Einleitung und Abbruch der künstlichen Ernährung beim einwilligungsunfähigen Patienten

Definition of the problem: In Austria the legal discussion on initiating and withdrawing artificial nutrition in incompetent patients has just begun. Arguments and conclusion: Legal regulations are lacking, but there appears to be agreement on accepting advance directives under specific criteria. This would mean that a presumed will and documented refusal of treatment and nutrition has to be respected by physicians. However, there is no consensus with regard to the “supposed will” of an incompetent patient to refuse treatment and nutrition. At present, surrogate decision making with regard to refusing life-sustaining treatment or nutrition is only accepted according to a declared and documented directive of the patient himself. When the patient’s will has to be “surmised” the protection of life has priority. In Austria this concept is based on the national constitution and its duty to protect life.     

Linear shape from shading

In many situations the reflectance function of a surface is approximately linear, and there is an effielent closed-form solution to the shape-from-shading problem. When boundary conditions (e.g., edges, singular points) are not available, good estimates of shape may still be extracted by using the assumption of general viewing position. An improved method for estimating the illuminant direction is also presented.     

Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.     

Glioblastoma Extracellular Vesicle-Specific Peptides Inhibit EV-Induced Neuronal Cytotoxicity

WHO Grade 4 IDH-wild type astrocytoma (GBM) is the deadliest brain tumor with a poor prognosis. Meningioma (MMA) is a more common “benign” central nervous system tumor but with significant recurrence rates. There is an urgent need for brain tumor biomarkers for early diagnosis and effective treatment options. Extracellular vesicles (EVs) are tiny membrane-enclosed vesicles that play essential functions in cell-to-cell communications among tumor cells. We aimed to identify epitopes of brain tumor EVs by phage peptide libraries. EVs from GBM plasma, MMA plasma, or brain tumor cell lines were used to screen phage-displayed random peptide libraries to identify high-affinity peptides. We purified EVs from three GBM plasma pools (23 patients), one MMA pool (10 patients), and four brain tumor cell lines. We identified a total of 21 high-affinity phage peptides (12 unique) specific to brain tumor EVs. The peptides shared high sequence homologies among those selected by the same EVs. Dose–response ELISA demonstrated that phage peptides were specific to brain tumor EVs compared to controls. Peptide affinity purification identified unique brain tumor EV subpopulations. Significantly, GBM EV peptides inhibit brain tumor EV-induced complement-dependent cytotoxicity (necrosis) in neurons. We conclude that phage display technology could identify specific peptides to isolate and characterize tumor EVs.     

Software specification using graph grammars

The following paper demonstrates that programmed sequential graph grammars can be used in a systematic proceeding to specify the changes of high level intermediate data structures arising in a programming support environment, in which all tools work in an incremental and syntax-driven mode. In this paper we lay stress upon the way to get the specification rather than on the result of this process. Therefore, we give here some approach to “specification engineering” using graph grammars. This approach is influenced by the syntactical definition of the underlying language for Programming in the Small, the module concept etc. to be supported on one side but also by the idea of the user interface.     

Mass Spectrometry-Based Disulfide Mapping of Lysyl Oxidase-like 2

Lysyl oxidase-like 2 (LOXL2) catalyzes the oxidative deamination of peptidyl lysines and hydroxylysines to promote extracellular matrix remodeling. Aberrant activity of LOXL2 has been associated with organ fibrosis and tumor metastasis. The lysine tyrosylquinone (LTQ) cofactor is derived from Lys653 and Tyr689 in the amine oxidase domain via post-translational modification. Based on the similarity in hydrodynamic radius and radius of gyration, we recently proposed that the overall structures of the mature LOXL2 (containing LTQ) and the precursor LOXL2 (no LTQ) are very similar. In this study, we conducted a mass spectrometry-based disulfide mapping analysis of recombinant LOXL2 in three forms: a full-length LOXL2 (fl-LOXL2) containing a nearly stoichiometric amount of LTQ, Δ1-2SRCR-LOXL2 (SRCR1 and SRCR2 are truncated) in the precursor form, and Δ1-3SRCR-LOXL2 (SRCR1, SRCR2, SRCR3 are truncated) in a mixture of the precursor and the mature forms. We detected a set of five disulfide bonds that is conserved in both the precursor and the mature recombinant LOXL2s. In addition, we detected a set of four alternative disulfide bonds in low abundance that is not associated with the mature LOXL2. These results suggest that the major set of five disulfide bonds is retained post-LTQ formation.