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The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis1–9. Deep learning approaches have aided in exploring chemical spaces1,10–15; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics. We tested this hypothesis by developing an explainable, substructure-based approach for the efficient, deep learning-guided exploration of chemical spaces. We determined the antibiotic activities and human cell cytotoxicity profiles of 39,312 compounds and applied ensembles of graph neural networks to predict antibiotic activity and cytotoxicity for 12,076,365 compounds. Using explainable graph algorithms, we identified substructure-based rationales for compounds with high predicted antibiotic activity and low predicted cytotoxicity. We empirically tested 283 compounds and found that compounds exhibiting antibiotic activity against Staphylococcus aureus were enriched in putative structural classes arising from rationales. Of these structural classes of compounds, one is selective against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci, evades substantial resistance, and reduces bacterial titres in mouse models of MRSA skin and systemic thigh infection. Our approach enables the deep learning-guided discovery of structural classes of antibiotics and demonstrates that machine learning models in drug discovery can be explainable, providing insights into the chemical substructures that underlie selective antibiotic activity.An explainable deep learning model using a chemical substructure-based approach for the exploration of chemical compound libraries identified structural classes of compounds with antibiotic activity and low toxicity. [ABSTRACT FROM AUTHOR]

Control of adhesion is a striking feature of living matter that is of particular interest regarding technological translation1–3. We discovered that entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion. Moreover, we found that intrinsically adhesive wax ester layers become similarly antibioadhesive when containing small quantities (under 10 wt%) of cholesterol. Wetting, adsorption and adhesion experiments, as well as atomistic simulations, showed that repulsive characteristics depend on the specific molecular structure of cholesterol that encodes a finely balanced fluctuating reorientation at the interface of unconstrained supramolecular assemblies: layers of cholesterol analogues differing only in minute molecular variations showed markedly different interfacial mobility and no antiadhesive effects. Also, orientationally fixed cholesterol layers did not resist bioadhesion. Our insights provide a conceptually new physicochemical perspective on biointerfaces and may guide future material design in regulation of adhesion.Entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion, providing a conceptually new physicochemical perspective on biointerfaces that may guide future material design in regulation of adhesion. [ABSTRACT FROM AUTHOR]

We report on a case with severe facial nerve stimulation via a cochlea‐facial nerve dehiscence that was most likely the result of prolonged occlusive hydrocephalus. The successful treatment of this adverse effect demonstrates for the first time its complete resolution using a multi‐mode grounding and monophasic passive discharge stimulation. [ABSTRACT FROM AUTHOR]

Mechanical rupture, or lysis, of the cytoplasmic membrane is a common cell death pathway in bacteria occurring in response to β-lactam antibiotics. A better understanding of the cellular design principles governing the susceptibility and response of individual cells to lysis could indicate methods of potentiating β-lactam antibiotics and clarify relevant aspects of cellular physiology. Here, we take a single-cell approach to bacterial cell lysis to examine three cellular features—turgor pressure, mechanosensitive channels, and cell shape changes—that are expected to modulate lysis. We develop a mechanical model of bacterial cell lysis and experimentally analyze the dynamics of lysis in hundreds of single Escherichia coli cells. We find that turgor pressure is the only factor, of these three cellular features, which robustly modulates lysis. We show that mechanosensitive channels do not modulate lysis due to insufficiently fast solute outflow, and that cell shape changes result in more severe cellular lesions but do not influence the dynamics of lysis. These results inform a single-cell view of bacterial cell lysis and underscore approaches of combatting antibiotic tolerance to β-lactams aimed at targeting cellular turgor. [ABSTRACT FROM AUTHOR]

Background: All soft and solid surface structures in the oral cavity are covered by the acquired pellicle followed by bacterial colonization. This applies for natural structures as well as for restorative or prosthetic materials; the adherent bacterial biofilm is associated among others with the development of caries, periodontal diseases, peri-implantitis, or denture-associated stomatitis. Accordingly, there is a considerable demand for novel materials and coatings that limit and modulate bacterial attachment and/or propagation of microorganisms. Objectives and findings: The present paper depicts the current knowledge on the impact of different physicochemical surface characteristics on bioadsorption in the oral cavity. Furthermore, it was carved out which strategies were developed in dental research and general surface science to inhibit bacterial colonization and to delay biofilm formation by low-fouling or "easy-to-clean" surfaces. These include the modulation of physicochemical properties such as periodic topographies, roughness, surface free energy, or hardness. In recent years, a large emphasis was laid on micro- and nanostructured surfaces and on liquid repellent superhydrophic as well as superhydrophilic interfaces. Materials incorporating mobile or bound nanoparticles promoting bacteriostatic or bacteriotoxic properties were also used. Recently, chemically textured interfaces gained increasing interest and could represent promising solutions for innovative antibioadhesion interfaces. Due to the unique conditions in the oral cavity, mainly in vivo or in situ studies were considered in the review. Conclusion: Despite many promising approaches for modulation of biofilm formation in the oral cavity, the ubiquitous phenomenon of bioadsorption and adhesion pellicle formation in the challenging oral milieu masks surface properties and therewith hampers low-fouling strategies. Clinical relevance: Improved dental materials and surface coatings with easy-to-clean properties have the potential to improve oral health, but extensive and systematic research is required in this field to develop biocompatible and effective substances. [ABSTRACT FROM AUTHOR]

A mid-scala cochlear implant electrode array, which was inserted with an atraumatic round window approach, could be replaced with longer lateral wall electrode array. Deeper electrode insertion seems to have beneficial influence on the hearing quality. [ABSTRACT FROM AUTHOR]

