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Using the biomarker hypermethylated DNA (hmDNA) for cancer detection requires a pretreatment to isolate or concentrate hmDNA from nonmethylated DNA. Affinity chromatography using a methyl binding domain-2 (MBD2) protein can be used, but the relatively low enrichment selectivity of MBD2 limits its clinical applicability. Here, we developed a superselective, multivalent, MBD2-coated platform to improve the selectivity of hmDNA enrichment. The multivalent platform employs control over the MBD2 surface receptor density, which is shown to strongly affect the binding of DNA with varying degrees of methylation, improving both the selectivity and the affinity of DNAs with higher numbers of methylation sites. Histidine-10-tagged MBD2 was immobilized on gold surfaces with receptor density control by tuning the amount of nickel nitrilotriacetic acid (NiNTA)-functionalized thiols in a thiol-based self-assembled monolayer. The required MBD2 surface receptor densities for DNA surface binding decreases for DNA with higher degrees of methylation. Both higher degrees of superselectivity and surface coverages were observed upon DNA binding at increasing methylation levels. Adopting the findings of this study into hmDNA enrichment of clinical samples has the potential to become more selective and sensitive than current MBD2-based methods and, therefore, to improve cancer diagnostics.

This study aimed to investigate the potential progressiveness of mandibular asymmetry and to study factors that influence chin point deviation in patients with unilateral craniofacial microsomia (CFM). Paediatric patients with unilateral CFM with available radiologic imaging and medical photographs were included. Chin point deviation was measured on clinical photographs. A Jonckheere-Terpstra test and linear mixed model for repeated measurements assessed the relation of chin point deviation on natural growth, Pruzansky−Kaban score, and soft tissue score. A total of 110 patients were included. The linear mixed model showed no statistically significant changes of chin point deviation during growth (effect estimate −0.006°, 95% CI –0.04° to −0.03°, p = 0.74). A statistical significant relation between both the Pruzansky-Kaban and soft tissue score on chin point deviation was found (effect estimate −5.10°, 95% CI –6.45° to −3.75°, p ≤ 0.001 and effect estimate −3.42°, CI –5.86° to −0.98°, p ≤ 0.001, respectively). Within the limitations of the study it seems that craniofacial microsomia may be a non-progressive disorder, because chin point deviation did not change over time.

Funder: Dutch Research Council (NWO), Colloidal molecules are designed to mimic their molecular analogues through their anisotropic shape and interactions. However, current experimental realizations are missing the structural flexibility present in real molecules thereby restricting their use as model systems. We overcome this limitation by assembling reconfigurable colloidal molecules from silica particles functionalized with mobile DNA linkers in high yields. We achieve this by steering the self-assembly pathway toward the formation of finite-sized clusters by employing high number ratios of particles functionalized with complementary DNA strands. The size ratio of the two species of particles provides control over the overall cluster size, i.e., the number of bound particles N, as well as the degree of reconfigurability. The bond flexibility provided by the mobile linkers allows the successful assembly of colloidal clusters with the geometrically expected maximum number of bound particles and shape. We quantitatively examine the self-assembly dynamics of these flexible colloidal molecules by a combination of experiments, agent-based simulations, and an analytical model. Our "flexible colloidal molecules" are exciting building blocks for investigating and exploiting the self-assembly of complex hierarchical structures, photonic crystals, and colloidal metamaterials.

