth factor receptor mutation predicts favorable outcomes in non-small cell lung cancer patients with brain metastases treated with stereotactic radiosurgery”, by Yang WC et al.

We read with great interest the article from Yang et al. named "Epidermal growth factor receptor mutation predicts favorable outcomes in non-small cell lung cancer patients with brain metastases treated with stereotactic radiosurgery" [1]. In this large retrospective review of 147 patients undergoing stereotactic radiosurgery (SRS) for brain metastasis (BM) of non-small cell lung cancer (NSCLC), the authors were able to conclude that the presence of an Epidermal Growth Factor Receptor mutation (EGFR) was associated with better outcomes compared to wild type (wt) EGFR.

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WEB Treatment of Ruptured Intracranial Aneurysms: A Single-Center Cohort of 100 Patients [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The Woven EndoBridge device was recently introduced for the intrasaccular treatment of wide-neck aneurysms without the need for adjunctive devices. We present our results of the primary treatment of ruptured aneurysms with the Woven EndoBridge regardless of location or neck size.

MATERIALS AND METHODS:

Between February 2015 and April 2017, 100 ruptured aneurysms were selectively treated with the Woven EndoBridge. No supporting stents or balloons were used. There were 71 women treated (mean patient age, 59 years; median age, 60 years; range, 23–82 years).

RESULTS:

The mean aneurysm size was 5.6 mm (range, 3–13 mm), and 42 aneurysms were ≤4 mm. Sixty-six aneurysms (66%) had a wide neck, defined as ≥4 mm or a dome-neck ratio ≤1.5. There was 1 procedural rupture without sequelae. In 9 patients (9%), thromboembolic complications occurred. One poor grade patient died; neurologic deficits remained in 3. Overall treatment-related morbidity-mortality was 4% (4 of 100; 95% CI, 1.2%–10.2%).

Two of 100 aneurysms were initially incompletely occluded and were additionally treated early after initial intervention. Of 80 eligible patients, 74 (93%) had 3-month angiographic follow-up. Fifty-four aneurysms (73%) were completely occluded, 17 (23%) had a small neck remnant, and 3 (4%) were incompletely occluded. One patient was additionally treated with a second Woven EndoBridge, and in 2 patients, additional treatment is scheduled. The overall reopening/retreatment rate was 6.8% (5 of 74; 95% CI, 2.6%–15.2%). There were no rebleeds during follow-up.

CONCLUSIONS:

Treatment of small ruptured aneurysms with the Woven EndoBridge was safe and effective. The Woven EndoBridge proved to be a valuable alternative to coils without the need for stents or balloons.



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Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.

MATERIALS AND METHODS:

Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%–80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.

RESULTS:

The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8–49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0–3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%–100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.

CONCLUSIONS:

Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.



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Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient.

MATERIALS AND METHODS:

Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests.

RESULTS:

In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms.

CONCLUSIONS:

High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.



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Regarding "Perfusion MR Imaging Using a 3D Pulsed Continuous Arterial Spin-Labeling Method for Acute Cerebral Infarction Classified as Branch Atheromatous Disease Involving the Lenticulostriate Artery Territory" [LETTERS]



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Zika Virus Iceberg: Very Large [LETTERS]



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Reply: [LETTERS]



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Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy.

MATERIALS AND METHODS:

Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping–oxygen extraction fraction images.

RESULTS:

Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping–oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5–249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping–oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively.

CONCLUSIONS:

Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.



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Regarding "Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy" [LETTERS]



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Basion-Cartilaginous Dens Interval: An Imaging Parameter for Craniovertebral Junction Assessment in Children [PEDIATRICS]

BACKGROUND AND PURPOSE:

Widening of the basion-dens interval is an important sign of cranioverterbral junction injury. The current literature on basion-dens interval in children is sparse and based on bony measurements with variable values. Our goal was to establish the normal values of a recently described new imaging parameter, the basion–cartilaginous dens interval in children.

MATERIALS AND METHODS:

Three hundred healthy pediatric patients (0–10 years of age) were selected retrospectively. These patients were divided into 3 different groups: A (0–3 years), B (3–6 years), and C (6–10 years). The basion–cartilaginous dens interval was calculated on the sagittal MPR image of cervical spine CT in a soft-tissue window. The mean, SD, and the upper limit of normal (mean +2 SDs) of the 3 groups were calculated, and statistical tests were used to check for significant differences of the basion–cartilaginous dens interval among these 3 groups.

RESULTS:

The upper limits of the basion–cartilaginous dens interval for the 3 groups were 5.34 mm in group A, 5.64 mm in group B, and 7.24 mm in group C. There were statistically significant differences in the basion–cartilaginous dens interval values among the 3 groups. There was no statistically significant difference in basion–cartilaginous dens interval values between groups A and B; however, values in group C were significantly different from those in both A and B. There was no statistically significant difference in the basion–cartilaginous dens interval values between males and females.

CONCLUSIONS:

The basion–cartilaginous dens interval is a novel imaging parameter to assess cranioverterbral junction integrity in children, which includes the nonossified cartilage in the measurement.



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Treatment of Middle Cerebral Artery Aneurysms with Flow-Diverter Stents: A Systematic Review and Meta-Analysis [INTERVENTIONAL]

BACKGROUND:

The safety and efficacy of flow-diversion treatment of MCA aneurysms have not been well-established.

PURPOSE:

Our aim was to evaluate angiographic and clinical outcomes after flow diversions for MCA aneurysms.

DATA SOURCES:

A systematic search of PubMed, MEDLINE, and Embase was performed for studies published from 2008 to May 2017.

STUDY SELECTION:

According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we selected studies with >5 patients describing angiographic and clinical outcomes after flow-diversion treatment of MCA aneurysms.

DATA ANALYSIS:

Random-effects meta-analysis was used to pool the following outcomes: aneurysm occlusion rate, procedure-related complications, rupture rate of treated aneurysms, and occlusion of the jailed branches.

DATA SYNTHESIS:

Twelve studies evaluating 244 MCA aneurysms were included in this meta-analysis. Complete/near-complete occlusion was obtained in 78.7% (95% CI, 67.8%–89.7%) of aneurysms. The rupture rate of treated aneurysms during follow-up was 0.4% per aneurysm-year. The rate of treatment-related complications was 20.7% (95% CI, 14%–27.5%), and approximately 10% of complications were permanent. The mortality rate was close to 2%. Nearly 10% (95% CI, 4.7%–15.5%) of jailed arteries were occluded during follow-up, whereas 26% (95% CI, 14.4%–37.6%) had slow flow. Rates of symptoms related to occlusion and slow flow were close to 5%.

LIMITATIONS:

Small and retrospective series could affect the strength of the reported results.

CONCLUSIONS:

Given the not negligible rate of treatment-related complications, flow diversion for MCA aneurysms should be considered an alternative treatment when traditional treatment methods are not feasible. However, when performed in this select treatment group, high rates of aneurysm occlusion and protection against re-rupture can be achieved.



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Safety and Efficacy of Aneurysm Treatment with the WEB [LETTERS]



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Pial Artery Supply as an Anatomic Risk Factor for Ischemic Stroke in the Treatment of Intracranial Dural Arteriovenous Fistulas [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Although intracranial dural arteriovenous fistulas are principally supplied by dural branches of the external carotid, internal carotid, and vertebral arteries, they can also be fed by pial arteries that supply the brain. We sought to determine the frequency of neurologic deficits following treatment of intracranial dural arteriovenous fistulas with and without pial artery supply.

MATERIALS AND METHODS:

One hundred twenty-two consecutive patients who underwent treatment for intracranial dural arteriovenous fistulas at our hospital from 2008 to 2015 were retrospectively reviewed. Patient data were examined for posttreatment neurologic deficits; patients with such deficits were evaluated for imaging evidence of cerebral infarction. Data were analyzed with multivariable logistic regression.

RESULTS:

Of 122 treated patients, 29 (23.8%) had dural arteriovenous fistulas with pial artery supply and 93 (76.2%) had dural arteriovenous fistulas without pial arterial supply. Of patients with pial artery supply, 4 (13.8%) had posttreatment neurologic deficits, compared with 2 patients (2.2%) without pial artery supply (P = .04). Imaging confirmed that 3 patients with pial artery supply (10.3%) had cerebral infarcts, compared with only 1 patient without pial artery supply (1.1%, P = .03). Increasing patient age was also positively associated with pial supply and treatment-related complications.

