CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research.

Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms.

ORAOV1, CCND1, and MIR548K Are the Driver Oncogenes of the 11q13 Amplicon in Squamous Cell Carcinoma.

Unlabelled: 11q13 amplification is a frequent event in human cancer and in particular in squamous cell carcinomas (SCC). Despite almost invariably spanning 10 genes, it is unclear which genetic components of the amplicon are the key driver events in SCC. A combination of computational, in vitro, ex vivo, and in vivo models leveraging efficient primary human keratinocyte genome editing by Cas9-RNP electroporation, identified ORAOV1, CCND1, and MIR548K as the critical drivers of the amplicon in head and neck SCC.

Epimorphic regeneration in the mammalian tympanic membrane.

Adult mammals are generally believed to have limited ability to regenerate complex tissues and instead, repair wounds by forming scars. In humans and across mammalian species, the tympanic membrane (TM) rapidly repairs perforations without intervention. Using mouse models, we demonstrate that the TM repairs itself through a process that bears many hallmarks of epimorphic regeneration rather than typical wound healing.

Specific Oral Microbial Differences in Proteobacteria and Bacteroidetes Are Associated with Distinct Sites When Moving from Healthy Mucosa to Oral Dysplasia-A Microbiome and Gene Profiling Study and Focused Review.

Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established.

Electrical Determinants of Tinnitus Extinction in a Cochlear Implant Patient.

Hypothesis: Electrical tinnitus suppression by cochlear implants requires stimulation of a subset of neural elements in the cochlea.

Background: Tinnitus is the phantom perception of sound in the ears and is a known correlate of hearing loss. Cochlear implants restore hearing and are known to lessen or extinguish tinnitus.

Endoscopic Medial Reepithelization for Inflammatory Canal Stenosis.

Objective: Inflammatory external auditory canal (EAC) Stenosis arises from infiltration of inflammatory cells, edema and eventual sclerosing of the medial EAC, leading to complete obstruction and conductive hearing loss. Current treatment includes surgical resection of the affected area with widening and reepithelization of the EAC via postauricular incision, but the condition is reported to recur with high frequency. Our aim was to assess the feasibility of endoscopic transcanal treatment as an alternative to postauricular canalplasty and understand its effect on recurrence rates.

A Rare Complication of Chronic Otitis Media: Central Skull Base Osteomyelitis Managed With Combined Endoscopic Transmastoid and Transsphenoidal Debridement.

Objective: This report describes a case of otogenic central skull base osteomyelitis (CSBO) requiring complex surgical intervention and reviews the literature on management of this entity.

Patient: A 76-year-old man presented with a nearly 20-year history of chronic otomastoiditis and cholesteatoma with ultimate progression to severe CSBO with involvement of the petrous apex, clivus, and craniocervical junction.

Interventions: CSBO was managed with culture-directed antibiotic therapy, hyperbaric oxygen, and surgical intervention including serial combined endoscopic transmastoid and transsphenoidal debridements.

Human melanocyte development and melanoma dedifferentiation at single-cell resolution.

In humans, epidermal melanocytes are responsible for skin pigmentation, defence against ultraviolet radiation and the deadliest common skin cancer, melanoma. Although there is substantial overlap in melanocyte development pathways between different model organisms, species-dependent differences are frequent and the conservation of these processes in human skin remains unresolved. Here, we used a single-cell enrichment and RNA-sequencing pipeline to study human epidermal melanocytes directly from the skin, capturing transcriptomes across different anatomical sites, developmental age, sexes and multiple skin tones.

A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane.

The tympanic membrane (TM) is critical for hearing and requires continuous clearing of cellular debris, but little is known about homeostatic mechanisms in the TM epidermis. Using single-cell RNA sequencing, lineage tracing, whole-organ explant, and live-cell imaging, we show that homeostatic TM epidermis is distinct from other epidermal sites and has discrete proliferative zones with a three-dimensional hierarchy of multiple keratinocyte populations. TM stem cells reside in a discrete location of the superior TM and generate long-lived clones and committed progenitors (CPs).

A single-cell atlas and lineage analysis of the adult Drosophila ovary.

The Drosophila ovary is a widely used model for germ cell and somatic tissue biology. Here we use single-cell RNA-sequencing (scRNA-seq) to build a comprehensive cell atlas of the adult Drosophila ovary that contains transcriptional profiles for every major cell type in the ovary, including the germline stem cells and their niche cells, follicle stem cells, and previously undescribed subpopulations of escort cells. In addition, we identify Gal4 lines with specific expression patterns and perform lineage tracing of subpopulations of escort cells and follicle cells.

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells.

Cellular Dynamics in Early Healing of Mouse Tympanic Membranes.

Aim: To better elucidate the cellular dynamics by which perforations in the tympanic membrane (TM) are healed.

Background: Under normal conditions, epidermal cells are born and then migrate radially outward from the malleus in the TM. It is unknown what the relative contribution of newly proliferated cells from different lineages is in the healing of TM perforations.

Impact of pretreatment growth on Tumor control for vestibular schwannomas following gamma knife.

Objectives/hypothesis: To determine if volumetric growth prior to gamma knife (GK) radiosurgery predicts long-term tumor control.

Study Design: Retrospective cohort study.

Methods: Sporadic vestibular schwannomas (VS) treated with GK between 2002 and 2014 at a single tertiary care center were identified.

Lineage dynamics of murine pancreatic development at single-cell resolution.

Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types.

Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity.

Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement.

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown.

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland.

The tear-producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. The lacrimal gland possesses many features that make it an excellent model in which to investigate tubulogenesis, but the cell types and lineage relationships that drive lacrimal gland formation are unclear. Using single-cell sequencing and other molecular tools, we reveal novel cell identities and epithelial lineage dynamics that underlie lacrimal gland development.

Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

Background: Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH).

Auditory brainstem implantation in a 16-month-old boy with cochlear hypoplasia.

Objective: To determine the safety and feasibility of auditory brainstem implantation in children younger than 5 years.

Patient(s): Patients younger than 5 years who were not candidates for cochlear implantation because of anatomic considerations were included in the analyses.

Intervention(s): Auditory brainstem implantation via retrosigmoid craniotomy.

High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma.

Background: Although the presence of genetic heterogeneity within the tumors of individual patients is established, it is unclear whether greater heterogeneity predicts a worse outcome. A quantitative measure of genetic heterogeneity based on next-generation sequencing (NGS) data, mutant-allele tumor heterogeneity (MATH), was previously developed and applied to a data set on head and neck squamous cell carcinoma (HNSCC). Whether this measure correlates with clinical outcome was not previously assessed.

The mutational landscape of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors.

Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer.

Unlabelled: Hepatocellular carcinoma (HCC) is 1 of the leading causes of cancer-related deaths worldwide, yet the molecular genetics underlying this malignancy are still poorly understood. In our study, we applied statistical methods to correlate human HCC gene expression data obtained from complementary DNA (cDNA) microarrays and corresponding DNA copy number variation data obtained from array-based comparative genomic hybridization. We have thus identified 76 genes that are up-regulated and show frequent DNA copy number gain, and 37 genes that are down-regulated and show frequent DNA copy loss in human HCC samples.

Distinct pathways of genomic progression to benign and malignant tumors of the liver.

We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of beta-catenin.