Integrative identification of non-coding regulatory regions driving metastatic prostate cancer.

Large-scale sequencing efforts have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of variants occur within non-coding genomic regions. We designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression.

Direct transposition of native DNA for sensitive multimodal single-molecule sequencing.

Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility.

Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers.

From extrachromosomal DNA to neo-peptides, the broad reprogramming of the cancer genome leads to the emergence of molecules that are specific to the cancer state. We recently described orphan non-coding RNAs (oncRNAs) as a class of cancer-specific small RNAs with the potential to play functional roles in breast cancer progression. Here, we report a systematic and comprehensive search to identify, annotate, and characterize cancer-emergent oncRNAs across 32 tumor types.

Integrative identification of non-coding regulatory regions driving metastatic prostate cancer.

Large-scale sequencing efforts of thousands of tumor samples have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of germline and somatic variants occur within non-coding portions of the genome. These genomic regions do not directly encode for specific proteins, but can play key roles in cancer progression, for example by driving aberrant gene expression control.

A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression.

Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NADPH quinone dehydrogenase 1 (NQO1), and named it NQO1-AS.

A Novel Use of the Exoscope for In-Vivo Microvascular Free Flaps.

Recent innovations in camera and display technologies have created a new potential modus for the microvascular surgeon. An exoscope consists of cameras mounted to a flexible arm that broadcasts the image to a nearby high-definition monitor. This article details the experience using this emerging technology to perform microvascular anastomosis for 46 cases of head and neck free flaps reconstruction.

Management of Ear Trauma.

Facial trauma remains a common reason for visits to the emergency department or urgent care facility. The ear remains susceptible to trauma given its delicate anatomy and position in the maxillofacial region. Understanding the anatomy and recognizing the circumstances regarding the mechanism of injury help dictate treatment.

Release from UNC93B1 reinforces the compartmentalized activation of select TLRs.

Nucleic acid-sensing Toll-like receptors (TLRs) are subject to complex regulation to facilitate the recognition of microbial DNA and RNA while limiting the recognition of an organism's own nucleic acids. Failure to properly regulate these TLRs can lead to autoimmune and autoinflammatory diseases. Intracellular localization of these receptors is thought to be crucial for the discrimination between self and non-self, but the molecular mechanisms that reinforce compartmentalized activation of intracellular TLRs remain poorly understood.

Unusual Case of Transdural Extension of Glioblastoma Multiforme in the Maxillofacial Region and a Review of the Literature.

Glioblastoma multiforme is the most common primary brain tumor. It is locally aggressive but rarely spreads outside the central nervous system. We present an unusual case of a 57-year-old woman who had presented 1 year after surgical resection and adjuvant therapy, with evidence of recurrent tumor invading through the skull base into the orbital apex, masticator, and pterygoid space.

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.

Rationale: Endothelial-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD.

Objective: We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis.

Oral/Head and Neck Oncologic and Reconstructive Surgery Fellowship Training Programs: Transformation of the Specialty From 2005 to 2015: Report from the AAOMS Committee on Maxillofacial Oncology and Reconstructive Surgery.

Oral and Maxillofacial Surgeons have increasing opportunities to train in head and neck oncologic and reconstructive surgery. The development of a fellowship training programs within our speciality has had a transformative effect on the speciality. This survey by the commitee on Maxillofacial Oncology and Reconstructive is aimed to evaluate the impact of fellowship training on the careers of the fellows and speciality from 2005-2015.

Immune DNA signature of T-cell infiltration in breast tumor exomes.

Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature.

BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.

Background: Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%).

Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state.

Endothelial functions are highly regulated by imposed shear stress in vivo. The characteristics of shear stress determine mechanotransduction events that regulate phenotypic outcomes including redox and inflammatory states. Recent data indicate that microRNAs (miRs) in vascular endothelial cells play an essential role in shear stress-regulated endothelial responses.

AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6.

B-cell lymphoma-6 protein (Bcl-6) is a corepressor for inflammatory mediators such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and -3, which function to recruit monocytes to vascular endothelial cells upon inflammation. Poly [ADP ribose] polymerase 1 (PARP-1) is proinflammatory, in part through its binding at the Bcl-6 intron 1 to suppress Bcl-6 expression. We investigated the mechanisms by which PARP-1 dissociates from the Bcl-6 intron 1, ultimately leading to attenuation of endothelial inflammation.

Fibular free flaps in the management of osteomyelitis of the mandible.

Background: Fibular free flaps are an alternative method in the management of chronic osteomyelitis of the mandible without osteoradionecrosis.

Methods: A prospective review of 2 cases of chronic osteomyelitis of the mandible managed with a fibular free flap was conducted. Patient satisfaction and aesthetic results were examined.

Sonographic assessment of blunt abdominal trauma: a 4-year prospective study.

Purpose: Emergency abdominal sonography has become a common modality worldwide in the evaluation of injuries caused by blunt trauma. The sensitivity of sonography in the detection of hemoperitoneum varies, and little is known about the accuracy of sonography in the detection of injuries to specific organs. The purpose of this study was to determine the overall accuracy of sonography in the detection of hemoperitoneum and solid-organ injury caused by blunt trauma.