bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and validation of an MR‐conditional robot for transcranial focused ultrasound surgery in infants
Authors: Price Karl D. , Sin Vivian W. , Mougenot Charles , Pichardo Samuel , Looi Thomas , Waspe Adam C. , Drake James M. 
Published: August 2016

Purpose:Current treatment of intraventricular hemorrhage (IVH) involves cerebral shunt placement or an invasive brain surgery. Magnetic resonance‐guided focused ultrasound (MRgFUS) applied to the brains of pediatric patients presents an opportunity to treat IVH in a noninvasive manner, termed “incision‐less surgery.” Current clinical and research focused ultrasound systems lack the capability to perform neonatal transcranial surgeries due to either range of motion or dexterity requirements. A novel robotic system is proposed to position a focused ultrasound transducer accurately above the head of a neonatal patient inside an MRI machine to deliver the therapy.Methods:A clinical Philips Sonalleve MRgFUS system was expanded to perform transcranial treatment. A five degree‐of‐freedom MR‐conditional robot was designed and manufactured using MR compatible materials. The robot electronics and control were integrated into existing Philips electronics and software interfaces. The user commands the position of the robot with a graphical user interface, and is presented with real‐time MR imaging of the patient throughout the surgery. The robot is validated through a series of experiments that characterize accuracy, signal‐to‐noise ratio degeneration of an MR image as a result of the robot, MR imaging artifacts generated by the robot, and the robot's ability to operate in a representative surgical environment inside an MR machine.Results:Experimental results show the robot responds reliably within an MR environment, has achieved 0.59 ± 0.25 mm accuracy, does not produce severe MR‐imaging artifacts, has a workspace providing sufficient coverage of a neonatal brain, and can manipulate a 5 kg payload. A full system demonstration shows these characteristics apply in an application environment.Conclusions:This paper presents a comprehensive look at the process of designing and validating a new robot from concept to implementation for use in an MR environment. An MR conditional robot has been designed and manufactured to design specifications. The system has demonstrated its feasibility as a platform for MRgFUS interventions for neonatal patients. The success of the system in experimental trials suggests that it is ready to be used for validation of the transcranial intervention in animal studies.
Color standard display function: A proposed extension of DICOM GSDF
Authors: Kimpe Tom , Rostang Johan , Van Hoey Gert , Xthona Albert 
Published: August 2016

Purpose:Color images are being used more in medical imaging for a broad range of modalities and applications. While in the past, color was mostly used for annotations, today color is also widely being used for diagnostic purposes. Surprisingly enough, there is no agreed upon standard yet that describes how color medical images need to be visualized and how calibration and quality assurance of color medical displays need to be performed. This paper proposes color standard display function (CSDF) which is an extension of the DICOM GSDF standard toward color. CSDF defines how color medical displays need to be calibrated and how QA can be performed to obtain perceptually linear behavior not only for grayscale but also for color.Methods:The proposed CSDF algorithm uses DICOM GSDF calibration as a starting point and subsequently uses a color visual difference metric to redistribute colors in order to obtain perceptual linearity not only for the grayscale behavior but also for the color behavior. A clear calibration and quality assurance algorithm is defined and is validated on a wide range of different display systems.Results:A detailed description of the proposed CSDF calibration and quality assurance algorithms is provided. These algorithms have been tested extensively on three types of display systems: consumer displays, professional displays, and medical grade displays. Test results are reported both for the calibration algorithm as well as for the quantitative and visual quality assurance methods. The tests confirm that the described algorithm generates consistent results and is able to increase perceptual linearity for color and grayscale visualization. Moreover the proposed algorithms are working well on a wide range of display systems.Conclusions:CSDF has been proposed as an extension of the DICOM GSDF standard toward color. Calibration and QA algorithms for CSDF have been described in detail. The proposed algorithms have been tested on several types of display systems and the results confirm that CSDF largely increases the perceptual linearity of visualized colors, while at the same time remaining compliant with DICOM GSDF.
Molecular Diagnostic Testing for Aspergillus
Authors: Powers-Fletcher Margaret V. , Hanson Kimberly E. 
Published: August 2016

ABSTRACT

The direct detection of
Aspergillus
nucleic acid in clinical specimens has the potential to improve the diagnosis of aspergillosis by offering more rapid and sensitive identification of invasive infections than is possible with traditional techniques, such as culture or histopathology. Molecular tests for
Aspergillus
have been limited historically by lack of standardization and variable sensitivities and specificities. Recent efforts have been directed at addressing these limitations and optimizing assay performance using a variety of specimen types. This review provides a summary of standardization efforts and outlines the complexities of molecular testing for
Aspergillus
in clinical mycology.
A Novel SimpleProbe PCR Assay for Detection of Mutations in the 23S rRNA Gene Associated with Macrolide Resistance in Mycoplasma genitalium in Clinical Samples
Authors: Gossé Marianne , Lysvand Hilde , Pukstad Brita , Nordbø Svein Arne 
Published: August 2016

