This study aims to address the critical issue of emergency department (ED) overcrowding, which negatively affects patient outcomes, wait times, and resource efficiency. Accurate prediction of ED length of stay (LOS) can streamline operations and improve care delivery. We utilized the MIMIC IV-ED dataset, comprising over 400,000 patient records, to classify ED LOS into short (≤4.5 hours) and long (>4.5 hours) categories. Using machine learning models, including Gradient Boosting (GB), Random Forest (RF), Logistic Regression (LR), and Multilayer Perceptron (MLP), we identified GB as the best performing model outperforming the other models with an AUC of 0.730, accuracy of 69.93%, sensitivity of 88.20%, and specificity of 40.95% on the original dataset. In the balanced dataset, GB had an AUC of 0.729, accuracy of 68.86%, sensitivity of 75.39%, and specificity of 58.59%. To enhance interpretability, a novel rule extraction method for GB model was implemented using relevant important predictors, such as triage acuity, comorbidity scores, and arrival methods. By combining predictive analytics with interpretable rule-based methods, this research provides actionable insights for optimizing patient flow and resource allocation. The findings highlight the importance of transparency in machine learning applications for healthcare, paving the way for future improvements in model performance and clinical adoption.

Background   Ultrasound (US) surveillance for transjugular intrahepatic portosystemic shunt (TIPS) dysfunction has yet to be standardized, as clear-cut criteria have not been conventionally defined. This study evaluated the role of US-based parameters in detecting hemodynamic TIPS dysfunction (HD). Methods   We included consecutive patients treated with TIPS. All patients were scheduled within the first six weeks after the procedure for TIPS revision, comprised of a Doppler US exam and invasive hemodynamic reassessment. Clinical TIPS dysfunction (CD) was defined as symptom recurrence, while HD was defined by a portal pressure gradient (PPG)≥12 mmHg. The predictive capabilities of Doppler US for predicting TIPS dysfunction were tested against the hemodynamic gold standard. Results   86 patients were included. Secondary prophylaxis of variceal bleeding was the main indication for TIPS in 72 patients (83.7%), while 27 (31.4%) had refractory ascites. HD occurred in 37 cases (43%), of which 25 patients (67.5%) had no CD. Patients with HD had a significantly lower portal vein velocity (PVV): 35 (20-45) cm/s vs. 40.5 (35-50) cm/s, p=0.02. Compared to the immediate post-TIPS assessment, the patients without HD had a ΔPVV of 6.08±19.8 cm/s vs. a decrease of - 8.2±20.2 cm/s in HD (p=0.04). Using a cut-off value of 40.5 cm/s, PVV had an AUROC of 0.705 for predicting HD, while the addition of ΔPVV (cut-off 9.5 cm/s) improved the AUROC to 0.78. Conclusion   Despite adequate symptom control, a considerable percentage of patients have a post-TIPS PPG≥12 mmHg. The dynamic assessment of PVV and its temporal dynamics can reliably predict TIPS dysfunction.

To identify the potential genetic factors responsible for retinal capillary hemangioblastoma (RCH) and Type II granular corneal dystrophy (GCDII), with autosomal dominant inheritance. We used whole-exome sequencing (WES) in an Iranian family to identify the possible genetic etiology of RCH and GCDII with other manifestations of von Hippel-Lindau (VHL) disease.

The 2020 FDA drug-drug interaction (DDI) guidance includes a consideration for metabolites with structural alerts for potential mechanism-based inhibition (MBI) and describes how this information may be used to determine whether in vitro studies need to be conducted to evaluate the inhibitory potential of a metabolite on CYP enzymes. To facilitate identification of structural alerts, an extensive literature search was performed and alerts for mechanism-based inhibition of cytochrome P450 enzymes (CYP) were collected. Furthermore, five quantitative structure-activity relationship (QSAR) models were developed to predict not only time-dependent inhibition of CYP3A4, an enzyme that metabolizes approximately 50% of all marketed drugs, but also reversible inhibition of 3A4, 2C9, 2C19 and 2D6. The non-proprietary training database for the QSAR models contains data for 10,129 chemicals harvested from FDA drug approval packages and published literature. The cross-validation performance statistics for the new CYP QSAR models range from 78% to 84% sensitivity and 79%-84% normalized negative predictivity. Additionally, the performance of the newly developed QSAR models was assessed using external validation sets. Overall performance statistics showed up to 75% in sensitivity and up to 80% in normalized negative predictivity. The newly developed models will provide a faster and more effective evaluation of potential drug-drug interaction caused by metabolites.

