Browse Articles
Discover research articles across all indexed journals
Combined In‐Solution and On‐Surface Synthesis of a Fully Fused Cross‐Shaped Phthalocyanine Pentamer
Abstract Phthalocyanines (Pcs) are a class of technologically relevant tetrapyrrolic macrocycles that offer rich photophysical properties as well as excellent tunability by means of chemical functionalization. Among such functionalization strategies, the synthesis of multinuclear, fully fused Pcs – adjacent macrocycles seamlessly fused through a shared aromatic ring into a continuous π‐system – is particularly appealing for the preparation of new, exotic, atomically precise carbon frameworks. However, the notoriously low solubility of Pcs typically impedes the synthesis of oligomers beyond trimers. In addition, the positional control for specific units in large low‐symmetry frameworks is particularly challenging. In this work, taking advantage of the benefits of on‐surface synthesis under ultra‐high vacuum (UHV) conditions, we present a strategy that allows the on‐surface synthesis of cross‐shaped Pc pentamers. This pentamer, which bears two different metal ions with pre‐defined positional control, shows a small transport gap of 1.15 eV on Au(111).
Hybrid Aquila optimizer–Harris Hawks optimization for CNN hyperparameter tuning in brain tumor classification
Abstract Magnetic resonance imaging (MRI) is hard to categorize properly in terms of interclass similarity, there is data imbalance, and sensitive clinical decision-making: but the performance of convolutional neural networks (CNNs) highly relies on effective, yet computationally costly, hyperparameter tuning. To find solutions to such issues, the given paper proposes a hybrid solution to the problems of the Aquila Optimizer and Harris Hawks Optimization, i.e., Aquila Optimizer-Harris Hawks Optimization (AO-HHO) framework, to integrate the positive qualities of extremely good global exploration of the Aquila Optimizer and the good local exploitation process of a Harris Hawks Optimization to achieve balanced and robust CNN hyperparameter optimization. On a publicly accessible dataset of 7, 023 brain MRI images divided into glioma, meningioma, pituitary tumor, and non-tumor, the proposed algorithm has been tested on with fine-tuning critical hyperparameters, such as learning rate, batch size, number of filters, dropout rate, and optimizer type. The rate of accuracy, precision, recall and F1-score of the AO-HHO-tuned CNN is invariably high than the conventional metaheuristic algorithms, including the Particle Swarm Optimization (PSO), Genetic Algorithm (GA), and Whale Optimization Algorithm (WOA) that are approximately 78–83. The proposed method also helps in reducing the cost of computing. It takes only 77.85 s to train, while the baseline optimizers take more than 300 s. This shows that AO–HHO is a reliable, accurate, and computationally efficient framework that can be used for medical imaging decision-support applications that need to be done in real time and with limited resources.
Unsaturated Phosphorus Electrophiles to Probe Protein Tyrosine Phosphatases
ABSTRACT Protein tyrosine phosphatases (PTPs) represent an important pharmacological target and subject of study. Although a number of broad‐spectrum electrophilic, phosphotyrosine‐mimicking probes have been developed to covalently capture the catalytic site of these enzymes, there is still a high demand for PTP probes with high target selectivity that are accessible in a synthetically straightforward way. Unsaturated phosphorus (V) (P(V)) compounds have recently emerged as powerful cysteine‐selective bioconjugation reagents (P5‐labeling). Herein, we introduce ethynyl‐substituted aryl phosphonamidic and phosphonic acids as phosphotyrosine mimics, which serve as active‐site‐directed, covalent probes for tyrosine phosphatases. We show that these P(V) electrophiles can be readily incorporated into a peptide sequence, allowing proximity‐enabled reactivity and selective targeting of the catalytic cysteine residue of an interacting phosphatase, as exemplified for PTP1B, a protein tyrosine phosphatase that acts as a key negative regulator of insulin signaling. Both ethynyl phosphonamidic acid and ethynyl phosphonic acid show no reactivity towards nontarget cysteine residues, though the phosphonamidic acid probe was notably less reactive toward its intended target. Proteomics experiments in human cell lysates demonstrated that the phosphonic acid probe selectively enriches its interacting phosphatase in the human proteome. Our study highlights a versatile strategy to obtain remarkably precise peptide‐based PTP probes, thereby enabling the characterization of phosphatase interactions with high specificity.