Background: Craniofacial microsomia (CFM) is characterized by several malformations related to the first and second pharyngeal arch. Patients typically present with facial asymmetry, but extracraniofacial organ systems might be involved, including limb anomalies. The purpose of this study was to analyze the occurrence of upper and lower limb anomalies in CFM patients. Furthermore, the relation between limb anomalies and the OMENS+ (orbital distortion; mandibular hypoplasia; ear anomaly; nerve involvement; soft-tissue deficiency; and associated extracraniofacial anomalies) classification was examined. Methods: A retrospective study was conducted including patients with CFM from craniofacial units in three different countries. Patients were included when clinical and/or radiographic images were available. Demographic, radiographic, and clinical information was obtained. Results: A cohort of 688 patients was available and selected for analysis. In total, 18.2% of the patients were diagnosed with at least one upper and/or lower limb anomaly. Upper and lower limb anomalies were seen in, respectively, 13.4% and 7.8% of patients. Patients with other extracraniofacial anomalies had a significantly higher risk for limb anomalies (OR, 27.98; P = 0.005). Laterality of CFM and a higher OMENS score were not associated with limb anomalies. Conclusions: More than one in six patients with craniofacial microsomia have limb anomalies. Therefore, clinical awareness for these anomalies is warranted. Examination and, if present, follow-up on limb abnormalities in patients with CFM should be implemented in the standard assessment of CFM patients.

Background: Revascularisation of a chronic total coronary occlusion (CTO) impacts on the coronary physiology of the remote myocardial territory. Aims: This study aimed to evaluate the intrinsic effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium. Methods: A total of 164 patients who underwent serial [ 15O]H 2O positron emission tomography (PET) perfusion imaging at baseline and three months after successful single-vessel CTO PCI were included to evaluate changes in hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardium supplied by both non-target coronary arteries. Results: Perfusion indices in CTO and remote myocardium showed a positive correlation before (resting MBF: r=0.84, hMBF: r =0.75, and CFR: r =0.77, p–1·g –1 and from 2.48±0.76 to 2.74±0.85, respectively, p

Logistics planning is a complex optimization problem involving multiple decision makers. Automated scheduling systems offer support to human planners; however state-of-the-art approaches often employ a centralized control paradigm. While these approaches have shown great value, their application is hindered in dynamic settings with no central authority. Motivated by real-world scenarios, we present a decentralized approach to collaborative multi-agent scheduling by casting the problem as a Distributed Constraint Optimization Problem (DCOP). Our model-based heuristic approach uses message passing with a novel pruning technique to allow agents to cooperate on mutual agreement, leading to a near-optimal solution while offering low computational costs and flexibility in case of disruptions. Performance is evaluated in three real-world field trials with a logistics carrier and compared against a centralized model-free Deep Q-Network (DQN)-based Reinforcement Learning (RL) approach, a Mixed-Integer Linear Programming (MILP)-based solver, and both human and heuristic baselines. The results demonstrate that it is feasible to have virtual agents make autonomous decisions using our DCOP method, leading to an efficient distributed solution. To facilitate further research in Self-Organizing Logistics (SOL), we provide a novel real-life dataset.

Aims Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. Methods and results A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories: myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and −0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1–3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19–0.98, P = 0.04). Conclusion Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.

Can conscientiousness, academic achievement, and a student’s perceived control over it predict metacognitive ability in undergraduate students. If so, are the relationships for conscientiousness and academic achievement in line with previous research

The preselection of hypermethylated DNA (hmDNA) from liquid biopsy samples is key to enable early-stage cancer diagnostics. Due to limited selectivity of the existing preselection approaches, however, wide integration in the clinic is currently prohibited. Here, it is argued that an affinity method on a surface, such as used in affinity chromatography, can be significantly improved by employing the principles of multivalency and superselectivity. In the here proposed method, a methyl binding domain (MBD) protein immobilized at a surface is used as a receptor for (hyper)methylated DNA. By the organization of multiple MBDs on a surface, a multivalent binding platform is achieved. The MBD surface receptor density on that platform is key to increase the enrichment selectivity of hmDNA as a single MBD protein binds both methylated and non-methylated DNA with a small difference in affinity. When the receptor density is varied, multivalent analyte binding typically responds in a non-linear fashion, which phenomenon is called superselectivity. By careful tuning of the MBD density, it is envisaged that the selectivity for methylated over non-methylated DNA can be optimized. Strong applicability is foreseen in a medical setting by implementing such an enrichment step in an analytical process or a lab-on-a-chip device.

