A comment on a controversial interpretation of an apparent thyroid phenotype in the paintings of Henri Matisse.
Thyroid. 2018 Nov 29;:
Authors: Gemsenjaeger-Mercier E, Gemsenjaeger-Mercier H
Abstract
n.a.
PMID: 30489225 [PubMed - as supplied by publisher]
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European perspective on the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Proceedings of an interactive international symposium.
Thyroid. 2018 Nov 28;:
Authors: Luster M, Aktolun C, Amendoeira I, Barczyński M, Bible KC, Duntas LH, Elisei R, Handkiewicz-Junak D, Hoffmann M, Jarzab B, Leenhardt L, Musholt TJ, Newbold K, Nixon IJ, Smit J, Sobrinho-Simões M, Sosa JA, Tuttle RM, Verburg F, Wartofsky L, Führer-Sakel D
Abstract
BACKGROUND: The American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer (DTC) are highly influential practice recommendations. The latest revision appeared in 2015 ("ATA 2015"). These guidelines were developed predominantly by North American experts. European experts frequently have different perspectives, given epidemiological, technological/methodological, practice organization, and medicolegal differences between the respective regions.
SUMMARY: Divergent viewpoints were the focus of an invited symposium organized by the European Association of Nuclear Medicine involving 17 European thyroidologists, 4 ATA Guidelines Taskforce members, and an audience of 200 international experts. The group discussed "preoperative assessment of thyroid nodules," "surgery and role of pathology," "radioiodine therapy (RAIT)," "assessment of initial therapy and dynamic risk stratification," and "treatment of persistent disease, recurrences, and advanced thyroid cancer." The dialogue resulted in this position paper contrasting European and ATA 2015 perspectives on key issues. One difference pertains to ATA 2015's permissiveness of lobectomy for primary tumors ≤4 cm. European panelists cited preclusion of RAIT, potential need for completion thyroidectomy, frequent inability to avoid chronic thyroid hormone replacement, and limitations of supportive evidence as arguments against widely applying lobectomy. Significant divergence involved ATA 2015's guidance regarding RAIT. European panelists favored wider use of post-operative RAIT than does ATA 2015. Rationales included the modality's association with favorable patient outcomes and generally limited toxicity, and lack of high-quality evidence supporting withholding RAIT. Additionally, European panelists favored recombinant human thyrotropin in more settings than does ATA 2015, citing avoidance of hypothyroid morbidity and quality-of-life impairment, without apparent sacrifice in oncologic outcomes. Based on clinicial evidence plus theoretical advantages, European experts advocated dosimetric versus fixed-activity RAIT approaches for advanced DTC. European panelists noted that the ATA 2015 risk stratification system requires information sometimes unavailable in everyday practice. ATA 2015 recommendations regarding radioiodine-refractory DTC should consider potential palliative benefits of RAIT in patients who also have radioiodine-susceptible lesions.
CONCLUSIONS: European panelists suggested modifications to approximately one-third of ATA 2015 recommendations. Varying European and ATA 2015 perspectives can stimulate analysis and discussion of literature and performance of primary research to resolve discrepant recommendations and potentially improve patient outcomes.
PMID: 30484394 [PubMed - as supplied by publisher]
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A Case Series of Granulomatosis With Polyangiitis Primarily Diagnosed by Otological Manifestations.
Ann Otol Rhinol Laryngol. 2018 Nov 28;:3489418815517
Authors: Sahyouni R, Moshtaghi O, Abouzari M, Le P, Birkenbeuel J, Cheung D, Lin HW, Djalilian HR
Abstract
OBJECTIVE:: To describe a case series of previously undiagnosed granulomatosis with polyangiitis (GPA) patients who presented primarily with otological manifestations.
METHOD:: We report a series of patients visited at a neurotology clinic who were eventually diagnosed with GPA based on their otologic complaints and had no prior knowledge of having this condition.
RESULTS:: In this series, 10 (91%) patients presented with hearing loss (HL), more than half of which were bilateral (60%). Upon audiometric examination, all but 1 patient had mixed, conductive, or sensorineural HL. All patients presented with eustachian tube dysfunction (ETD), otitis media with effusion (OME), or both. Nasal endoscopy showed intranasal pathology in 3 (27%) patients. Otologic symptoms were improved in all patients after treatment with an average of 4 in-office follow-up appointments.