Non-destructive environmental DNA extracted from owl pellet contents: A valuable tool for monitoring mammalian species richness
Environmental DNA (eDNA) offers valuable presence/absence data for populations and has been widely used in comprehensive biodiversity assessments. However, applying eDNA in terrestrial environments poses unique challenges, particularly in obtaining samples that are representative of ecological communities. eDNA extracted from top-predator dietary samples can be an effective sampling source in monitoring prey populations. In this study, we tested a novel, non-destructive protocol to assess the efficacy of eDNA from barn owl ( Tyto javanica delicatula ) pellets as a tool for monitoring small mammal communities in an arid environment. We assessed the species composition and abundance of small mammals from owl pellets collected in the Simpson Desert in far western Queensland, Australia, using a three-tiered approach. We extracted DNA from 50 owl pellets and targeted a 16S mini-barcode for metabarcoding. We compared species detection via genetic analysis with that of morphological analysis, and finally with historical small mammal trapping data. The DNA extraction method presented here resulted in full preservation of prey bones and fur material for museum archival. eDNA detected four mammal species that were not detected via morphological pellet analysis, three of which are significant detections that had not been observed at this location before but were expected to occur based on likely distribution ranges. However, a key limitation of the eDNA approach demonstrated in this study, is that taxonomic identification was constrained by the completeness of reference databases, which can result in false negatives or ambiguous assignments. The results of the present study demonstrate that the specificity of an eDNA approach can offer advantages compared with morphological identification of mammalian remains from owl pellets, and that genetic owl pellet analysis may be particularly useful in full vertebrate diversity assessments that include reptiles, birds and amphibians that are unidentifiable from skeletal remains.
Dynamic velocity scaling for industrial collaborative robots: a gaze-driven approach
Dynamic Binder Exchange Improves Protein Labeling Efficiency in DNA‐PAINT up to 15‐Fold
Abstract Dynamic Binder Exchange (DyBE) enhances DNA‐PAINT (Point Accumulation for Imaging in Nanoscale Topography) super‐resolution microscopy by exploiting transient, reversible binder‐target interactions. DyBE uses DNA‐conjugated binders such as nanobodies as both targeting and docking moieties, integrating their characteristic higher off‐rates with DNA‐PAINT blinking to efficiently sample target sites. This dual‐kinetic scheme increases labeling efficiency up to 15‐fold, enabling sensitive detection of targets previously inaccessible due to limitations of high‐off‐rate binders. Using DyBE, the study reveals pre‐existing HER2 homodimers and ligand‐induced EGFR‐HER2 heterodimers at single‐protein resolution with high fidelity. DyBE expands the usable binder repertoire, advancing spatial proteomics and enabling mechanistic drug studies of receptor organization and signaling.
Exploring equity in audit and feedback trials: Secondary analysis of a systematic review
Background One potential approach to eliminating or reducing health inequities for health systems is audit and feedback (A&F). A&F involves providing measurements of quality indicators to health professionals to support continuous quality improvement, and to increase clinicians’ adherence to clinical practice guidelines. In theory, A&F could help direct efforts toward equity deserving sub-groups (e.g., gender-diverse individuals or those living with low-income) by highlighting factors that may place such sub-groups at higher risk of poor health outcomes. In cases where healthcare professionals can make adjustments to their practice or advocate for mitigating supports or services, A&F – when applied broadly – could help to address some health inequities. However, it is unknown whether and how A&F interventions are currently being used to support equity-oriented quality improvement. In this study, we sought to examine the extent to which trials evaluating A&F interventions address health equity. Methods We conducted a secondary analysis of randomized controlled trials included in the latest Cochrane systematic review on the effects of A&F on professional practice, which included articles published up to 2020. We used the PROGRESS-Plus framework to consider the extent to which variables related to equity were examined in the trials. Based on extracted data, studies were categorized as not equity-oriented, equity-informed, or equity-focused. Results Of the 271 articles included within this analysis, 44% of trials were classified as not equity-oriented (n = 120), 35% as equity-informed (n = 95), and 21% as equity-focused (n = 56). The proportion of equity-focused and informed trials increased over the timeline assessed. Only two articles described an equity-oriented framework approach. Only three articles explicitly reported how equity was embedded in their A&F process by highlighting factors including age, gender/sex, and substance use as part of the patient data presented in their feedback. The PROGRESS-Plus factors most commonly considered in the methods or analysis of the trials were age, insurance status, place of residence, and gender/sex. Conclusions A&F trials rarely examine or report the extent to which equity issues inform trial design, A&F processes, analyses, and/or interpretations. Our findings suggest a need for future A&F trials that test explicit approaches to incorporating equity-related interventions to address health equity by helping healthcare professionals, teams, and organizations to be more aware of inappropriate discrepancies in care.
