Trends in the pre-operative diagnosis and surgical management of axillary lymph node metastases in women with screen-detected breast cancer.

Aim: The aim of the current study was to investigate time-trends in pre-operative diagnosis and surgical treatment of axillary lymph node metastases in breast cancers detected at screening mammography.

Methods: We included all women who underwent screening mammography in the South of the Netherlands between 2005 and 2020. During a follow-up period of at least two years, data on clinical radiological examinations, biopsy procedures and surgical interventions were obtained.

Effects of nonparticipation at previous screening rounds on the characteristics of screen-detected breast cancers.

Purpose: We determined the incidence and effects of different screening intervals prior to a true positive recall on the tumour characteristics of screen-detected cancers (SDC) and interval cancers (ICs) at biennial screening mammography.

Methods: A consecutive series of 553020 subsequent screens was included, obtained in a Dutch screening region between January 2009 and July 2019. During 2-year follow-up, we obtained data on radiological procedures, pathology and surgical interventions of all recalled women.

Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer.

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic ascorbate (P-AscH, high-dose, intravenous vitamin C) is being investigated in clinical trials as an adjunct to standard-of-care chemoradiation treatments.

Failure of stereotactic core needle biopsy in women recalled for suspicious calcifications at screening mammography: frequency, causes, and final outcome in a multi-institutional, observational follow-up study.

Objectives: We determined the failure rate of stereotactic core needle biopsy (SCNB) and its causes and final outcome in women recalled for calcifications at screening mammography.

Methods: We included a consecutive series of 624,039 screens obtained in a Dutch screening region between January 2009 and July 2019. Radiology reports and pathology results were obtained of all recalled women during 2-year follow-up.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity.

Breast magnetic resonance imaging as a problem solving tool in women recalled at biennial screening mammography: A population-based study in the Netherlands.

Purpose: Problem solving magnetic resonance imaging (MRI) is used to exclude malignancy in women with equivocal findings on conventional imaging. However, recommendations on its use for women recalled after screening are lacking. This study evaluates the impact of problem solving MRI on diagnostic workup among women recalled from the Dutch screening program, as well as time trends and inter-hospital variation in its use.

Pregnant Women After Bariatric Surgery: Diagnostic Accuracy of Magnetic Resonance Imaging for Small Bowel Obstruction.

Background: Small bowel obstruction (SBO) is a late complication of Roux-en-Y gastric bypass (RYGB). In non-pregnant patients, computed tomography (CT) is the first choice of imaging. During pregnancy, magnetic resonance imaging (MRI) is preferred to limit exposure to ionizing radiation.

Engineering and application of a biosensor with focused ligand specificity.

Cell factories converting bio-based precursors to chemicals present an attractive avenue to a sustainable economy, yet screening of genetically diverse strain libraries to identify the best-performing whole-cell biocatalysts is a low-throughput endeavor. For this reason, transcriptional biosensors attract attention as they allow the screening of vast libraries when used in combination with fluorescence-activated cell sorting (FACS). However, broad ligand specificity of transcriptional regulators (TRs) often prohibits the development of such ultra-high-throughput screens.

Rationale, Theoretical Underpinnings, and Design of HEAR-aware: Providing Adults With Hearing Loss With Tailored Support to Self-Manage Their Hearing Problems via a Smartphone App, as an Alternative to Hearing Aids.

Purpose An alarming two thirds of adults aged 50 years or over with hearing impairment who could benefit from hearing aids do not own any, leaving these adults with no support to self-manage their hearing problems. In the HEAR-aware project, it is hypothesized that self-management can be facilitated via a smartphone app if its educational content is tailored to a person's dynamic stage of readiness to take action on their hearing (stage of change) and to a person's dynamic acoustical situations (as measured via a wearable microphone) and associated challenges (as captured via ecological momentary assessment). As such, the HEAR-aware app would be an ecological momentary intervention.

NADPH biosensor-based identification of an alcohol dehydrogenase variant with improved catalytic properties caused by a single charge reversal at the protein surface.

Alcohol dehydrogenases (ADHs) are used in reductive biotransformations for the production of valuable chiral alcohols. In this study, we used a high-throughput screening approach based on the NADPH biosensor pSenSox and fluorescence-activated cell sorting (FACS) to search for variants of the NADPH-dependent ADH of Lactobacillus brevis (LbADH) with improved activity for the reduction of 2,5-hexanedione to (2R,5R)-hexanediol. In a library of approx.

The activity of the DNA repair enzyme hOGG1 can be directly modulated by ubiquinol.

The DNA of human cells suffers about 1.000-100.000 oxidative lesions per day.

Structure-Based Redesign of a Self-Sufficient Flavin-Containing Monooxygenase towards Indigo Production.

