How Highly Heterogeneous Sensors with Single-Molecule Resolution can Result in Robust Continuous Monitoring Over Long Time Spans.

Biomolecular sensors with single-molecule resolution are composed of multitudes of transducers that measure state changes related to single-molecular binding and unbinding events. Conventionally, signals are aggregated from many individual transducers in order to achieve sufficient statistics. However, by aggregating signals, transducer-to-transducer differences are lost and heterogeneities cannot be studied.

Steering perovskite precursor solutions for multijunction photovoltaics.

Multijunction photovoltaics (PVs) are gaining prominence owing to their superior capability of achieving power conversion efficiencies (PCEs) beyond the radiative limit of single-junction cells, where improving narrow bandgap tin-lead perovskites is critical for thin-film devices. With a focus on understanding the chemistry of tin-lead perovskite precursor solutions, we herein find that Sn(II) species dominate interactions with precursors and additives and uncover the exclusive role of carboxylic acid in regulating solution colloidal properties and film crystallisation, and ammonium in improving film optoelectronic properties. Materials that combine these two function groups, amino acid salts, considerably improve the semiconducting quality and homogeneity of perovskite films, surpassing the effect of the individual functional groups when introduced as part of separate molecules.

Harnessing Imine Chemistry for the Debonding-on-Demand of Polyurethane Adhesives.

Traditional adhesives often result in irreversible bonds, hindering disassembly and recycling processes. In response to the growing demand for sustainable practices, researchers have explored alternative bonding solutions. Debonding-on-demand adhesives represent a breakthrough, enabling selective weakening or breaking of adhesive bonds when desired and facilitating efficient disassembly, repair, and recycling of bonded materials.

Mechanism and Kinetics of Hydration of CuSO·HO in the Presence of an Intermediate Step.

The hydration of salt hydrates is often described as a solution mediated nucleation and growth mechanism, occurring between a reagent and a product in thermodynamic equilibrium with each other. If a system possesses more than one hydrate phase, the kinetic pathway may involve additional mechanisms due to the formation of intermediate hydrate species. We elected CuSO as our model system and analyzed the pathway leading from CuSO·HO (C1H) to CuSO·5HO (C5H), while CuSO·3HO (C3H) being a possible intermediate.

Considering future qualification for regulatory science in the early development of microphysiological systems: a case study of microthrombosis in a Vessel-on-Chip.

Microphysiological systems (MPS) and Organs-on-Chips (OoCs) hold significant potential for replicating complex human biological processes . However, their widespread adoption by industry and regulatory bodies depends on effective qualification to demonstrate that these models are fit for purpose. Many models developed in academia are not initially designed with qualification in mind, which limits their future implementation in end-user settings.

Bothersome Back Exchange in MALDI Plume and Its Impact on Hydrogen/Deuterium Exchange Mass Spectrometry Analysis.

One critical issue in hydrogen/deuterium exchange mass spectrometry (HDX MS) analysis is the deleterious back exchange. Herein, we report that when matrix-assisted laser desorption/ionization (MALDI) is used, the MALDI process itself can also cause significant back exchange. The back exchange occurred inside the reactive MALDI plume was investigated by depositing a fully deuterated sample prepared in DO on top of a preloaded dried layer of matrix.

Immunoaffinity Intact Top-Down Mass Spectrometry for Quantification of Neuron-Specific Enolase Gamma, a Low-Abundance Protein Biomarker.

Quantification of intact proteins in serum by liquid chromatography high-resolution mass spectrometry (HRMS) may be a useful alternative to bottom-up LC-MS or conventional ligand binding assays, due to reduced assay complexity and by providing additional information, such as isoform differentiation or detection of post-translational modifications. The 47.2 kDa lung cancer tumor marker neuron-specific enolase γ (NSEγ) was quantified in a clinically relevant concentration range of 6.

Predicting preterm birth using electronic medical records from multiple prenatal visits.

This study aimed to predict preterm birth in nulliparous women using machine learning and easily accessible variables from prenatal visits. Elastic net regularized logistic regression models were developed and evaluated using 5-fold cross-validation on data from 8,830 women in the Nulliparous Pregnancy Outcomes Study: New Mothers-to-Be (nuMoM2b) dataset at three prenatal visits: - , - , and - weeks of gestational age (GA). The models' performance, assessed using Area Under the Curve (AUC), sensitivity, specificity, and accuracy, consistently improved with the incorporation of data from later prenatal visits.