The importance of the cGAS-STING pathway and type I interferon (IFN) in anti-tumor immunity has been widely studied. However, there is limited knowledge about the role of type III IFNs in cancer settings. Type III IFNs, comprising IFNλ1-4, are opposite to type I IFN only expressed by a few cell types, including epithelial cells, and the receptor subunit IFNLR1, is equally only expressed on limited types of cells.

Public health research presents compelling evidence that health is socially determined. To address structural inequalities and inequities in health, public policies require intersectoral development and implementation. Health Impact Assessment (HIA) is an established approach for analysing potentially detrimental health impacts of policies, programmes, and projects, as well as potentially positive impacts and opportunities. National public health policy, Healthy Ireland (2013-2025), endorses an intersectoral whole-of-system approach to ensure that health is a central part of all relevant policy areas. HIA is endorsed in this policy as one way to drive this agenda. Synergising with this policy commitment for HIA, the all-island Institute of Public Health Ireland produced revised HIA guidance in 2021. Two HIAs will be carried out as part of this project, including one at a local policy level, addressing the Cork City Development Plan (2022-2028), and the second HIA at a national policy level, addressing the Irish Government's Climate Action Plan (2024). The updated HIA guidance will be used in the conduct of these HIAs. This research project involves a co-creation of a Health Impact Assessment Implementation Model by employing an action research approach with implementation science frameworks to the conduct of the two HIAs. Therefore, the process of doing the HIAs will form the basis for the research study. In order to enhance meaningful community involvement in HIA in Ireland, the project will co-create a Community Engagement Toolkit for HIA. This Model will strengthen researcher, policy actor, practitioner, community, and voluntary sector capacity to collaboratively develop and implement intersectoral and equitable policy responses to major population health issues.

Dendritic cells (DCs) are central regulators of the immune response by detecting inflammatory signals, aberrant cells, or pathogens. DC-mediated immune surveillance requires morphology changes to adapt to the physical and biochemical cues of the external environment. These changes are assisted by a dynamic actin cytoskeleton-membrane interface connected to surface receptors that will trigger signaling cascades. In recent years, the development of synthetic immune environments has allowed to investigate the impact of the external environment in the immune cell response. In this direction, the bioengineering of functional topographical features should make it possible to establish how membrane morphology modulates specific cellular functions in DCs. Herein, the engineering of one-dimensional nanostructured SiO2 surfaces by soft-nanoimprint lithography to manipulate the membrane morphology of ex vivo human DCs is reported. Super-resolution microscopy and live-cell imaging studies show that vertical pillar topographies promote the patterning and stabilization of adhesive actin-enriched structures in DCs. Furthermore, vertical topographies stimulate the spatial organization of innate immune receptors and regulate the Syk- and ERK-mediated signaling pathways across the cell membrane. In conclusion, engineered SiO2 surface topographies can modulate the cellular response of ex vivo human immune cells by imposing local plasma membrane nano-deformations.

Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated.

The regulation of glial cell activation is a critical step for the treatment or prevention of neuroinflammation-based brain diseases. However, the development of therapeutic drugs that pass the blood-brain barrier (BBB) and inhibit the glia cell activation remains a significant challenge. Herein, an ultrasmall 2D vanadium carbide quantum dots (V2C QDs) that are capable of crossing the BBB are prepared, and the admirable anti-neuroinflammatory effects are presented. The prepared 2D V2C QDs with an average size of 2.54 nm show good hydrophilicity, physiological stability, and effective BBB-crossing ability. The biological effect of V2C QDs on inflammatory reactions demonstrates fascinating results in preventing the impairment of learning and memory in BALB/c mice stimulated by lipopolysaccharide. Investigation of molecular mechanism reveals that V2C QDs not only inhibit the toll-like receptor 4/myeloid differentiation factor 88-mediated nuclear factor kappa B and mitogen-activated protein kinase pathways, but also prevent eukaryotic translation initiation factor 2α/activating transcription factor 4/C/EBP homologous protein-signaling pathway and reduce oxidative stress via activating the NF-E2-related factor-2/heme oxygenase-1-signaling pathway, leading to greatly inhibited activation of microglia and astrocytes and weakened production of inflammatory cytokines. In summary, V2C QDs exert potent anti-inflammatory effects through multiple pathways, thus offer great potential for the treatment of neurodegenerative diseases.

