Genomic ALK alterations in primary and relapsed neuroblastoma.

Background: Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse.

Methods: ALK alterations were assessed in neuroblastomas at diagnosis and/or relapse from a total of 943 patients, covering all stages of disease.

Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies.

Unlabelled: Genomic profiling revealed the identity of at least 5 subtypes of diffuse large B-cell lymphoma (DLBCL), including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1, and/or SPIB. We generated mouse models harboring B cell-specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole-exome sequencing, transcriptome, flow-cytometry, and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with prememory B cells and light-zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets.

Risk of Acute Kidney Injury Associated With Medication Administration in the Emergency Department.

Background: Patients who develop acute kidney injury (AKI) have a 2-fold increased risk for major adverse events within 1 year. An estimated 19-26% of all cases of hospital-acquired AKI may be attributable to drug-induced kidney disease (DIKD). Patients evaluated in the emergency department (ED) are often prescribed potentially nephrotoxic drugs, yet the role of ED prescribing in DIKD is unknown.

Telomerase Is a Prognostic Marker of Poor Outcome and a Therapeutic Target in Neuroblastoma.

Purpose: Telomere maintenance is a hallmark of high-risk neuroblastoma; however, the contribution of telomerase and alternative lengthening of telomeres (ALT) to clinical phenotypes has remained unclear. We aimed to determine the clinical relevance of telomerase activation versus ALT as biomarkers in pretreatment neuroblastoma and to assess the potential value of telomerase as a therapeutic target.

Materials And Methods: The genomic status of and was assessed in 457 pretreatment neuroblastomas by fluorescence in situ hybridization.

ATM activity in T cells is critical for immune surveillance of lymphoma in vivo.

The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear.

A mechanistic classification of clinical phenotypes in neuroblastoma.

Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors.

Development and implementation of procedures for outpatient naloxone prescribing at a large academic medical center.

Purpose: An interprofessional initiative to operationalize outpatient naloxone prescribing at a large academic medical center is described.

Summary: The initiative was carried out by a work group of clinical pharmacists and pharmacy administrators in collaboration with physicians and nursing staff leaders from multiple practice settings. An opioid overdose risk-assessment guide was developed on the basis of literature review and expert opinion.

Lymphnode tuberculosis in a 4-year-old boy with relapsed ganglioneuroblastoma: a case report.

Background: Mycobacterium tuberculosis (M. tuberculosis) disease is a generally well-known problem among immunocompromised adults and children. In pediatric oncology, only few cases of M.

Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy?

Background/aims: To report a case and the histopathology of uveal melanoma cell seeding following transretinal tumor biopsy for a suspected uveal lesion.

Methods: Interventional case report.

Results: A 66-year-old male presented with a pigmented perilimbal episcleral lesion overlying an intraocular mass at the pars plana, 3.

Validating a Method to Assess Lipreading, Audiovisual Gain, and Integration During Speech Reception With Cochlear-Implanted and Normal-Hearing Subjects Using a Talking Head.

Objectives: Watching a talker's mouth is beneficial for speech reception (SR) in many communication settings, especially in noise and when hearing is impaired. Measures for audiovisual (AV) SR can be valuable in the framework of diagnosing or treating hearing disorders. This study addresses the lack of standardized methods in many languages for assessing lipreading, AV gain, and integration.

Influence of backside loading on the floating mass transducer: An in vitro experimental study.

Hypothesis: The vibration of the floating mass transducer (FMT) of a single active middle-ear implant (AMEI) is distinctly influenced by the properties of the material coupled to its back side.

Background: In round window vibroplasty, the FMT needs to be padded against the surrounding bone opposite from the round window membrane. This represents one factor influencing its performance as a round window driver.

Surgical Treatment for Early Stage Glottic Carcinoma with Involvement of the Anterior Commissure.

Objective Assessment of the value of transoral laser microsurgery (TLM) compared with open surgery (OS) for early stage squamous cell carcinoma of the glottic larynx with special regard to involvement of the anterior commissure (AC). Study Design Case series with chart review. Setting Tertiary care otolaryngology clinic.

Discordance and Conversion Rates of Progesterone-, Estrogen-, and HER2/neu-Receptor Status in Primary Breast Cancer and Brain Metastasis Mainly Triggered by Hormone Therapy.

Background/aim: Knowing the molecular footprint of tumors is a precondition for personalized medicine. For breast cancer, targeted therapies are frequently based on the molecular status of the tissue gained from the primary tumor operation. However, it is unclear whether metastases in different organs maintain the same status.

Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent cytogenetic aberrations, namely del(17p), affecting TP53, and del(11q), affecting ATM, are associated with resistance against genotoxic chemotherapy (del17p) and poor outcome (del11q and del17p). Both del(17p) and del(11q) are also associated with inferior outcome to the novel targeted agents, such as the BTK inhibitor ibrutinib.

The Impact of a Cochlear Implant Electrode Array on the Middle Ear Transfer Function.

Objectives: As a treatment for partial deafness with residual hearing in the lower frequency range, the combined acoustic and electric stimulation of the cochlea has become widespread. Acoustic stimulation is provided by a hearing aid's airborne sound and the electric stimulation by a cochlear implant electrode array, which may be inserted through the round window or a cochleostomy. To take advantage of that concept, it is essential to preserve residual hearing after surgery.

When Hearing Is Tricky: Speech Processing Strategies in Prelingually Deafened Children and Adolescents with Cochlear Implants Having Good and Poor Speech Performance.

Cochlear implants provide individuals who are deaf with access to speech. Although substantial advancements have been made by novel technologies, there still is high variability in language development during childhood, depending on adaptation and neural plasticity. These factors have often been investigated in the auditory domain, with the mismatch negativity as an index for sensory and phonological processing.

Efficient orbit-aware triad and quad census in directed and undirected graphs.

The prevalence of select substructures is an indicator of network effects in applications such as social network analysis and systems biology. Moreover, subgraph statistics are pervasive in stochastic network models, and they need to be assessed repeatedly in MCMC sampling and estimation algorithms. We present a new approach to count all induced and non-induced four-node subgraphs (the quad census) on a per-node and per-edge basis, complete with a separation into their non-automorphic roles in these subgraphs.