bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains
Authors: Kronfeld Andrea , Buchholz Hans‐Georg , Maus Stephan , Reuss Stefan , Müller‐Forell Wibke , Lutz Beat , Schreckenberger Mathias , Miederer Isabelle 
Published: November 2015

Purpose:Image registration is one prerequisite for the analysis of brain regions in magnetic‐resonance‐imaging (MRI) or positron‐emission‐tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms.Methods:Five male Sprague Dawley rats were investigated for template construction using MRI and [18F]MK‐9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back‐projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates.Results:The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI‐based spatial normalization was most accurate, but results of the PET‐based spatial normalization were quite comparable.Conclusions:Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL templates together with nonlinear registration algorithms allows for accurate spatial normalization of combined MRI/PET or PET‐only studies.
TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry
Authors: Garcia Marie‐Paule , Villoing Daphnée , McKay Erin , Ferrer Ludovic , Cremonesi Marta , Botta Francesca , Ferrari Mahila , Bardiès Manuel 
Published: November 2015

Purpose:The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols.Methods:The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of a given radiopharmaceutical in each defined compartment at various time‐points. The Monte Carlo simulation toolkit gate offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on gate to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user's imaging requirements and generates automatically command files used as input for gate. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant gate input files are generated for the virtual patient model and associated pharmacokinetics.Results:Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole‐body “step and shoot” acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry computation performed on the ICRP 110 model is also presented.Conclusions:The proposed platform offers a generic framework to implement any scintigraphic imaging protocols and voxel/organ‐based dosimetry computation. Thanks to the modular nature of TestDose, other imaging modalities could be supported in the future such as positron emission tomography.
Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations
Authors: Bojechko C. , Ford E. C. 
Published: November 2015

Purpose:To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment.Methods:Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram.Results:Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D99 change <7%]. Larger variations have even higher detectability. Displacements in the patient's position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D99 of the PTV changed by up to 57% for the patient position shifts considered here.Conclusions:In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC's, and changes in the patient habitus. Shifts in the patient's position which can introduce large changes in the target dose coverage were not readily detected.
Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on‐treatment EPID images and a model‐based forward‐calculation algorithm
Authors: Van Uytven Eric , Van Beek Timothy , McCowan Peter M. , Chytyk‐Praznik Krista , Greer Peter B. , McCurdy Boyd M. C. 
Published: November 2015

Purpose:Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model‐based technique to compute full three‐dimensional patient dose reconstructed from on‐treatment EPID portal images (i.e., transmission images).Methods:EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back‐projecting the primary source component of the EPID fluence upstream of the patient. Incident fluence is then recombined with predicted extra‐focal fluence and used to calculate 3D patient dose via a collapsed‐cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT).Results:Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build‐up region).Conclusions:An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient data sets, as well as for dynamic IMRT and VMAT delivery techniques. Results indicate that the EPID dose reconstruction algorithm presented in this work is suitable for clinical implementation.
The Effectiveness of Open Repair Versus Percutaneous Repair for an Acute Achilles Tendon Rupture
Authors: Krueger Heidi , David Shannon 
Published: November 2015

Clinical Scenario:There are 2 approaches available for surgical repair of the Achilles tendon: open or percutaneous. However, there is controversy over which repair is superior.Focused Clinical Question:Which type of surgery is better in providing the best overall patient outcome, open or percutaneous repair, in physically active men and women with acute Achilles tendon ruptures?Summary of Search, “Best Evidence” Appraised, and Key Findings:The literature was searched for studies of level 3 evidence or higher that investigated the effectiveness of open repair versus percutaneous repair on acute Achilles tendon ruptures in physically active men and women. The literature search resulted in 3 studies for possible inclusion. All 3 good-quality studies were included.Clinical Bottom Line:There is supporting evidence to indicate that percutaneous repair is the best option for Achilles tendon surgery when it comes to the physically active population. Percutaneous repair has faster surgery times, less risk of complications, and faster recovery times over having an open repair, although it is acknowledged that every patient has a different situation and best individual option may vary patient to patient.
Chlamydial Lytic Exit from Host Cells Is Plasmid Regulated
Authors: Yang Chunfu , Starr Tregei , Song Lihua , Carlson John H. , Sturdevant Gail L. , Beare Paul A. , Whitmire William M. , Caldwell Harlan D. 
Published: November 2015

