Image-based assessment of natural killer cell activity against glioblastoma stem cells.

Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.

The cost-effectiveness of a real-time seizure detection application for people with epilepsy.

OBJECTIVES: Automated seizure detection modalities can increase safety among people with epilepsy (PWE) and reduce seizure-related anxiety. We evaluated the potential cost-effectiveness of a seizure detection mobile application for PWE in Singapore. METHODS: We used a Markov cohort model to estimate the expected changes to total costs and health outcomes from a decision to adopt the seizure detection application versus the current standard of care from the health provider perspective. The time horizon is ten years and cycle duration is one month. Parameter values were updated from national databases and published literature. As we do not know the application efficacy in reducing seizure-related injuries, a conservative estimate of 1% reduction was used. Probabilistic sensitivity analysis, scenario analyses, and value of information analysis were performed. RESULTS: At a willingness-to-pay of $45,000/ quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio was $1,096/QALY, and the incremental net monetary benefit was $13,656. Probabilistic sensitivity analyses reported that the application had a 99.5% chance of being cost-effective. In a scenario analysis in which the reduction in risk of seizure-related injury was 20%, there was a 99.8% chance that the application was cost-effective. Value of information analysis revealed that health utilities was the most important parameter group contributing to model uncertainty. CONCLUSIONS: This early-stage modeling study reveals that the seizure detection application is likely to be cost-effective compared to current standard of care. Future prospective trials will be needed to demonstrate the real-world impact of the application. Changes in health-related quality of life should also be measured in future trials.

The finest diamond must be green: a closer look at the roles of institution in shipping firms' sustainable practices.

Shipping companies' implementation of sustainable shipping management is an important means of protecting major water bodies in the marine environment. This research establishes a theoretical model based on institutional theory and incorporates a micro-consciousness level to explore the factors influencing companies' implementation of sustainable shipping practices. After surveying the management of Chinese shipping companies, a total of 282 datasets were obtained for analysis. This study demonstrated that rules and regulations, societal norms, environmental awareness, and legal awareness can improve shipping companies' sustainable shipping practices. Meanwhile, these practices have a positive impact on the environmental, financial, and competitive performance of shipping companies. Moreover, these findings are highly significant for maritime environmental protection and sustainability.

Nitrogen-doped magnetic porous carbon material from low-cost anion-exchange resin as an efficient adsorbent for tetracyclines in water.

In this work, nitrogen-doped magnetic porous carbon material (N-MPC) was prepared through the high-temperature calcination of low-cost [Fe(CN)6]3--loaded anion-exchange resin, which was experimentally demonstrated to have significant adsorption performance for tetracycline (TC) in water. The N-MPC adsorbent with a large specific surface area (781.1 m2 g-1) was able to maintain excellent performance in a wide pH range from 4 to 10 or in high ionic strength solution. The adsorption of TC on N-MPC was found to be more consistent with the pseudo-second-order model and Langmuir adsorption model, and the maximum adsorption capacity (qm, cal) was calculated to be 603.4 mg g-1. As a recoverable magnetic adsorbent, the N-MPC remained a TC removal rate higher than 70% after four adsorption cycles. The adsorption mechanism was speculated on the basis of characterizations, where pore filling, hydrogen bonding interaction, and π-π electron donor-acceptor (EDA) interaction were crucial adsorption mechanisms. A variety of antibiotics were selected for adsorption, and excellent performance was found especially for TCs, indicating that the N-MPC can be used for the efficient removal of TCs from water.

Image-Based Assessment of Natural Killer Cell Activity against Glioblastoma Stem Cells.

Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.

[Multimedia Distribution Characteristics and Risk Assessment of 22 PPCPs in the Water Environment of Qingpu District, Yangtze River Delta Demonstration Area].

