Importance: There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment.
Objectives: To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based transforming growth factor β1 (TGF-β1).
Design, Setting, And Participants: A total of 891 patients with advanced HNSCC from a phase 3 trial of cisplatin plus radiotherapy with or without cetuximab (NRG Oncology RTOG 0522) were included in this study, and 413 patients with available samples were genotyped for the KRAS-variant.
Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged 75 nmol/l).
View Article and Find Full Text PDFBackground: Atypical meningioma (AM) is an aggressive subtype of meningioma associated with a high recurrence rates (RR) following surgical resection. Recent studies have compared outcomes of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, we systematically analyzed the current literature on AM and compared outcomes of ARS versus SS after STR.
View Article and Find Full Text PDFStrategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation.
View Article and Find Full Text PDFObjective: To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder.
Methods: Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences.
Purpose: To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC).
Methods: The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16 (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC).
Background: The purpose of this study was to compare outcomes of patients with p16-positive oropharyngeal squamous cell carcinoma (SCC) treated with postoperative intensity-modulated radiotherapy (IMRT) before and after an institutional dose reduction policy effective on February 2009.
Methods: Between 1998 and 2013, 175 consecutive patients with p16-positive oropharyngeal SCC with extracapsular extension (ECE) and/or close or positive margins were treated postoperatively to 66 Gy (n = 109) or 60 Gy (n = 66) in 2 Gy/fx.
Results: Between the 66 and 60 Gy groups, there was no difference in tumor classification (pT4 vs pT1-T3; p = .
Background: Since the completion of the Human Genome Project in 2003, it is estimated that more than 200,000 individual whole human genomes have been sequenced. A stunning accomplishment in such a short period of time. However, most of these were sequenced without experimental haplotype data and are therefore missing an important aspect of genome biology.
View Article and Find Full Text PDFBackground: Approximately 50,000 women in the United States undergo mastectomy and immediate prosthetic breast reconstruction annually, and most receive postoperative prophylactic antibiotics. The effect of these antibiotics on the risk of surgical-site infections remains unclear.
Methods: The authors searched the Medline, Embase, and Cochrane Library databases for studies that compared less than 24 hours and greater than 24 hours of antibiotics following immediate prosthetic breast reconstruction.
Background And Objective: Children with epilepsy are at increased risk of other disorders and difficulties, preceding, cooccurring with, or after the diagnosis of epilepsy. Risk estimates vary, few studies are population-based, and few provide comprehensive assessments of comorbidities. We used nationwide registry data to describe frequencies of medical, neurologic, developmental, and psychiatric conditions occurring before and after children are diagnosed with childhood epilepsy.
View Article and Find Full Text PDFBackground: Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF1A2, encoding a neuromuscular specific translation elongation factor, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each with a different mutation, of which five are newly described.
View Article and Find Full Text PDFIn April 2014, poor fertility in a major commercial goose breeder operation in California triggered the submission of six live affected Toulouse ganders ( Anser anser ) to the California Animal Health and Food Safety Laboratory, Turlock branch (University of California-Davis). Toulouse were principally affected among all breeds, and their egg fertility dropped from 65.7% to less than 33.
View Article and Find Full Text PDFLiving with epilepsy in childhood has implications for the child and their family beyond the physical effects associated with epileptic seizures. Qualitative research has emerged, aiming to deliver a greater depth of understanding of the experiences of living with epilepsy from the perspectives of children with epilepsy, their parents, and their siblings. This review of qualitative research had three aims: first, to synthesize the demographic and epilepsy profiles of research participants in eligible studies in order to provide a clear picture of who are included and excluded when studying families' experiences; second, to present and discuss the methodological concerns and implications of research involving children with epilepsy; and third, to synthesize the findings arising from qualitative research with families in order to identify common themes across all relevant studies to date.
View Article and Find Full Text PDFJ Clin Neuromuscul Dis
June 2016
Abnormal concentrations of nutritional factors were found in 24.1% of 187 patients with neuropathy who were newly seen at our academic neuropathy referral center over a 1-year period. All patients presented with sensory axonal or small fiber neuropathy.
View Article and Find Full Text PDFIn recurrent hepatitis C (HCV) post-liver transplantation (OLT), the combination of immunosuppressants and HCV is postulated to increase hepatocyte apoptosis and liver fibrosis. We evaluated hepatocyte apoptosis within the liver tissue of patients with postOLT HCV recurrence compared to HCV-negative individuals and correlated these findings with the effects of immunosuppressants on HCV-induced cell death and its inhibition in primary mouse hepatocytes (PMoH). Liver biopsies from patients with and without HCV were evaluated by immunohistochemistry for markers of apoptosis M30 CytoDEATH (M30) and cleaved PARP (clPARP).
View Article and Find Full Text PDFAn effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and class II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles.
View Article and Find Full Text PDFObjectives: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons.
View Article and Find Full Text PDFBackground: The cell line BT-474 is a popular cell line for studying the biology of cancer and developing novel drugs. However, there is no complete, published genome sequence for this highly utilized scientific resource. In this study we sought to provide a comprehensive and useful data set for the scientific community by generating a whole genome sequence for BT-474.
View Article and Find Full Text PDFAn asymptomatic 14-year old, male black swan ( Cygnus atratus ) housed at a zoological institution was presented for routine preshipment examination. Hematologic findings indicated that the bird had a severe lymphocytic leukocytosis, consistent with chronic lymphocytic leukemia. Radiographs showed the presence of multiple soft tissue masses within the caudal coelomic cavity; ultrasound showed one mass to be an enlarged spleen, a cystic mass near the gonads, and a mass suspected to be associated with the ventriculus.
View Article and Find Full Text PDFObjective: To evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease and distant metastases in patients with head and neck squamous cell carcinomas (HNSCCs) following radiotherapy with or without chemotherapy.
Data Sources: A systematic review with no language restrictions was conducted using PREMEDLINE, MEDLINE, EMBASE, and Google Scholar.
Review Methods: Only prospective studies with histopathological and/or clinical follow-up that assessed the diagnostic accuracy of PET and PET/CT in detecting residual and/or recurrent disease following radiotherapy with or without chemotherapy in patients with HNSCCs were included.
Recent data from genetic and brain imaging studies have urged rethinking of bipolar disorder (BD) and schizophrenia (SCZ) as lying along a continuum of major endogenous psychoses rather than dichotomous disorders. We systematically reviewed extant studies (from January 2000 to July 2015) that directly compared neurocognitive impairments in adults with SCZ and BD. Within 36 included studies, comparable neurocognitive impairments were found in SCZ and BD involving executive functioning, working memory, verbal fluency and motor speed.
View Article and Find Full Text PDFCholesterol and fatty acid biosynthesis are regulated by the sterol regulatory element-binding proteins (SREBPs), encoded by Srebf1 and Srebf2. We generated mice that were either deficient or hypomorphic for SREBP-2. SREBP-2 deficiency generally caused death during embryonic development.
View Article and Find Full Text PDF