CONCLUSION:: GPA should be included in the differential diagnosis of adults with unexplained mixed hearing loss, new onset serous effusion, or acute otitis media in the absence of a previous history of ETD. Laboratory tests (ie, anti-neutrophil cytoplasmic autoantibody, erythrocyte sedimentation rate, and C-reactive protein) along with a urinalysis can aid in screening these patients. In cases in which the index of suspicion is high, repeated testing could reduce the risk of false negative findings.
PMID: 30486667 [PubMed - as supplied by publisher]
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Heterocellular Coupling Between Amacrine Cells and Ganglion Cells.
Front Neural Circuits. 2018;12:90
Authors: Marc RE, Sigulinsky CL, Pfeiffer RL, Emrich D, Anderson JR, Jones BW
Abstract
All superclasses of retinal neurons, including bipolar cells (BCs), amacrine cells (ACs) and ganglion cells (GCs), display gap junctional coupling. However, coupling varies extensively by class. Heterocellular AC coupling is common in many mammalian GC classes. Yet, the topology and functions of coupling networks remains largely undefined. GCs are the least frequent superclass in the inner plexiform layer and the gap junctions mediating GC-to-AC coupling (GC::AC) are sparsely arrayed amidst large cohorts of homocellular AC::AC, BC::BC, GC::GC and heterocellular AC::BC gap junctions. Here, we report quantitative coupling for identified GCs in retinal connectome 1 (RC1), a high resolution (2 nm) transmission electron microscopy-based volume of rabbit retina. These reveal that most GC gap junctions in RC1 are suboptical. GC classes lack direct cross-class homocellular coupling with other GCs, despite opportunities via direct membrane contact, while OFF alpha GCs and transient ON directionally selective (DS) GCs are strongly coupled to distinct AC cohorts. Integrated small molecule immunocytochemistry identifies these as GABAergic ACs (γ+ ACs). Multi-hop synaptic queries of RC1 connectome further profile these coupled γ+ ACs. Notably, OFF alpha GCs couple to OFF γ+ ACs and transient ON DS GCs couple to ON γ+ ACs, including a large interstitial amacrine cell, revealing matched ON/OFF photic drive polarities within coupled networks. Furthermore, BC input to these γ+ ACs is tightly matched to the GCs with which they couple. Evaluation of the coupled versus inhibitory targets of the γ+ ACs reveals that in both ON and OFF coupled GC networks these ACs are presynaptic to GC classes that are different than the classes with which they couple. These heterocellular coupling patterns provide a potential mechanism for an excited GC to indirectly inhibit nearby GCs of different classes. Similarly, coupled γ+ ACs engaged in feedback networks can leverage the additional gain of BC synapses in shaping the signaling of downstream targets based on their own selective coupling with GCs. A consequence of coupling is intercellular fluxes of small molecules. GC::AC coupling involves primarily γ+ cells, likely resulting in GABA diffusion into GCs. Surveying GABA signatures in the GC layer across diverse species suggests the majority of vertebrate retinas engage in GC::γ+ AC coupling.
PMID: 30487737 [PubMed - in process]
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Analyzing Image Segmentation for Connectomics.
Front Neural Circuits. 2018;12:102
Authors: Plaza SM, Funke J
Abstract
Automatic image segmentation is critical to scale up electron microscope (EM) connectome reconstruction. To this end, segmentation competitions, such as CREMI and SNEMI, exist to help researchers evaluate segmentation algorithms with the goal of improving them. Because generating ground truth is time-consuming, these competitions often fail to capture the challenges in segmenting larger datasets required in connectomics. More generally, the common metrics for EM image segmentation do not emphasize impact on downstream analysis and are often not very useful for isolating problem areas in the segmentation. For example, they do not capture connectivity information and often over-rate the quality of a segmentation as we demonstrate later. To address these issues, we introduce a novel strategy to enable evaluation of segmentation at large scales both in a supervised setting, where ground truth is available, or an unsupervised setting. To achieve this, we first introduce new metrics more closely aligned with the use of segmentation in downstream analysis and reconstruction. In particular, these include synapse connectivity and completeness metrics that provide both meaningful and intuitive interpretations of segmentation quality as it relates to the preservation of neuron connectivity. Also, we propose measures of segmentation correctness and completeness with respect to the percentage of "orphan" fragments and the concentrations of self-loops formed by segmentation failures, which are helpful in analysis and can be computed without ground truth. The introduction of new metrics intended to be used for practical applications involving large datasets necessitates a scalable software ecosystem, which is a critical contribution of this paper. To this end, we introduce a scalable, flexible software framework that enables integration of several different metrics and provides mechanisms to evaluate and debug differences between segmentations. We also introduce visualization software to help users to consume the various metrics collected. We evaluate our framework on two relatively large public groundtruth datasets providing novel insights on example segmentations.
