Motivation: Machine learning-based scoring functions (MLBSFs) have been found to exhibit inconsistent performance on different benchmarks and be prone to learning dataset bias. For the field to develop MLBSFs that learn a generalisable understanding of physics, a more rigorous understanding of how they perform is required.
Results: In this work, we compared the performance of a diverse set of popular MLBSFs (RFScore, SIGN, OnionNet-2, Pafnucy, and PointVS) to our proposed baseline models that can only learn dataset biases on a range of benchmarks.
Introduction: Cancer multi-disciplinary team meetings (MDTM) assemble clinical experts to make diagnostic and treatment recommendations. MDTMs can take place in person, virtually, or in a hybrid format. Virtual and hybrid MDTMs have been in use for over two decades.
View Article and Find Full Text PDF: The Measles-Rubella Microarray Patch (MR-MAP) is an important technology that is expected to reduce coverage and equity gaps for measles-containing vaccines (MCVs), reach zero-dose children, and contribute to elimination of measles and rubella. MR-MAPs are anticipated to be easier to deploy programmatically and could be delivered by lesser-trained health workers, thereby increasing immunization coverage. The most advanced MR-MAP has reached clinical proof-of-concept through a Phase I/II trial in the target population of infants and young children.
View Article and Find Full Text PDFIntroduction: Bacterial infection of the intervertebral disc can lead to vertebral endplate edema known as Modic changes, with associated chronic low back pain. Oral antimicrobial therapy has shown efficacy but relies on prolonged dosing and may not be optimal in terms of patient outcome, side effects, or antibiotic stewardship. There is no antibiotic formulation approved for intradiscal administration.
View Article and Find Full Text PDFDespite the proliferation of studies on waste governance over the past decades, comparative research on advancing sustainable municipal solid waste management (MSWM) in medium-sized cities across various political regimes and remote geographies has been overlooked. Comprehending factors for governance advancement is critical for Arctic cities, as they face unique challenges due to their geographical remoteness, population size, economic constraints, and severe weather conditions. This qualitative study, drawn from the cases of Anchorage (USA), Murmansk (Russia), and Tromsø (Norway), uses Evolutionary Governance Theory (EGT) to examine how dependencies between actors and institutions enable and create barriers to the advancement of MSWM.
View Article and Find Full Text PDFNMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases.
View Article and Find Full Text PDFMany studies have prophesied that the integration of machine learning techniques into small-molecule therapeutics development will help to deliver a true leap forward in drug discovery. However, increasingly advanced algorithms and novel architectures have not always yielded substantial improvements in results. In this Perspective, we propose that a greater focus on the data for training and benchmarking these models is more likely to drive future improvement, and explore avenues for future research and strategies to address these data challenges.
View Article and Find Full Text PDFLow-field NMR has emerged as a new analytical technique for the investigation of molecular structure and dynamics. Here, we introduce a highly integrated ultralow-frequency NMR spectrometer designed for the purpose of ultralow-field NMR polarimetry of hyperpolarized contrast media. The device measures 10 cm × 10 cm × 2.
View Article and Find Full Text PDFBackground: Lichen sclerosus (LS) is a chronic inflammatory condition mainly affecting genital skin. It causes distressing symptoms that impact daily quality of life as well as progressive anatomical changes and potential risk of cancer. Vulval LS is often misdiagnosed and treatment delayed.
View Article and Find Full Text PDFBone matrix exhibits exceptional mechanical properties due to its unique nanocomposite structure of type I collagen fibrils and hydroxyapatite (HAp) nanoparticles in hierarchical liquid crystalline (LC) order. However, the regeneration mechanism of this LC structure is elusive. This study investigates the role of the LC structure of HAp nanorods in guiding aligned mineralization and its underlying molecular mechanism.
View Article and Find Full Text PDFIntroduction: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions.
Methods: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development.
