Brain implantation of tissue-level-soft bioelectronics via embryonic development.

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

Handheld methanol detector for beverage analysis: interlaboratory validation.

Methanol is a toxic alcohol contained in alcoholic beverages as a natural byproduct of fermentation or added intentionally to counterfeits to increase profit. To ensure consumer safety, many countries and the EU have established strict legislation limits for methanol content. Methanol concentration is mostly detected by laboratory instrumentation since mobile devices for routine on-site testing of beverages in distilleries, at border stations or even at home are not available. Here, we validated a handheld methanol detector for beverage analysis in an ISO 5725 interlaboratory trial: a total of 119 measurements were performed by 17 independent participants (distilleries, universities, authorities, and competence centers) from six countries on samples with relevant methanol concentrations (0.1, 1.5 vol%). The detector was based on a microporous separation filter and a nanostructured gas sensor allowing on-site measurement of methanol down to 0.01 vol% (in the liquid) within only 2 min by laymen. The detector showed excellent repeatability (<5.4%), reproducibility (<9.5%) and small bias (<0.012 vol%). Additional measurements on various methanol-spiked alcoholic beverages (whisky, rum, gin, vodka, tequila, port, sherry, liqueur) indicated that the detector is not interfered by environmental temperature and spirit composition, featuring excellent linearity (R2 > 0.99) down to methanol concentrations of 0.01 vol%. This device has been recently commercialized (Alivion Spark M-20) with comparable accuracy to the gold-standard gas chromatography and can be readily applied for final product inspection, intake control of raw materials or to identify toxic counterfeit products.

Engineered heart tissue: Design considerations and the state of the art.

Originally developed more than 20 years ago, engineered heart tissue (EHT) has become an important tool in cardiovascular research for applications such as disease modeling and drug screening. Innovations in biomaterials, stem cell biology, and bioengineering, among other fields, have enabled EHT technologies to recapitulate many aspects of cardiac physiology and pathophysiology. While initial EHT designs were inspired by the isolated-trabecula culture system, current designs encompass a variety of formats, each of which have unique strengths and limitations. In this review, we describe the most common EHT formats, and then systematically evaluate each aspect of their design, emphasizing the rational selection of components for each application.

Extraordinary Thermal Stability and Sinter Resistance of Sub-2 nm Platinum Nanoparticles Anchored to a Carbon Support by Selenium.

Nanoparticle sintering has long been a major challenge in developing catalytic systems for use at elevated temperatures. Here we report an in situ electron microscopy study of the extraordinary sinter resistance of a catalytic system comprised of sub-2 nm Pt nanoparticles on a Se-decorated carbon support. When heated to 700 °C, the average size of the Pt nanoparticles only increased from 1.6 to 2.2 nm, while the crystal structure, together with the {111} and {100} facets, of the Pt nanoparticles was well retained. Our electron microscopy analyses suggested that the superior resistance against sintering originated from the Pt-Se interaction. Confirmed by energy-dispersive X-ray elemental mapping and electron energy loss spectra, the Se atoms surrounding the Pt nanoparticles could survive the heating. This work not only offers an understanding of the physics behind the thermal behavior of this catalytic material but also sheds light on the future development of sinter-resistant catalytic systems.

Influence of Anaesthesia on Harvesting the Semitendinosus Tendon for Anterior Cruciate Ligament Replacement.

Aim The aim of the study was to investigate if the mode of anesthesia is a relevant factor influencing the length of the semitendinosus tendon harvested for anterior cruciate ligament (ACL) replacement.  Methods Patients undergoing ACL replacement were given the choice between spinal and general anesthesia. If general anesthesia was chosen, a short relaxation period was applied while harvesting the Semitendinosus (ST) tendon. The data for tendon length, the folding factor, and the diameter of the graft were collected. Except for redo procedures and ACL replacement with allograft all patients undergoing an ACL replacement were enrolled. Results Thirty-one patients with general anesthesia (GA) and 14 patients with spinal anesthesia (SA) were examined. The ST tendon length was 29.03 cm ± 2.6 cm in the GA group and 25.4 cm ± 2.70 in the SA group (t value 4.245, p=0.0001). The ST tendon could be quadrupled in 23 patients in the GA and 6 patients in the SA group (χ2=4.13, p=0.04). The graft diameter obtained was 8.53 mm ± 0.62 mm in the GA group and 7.71 mm ± 0.47 mm in the SA group (t value 4.885, p<0.0001). Conclusion General anesthesia with short-time relaxation while harvesting the ST tendon for ACL grafting allows to harvest longer ST tendons and consequently yields better results regarding the graft dimensions and should be offered to patients as a first-choice procedure. There is no other paper published yet, analyzing this relationship and if validated on a larger cohort, this might change clinical practice.