CONCLUSIONS:

Patients with dural arteriovenous fistulas supplied by the pial arteries were more likely to experience posttreatment complications, including ischemic strokes, than patients with no pial artery supply. The approach to dural arteriovenous fistula treatment should be made on a case-by-case basis so that the risk of complications can be minimized.



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CT Texture Analysis: Defining and Integrating New Biomarkers for Advanced Oncologic Imaging in Precision Medicine: A Comment on "CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy" [article-commentary]



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[other]



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Quantitative Synthetic MRI in Children: Normative Intracranial Tissue Segmentation Values during Development [PEDIATRICS]

BACKGROUND AND PURPOSE:

Synthetic MR imaging is a new technique to create absolute R1 relaxivity (1/T1), R2 relaxivity (1/T2), and proton-density maps using a single multiple-spin-echo saturation recovery sequence. These relaxivity maps allow rapid automated intracranial segmentation of tissue types. To assess its utility in children, we created a normative data base of intracranial volume and brain parenchymal, GM, WM, CSF, and myelin volumes in a pediatric population with normal brain MRI findings using synthetic MR imaging.

MATERIALS AND METHODS:

All multiple-spin-echo saturation recovery sequences containing brain MR imaging examinations performed during 34 months were retrospectively reviewed. Abnormal examination findings were excluded following a detailed radiographic and clinical chart review. The remaining normal examination findings were then quantitatively analyzed with synthetic MR imaging. Intracranial, brain parenchymal, GM, WM, CSF, and myelin volumes were plotted versus age. Qualitative assessment of segmentation accuracy was performed. Selected abnormal examination findings were compared with these normative curves.

RESULTS:

One hundred twenty-two MRI examinations with normal findings were included of individuals ranging from 0.1 to 21.5 years of age (median, 11.8 years). Resulting normative data plots compared favorably with previously published data obtained using more onerous techniques. Differentiation from pathologic states was possible using quantitative values in select cases.

CONCLUSIONS:

A pediatric data base of normal intracranial tissue volumes using a single sequence and rapid software analysis has been compiled and correlates with previously published data. This provides a framework for clinical interpretation of quantitative synthetic MR images during development. Improved age-based segmentation algorithms in young children are needed.



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Bring Back the Joy in Neuroradiology [editorial]



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Predictive Models in Differentiating Vertebral Lesions Using Multiparametric MRI [SPINE]

BACKGROUND AND PURPOSE:

Conventional MR imaging has high sensitivity but limited specificity in differentiating various vertebral lesions. We aimed to assess the ability of multiparametric MR imaging in differentiating spinal vertebral lesions and to develop statistical models for predicting the probability of malignant vertebral lesions.

MATERIALS AND METHODS:

One hundred twenty-six consecutive patients underwent multiparametric MRI (conventional MR imaging, diffusion-weighted MR imaging, and in-phase/opposed-phase imaging) for vertebral lesions. Vertebral lesions were divided into 3 subgroups: infectious, noninfectious benign, and malignant. The cutoffs for apparent diffusion coefficient (expressed as 10–3 mm2/s) and signal intensity ratio values were calculated, and 3 predictive models were established for differentiating these subgroups.

RESULTS:

Of the lesions of the 126 patients, 62 were infectious, 22 were noninfectious benign, and 42 were malignant. The mean ADC was 1.23 ± 0.16 for infectious, 1.41 ± 0.31 for noninfectious benign, and 1.01 ± 0.22 mm2/s for malignant lesions. The mean signal intensity ratio was 0.80 ± 0.13 for infectious, 0.75 ± 0.19 for noninfectious benign, and 0.98 ± 0.11 for the malignant group. The combination of ADC and signal intensity ratio showed strong discriminatory ability to differentiate lesion type. We found an area under the curve of 0.92 for the predictive model in differentiating infectious from malignant lesions and an area under the curve of 0.91 for the predictive model in differentiating noninfectious benign from malignant lesions. On the basis of the mean ADC and signal intensity ratio, we established automated statistical models that would be helpful in differentiating vertebral lesions.

CONCLUSIONS:

Our study shows that multiparametric MRI differentiates various vertebral lesions, and we established prediction models for the same.



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Pacemakers in MRI for the Neuroradiologist [review-article]

SUMMARY:

Cardiac implantable electronic devices are frequently encountered in clinical practice in patients being screened for MR imaging examinations. Traditionally, the presence of these devices has been considered a contraindication to undergoing MR imaging. Growing evidence suggests that most of these patients can safely undergo an MR imaging examination if certain conditions are met. This document will review the relevant cardiac implantable electronic devices encountered in practice today, the background physics/technical factors related to scanning these devices, the multidisciplinary screening protocol used at our institution for scanning patients with implantable cardiac devices, and our experience in safely performing these examinations since 2010.



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WEB Device: Ready for Ruptured Aneurysms? [article-commentary]



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Comment on “Epidermal growth factor receptor mutation predicts favorable outcomes in non-small cell lung cancer patients with brain metastases treated with stereotactic radiosurgery”, by Yang WC et al.

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Publication date: Available online 15 December 2017
Source:Radiotherapy and Oncology
Author(s): Stéphane Renaud, Joseph Seitlinger, Pierre Truntzer, Georges Noel, Gilbert Massard




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Multiparametric MR Imaging of Age-related Changes in Healthy Thigh Muscles.

Multiparametric MR Imaging of Age-related Changes in Healthy Thigh Muscles.

Radiology. 2017 Dec 14;:171316

Authors: Yoon MA, Hong SJ, Ku MC, Kang CH, Ahn KS, Kim BH

Abstract
Purpose To use multiparametric magnetic resonance (MR) imaging to assess for and establish age-related differences in healthy thigh muscles. Materials and Methods Ninety-five subjects (47 men, 48 women; median age, 47 years) with healthy body mass index were grouped according to age: 30-39 years (n = 25), 40-49 years (n = 25), 50-59 years (n = 25), and 60-69 years (n = 20). Multiparametric MR imaging (intravoxel incoherent motion diffusion-weighted, diffusion-tensor, multiecho Dixon, and dynamic contrast material-enhanced MR imaging) was performed at 3.0 T. Two radiologists independently evaluated parametric maps of the anterior, medial, and posterior compartments. Welch-modified one-way analysis of variance and post hoc Dunnet T3 test were used to evaluate differences in apparent diffusion, true diffusion, and pseudodiffusion coefficients; perfusion fraction; fractional anisotropy (FA); fat percentage; volume transfer constant; constant efflux rate from the extravascular-extracellular space to plasma; volume fraction of the extravascular-extracellular space (Ve); incremental area under the curve; and Pearson and Spearman correlation coefficients were used to evaluate relationship strength. Multiple regression analysis was performed to identify independent predictors of age, and interrater reliability was assessed with intraclass correlation coefficients. Results There were significant differences among the age groups in apparent diffusion coefficients (P = .010), true diffusion coefficients (P = .045), FA (P < .001), Ve (P = .029) of the anterior compartment muscles, and fat percentages of all three compartments (P ≤ .001). Moreover, FA (Pearson r = 0.428, Spearman ρ = 0.431; P < .001) and Ve (r = 0.226, P = .030 and ρ = 0.309, P = .003) in the anterior compartment and fat percentages in all three compartments (r = 0.481, 0.475, and 0.573; ρ = 0.515, 0.487, and 0.667; respectively; P < .001) were positively associated with age. Multiple regression analysis showed that age was predictive of fat percentage in the posterior compartment (β = 0.500, P < .001) and of FA in the anterior compartment (β = 0.194, P = .042). Interrater reliability was excellent (intraclass correlation coefficient, 0.745-0.992). Conclusion Multiple MR imaging parameters were significantly associated with age in thigh muscles. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29239712 [PubMed - as supplied by publisher]



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Interval Breast Cancer Rates and Histopathologic Tumor Characteristics after False-Positive Findings at Mammography in a Population-based Screening Program.

Interval Breast Cancer Rates and Histopathologic Tumor Characteristics after False-Positive Findings at Mammography in a Population-based Screening Program.