PMID: 30483069 [PubMed - in process]
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NeuTu: Software for Collaborative, Large-Scale, Segmentation-Based Connectome Reconstruction.
Front Neural Circuits. 2018;12:101
Authors: Zhao T, Olbris DJ, Yu Y, Plaza SM
Abstract
Reconstructing a connectome from an EM dataset often requires a large effort of proofreading automatically generated segmentations. While many tools exist to enable tracing or proofreading, recent advances in EM imaging and segmentation quality suggest new strategies and pose unique challenges for tool design to accelerate proofreading. Namely, we now have access to very large multi-TB EM datasets where (1) many segments are largely correct, (2) segments can be very large (several GigaVoxels), and where (3) several proofreaders and scientists are expected to collaborate simultaneously. In this paper, we introduce NeuTu as a solution to efficiently proofread large, high-quality segmentation in a collaborative setting. NeuTu is a client program of our high-performance, scalable image database called DVID so that it can easily be scaled up. Besides common features of typical proofreading software, NeuTu tames unprecedentedly large data with its distinguishing functions, including: (1) low-latency 3D visualization of large mutable segmentations; (2) interactive splitting of very large false merges with highly optimized semi-automatic segmentation; (3) intuitive user operations for investigating or marking interesting points in 3D visualization; (4) visualizing proofreading history of a segmentation; and (5) real-time collaborative proofreading with lock-based concurrency control. These unique features have allowed us to manage the workflow of proofreading a large dataset smoothly without dividing them into subsets as in other segmentation-based tools. Most importantly, NeuTu has enabled some of the largest connectome reconstructions as well as interesting discoveries in the fly brain.
PMID: 30483068 [PubMed - in process]
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Different Subgroups of Cholinergic Neurons in the Basal Forebrain Are Distinctly Innervated by the Olfactory Regions and Activated Differentially in Olfactory Memory Retrieval.
Front Neural Circuits. 2018;12:99
Authors: Zheng Y, Feng S, Zhu X, Jiang W, Wen P, Ye F, Rao X, Jin S, He X, Xu F
Abstract
The mammalian basal forebrain (BF), a heterogenous structure providing the primary cholinergic inputs to cortical and limbic structures, plays a crucial role in various physiological processes such as learning/memory and attention. Despite the involvement of the BF cholinergic neurons (BFCNs) in olfaction related memory has been reported, the underlying neural circuits remain poorly understood. Here, we combined viral trans-synaptic tracing systems and ChAT-cre transgenic mice to systematically reveal the relationship between the olfactory system and the different subsets of BFCNs. The retrograde adeno-associated virus and rabies virus (AAV-RV) tracing showed that different subregional BFCNs received diverse inputs from multiple olfactory cortices. The cholinergic neurons in medial and caudal horizontal diagonal band Broca (HDB), magnocellular preoptic area (MCPO) and ventral substantia innominate (SI; hereafter HMS complex, HMSc) received the inputs from the entire olfactory system such as the olfactory bulb (OB), anterior olfactory nucleus (AON), entorhinal cortex (ENT), basolateral amygdala and especially the piriform cortex (PC) and hippocampus (HIP); while medial septum (MS/DB) and a part of rostral HDB (hereafter MS/DB complex, MS/DBc), predominantly from HIP; and nucleus basalis Meynert (NBM) and dorsal SI (hereafter NBM complex, NBMc), mainly from the central amygdala. The anterograde vesicular stomatitis virus (VSV) tracing further validated that the major target of the OB to the BF is HMSc. To correlate these structural relations between the BFCNs and olfactory functions, the neurons activated in the BF during olfaction related task were mapped with c-fos immunostaining. It was found that some of the BFCNs were activated in go/no-go olfactory discrimination task, but with different activated patterns. Interestingly, the BFCNs in HMSc were more significantly activated than the other subregions. Therefore, our data have demonstrated that among the different subgroups of BFCNs, HMSc is more closely related to the olfactory system, both structurally and functionally. This work provides the evidence for distinct roles of different subsets of BFNCs in olfaction associated memory.
PMID: 30483067 [PubMed - in process]
