Primary Thyroid Gland Alveolar Soft Part Sarcoma

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor of unknown histogenesis generally characterized by the der(17)t(X;17)(p11.2;q25) translocation which results in the ASPSCR1-TFE3 gene fusion. Primary ASPS of the thyroid gland has not yet been reported. During oncology follow-up for breast cancer, a pulmonary nodule and thyroid gland mass were identified in a 71-year-old Korean male. Thyroid ultrasound showed a 5.7 cm left thyroid gland mass. After several fine needle aspirations, a thyroid gland lobectomy was performed after documenting only non-caseating granulomatous inflammation in a biopsy of the lung nodule. A 7.6 cm bulging nodular thyroid gland mass was identified, showing significant destructive invasion. Alveolar nests of large polygonal, eosinophilic, granular neoplastic cells were separated by vascularized stroma. Colloid was absent. Tumor necrosis and increased mitoses were identified. The neoplastic cells were positive with TFE3 and CD68, but negative with pancytokeratin, thyroglobulin, TTF-1, napsin-A, calcitonin, PAX8, CAIX, S100 protein, HMB45, SMA, and desmin. FISH confirmed a TFE3 gene rearrangement. The differential includes several primary thyroid gland epithelial neoplasms, paraganglioma, PEComa, melanoma, crystal storage disease, and metastatic carcinomas, especially Xp11 translocation renal cell carcinoma. The patient has refused additional therapy, but is alive without tumor identified (primary or metastatic)

Machine learning methods for automated classification of tumors with papillary thyroid carcinoma-like nuclei : A quantitative analysis

When approaching thyroid gland tumor classification, the differentiation between samples with and without “papillary thyroid carcinoma-like” nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen’s Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen’s Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen’s Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen’s Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets

Evaluation of Sample Design and Estimation Methods for Great Lakes Angler Surveys

The waters of the Great Lakes support outstanding recreational fishing opportunities. Total catch and effort estimates obtained from on‐site angler surveys are essential for the management of the recreational fisheries. However, quality of angler survey estimates can be greatly affected by the survey design and estimation approaches used. Using Monte Carlo simulation techniques, we evaluated the effects of two potential sources of bias (disproportional sampling of angler trips and subsampling of the fishing day) on two catch estimators: (1) a multiple‐day estimator that ignores day effects and pools the angler trip data over a multiple‐day period, and (2) a daily estimator that treats the trip data in each day separately. When catch rates are constant among different time periods of the fishing day, the daily estimator produces total catch estimates with little bias, whereas the multiple‐day estimator is prone to bias caused by disproportional sampling of angler trips. When catch rates vary among different periods of a fishing day, the daily estimator produces biased estimates of total catch when the fishing day is subsampled, whereas the multiple‐day estimator is less affected by the variation in daily time‐period catch rates and subsampling of fishing days. Quality of total catch and effort estimates, in terms of root mean square error and coverage probability of confidence intervals, is poor when the number of days sampled each month is low and fishing days are subsampled.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141929/1/tafs0234.pd

Developing Classifications of Laryngeal Dysplasia: The Historical Basis

During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.Peer reviewe

Spectrophotometric Distances to Galactic H\,{\sc{ii}} Regions

We present a near infrared study of the stellar content of 35 H\,{\sc{ii}} regions in the Galactic plane. In this work, we have used the near infrared domain $J-$, $H-$ and $K_{s}-$ band color images to visually inspect the sample. Also, color-color and color-magnitude diagrams were used to indicate ionizing star candidates, as well as, the presence of young stellar objects such as classical TTauri Stars (CTTS) and massive young stellar objects (MYSOs). We have obtained {\it Spitzer} IRAC images for each region to help further characterize them. {\it Spitzer} and near infrared morphology to place each cluster in an evolutionary phase of development. {\it Spitzer} photometry was also used to classify the MYSOs. Comparison of the main sequence in color-magnitude diagrams to each observed cluster was used to infer whether or not the cluster kinematic distance is consistent with brightnesses of the stellar sources. We find qualitative agreement for a dozen of the regions, but about half the regions have near infrared photometry that suggests they may be closer than the kinematic distance. A significant fraction of these already have spectrophotometric parallaxes which support smaller distances. These discrepancies between kinematic and spectrophotometric distances are not due to the spectrophotometric methodologies, since independent non-kinematic measurements are in agreement with the spectrophotometric results. For instance, trigonometric parallaxes of star-forming regions were collected from the literature and show the same effect of smaller distances when compared to the kinematic results. In our sample of H\,{\sc{ii}} regions, most of the clusters are evident in the near infrared images. Finally, it is possible to distinguish among qualitative evolutionary stages for these objects.Comment: 59 pages, 146 figures and 4 tables. MNRAS accepte

MAKING ANIMALS ALCOHOLIC: SHIFTING LABORATORY MODELS OF ADDICTION

The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp

Placental 11-Beta Hydroxysteroid Dehydrogenase Methylation Is Associated with Newborn Growth and a Measure of Neurobehavioral Outcome

Background: There is growing evidence that the intrauterine environment can impact the neurodevelopment of the fetus through alterations in the functional epigenome of the placenta. In the placenta, the HSD11B2 gene encoding the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol, is regulated by DNA methylation, and has been shown to be susceptible to stressors from the maternal environment. Methodology/Principal Findings: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 185 healthy newborn infants and infant and maternal characteristics, as well as the association between this epigenetic variability and newborn neurobehavioral outcome assessed with the NICU Network Neurobehavioral Scales. Controlling for confounders, HSD11B2 methylation extent is greatest in infants with the lowest birthweights (P = 0.04), and this increasing methylation was associated with reduced scores of quality of movement (P = 0.04). Conclusions/Significance: These results suggest that factors in the intrauterine environment which contribute to birth outcome may be associated with placental methylation of the HSD11B2 gene and that this epigenetic alteration is in turn associated with a prospectively predictive early neurobehavioral outcome, suggesting in some part a mechanism for th

Ligand Activation of the Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC

While the pentameric ligand-gated ion channel ELIC has recently provided first insight into the architecture of the family at high resolution, its detailed investigation was so far prevented by the fact that activating ligands were unknown. Here we describe a study on the functional characterization of ELIC by electrophysiology and X-ray crystallography. ELIC is activated by a class of primary amines that include the neurotransmitter GABA at high micro- to millimolar concentrations. The ligands bind to a conserved site and evoke currents that slowly desensitize over time. The protein forms cation selective channels with properties that resemble the nicotinic acetylcholine receptor. The high single channel conductance and the comparably simple functional behavior make ELIC an attractive model system to study general mechanisms of ion conduction and gating in this important family of neurotransmitter receptors