Atomically Dispersed Platinum in Surface and Subsurface Sites on MgO Have Contrasting Catalytic Properties for CO Oxidation.

Atomically dispersed metals on metal oxide supports are a rapidly growing class of catalysts. Developing an understanding of where and how the metals are bonded to the supports is challenging because support surfaces are heterogeneous, and most reports lack a detailed consideration of these points. Herein, we report two atomically dispersed CO oxidation catalysts having markedly different metal-support interactions: platinum in the first layer of crystalline MgO powder and platinum in the second layer of this support. Structural models have been determined on the basis of data and computations, including those determined by extended X-ray absorption fine structure and X-ray absorption near edge structure spectroscopies, infrared spectroscopy of adsorbed CO, and scanning transmission electron microscopy. The data demonstrate the transformation of surface to subsurface platinum as the temperature of sample calcination increased. Catalyst performance data demonstrate the lower activity but greater stability of the subsurface platinum than of the surface platinum.

Multi-principal elemental intermetallic nanoparticles synthesized via a disorder-to-order transition.

Nanoscale multi-principal element intermetallics (MPEIs) may provide a broad and tunable compositional space of active, high-surface area materials with potential applications such as catalysis and magnetics. However, MPEI nanoparticles are challenging to fabricate because of the tendency of the particles to grow/agglomerate or phase-separated during annealing. Here, we demonstrate a disorder-to-order phase transition approach that enables the synthesis of ultrasmall (4 to 5 nm) and stable MPEI nanoparticles (up to eight elements). We apply just 5 min of Joule heating to promote the phase transition of the nanoparticles into L10 intermetallic structure, which is then preserved by rapidly cooling. This disorder-to-order transition results in phase-stable nanoscale MPEIs with compositions (e.g., PtPdAuFeCoNiCuSn), which have not been previously attained by traditional synthetic methods. This synthesis strategy offers a new paradigm for developing previously unexplored MPEI nanoparticles by accessing a nanoscale-size regime and novel compositions with potentially broad applications.

Machine Learning Method Reveals Hidden Strong Metal-Support Interaction in Microscopy Datasets.

Forming an ultra-thin, permeable encapsulation oxide-support layer on a metal catalyst surface is considered an effective strategy for achieving a balance between high stability and high activity in heterogenous catalysts. The success of such a design relies not only on the thickness, ideally one to two atomic layers thick, but also on the morphology and chemistry of the encapsulation layer. Reliably identifying the presence and chemical nature of such a trace layer has been challenging. Electron energy-loss spectroscopy (EELS) performed in a scanning transmission electron microscope (STEM), the primary technique utilized for such studies, is limited by a weak signal on overlayers when using conventional analysis methods, often leading to misinterpreted or missed information. Here, a robust, unsupervised machine learning data analysis method is developed to reveal trace encapsulation layers that are otherwise overlooked in STEM-EELS datasets. This method provides a reliable tool for analyzing encapsulation of catalysts and is generally applicable to any spectroscopic analysis of materials and devices where revealing a trace signal and its spatial distribution is challenging.

A Theory-Guided X-ray Absorption Spectroscopy Approach for Identifying Active Sites in Atomically Dispersed Transition-Metal Catalysts.

