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Transition metal phosphides are crucial for various environmental and energy applications. In this study, porous Ni12P5 and Ni12P5-rGO were synthesized using a one-step solvothermal method. Red phosphorus served as the phosphorus source, while ethylene glycol acted as a capping agent to promote the formation of nanomaterials within a nitrogen-rich atmosphere. The catalytic performance of these materials was evaluated through their hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and capacitance properties. Notably, Ni12P5-rGO exhibited Tafel slopes of 66 mV/dec for OER and 33 mV/dec for HER, indicating enhanced charge transfer efficiency compared to Ni12P5, which showed slopes of 78 mV/dec and 102 mV/dec, respectively. This improvement suggests that Ni12P5-rGO facilitates faster electron transfer, resulting in superior catalytic performance. Additionally, the synergistic effect of reduced graphene oxide (rGO) contributes to improved charge storage capabilities. The Ni12P5-rGO demonstrated a specific capacitance of 192 F/g, significantly higher than the 110 F/g observed for Ni12P5 at a current density of 1 A/g. Remarkably, these materials maintained their capacity over 5000 cycles, achieving a commendable 98 % coulombic efficiency. These findings highlight the potential of Ni12P5-rGO as an effective material for energy conversion and storage applications, showcasing its promising role in advancing the efficiency of related technologies.

Introduction: Reduced white matter integrity outside the stroke lesion may be a potential contributor of post-stroke cognitive impairment. We aimed to investigate how a stroke lesion affects the integrity of surrounding white matter, and whether the integrity of the non-lesioned part of white matter tracts is associated with cognitive performance after ischemic stroke in young adults. Methods: Patients from the ODYSSEY study, aged 18–49 years, with a first-ever ischemic stroke, underwent 3T MRI and cognitive assessment within six months after the index event. Using TractSeg and free water imaging, we analyzed free water corrected fractional anisotropy (FAT), free water corrected mean diffusivity (MDT), and free water (FW) of all white matter tracts outside the stroke lesion. We calculated FAT and FW in the lesioned white matter tracts at 2 mm incremental distances from the lesion, extending up to 10 mm, represented as Z-scores using the diffusion measures of controls. We categorized patients as no/mild or major vascular cognitive disorder (VCD) and compared with a stroke-free control group (n = 23). Group differences in diffusion measures were examined. We investigated associations between FAT, FW and cognitive performance across seven domains. Results: Among 66 patients (median age 40.3 years (IQR 31.3–46.2); 54.5 % women), 22 had major VCD. In the different lesion expansions, we found differences in FAT (p = 0.009) and FW (p = 0.049). Patients with major VCD had lower FAT [range of Cohen’s d (0.65; 1.65)] and higher FW [Cohen’s d (−1.40; −0.64)] values compared to controls, both in the hemisphere affected by the lesion and the unaffected hemisphere. Performance in processing speed correlated with FAT across eight tracts in the affected hemisphere [range of R2adj (0.30; 0.37)], and with FW in four tracts in the affected and three in the unaffected hemisphere [R2adj (0.28; 0.38)]. Discussion: In the first months after a stroke, we observed a trend of microstructural changes remote from the lesion that diminish as the distance from the lesion increases. Tissue changes in the white matter outside the lesion are present in both hemispheres, but are more pronounced in the hemisphere affected by the stroke, and may contribute to worse cognitive performance.

Purpose: There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with white matter hyperintensity (WMH) progression over 14 years and MRI markers after 14 years.Materials and methods: We included participants with SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance-imaging Cohort (RUNDMC) who underwent baseline assessment in 2006 and follow-up in 2011, 2015 and 2020. BPV was calculated as coefficient of variation (CV) of BP at all visits. Association between WMH progression rates over 14 years and BPV was examined using linear-mixed effects (LME) model. Regression models were used to examine association between BPV and MRI markers at final visit in participants.Results: A total of 199 participants (60.5 SD 6.6 years) who underwent four MRI scans and BP measurements were included, with mean follow-up of 13.7 (SD 0.5) years. Systolic BPV was associated with higher progression of WMH (β = 0.013, 95% CI 0.005 − 0.022) and higher risk of incident lacunes (OR: 1.10, 95% CI 1.01–1.21). There was no association between systolic BPV and grey and white matter volumes, Peak Skeleton of Mean Diffusivity (PSMD) or microbleed count after 13.7 years.Conclusions: Visit-to-visit systolic BPV is associated with increased progression of WMH volumes and higher risk of incident lacunes over 14 years in participants with SVD. Future studies are needed to examine causality of this association.