Predictive value of the Naples Prognostic Score for rapid kidney function decline in stage 3–4 CKD: a multicenter study
Tuning Circular Dichroism and Circularly Polarised Luminescence in Single Crystals of a Perylene Diimide Macrocycle
Abstract Chiral materials that manipulate circularly polarised light have burgeoning applications across optoelectronics, sensing and information encoding, yet the functionality of organic molecular materials is often limited by their relatively low dissymmetry factors ( g abs/lum < 10 − 2 ), including towards the near infrared ( λ > 700 nm). An effective strategy to amplifying g abs/lum is to optimise the chiral arrangement of chromophores, with single crystals providing intrinsic molecular ordering. Herein, we quantify the circular dichroism and circularly polarised luminescence of single crystals of a chiral L‐valinol bis‐perylene diimide macrocycle by Mueller–Matrix polarimetry and circularly polarised luminescence microscopy, as required for the analysis of such anisotropic materials. Through this, we see that organic crystals are valuable for understanding how supramolecular structure can be used to modify the sign, strength and energy of the chiroptical signal. Indeed, by tuning the macrocycle's π–π stacking interactions, our materials deliver strong chiroptical properties ( g abs/lum > 10 − 2 ), including circularly polarised luminescence into the near infrared ( λ = 780 nm).
Correction: Concurrent coverage and determinants of vitamin A supplementation and deworming among children aged 12–59 months in 15 Sub-Saharan African countries
Retraction Note: Methylation-induced suppression of BEX1 activates AKT/ERK/STAT3 signaling pathways regulating cell cycle and apoptosis in glioma
Bioinspired Total Synthesis of Curtachalasin B and Biosynthetically Related Cytochalasans
Abstract We report the first total syntheses of curtachalasin B and a series of biosynthetically related cytochalasans, including ketocytochalasin, xylariasins, brunnesins, zygosporins, arbuschalasins, cytochalasins, and curtachalasin Q, derived from the common precursor zygosporin G. The key intermediate was strategically assembled through an intermolecular Diels–Alder reaction, two Horner–Wadsworth–Emmons (HWE) macrocyclizations, and a late‐stage methyl 1,2‐addition. The highly functionalized 6/6 ring system of curtachalasin B was efficiently constructed through a biosynthetic network analysis inspired transannular cyclization and α‐ketol rearrangement cascade. This unified skeletal reorganization strategy not only accomplished the first total synthesis of fifteen cytochalasans but also provided compelling experimental support for the proposed biosynthetic pathway of curtachalasin B, thereby establishing a chemical link between multiple subclasses of this family.
Modelling approaches for estimating vaccine effectiveness of consecutive SARS-CoV-2 variant sublineages in the absence of study-specific genetic sequencing data, VEBIS hospital network, Europe, 2023/24
Introduction Genetic changes in COVID-19 variants/sublineages (VSLs) can reduce vaccine effectiveness (VE). Timely VSL-specific VE estimates are essential, but study-specific VSL identification by whole genome sequencing (the “gold standard”) is expensive and time-consuming. Alternatively, VSL-specific VE has been estimated from external sequencing data (VSL predominance period by proxy: PP). We propose two novel approaches for use in test-negative design (TND) studies to estimate VSL-specific VE when study-specific VSL identification is not possible. Methods We demonstrate the variant category model (VCM) and the variant proportion model (VPM) approaches. Using data from a hospital-based TND study among adults ≥65 years, during the period of sequential predominance of XBB and BA.2.86 in 2023/24, we estimated the VE as (1-OR) x 100%. For the VCM, we used a binary variable categorising “most likely underlying sublineage” based on publicly available sequencing data. For the VPM, we used a continuous variable with values from 0 to 1 representing the weekly proportion of BA.2.86. We validated results using study-specific VSL identification from sequenced study data (SD) and the standard PP approach. Results Overall, at 14–59 days post vaccination, VE point estimates against XBB were within ±3% absolute for the VE estimated using both models, with an equivalent standard PP validation. We could not validate using SD, as there were no vaccinated XBB cases. Against BA.2.86, VE was lower than against XBB, and the VCM and VPM results were within ±7% absolute of each other, with lowest validation results from SD but equivalent results from the PP. Conclusions Both proposed approaches produced similar VE estimates to those from well-known methods. The VPM could also provide VE estimates when the validation techniques were limited by low sample size.