Atomically dispersed supported metal catalysts offer new properties and the benefits of maximized metal accessibility and utilization. The characterization of these materials, however, remains challenging. Using atomically dispersed platinum supported on crystalline MgO (chosen for its well-defined bonding sites) as a prototypical example, we demonstrate how systematic density functional theory calculations for assessing all the potentially stable platinum sites, combined with automated analysis of extended X-ray absorption fine structure (EXAFS) spectra, leads to unbiased identification of isolated, surface-enveloped platinum cations as the catalytic species for CO oxidation. The catalyst has been characterized by atomic-resolution imaging and EXAFS and high-energy resolution fluorescence detection X-ray absorption near edge spectroscopy. The proposed platinum sites are in agreement with experiment. This theory-guided workflow leads to rigorously determined structural models and provides a more detailed picture of the structure of the catalytically active site than what is currently possible with conventional EXAFS analyses. As this approach is efficient and agnostic to the metal, support, and catalytic reaction, we posit that it will be of broad interest to the materials characterization and catalysis communities.

Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England.

OBJECTIVES: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England. METHODS: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk. RESULTS: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries. CONCLUSIONS: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections.

Danger perception and stress response through an olfactory sensor for the bacterial metabolite hydrogen sulfide.

The olfactory system serves a critical function as a danger detection system to trigger defense responses essential for survival. The cellular and molecular mechanisms that drive such defenses in mammals are incompletely understood. Here, we have discovered an ultrasensitive olfactory sensor for the highly poisonous bacterial metabolite hydrogen sulfide (H2S) in mice. An atypical class of sensory neurons in the main olfactory epithelium, the type B cells, is activated by both H2S and low O2. These two stimuli trigger, respectively, Cnga2- and Trpc2-signaling pathways, which operate in separate subcellular compartments, the cilia and the dendritic knob. This activation drives essential defensive responses: elevation of the stress hormone ACTH, stress-related self-grooming behavior, and conditioned place avoidance. Our findings identify a previously unknown signaling paradigm in mammalian olfaction and define type B cells as chemosensory neurons that integrate distinct danger inputs from the external environment with appropriate defense outputs.

Hadronic Light-by-Light Scattering Contribution to the Muon Anomalous Magnetic Moment from Lattice QCD.

We report the first result for the hadronic light-by-light scattering contribution to the muon anomalous magnetic moment with all errors systematically controlled. Several ensembles using 2+1 flavors of physical mass Möbius domain-wall fermions, generated by the RBC and UKQCD collaborations, are employed to take the continuum and infinite volume limits of finite volume lattice QED+QCD. We find a_{µ}^{HLbL}=7.87(3.06)_{stat}(1.77)_{sys}×10^{-10}. Our value is consistent with previous model results and leaves little room for this notoriously difficult hadronic contribution to explain the difference between the standard model and the BNL experiment.

Evaluation of a new ultralow-dose radiation protocol for electrophysiological device implantation: A near-zero fluoroscopy approach for device implantation.

BACKGROUND: Radiation is one of the main hazards of electrophysiological device implantation, and insertion of cardiac resynchronization therapy (CRT) devices in particular is associated with high radiation doses. OBJECTIVE: The purpose of this study was to evaluate the impact of a new ultralow-dose radiation protocol on radiation doses, success rate, and safety of electrophysiological device implantations. METHODS: In 2018, we established a new ultralow-dose radiation protocol (reduced pulse width, increased thickness of minimum copper filters, reduced detector entrance dose, reduced pulse rate, optimized image postprocessing settings) for de novo device implantation at our hospital. A total of 1173 patients (11% single-chamber devices, 69% dual-chamber devices, 20% CRT devices) were analyzed. Five hundred twelve patients (44%) in the ultralow-dose group were compared to 661 patients (66%) treated during 2017 with a conventional low-dose protocol. RESULTS: With the ultralow-dose radiation protocol, effective doses could be reduced by 59% (median 0.25 [interquartile range: 0.11-0.63] vs median 0.10 [interquartile range: 0.03-0.28] mSv; P <.0001) per procedure without a significant change in procedure time (P = .5). This dose reduction could be achieved without decreasing procedure success (P = 1) or increasing complication rate (P = .8). Male gender, higher body mass index, increased procedure and fluoroscopy times, and use of the conventional radiation protocol were independent predictors of higher radiation doses in multivariate regression analysis. CONCLUSION: By establishing a new ultralow-dose radiation protocol, we could significantly decrease radiation exposure, reaching the lowest radiation doses for electrophysiological device implantation reported to date.

