Highly Sensitive Multiplex Detection of Molecular Biomarkers Using Hybridization Chain Reaction in an Encoded Particle Microfluidic Platform.

In the continuous combat against diseases, there is the need for tools that enable an improved diagnostic efficiency towards higher information density combined with reduced time-to-result and cost. Here, a novel fully integrated microfluidic platform, the Evalution™, is evaluated as a potential solution to this need. Encoded microparticles combined with channel-based microfluidics allow a fast, sensitive and simultaneous detection of several disease-related biomarkers.

FLUIDOT: A Modular Microfluidic Platform for Single-Cell Study and Retrieval, with Applications in Drug Tolerance Screening and Antibody Mining.

Advancements in lab-on-a-chip technologies have revolutionized the single-cell analysis field. However, an accessible platform for in-depth screening and specific retrieval of single cells, which moreover enables studying diverse cell types and performing various downstream analyses, is still lacking. As a solution, FLUIDOT is introduced, a versatile microfluidic platform incorporating customizable microwells, optical tweezers and an interchangeable cell-retrieval system.

Highly flexible and accurate serial picoinjection in droplets by combined pressure and flow rate control.

Picoinjection is a robust method for reagent addition into microfluidic droplets and has enabled the implementation of numerous multistep droplet assays. Although serial picoinjectors allow to screen many conditions in one run by injecting different combinations of reagents, their use is limited because it is complex to accurately control each injector independently. Here, we present a novel method for flexible, individual picoinjector control that allows to inject a predefined range of volumes by controlling the flow rate of the injector as well as turning off injection by setting the equilibrium pressure, which resulted in a stable interface of the injector liquid with the main microfluidic channel.

Cartilaginous spheroid-assembly design considerations for endochondral ossification: towards robotic-driven biomanufacturing.

Spheroids have become essential building blocks for biofabrication of functional tissues. Spheroid formats allow high cell-densities to be efficiently engineered into tissue structures closely resembling the native tissues. In this work, we explore the assembly capacity of cartilaginous spheroids (∼ 150m) in the context of endochondral bone formation.

From Initial Encounter With Mid-Air Haptic Feedback to Repeated Use: The Role of the Novelty Effect in User Experience.

Mid-air haptic (MAH) feedback is an interesting means to provide augmented haptic feedback for gesture-based technology as it enables a sense of touch without physical contact with an actuator. Although quite some work already investigated the user experience (UX) of MAH feedback during initial encounter, we are not aware of studies testing the UX after repeated use, with regard to both pragmatic and hedonic UX, as well as emotional reactions. In this article, we tested how the UX of MAH feedback changed over the course of five weeks by collecting both questionnaire as well as interview data of 31 participants.

Neuromedin U signaling regulates retrieval of learned salt avoidance in a C. elegans gustatory circuit.

Learning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of C. elegans gustatory aversive learning.

DNA-only, microwell-based bioassay for multiplex nucleic acid detection with single base-pair resolution using MNAzymes.

In disease diagnostics, single- and multiplex nucleic acid (NA) detection, with the potential to discriminate mutated strands, is of paramount importance. Current techniques that rely on target amplification or protein-enzyme based signal amplification are highly relevant, yet still plagued by diverse drawbacks including erroneous target amplification, and the limited stability of protein enzymes. As a solution, we present a multicomponent nucleic acid enzymes (MNAzymes)-based system for singleplex and multiplex detection of NA targets in microwells down to femtomolar (fM) concentrations, without the need for any target amplification or protein enzymes, while operating at room temperature and with single base-pair resolution.

Boosting biomolecular interactions through DNA origami nano-tailored biosensing interfaces.

The interaction between a bioreceptor and its target is key in developing sensitive, specific and robust diagnostic devices. Suboptimal interbioreceptor distances and bioreceptor orientation on the sensor surface, resulting from uncontrolled deposition, impede biomolecular interactions and lead to a decreased biosensor performance. In this work, we studied and implemented a 3D DNA origami design, for the first time comprised of assay specifically tailored anchoring points for the nanostructuring of the bioreceptor layer on the surface of disc-shaped microparticles in the continuous microfluidic environment of the innovative EvalutionTM platform.

Controlling the Bioreceptor Spatial Distribution at the Nanoscale for Single Molecule Counting in Microwell Arrays.

The ability to detect low concentrations of protein biomarkers is crucial for the early-stage detection of many diseases and therefore indispensable for improving diagnostic devices for healthcare. Here, we demonstrate that by integrating DNA nanotechnologies like DNA origami and aptamers, we can design innovative biosensing concepts for reproducible and sensitive detection of specific targets. DNA origami structures decorated with aptamers were studied as a novel tool to structure the biosensor surface with nanoscale precision in a digital detection bioassay, enabling control of the density, orientation, and accessibility of the bioreceptor to optimize the interaction between target and aptamer.

Complex affect dynamics add limited information to the prediction of psychological well-being.

Over the years, many studies have demonstrated a relation between emotion dynamics and psychological well-being. Because our emotional life is inherently time-dynamic, affective scientists argue that, next to how positive or negative we feel on average, patterns of emotional change are informative for mental health. This growing interest initiated a surge in new affect dynamic measures, each claiming to capture a unique dynamical aspect of our emotional life, crucial for understanding well-being.

Teflon-on-Glass Molding Enables High-Throughput Fabrication of Hydrophilic-in-Hydrophobic Microwells for Bead-Based Digital Bioassays.

In recent years, Teflon-on-glass microwells have been successfully implemented in bead-based digital bioassays for the sensitive detection of single target molecules. Their hydrophilic-in-hydrophobic (HIH) nature enables the isolation and analysis of individual beads, carrying the target molecules, which can be further manipulated accurately through optical tweezer (OT) setups. However, these Teflon HIH-microwell platforms are conventionally fabricated through a complex, time-consuming and labor-intensive dry lift-off procedure which involves a series of major steps, limiting the up-scaling potential of these platforms.