Efficient water treatment ideally combines ion exchange for the removal of hardness elements and toxic trace metals as well as ultrafiltration for the removal of particulate matter. Although promising for adsorption, many high-surface-area polymer materials cannot be easily processed into freestanding membranes or packed bed columns, due to poor solution processability and high back pressures, respectively. The preparation of hybrid membranes comprising sulfonated hypercrosslinked polymers entrapped in nanocellulose papers is described. The hybrid membranes are effective for simultaneous ultrafiltration and ion exchange. Increasing the polymer loading of the hybrid membrane produces synergy by increasing the permeance of the membranes while enhancing the ion adsorption capacity to values exceeding those of bulk hypercrosslinked polymers. The maximum ion adsorption capacity for copper is determined to be ≈100 mg g-1 outperforming that of pure polymer (71 mg g-1) and commercially available ion exchange resins. Competitive adsorption is tested in samples containing water hardness elements and trace toxic metal ions showing high ion-exchange capacities. Even when fully loaded with water hardness elements, Ba2+ and Sr2+ are still removed from solution.

Constructing artificial ion channels is a challenging task. Herein, the de novo design of transmembrane ion channels made up of amphiphilic peptide-oligourea chimeric helices is described. They consist of an oligourea segment (7-mer) attached to the C-terminus of a short peptide (8-mer). Mass spectrometry (MS) and transmission electron microscopy (TEM) analyses show that in an aqueous solution, two of these chimeras (HPU-E and HPU-N) independently form defined oligomeric structures. TEM also shows that they form fiber bundles. The third related chimera HPU-F does not oligomerize (MS) but forms spherical nanostructures (TEM). HPU-E and HPU-N exhibit anion transport activity across lipid bilayers via antiport mechanism (HPU-N > HPU-E). The anion selectivity of HPU-N is Cl->NO3 - > Br->SCN- > I- > AcO->F-, which can be due to anion binding within the channels rather than size exclusion. Patch-clamp data support HPU-N's Cl- selectivity (PCl-/PI- = 3.26). X-ray crystal structure (1.77 Å) of HPU-N reveals well-packed α-helices, and cryo-electron microscopy data shows the formation of nanotubes (13.7 Å diameter pores) and transmembrane channels. The study shows that α-peptide-oligourea-based de novo design can yield unique bioactive molecules with defined structures and functions.

Herein, the stabilization of 2D single-atom high gold rafts containing up to ≈60 Au atoms on amorphous carbon, fabricated by sputtering of atoms and imaged by aberration-corrected scanning transmission electron microscopy, is demonstrated. These rafts deviate from the established cluster transition from 2D to 3D Au structural motifs in free clusters, which occurs in the region of 10-14 atoms. The experimental findings are supported by explicit ab initio calculations of Au n (n = 3-147) clusters on graphene and the role of cluster-surface interactions in the stabilization of the 2D single-atom high Au cluster rafts on graphene is revealed. The transition from equilibrium 2D-3D structures is delayed to n = 19, while metastable 2D single-atom high rafts compete with 3D structures up to about n = 60 atoms. The catalytic activity of supported nanoclusters depends strongly on their structure (and carbon-based supports are used for a number of reactions); therefore these results are relevant to the catalytic performance of nanocluster-based catalysts.

Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone crystallization techniques have previously reported. Among these techniques, solvent crystallization and different solvent:anti-solvent systems are considered. Herein, the selective development of either hollow-like or condensed progesterone microcrystals in elevated yield with controlled polymorphism, habit, and release is described for the first time. For the hollow microcrystals, isopropyl alcohol (IPA) and double-deionized water (DDW) system is developed as solvent:anti-solvent, while acetonitrile (AcN) and DDW system are developed for the condensed microcrystals. The microcrystals obtained from both developed crystallization systems are thoroughly investigated with varied microscopic techniques, including brightfield and scanning electron microscopy (SEM), thermal analysis by differential scanning calorimetry (DSC), and crystallography by powder X-ray diffraction (PXRD) and single XRD, and have been compared. Results show that the crystals of the IPA:DDW crystallization system are hollow and exhibit several habits, whereas the microcrystals of the AcN:DDW crystallization system are more condensed. However, both systems are found to have a wide crystal size distribution of one stable polymorph and are thus highly useful for tunable release. More importantly, these microcrystals exhibit elongated and slow release for 14 days under an expedited release conditions model, indicating suitability for long-term and potential localized release applications.