Radiology. 2017 Dec 14;:162159

Authors: Hofvind S, Sagstad S, Sebuødegård S, Chen Y, Roman M, Lee CI

Abstract
Purpose To compare rates and tumor characteristics of interval breast cancers (IBCs) detected after a negative versus false-positive screening among women participating in the Norwegian Breast Cancer Screening Program. Materials and Methods The Cancer Registry Regulation approved this retrospective study. Information about 423 445 women aged 49-71 years who underwent 789 481 full-field digital mammographic screening examinations during 2004-2012 was extracted from the Cancer Registry of Norway. Rates and odds ratios of IBC among women with a negative (the reference group) versus a false-positive screening were estimated by using logistic regression models adjusted for age at diagnosis and county of residence. Results A total of 1302 IBCs were diagnosed after 789 481 screening examinations, of which 7.0% (91 of 1302) were detected among women with a false-positive screening as the most recent breast imaging examination before detection. By using negative screening as the reference, adjusted odds ratios of IBCs were 3.3 (95% confidence interval [CI]: 2.6, 4.2) and 2.8 (95% CI: 1.8, 4.4) for women with a false-positive screening without and with needle biopsy, respectively. Women with a previous negative screening had a significantly lower proportion of tumors that were 10 mm or less (14.3% [150 of 1049] vs 50.0% [seven of 14], respectively; P < .01) and grade I tumors (13.2% [147 of 1114] vs 42.9% [six of 14]; P < .01), but a higher proportion of cases with lymph nodes positive for cancer (40.9% [442 of 1080] vs 13.3% [two of 15], respectively; P = .03) compared with women with a previous false-positive screening with benign biopsy. A retrospective review of the screening mammographic examinations identified 42.9% (39 of 91) of the false-positive cases to be the same lesion as the IBC. Conclusion By using a negative screening as the reference, a false-positive screening examination increased the risk of an IBC three-fold. The tumor characteristics of IBC after a negative screening were less favorable compared with those detected after a previous false-positive screening. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29239711 [PubMed - as supplied by publisher]



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Liver Fibrosis: Deep Convolutional Neural Network for Staging by Using Gadoxetic Acid-enhanced Hepatobiliary Phase MR Images.

Liver Fibrosis: Deep Convolutional Neural Network for Staging by Using Gadoxetic Acid-enhanced Hepatobiliary Phase MR Images.

Radiology. 2017 Dec 14;:171928

Authors: Yasaka K, Akai H, Kunimatsu A, Abe O, Kiryu S

Abstract
Purpose To investigate the performance of a deep convolutional neural network (DCNN) model in the staging of liver fibrosis using gadoxetic acid-enhanced hepatobiliary phase magnetic resonance (MR) imaging. Materials and Methods This retrospective study included patients for whom input data (hepatobiliary phase MR images, static magnetic field of the imaging unit, and hepatitis B and C virus testing results available, either positive or negative) and reference standard data (liver fibrosis stage evaluated from biopsy or surgical specimens obtained within 6 months of the MR examinations) were available were assigned to the training (534 patients) or the test (100 patients) group. For the training group (54, 53, 81, 113, and 233 patients with fibrosis stages F0, F1, F2, F3, and F4, respectively; mean patient age, 67.4 ± 9.7 years; 388 males and 146 females), MR images with three different section levels were augmented 90-fold (rotated, parallel-shifted, brightness-changed and contrast-changed images were generated; a total of 144 180 images). Supervised training was performed by using the DCNN model to minimize the difference between the output data (fibrosis score obtained through deep learning [FDL score]) and liver fibrosis stage. The performance of the DCNN model was evaluated in the test group (10, 10, 15, 20, and 45 patients with fibrosis stages F0, F1, F2, F3, and F4, respectively; mean patient age, 66.8 years ± 10.7; 71 male patients and 29 female patients) with receiver operating characteristic (ROC) analyses. Results The FDL score was correlated significantly with fibrosis stage (Spearman rank correlation coefficient: 0.63; P < .001). Fibrosis stages F4, F3, and F2 were diagnosed with areas under the ROC curve of 0.84, 0.84, and 0.85, respectively. Conclusion The DCNN model exhibited a high diagnostic performance in the staging of liver fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

PMID: 29239710 [PubMed - as supplied by publisher]



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The Wnt/β-catenin pathway is deregulated in cemento-ossifying fibromas.

The Wnt/β-catenin pathway is deregulated in cemento-ossifying fibromas.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Nov 24;:

Authors: Pereira TDSF, Diniz MG, França JA, Moreira RG, Menezes GHF, Sousa SF, Castro WH, Gomes CC, Gomez RS

Abstract
OBJECTIVE: The molecular pathogenesis of cemento ossifying fibroma (COF) is unclear. The purpose of this study was to investigate mutations in 50 oncogenes and tumor suppressor genes, including APC and CTNNB1, in which mutations in COF have been previously reported. In addition, we assessed the transcriptional levels of the Wnt/β-catenin pathway genes in COF.
STUDY DESIGN: We used a quantitative polymerase chain reaction array to evaluate the transcriptional levels of 44 Wnt/β-catenin pathway genes in 6 COF samples, in comparison with 6 samples of healthy jaws. By using next-generation sequencing (NGS) in 7 COF samples, we investigated approximately 2800 mutations in 50 genes.
RESULTS: The expression assay revealed 12 differentially expressed Wnt/β-catenin pathway genes in COF, including the upregulation of CTNNB1, TCF7, NKD1, and WNT5 A, and downregulation of CTNNBIP1, FRZB, FZD6, RHOU, SFRP4, WNT10 A, WNT3 A, and WNT4, suggesting activation of the Wnt/β-catenin signaling pathway. NGS revealed 5 single nucleotide variants: TP53 (rs1042522), PIK3 CA (rs2230461), MET (rs33917957), KIT (rs3822214), and APC (rs33974176), but none of them was pathogenic.
CONCLUSIONS: Although NGS detected no oncogenic mutation, deregulation of key Wnt/β-catenin signaling pathway genes appears to be relevant to the molecular pathogenesis of COF.

PMID: 29239811 [PubMed - as supplied by publisher]



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Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

Eur J Surg Oncol. 2017 Nov 20;:

Authors: Janssen NNY, van la Parra RFD, Loo CE, Groen EJ, van den Berg MJ, Oldenburg HSA, Nijkamp J, Vrancken Peeters MTFD

Abstract
BACKGROUND AND OBJECTIVES: Breast conserving surgery (BCS) can be challenging for large regions of ductal carcinoma in situ (DCIS), resulting in high rates of positive resection margins. Radioactive seed localization (RSL) using multiple radioactive iodine (125I) seeds can be used to bracket extensive DCIS (eDCIS). The goal of this study was to retrospectively compare the use of a single or multiple 125I seeds in RSL to enable BCS in patients with eDCIS.
METHODS: All patients with eDCIS (area of ≥3.0 cm) who underwent either single or multiple-seed RSL between January 2008 and December 2016 were included. Patient, tumor and surgery characteristics were compared between both groups. Primary outcome measures were positive resection margin and re-operation rates.
RESULTS: Respectively 48 and 58 patients with eDCIS underwent single- and multiple-seed RSL and subsequent BCS. The rate of positive resection margin (focal and more than focal) with single-seed RSL was 47.9%, compared to 29.3% with multiple-seed RSL (p = 0.06). The re-operation rate was 39.6% with single-seed RSL and 20.7% in the multiple-seed RSL group (p = 0.05).
CONCLUSION: Multiple-seed RSL enables bracketing of large areas of DCIS, with the potential to decrease the high rate of positive resection margins in this patient group.

PMID: 29239733 [PubMed - as supplied by publisher]



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Sleep/Wake Behaviours in Elite Athletes from Three Different Football Codes.

Related Articles

Sleep/Wake Behaviours in Elite Athletes from Three Different Football Codes.

J Sports Sci Med. 2017 Dec;16(4):604-605

Authors: Miller DJ, Sargent C, Vincent GE, Roach GD, Halson SL, Lastella M

PMID: 29238263 [PubMed]



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Sleep: Let sleeping flies lie.

Related Articles

Sleep: Let sleeping flies lie.

Nat Rev Neurosci. 2017 Dec 14;19(1):7

Authors: Whalley K

PMID: 29238092 [PubMed - in process]



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Persistence of a vegetation mosaic in a peripheral region: could turbulent medieval history disrupt Holocene continuity of extremely species-rich grasslands?