ABSTRACT

Macrolide-resistant strains of
Mycoplasma genitalium
are an increasing problem throughout the world, and the implementation of a rapid and sensitive assay for mutation detection to guide treatment is needed. Macrolide-resistant strains have been shown to contain base substitutions in positions 2058 and 2059 (
Escherichia coli
numbering) in region V of the 23S rRNA gene. In this study, we present a SimpleProbe PCR followed by melting curve analysis to differentiate between macrolide-resistant mutants and wild types. The assay was performed on 159
Mycoplasma genitalium
-positive samples, and the results were compared with DNA sequencing. We also looked at the prevalence of macrolide-resistant strains in a Norwegian population. Of 139 samples characterized successfully by sequencing, 54 (39%) were wild types and 85 (61%) were mutants, consisting of 59 (42%) A2059G, 24 (17%) A2058G, 1 (1%) A2058T, and 1 (1%) A2059C mutation. The melting curve analysis correctly differentiated between wild-type and mutant strains in all cases, but it could not identify the different mutant types. The SimpleProbe PCR proved to be a simple, rapid, and reliable method for the detection of macrolide-resistant isolates of
Mycoplasma genitalium
in a clinical setting.
Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus
Authors: Chan Che-Man , Chu Hin , Wang Yixin , Wong Bosco Ho-Yin , Zhao Xiaoyu , Zhou Jie , Yang Dong , Leung Sze Pui , Chan Jasper Fuk-Woo , Yeung Man-Lung , Yan Jinghua , Lu Guangwen , Gao George Fu , Yuen Kwok-Yung 
Published: August 2016

ABSTRACT
The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface.

IMPORTANCE
Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The identification of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV advanced our knowledge on the cell binding biology of MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by functioning as an attachment factor. In this regard, CEACAM5 could serve as a novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of antiviral strategies for MERS-CoV.
Neuroinvasion of α-Synuclein Prionoids after Intraperitoneal and Intraglossal Inoculation
Authors: Breid Sara , Bernis Maria E. , Babila Julius T. , Garza Maria C. , Wille Holger , Tamgüney Gültekin 
Published: August 2016

ABSTRACT

α-Synuclein is a soluble, cellular protein that in a number of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy, forms pathological deposits of protein aggregates. Because misfolded α-synuclein has some characteristics that resemble those of prions, we investigated its potential to induce disease after intraperitoneal or intraglossal challenge injection into bigenic Tg(M83
+/−
:
Gfap
-luc
+/−
) mice, which express the A53T mutant of human α-synuclein and firefly luciferase. After a single intraperitoneal injection with α-synuclein fibrils, four of five mice developed paralysis and α-synuclein pathology in the central nervous system, with a median incubation time of 229 ± 17 days. Diseased mice accumulated aggregates of Sarkosyl-insoluble and phosphorylated α-synuclein in the brain and spinal cord, which colocalized with ubiquitin and p62 and were accompanied by gliosis. In contrast, only one of five mice developed α-synuclein pathology in the central nervous system after intraglossal injection with α-synuclein fibrils, after 285 days. These findings are novel and important because they show that, similar to prions, α-synuclein prionoids can neuroinvade the central nervous system after intraperitoneal or intraglossal injection and can cause neuropathology and disease.

IMPORTANCE
Synucleinopathies are neurodegenerative diseases that are characterized by the pathological presence of aggregated α-synuclein in cells of the nervous system. Previous studies have shown that α-synuclein aggregates made of recombinant protein or derived from brains of patients can spread in the central nervous system in a spatiotemporal manner when inoculated into the brains of animals and can induce pathology and neurologic disease, suggesting that misfolded α-synuclein can behave similarly to prions. Here we show that α-synuclein inoculation into the peritoneal cavity or the tongue in mice overexpressing α-synuclein causes neurodegeneration after neuroinvasion from the periphery, which further corroborates the prionoid character of misfolded α-synuclein.
Long-term changes in the heat–mortality relationship according to heterogeneous regional climate: a time-series study in South Korea
Authors: Heo Seulkee , Lee Eunil , Kwon Bo Yeon , Lee Suji , Jo Kyung Hee , Kim Jinsun 
Published: August 2016