Implant-associated complications arise due to non-optimized cell-biomaterial interactions. It is well known that cells respond to their physicochemical microenvironment on 2D interfaces and 3D networks. Attempts to manipulate this interaction target surface parameters such as wettability (W), stiffness (S), and topography (T) to influence cell differentiation, adhesion, and morphology, due to induction of gene activation and protein expression. Investigating the combinatorial influence of all three mentioned parameters simultaneously remains challenging, though most realistic, since all three parameters are inherently present on a surface. Herein, a novel high-throughput screening technology, which allows investigating the cell response of human bone-marrow-derived mesenchymal stem cells toward three varying biomaterial surface parameters simultaneously, is presented. The platform provides efficient screening and cell response readout to a vast amount of combined biomaterial surface properties, in a single-cell experiment. Surface gradients of aligned wrinkle T, S, and W are orthogonally combined giving four combinatorial surfaces. The screening outcome is validated by translating interesting regions to homogeneous surfaces. Cells are found to behave similar to the screening in terms of adhesion, spreading, and vimentin expression. The technology tremendously supports the identification of optimal surface parameter combinations and potentially addressing many of the current implant-associated complications.

New material solutions are searched for the manufacturing and safety of current batteries. Herein, an extrusion printable polymer separator for lithium batteries based on single-ion polymer electrolytes is presented. The polymer electrolytes are based on methacrylic polymeric nanoparticles (NPs) functionalized with a lithium sulfonamide group combined with different organic plasticizers such as sulfolane and carbonates. The synthesis of the polymer NPs is carried out by emulsion copolymerization of methyl methacrylate and lithium sulfonamide methacrylate in the presence of a crosslinker, resulting in particle sizes of less than 30 nm, as shown by electron microscopy. Then polymer electrolytes are prepared by mixing polymer NPs with varying lithium sulfonamide content and different plasticizers such as carbonates and sulfolane. The polymer electrolytes show ionic conductivities between 2.9 × 10-4 and 2.3 × 10-5 S cm-1 at 85 °C with the highest values for the small-sized NPs with the highest lithium content. As a proof-of-concept application, layer-by-layer printing of a sulfolane-based polymer electrolyte is evaluated via direct ink writing directly onto classic battery electrodes. The electrochemical characterization of the printed solid electrolyte indicates favorable properties, ionic conductivity, lithium transfer number, electrochemical stability window, and cyclability in lithium symmetrical cells, to be used in lithium batteries.

The role of the gut microbiome in various aspects of health and disease is now a well-established concept in modern biomedicine. Numerous studies have revealed links between host health and microbial activity, spanning from digestion and metabolism to autoimmune disorders, stress and neuroinflammation. However, the exact mechanisms underlying this complex cross-talk still remain a mystery. Conventionally, studies examining host-microbiome interactions rely on animal models, but translation of such findings into human systems is challenging. Bioengineered models represent a highly promisingapproach for tackling such challenges. Here, a bioelectronic platform, the e-transmembrane, is used to establish a 3D model of human intestine, to study the effects of microbiota on gut barrier integrity. More specifically, how postbiotics and live bacteria impact the morphology and function of the intestinal barrier is evaluated. e-Transmembrane devices provide a means for in-line and label-free continuous monitoring of host-microbe cross-talk using electrochemical impedance spectroscopy, revealing distinct patterns that emerge over 24 hours. Microscopy and quantification of molecular biomarkers further validate the differential effects of each bacterial intervention on the host tissue. In addition, a framework to better study and screen drug candidates and potential therapeutic/dietary interventions, such as postbiotics and probiotics, in more physiologically relevant human models is provided.