The objective of this retrospective study was to investigate the horizontal vestibulo-ocular reflex (hVOR) pathway with caloric test (low-frequency hVOR) and video head impulse test (vHIT) (high-frequency hVOR) in patients with sporadic vestibular schwannoma (69 patients, 27-86 years, mean age 58.1 years) and to compare both test methods in terms of their sensitivity and specificity to detect a retrocochlear lesion. Test results with a unilateral weakness (UW) >25 % (caloric test) or a Mean-Gain <0.79/asymmetry ratio of Gain (AR-Gain) >8.5 % and accompanied refixation saccades (vHIT) were considered abnormal. The overall sensitivity of the caloric test was 72 %. The evaluation of AR-Gain detected more abnormal cases than did Mean-Gain (44 vs. 36 %). In up to 4 %, a normal caloric test result was related to an abnormal vHIT. There was only a moderate correlation of UW and AR-Gain ( r = 0.54, p < 0.05) with a linear regression line intercept/slope of 32.2/0.9 ( p < 0.05). Receiver operating characteristics curve analysis exhibited at a UW of 50 % a vHIT sensitivity/specificity/positive predictive value/negative predictive value of 0.45/0.9/0.94/0.42. Vestibular testing at varying frequencies provides deeper insights into hVOR function and is helpful in detecting a cerebello-pontine lesion. Whereas caloric test yields a high sensitivity for nerve dysfunction, vHIT test reveals a remaining function of hVOR in the high-frequency range. [ABSTRACT FROM AUTHOR]

Collembola (springtails) are soil arthropods, representing the most widespread hexapod group worldwide. Being skin-breathing animals, Collembola evolved special cuticular patterns, which are robust and antiadhesive allowing cuticular respiration under humid conditions in the soil environment. Details about function and formation of these unique cuticle characters are still unknown. Here we demonstrate that a high diversity of cuticular structures exists and that the different observed structural patterns of Collembola cuticles might go along with specific adaptations to life in soil. We examined the cuticle structures of 40 different species using scanning electron microscopy and compared the cuticle patterns of the different species with information about their preferred habitat. In addition, we compare the results with current systematic concepts, showing that certain cuticle structures are typical for different collembolan groups. [ABSTRACT FROM AUTHOR]

Springtails, arthropods who live in soil, in decaying material, and on plants, have adapted to demanding conditions by evolving extremely effective and robust anti-adhesive skin patterns. However, details of these unique properties and their structural basis are still unknown. Here we demonstrate that collembolan skin can resist wetting by many organic liquids and at elevated pressures. We show that the combination of bristles and a comb-like hexagonal or rhombic mesh of interconnected nanoscopic granules distinguish the skin of springtails from anti-adhesive plant surfaces. Furthermore, the negative overhang in the profile of the ridges and granules were revealed to be a highly effective, but as yet neglected, design principle of collembolan skin. We suggest an explanation for the non-wetting characteristics of surfaces consisting of such profiles irrespective of the chemical composition. Many valuable opportunities arise from the translation of the described comb-like patterns and overhanging profiles of collembolan skin into man-made surfaces that combine stability against wear and friction with superior non-wetting and anti-adhesive characteristics. [ABSTRACT FROM AUTHOR]

Extensive biofilm formation on materials used in restorative dentistry is a common reason for their failure and the development of oral diseases like peri-implantitis or secondary caries. Therefore, novel materials and strategies that result in reduced biofouling capacities are urgently sought. Previous research suggests that surface structures in the range of bacterial cell sizes seem to be a promising approach to modulate bacterial adhesion and biofilm formation. Here we investigated bioadhesion within the oral cavity on a low surface energy material (perfluorpolyether) with different texture types (line-, hole-, pillar-like), feature sizes in a range from 0.7–4.5 µm and graded distances (0.7–130.5 µm). As a model system, the materials were fixed on splints and exposed to the oral cavity. We analyzed the enzymatic activity of amylase and lysozyme, pellicle formation, and bacterial colonization after 8 h intraoral exposure. In opposite to in vitro experiments, these in situ experiments revealed no clear signs of altered bacterial surface colonization regarding structure dimensions and texture types compared to unstructured substrates or natural enamel. In part, there seemed to be a decreasing trend of adherent cells with increasing periodicities and structure sizes, but this pattern was weak and irregular. Pellicle formation took place on all substrates in an unaltered manner. However, pellicle formation was most pronounced within recessed areas thereby partially masking the three-dimensional character of the surfaces. As the natural pellicle layer is obviously the most dominant prerequisite for bacterial adhesion, colonization in the oral environment cannot be easily controlled by structural means. [ABSTRACT FROM AUTHOR]

Textured implant surfaces with micrometer and sub-micrometer features can improve contact properties like cell adhesion and bacteria repellency. A critical point of these surfaces is their mechanical stability during implantation. Therefore, strategies capable to provide both biocompatibility for an improved implant healing and resistance to wear for protecting the functional surface are required. In this work, laser-based fabrication methods have been used to produce hierarchical patterns on titanium surfaces. Using Direct Laser Writing with a nanosecond pulsed laser, crater-like structures with a separation distance of 50 µm are produced on unpolished titanium surfaces. Directly on this texture, a hole-like pattern with 5 µm spatial period is generated using Direct Laser Interference Patterning with picosecond pulses. While the smaller features should reduce the bacterial adhesion, the larger geometry was designed to protect the smaller features from wear. On the multifunctional surface, the adherence of E. Coli bacteria is reduced by 30% compared to the untreated reference. In addition, wear test performed on the multiple-scale patterns demonstrated the possibility to protect the smaller features by the larger craters. Also, the influence of the laser treatment on the growth of a titanium oxide layer was evaluated using Energy Dispersive X-Ray Spectroscopy analysis. [ABSTRACT FROM AUTHOR]