Pneumatic coding blocks enable programmability of electronics-free fluidic soft robots.

Decision-making based on environmental cues is a crucial feature of autonomous systems. Embodying this feature in soft robots poses nontrivial challenges on both hardware and software that can undermine the simplicity and autonomy of such devices. Existing pneumatic electronics-free soft robots have so far mostly been approached by using system fluidic circuit architectures analogous to digital electronics.

Ortho-functionalized pyridinyl-tetrazines break the inverse correlation between click reactivity and cleavage yields in click-to-release chemistry.

The bioorthogonal tetrazine-triggered cleavage of trans-cyclooctene(TCO)-linked payloads has strong potential for widespread use in drug delivery and in particular in click-cleavable antibody-drug conjugates (ADCs). However, clinical translation is hampered by an inverse correlation between click reactivity and payload release yield, requiring high doses of less reactive tetrazines to drive in vivo TCO reactions and payload release to completion. Herein we report that the cause for the low release when using the highly reactive bis-(2-pyridinyl)-tetrazine is the stability of the initially formed 4,5-dihydropyridazine product, precluding tautomerization to the releasing 1,4-dihydropyridazine tautomer.

Exploring the association of metabolic factors and chronic musculoskeletal pain over a period of 10 years - the Doetinchem Cohort Study.

Objective: To examine (a) the association between metabolic factors and chronic musculoskeletal pain (CMP), (b) metabolic predictors of CMP 10 years later, and (c) the association and evolution of metabolic factors across different CMP trajectory groups.

Design: Data from the longitudinal Doetinchem Cohort Study were used. We used round 4 (2003-2007), with 4519 participants aged 36-75 years, as the baseline for the present study, with follow-up measurements in round 5 (2008-2012), and 6 (2013-2017), including self-reported pain and metabolic factors, which were measured either via self-report or physical assessment.

Thin liquid films stabilized by plant proteins: Implications for foam stability.

Hypothesis: Plant-based proteins offer a sustainable solution for stabilizing multiphase food materials like edible foams and emulsions. However, challenges in understanding and engineering plant protein-stabilized interfaces persist, mostly because of the commonly poorer functionality and complex composition of the respective protein isolates. We hypothesize that part of the limited understanding is related to the lack of experimental data on the length-scale of the thin liquid film that separates two neighboring bubbles.

Brain-Computer Interfaces Using Flexible Electronics: An a-IGZO Front-End for Active ECoG Electrodes.

Brain-computer interfaces (BCIs) are evolving toward higher electrode count and fully implantable solutions, which require extremely low power densities (<15mW cm). To achieve this target, and allow for a large and scalable number of channels, flexible electronics can be used as a multiplexing interface. This work introduces an active analog front-end fabricated with amorphous Indium-Gallium-Zinx-Oxide (a-IGZO) Thin-Film Transistors (TFTs) on foil capable of active matrix multiplexing.

Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance.

Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data.

Gold Nanoparticles Decorated with HPLC6-Derived Peptides as a Platform for Ice Recrystallization Inhibition.

In nature, organisms living in extreme environmental conditions produce antifreeze proteins (AFPs) that prevent the growth of ice crystals and depress the freezing point of body fluids. In this study, three different peptides derived from the N-terminal sequence of the helical type I AFP HPLC6, along with a stapled derivative produced via on-resin microwave-assisted copper(I)-catalyzed azide-alkyne cycloaddition, were conjugated to gold nanoparticles. The aim of decorating the surface of the nanoparticles with multiple copies of the peptides was to combine the ice-binding capability of the peptides with the size of a nanoparticle, thus, mimicking the protein bulkiness to enhance the peptide antifreeze activity.

Single-Molecule Multivalent Interactions Revealed by Plasmon-Enhanced Fluorescence.

Multivalency as an interaction principle is widely utilized in nature. It enables specific and strong binding by multiple weak interactions through enhanced avidity and is a core process in immune recognition and cellular signaling, which is also a current concept in drug design. Here, we use the high signals from plasmon-enhanced fluorescence of nanoparticles to extract binding kinetics and dynamics of multivalent interactions on the single-molecule level and in real time.

