Sealing Zone Failure Decreases the Long Term Durability of Endovascular Aneurysm Repair.

Objective: Endovascular aneurysm repair (EVAR) has a higher long term aneurysm related mortality rate compared with open surgery, mainly due to aneurysm rupture. Loss of stent graft to vessel apposition at the EVAR sealing zones is a potential cause of post-EVAR rupture. This study aimed to investigate sealing zone failure and its relationship with post-EVAR rupture.

Automated surveillance of antimicrobial consumption in intensive care, northern Sweden: an observational case study.

Background: The digitalization of information systems allows automatic measurement of antimicrobial consumption (AMC), helping address antibiotic resistance from inappropriate drug use without compromising patient safety.

Objectives: Describe and characterize a new automated AMC surveillance service for intensive care units (ICUs), with data stratified by referral clinic and linked with individual patient risk factors, disease severity, and mortality.

Methods: An automated service collecting data from the electronic medical record was developed, implemented, and validated in a healthcare region in northern Sweden.

MYB alternative promoter activity is increased in adenoid cystic carcinoma metastases and is associated with a specific gene expression signature.

Objective: Adenoid cystic carcinoma (ACC) is a head and neck cancer with a poor long-term prognosis that shows frequent local recurrences and distant metastases. The tumors are characterized by MYB oncogene activation and are notoriously unresponsive to systemic therapies. The biological underpinnings behind therapy resistance of disseminated ACC are largely unknown.

The mitotic checkpoint kinase BUB1 is a direct and actionable target of MYB in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a head and neck cancer that frequently originates in salivary glands, but can also strike other exocrine glands such as the breast. A key molecular alteration found in the majority of ACC cases is MYB gene rearrangements, leading to activation of the oncogenic transcription factor MYB. In this study, we used immortalised breast epithelial cells and an inducible MYB transgene as a model of ACC.

Comprehensive molecular characterization of adenoid cystic carcinoma reveals tumor suppressors as novel drivers and prognostic biomarkers.

Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers.

Increased MYB alternative promoter usage is associated with relapse in acute lymphoblastic leukemia.

Therapy-resistant disease is a major cause of death in patients with acute lymphoblastic leukemia (ALL). Activation of the MYB oncogene is associated with ALL and leads to uncontrolled neoplastic cell proliferation and blocked differentiation. Here, we used RNA-seq to study the clinical significance of MYB expression and MYB alternative promoter (TSS2) usage in 133 pediatric ALLs.

Synthetic oleanane triterpenoids suppress oncogene activity and sensitize T-cell acute lymphoblastic leukemia cells to chemotherapy.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with poor prognosis. The oncogene encodes a master transcription factor that is activated in the majority of human T-ALLs. In the present study, we have performed a large-scale screening with small-molecule drugs to find clinically useful inhibitors of gene expression in T-ALL.

Chromosome Translocations, Gene Fusions, and Their Molecular Consequences in Pleomorphic Salivary Gland Adenomas.

Salivary gland tumors are a heterogeneous group of tumors originating from the major and minor salivary glands. The pleomorphic adenoma (PA), which is the most common subtype, is a benign lesion showing a remarkable morphologic diversity and that, upon recurrence or malignant transformation, can cause significant clinical problems. Cytogenetic studies of >500 PAs have revealed a complex and recurrent pattern of chromosome rearrangements.

Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study.

Adenoid cystic carcinoma (ACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an gene fusion or, more rarely, an fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of alterations by FISH and immunohistochemistry.

Editor's Choice - Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture.

Objective: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture.

The outcome of targeted NGS screening in patients with syndromic forms of sagittal and pansynostosis - IL11RA is an emerging core-gene for pansynostosis.

Here, we have studied the prevalence and spectrum of genetic alterations in syndromic forms of sagittal and pansynostosis. Eighteen patients with sagittal synostosis (isolated or combined with other synostoses, except coronal) or pansynostosis were phenotypically assessed by retrospective analysis of medical records, three-dimensional computed tomography skull reconstructions, and registered photos. Patient DNAs were analyzed using a targeted next-generation sequencing (NGS) panel including 63 craniosynostosis (CS) related genes.

Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity.

Studies of the role of MYB in human malignancies have highlighted MYB as a potential drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC). Here, we present the initial characterization of 2-amino-4-(3,4,5-trimethoxyphenyl)-4-naphtho[1,2-]pyran-3-carbonitrile (Bcr-TMP), a nanomolar-active MYB-inhibitory compound identified in a screen for novel MYB inhibitors. Bcr-TMP affects MYB function in a dual manner by inducing its degradation and suppressing its transactivation potential by disrupting its cooperation with co-activator p300.

Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner.

Studies of the role of MYB in human malignancies have highlighted MYB as a potential drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC). Although transcription factors are often considered un-druggable, recent work has demonstrated successful targeting of MYB by low molecular weight compounds. This has fueled the notion that inhibition of MYB has potential as a therapeutic approach against MYB-driven malignancies.

A population-based study of post-endovascular aortic repair rupture during 15 years.

Objective: The devastating event of a ruptured abdominal aortic aneurysm (rAAA) in patients who have survived a previous AAA repair, either elective or urgent, is a feared and quite uncommon event. It has been suggested to partly explain the loss of the early survival benefit for endovascular aortic repair (EVAR) vs open surgical repair (OSR). The main objective of this study was to report the national incidence rate, risk factors and outcome of post-EVAR ruptures.

Paperboard Coating Detection Based on Full-Stokes Imaging Polarimetry.

The manufacturing of high-quality extruded low-density polyethylene (PE) paperboard intended for the food packaging industry relies on manual, intrusive, and destructive off-line inspection by the process operators to assess the overall quality and functionality of the product. Defects such as cracks, pinholes, and local thickness variations in the coating can occur at any location in the reel, affecting the sealable property of the product. To detect these defects locally, imaging systems must discriminate between the substrate and the coating.

Development and Evaluation of Drug Loaded Regenerated Bacterial Cellulose-Based Matrices as a Potential Dosage Form.

Bacterial cellulose (BC) is a highly pure form of cellulose and possesses superior physico-mechanical properties with wide range of applications. These properties of BC can further be improved by various modifications, including its regeneration from the BC solution. In the current research work, regenerated BC (R-BC) matrices were prepared using N-methyl-morpholine-oxide (NMMO; 50% w/w solution in water) and loaded with model drugs, i.

Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.

Background: The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.

Methods: We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients).

Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB.

The pleomorphic adenoma (PA), which is the most common salivary gland neoplasm, is a benign tumor characterized by recurrent chromosome rearrangements involving 8q12 and 12q14-15. We have previously shown that the PLAG1 and HMGA2 oncogenes are the targets of these rearrangements. Here, we have identified previously unrecognized subsets of PAs with ins(9;8)/t(8;9) (n = 5) and ins(9;12)/t(9;12) (n = 8) and breakpoints located in the vicinity of the PLAG1 and HMGA2 loci.

ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer that preferentially occurs in the head and neck, breast, as well as in other sites. It is an aggressive cancer with high rates of recurrence and distant metastasis. Patients with advanced disease are generally incurable due to the lack of effective systemic therapies.

NGS targeted screening of 100 Scandinavian patients with coronal synostosis.

Craniosynostosis (CS), the premature closure of one or more cranial sutures, occurs both as part of a syndrome or in isolation (nonsyndromic form). Here, we have studied the prevalence and spectrum of genetic alterations associated with coronal suture closure in 100 Scandinavian patients treated at a single craniofacial unit. All patients were phenotypically assessed and analyzed with a custom-designed 63 gene NGS-panel.

Clinical and genomic features of adult and paediatric acute leukaemias with ophthalmic manifestations.

Objective: To describe the clinicopathological and genomic features of nine patients with primary and secondary orbital/ocular manifestations of leukaemia.

Methods: All orbital/ocular leukaemic specimens from 1980 to 2009 were collected from the Danish Register of Pathology. In six cases, medical records and formalin-fixed, paraffin-embedded blocks were available.

IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors.

Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription factors, transcriptional co-regulators, growth factor receptors, tyrosine kinases, and chromatin modifiers. In addition to being useful diagnostic biomarkers, they are also targets for development of new molecularly targeted therapies.

Clinical, genetic and experimental studies of the Brooke-Spiegler (CYLD) skin tumor syndrome.

Brooke-Spiegler syndrome (BSS; a.k.a.

Estrous detection by continuous measurements of vaginal temperature and conductivity with supervised machine learning in cattle.

This study aimed to evaluate the effectiveness of estrous detection technique based on continuous measurements of vaginal temperature (VT) and conductivity (VC) with supervised machine learning in cattle. The VT and VC of 17 cows in tie-stalls were measured using our developed wearable vaginal sensor from Day 11 (Day 0 = ovulation day) to Day 11 of the subsequent estrous cycle at 15-min interval. After the maximum VT and VC were extracted hourly, their changes were expressed as residual VT (rVT = actual VT - mean VT for the same time on the previous 3 days) and as VC ratio (VCr = actual VC/mean VC for the same time on Day 11-13), respectively, and were used for analysis.