Summary: Background: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. Methods: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward’s minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. Findings: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. Interpretation: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. Funding: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).

ObjectivesSARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID.Materials and methodsWe included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics.

AbstractGenistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon®90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, in vitro dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon®90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon®90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon®90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.

Purpose: Cement distribution in spinal stabilization with fenestrated screws is unpredictable in patients with osteoporosis. The objective of our study was an assessment of cement distribution while using fenestrated screws and to establish an association between cement distribution and the Dual Emission X-ray Absorptiometry (DEXA) scan T scores. Materials and Methods: Osteoporotic patients who underwent spinal stabilization with fenestrated screws by a single surgeon with a minimum follow-up of one year were included. Cement distribution (four zones comprising the vertebral body and the pedicle), a pattern of distribution (concentrated or scattered) and cement leakage were assessed on CT scans. Patients were categorized into two groups based on their DEXA scan T scores to test an association between the pattern of distribution of cement and the scores. Clinical improvement was determined using visual analogue scale and Oswestry disability index scores. Results: A total of 126 screws were analyzed in 20 patients with a mean age of 69 years and a mean follow-up of 18 months. Out of 126 screws, 114 (90.47%) had cement in Zones 1 and 2. In total, 58 screws had a concentrated pattern of distribution of cement, whereas 68 screws had a scattered distribution, and the odds ratio of a scattered pattern of distribution was 6.31:1 if the DEXA scan T score was “below (−)3.0.” Clinical improvement was calculated in percentage of change from the preoperative value (mean % visual analogue scale change = 65.13 ± 7.59 and mean % Oswestry disability index change = 43.14 ± 7.24). Conclusion: The pattern of cement distribution in fenestrated screws relates well with the DEXA scan T scores and their usage should be strongly considered in patients with poorer scores. However, there is no relevant difference between the pattern of distribution and the clinical outcome.

The study of learning algorithms in the neocortex requires comprehensive knowledge of synaptic plasticity between its diverse cell types, which is currently lacking. Chindemi et al. describe a modeling approach to fill these gaps in experimental literature, and predict the features of synaptic plasticity in vivo.

Lifitegrast is a lymphocyte function‐associated antigen‐1 (LFA‐1) antagonist, which is approved for treatment of dry eye disease. In this work we explored the effect of lifitegrast in imiquimod induced psoriasis model in mice. Lifitegrast (5% solution) was tested in imiquimod‐induced psoriasis model in C57 mice. Lifitegrast was topically administered twice a day to the psoriatic skin for 6 days and epidermal skin thickness, psoriasis area and severity index (PASI) score and inflammation markers were assessed. Lifitegrast inhibited the imiquimod‐induced increase in the epidermal thickness, histopathological changes and PASI score. This decrease in psoriasis inflammation was accompanied by decrease in TNF‐α, IL‐6, IL‐22 and IL‐17/IL‐23 axis gene expression in the skin, and the effect is comparable to the oral cyclosporine A(5 mg/kg, twice a day) treatment. Lifitegrast demonstrated significant anti‐inflammatory activity, mainly through reduction in cytokine gene expression related to psoriasis and decreased the severity of psoriasis in vivo. The significant effect shown by this LFA‐1 and ICAM‐1 antagonist indicates a novel topical treatment for psoriasis. [ABSTRACT FROM AUTHOR]

Abstract Background With a growing, younger population of head and neck cancer survivors, attention to long-term side-effects of prior, often radiotherapeutic, treatment is warranted. Therefore, we studied the long-term cognitive effects in young adult patients irradiated for head and neck neoplasms (HNN). Methods Young to middle-aged adults with HNN (aged 18-40 years) and treated with unilateral neck irradiation ≥ 5 years before inclusion underwent cardiovascular risk and neuropsychological assessments and answered validated questionnaires regarding subjective cognitive complaints, fatigue, depression, quality of life, and cancer-specific distress. Additionally, magnetic resonance imaging (MRI) of the brain was performed to assess white matter hyperintensities (WMH), infarctions, and atrophy. Results Twenty-nine patients (aged 24–61, 13 men) median 9.2 [7.3–12.9] years post-treatment were included. HNN patients performed worse in episodic memory (Z-score = -1.16 [-1.58–0.34], p