Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA1 RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and
Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.
Background: Fibrolamellar carcinoma (FLC) is a rare malignancy of the liver that differs from typical hepatocellular carcinoma (HCC) in several aspects such as the absence of underlying liver disease and occurrence in younger patients. Even though the survival rates in FLC are slightly better than in typical HCC, the prognosis of metastatic FLC remains deleterious. Several reports suggest that systemic chemotherapy regimens can successfully be used to halt disease progression in FLC, while targeted tumor therapy with sorafenib seems to be of limited efficiency. However, results from controlled clinical trials investigating systemic therapies in FLC are virtually nonexistent. Therefore, the choice of treatment often relies on case series with limited numbers of patients. Immunotherapy with checkpoint inhibitors is an emerging cancer therapy in several solid malignancies including HCC. Currently, there do not exist any reports on the use of checkpoint inhibitors in FLC. Case Report: Here, we describe a case of advanced FLC in a young man receiving immunotherapy, who progressed after 3 months of treatment – similar to 2 other patients with advanced FLC at our hospital. Conclusion: While immunotherapy seems to be a promising treatment with limited side effects in several other tumor entities, there is currently no data supporting tumor response in FLC.
As herd sizes have increased in the last decades, computerized monitoring solutions, which provide fast, objective and accurate evaluations of the herd status, gain more and more importance. This study analyzes the feasibility of a Time-of-Flight-camera-based system for gathering body traits in dairy cows for use under cow barn conditions. Recording, determination of body condition score on a 5 point scale by visual and manual inspection, and measuring the backfat thickness with ultrasound took place from July 2011 to May 2012 at the dairy research farm Karkendamm of the Institute of Animal Breeding and Husbandry, Christian-Albrechts-University Kiel (Germany) and between August 2010 and July 2012 at the Institute for Agricultural Engineering and Animal Husbandry of Bavarian State Research Center for Agriculture in Grub (Germany). The two breeds Holstein Friesian cows (Karkendamm) and Fleckvieh (Grub) were considered in this study. Software for recording, image sorting and evaluation, determining the body parts needed, and extracting traits from the images was written and assembled to an automated system. Sorting the images and finding ischeal tuberosities, base of the tail, and dishes of the rump, backbone, and hips had error rates of 0.2%, 1.5%, 0.1%, and 2.6%, respectively. 13 traits were extracted and compared to backfat thickness and body condition score as well as between breeds. All traits depend significantly on the animal and showed very large effect sizes. Coefficients of determination restricted to individual animals were reaching up to 0.89. The precision in measuring the traits and gathering backfat thickness was comparable. Results indicated that the application of Time-Of-Flight in determination of body traits is feasible.
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