ABSTRACT

Chlamydia trachomatis
is an obligate intracellular bacterium that is a globally important human pathogen. The chlamydial plasmid is an attenuating virulence factor, but the molecular basis for attenuation is not understood. Chlamydiae replicate within a membrane-bound vacuole termed an inclusion, where they undergo a biphasic developmental growth cycle and differentiate from noninfectious into infectious organisms. Late in the developmental cycle, the fragile chlamydia-laden inclusion retains its integrity by surrounding itself with scaffolds of host cytoskeletal proteins. The ability of chlamydiae to developmentally free themselves from this cytoskeleton network is a fundamental virulence trait of the pathogen. Here, we show that plasmidless chlamydiae are incapable of disrupting their cytoskeletal entrapment and remain intracellular as stable mature inclusions that support high numbers of infectious organisms. By using deletion mutants of the eight plasmid-carried genes (Δ
pgp1
to Δ
pgp8
), we show that Pgp4, a transcriptional regulator of multiple chromosomal genes, is required for exit. Exit of chlamydiae is dependent on protein synthesis and is inhibited by the compound C1, an inhibitor of the type III secretion system (T3S). Exit of plasmid-free and Δ
pgp4
organisms, which failed to lyse infected cells, was rescued by latrunculin B, an inhibitor of actin polymerization. Our findings describe a genetic mechanism of chlamydial exit from host cells that is dependent on an unknown
pgp4
-regulated chromosomal T3S effector gene.

IMPORTANCE
Chlamydia's obligate intracellular life style requires both entry into and exit from host cells. Virulence factors that function in exiting are unknown. The chlamydial inclusion is stabilized late in the infection cycle by F-actin. A prerequisite of chlamydial exit is its ability to disassemble actin from the inclusion. We show that chlamydial plasmid-free organisms, and also a plasmid gene protein 4 (
pgp4
) null mutant, do not disassociate actin from the inclusion and fail to exit cells. We further provide evidence that Pgp4-regulated exit is dependent on the chlamydial type III secretion system. This study is the first to define a genetic mechanism that functions in chlamydial lytic exit from host cells. The findings also have practical implications for understanding why plasmid-free chlamydiae are highly attenuated and have the ability to elicit robust protective immune responses.
Riboflavin Provisioning Underlies
Wolbachia
's Fitness Contribution to Its Insect Host
Authors: Moriyama Minoru , Nikoh Naruo , Hosokawa Takahiro , Fukatsu Takema 
Published: November 2015

ABSTRACT

Endosymbiotic bacteria of the genus
Wolbachia
represent the most successful symbiotic bacteria in the terrestrial ecosystem. The success of
Wolbachia
has been ascribed to its remarkable phenotypic effects on host reproduction, such as cytoplasmic incompatibility, whereby maternally inherited bacteria can spread in their host populations at the expense of their host's fitness. Meanwhile, recent theoretical as well as empirical studies have unveiled that weak and/or conditional positive fitness effects may significantly facilitate invasion and spread of
Wolbachia
infections in host populations. Here, we report a previously unrecognized nutritional aspect, the provision of riboflavin (vitamin B
2
), that potentially underpins the
Wolbachia
-mediated fitness benefit to insect hosts. A comparative genomic survey for synthetic capability of B vitamins revealed that only the synthesis pathway for riboflavin is highly conserved among diverse insect-associated
Wolbachia
strains, while the synthesis pathways for other B vitamins were either incomplete or absent. Molecular phylogenetic and genomic analyses of riboflavin synthesis genes from diverse
Wolbachia
strains revealed that, in general, their phylogenetic relationships are concordant with
Wolbachia
's genomic phylogeny, suggesting that the riboflavin synthesis genes have been stably maintained in the course of
Wolbachia
evolution. In rearing experiments with bedbugs (
Cimex lectularius
) on blood meals in which B vitamin contents were manipulated, we demonstrated that
Wolbachia
's riboflavin provisioning significantly contributes to growth, survival, and reproduction of the insect host. These results provide a physiological basis upon which
Wolbachia
-mediated positive fitness consequences are manifested and shed new light on the ecological and evolutionary relevance of
Wolbachia
infections.

IMPORTANCE
Conventionally,
Wolbachia
has been regarded as a parasitic bacterial endosymbiont that manipulates the host insect's reproduction in a selfish manner, which tends to affect a host's fitness negatively. Meanwhile, some theories predict that, at the same time,
Wolbachia
can directly affect the host's fitness positively, which may potentially reconcile the negative effect and facilitate spread and stability of the symbiotic association. Here we demonstrate, by using comparative genomic and experimental approaches, that among synthetic pathways for B vitamins, the synthetic pathway for riboflavin (vitamin B
2
) is exceptionally conserved among diverse insect-associated
Wolbachia
strains, and
Wolbachia
's riboflavin provisioning certainly contributes to growth, survival, and reproduction in an insect. These findings uncover a nutritional mechanism of a
Wolbachia
-mediated fitness benefit, which provides empirical evidence highlighting a “Jekyll and Hyde” aspect of
Wolbachia
infection.
Probing the Viromic Frontiers
Authors: Rasmussen Angela L. 
Published: November 2015

