AVONET: morphological, ecological and geographical data for all birds.

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.

Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.

DNA methylation, a key epigenetic driver of transcriptional silencing, is universally dysregulated in cancer. Reversal of DNA methylation by hypomethylating agents, such as the cytidine analogs decitabine or azacytidine, has demonstrated clinical benefit in hematologic malignancies. These nucleoside analogs are incorporated into replicating DNA where they inhibit DNA cytosine methyltransferases DNMT1, DNMT3A and DNMT3B through irreversible covalent interactions. These agents induce notable toxicity to normal blood cells thus limiting their clinical doses. Herein we report the discovery of GSK3685032, a potent first-in-class DNMT1-selective inhibitor that was shown via crystallographic studies to compete with the active-site loop of DNMT1 for penetration into hemi-methylated DNA between two CpG base pairs. GSK3685032 induces robust loss of DNA methylation, transcriptional activation and cancer cell growth inhibition in vitro. Due to improved in vivo tolerability compared with decitabine, GSK3685032 yields superior tumor regression and survival mouse models of acute myeloid leukemia.

Skull base osteomyelitis imaging.

PURPOSE OF REVIEW: Skull base osteomyelitis (SBO) is a challenging entity to diagnose and treat. The goal of this review is to summarize the imaging findings of SBO and present these in the context of recent studies on imaging of SBO. RECENT FINDINGS: This review discusses the clinical presentation, pathophysiology and imaging appearances of SBO. The review further emphasizes the results of latest studies on imaging of SBO, and the role of different modalities in diagnosis and evaluation of disease course and treatment response. Brief discussion on differential diagnoses from an imaging standpoint is also included. SUMMARY: Various imaging modalities play different and complimentary roles in diagnosis and management of SBO, which are discussed in this review.

Heavily calcified parapharyngeal space mesenchymal chondrosarcoma: Imaging and pathological findings and a review of the literature.

Parapharyngeal space (PPS) masses are relatively rare lesions of the head and neck, and account for 0.5-1.5% of head and neck lesions. The most common lesion to occur in the PPS is a benign salivary neoplasm, typically pleomorphic adenoma either from the deep parotid or from ectopic parotid tissue rests within the PPS. A calcified or ossified mass in this location is exceedingly rare, but a calcified variant of pleomorphic adenoma has been reported. In this study, we present a patient with a heavily calcified PPS mesenchymal chondrosarcoma with an unusual presentation. We discuss the imaging and pathologic findings followed by a review of the current literature.

Neuroimaging of the Pituitary Gland: Practical Anatomy and Pathology.

The pituitary gland is a small endocrine organ located within the sella turcica. Various pathologic conditions affect the pituitary gland and produce endocrinologic and neurologic abnormalities. The most common lesion of the pituitary gland is the adenoma, a benign neoplasm. Dedicated MR imaging of the pituitary is radiologic study of choice for evaluating pituitary gland and central skull region. Computed tomography is complimentary and allows for identification of calcification and adjacent abnormalities of the osseous skull base. This review emphasizes basic anatomy, current imaging techniques, and highlights the spectrum of pathologic conditions that affect the pituitary gland and sellar region.

Critical illness-associated cerebral microbleed in a patient with sickle cell disease: A case report and review of the literature.

Critical illness-associated cerebral microbleed (CICM) is a relatively rare and newly described condition. It can occur in critically ill ICU patients and can be secondary to many underlying etiologies. CICM is associated with high mortality and permanent neurologic deficits in surviving patients. Distribution of cerebral microhemorrhages in neuroimaging findings is critical for accurate diagnosis of this condition. Here, we present an ICU admitted patient with sickle cell disease crisis and CICM and will discuss their clinically and radiologically distinct phenomenon followed by a review of current literature.

Pseudohypoxic Brain Swelling: Report of 2 Cases and Introduction of the Lentiform Rim Sign as Potential MRI Marker.

BACKGROUND: A rare but important complication related to otherwise uneventful brain and spine surgery is becoming more recognized and more frequently reported in the medical literature. This has been variably labeled as pseudohypoxic brain swelling or postoperative hypotension-associated venous congestion. This poorly understood condition occurs in the setting of surgical intervention and is thought to be related to cerebrospinal fluid leak or evacuation, decreased intracranial pressure, and subsequent development of deep venous congestion affecting the basal ganglia, thalami, and cerebellum. Clinically, patients may have global neurologic deficit and outcomes range from full recovery to vegetative state or death. The imaging correlate includes atypical edema, infarction, or hemorrhage and can overlap the appearance of diffuse hypoxic injury, for which this condition can be mistaken both clinically and radiologically. Although this deep brain tissue edema can be associated with other signs of cerebrospinal fluid hypotension such as dural thickening, brain sagging, and cerebellar herniation, it can be isolated, making the diagnosis challenging. CASE DESCRIPTION: We present 2 cases of unexpected clinical deterioration occurring in patients with otherwise uncomplicated neurosurgery, 1 with craniotomy and the other with lumbar spine intervention. Both patients exhibit similar appearing edema in the deep gray structures on postoperative magnetic resonance imaging scans. In addition to reviewing the prior literature and imaging findings, we evaluate the imaging findings to determine if there are unique features or signatures that might allow differentiation of PHBS from hypoxic-ischemic encephalopathy. CONCLUSIONS: The lentiform rim sign can be helpful for differentiation of pseudohypoxic brain swelling versus hypoxic-ischemic encephalopathy.

Spontaneous "pneumo-apoplexy" as a presentation of pituitary adenoma.

