Exploring the Potential of Adaptive, Local Machine Learning in Comparison to the Prediction Performance of Global Models: A Case Study from Bayer's Caco-2 Permeability Database.

Machine learning (ML) techniques are being widely implemented to fill the gap in simple molecular design guidelines for newer therapeutic modalities in the extended and beyond rule of five chemical space (eRo5, bRo5). These ML techniques predict molecular properties directly from the structure, allowing for the prioritization of promising compounds. However, the performance of models varies greatly among ML use cases.

Vulnerability of transport through evolving spatial networks.

Insight into the blockage vulnerability of evolving spatial networks is important for understanding transport resilience, robustness, and failure of a broad class of real-world structures such as porous media and utility, urban traffic, and infrastructure networks. By exhaustive search for central transport hubs on porous lattice structures, we recursively determine and block the emerging main hub until the evolving network reaches the impenetrability limit. We find that the blockage backbone is a self-similar path with a fractal dimension which is distinctly smaller than that of the universality class of optimal path crack models.

Nanotechnological approaches for efficient N2B delivery: from small-molecule drugs to biopharmaceuticals.

Central nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood-brain barrier. While protecting the brain's homeostasis, the barrier limits the passage of almost all large-molecule drugs and most small-molecule drugs.

Benchmarking Cross-Docking Strategies in Kinase Drug Discovery.

In recent years, machine learning has transformed many aspects of the drug discovery process, including small molecule design, for which the prediction of bioactivity is an integral part. Leveraging structural information about the interactions between a small molecule and its protein target has great potential for downstream machine learning scoring approaches but is fundamentally limited by the accuracy with which protein-ligand complex structures can be predicted in a reliable and automated fashion. With the goal of finding practical approaches to generating useful kinase-inhibitor complex geometries for downstream machine learning scoring approaches, we present a kinase-centric docking benchmark assessing the performance of different classes of docking and pose selection strategies to assess how well experimentally observed binding modes are recapitulated in a realistic cross-docking scenario.

The self-relevant spotlight metaphor: Self-relevant targets diminish distractor-response-binding effects.

Recently, it has been proposed that self-relevance of a stimulus enhances executive control and reduces the impact of distractors on current task performance. The present study aimed to test whether the binding between a distractor and a response is influenced by self-relevance, too. We assumed that targets' self-relevance should increase executive control processes and therefore reduce the influence of distractors on current performance.

In vitro activity of ceftazidime-avibactam/aztreonam combination against MBL-producing Pseudomonas aeruginosa strains.

Purpose: The emergence of multidrug-resistant P. aeruginosa isolates poses a challenge to healthcare systems worldwide. Rising numbers in deaths, duration of hospitalization as well as failing treatments prove the hazards posed by these pathogens.

Towards sustainability of volatile anaesthetics: capture and beyond.

The first measures to reduce the environmental harm from volatile anaesthetics are implementation of minimal fresh gas flow strategies and avoidance of desflurane. Although anaesthetic waste gas capture systems generally exert high capturing efficiencies, only about half of volatile anaesthetics used in the operating room are accessible for capture. Industry-sponsored reports promise a reduction of the global warming potential by both incineration and recycling of captured volatile anaesthetics.

Microvascular Reconstructions in Elderly Patients With Oral Squamous Cell Carcinoma - Too Old for Surgical Treatment?

Study Design: Retrospective cohort study.

Objective: A major risk factor for oral squamous cell carcinoma (OSCC) is advanced age. Ablative surgery combined with microvascular reconstruction has become routine for OSCC.

Novel approaches to define responders to interventional treatment in hypertension: insights from the SPYRAL HTN-OFF and HTN-ON MED trials.

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN "responders" prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN.

Heavy Pentaisopropylcyclopentadienyltriylenes and their Heterobimetallic Complexes.

A series of triylenes of the heavy group 13 elements gallium, indium and thallium, carrying the pentaisopropylcyclopentadienyl ligand is reported. The compounds were characterized in solution and in the solid-state and their donor ligand properties in heterobimetallic complexes were investigated, whereby a series of tungsten carbonyl complexes was isolated. Furthermore, a new synthetic route towards a previously described lithium-aluminum heterobimetallic dimetallocene is reported, which also enabled the isolation of a heterobimetallic polydecker of lithium and gallium.

Chemical diversity of cyanobacterial natural products.

Covering: 2010 to 2023Cyanobacterial natural products are a diverse group of molecules with promising biotechnological applications. This review examines the chemical diversity of 995 cyanobacterial metabolites reported from 2010 to 2023. A computational analysis using similarity networking was applied to visualize the chemical space and to compare the diversity of cyanobacterial metabolites among taxonomic orders and environmental sources.

Deficiency of NLRP3 protects cerebral pericytes and attenuates Alzheimer's pathology in tau-transgenic mice.

Introduction: Activation of NLRP3-containing inflammasome, which is responsible for IL-1β maturation, has been shown to contribute to Alzheimer's disease (AD)-associated pathogenesis in both APP- and tau-transgenic mice. However, effects of NLRP3 on pericytes and subsequent cerebrovascular pathology in AD remain unknown.

Methods: NLRP3-deficient and wild-type AD animal models were generated by crossing human P301S tau-transgenic mice and knockout mice.

Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic.

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use.

Clotting Promotes Glioma Growth and Infiltration Through Activation of Focal Adhesion Kinase.

High-grade gliomas are associated with intratumoral thrombosis, tumor cell necrosis, and hemorrhage. The resulting blood clot serves as an adhesive matrix for glioma cell integrins that activate FAK. Knocking down FAK with CRISPR cas9, on the other hand, is highly effective at halting GBM growth in mice.

Dissipative split-charge formalism: Ohm's law, Nyquist noise, and non-contact friction.

The split-charge equilibration method is extended to describe dissipative charge transfer similarly as the Drude model, whereby the complex-valued frequency-dependent dielectric permittivities or conductivities of dielectrics and metals can be mimicked at non-zero frequencies. To demonstrate its feasibility, a resistor-capacitor circuit is simulated using an all-atom representation for the resistor and capacitor. The dynamics reproduce the expected charging process and Nyquist noise, the latter resulting from the thermal voltages acting on individual split charges.

Evaluation of training models for intraventricular neuroendoscopy.

Structured surgical education has become increasingly important in recent years. Intraventricular neuroendoscopic procedures have been widely established. However, training surgical skills with these techniques is crucial for young residents due to the potential harm to adjacent tissue.

Targeting the IspE Enzyme.

The enzyme IspE in is considered an attractive drug target, as it is essential for parasite survival and is absent in the human proteome. Yet it still has not been addressed by a small-molecule inhibitor. In this study, we conducted a high-throughput screening campaign against the IspE enzyme.

Infiltration of salivary proteins into dentin during erosive processes.

Objective: Ultrastructural analyses showed that during erosion under oral cavity conditions, dentin is infiltrated by a substrate morphologically similar to salivary proteins. This in-situ study aimed to investigate the presence of salivary proteins in demineralized dentin.

Methods: Bovine dentin specimens were attached to individual maxillary splints (n = 1 per subject and condition) and worn intraorally by four subjects for 1 min.