ABSTRACT

Modern molecular technology, and particularly high-throughput sequencing (HTS), has revolutionized virus discovery and expanded the depth and breadth of the virome. Recent HTS was used to identify and discover a previously undescribed member of the family
Flaviviridae
that has genomic features characteristic of both hepaciviruses and pegiviruses. This virus, designated human hepegivirus-1 (HHpgV-1), may represent a previously undescribed new genus in the
Flaviviridae
family with implications for public health and blood supply safety. Detecting uncharacterized viruses such as HHpgV-1 in clinical samples requires an unbiased screening method that is as sensitive as PCR, while simultaneously detecting multiple rare viral sequences. The virome-capture-sequencing platform for vertebrate viruses (VirCapSeq-VERT) uses positive-selection oligonucleotide capture to sensitively detect sequences from every known vertebrate virus, even in high-background specimens with low-abundance viruses. VirCapSeq-VERT can also detect uncharacterized viruses with sequence homology to known viruses, enabling a new paradigm for virus detection.
p73 and IGF1R Regulate Emergence of Aggressive Cancer Stem–like Features via miR-885-5p Control
Authors: Meier Claudia , Hardtstock Philip , Joost Sophie , Alla Vijay , Pützer Brigitte M. 
Published: November 2015

Abstract
Cancer stem–like cells (CSC) have been proposed to promote cancer progression by initiating tumor growth at distant sites, suggesting that stem-like cell features can support metastatic efficiency. Here, we demonstrate that oncogenic DNp73, a dominant-negative variant of the tumor-suppressor p73, confers cancer cells with enhanced stem-like properties. DNp73 overexpression in noninvasive melanoma and lung cancer cells increased anchorage-independent growth and elevated the expression of the pluripotency factors CD133, Nanog, and Oct4. Conversely, DNp73 depletion in metastatic cells downregulated stemness genes, attenuated sphere formation and reduced the tumor-initiating capability of spheroids in tumor xenograft models. Mechanistic investigations indicated that DNp73 acted by attenuating expression of miR-885-5p, a direct regulator of the IGF1 receptor (IGF1R) responsible for stemness marker expression. Modulating this pathway was sufficient to enhance chemosensitivity, overcoming DNp73-mediated drug resistance. Clinically, we established a correlation between low p73 function and high IGF1R/CD133/Nanog/Oct4 levels in melanoma specimens that associated with reduced patient survival. Our work shows how DNp73 promotes cancer stem–like features and provides a mechanistic rationale to target the DNp73–IGF1R cascade as a therapeutic strategy to eradicate CSC. Cancer Res; 76(2); 197–205. ©2015 AACR.
The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer
Authors: Möller Sören , Mucci Lorelei A. , Harris Jennifer R. , Scheike Thomas , Holst Klaus , Halekoh Ulrich , Adami Hans-Olov , Czene Kamila , Christensen Kaare , Holm Niels V. , Pukkala Eero , Skytthe Axel , Kaprio Jaakko , Hjelmborg Jacob B. 
Published: November 2015

Abstract
Background: Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear.
Methods: We estimated the familial concordance and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death.
Results: From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose co-twins had breast cancer was 28% among monozygotic and 20% among dizygotic twins. The heritability of liability to breast cancer was 31% [95% confidence interval (CI), 10%–51%] and the common environmental component was 16% (95% CI, 10%–32%). For premenopausal breast cancer these estimates were 27% and 12%, respectively, and for postmenopausal breast cancer 22% and 16%, respectively. The relative contributions of genetic and environmental factors were constant between ages 50 and 96. Our results are compatible with the Peto–Mack hypothesis.
Conclusion: Our findings indicate that familial factors explain almost half of the variation in liability to develop breast cancer, and results were similar for pre- and postmenopausal breast cancer
Impact: We estimate heritability of breast cancer, taking until now ignored sources of bias into account. Cancer Epidemiol Biomarkers Prev; 25(1); 145–50. ©2015 AACR.
Predictors of Stroke After Transient Ischemic Attack in Children
Authors: Lehman Laura L. , Watson Christopher G. , Kapur Kush , Danehy Amy R. , Rivkin Michael J. 
Published: November 2015

Background and Purpose—
Transient ischemic attack (TIA) in children has received far less attention compared with TIA in adults. The risk factors of stroke after TIA in children are relatively unknown. We aimed to determine the percentage of children who have stroke after TIA and the risk factors associated with stroke after TIA.

Methods—
We searched the medical records at Boston Children’s Hospital for the year 2010 to find children who were evaluated for TIA to determine associated risk factors of stroke after TIA. We included children who were evaluated in 2009 through 2010 for TIA and had magnetic resonance imaging. We examined follow-up imaging through August 2014 for subsequent stroke. Logistic regression was used to calculate odds ratios for factors in our cohort who are associated with stroke after presentation with TIA.

Results—
We identified 63 children who experienced a TIA. The mean time of imaging follow-up was 4.5 years after TIA presentation. Of the 63 children, 10 (16%) developed radiological evidence of ischemic cerebral injury within the follow-up period. Four of the 10 (6%) demonstrated diffusion abnormalities on magnetic resonance imaging at TIA presentation, whereas 8 (13%) had a stroke after their TIA. Arteriopathy, female sex, and autoimmune disorders were significantly associated with stroke after TIA.

Conclusions—
In our cohort of children, stroke occurred after TIA at a rate similar to that seen in adults, but the risk factors for stroke after TIA in children are different.