Borosilicate glass surpasses polystyrene in optical quality; however, it is less frequently used for cell culture due to poor protein and cell adhesion. To overcome this impasse, the surface of glass coverslips requires functionalization to enable facile covalent attachment of proteins to promote cell attachment and differentiation. Herein, a novel approach is presented to covalently attach proteins to glass by depositing a thin layer of radical-rich carbon film using a plasma polymerization process. The surface chemistry of these plasma-activated coatings can be controlled by varying the gas composition used during the deposition. Mass spectrometry reveals different protein profiles attached to functionalized glass coverslips when they are exposed to cell culture media. Mouse embryonic stem cell adhesion and subsequent differentiation into neural lineage on plasma-treated coverslips are significantly enhanced compared to bare coverslips. Importantly, the coatings are in the nanometer range, preserve the optical properties of the glass coverslips for imaging, and remain stable for at least 4 weeks in simulated body fluid. These results demonstrate the utility of covalently attaching proteins to glass for enhanced cell attachment and stem cell differentiation and provide a promising technique to achieve better outcomes in cell culture in a range of biomedical applications.

Organ-selective targeting of mRNA polyplexes has been rarely explored despite the substantial potential of polymer-based systems in mRNA delivery. In this study, spleen-selective delivery of polyplexes is achieved by employing mRNA engineering to coat them with poly(ethylene glycol) (PEG). In this approach, mRNA is hybridized with PEGylated complementary RNA oligonucleotides (PEG-OligoRNAs), followed by the addition of linear poly(ethyleneimine). In this method, it is ensured that nearly all added PEG strands bind to the polyplexes, thereby enabling precise control of PEG amounts on the surface. Following systemic injection into mice, non-PEGylated polyplexes yield robust protein expression in the lung and spleen. Intriguingly, adding a small number of PEG-OligoRNAs drastically reduces protein expression efficiency in the lung while preserving it in the spleen, realizing spleen targeting of mRNA polyplexes. Furthermore, PEGylated polyplexes demonstrate their potential utility in mRNA vaccination. In mechanistic analyses, non-PEGylated polyplexes immediately agglomerate in the blood and deposit in the lung. Coating polyplexes with a small amount of short PEG effectively prevents these processes. Notably, even slight changes in PEG amounts and lengths dramatically impact the physicochemical properties and biological functionalities of the polyplexes, emphasizing the benefits of an mRNA engineering-based approach for fine-tuning polyplex PEG coating.

Extensive research has been conducted on biomimetic interfaces mimicking the complex and diverse microenvironment of cell membranes to gain insights into bioactive compound interactions and membrane biophysics modulation. The present study proposes an innovative approach that combines five prospective label-free methodologies (derivative spectroscopy, synchrotron small- and wide-angle X-Ray scattering, attenuated total reflection-Fourier-transform infrared spectroscopy, quartz-crystal microbalance with dissipation, and surface plasmon resonance) to showcase their synergistic capabilities and complementarity in investigating drug-membrane interactions. This multitechnique approach combines the real-time monitoring of the adsorption process under continuous flow conditions with the steady-state perspective of this process. As a proof of concept, the interaction of three bioactive compounds (caffeine, testosterone, and diclofenac) with two biomimetic membrane interfaces (multistacked lipid bilayers and supported lipid bilayers) mimicking the more ordered lipid transient phases, with and without cholesterol (l o and s o), that are responsible for a variety of membrane-associated biological activities, is investigated. The biophysical effects of the bioactives are discussed using complementary data from real-time and steady-state experiments, including membrane adsorption and distribution, predicted location, and induced changes in order and fluidity, encompassing bilayer thickness, hydration, and area per lipid molecule.

Currently, there is no mechanistic model that fully explains the initial synthesis and organization of durable animal structure. As a result, our understanding of extracellular matrix (ECM) development and pathologies (e.g., persistent fibrosis) remains limited. Here, we identify and characterize cell-generated mechanical strains that direct the assembly of the ECM. Cell kinematics comprise cooperative retrograde "pulls" that organize and precipitate biopolymer structure along lines of tension. High-resolution optical microscopy revealed five unique classes of retrograde "pulls" that result in the production of filaments. Live-cell confocal imaging confirmed that retrograde pulls can directly cause the formation of fibronectin filaments that then colocalize with collagen aggregates exported from the cell, producing persistent elongated structures aligned with the direction of the tension. The findings suggest a new model for initial durable structure formation in animals. The results have important implications for ECM development and growth and life-threatening pathologies of the ECM, such as fibrosis.