Abstract

Fluctuations in intensity of human impact and corresponding vegetation changes have been reported from different parts of Europe for the period from the beginning of the 1st millennium ad to the high Middle Ages. In the Bílé Karpaty mountains (White Carpathians), a region well-known for its biologically valuable ancient grasslands, an extensive spread of woodland could have occurred in the Migration period (4th–6th century) and especially in the Confinium period (11th–12th century), when settling of this border region was legally prohibited. However, Holocene continuity of non-woodland vegetation was suggested as an explanation for the unique species richness of the local grasslands. If this explanation is true, then the turbulent times in medieval history could not have led to complete re-establishment of woodland. To test this idea palaeoecologically, we analysed four new profiles from wetland deposits for pollen, macrofossils and abiotic proxies, and re-dated some old profiles from the area. The results show the continual presence of human impact indicators since the Migration period in the southwest of the Bílé Karpaty, where these unique grasslands occur. Agricultural activities were indicated by pollen of crops, ruderals, weeds and grassland taxa and by macrofossils of fen-grassland plants. Grazing and burning seem to have been the main disturbances during the older period, while mowing of meadows by scythe became more important since the 17th century. Fossil records differed among the sites as a consequence of differences in altitude and disturbance regimes, but converged gradually with time. Despite intensification of human activities, the landscape remained mosaic-like. Indicators of undisturbed woodlands have been detected only in the northeast. Continuous yet perhaps never too intensive disturbances might therefore have maintained the ancient grassland species pool in the long term.



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Frontal EEG alpha asymmetry and emotion: From neural underpinnings and methodological considerations to psychopathology and social cognition



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Issue Information



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Cancer mechanobiology: Effects and therapeutic perspectives



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Precision Oncology: East Meets West



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Palbociclib synergizes with BRAF and MEK inhibitors in treatment naïve melanoma but not after the development of BRAF inhibitor resistance

Abstract

Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are currently in clinical trials for the treatment of melanoma. We hypothesize that the timing of the addition of CDK4/6 inhibitors to the current BRAF and MEK inhibitor regime will impact on the efficacy of this triplet drug combination. The efficacy of BRAF, MEK and CDK4/6 inhibitors as single agents and in combination were assessed in human BRAF mutant cell lines that were treatment naïve, BRAF inhibitor tolerant or had acquired resistance to BRAF inhibitors. Xenograft studies were then performed to test the in vivo efficacy of the BRAF and CDK4/6 inhibitor combination. Melanoma cells that had developed early reversible tolerance or acquired resistance to BRAF inhibition remained sensitive to palbociclib. In drug tolerant cells the efficacy of the combination of palbociclib with BRAF and/or MEK inhibitors was equivalent to single agent palbociclib. Similarly, acquired BRAF inhibitor resistance cells lost efficacy to the palbociclib and BRAF combination. In contrast upfront treatment of melanoma cells with palbociclib in combination with BRAF and/or MEK inhibitors induced either cell death or senescence, and was superior to a BRAF plus MEK inhibitor combination. In vivo palbociclib plus BRAF inhibitor induced rapid and sustained tumor regression without the development of therapy resistance. In summary, upfront dual targeting of CDK4/6 and mutant BRAF signalling enables tumor cells to evade resistance to monotherapy and is required for robust and sustained tumor regression. Melanoma patients whose tumors have acquired resistance to BRAF inhibition are less likely to have favourable responses to subsequent treatment with the triplet combination of BRAF, MEK and CDK4/6 inhibitors. This article is protected by copyright. All rights reserved.



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PD-1 blockade enhances the anti-tumor efficacy of GM-CSF surface-modified bladder cancer stem cells vaccine

Abstract

Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte -macrophage colony stimulating factor (SA-GM-CSF) surface-modified bladder cancer stem cells vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8+T-cells, a part of these CD8+T-cells expressed PD-1. Moreover, the CSCs vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1 blockade to the CSCs vaccine therapy increased the population of CD4+, CD8+ and CD8+IFN-γ+ but not CD4+ Foxp3+T-cells and induced the highest production of IFN-γ. PD-1 blockade could effectively enhance the functions of tumor-specific T lymphocytes generated by the CSCs vaccine. This combination therapy improved the cure rate among mice, and effectively protected the mice against a second CSCs cell challenge, but not a RM-1 cell challenge. These results indicate that PD-1 blockade combined with the GM-CSF-modified CSCs vaccine effectively induced a strong and specific anti-tumor immune response against bladder cancer. This article is protected by copyright. All rights reserved.



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Lung function in severe pediatric asthma: a longitudinal study in children and adolescents in Brazil

In severe asthma, high doses of inhaled corticosteroids (ICS) are used in order to achieve clinical and functional control. This study aimed to evaluate lung function in outpatients (children and adolescents) ...

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Investigating trehalose synthesis genes after cold acclimation in the Antarctic nematode Panagrolaimus sp. DAW1 [RESEARCH ARTICLE]

Anna C. Seybold, David A. Wharton, Michael A. S. Thorne, and Craig J. Marshall

Panagrolaimus sp. DAW1 is a freeze-tolerant Antarctic nematode which survives extensive intracellular ice formation. The molecular mechanisms of this extreme adaptation are still poorly understood. We recently showed that desiccation-enhanced RNA interference (RNAi) soaking can be used in conjunction with quantitative polymerase chain reaction (qPCR) to screen for phenotypes associated with reduced expression of candidate genes in Panagrolaimus sp. DAW1. Here, we present the use of this approach to investigate the role of trehalose synthesis genes in this remarkable organism. Previous studies have shown that acclimating Panagrolaimus sp. DAW1 at 5°C before freezing or desiccation substantially enhances survival. In this study, the expression of tps-2 and other genes associated with trehalose metabolism, as well as lea-1, hsp-70 and gpx-1, in cold-acclimated and non-acclimated nematodes was analyzed using qPCR. Pd-tps-2 and Pd-lea-1 were significantly upregulated after cold acclimation, indicating an inducible expression in the cold adaptation of Panagrolaimus sp. DAW1. The role of trehalose synthesis genes in Panagrolaimus sp. DAW1 was further investigated by RNAi. Compared to the controls, Pd-tps-2a(RNAi)-treated and cold-acclimated nematodes showed a significant decrease in mRNA, but no change in trehalose content or freezing survival. The involvement of two other trehalose synthesis genes (tps-2b and gob-1) was also investigated. These findings provide the first functional genomic investigation of trehalose synthesis genes in the non-model organism Panagrolaimus sp. DAW1. The presence of several trehalose synthesis genes with different RNAi sensitivities suggests the existence of multiple backup systems in Panagrolaimus sp. DAW1, underlining the importance of this sugar in preparation for freezing.



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Directional vibration sensing in the leafcutter ant Atta sexdens [RESEARCH ARTICLE]

Felix A. Hager, Lea Kirchner, and Wolfgang H. Kirchner

Leafcutter ants communicate with the substrate-borne component of the vibratory emission produced by stridulation. Stridulatory signals in the genus Atta have been described in different behavioural contexts, such as foraging, alarm signalling and collective nest building. Stridulatory vibrations are employed to recruit nestmates, which can localize the source of vibration, but there is little information about the underlying mechanisms. Our experiments reveal that time-of-arrival delays of the vibrational signals are used for tropotactic orientation in Atta sexdens. The detected time delays are in the same range as the time delays detected by termites. Chemical communication is also of great importance in foraging organization, and signals of different modalities may be combined in promoting the organization of collective foraging. Here we show that the tropotactic orientation to vibrational signals interacts with chemical communication signals.



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Quantitative control of mitochondria transfer between live single cells using a microfluidic device [METHODS AND TECHNIQUES]

Ken-Ichi Wada, Kazuo Hosokawa, Yoshihiro Ito, and Mizuo Maeda

Quantitative control of mitochondria transfer between live cells is a promising approach for genetic manipulation of mitochondrial DNA (mtDNA) because single mitochondrion transfer to a mtDNA-less (0) cell potentially leads to homoplasmy of mtDNA. In this paper, we describe a method for quantitative control of mitochondria transfer between live single cells. For this purpose, we fabricated novel microfluidic devices having cell paring structures with a 4.1, 5.6 or 10.0 μm-length microtunnel. When cells were fused through a microtunnel using the Sendai virus envelope-based method, a strictured cytoplasmic connection was achieved with a length corresponding to that of the microtunnel. Elongation of the cytoplasmic connection led to a decrease in mitochondria transfer to the fusion partner. Moreover, some cell pairs that fused through a 10.0 μm-length microtunnel showed single mitochondrion transfer. Fused cells were spontaneously disconnected from each other when they were recovered in a normal culture medium. These results suggest that our cell fusion method can perform quantitative control of mitochondria transfer that includes a single mitochondrion transfer.