A European guideline on craniofacial microsomia was developed within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose, and throat disorders and published in 2020. The guideline provides an overview of optimal care provisions for patients with craniofacial microsomia and recommendations for the improvement of care. This document seeks to provide a tailored overview of this guideline for patients and their families.

Aims To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (DT1) with [ 15O]H 2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. ................................................................................................................................................................................................... Methods Forty-three patients with suspected obstructed coronary artery disease underwent [ 15O]H 2O PET and CMR at and results 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. DT1 was determined for the three main vascular territories and compared with [ 15O]H 2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). DT1 showed a significant but poor correlation with stress MBF (R 2 = 0.04, P = 0.03) and MFR (R 2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. 15O]H 2O PET measurements of absolute myocardial perfusion. Stress T1 and DT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Objectives: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFRCT planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR. Background: Advances in FFRCT technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses. Methods: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFRCT was calculated using pre-PCI coronary CT angiography. Subsequently, FFRCT and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFRCT models in the same locations as PCI was performed. Relationships between invasive FFR and FFRCT, between post-PCI FFR and FFRCT planner, and between delta FFR and delta FFRCT were evaluated. Results: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFRCT was 0.64 ± 0.13 (p =.34) with a mean difference of 0.015 (95% CI: −0.23–0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFRCT planner was 0.85 ± 0.07 (p CT were 0.23 ± 0.12 and 0.21 ± 0.12 (p =.09) with a mean difference of 0.025 (95% CI: −0.20–0.25). Significant correlations were found between pre-PCI FFR and FFRCT (r = 0.53, p CT planner (r = 0.41, p =.001), and between delta FFR and delta FFRCT (r = 0.57, p CT planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFRCT planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.

The available active surface area and the density of probes immobilized on this surface are responsible for achieving high specificity and sensitivity in electrochemical biosensors that detect biologically relevant molecules, including DNA. Here, we report the design of gold-coated, silicon micropillar-structured electrodes functionalized with modified poly-l-lysine (PLL) as an adhesion layer to concomitantly assess the increase in sensitivity with the increase of the electrochemical area and control over the probe density. By systematically reducing the center-to-center distance between the pillars (pitch), denser micropillar arrays were formed at the electrode, resulting in a larger sensing area. Azido-modified peptide nucleic acid (PNA) probes were click-reacted onto the electrode interface, exploiting PLL with appended oligo(ethylene glycol) (OEG) and dibenzocyclooctyne (DBCO) moieties (PLL-OEG-DBCO) for antifouling and probe binding properties, respectively. The selective electrochemical sandwich assay formation, composed of consecutive hybridization steps of the target complementary DNA (cDNA) and reporter DNA modified with the electroactive ferrocene functionality (rDNA-Fc), was monitored by quartz crystal microbalance. The DNA detection performance of micropillared electrodes with different pitches was evaluated by quantifying the cyclic voltammetric response of the surface-confined rDNA-Fc. By decrease of the pitch of the pillar array, the area of the electrode was enhanced by up to a factor 10.6. A comparison of the electrochemical data with the geometrical area of the pillared electrodes confirmed the validity of the increased sensitivity of the DNA detection by the design of the micropillar array.

Introduction: Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. This study evaluated the impact of CTO percutaneous coronary intervention (PCI) on absolute perfusion in remote myocardium. Methods: A total of 164 patients underwent serial [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging at baseline and 3 months after successful CTO PCI to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium subtended by non-target collateral donor coronary arteries. Results: Absolute perfusion indices in the CTO and remote myocardium showed a positive linear correlation before (hMBF: r=0.75, p-1 ·g -1 , p Conclusions: Baseline and post-PCI perfusion indices in remote and CTO myocardium were positively correlated. An overall increase in remote myocardial perfusion was observed following CTO PCI and the absolute perfusion increase in the CTO territory was an independent predictor of remote myocardial perfusion improvement. Successful CTO PCI impacts coronary hemodynamics in the closely interlinked CTO and remote myocardium.