Innovative solutions for lossy nonlinear transmission lines model using a modified extended mapping approach with fractional effects
Abstract This study investigates soliton solutions of the lossy nonlinear electrical transmission line (Loss-NLETL) model using the Modified Extended Mapping (Mod-EM) technique. The model incorporates the effect of a conformable fractional derivative (Con-FD) with respect to the spatial variable $$x$$ , enabling a more generalized and exact depiction of the system’s behavior. A set of exact analytical solutions has been obtained, including composite hyperbolic-type solutions, trigonometric periodic waves, singular periodic wave solutions, dark soliton solutions, exponential traveling wave solutions, hyperbolic soliton solutions, singular hyperbolic waveforms, mixed-type soliton structures involving kink and rational hyperbolic components, and Jacobi elliptic wave solutions. Several of these solutions are novel and extend the existing literature. To illustrate the physical behavior and structural diversity of the solutions, 2D, 3D, and density plots have been generated. Furthermore, a parametric analysis has been conducted to explore the influence of the variation in $${\beta }_{1}$$ , a key parameter affecting the spatial evolution of the waveforms. The results demonstrate the effectiveness of the method in generating diverse soliton structures in complex nonlinear systems, with potential implications for applied physics and electrical engineering applications.
A Monkey‐Saddle‐Shaped Nanographene Embedding a Dicyclohepta[ <i>cd</i> , <i>fg</i> ]‐ <i>as</i> ‐Indacene Core and Two Additional Heptagons, and Its Paddle‐Wheel Co‐Assembly With Fullerenes
ABSTRACT We present a novel nanographene 1 that embeds a dicyclohepta[ cd , fg ]‐ as ‐indacene ( DCH‐ as ‐I ) motif and two additional heptagons. This defective π‐skeleton was efficiently synthesized from the oligophenylene precursors via the Scholl reaction, affording four heptagons in one shot. The integration of DCH‐ as ‐I and heptagons endows 1 with excellent solubility, superior fluorescence emission, multiple reversible redox processes, and exceptional supramolecular behavior. X‐ray crystallographic analysis shows that 1 adopts a chiral monkey‐saddle‐shaped conformation and exists as a pair of enantiomers in the crystal lattice. The saddles of 1 stack through π–π overlap into slipped π‐dimers, which further assemble into linear arrays with ellipsoidal cavities that encapsulate chloroform molecules, forming clathrate‐like structures. The supramolecular co‐assembly of saddle 1 with C 60 was confirmed both in solution and crystal states. Single‐crystal structures unequivocally revealed an unprecedented 4:4 complex (C 60 ) 4 ⊂( 1 ) 4 , in which four saddles of identical configuration and four C 60 spheres are alternately arranged into a chiral paddle‐wheel structure. Two such complexes of opposite chirality further dimerize in a staggered fashion to form an aesthetically‐striking octameric nanocubular supramolecular architecture. This study offers profound insights into the joint influence of DCH‐ as ‐I and heptagonal defects on the topology, electronic structure, photophysical properties, and supramolecular assembly behavior of nanographenes.
Integrating machine learning with SHAP to uncover multi-tissue molecular signatures in Osteoarthritis progression
Osteoarthritis (OA) is a chronic joint disorder characterized by pain, reduced mobility, and structural degeneration. Despite its complex etiology and multi-tissue involvement, the molecular mechanisms underlying OA remain poorly understood. This study aimed to identify tissue-specific diagnostic biomarkers using an integrative framework combining multiple machine learning (ML) algorithms and SHapley Additive exPlanations (SHAP). Gene expression profiles from cartilage, synovium, and peripheral blood were retrieved from the GEO database. DEGs were identified across tissues, followed by feature selection using Least Absolute Shrinkage and Selection Operator(LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Random Forest(RF). Functional enrichment, gene set variation analysis (GSVA), and immune infiltration analyses were conducted. 10 ML models were constructed to evaluate diagnostic performance. A total of 8, 28, and 61 DEGs were identified in cartilage, synovium, and blood, respectively. Enrichment analysis revealed the key roles in inflammatory signaling, metabolism, and immune pathways. Biomarkers identified included CSN1S1, ABCA6, RARRES1, NPTX2 (cartilage); SCRG1, CXCL2, PTGDS, CCL19, BGN, KLF9 (synovium); and GNL3L, C6orf111, NT5C3, ZNF148 (blood). Immune analysis indicated shifts in mast cells and CD8 + T cells in cartilage and dendritic cells in synovium, while no significant immune alterations were found in blood. Diagnostic models demonstrated strong performance, with AUCs of 0.839 (cartilage), 0.934 (synovium), and 0.892 (blood). SHAP analysis was employed to interpret each model by quantifying the contribution of individual genes to predict outcomes. In the optimal cartilage model, CSN1S1 and ABCA6 were the most influential features, with mean absolute SHAP values of 0.146 and 0.122, respectively. For synovium, SCRG1 (0.111) and CXCL2 (0.097) were top contributors, while in blood, GNL3L (0.148) and C6orf111 (0.143) showed the highest predictive importance. These results underscore the interpretability of the models and validate the functional relevance of selected biomarkers. Collectively, this study provides a robust ML-based framework for identifying and interpreting reliable OA biomarkers across multiple tissues, offering valuable insights into disease mechanisms and supporting the development of diagnostic tools.
