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Enzymatic Ligation involving Disulfide-Rich Canine Venom Proteins: Employing Sortase Any to create Double-Knotted Proteins.
The transfusion probability of patients with a hemoglobin of 9.0-10.0 g/dL, 10.0-11.0 g/dL, 11.0-12.0 g/dL and 12.0-13.0 g/dL was 100%, 33.3%, 10% and 5.6%, and the NNT 1.5, 4.3, 22.7 and 17.3, while it was 100%, 50%, 25% and 14.3% with a NNT of 2.0, 4.0, 9.3 and 7.0 in patients with a drain, respectively. Preoperative anemia and the insertion of drains are more predictive for RBC transfusions than the use of tranexamic acid. Based on this, a personalized transfusion probability can be computed, that may help to identify patients who could benefit from blood saving programs.Understanding how a tumour evolves and avoids immune recognition is paramount to improving cancer immunotherapy and patient outcome. Here we examine our recent integration of multi-region genomic, transcriptomic, epigenomic, pathology, and clinical data, highlight the need for a systematic examination of immune escape mechanisms, and discuss implications for immunotherapy approaches.Cannabis and its derivatives are being used increasingly by patients with cancer, including patients with glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy. Despite promising preclinical data suggesting potential anti-cancer effects for cannabinoids in GBM, clinical and safety data are lacking. This editorial will discuss a recent Phase 1b trial of nabiximols oromucosal spray in combination with dose-intense temozolomide in patients with recurrent GBM in the context of other relevant findings in this field.
Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.

Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored.

The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.

With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. learn more The observed survival differences support further exploration in an adequately powered randomised controlled trial.

ClinicalTrials.gov Part 1- NCT01812603; Part 2- NCT01812616.
ClinicalTrials.gov Part 1- NCT01812603; Part 2- NCT01812616.Subjective cognitive decline (SCD) has been proposed as a risk factor for future cognitive decline and dementia. Given the heterogeneity of SCD and the lack of consensus about how to classify this condition, different operationalization approaches still need to be compared. In this study, we used the same sample of individuals to compare different SCD operationalization approaches. We included 399 cognitively healthy individuals from a community-based cohort. SCD was assessed through nine questions about memory and non-memory subjective complaints. We applied four approaches to operationalize SCD two hypothesis-driven approaches and two data-driven approaches. We characterized the resulting groups from each operationalization approach using multivariate methods on comprehensive demographic, clinical, cognitive, and neuroimaging data. We identified two main phenotypes an amnestic phenotype characterized by an Alzheimer's Disease (AD) signature pattern of brain atrophy; and an anomic phenotype, which was mainly related to cerebrovascular pathology. Furthermore, language complaints other than naming helped to identify a subgroup with subclinical cognitive impairment and difficulties in activities of daily living. This subgroup also showed an AD signature pattern of atrophy. The identification of SCD phenotypes, characterized by different syndromic and biomarker profiles, varies depending on the operationalization approach used. In this study we discuss how these findings may be used in clinical practice and research.Temporal bone CT-scan is a prerequisite in most surgical procedures concerning the ear such as cochlear implants. The 3D vision of inner ear structures is crucial for diagnostic and surgical preplanning purposes. Since clinical CT-scans are acquired at relatively low resolutions, improved performance can be achieved by registering patient-specific CT images to a high-resolution inner ear model built from accurate 3D segmentations based on micro-CT of human temporal bone specimens. This paper presents a framework based on convolutional neural network for human inner ear segmentation from micro-CT images which can be used to build such a model from an extensive database. The proposed approach employs an auto-context based cascaded 2D U-net architecture with 3D connected component refinement to segment the cochlear scalae, semicircular canals, and the vestibule. The system was formulated on a data set composed of 17 micro-CT from public Hear-EU dataset. A Dice coefficient of 0.90 and Hausdorff distance of 0.74 mm were obtained. The system yielded precise and fast automatic inner-ear segmentations.Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against GAS infections and the T-antigen represents an attractive target for vaccination. We have generated a multivalent vaccine called TeeVax1, a recombinant protein that consists of a fusion of six T-antigen domains. Vaccination with TeeVax1 produces opsonophagocytic antibodies in rabbits and confers protective efficacy in mice against invasive disease. Two further recombinant proteins, TeeVax2 and TeeVax3 were constructed to cover 12 additional T-antigens. Combining TeeVax1-3 produced a robust antibody response in rabbits that was cross-reactive to a full panel of 21 T-antigens, expected to provide over 95% vaccine coverage. These results demonstrate the potential for a T-antigen-based vaccine to prevent GAS infections.
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