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FGF8 morphogen gradients are differentially regulated by heparan sulphotransferases Hs2st and Hs6st1 in the developing brain [RESEARCH ARTICLE]

Wai-Kit Chan, David J. Price, and Thomas Pratt

Fibroblast growth factor (FGF) morphogen signalling through the evolutionarily ancient extracellular signalling-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway recurs in many neural and non-neural developmental contexts, and understanding the mechanisms that regulate FGF/ERK function are correspondingly important. The glycosaminoglycan heparan sulphate (HS) binds to FGFs and exists in an enormous number of differentially sulphated forms produced by the action of HS modifying enzymes, and so has the potential to present an extremely large amount of information in FGF/ERK signalling. Although there have been many studies demonstrating that HS is an important regulator of FGF function, experimental evidence on the role of the different HS modifying enzymes on FGF gradient formation has been lacking until now. We challenged ex vivo developing mouse neural tissue, in which HS had either been enzymatically removed by heparanase treatment or lacking either the HS modifying enzymes Hs2st (Hs2st–/– tissue) or Hs6st1 (Hs6st1–/– tissue), with exogenous Fgf8 to gain insight on how HS and the function of these two HS modifying enzymes impacts on Fgf8 gradient formation from an exogenously supplied source of Fgf8 protein. We discover that two different HS modifying enzymes, Hs2st and Hs6st1, indeed differentially modulate the properties of emerging Fgf8 protein concentration gradients and the Erk signalling output in response to Fgf8 in living tissue in ex vivo cultures. Both Hs2st and Hs6st1 are required for stable Fgf8 gradients to form as rapidly as they do in wild-type tissue while only Hs6st1 has a significant effect on suppressing the levels of Fgf8 protein in the gradient compared to wild type. Next we show that Hs2st and Hs6st1 act to antagonise and agonise the Erk signalling in response to Fgf8 protein, respectively, in ex vivo cultures of living tissue. Examination of endogenous Fgf8 protein and Erk signalling outputs in Hs2st–/– and Hs6st1–/– embryos suggests that our ex vivo findings have physiological relevance in vivo. Our discovery identifies a new class of mechanism to tune Fgf8 function by regulated expression of Hs2st and Hs6st1 that is likely to have broader application to the >200 other signalling proteins that interact with HS and their function in neural development and disease.



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Contextual interference during adaptation to asymmetric split-belt treadmill walking results in transfer of unique gait mechanics [RESEARCH ARTICLE]

Jacob W. Hinkel-Lipsker and Michael E. Hahn

When humans make errors in stepping during walking due to a perturbation, they may adapt their gait as a way to correct for discrepancies between predicted and actual sensory feedback. This study sought to determine if increased contextual interference during acquisition of a novel asymmetric gait pattern would change lower-limb mechanical strategies generalized to different walking contexts. Such knowledge could help to clarify the role of contextual interference in locomotor adaptation, and demonstrate potential use in future gait rehabilitation paradigms. One belt on a split-belt treadmill was driven at a constant velocity while the other was driven at changing velocities according to one of three practice paradigms: serial, random blocked, or random training. Subjects returned to complete one of two different transfer tests. Results indicate that during acquisition, random practice requires unique gait mechanics to adapt to a challenging walking environment. Also, results from one transfer test close to that of the acquisition experience did not seem to demonstrate any contextual interference effect. Finally, random blocked practice resulted in highly unique changes in step length symmetry on a second, more challenging, transfer test. This perhaps indicates that a moderate level of contextual interference causes unique locomotor generalization strategies.



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High salinity conveys thermotolerance in the coral model Aiptasia [RESEARCH ARTICLE]

Hagen M. Gegner, Maren Ziegler, Nils Rädecker, Carol Buitrago-Lopez, Manuel Aranda, and Christian R. Voolstra

The endosymbiosis between dinoflagellate algae of the genus Symbiodinium and stony corals provides the foundation of coral reef ecosystems. Coral bleaching, the expulsion of endosymbionts from the coral host tissue as a consequence of heat or light stress, poses a threat to reef ecosystem functioning on a global scale. Hence, a better understanding of the factors contributing to heat stress susceptibility and tolerance is needed. In this regard, some of the most thermotolerant corals live in particularly saline habitats, but possible effects of high salinity on thermotolerance in corals are anecdotal. Here we test the hypothesis that high salinity may lead to increased thermotolerance. We conducted a heat stress experiment at low, intermediate, and high salinities using a set of host-endosymbiont combinations of the coral model Aiptasia. As expected, all host-endosymbiont combinations showed reduced photosynthetic efficiency and endosymbiont loss during heat stress, but the severity of bleaching was significantly reduced with increasing salinities for one of the host-endosymbiont combinations. Our results show that higher salinities can convey increased thermotolerance in Aiptasia, although this effect seems to be dependent on the particular host strain and/or associated symbiont type. This finding may help explain the extraordinarily high thermotolerance of corals in high salinity environments, such as the Red Sea and the Persian/Arabian Gulf, and provides novel insight regarding factors that contribute to thermotolerance. Since our results are based on a salinity effect in symbiotic sea anemones, it remains to be determined whether this salinity effect can also be observed in stony corals.



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How does the canine paw pad attenuate ground impacts? A multi-layer cushion system [RESEARCH ARTICLE]

Huaibin Miao, Jun Fu, Zhihui Qian, Luquan Ren, and Lei Ren

Macroscopic mechanical properties of digitigrade paw pads, such as non-linear elastic and variable stiffness, have been investigated in previous studies; however, little is known about the micro-scale structural characteristics of digitigrade paw pads, or the relationship between these characteristics and the exceptional cushioning of the pads. The digitigrade paw pad consists of a multi-layered structure, which is mainly comprised of a stratified epithelium layer, a dermis layer and a subcutaneous layer. The stratified epithelium layer and dermal papillae constitute the epidermis layer. Finite element analyses were carried out and showed that the epidermis layer effectively attenuated the ground impact across impact velocities of 0.05–0.4 m/s, and that the von Mises stresses were uniformly distributed in this layer. The dermis layer encompassing the subcutaneous layer can be viewed as a hydrostatic system, which can store, release and dissipate impact energy. All three layers in the paw pad work as a whole to meet the biomechanical requirements of animal locomotion. These findings provide insights into the biomechanical functioning of digitigrade paw pads and could be used to facilitate bio-inspired, ground-contacting component development for robots and machines, as well as contribute to footwear design.



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Mitochondrial dynamics and respiration within cells with increased open pore cytoskeletal meshes [RESEARCH ARTICLE]

David H. Jang, Sarah C. Seeger, Martha E. Grady, Frances S. Shofer, and David M. Eckmann

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of its energy production. This study illustrates the complex interaction between mitochondrial movement and respiration through the disruption of the cytoskeleton.



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The kinase domain residue serine 173 of Schizosaccharomyces pombe Chk1 kinase is critical for the response to DNA replication stress [RESEARCH ARTICLE]

Naomi Coulton and Thomas Caspari

While mammalian Chk1 kinase regulates replication origins, safeguards fork integrity and promotes fork progression, yeast Chk1 acts only in G1 and G2. We report here that the mutation of serine 173 (S173A) in the kinase domain of fission yeast Chk1 abolishes the G1-M and S-M checkpoints with little impact on the G2-M arrest. This separation-of-function mutation strongly reduces the Rad3-dependent phosphorylation of Chk1 at serine 345 during logarithmic growth, but not when cells experience exogenous DNA damage. Loss of S173 lowers the restrictive temperature of a catalytic DNA polymerase epsilon mutant (cdc20.M10) and is epistatic with a mutation in DNA polymerase delta (cdc6.23) when DNA is alkylated by methyl-methanesulfate (MMS). The chk1-S173A allele is uniquely sensitive to high MMS concentrations where it displays a partial checkpoint defect. A complete checkpoint defect occurs only when DNA replication forks break in cells without the intra-S phase checkpoint kinase Cds1. Chk1-S173A is also unable to block mitosis when the G1 transcription factor Cdc10 (cdc10.V50) is impaired. We conclude that serine 173, which is equivalent to lysine 166 in the activation loop of human Chk1, is only critical in DNA polymerase mutants or when forks collapse in the absence of Cds1.