Patient-Representative Cell Line Models in a Heterogeneous Disease: Comparison of Signaling Transduction Pathway Activity Between Ovarian Cancer Cell Lines and Ovarian Cancer.

: Advances in treatment options have barely improved the prognosis of ovarian carcinoma (OC) in recent decades. The inherent heterogeneity of OC underlies challenges in treatment (development) and patient stratification. One hurdle for effective drug development is the lack of patient-representative disease models available for preclinical drug research.

Cu-Ag interactions in bimetallic Cu-Ag catalysts enhance C product formation during electrochemical CO reduction.

The electroreduction of CO (CORR) is a promising alternative to the direct CO electroreduction reaction (CO2RR) to produce C products. Cu-based electrocatalysts enable the formation of C-C bonds, leading to various C hydrocarbon and oxygenate products. Herein, we investigated how the composition of bimetallic Cu-Ag catalysts impacted the nature of the Cu-Ag interactions and the product distribution of the CORR, aiming to improve the selectivity to C products.

Rheology of paste-like food inks for 3D printing: Effects of nutrient and water content.

This research delves into understanding the effects of composition on the rheological response of multi-component food inks for 3D food printing. Accordingly, the motivation is to decouple the nutrient and water content effects on the rheology. We formulated inks by combining pea fractions with water and employing a water-holding-capacity based hydration method.

Challenges in the Development and Evaluation of Pediatric Heart Valve Technologies.

Background: In October 2022, the Heart Valve Collaboratory and Food and Drug Administration convened a global multidisciplinary workshop to address the unmet clinical need to promote and accelerate the development of pediatric-specific heart valve technologies.

Methods: The Pediatric Heart Valve Global Multidisciplinary Workshop was convened in October 2022. Key stakeholders, including expert clinicians in pediatric cardiology and cardiac surgery, valve manufacturers, engineers and scientists were assembled to review the current state-of-the-art, discuss unique challenges in the pre-and post-market evaluation of pediatric valve therapies, and highlight emerging technologies that show potential to address some of the key unmet needs of children with valve disease.

Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers.

Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor.

A Computational Approach for Internal Tendon Routing Channels in a Tendon-Driven Continuum Joint.

Tendon-driven continuum soft robots are currently applied in research and are given a promising perspective for future applications. For the routing of the tendons from the actuator to the point where the loading is demanded, two routing possibilities exist in the literature: internal routing of the tendons with the help of structurally embedded Bowden sheaths and external tendon routing where the tendon is not in contact with the soft structure. The application of the latter is a clear disadvantage for applications due to the high risk of interference with the tendon, for example, causing the tendon to break.

A multi-aperture encoding scheme for increased SNR in photoacoustic Imaging.

Photoacoustic imaging creates light-induced ultrasonic signals to provide valuable information on internal body structures and tissue morphology non-invasively. A multi-aperture photoacoustic imaging (MP-PAI) system is an improvement over conventional photoacoustic imaging (PAI) systems in terms of resolution, contrast, and field of view. Previously, a prototype MP-PAI system was introduced based on multiple capacitive micromachined ultrasound transducers (CMUTs) with shared channels, such that each element in a CMUT shares its channel with its counterpart in other CMUTs.

Structure-property relationships to direct the dynamic properties of acylsemicarbazide-based materials.

Secondary interactions, such as hydrogen bonding or phase separation, can enhance the stability of dynamic covalent materials without compromising on desired dynamic properties. Here, we investigate the combination of multiple secondary interactions in dynamic covalent materials based on acylsemicarbazides (ASCs), with the aim of achieving tunable material properties. The effects of different ASC substituents on the dynamic covalent and hydrogen bonding capabilities were investigated in a small molecule study using a combined experimental and theoretical approach, and revealed the presence of cooperative hydrogen-bonding interactions in 2 directions in one of the derivatives.

Geometry and local wall thickness of abdominal aortic aneurysms using intravascular ultrasound.

Currently, abdominal aortic aneurysms (AAAs) are treated based on the diameter of the aorta, however, a more robust patient-specific marker is needed. The mean thickness of the wall is a potential indicator for AAA rupture risk, which varies significantly within and between patients. So far, regional thickness has not been used in previous rupture risk analysis studies, since it is challenging to measure in CT, MRI, and non-invasive ultrasound (US).