In this study, 50 surface water and sediment samples were collected from 25 sampling points in Qingpu District (including Taipu River basin, Jinze Reservoir, and Qingxi country park) in the Yangtze River Delta integration demonstration area, and 22 pharmaceuticals and personal care products (PPCPs) in the samples were analyzed using high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS). The distribution characteristics, sources, and influencing factors of targeted PPCPs in the study area were studied in detail. The ecological and health risks of the target PPCPs were evaluated using the quotients method. The results showed that a total of 19 PPCPs were detected in the surface water and sediment samples from 25 sampling points in Qingpu District, with total concentrations ranging from 0.06 to 178.67 ng·L-1 and 0.07 to 37.68 ng·g-1, respectively. The average value of sulfachloropyridazine (SCP) in the surface water was the highest with a concentration of 129.54 ng·L-1, whereas the average value of sulfamethoxazole (SMX) in the sediment was the highest with a concentration of 70.62 ng·g-1. The spatial distribution of the total amount of PPCPs showed a trend of Qingxi country park > Jinze Reservoir > Taipu River basin. Principal component analysis showed that the main sources of pollution were animal antibiotics used in aquaculture and the discharge of domestic sewage. There was a significant correlation between lg Koc and lg Kd (P<0.05), indicating that the organic carbon plays an important role in the distribution of the target PPCPs in water and sediments. The ecological risk assessment results revealed that the fungicides (TCC and TCS) in the surface waters showed a moderate risk to aquatic organisms of different trophic levels. The Qingxi country park and Jinze Reservoir were the regions with the highest ecological risks of PPCPs in surface water and sediment. The health risk entropy (HQ) of people of all age groups exposed through drinking was less than 1; however, with the continuous emission and accumulation of PPCPs, the pollution control of PPCPs in the environment still requires further attention.

Modeling Protein Aggregation Kinetics: The Method of Second Stochasticization.

The nucleation of protein aggregates and their growth are important in determining the structure of the cell's membraneless organelles as well as the pathogenesis of many diseases. The large number of molecular types of such aggregates along with the intrinsically stochastic nature of aggregation challenges our theoretical and computational abilities. Kinetic Monte Carlo simulation using the Gillespie algorithm is a powerful tool for modeling stochastic kinetics, but it is computationally demanding when a large number of diverse species is involved. To explore the mechanisms and statistics of aggregation more efficiently, we introduce a new approach to model stochastic aggregation kinetics which introduces noise into already statistically averaged equations obtained using mathematical moment closure schemes. Stochastic moment equations summarize succinctly the dynamics of the large diversity of species with different molecularity involved in aggregation but still take into account the stochastic fluctuations that accompany not only primary and secondary nucleation but also aggregate elongation, dissociation, and fragmentation. This method of "second stochasticization" works well where the fluctuations are modest in magnitude as is often encountered in vivo where the number of protein copies in some computations can be in the hundreds to thousands. Simulations using second stochasticization reveal a scaling law that correlates the size of the fluctuations in aggregate size and number with the total number of monomers. This scaling law is confirmed using experimental data. We believe second stochasticization schemes will prove valuable for bridging the gap between in vivo cell biology and detailed modeling. (The code is released on https://github.com/MYTLab/stoch-agg.).

Current challenges in cardiac rehabilitation: strategies to overcome social factors and attendance barriers.

INTRODUCTION: Cardiac rehabilitation (CR) significantly reduces secondary cardiovascular events and mortality and is a class 1A recommendation by the American Heart Association (AHA) and American College of Cardiology (ACC). However, it remains an underutilized intervention and many eligible patients fail to enroll or complete CR programs. The aim of this review is to identify barriers to CR attendance and discuss strategies to overcome them. AREAS COVERED: Specific barriers to CR attendance and participation will be reviewed. This will be followed by a discussion of solutions/strategies to help overcome these barriers with a particular focus on home-based CR (HBCR). EXPERT OPINION: HBCR alone or in combination with center-based CR (CBCR) can help overcome many barriers to traditional CBCR participation, such as schedule flexibility, time commitment, travel distance, cost, and patient preference. Using remote coaching with indirect exercise supervision, HBCR has been shown to have comparable benefits to CBCR. At this time, however, funding remains the main barrier to universal incorporation of HBCR into health systems, necessitating the need for additional cost benefit analysis and outcome studies. Ultimately, the choice for HBCR should be based on patient preference and availability of resources.

Noninvasive Assessment of Portal Hypertension Using Spectral Computed Tomography.