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Transcriptome sequencing of the naked mole rat (Heterocephalus glaber) and identification of hypoxia tolerance genes [RESEARCH ARTICLE]

Bang Xiao, Li Li, Chang Xu, Shanmin Zhao, Lifang Lin, Jishuai Cheng, Wenjing Yang, Wei Cong, Guanghan Kan, and Shufang Cui

The naked mole rat (NMR; Heterocephalus glaber) is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression. In this study, we examined the sequence and transcript abundance data of the muscle transcriptome of NMRs exposed to hypoxia using the Illumina HiSeq 2500 system to clarify the possible genomic adaptive responses to the hypoxic underground surroundings. The RNA-seq raw FastQ data were mapped against the NMR genome. We identified 2337 differentially expressed genes (DEGs) by comparison of the hypoxic and control groups. Functional annotation of the DEGs by gene ontology (GO) analysis revealed enrichment of hypoxia stress-related GO categories, including ‘biological regulation’, ‘cellular process’, ‘ion transport’ and ‘cell-cell signaling’. Enrichment of DEGs in signaling pathways was analyzed against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify possible interactions between DEGs. The results revealed significant enrichment of DEGs in focal adhesion, the mitogen-activated protein kinase (MAPK) signaling pathway and the glycine, serine and threonine metabolism pathway. Furthermore, inhibition of DEGs (STMN1, MAPK8IP1 and MAPK10) expression induced apoptosis and arrested cell growth in NMR fibroblasts following hypoxia. Thus, this global transcriptome analysis of NMRs can provide an important genetic resource for the study of hypoxia tolerance in mammals. Furthermore, the identified DEGs may provide important molecular targets for biomedical research into therapeutic strategies for stroke and cardiovascular diseases.



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Regulation of cortical stability by RhoGEF3 in mitotic Sensory Organ Precursor cells in Drosophila [RESEARCH ARTICLE]

Lydie Couturier, Khalil Mazouni, Fred Bernard, Charlotte Besson, Elodie Reynaud, and Francois Schweisguth

In epithelia, mitotic cells round up and push against their neighbors to divide. Mitotic rounding results from increased assembly of F-actin and cortical recruitment of Myosin II, leading to increased cortical stability. Whether this process is developmentally regulated is not well known. Here, we examined the regulation of cortical stability in Sensory Organ Precursor cells (SOPs) in the Drosophila pupal notum. SOPs differed in apical shape and actomyosin dynamics from their epidermal neighbors prior to division, and appeared to have a more rigid cortex at mitosis. We identified RhoGEF3 as an actin regulator expressed at higher levels in SOPs, and showed that RhoGEF3 had in vitro GTPase Exchange Factor (GEF) activity for Cdc42. Additionally, RhoGEF3 genetically interacted with both Cdc42 and Rac1 when overexpressed in the fly eye. Using a null RhoGEF3 mutation generated by CRISPR-mediated homologous recombination, we showed using live imaging that the RhoGEF3 gene, despite being dispensable for normal development, contributed to cortical stability in dividing SOPs. We therefore suggest that cortical stability is developmentally regulated in dividing SOPs of the fly notum.



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Myotube migration to cover and shape the testis of Drosophila depends on Heartless, Cadherin/Catenin, and myosin II [RESEARCH ARTICLE]

Silke Rothenbusch-Fender, Katharina Fritzen, Maik C. Bischoff, Detlev Buttgereit, Susanne F. Oenel, and Renate Renkawitz-Pohl

During Drosophila metamorphosis, nascent testis myotubes migrate from the prospective seminal vesicle of the genital disc onto pupal testes and then further to cover the testes with multinucleated smooth-like muscles. Here we show that DWnt2 is likely required for determination of testis-relevant myoblasts on the genital disc. Knock down of fibroblast growth factor receptor (FGFR) heartless by RNAi and a dominant-negative version revealed multiple functions of Heartless, namely regulation of the amount of myoblasts on the genital disc, connection of seminal vesicles and testes, and migration of muscles along the testes. Live imaging indicated that the downstream effector Stumps is required for migration of testis myotubes on the testis towards the apical tip. After myoblast fusion, myosin II is needed for migration of nascent testis myotubes, in which Thisbe-dependent fibroblast growth factor (FGF) signaling is activated. Cadherin-N is essential for connecting these single myofibers and for creating a firm testis muscle sheath that shapes and stabilizes the testis tubule. Based on these results, we propose a model for the migration of testis myotubes in which nascent testis myotubes migrate as a collective onto and along the testis, dependent on FGF-regulated expression of myosin II.



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Cell membrane disruption stimulates cAMP and Ca2+ signaling to potentiate cell membrane resealing in neighboring cells [RESEARCH ARTICLE]

Tatsuru Togo

Disruption of cellular plasma membranes is a common event in many animal tissues, and the membranes are usually rapidly resealed. Moreover, repeated membrane disruptions within a single cell reseal faster than the initial wound in a protein kinase A (PKA)- and protein kinase C (PKC)-dependent manner. In addition to wounded cells, recent studies have demonstrated that wounding of Madin-Darby canine kidney (MDCK) cells potentiates membrane resealing in neighboring cells in the short-term by purinergic signaling, and in the long-term by nitric oxide/protein kinase G signaling. In the present study, real-time imaging showed that cell membrane disruption stimulated cAMP synthesis and Ca2+ mobilization from intracellular stores by purinergic signaling in neighboring MDCK cells. Furthermore, inhibition of PKA and PKC suppressed the ATP-mediated short-term potentiation of membrane resealing in neighboring cells. These results suggest that cell membrane disruption stimulates PKA and PKC via purinergic signaling to potentiate cell membrane resealing in neighboring MDCK cells.



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Elimination of classically-activated macrophages in tumor-conditioned medium by alternatively-activated macrophages [RESEARCH ARTICLE]

Fidel-Nicolas Lolo, Cristina Rius, and Sergio Casas-Tinto

Cellular interactions are critical during development, tissue fitness and epithelial tumor development. The expression levels of specific genes confer to tumoral cells a survival advantage versus the normal neighboring cells. As a consequence, cells surrounding tumors are eliminated and engulfed by macrophages. We propose a novel scenario in which circulating cells facing a tumor can reproduce these cellular interactions. In vitro cultured macrophages from murine bone marrow were used to investigate this hypothesis. M1 macrophages in tumoral medium upregulated markers of a suboptimal condition, such as Sparc and TyrRS, and undergo apoptosis. However, M2 macrophages display higher Myc expression levels and proliferate at the expense of M1. Resulting M1 apoptotic debris is engulfed by M2 in a Sparc- and TyrRS-dependent manner. These findings suggest that tumor-dependent macrophage elimination could deplete immune response against tumors. This possibility could be relevant for macrophage based anti-tumoral strategies.



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Optogenetic activation of EphB2 receptor in dendrites induced actin polymerization by activating Arg kinase [RESEARCH ARTICLE]

Clifford Locke, Kazuya Machida, Yi Wu, and Ji Yu

Erythropoietin-producing hepatocellular (Eph) receptors regulate a wide array of developmental processes by responding to cell-cell contacts. EphB2 is well-expressed in the brain and known to be important for dendritic spine development, as well as for the maintenance of the synapses, although the mechanisms of these functions have not been fully understood. Here we studied EphB2's functions in hippocampal neurons with an optogenetic approach, which allowed us to specify spatial regions of signal activation and monitor in real-time the consequences of signal activation. We designed and constructed OptoEphB2, a genetically encoded photoactivatable EphB2. Photoactivation of OptoEphB2 in fibroblast cells induced receptor phosphorylation and resulted in cell rounding ­­­­­­– a well-known cellular response to EphB2 activation. In contrast, local activation of OptoEphb2 in dendrites of hippocampal neurons induces rapid actin polymerization, resulting dynamic dendritic filopodial growth. Inhibition of Rac1 and CDC42 did not abolish OptoEphB2-induced actin polymerization. Instead, we identified Abelson tyrosine-protein kinase 2 (Abl2/Arg) as a necessary effector in OptoEphB2-induced filopodia growth in dendrites. These findings provided new mechanistic insight into EphB2's role in neural development and demonstrated the advantage of OptoEphB as a new tool for studying EphB signaling.