Three-Dimensional DNA Origami as Programmable Anchoring Points for Bioreceptors in Fiber Optic Surface Plasmon Resonance Biosensing.

Many challenges in biosensing originate from the fact that the all-important nanoarchitecture of the biosensor surface, including precise density and orientation of bioreceptors, is not entirely comprehended. Here, we introduced a three-dimensional DNA origami as a bioreceptor carrier to functionalize the fiber optic surface plasmon resonance (FO-SPR) sensor with nanoscale precision. Starting from a 24-helix bundle, two distinct DNA origami structures were designed to position thrombin-specific aptamers with different densities and distances (27 and 113 nm) from the FO-SPR surface.

Depressive Symptoms and Category Learning: A Preregistered Conceptual Replication Study.

We present a fully preregistered, high-powered conceptual replication of Experiment 1 by Smith, Tracy, and Murray (1993). They observed a cognitive deficit in people with elevated depressive symptoms in a task requiring flexible analytic processing and deliberate hypothesis testing, but no deficit in a task assumed to require more automatic, holistic processing. Specifically, they found that individuals with depressive symptoms showed impaired performance on a criterial-attribute classification task, requiring flexible analysis of the attributes and deliberate hypothesis testing, but not on a family-resemblance classification task, assumed to rely on holistic processing.

Simple Rules, Not So Simple: The Use of International Ovarian Tumor Analysis (IOTA) Terminology and Simple Rules in Inexperienced Hands in a Prospective Multicenter Cohort Study.

Objectives:  To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert.

Methods:  This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert.

Psoas muscle area is not representative of total skeletal muscle area in the assessment of sarcopenia in ovarian cancer.

Background: Computed tomography measurements of total skeletal muscle area can detect changes and predict overall survival (OS) in patients with advanced ovarian cancer. This study investigates whether assessment of psoas muscle area reflects total muscle area and can be used to assess sarcopenia in ovarian cancer patients.

Methods: Ovarian cancer patients (n = 150) treated with induction chemotherapy and interval debulking were enrolled retrospectively in this longitudinal study.

Sensitivity to the prototype in children with high-functioning autism spectrum disorder: An example of Bayesian cognitive psychometrics.

We present a case study of hierarchical Bayesian explanatory cognitive psychometrics, examining information processing characteristics of individuals with high-functioning autism spectrum disorder (HFASD). On the basis of previously published data, we compare the classification behavior of a group of children with HFASD with that of typically developing (TD) controls using a computational model of categorization. The parameters in the model reflect characteristics of information processing that are theoretically related to HFASD.

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

Background: Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS).

Methods: Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively.

Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients.

Background: Malnutrition, weight loss, and muscle wasting (sarcopenia) are common among women with advanced ovarian cancer and have been associated with adverse clinical outcomes and survival. Our objective is to investigate overall survival (OS) related to changes in skeletal muscle (SM) for patients with advanced ovarian cancer treated with neoadjuvant chemotherapy and interval debulking.

Methods: Ovarian cancer patients (n = 123) treated with neoadjuvant chemotherapy and interval debulking in the area of Maastricht (the Netherlands) between 2000 and 2014 were included retrospectively.

Prediction of incomplete primary debulking surgery in patients with advanced ovarian cancer: An external validation study of three models using computed tomography.

Objective: To test the ability of three prospectively developed computed tomography (CT) models to predict incomplete primary debulking surgery in patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer.

Methods: Three prediction models to predict incomplete surgery (any tumor residual >1cm in diameter) previously published by Ferrandina (models A and B) and by Gerestein were applied to a validation cohort consisting of 151 patients with advanced epithelial ovarian cancer. All patients were treated with primary debulking surgery in the Eastern part of the Netherlands between 2000 and 2009 and data were retrospectively collected.

Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands.

Background: Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75-80% and specificity 85-90%).

Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy.

Objective: Since the Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations for 3D MRI-based image-guided adaptive brachytherapy (IGBT) in the treatment of cervical cancer, many institutions have implemented this technique and favourable results were documented. We investigated if introduction of IGBT in our centre indeed improved treatment outcomes and reduced toxicity compared to conventional brachytherapy (CBT).

Methods: A retrospective analysis was done of outcomes of patients with stage IB-IVA cervical cancer treated with primary radiation therapy with curative intent between 2000 and 2012.

Relocatable fixation systems in intracranial stereotactic radiotherapy. Accuracy of serial CT scans and patient acceptance in a randomized design.

Purpose: The goal was to provide a quantitative evaluation of the accuracy of three different fixation systems for stereotactic radiotherapy and to evaluate patients' acceptance for all fixations.

Methods: A total of 16 consecutive patients with brain tumours undergoing fractionated stereotactic radiotherapy (SCRT) were enrolled after informed consent (Clinical trials.gov: NCT00181350).

What is the most accurate whole-body imaging modality for assessment of local and distant recurrent disease in colorectal cancer? A meta-analysis : imaging for recurrent colorectal cancer.

Purpose: The objective of this study was to compare the diagnostic performance of positron emission tomography (PET), PET/CT, CT and MRI as whole-body imaging modalities for the detection of local and/or distant recurrent disease in colorectal cancer (CRC) patients who have a (high) suspicion of recurrent disease, based on clinical findings or rise in carcinoembryonic antigen (CEA).

Methods: A meta-analysis was undertaken. PubMed and Embase were searched for studies on the accuracy of whole-body imaging for patients with suspected local and/or distant recurrence of their CRC.