Prediction of trends in unfavorable prognosis in patients with acute ischemic stroke according to low left ventricular ejection fraction levels.

As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis. After adjusting for confounding factors, patients in tertile 3 exhibited an increased risk of poor functional outcome and mortality [odds ratio (OR), 2.656 (95% CI: 1.443-4.889); OR, 7.586 (95% CI: 2.102-27.375)]. A systematic search of PubMed, EMBASE and Cochrane Library was performed. Our meta-analysis revealed that LVEF < 40% was significantly associated with poor functional outcome [OR 1.94 (95% CI: 1.08-3.50)], mortality [OR 3.69 (95% CI: 1.22-11.11)], as well as LVEF < 55% [OR 1.68 (95% CI: 1.22-2.32); 2.27 (95% CI: 1.30-3.96)], respectively. A decreased LVEF could predict an inferior prognosis for AIS; therefore, it could aid in clinical decision-making in this patient population.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

The white blood cell count to mean platelet volume ratio for ischemic stroke patients after intravenous thrombolysis.

Background and Purpose: White blood cell count to mean platelet volume ratio (WMR) is increasingly recognized as a promising biomarker. However, its predictive capability for acute ischemic stroke (AIS) patients is relatively less researched. The primary aim of this study is to explore its prognostic value in AIS patients after reperfusion regarding 3-month poor functional outcome. Methods: A total of 549 AIS patients who had undergone vascular reperfusion procedure with complete 3-month follow-up were retrospectively recruited in this study. White blood cell count, mean platelet volume at 24 h of admission were recorded. Stroke severity had been estimated using the National Institutes of Health Stroke Scale (NIHSS) and poor outcome was defined as modified Rankin Scale (mRS) 3-6 at 3 months. Results: AIS patients with poor functional outcome at 3 months displayed higher WMR. A positive correlation between WMR and NIHSS score was found (r = 0.334, p < 0.001). After adjusting potential confounders, WMR was still an independent risk factor for poor prognosis at 3 months (OR = 2.257, 95% CI [1.117-4.564], p = 0.023) in multivariate logistic regression model. Subgroup analyses further suggested a significant association between WMR and poor outcome in high baseline NIHSS (per 0.1-point increase: OR = 1.153, 95% CI [1.014-1.312], p = 0.030) group. Receiver operating characteristic (ROC) curves analysis was utilized to assess the predictive ability of WMR, indicating a cut-off value of 0.86. A nomogram that includes age, sex, NIHSS on admission, high WMR for predicting 1-year all-cause survival was also developed (C-index = 0.628). Conclusions: WMR is significantly correlated with stroke severity on admission and is proved to be an important prognostic indicator for AIS outcomes, especially in high NIHSS on admission group. Additionally, the developed nomogram that includes high WMR for predicting 1-year survival provides us with an effective visualization tool.

The Collapse and Expansion of Liquid-Filled Elastic Channels and Cracks.

The rate at which fluid drains from a collapsing channel or crack depends on the interaction between the elastic properties of the solid and the fluid flow. The same interaction controls the rate at which a pressurized fluid can flow into a crack. In this paper, we present an analysis for the interaction between the viscous flow and the elastic field associated with an expanding or collapsing fluid-filled channel. We first examine an axisymmetric problem for which a completely analytical solution can be developed. A thick-walled elastic cylinder is opened by external surface tractions, and its core is filled by a fluid. When the applied tractions are relaxed, a hydrostatic pressure gradient drives the fluid to the mouth of the cylinder. The relationship between the change in dimensions, time, and position along the cylinder is given by the diffusion equation, with the diffusion coefficient being dependent on the modulus of the substrate, the viscosity of the fluid, and the ratio of the core radius to the exterior radius of the cylinder. The second part of the paper examines the collapse of elliptical channels with arbitrary aspect ratios, so as to model the behavior of fluid-filled cracks. The channels are opened by a uniaxial tension parallel to their minor axes, filled with a fluid, and then allowed to collapse. The form of the analysis follows that of the axisymmetric calculations, but is complicated by the fact that the aspect ratio of the ellipse changes in response to the local pressure. Approximate analytical solutions in the form of the diffusion equation can be found for small aspect ratios. Numerical solutions are given for more extreme aspect ratios, such as those appropriate for cracks. Of particular note is that, for a given cross-sectional area, the rate of collapse is slower for larger aspect ratios. With minor modifications to the initial conditions and the boundary conditions, the analysis is also valid for cracks being opened by a pressurized fluid.