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Competitive pressures affect sexual signal complexity in Kurixalus odontotarsus: insights into the evolution of compound calls [RESEARCH ARTICLE]

Bicheng Zhu, Jichao Wang, Zhixin Sun, Yue Yang, Tongliang Wang, Steven E. Brauth, Yezhong Tang, and Jianguo Cui

Male-male vocal competition in anuran species is critical for mating success; however, it is also energetically demanding and highly time-consuming. Thus, we hypothesized that males may change signal elaboration in response to competition in real time. Male serrate-legged small treefrogs (Kurixalus odontotarsus) produce compound calls that contain two kinds of notes, harmonic sounds called ‘A notes’ and short broadband sounds called ‘B notes’. Using male evoked vocal response experiments, we found that competition influences the temporal structure and complexity of vocal signals produced by males. Males produce calls with a higher ratio of notes:call, and more compound calls including more A notes but fewer B notes with contest escalation. In doing so, males minimize the energy costs and maximize the benefits of competition when the level of competition is high. This means that the evolution of sexual signal complexity in frogs may be susceptible to selection for plasticity related to adjusting performance to the pressures of competition, and supports the idea that more complex social contexts can lead to greater vocal complexity.



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A computational study on the influence of insect wing geometry on bee flight mechanics [RESEARCH ARTICLE]

Jeffrey Feaster, Francine Battaglia, and Javid Bayandor

Two-dimensional computational fluid dynamics (CFD) is applied to better understand the effects of wing cross-sectional morphology on flow field and force production. This study investigates the influence of wing cross-section on insect scale flapping flight performance, for the first time, using a morphologically representative model of a bee (Bombus pensylvanicus) wing. The bee wing cross-section was determined using a micro-computed tomography scanner. The results of the bee wing are compared with flat and elliptical cross-sections, representative of those used in modern literature, to determine the impact of profile variation on aerodynamic performance. The flow field surrounding each cross-section and the resulting forces are resolved using CFD for a flight speed range of 1 to 5 m/s. A significant variation in vortex formation is found when comparing the ellipse and flat plate with the true bee wing. During the upstroke, the bee and approximate wing cross-sections have a much shorter wake structure than the flat plate or ellipse. During the downstroke, the flat plate and elliptical cross-sections generate a single leading edge vortex, while the approximate and bee wings generate numerous, smaller structures that are shed throughout the stroke. Comparing the instantaneous aerodynamic forces on the wing, the ellipse and flat plate sections deviate progressively with velocity from the true bee wing. Based on the present findings, a simplified cross-section of an insect wing can misrepresent the flow field and force production. We present the first aerodynamic study using a true insect wing cross-section and show that the wing corrugation increases the leading edge vortex formation frequency for a given set of kinematics.



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Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome [RESEARCH ARTICLE]

Rajeswari Banerji, Robert V. Skibbens, and M. Kathryn Iovine

Robert syndrome (RBS) and Cornelia de Lange syndrome (CdLS) are human developmental disorders characterized by craniofacial deformities, limb malformation and mental retardation. These birth defects are collectively termed cohesinopathies as both arise from mutations in cohesion genes. CdLS arises due to autosomal dominant mutations or haploinsufficiencies in cohesin subunits (SMC1A, SMC3 and RAD21) or cohesin auxiliary factors (NIPBL and HDAC8) that result in transcriptional dysregulation of developmental programs. RBS arises due to autosomal recessive mutations in cohesin auxiliary factor ESCO2, the gene that encodes an N-acetyltransferase which targets the SMC3 subunit of the cohesin complex. The mechanism that underlies RBS, however, remains unknown. A popular model states that RBS arises due to mitotic failure and loss of progenitor stem cells through apoptosis. Previous findings in the zebrafish regenerating fin, however, suggest that Esco2-knockdown results in transcription dysregulation, independent of apoptosis, similar to that observed in CdLS patients. Previously, we used the clinically relevant CX43 to demonstrate a transcriptional role for Esco2. CX43 is a gap junction gene conserved among all vertebrates that is required for direct cell-cell communication between adjacent cells such that cx43 mutations result in oculodentodigital dysplasia. Here, we show that morpholino-mediated knockdown of smc3 reduces cx43 expression and perturbs zebrafish bone and tissue regeneration similar to those previously reported for esco2 knockdown. Also similar to Esco2-dependent phenotypes, Smc3-dependent bone and tissue regeneration defects are rescued by transgenic Cx43 overexpression, suggesting that Smc3 and Esco2 cooperatively act to regulate cx43 transcription. In support of this model, chromatin immunoprecipitation assays reveal that Smc3 binds to a discrete region of the cx43 promoter, suggesting that Esco2 exerts transcriptional regulation of cx43 through modification of Smc3 bound to the cx43 promoter. These findings have the potential to unify RBS and CdLS as transcription-based mechanisms.



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The addition of a developmental factor, unc-62, to already long-lived worms increases lifespan and healthspan [RESEARCH ARTICLE]

Dror Sagi

Aging is a complex trait that is affected by multiple genetic pathways. A relatively unexplored approach is to manipulate multiple independent aging pathways simultaneously in order to observe their cumulative effect on lifespan. Here, we report the phenotypic characterization of a strain with changes in five aging pathways: (1) mitochondrial reactive oxygen species (ROS) production, (2) innate immunity, (3) stress response, (4) metabolic control and (5) developmental regulation in old age. The quintuply modified strain has a lifespan that is 160% longer than the transgenic control strain. Additionally, the quintuply modified strain maintains several physiological markers of aging for a longer time than the transgenic control. Our results support a modular approach as a general scheme to study how multiple pathways interact to achieve extreme longevity.



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Organochlorine pesticides in placenta in Kyrgyzstan and the effect on pregnancy, childbirth, and newborn health

Abstract

Organochlorine pesticides (OCPs) were determined by gas chromatography in 241 placentas from cotton-growing regions, 121 placentas from an urban area (city of Osh), and 146 placentas from unpolluted mountain regions of Kyrgyzstan. Manifestations of disease were recorded in the mothers during pregnancy and parturition and in their newborns during the first 6 days of life. OCPs were detected in 240 out of 508 placentas (47.2%), with increased incidence in the two polluted regions (65%), particularly in placentas from women living near former pesticide storehouses and agro air-strips (99%), but only in 2.7% of placentas from the unpolluted region. α-, β-, and γ-hexachlorocyclohexane (HCH); DDT; DDE; aldrin; and heptachlor were detected. The sum of concentrations of all OCPs (total OCPs) was calculated for each of the 240 placentas with detectable OCPs (median 9.5 μg/kg placenta, mean 88.3 μg/kg, range 0.1–3070 μg/kg). The incidence of health problems in four subgroups of this data set, with increasing levels of total OCPs, was compared with the incidence of health problems in the group of 268 placentas, where OCPs were undetectable. Relative risk of health problems in both, mothers and newborns, increased significantly, in a concentration-dependent manner, with increasing levels of total OCPs (p < 0.0001). Health complications with increased incidence in OCP-exposed newborns included, i.a., low birth weight, congenital malformations, infections, and stillbirths, in OCP-exposed mothers preterm delivery, (pre-)eclampsia/gestosis, and frequency of hospitalizations after delivery (infections). Women living near former pesticide storehouses and agro airstrips should be considered as being at risk. Reduction of exposure is urgently needed.



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Contrasted effects of an anti-cyanobacterial ultrasound device on the non-target freshwater invertebrate species Gammarus roeseli

Abstract

The aim of this work was to investigate the effects of an anti-cyanobacterial ultrasound device (supplied by an electrical power of 15 W and emitting at 23 and 46 kHz) on the widespread freshwater amphipod species Gammarus roeseli. First, laboratory scale experiments in 8-L glass tanks showed that an ultrasound exposure of 2 h and 40 min was sufficient to produce 50% mortality, along with a 6.5 °C water temperature increase. Avoiding excessive heating by using a water-cooling and recirculation system permitted an exposure time of 29 h for the same mortality rate. A potential relationship between temperature’s rise and amphipod mortality was hence highlighted. Moreover, the use of plastic mesh bag (0.5 mm mesh size) as a physical barrier has not shown any lethal effects of ultrasound exposure. Furthermore, the induction of GPx or GST activity as oxidative stress biomarkers was not observed. This could be explained by reduced ultrasound intensity inside the mesh bags. Thus, according to these results, the tested ultrasound system is not expected to be acutely harmful in the field.