Physics-guided estimation of freight vehicle loading status using digital tachograph data
Anodic H <sub>2</sub> O <sub>2</sub> Production via CO <sub>3</sub> <sup>2−</sup> /HCO <sub>3</sub> <sup>−</sup> ‐Mediated Spillover Effect in Three‐Phase Electrochemical System
ABSTRACT Two‐electron water oxidation reaction (2e − WOR) mediated by (bi)carbonate (CO 3 2− /HCO 3 − ) is promising for anodic H 2 O 2 production. However, previous H 2 O 2 yields are usually unsatisfactory due to low local CO 3 2− /HCO 3 − concentration at the solid/liquid interface. These sluggish reaction rates mainly result from the restricted ion diffusion, and the obstacle of by‐product O 2 bubbles. To resolve this puzzle, a three‐phase WOR system based on CO 2 (g)/dual‐catalyst composite (s)/KOH (l) is adopted. At the three‐phase interface, a high local concentration of CO 3 2− /HCO 3 − can form in the CO 2 adsorption unit and transfer to the WOR catalyst unit via the CO 3 2− /HCO 3 − ‐mediated spillover effect. As a result, the largest H 2 O 2 yield of 51.62 mM at 50 mA cm −2 was realized, superior to that of the conventional two‐phase system. Density functional theory (DFT) calculations, electrochemical and CO 2 adsorption tests, and in situ Fourier transform infrared spectra (FTIR) results jointly confirmed the larger adsorption amount of CO 3 2− /HCO 3 − ions, the spillover of CO 3 2− /HCO 3 − and their transformation to HCO 4 − , and the whole reaction processes from CO 2 adsorption to final H 2 O 2 production at the three‐phase interface. This is the first application of the three‐phase design in WOR, which can provide guidance for efficient H 2 O 2 synthesis in 2e − WORs and can also be applied in other electrochemical WORs.
Factors correlated with financial hardship among cancer patients during the COVID-19 pandemic
Purpose Financial hardship from cancer care is associated with poor patient outcomes. Economic disruption during the COVID-19 pandemic may have exacerbated patients’ financial concerns. We explore how social deprivation index (SDI), clinical, and treatment-related factors impacted financial hardship in this observational secondary analysis using data collected prospectively during implementation of financial hardship screening from our NCI-designated center during COVID-19. Methods Adults aged ≥18 years undergoing active treatment for stage 0-IV breast or lung cancer and who completed a 5-point Likert response-item screening for financial difficulty between 11/2020 and 11/2021 were included. Generalized estimating equations assessed associations between quartiles of zip-code level SDI, a composite obtained using data from US Census and American Community Survey, and binary outcome of financial hardship adjusting for relevant covariates . Results Of 2245 patients, 87% identified as White, 9% as Black, 2% as Asian. The majority of patients identified as non-Hispanic (99%). Median age was 62 years old (IQR 53–71).The majority were treated for breast cancer (79%). Significant financial hardship (Likert responses ≥2) was reported by 7%. Most were married, had managed-care insurance, resided in urban settings, and had early-stage cancers (all p < 0.001). Of those included, 83% received surgery, 52% received chemotherapy, and 65% received radiation. Compared to the lowest SDI quartile, penultimate and highest quartiles were associated with financial hardship (Q3 aOR 1.86; 95%CI 1.13–3.05); Q4 aOR 2.05; 95%CI 1.15–3.63). Younger age, Black race, comorbidities, radiation, and chemotherapy were also associated with greater financial hardship (p < 0.05). Conclusion In this study, greater SDI, younger age, Black race, comorbidities, receipt of radiation and/or chemotherapy were associated with financial hardship. These factors may guide focused screening of vulnerable populations to assist with equitable access to resources that offset the economic effects of cancer care.