Indigo is currently produced by a century-old petrochemical-based process, therefore it is highly attractive to develop a more environmentally benign and efficient biotechnological process to produce this timeless dye. Flavin-containing monooxygenases (FMOs) are able to oxidize a wide variety of substrates. In this paper we show that the bacterial mFMO can be adapted to improve its ability to convert indole into indigo.

Diagnostic performance of axillary ultrasound and standard breast MRI for differentiation between limited and advanced axillary nodal disease in clinically node-positive breast cancer patients.

Preoperative differentiation between limited (pN1; 1-3 axillary metastases) and advanced (pN2-3; ≥4 axillary metastases) nodal disease can provide relevant information regarding surgical planning and guiding adjuvant radiation therapy. The aim was to evaluate the diagnostic performance of preoperative axillary ultrasound (US) and breast MRI for differentiation between pN1 and pN2-3 in clinically node-positive breast cancer. A total of 49 patients were included with axillary metastasis confirmed by US-guided tissue sampling.

A forensic visual aid: Traces versus knowledge.

In this paper, I introduce the Forensic Field Map (FFM) that provides a two-dimensional view on the forensic field. This field is by definition very broad, encompassing a wide range of scientific areas and activities. The forensic work that supports solving criminal cases ranges from recognizing and preserving traces at crime scenes to explaining forensic results as expert witness in court.

Advancing Coordinated Cyber-investigations and Tool Interoperability using a Community Developed Specification Language.

Any investigation can have a digital dimension, often involving information from multiple data sources, organizations and jurisdictions. Existing approaches to representing and exchanging cyber-investigation information are inadequate, particularly when combining data sources from numerous organizations or dealing with large amounts of data from various tools. To perform digital investigations effectively, there is a pressing need to harmonize how information relevant to cyber-investigations is represented and exchanged.

Engineering Cyclohexanone Monooxygenase for the Production of Methyl Propanoate.

A previous study showed that cyclohexanone monooxygenase from Acinetobacter calcoaceticus (AcCHMO) catalyzes the Baeyer-Villiger oxidation of 2-butanone, yielding ethyl acetate and methyl propanoate as products. Methyl propanoate is of industrial interest as a precursor of acrylic plastic. Here, various residues near the substrate and NADP binding sites in AcCHMO were subjected to saturation mutagenesis to enhance both the activity on 2-butanone and the regioselectivity toward methyl propanoate.

Covalent immobilization of a flavoprotein monooxygenase via its flavin cofactor.

A generic approach for flavoenzyme immobilization was developed in which the flavin cofactor is used for anchoring enzymes onto the carrier. It exploits the tight binding of flavin cofactors to their target apo proteins. The method was tested for phenylacetone monooxygenase (PAMO) which is a well-studied and industrially interesting biocatalyst.

Lyophilization conditions for the storage of monooxygenases.

Cyclohexanone monooxygenase (CHMO) was used as a model enzyme to find suitable freeze-drying conditions for long-term storage of an isolated monooxygenase. CHMO is a Baeyer-Villiger monooxygenase (BVMO) known for its ability to catalyze a large number of oxidation reactions. With a focus on establishing the optimal formulation, additives were tested for enzyme stabilization during and after lyophilization.

Synthesis of methyl propanoate by Baeyer-Villiger monooxygenases.

Methyl propanoate is an important precursor for polymethyl methacrylates. The use of a Baeyer-Villiger monooxygenase (BVMO) to produce this compound was investigated. Several BVMOs were identified that produce the chemically non-preferred product methyl propanoate in addition to the normal product ethyl acetate.

Stabilization of cyclohexanone monooxygenase by a computationally designed disulfide bond spanning only one residue.

Enzyme stability is an important parameter in biocatalytic applications, and there is a strong need for efficient methods to generate robust enzymes. We investigated whether stabilizing disulfide bonds can be computationally designed based on a model structure. In our approach, unlike in previous disulfide engineering studies, short bonds spanning only a few residues were included.

[Interceptive treatment of maxillary hypoplasia with the use of bone anchors. A review of the literature].

A Class III malocclusion is mainly caused by a hypoplastic maxilla and therefore the treatment is principally aimed at stimulating the growth of the maxilla. Disadvantages of conventional treatment methods are that treatment effects are mainly dentoalveolar rather than skeletal and that there is often an increase in the height of the lowerface. Moreover, patients are not always cooperative about wearing extra-oral appliances.

Exploring the structural basis of substrate preferences in Baeyer-Villiger monooxygenases: insight from steroid monooxygenase.

Steroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer-Villiger conversion of progesterone into progesterone acetate using FAD as prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence similarity with well characterized Baeyer-Villiger monooxygenases, including phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative biochemical and structural analysis of STMO can be particularly insightful with regard to the understanding of the substrate-specificity properties of Baeyer-Villiger monooxygenases that are emerging as promising tools in biocatalytic applications and as targets for prodrug activation.