Machine learning application in ischemic stroke diagnosis, management, and outcome prediction: a narrative review

Stroke is a leading cause of disability and death. The condition requires prompt diagnosis and treatment. The quality of care provided to patients with stroke can vary depending on the availability of medical resources, which in turn, can affect prognosis. Recently, there has been growing interest in using machine learning (ML) to support stroke diagnosis and treatment decisions based on large medical data sets. Current ML applications in stroke care can be divided into two categories: analysis of neuroimaging data and clinical informationbased predictive models. Using ML to analyze neuroimaging data can increase the efficiency and accuracy of diagnoses. Commercial software that uses ML algorithms is already being used in the medical field. Additionally, the accuracy of predictive ML models is improving with the integration of radiomics and clinical data. is expected to be important for improving the quality of care for patients with stroke

Pivotal-based inference for a Pareto distribution under the adaptive progressive Type-II censoring scheme

This paper proposes an inference approach based on a pivotal quantity under the adaptive progressive Type-II censoring scheme. To exemplify the proposed methodology, an extensively employed distribution, a Pareto distribution, is utilized. This distribution has limitations in estimating confidence intervals for unknown parameters from classical methods such as the maximum likelihood and bootstrap methods. For example, in the maximum likelihood method, the asymptotic variance-covariance matrix does not always exist. In addition, both classical methods can yield confidence intervals that do not satisfy nominal levels when a sample size is not large enough. Our approach resolves these limitations by allowing us to construct exact intervals for unknown parameters with computational simplicity. Aside from this, the proposed approach leads to closed-form estimators with properties such as unbiasedness and consistency. To verify the validity of the proposed methodology, two approaches, a Monte Carlo simulation and a real-world data analysis, are conducted. The simulation testifies to the superior performance of the proposed methodology as compared to the maximum likelihood method, and the real-world data analysis examines the applicability and scalability of the proposed methodology

Menthol Enhances an Antiproliferative Activity of 1α,25-Dihydroxyvitamin D3 in LNCaP Cells

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the most active form of vitamin D3, and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1α,25(OH)2D3 for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1α,25(OH)2D3 in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1α,25(OH)2D3-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1α,25(OH)2D3 does not induce acute Ca2+ response, whereas menthol evokes an increase in [Ca2+]i, which suggests that cross-talks of menthol-induced Ca2+ signaling with 1α,25(OH)2D3-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1α,25(OH)2D3 and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1α,25(OH)2D3-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1α,25(OH)2D3

The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia.

Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases

Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy

Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation

Background The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. Methods A total of 1190 EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions, acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy was diagnosed by computed tomography coronary angiography. Clinical information, including the patients’ survival was retrieved by a review of medical records. Results Eighty-eight patients (75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellular rejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patient sdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesions from transplantation was longer than that of acute cellular rejections. We found a significant association between Quilty lesions and cardiac allograft vasculopathy. No significant relationship was found between Quilty lesions and the patients’ survival. Conclusions Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection

Malignant Melanoma of Unknown Primary Origin Presenting as Cardiac Metastasis

Malignant melanoma has a very high propensity to metastasize to the heart. However, melanoma may sometimes present as a metastatic lesion in the absence of a primary lesion, which are called melanomas of unknown primary origin. We report a case in which a patient presented with a metastatic maligant melanoma in the right atrium with pericardial effusion and without a primary origin

Gypsum-Dependent Effect of NaCl on Strength Enhancement of CaO-Activated Slag Binders

This study explores the combined effect of NaCl and gypsum on the strength of the CaO-activated ground-granulated blast furnace slag (GGBFS) binder system. In the CaO-activated GGBFS system, the incorporation of NaCl without gypsum did not improve the strength of the system. However, with the presence of gypsum, the use of NaCl yielded significantly greater strength than the use of either gypsum or NaCl alone. The presence of NaCl largely increases the solubility of gypsum in a solution, leading to a higher concentration of sulfate ions, which is essential for generating more and faster formations of ettringite in a fresh mixture of paste. The significant strength enhancement of gypsum was likely due to the accelerated and increased formation of ettringite, accompanied by more efficient filling of pores in the system