Cases of spontaneous CSF leak associated with pituitary tumor apoplexy are uncommon in the literature with pneumocephalus or pneumosella being rare, especially spontaneous occurrence of pneumocephalus being extremely rare. We present a case of pituitary macroadenoma apoplexy resulting in spontaneous CSF leak and a large volume of intra-tumoral gas. A 65-year-old female presented with severe headache, profuse rhinorrhea and acute vision loss and was found to have a large sellar and suprasellar lesion with air and hemorrhage with mild peripheral enhancement. The patient underwent trans-sphenoidal tumor resection and repair of skull base for CSF leak with nasoseptal flap placement. Pathology demonstrated a pituitary adenoma exhibiting immunoreactivity for ACTH. To our best knowledge, our case is the first report of features of pituitary tumor apoplexy with hemorrhage and pneumosella, which could be summarized by the term "pneumo-apoplexy".

Global transcriptomic analysis of the arcuate nucleus following chronic glucocorticoid treatment.

OBJECTIVE: Glucocorticoids (GCs) are widely prescribed medications that are well recognized to cause adverse metabolic effects including hyperphagia, obesity, and hyperglycemia. These effects have been recapitulated in a murine model of GC excess, and we hypothesize that they are mediated, in part, through central mechanisms. This study aimed to identify genes in the hypothalamic arcuate nucleus (ARC) that are altered with GC treatment and evaluate their contribution to GC-induced metabolic abnormalities. METHODS: Corticosterone (Cort; 75 µg/ml) was administered in the drinking water to male C57Bl/6J mice for 2 days or 4 weeks. Phenotypic analysis of each group was undertaken and central and peripheral tissues were collected for biochemical and mRNA analyses. Arcuate nuclei were isolated by laser capture microdissection and tissue analyzed by RNA-seq. RESULTS: RNA-seq analysis of ARC tissue from 4 week Cort treated mice revealed 21 upregulated and 22 downregulated genes at a time when mice had increased food intake, expansion of adipose tissue mass, and insulin resistance. In comparison, after 2 days Cort treatment, when the main phenotypic change was increased food intake, RNA-seq identified 30 upregulated and 16 downregulated genes. Within the genes altered at 2 days were a range of novel genes but also those known to be regulated by GCs, including Fkbp5, Mt2, Fam107a, as well as some involved in the control of energy balance, such as Agrp, Sepp1, Dio2, and Nmb. Of the candidate genes identified by RNA-seq, type-II iodothyronine deiodinase (Dio2) was chosen for further investigation as it was increased (2-fold) with Cort, and has been implicated in the control of energy balance via the modulation of hypothalamic thyroid hormone availability. Targeted knockdown of Dio2 in the MBH using AAV-mediated CRISPR-Cas9 produced a mild attenuation in GC-induced brown adipose tissue weight gain, as well as a 56% reduction in the GC-induced increase in Agrp. However, this conferred no protection from GC-induced hyperphagia, obesity, or hyperglycemia. CONCLUSIONS: This study identified a comprehensive set of genes altered by GCs in the ARC and enabled the selection of key candidate genes. Targeted knockdown of hypothalamic Dio2 revealed that it did not mediate the chronic GC effects on hyperphagia and hyperglycemia.

Imaging of Inflammatory Disorders of Salivary Glands.

Sialadenitis is among the most common conditions that affect the salivary glands. Inflammation of the salivary glands occurs as the end result of a variety of pathologic conditions, including infectious, autoimmune, and idiopathic causes. Clinically, inflammation of the salivary gland causes pain and localized swelling. The presentation may be acute or chronic, and can be recurrent. Because there is significant overlap of underlying disease mechanisms and clinical presentations, radiologic evaluation often plays a significant role in evaluation. This article is a brief review of sialadenitis, including disease mechanisms, causes, and the practical imaging of the salivary glands.

Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review.

The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous "amyloid-like" material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red-negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

IncucyteDRC: An R package for the dose response analysis of live cell imaging data.

We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web interface, implemented using shiny, is provided for the benefit of non-R users. The software is potentially useful to any research group studying the impact of small molecule inhibitors on cell proliferation using the IncuCyte ZOOM.

The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR.

Prolonged treatment with bevacizumab is associated with brain atrophy: a pilot study in patients with high-grade gliomas.

Bevacizumab is widely used for treatment of high-grade gliomas and other malignancies. Because bevacizumab has been shown to be associated with neurocognitive decline, this study is designed to investigate whether prolonged treatment with bevacizumab is also associated with brain atrophy. We identified 12 high-grade glioma patients who received bevacizumab for 12 months at the first recurrence and 13 matched controls and blindly compared the volumes of the contralateral hemispheres and contralateral ventricle in these two groups at baseline and after 12 ± 2 months of the baseline scan by two independent analyses. The volumes of the contralateral hemispheres and ventricles did not differ significantly between the two groups at baseline. Whereas, in the control group the volumes of the contralateral hemisphere changed subtly from baseline to follow-up (p = 0.23), in the bevacizumab-treated group the volumes significantly decreased from baseline to follow-up (p = 0.03). There was significant increase in the contralateral ventricle volume from base line to follow-up scans in both the control group (p = 0.01) and in the bevacizumab group (p = 0.005). Both the absolute and the percentage changes of contralateral hemisphere volumes and contralateral ventricular volumes between the two patient groups were statistically significant (p < 0.05). Results of this study demonstrate prolonged treatment with bevacizumab is associated with atrophy of the contralateral brain hemisphere.

Practical imaging of the parotid gland.

The parotid gland may be affected by numerous pathologies, and physicians from many different medical and surgical specialties request parotid imaging. Mastering the typical imaging features of various types of parotid pathology is facilitated by understanding how various diseases produce their characteristic imaging findings. In this review article, we present succinct overviews of the normal anatomy and the common pathologies of the parotid gland and recommend a practical approach to differential diagnosis that can be easily implemented in day-to-day radiology practice.