Fracture-based fabrication of normally closed, adjustable, and fully reversible microscale fluidic channels.

Adjustable fluidic structures play an important role in microfluidic systems. Fracture of multilayered materials under applied tension has been previously demonstrated as a convenient, simple, and inexpensive approach to fabricate nanoscale adjustable structures; here, it is demonstrated how to extend this concept to the microscale. This is achieved by a novel pairing of materials that leverages fracture mechanics to limit crack formation to a specified region, allowing to create size-controllable and adjustable microfluidic structures. This technique can be used to fabricate "normally closed" microfluidic channels that are completely reversible, a feature that is challenging to achieve in conventional systems without careful engineering controls. The adjustable microfluidic channels are then applied to mechanically lyse single cells, and subsequently manipulate the released nuclear chromatin, creating new possibilities for epigenetic analysis of single cells. This simple, versatile, and robust technology provides an easily accessible pathway to construct adjustable microfluidic structures, which will be useful in developing complex assays and experiments even in resource-limited settings.

Fracture-based micro- and nanofabrication for biological applications.

While fracture is generally considered to be undesirable in various manufacturing processes, delicate control of fracture can be successfully implemented to generate structures at micro/nano length scales. Fracture-based fabrication techniques can serve as a template-free manufacturing method, and enables highly-ordered patterns or fluidic channels to be formed over large areas in a simple and cost-effective manner. Such technologies can be leveraged to address biologically-relevant problems, such as in the analysis of biomolecules or in the design of culture systems that imitate the cellular or molecular environment. This mini review provides an overview of current fracture-guided fabrication techniques and their biological applications. We first survey the mechanical principles of fracture-based approaches. Then we describe biological applications at the cellular and molecular levels. Finally, we discuss unique advantages of the different system for biological studies.

The Control of Crack Arrays in Thin Films.

Thin-film fracture can be used as a nano-fabrication technique but, generally, it is a stochastic process that results in non-uniform patterns. Crack spacings depend on the interaction between intrinsic flaw populations and the fracture mechanics of crack channeling. Geometrical features can be used to trigger cracks at specific locations to generate controlled crack patterns. However, while this basic idea is intuitive, it is not so obvious how to realize the concept in practice, nor what the limitations are. The control of crack arrays depends on the nature of the intrinsic flaw population. If there is a relatively large density of long flaws, as commonly assumed in fracture-mechanics analyses, reliable crack patterns can be obtained fairly robustly using relatively blunt geometrical features to initiate cracks, provided the applied strain is carefully matched to the properties of the system and the desired crack spacing. This process is analyzed both for cracks confined to the thickness of a film and for cracks growing into a substrate. The latter analysis is complicated by the fact that increases in strain can either drive cracks deeper into the substrate or generate new cracks at shallower depths. If the intrinsic flaws are all very short, the geometrical features need to be very sharp to achieve the desired patterns. While careful control of the applied strain is not required, the strain needs to be relatively large compared to that which would be required to propagate a large flaw across the film. This results in an approach that is not robust against the introduction of accidental damage or a few large flaws.

Guided fracture of films on soft substrates to create micro/nano-feature arrays with controlled periodicity.

While the formation of cracks is often stochastic and considered undesirable, controlled fracture would enable rapid and low cost manufacture of micro/nanostructures. Here, we report a propagation-controlled technique to guide fracture of thin films supported on soft substrates to create crack arrays with highly controlled periodicity. Precision crack patterns are obtained by the use of strategically positioned stress-focusing V-notch features under conditions of slow application of strain to a degree where the notch features and intrinsic crack spacing match. This simple but robust approach provides a variety of precisely spaced crack arrays on both flat and curved surfaces. The general principles are applicable to a wide variety of multi-layered materials systems because the method does not require the careful control of defects associated with initiation-controlled approaches. There are also no intrinsic limitations on the area over which such patterning can be performed opening the way for large area micro/nano-manufacturing.

Nanoscale squeezing in elastomeric nanochannels for single chromatin linearization.

This paper describes a novel nanofluidic phenomenon where untethered DNA and chromatin are linearized by rapidly narrowing an elastomeric nanochannel filled with solutions of the biopolymers. This nanoscale squeezing procedure generates hydrodynamic flows while also confining the biopolymers into smaller and smaller volumes. The unique features of this technique enable full linearization then trapping of biopolymers such as DNA. The versatility of the method is also demonstrated by analysis of chromatin stretchability and mapping of histone states using single strands of chromatin.