CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.

Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of the highly penetrant CARD14E138A alteration is described. In addition to BCL10 and MALT1, CARD14E138A associated with several proteins important in innate immune signalling.

An Early Oligocene age for the oldest known monkeys and rodents of South America.

The Santa Rosa fossil locality in eastern Perú produced the first Paleogene vertebrate fauna from the Amazon Basin, including the oldest known monkeys from South America. This diverse paleofauna was originally assigned an Eocene age based largely on the stage of evolution of the site's caviomorph rodents and marsupials. Here, we present detrital zircon dates that indicate that the maximum composite age of Santa Rosa is 29.

Clinical Utility of Cxbladder Monitor for Patients with a History of Urothelial Carcinoma: A Physician-Patient Real-World Clinical Data Analysis.

Introduction: International guidelines advocate regular surveillance of patients following urothelial carcinoma (UC). A validated molecular diagnostic non-invasive urine test, Cxbladder Monitor, correctly identifies patients with a UC history who have low-probability of recurrence. The present study assesses the clinical utility of Cxbladder Monitor in reducing the number and frequency of urologic procedures ordered without missing detection of recurrent UC.

Clinical utility of a non-invasive urine test for risk assessing patients with no obvious benign cause of hematuria: a physician-patient real world data analysis.

Background: The non-invasive Cxbladder urine test system has demonstrated clinical utility in ruling out urothelial carcinoma (UC) in patients with asymptomatic microscopic hematuria (AMH), suggesting that the number of invasive diagnostic tests, including cystoscopy, used in this patient population may be reduced by Cxbladder testing prior to conducting a full urological work-up. The aim of this study was to demonstrate the enhanced clinical utility of communicating objective information on diagnostic decisions made by individual physicians on individual patients with AMH.

Methods: Three hundred ninety-six physician-patient decisions were generated from twelve participant physicians evaluating real world case notes from the same 33 patients presenting with AMH.

Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma.

Objective: Patients with urothelial carcinoma (UC) undergo rigorous surveillance for recurrence. Noninvasive urine tests are not currently recommended by guideline panels owing to insufficient clinical benefit. The objective of this study was to prospectively compare the performance of the Cxbladder Monitor test to other commonly available urine markers and cytology for surveillance of patients with UC.

Clinical Utility of Cxbladder for the Diagnosis of Urothelial Carcinoma.

Introduction: This study aimed to demonstrate the clinical utility of non-invasive multigene Cxbladder urine tests in reducing the overall number of diagnostic tests and invasive procedures used in the clinical evaluation of patients presenting with microhematuria, a key symptom of urothelial carcinoma (UC). There is a belief that using non-invasive molecular diagnostic tests in patients with hematuria may lead to patients undergoing unnecessary and costly invasive procedures that can cause adverse events and decrease patient quality of life. The objective of this study was to determine whether or not this was the case, using Cxbladder.

Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study.

Purpose: Urothelial carcinoma is associated with a high rate of recurrence. Guidelines recommend rigorous, regular surveillance programs that are invasive and expensive. This study describes a noninvasive urine test with sufficient sensitivity to rule out recurrent urothelial carcinoma, thereby reducing invasive diagnostic evaluations without compromising patient care.

Composite Blastoid Variant of Mantle Cell Lymphoma and Classical Hodgkin Lymphoma.

Composite lymphoma (CL) describes the rare occurrence of 2 or more distinct types of lymphoma in a single anatomical location. We present the case of a 78-year-old man presenting with a 3-month history of weakness, malaise, and increasing dyspnea. A lymph node excised from the posterior triangle of the neck revealed the coexistence of 2 morphologically and phenotypically distinct lymphoid neoplasms consistent with a blastoid variant of mantle cell lymphoma (MCL) occurring in composite with classical Hodgkin lymphoma (cHL), mixed cellularity subtype.

Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation.

Inherited and de novo mutations in the CARD14 gene promote the development of psoriasis, an inflammatory disease of the skin. Caspase recruitment domain-containing protein 14 (CARD14) is a member of the CARMA protein family that includes the structurally related CARD11 adaptor that mediates NF-κB activation by antigen receptors. We investigated the mechanism by which CARD14 mutation in psoriasis activates NF-κB.

A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a study of Cxbladder Detect, UroVysion® FISH, NMP22® and cytology based on imputation of multiple datasets.

Background: Comparing the relative utility of diagnostic tests is challenging when available datasets are small, partial or incomplete. The analytical leverage associated with a large sample size can be gained by integrating several small datasets to enable effective and accurate across-dataset comparisons. Accordingly, we propose a methodology for a holistic comparative analysis and ranking of cancer diagnostic tests through dataset integration and imputation of missing values, using urothelial carcinoma (UC) as a case study.

A segregation index combining phenotypic (clinical characteristics) and genotypic (gene expression) biomarkers from a urine sample to triage out patients presenting with hematuria who have a low probability of urothelial carcinoma.

Background: Hematuria can be symptomatic of urothelial carcinoma (UC) and ruling out patients with benign causes during primary evaluation is challenging. Patients with hematuria undergoing urological work-ups place significant clinical and financial burdens on healthcare systems. Current clinical evaluation involves processes that individually lack the sensitivity for accurate determination of UC.