ObjectivesSeveral studies identified a heterogeneous impact of heat on mortality in hot and cool regions during a fixed period, whereas less evidence is available for changes in risk over time due to climate change in these regions. We compared changes in risk during periods without (1996–2000) and with (2008–2012) heatwave warning forecasts in regions of South Korea with different climates.MethodsStudy areas were categorised into 3 clusters based on the spatial clustering of cooling degree days in the period 1993–2012: hottest cluster (cluster H), moderate cluster (cluster M) and cool cluster (cluster C). The risk was estimated according to increases in the daily all-cause, cardiovascular and respiratory mortality per 1°C change in daily temperature above the threshold, using a generalised additive model.ResultsThe risk of all types of mortality increased in cluster H in 2008–2012, compared with 1996–2000, whereas the risks in all-combined regions and cooler clusters decreased. Temporal increases in mortality risk were larger for some vulnerable subgroups, including younger adults (<75 years), those with a lower education and blue-collar workers, in cluster H as well as all-combined regions. Different patterns of risk change among clusters might be attributable to large increases in heatwave frequency or duration during study periods and the degree of urbanisation in cluster H.ConclusionsPeople living in hotter regions or with a lower socioeconomic status are at higher risk following an increasing trend of heat-related mortality risks. Continuous efforts are needed to understand factors which affect changes in heat-related mortality risks.
Does a mandibular overdenture improve nutrient intake and markers of nutritional status better than conventional complete denture? A systematic review and meta-analysis
Authors: Yamazaki Toru , Martiniuk Alexandra LC , Irie Koichiro , Sokejima Shigeru , Lee Crystal Man Ying 
Published: August 2016

ObjectivesThe need for denture treatment in public health will increase as the population ages. However, the impact of dentures on nutrition, particularly overdenture treatment, remains unclear although the physical and psychological effects are known. We investigated whether treatment with a mandibular implant supported overdenture improves nutrient intake and markers of nutritional status better than a conventional complete denture in edentulous patients.DesignSystematic review and meta-analysis.MethodsMedline, EMBASE and the Cochrane Central Register of Controlled Trials were searched for eligible studies published up to April 2016. We included studies which compared the treatment effect of an overdenture to conventional denture on nutrition, in which primary outcomes included changes in intake of macronutrients and/or micronutrients and/or indicators of nutritional status. Two reviewers independently evaluated eligible studies and assessed the risk of bias. We used a fixed effects model to estimate the weighted mean difference (WMD) and 95% CI for change in body mass index (BMI), albumin and serum vitamin B12 between overdenture and conventional denture 6 months after treatment.ResultsOf 108 eligible studies, 8 studies involving 901 participants were included in the narrative appraisal. Four studies reported changes in markers of nutritional status and nutrient intake after treatment with a prosthetic, regardless of type. In a meta-analysis of 322 participants aged 65 years or older from three studies, pooled analysis suggested no significant difference in change in BMI between an overdenture and conventional denture 6 months after treatment (WMD=−0.18 kg/m2(95% CI −0.52 to 0.16)), and no significant difference in change in albumin or vitamin B12 between the two treatments.ConclusionsThe modifying effect of overdenture treatment on nutritional status might be limited. Further studies are needed to evaluate the effectiveness and efficacy of denture treatments.
The global
Annulata
Events: review and new data from the Rheris Basin (northern Tafilalt) of SE Morocco
Authors: Hartenfels S. , Becker R. T. 
Published: August 2016

Abstract

A review of the literature shows that the Famennian global
Annulata
Event(s) can be recognized as a transgressive, often hypoxic and eutrophic, interval that interrupts an overall regressive eustatic trend in more than 40 regions of North America, Europe, North Africa, Asia and Australia. According to differences in palaeogeography, sedimentology and biota, these occurrences are assigned to 10 event settings. The first detailed data on facies, ammonoid and conodont faunas are presented for the Rheris Basin of the eastern Anti-Atlas (southern Morocco) and compared with previously studied sections of the adjacent Tafilalt Platform, Tafilalt Basin and Maider Basin. The rather argillaceous succession at El Gara resembles the Tafilalt Basin (Hassi Nebech section) in its lack of black shales/limestones and similar ammonoid and conodont assemblages. However, the
Sulcoclymenia sulcata
Zone (Upper Devonian III-C2) below the
Annulata
Events contains ammonoid taxa that are unique for all of the Anti-Atlas and North Africa:
Protornoceras ornatum
Dybczynski, 1913,
Genuclymenia
aff.
angelini
(Wedekind, 1908),
Protactoclymenia
aff.
implana
(Czarnocki, 1989) and ?
Pleuroclymenia
sp. juv. The first regional record of the marker conodont
Pseudopolygnathus granulosus
Ziegler, 1962 also distinguishes the pre-event assemblage. As in many other regions, there is a major decline in ammonoids well before the Lower
Annulata
Event, which suggests an episode of extreme oligotrophy. Both
Annulata
Events at El Gara are whitish-weathered marly shales with only small specimens of
Platyclymenia
and
Prionoceras
(
sensu lato
), which are also typical for the
annulata
Zone (UD IV-A) of other Tafilalt sections, but benthonic organisms are nearly absent. This suggests local low-oxygen conditions, but only a moderate production of organic carbon, insufficient for black shale formation, unlike many German sections or in the Maider Basin (section Mrakib). The latter region represents a deeper shelf basin that had much higher productivity and a unique ‘
Gundolficeras
–
Erfoudites
–
Protactoclymenia
–
Stenoclymenia
–
Guerichia
biofacies’ of the Lower
Annulata
Shale. The upper part of the
annulata
Zone at El Gara is characterized by
Platyclymenia
(
Platyclymenia
)
levata
n. sp. Other new taxa of the same zone in the Anti-Atlas are
Posttornoceras ascendens
n. sp. and
Stenoclymenia rectangula
n. sp. Whilst the ammonoid faunal overturn between UD III-C and UD IV-A was severe, the strong reduction in conodont diversity with the two
Annulata
Events was mostly (apart from two taxa) a palaeoecologically triggered, only episodic, feature. The comparison of the various Anti-Atlas
Annulata
Event beds and assemblages enables the distinction of event biofacies types, which reflect local differences of bathymetry, trophic conditions and seafloor ventilation.
Annotation of dicom information
Authors: Vizza Patrizia , Cascini Giuseppe Lucio , Curia Rosario , Sisca Loredana , Aiello Filippo 
Published: August 2016

