Notes

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7 (IQR 11.3-18.5) and 14.5days (IQR 11.8-20.0), respectively. Multivariate analysis showed increased Hazards Ratio of disease progression associated with older age, lymphocyte count<1.1×10⁹/L, blood urea nitrogen (BUN)> 9.5mmol/L, lactate dehydrogenase>250 U/L and procalcitonin>0.1ng/mL at admission. These factors were also associated with the risk of death except for BUN. Prediction models in terms of nomogram for clinical deterioration and death were established to illustrate the probability.

These findings provide insights for early detection and management of patients at risk of disease progression or even death, especially older patients and those with comorbidities.
These findings provide insights for early detection and management of patients at risk of disease progression or even death, especially older patients and those with comorbidities.DRB1*112302 differs from DRB1*112301 by one nucleotide change at nucleotide 357 in exon 2 from G to A.
To develop a prediction model to predict vestibular schwannoma (VS) growth for patients in a wait and scan (W&S) strategy.

Retrospective cohort study.

Tertiary hospital (Radboud university medical center, Nijmegen, the Netherlands).

Patients with unilateral VS, entering a W&S strategy and at least one follow-up MRI available. Data on demographics, symptoms, audiometry and MRI characteristics at time of diagnosis were collected from medical records.

Following multiple imputation, a multivariable Cox regression model was used to select variables, using VS growth (≥2mm) as outcome. Decision curve analyses (DCA) were performed to compare the model to the current strategy.

Of 1217 analysed VS patients, 653 (53.7%) showed growth during follow-up. Balance complaints (HR 1.57 (95% CI 1.31-1.88)) and tinnitus complaints in the affected ear (HR 1.36 (95% CI 1.15-1.61)), Koos grade (Koos 1 is reference, Koos 2 HR 1.03 (95% CI 0.80-1.31), Koos 3 HR 1.55 (95% CI 1.16-2.06), Koos 4 HR 2.18 (95% CI 1.60-alidation, this model may be used to inform patients about their prognosis, individualise the W&S strategy and improve (cost-)effectiveness.Levulinic acid (LA) is acknowledged one of the most promising biomass-derived platform molecules and can be transformed into various value-added chemicals. Here, we report a new reaction process for the valorization of LA derivatives under transition-metal-free condition. The protocol combined with the conversion of the levulinate to tosylhydrazone and base promoted arylation, acylation, and etherification cross-coupling. Moreover, our method was applied to synthesize three biologically active molecules, rac-curcumene, rac-xanthorrhizol and rac-4,7-dimethyl-l-tetralone. This reaction discloses a new avenue for the high-value utilization of platform molecules.Circular RNAs (circRNAs) represent a newly discovered class of endogenous non-coding RNAs which are widely expressed and play important roles in disease progression. However, the function of circRNAs in oral squamous cell carcinoma (OSCC) still remains largely unknown. In this research, we found that circ_SEPT9 was highly expressed in OSCC cell lines and tumour tissues. Results showed that circ_SEPT9 promoted OSCC proliferation and tumour growth. And, circ_SEPT9 also enhanced the migration and invasion of OSCC cells. Mechanically, we found that circ_SEPT9 acted as a sponge for miR-1225 to rescue PKN2 expression in OSCC cells. Aristolochic acid A in vitro Inhibition of circ_SEPT9/miR-1225/PKN2 pathway could effectively block the proliferation and metastasis of OSCC cells. Our study provides strong evidence that circ_SEPT9/miR-1225/PKN2 axis is a promising target for OSCC treatment.Atherosclerosis remains a leading cause of death and disability around the world and a major driver of health care spending. Nanomaterials have gained widespread attention due to their promising potential for clinical translation and use. We have developed a collagen-targeted peptide amphiphile (PA)-based nanofiber for the prevention of neointimal hyperplasia after arterial injury. Our goal was to characterize the pharmacokinetics and biodistribution of the collagen-targeted PA to further its advancement into clinical trials. Collagen-targeted PA was injected into the internal jugular vein of Sprague Dawley rats. PA concentrations in plasma collected at various times after injection (0 to 72 hours) were measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetics of the collagen-targeted PA were characterized by a three-compartment model, with an extremely rapid apparent elimination clearance resulting in a plasma concentration decrease of more than two orders of magnitude within the first hour after injection. This rapid initial decline in plasma concentration was not due to degradation by plasma components, as collagen-targeted PA was stable in plasma ex vivo for up to 3 hours. Indeed, cellular blood components appear to be partly responsible, as only 15% of collagen-targeted PA were recovered following incubation with whole blood. Nanofibers in whole blood also adhered to red blood cells (RBCs) and were engulfed by mononuclear cells. This work highlights the unique pharmacokinetics of our collagen-targeted PA, which differ from pharmacokinetics of small molecules. Because of their targeted nature, these nanomaterials should not require sustained elevated plasma concentrations to achieve a therapeutic effect the way small molecules typically do.The development of novel water oxidation catalysts is important in the context of renewable fuels production. Ligand design is one of the key tools to improve the activity and stability of molecular catalysts. The establishment of ligand design rules can facilitate the development of improved molecular catalysts. In this paper it is shown that chemical oxidants can be used to probe oxygen evolution activity for nickel-based systems, and trends are reported that can improve future ligand design. Interestingly, different ligand effects were observed in comparison to other first-row transition metal complexes. For example, nickel complexes with secondary amine donors were more active than with tertiary amine donors, which is the opposite for iron complexes. The incorporation of imine donor groups in a cyclam ligand resulted in the fastest and most durable nickel catalyst of our series, achieving oxygen evolution turnover numbers up to 380 and turnover frequencies up to 68 min-1 in a pH 5.0 acetate buffer using Oxone as oxidant. Initial kinetic experiments with this catalyst revealed a first order in chemical oxidant and a half order in catalyst. This implies a rate-determining oxidation step from a dimeric species that needs to break up to generate the active catalyst. These findings lay the foundation for the rational design of molecular nickel catalysts for water oxidation and highlight that catalyst design rules are not generally applicable for different metals.The aim of the study was to explore the mechanism of mesenchymal stem cell-derived exosomes (MSC-EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)-induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC-EXO via tail vein injection. Post-operation, our results showed that MSC-EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo. In vitro experiment, the hypoxia models of pulmonary artery endothelial cell (PAEC) and pulmonary vascular smooth muscle cell (PASMC) were used. We found that the expression levels of Wnt5a, Wnt11, BMPR2, BMP4 and BMP9 were increased, but β-catenin, cyclin D1 and TGF-β1 were decreased in MSC-EXO group as compared with MCT or hypoxia group in vivo or vitro. However, these increased could be blocked when cells were transfected with Wnt5a siRNA in vitro. Taken together, these results suggested that the mechanism of MSC-EXO to prevent PH vascular remodelling may be via regulation of Wnt5a/BMP signalling pathway.
Most older Americans use drug therapies for chronic conditions. Several are associated with risk of Alzheimer's disease and related dementias (ADRD).