BACKGROUND: Early diagnosis of portal hypertension is imperative for timely treatment to reduce the mortality rate. However, there is still no adequate method to noninvasively and accurately assess the portal hypertension in routine clinical practice. PURPOSE: We aimed to evaluate the accuracy of parameters measured using dual energy spectral computed tomography (LightSpeed CT750 HD) in assessing portal venous pressure in patients with liver cirrhosis. STUDY: Forty-five patients with liver cirrhosis who underwent percutaneous transhepatic portal vein puncture as part of their treatment for liver disease were enrolled in this study. Measurement of direct portal venous pressure was performed preoperatively. All patients underwent dual energy spectral computed tomography within 3 days before their operations. RESULTS: The iodine concentrations of portal vein and hepatic parenchyma during the portal venous phase and the alanine aminotransferase level were found to be independently correlated with the direct portal venous pressure according to stepwise multivariate linear regression analysis (P<0.001, 0.004, and 0.024, respectively). In a receiver operating characteristic analysis, the area under the receiver operating characteristic of iodine concentrations of the portal vein (ICPV) for identifying clinically significant portal hypertension (≥10 mm Hg) was significantly higher than that of iodine concentrations of hepatic parenchyma (ICliver) and the alanine aminotransferase level (0.944, 0.825, and 0.301, respectively). The threshold ICPV of 58.27 yielded a sensitivity of 93.8%, specificity of 69.2%, positive predictive value of 88.2%, and negative predictive value of 81.8%, respectively. CONCLUSIONS: ICPV values may be a useful tool in noninvasively assessing the portal venous pressure and identifying clinically significant portal hypertension in liver cirrhosis.

WISP-1 drives bone formation at the expense of fat formation in human perivascular stem cells.

The vascular wall within adipose tissue is a source of mesenchymal progenitors, referred to as perivascular stem/stromal cells (PSC). PSC are isolated via fluorescence activated cell sorting (FACS), and defined as a bipartite population of pericytes and adventitial progenitor cells (APCs). Those factors that promote the differentiation of PSC into bone or fat cell types are not well understood. Here, we observed high expression of WISP-1 among human PSC in vivo, after purification, and upon transplantation in a bone defect. Next, modulation of WISP-1 expression was performed, using WISP-1 overexpression, WISP-1 protein, or WISP-1 siRNA. Results demonstrated that WISP-1 is expressed in the perivascular niche, and high expression is maintained after purification of PSC, and upon transplantation in a bone microenvironment. In vitro studies demonstrate that WISP-1 has pro-osteogenic/anti-adipocytic effects in human PSC, and that regulation of BMP signaling activity may underlie these effects. In summary, our results demonstrate the importance of the matricellular protein WISP-1 in regulation of the differentiation of human stem cell types within the perivascular niche. WISP-1 signaling upregulation may be of future benefit in cell therapy mediated bone tissue engineering, for the healing of bone defects or other orthopaedic applications.

Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis.

Previous studies have explored the association between toll-like receptor 4 (TLR4) polymorphisms and risk of various cancers, but the results remained controversial. To obtain an assessment of the effect of TLR4 polymorphisms (rs4986790, rs4986791 and rs11536889) on cancer risk, fifty-five articles (containing 20107 cases and 28244 controls) were recruited for meta-analysis. Our result indicated that two Single Nucleotide Polymorphisms (SNP) in TLR4 were associated with decreased cancer risk for rs4986791: OR = 0.764, 95% CI: 0.652-0.894, P = 0.001 in allele model; OR = 0.769, 95%CI: 0.650-0.909, P = 0.002 in recessive model; OR = 0.505, 95% CI: 0.352-0.726, P = 0.000 in dominant model; for 11536889: OR = 0.927, 95% CI: 0.872-0.984, P = 0.013 in allele model; OR = 0.926, 95% CI: 0.862-0.944,P = 0.034 in recessive model. In terms of subgroup analyses sorted by ethnicity, only polymorphism of rs4986791 had a significant influence on decrease of cancer risk among both Caucasian and Asian populations. The findings suggested that TLR4 polymorphisms may serve as a genetic risk factor for cancers.

[Epidemiological features of the injured in road traffic accidents in Shanghai].

OBJECTIVE: To provide reference data for enacting and revising the laws and regulations of the disability expertise. METHODS: The epidemiological features of the disabled caused by road traffic accident in Shanghai during 2005 were retrospectively analyzed. RESULTS: The most common injuries were in extremities (53.3%), followed by head (23.3%), spine (9.7%), thorax (5.8%), and abdomen (4.4%). The cumulative incidence rate of disability due to traffic injuries was 414.8 cases per 100,000 inhabitants, higher for men (505.7/100,000) than women (318.7/100,000). The highest incidence rate of disability was between age 35 and 59 (538.2/100,000). The most disabled was bicyclist, followed by pedestrian. CONCLUSION: The incidence rate of disability among 35-59 age group was the highest in Shanghai during 2005. It has resulted in loss of labor force with a negative effect on the economic development.