Radiographic evaluation of the pleural fluid accumulation rate after pneumonectomy.

Purpose: Understanding the radiographic appearance and normal rate of fluid accumulation after pneumonectomy is important in order to detect postoperative complications.

Methods: Upright posterior-anterior chest radiographs of 94 postpneumonectomy patients were assessed for the rate of pleural fluid accumulation as a percentage of hemithorax volume.

Results: Overall median time to 70% hemithoracic opacification was 3 days and mean time was 27 days.

A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.

Purpose: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification.

Materials And Methods: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy.

The "memory effect" for repeated radiologic observations.

Objective: It is assumed that memory has a role to play in repeated radiologic observation studies. The main objective of this study was to examine this assumption and evaluate the effect that memory may have on receiver operating characteristic (ROC) methods.

Materials And Methods: A two-center observer study was performed with a total of 24 experienced radiologists.

Imaging of soft tissue and osseous sarcomas of the extremities.

Soft tissue and osseous sarcomas of the extremities are uncommon malignancies that represent very important diagnostic entities because of their aggressive nature. Radiologic investigations, including plain film, computed tomography, contrast-enhanced magnetic resonance imaging; scintigraphy, ultrasound, and positron emission tomography-computed tomography, play critical roles in providing a differential, establishing the diagnosis, demonstrating prognostic characteristics, and tailoring tumor treatment. The purpose of this review is to describe the most common soft tissue and osseous sarcomas of the extremities, with emphasis on their plain film and magnetic resonance imaging characteristics with the aim of aiding the reader to accurately describe the important imaging features and generate an appropriate differential diagnosis to aid the referring clinician with prompt appropriate management and treatment.

Imaging of thoracic sarcomas of the chest wall, pleura, and lung.

Primary sarcomas of the thorax are uncommon. The purpose of this review is to describe the radiologic findings of sarcomas affecting the thorax, in particular the chest wall, pleura, and lungs. Most primary sarcomas affecting the thorax arise in the chest wall, and the most common sarcomas of the chest wall are chondrosarcoma, osteosarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, malignant fibrous histiocytoma, and fibrosarcoma.

Central venous line placement in the superior vena cava and the azygos vein: differentiation on posteroanterior chest radiographs.

Objective: The purpose of this study was to determine, first, the accuracy with which radiologists reading posteroanterior chest radiographs differentiate whether a central venous line is in the superior vena cava or the azygos vein and, second, the circumstances in which radiologists may omit the lateral view to determine the position of a central venous line.

Materials And Methods: Twenty-four radiologists evaluated 60 posteroanterior chest radiographs to determine the position of a central venous line in the superior vena cava or azygos vein. Investigators evaluated the appearance of the central venous lines to refine rules for determining central venous line position on a frontal radiograph and omitting the lateral view.

Positron emission tomography-CT imaging in guiding musculoskeletal biopsy.

Positron emission tomography (PET)-computed tomography (CT) is a useful device in identifying musculoskeletal lesions that require biopsy. It can be used to localize the primary lesion, identify a site to biopsy, and evaluate metastatic lesions that require follow-up biopsies. Not all malignant tumors have hypermetabolic activity, and there are many benign lesions and physiologic processes that do have increased F-18 fluorodeoxyglucose uptake.

The current status of percutaneous vertebroplasty in Canada.

Objective: To provide an overview of the current status of percutaneous vertebroplasty (PVP) practice in Canada, including the preprocedure work up, operative technique and follow-up practice of physicians performing the procedure in this country.

Methods: Questionnaires were emailed to 31 institutions performing percutaneous vertebroplasty across Canada.

Results: Twenty-three (74.

Imaging of pulmonary fusariosis in patients with hematologic malignancies.

Objective: The purpose of this study was to assess the radiographic features of pulmonary fusariosis, an increasingly encountered cause of severe opportunistic mold pneumonia.

Conclusion: Pulmonary fusariosis has radiographic manifestations that are suggestive of an angioinvasive mold. Nodules or masses were the most common findings at CT, seen in 82% of patients compared with only 45% on chest radiography.

The Claisen rearrangement approach to fused bicyclic medium-ring oxacycles.

The synthesis of five fused-bicyclic medium-ring lactones carrying identical ring-fusion to that in the polyether toxins is described using an enolate hydroxylation, intramolecular hydrosilation, Claisen rearrangement sequence.

Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder.

Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage > or =T1 disease.

Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.

Homogeneous time-resolved fluorescence assays for the detection of activity and inhibition of phosphatase enzymes employing phosphorescently labeled peptide substrates.

A rapid, homogenous, antibody-free assay for phosphatase enzymes was developed using the phosphorescent platinum (II)-coproporphyrin label (PtCP) and time-resolved fluorescent detection. An internally quenched decameric peptide substrate containing a phospho-tyrosine residue, labeled with PtCP-maleimide and dabcyl-NHS at its termini was designed. Phosphatase catalysed dephosphorylation of the substrate resulted in a minor increase in PtCP signal, while subsequent cleavage by chymotrypsin at the dephosphorylated Tyr-Leu site provided a 3.