Objective: Laryngeal dystonia (LD), previously termed spasmodic dysphonia, is an isolated focal dystonia that involves involuntary, uncontrolled contractions of the laryngeal muscles during speech. It is a severely disabling condition affecting patients' work and social lives through prevention of normal speech production. Our understanding of the pathophysiology of LD and available therapeutic options are currently limited.
View Article and Find Full Text PDFMacromolecule branching upon polyhedral oligomeric silsesquioxanes (POSS) "click" chemistry has previously been reported for promoting natural biological responses , particularly when regarding their demonstrated biocompatibility and structural robustness as potential macromolecule anchoring points. However, "clicking" of large molecules around POSS structures uncovers two main challenges: (1) a synthetic challenge encompassing multi-covalent attachment of macromolecules to a single nanoscale-central position, and (2) purification and separation of fully adorned nanocages from those that are incomplete due to their similar physical characteristics. Here we present peptide decoration to a TPOSS nanocage through the attachment of azido-modified trimers.
View Article and Find Full Text PDFBackground: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss.
Objective: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally.
A chromium complex carrying two benzanellated N-heterocyclic phosphenium (bzNHP) ligands was prepared by a salt metathesis approach. Spectroscopic studies suggest that the anellation enhances the π-acceptor ability of the NHP-units, which is confirmed by the facile electrochemical reduction of the complex to a spectroscopically characterized radical anion. Co-photolysis with H allowed extensive conversion into a σ-H-complex, which shows a diverse reactivity towards donors and isomerizes under H-H bond fission and shift of a hydride to a P-ligand.
View Article and Find Full Text PDFObjectives: This scoping review aims to comprehensively assess current surgical interventions for bilateral vocal fold paralysis (BVFP), addressing the heterogeneity in treatment outcomes. Additionally, it explores the potential role of soft robotics as an innovative approach to improve outcomes in BVFP management.
Methods: This scoping review systematically examines literature from MEDLINE, Embase, and Scopus databases.
Objectives: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs.
Materials And Methods: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B non-uniformity on TSC measurements were corrected using the double-angle method.
Targeted protein degradation (TPD) is a rapidly expanding field, with various PROTACs (proteolysis-targeting chimeras) in clinical trials and molecular glues such as immunomodulatory imide drugs (IMiDs) already well established in the treatment of certain blood cancers. Many current approaches are focused on oncology targets, leaving numerous potential applications underexplored. Targeting proteins for degradation offers a novel therapeutic route for targets whose inhibition remains challenging, such as protein aggregates in neurodegenerative diseases.
View Article and Find Full Text PDFLight-driven soft actuators based on photoresponsive materials can be used to mimic biological motion, such as hand movements, without involving rigid or bulky electromechanical actuations. However, to our knowledge, no robust photoresponsive material with desireable mechanical and biological properties and relatively simple manufacture exists for robotics and biomedical applications. Herein, we report a new visible-light-responsive thermoplastic elastomer synthesized by introducing photoswitchable moieties (i.
View Article and Find Full Text PDFThe synthesis of a new bis-NHP complex (NHP=N-heterocyclic phosphenium) of chromium via salt metathesis and studies of its reactivity are reported. Photochemical reactions with H and selected olefins give rise to non-isolable H- and π-alkene complexes identified spectroscopically, while internal alkynes react via activation of the triple bond to yield isolable metalla-phospha-cyclobutenes characterized by spectroscopic and XRD data. DFT studies give a preliminary account of the bonding in H- and alkene-complexes and explain the different reactivity towards alkenes and alkynes as the consequence of kinetic effects.
View Article and Find Full Text PDFPediatric injuries are a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). The recovery of injured children in LMICs is often impeded by barriers in accessing and receiving timely and quality care at healthcare facilities. The purpose of this study was to identify the barriers and the facilitators in pediatric injury care at Kilimanjaro Christian Medical Center (KCMC), a tertiary zonal referral hospital in Northern Tanzania.
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