Today, the management of medical information is related to specific systems of individual hospital wards and this solution does not allow the integration and portability of these information among clinical structures.
This is a two pages contribution describing a project that aims to define a general purpose system for the management of clinical information in oncology environment based on the annotation of DICOM images. The system integrates different diagnostic sources to support medical decision in care pathways definition and to facilitate the retrieval of information.
Acidosis Acts through HSP90 in a PHD/VHL-Independent Manner to Promote HIF Function and Stem Cell Maintenance in Glioma
Authors: Filatova Alina , Seidel Sascha , Böğürcü Nuray , Gräf Sabine , Garvalov Boyan K. , Acker Till 
Published: August 2016

Abstract
Hypoxia is a common feature of solid tumors, which controls multiple aspects of cancer progression. One important function of hypoxia and the hypoxia-inducible factors (HIF) is the maintenance of cancer stem-like cells (CSC), a population of tumor cells that possess stem cell-like properties and drives tumor growth. Among the changes promoted by hypoxia is a metabolic shift resulting in acidification of the tumor microenvironment. Here, we show that glioma hypoxia and acidosis functionally cooperate in inducing HIF transcription factors and CSC maintenance. We found that these effects did not involve the classical PHD/VHL pathway for HIF upregulation, but instead involved the stress-induced chaperone protein HSP90. Genetic or pharmacologic inactivation of HSP90 inhibited the increase in HIF levels and abolished the self-renewal and tumorigenic properties of CSCs induced by acidosis. In clinical specimens of glioma, HSP90 was upregulated in the hypoxic niche and was correlated with a CSC phenotype. Our findings highlight the role of tumor acidification within the hypoxic niche in the regulation of HIF and CSC function through HSP90, with implications for therapeutic strategies to target CSC in gliomas and other hypoxic tumors. Cancer Res; 76(19); 5845–56. ©2016 AACR.
Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting Cancer Drugs
Authors: Smith Jennifer A. , Slusher Barbara S. , Wozniak Krystyna M. , Farah Mohamed H. , Smiyun Gregoriy , Wilson Leslie , Feinstein Stuart , Jordan Mary Ann 
Published: August 2016

Abstract
Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a “stocking-glove” distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixabepilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves. Antiproliferative concentrations of paclitaxel and ixabepilone significantly inhibited the anterograde transport velocity of mitochondria in neuronal cells, whereas eribulin and vincristine inhibited transport only at significantly higher concentrations. Confirming these observations, anterogradely transported amyloid precursor protein accumulated in ligated sciatic nerves of control and eribulin-treated mice, but not in paclitaxel-treated mice, indicating that paclitaxel inhibited anterograde axonal transport, whereas eribulin did not. Electron microscopy of sciatic nerves of paclitaxel-treated mice showed reduced organelle accumulation proximal to the ligation consistent with inhibition of anterograde (kinesin based) transport by paclitaxel. In contrast, none of the drugs significantly affected retrograde (dynein based) transport in neuronal cells or mouse nerves. Collectively, these results suggest that paclitaxel and ixabepilone, which bind along the lengths and stabilize microtubules, inhibit kinesin-based axonal transport, but not dynein-based transport, whereas the microtubule-destabilizing drugs, eribulin and vincristine, which bind preferentially to microtubule ends, have significantly less effect on all microtubule-based axonal transport. Cancer Res; 76(17); 5115–23. ©2016 AACR.