A scoping review was used to identify drug classes associated with increasing or decreasing ADRD risk. We analyzed size, type, and findings of the evidence.

We identified 29 drug classes across 11 therapeutic areas, and 404 human studies. Most common were studies on drugs for hypertension (93) or hyperlipidemia (81). Fewer than five studies were identified for several anti-diabetic and anti-inflammatory drugs. Evidence was observational only for beta blockers, proton pump inhibitors, benzodiazepines, and disease-modifying anti-rheumatic drugs. For 13 drug classes, 50% or more of the studies reported consistent direction of effect on risk of ADRD.

Future research targeting drug classes with limited/non-robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.
Future research targeting drug classes with limited/non-robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.
Triggering receptor expressed on myeloid cells-2 (TREM2) is an immune receptor expressed on microglia that also can become soluble (sTREM2). How TREM2 engages different ligands remains poorly understood.

We used comprehensive biolayer interferometry (BLI) analysis to investigate TREM2 and sTREM2 interactions with apolipoprotein E (apoE) and monomeric amyloid beta (Aβ) (mAβ42).

TREM2 engagement of apoE was protein mediated with little effect of lipidation, showing slight affinity differences between isoforms (E4>E3>E2). Another family member, TREML2, did not bind apoE. Disease-linked TREM2 variants within a "basic patch" minimally impact apoE binding. Instead, TREM2 uses a unique hydrophobic surface to bind apoE, which requires the apoE hinge region. TREM2 and sTREM2 directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role for soluble sTREM2 in preventing AD pathogenesis.

These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.
These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.
This study examined the possible associations between frailty and patient-reported outcomes (PROs) in elderly patients with asthma.

Participants completed the Kihon Checklist for frailty screening as well as the following tools for measuring generic- and disease-specific health-related quality of life (HRQOL) and asthma control; the Medical Outcomes Study 36-item short form (SF-36), the Hyland Scale (global scale), the Asthma Quality of Life Questionnaire (AQLQ), the Asthma Control Test (ACT), and the Asthma Control Questionnaire (ACQ).

Of 69 consecutive outpatients with asthma, 38 (55.1%), 21 (30.4%), and 10 (14.5%) were classified as robust, pre-frail, and frail, respectively. Eight out of 52 patients with asthma in the elderly (AIE) (>65 years old) (15.4%) were considered as being frail. The Kihon Checklist total score was significantly correlated with all the scores obtained from the SF-36, Hyland Scale, AQLQ, ACT, and ACQ. All these scores were significantly different between groups with and without frailty.
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