Real-space charge-density imaging with sub-ångström resolution by four-dimensional electron microscopy.

The distribution of charge density in materials dictates their chemical bonding, electronic transport, and optical and mechanical properties. Indirectly measuring the charge density of bulk materials is possible through X-ray or electron diffraction techniques by fitting their structure factors1-3, but only if the sample is perfectly homogeneous within the area illuminated by the beam. Meanwhile, scanning tunnelling microscopy and atomic force microscopy enable us to see chemical bonds, but only on the surface4-6. It remains a challenge to resolve charge density in nanostructures and functional materials with imperfect crystalline structures-such as those with defects, interfaces or boundaries at which new physics emerges. Here we describe the development of a real-space imaging technique that can directly map the local charge density of crystalline materials with sub-ångström resolution, using scanning transmission electron microscopy alongside an angle-resolved pixellated fast-electron detector. Using this technique, we image the interfacial charge distribution and ferroelectric polarization in a SrTiO3/BiFeO3 heterojunction in four dimensions, and discover charge accumulation at the interface that is induced by the penetration of the polarization field of BiFeO3. We validate this finding through side-by-side comparison with density functional theory calculations. Our charge-density imaging method advances electron microscopy from detecting atoms to imaging electron distributions, providing a new way of studying local bonding in crystalline solids.

Need for pacemaker implantation in patients with normal QRS duration immediately after transcatheter aortic valve implantation.

AIMS: We sought to assess the need for permanent pacemaker implantation (PPI) in patients with QRS <120 ms in electrocardiogram (ECG) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We retrospectively analysed 1139 consecutive patients who underwent transfemoral TAVI between 2008 and 2016, receiving different valve types. All patients were surveyed by continuous ECG monitoring for 48 h, 12-lead ECGs starting immediately after procedure, as well as 24-h Holter recording the day before discharge. Indication for PPI was at the discretion of the attending physician. Among 760 patients with QRS <120 ms prior to the TAVI procedure, 400 patients showed QRS <120 ms immediately after procedure, whereas 360 patients had QRS ≥120 ms. In the group with QRS <120 ms, PPI was performed in 34 patients [8.5%; 95% confidence interval (CI) 5.6-11.2%] during the first week. Eight of the PPIs in the group with QRS <120 ms (2%; CI 0.8-3.5%) fulfilled Class I indications for PPI after TAVI, whereas 26 PPIs had different indications [left bundle branch block, sick sinus, low-grade atrioventricular (AV) block]. Complete AV block developed in three patients of the group of QRS <120 ms (0.75%; CI 0.0-1.7%), which in all cases occurred after the 48 h-surveillance period. During 1-year follow-up, 11 PPIs were performed (2.8%; CI 1.2-4.5%), thereof three PPI for Class I indications including one complete AV block. CONCLUSION: In patients with QRS duration <120 ms immediately after TAVI, the risk for complete AV block was low during the first week after TAVI and 1-year follow-up.

Observation of Strong Polarization Enhancement in Ferroelectric Tunnel Junctions.

Ferroelectric heterostructures, with capability of storing data at ultrahigh densities, could act as the platform for next-generation memories. The development of new device paradigms has been hampered by the long-standing notion of inevitable ferroelectricity suppression under reduced dimensions. Despite recent experimental observation of stable polarized states in ferroelectric ultrathin films, the out-of-plane polarization components in these films are strongly attenuated compared to thicker films, implying a degradation of device performance in electronic miniaturization processes. Here, in a model system of BiFeO3/La0.7Sr0.3MnO3, we report observation of a dramatic out-of-plane polarization enhancement that occurs with decreasing film thickness. Our electron microscopy analysis coupled with phase-field simulations reveals a polarization-enhancement mechanism that is dominated by the accumulation of oxygen vacancies at interfacial layers. The results shed light on the interplay between polarization and defects in nanoscale ferroelectrics and suggest a route to enhance functionality in oxide devices.

Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology.

Tissue-wide electrophysiology with single-cell and millisecond spatiotemporal resolution is critical for heart and brain studies. Issues arise, however, from the invasive, localized implantation of electronics that destroys well-connected cellular networks within matured organs. Here, we report the creation of cyborg organoids: the three-dimensional (3D) assembly of soft, stretchable mesh nanoelectronics across the entire organoid by the cell-cell attraction forces from 2D-to-3D tissue reconfiguration during organogenesis. We demonstrate that stretchable mesh nanoelectronics can migrate with and grow into the initial 2D cell layers to form the 3D organoid structure with minimal impact on tissue growth and differentiation. The intimate contact between the dispersed nanoelectronics and cells enables us to chronically and systematically observe the evolution, propagation, and synchronization of the bursting dynamics in human cardiac organoids through their entire organogenesis.

Trpc5 deficiency causes hypoprolactinemia and altered function of oscillatory dopamine neurons in the arcuate nucleus.

Dopamine neurons of the hypothalamic arcuate nucleus (ARC) tonically inhibit the release of the protein hormone prolactin from lactotropic cells in the anterior pituitary gland and thus play a central role in prolactin homeostasis of the body. Prolactin, in turn, orchestrates numerous important biological functions such as maternal behavior, reproduction, and sexual arousal. Here, we identify the canonical transient receptor potential channel Trpc5 as an essential requirement for normal function of dopamine ARC neurons and prolactin homeostasis. By analyzing female mice carrying targeted mutations in the Trpc5 gene including a conditional Trpc5 deletion, we show that Trpc5 is required for maintaining highly stereotyped infraslow membrane potential oscillations of dopamine ARC neurons. Trpc5 is also required for eliciting prolactin-evoked tonic plateau potentials in these neurons that are part of a regulatory feedback circuit. Trpc5 mutant females show severe prolactin deficiency or hypoprolactinemia that is associated with irregular reproductive cyclicity, gonadotropin imbalance, and impaired reproductive capabilities. These results reveal a previously unknown role for the cation channel Trpc5 in prolactin homeostasis of female mice and provide strategies to explore the genetic basis of reproductive disorders and other malfunctions associated with defective prolactin regulation in humans.

Perfect Andreev reflection due to the Klein paradox in a topological superconducting state.

In 1928, Dirac proposed a wave equation to describe relativistic electrons1. Shortly afterwards, Klein solved a simple potential step problem for the Dirac equation and encountered an apparent paradox: the potential barrier becomes transparent when its height is larger than the electron energy. For massless particles, backscattering is completely forbidden in Klein tunnelling, leading to perfect transmission through any potential barrier2,3. The recent advent of condensed-matter systems with Dirac-like excitations, such as graphene and topological insulators, has opened up the possibility of observing Klein tunnelling experimentally4-6. In the surface states of topological insulators, fermions are bound by spin-momentum locking and are thus immune from backscattering, which is prohibited by time-reversal symmetry. Here we report the observation of perfect Andreev reflection in point-contact spectroscopy-a clear signature of Klein tunnelling and a manifestation of the underlying 'relativistic' physics of a proximity-induced superconducting state in a topological Kondo insulator. Our findings shed light on a previously overlooked aspect of topological superconductivity and can serve as the basis for a unique family of spintronic and superconducting devices, the interface transport phenomena of which are completely governed by their helical topological states.

Double-tilt in situ TEM holder with ultra-high stability.

A double tilting holder with high stability is essential for acquiring atomic-scale information by transmission electron microscopy (TEM), but the availability of such holders for in situ TEM studies under various external stimuli is limited. Here, we report a unique design of seal-bearing components that provides ultra-high stability and multifunctionality (including double tilting) in an in situ TEM holder. The seal-bearing subsystem provides superior vibration damping and electrical insulation while maintaining excellent vacuum sealing and small form factor. A wide variety of in situ TEM applications including electrical measurement, STM mapping, photovoltaic studies, and CL spectroscopy can be performed on this platform with high spatial resolution imaging and electrical sensitivity at the pA scale.