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Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base

BACKGROUND

The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base.

METHODS

A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted.

RESULTS

For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy.

CONCLUSIONS

Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in this group. Cancer 2017. © 2017 American Cancer Society.



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Six-year survival of reimplanted talus after isolated total talar extrusion: a case report

Open total extrusion of the talus without concomitant fracture is an extremely rare injury. We present 6-year follow-up data of a patient treated using a temporary spanning external fixator and less invasive s...

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Genes, Vol. 8, Pages 389: Transcriptome Analysis of Paraburkholderia phymatum under Nitrogen Starvation and during Symbiosis with Phaseolus Vulgaris

Genes, Vol. 8, Pages 389: Transcriptome Analysis of Paraburkholderia phymatum under Nitrogen Starvation and during Symbiosis with Phaseolus Vulgaris

Genes doi: 10.3390/genes8120389

Authors: Martina Lardi Yilei Liu Gabriela Purtschert Samanta Bolzan de Campos Gabriella Pessi

Paraburkholderia phymatum belongs to the β-subclass of proteobacteria. It has recently been shown to be able to nodulate and fix nitrogen in symbiosis with several mimosoid and papilionoid legumes. In contrast to the symbiosis of legumes with α-proteobacteria, very little is known about the molecular determinants underlying the successful establishment of this mutualistic relationship with β-proteobacteria. In this study, we performed an RNA-sequencing (RNA-seq) analysis of free-living P. phymatum growing under nitrogen-replete and -limited conditions, the latter partially mimicking the situation in nitrogen-deprived soils. Among the genes upregulated under nitrogen limitation, we found genes involved in exopolysaccharides production and in motility, two traits relevant for plant root infection. Next, RNA-seq data of P. phymatum grown under free-living conditions and from symbiotic root nodules of Phaseolus vulgaris (common bean) were generated and compared. Among the genes highly upregulated during symbiosis, we identified—besides the nif gene cluster—an operon encoding a potential cytochrome o ubiquinol oxidase (Bphy_3646-49). Bean root nodules induced by a cyoB mutant strain showed reduced nitrogenase and nitrogen fixation abilities, suggesting an important role of the cytochrome for respiration inside the nodule. The analysis of mutant strains for the RNA polymerase transcription factor RpoN (σ54) and its activator NifA indicated that—similar to the situation in α-rhizobia—P. phymatum RpoN and NifA are key regulators during symbiosis with P. vulgaris.



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Senior Visiting Scientist Award 2017

The International Agency for Research on Cancer (IARC) is pleased to announce that the recipient of the 2017 Senior Visiting Scientist Award is Dr Brent Richards, Associate Professor of Medicine at the Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada.


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Oral immunization of mice with Omp31-loaded N-trimethyl chitosan nanoparticles induces high protection against Brucella melitensis infection

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Zygomatic Hypoplasia in Patients with Non-syndromic Cleft Lip and Palate: A Case–Control Study

Abstract

Background

Patients operated for cleft deformities may have zygomatic hypoplasia secondary to impaired growth of the maxilla. This has, however, not been evaluated in the past.

Subjects and Methods

This study was a prospective, case–control study. This included 32 patients, aged between 19 and 25 years, who were divided into cleft and non-cleft groups. The cleft group was further divided into unilateral clefts, bilateral clefts and isolated palatal clefts. In both groups, the zygoma was assessed and compared on both sides clinically using indirect photogrammetry and radiographically using 3D CT. The results were analyzed statistically using the unpaired t test.

Results

There was a significant difference in the zygomatic projection on cleft and non-cleft sides in the unilateral cleft group. There was no significant difference in the zygomatic projection of both sides in the other subgroups and the control group.

Conclusion

The present study shows that there is a global effect of palato-alveolar cleft repair on the midfacial skeleton. Further studies are required to correlate the impact of age, gender and the technique of palato-alveolar cleft repair with the quantum of malar hypoplasia.



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First in human evaluation of the vascular biocompatibility and biomechanical performance of a novel ultra high molecular weight amorphous PLLA bioresorbable scaffold in the absence of anti-proliferative drugs: Two-year imaging results in humans

Abstract

Objectives

In this first-in-human study, we prospectively studied the vascular compatibility and mechanical performance of a novel bare ultra-high molecular weight amorphous PLLA bioresorbable scaffold (BRS, FORTITUDE®, Amaranth Medical, Mountain View, California) up to two years after implantation using multimodality imaging techniques.

Background

The vascular biocompatibility of polymers used in BRS has not been fully characterized in the absence of anti-proliferative drugs.

Methods

A total of 10 patients undergoing single scaffold implantation were included in the final analysis and were followed up using optical coherence tomography (OCT) at 2-years. All devices were implanted under angiographic and intravascular ultrasound (IVUS) guidance. Angiographic and IVUS follow up was performed at 6 months. Additionally, angiography and OCT imaging were performed at 2-years.

Results

At 6 months, mean intra-scaffold angiographic MLD slightly decreased from baseline procedural values. However, at 2 years, mean angiographic MLD increased (post procedure; 2.9 [2.7, 3.1] mm vs. 6 months; 2.1 [1.6, 2.5] vs. 2 years; 2.4 [2.1, 2.6], P = .001). Also, angiographic percent diameter stenosis decreased and late lumen gain increased between 6 months and 2 years follow up. Mean neointimal hyperplasia volume assessed by IVUS at 6 months was 26% [15.2, 29.3]. At 2 years OCT follow up neointimal hyperplasia volume was 24.2% [19.4, 28.9]. No presence of neoatherosclerosis was identified in any of the analyzed cases.

Conclusion

At 2 years, this novel PLLA-based BRS induced expansive vascular remodeling from 6 to 24 months, a biological phenomenon that appears to be independent of the presence of anti-proliferative drugs.



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rCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer’s disease after 18 months of treatment with the cholinesterase inhibitors donepezil or galantamine

Abstract

Late-onset Alzheimer’s disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.



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Work-related social support modulates effects of early life stress on limbic reactivity during stress

Abstract

Early life stress (ELS) affects stress- reactivity via limbic brain regions implicated such as hippocampus and amygdala. Social support is a major protective factor against ELS effects, while subjects with ELS experience reportedly perceive less of it in their daily life. The workplace, where most adults spend a substantial amount of time in their daily lives, might serve as a major resource for social support. Since previous data demonstrated that social support attenuates stress reactivity, we here used a psychosocial stress task to test the hypothesis that work-related social support modulates the effects of ELS. Results show decreased amygdala reactivity during stress in ELS subjects who report high levels of work- related social support, thereby indicating a signature for reduced stress reactivity. However, this effect was only observable on the neural, but not on the behavioral level, since social support had no buffering effect regarding the subjective experience of stress in daily life as well as regarding feelings of uncontrollability induced by the stress task. Accordingly, our data suggest that subjects with ELS experiences might benefit from interventions targeted at lowering their subjective stress levels by helping them to better perceive the availability of social support in their daily lives.



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Predicting calvarial growth in normal and craniosynostotic mice using a computational approach

Abstract

During postnatal calvarial growth the brain grows gradually and the overlying bones and sutures accommodate that growth until the later juvenile stages. The whole process is coordinated through a complex series of biological, chemical and perhaps mechanical signals between various elements of the craniofacial system. The aim of this study was to investigate to what extent a computational model can accurately predict the calvarial growth in wild-type (WT) and mutant type (MT) Fgfr2C342Y/+ mice displaying bicoronal suture fusion. A series of morphological studies were carried out to quantify the calvarial growth at P3, P10 and P20 in both mouse types. MicroCT images of a P3 specimen were used to develop a finite element model of skull growth to predict the calvarial shape of WT and MT mice at P10. Sensitivity tests were performed and the results compared with ex vivo P10 data. Although the models were sensitive to the choice of input parameters, they predicted the overall skull growth in the WT and MT mice. The models also captured the difference between the ex vivoWT and MT mice. This modelling approach has the potential to be translated to human skull growth and to enhance our understanding of the different reconstruction methods used to manage clinically the different forms of craniosynostosis, and in the long term possibly reduce the number of re-operations in children displaying this condition and thereby enhance their quality of life.



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