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Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology -  相似文献   
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Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.  相似文献   
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Background: Sepsisis one of the mostserious complications and a leading cause of death in patients with coronavirus disease 2019 (COVID-19). In general, it isthe result of an unregulated inflammatory cascade such as a postinfection “cytokine storm.” The conventional treatment mainly relies on glucocorticoids, of which curative effects are not ideal, as they come with significant side effects. It is critical to seek or develop other effective therapeutics in dealing cytokine storm to fight COVID-19 with sepsis. Aims and Objectives: Raise awareness of the significance applying anti-inflammatory acupuncture in dealing COVID-19 patients with sepsis and provide an appropriate acupuncture protocol that can be easily integrated into existing medical guideline. Materials and Methods: Current evidences from animal experiments and clinical trials about acupuncture in treating infectious sepsis are reviewed, and a detailed discussion on advantages of anti?inflammatory acupuncture is followed, then the rationality on the point selection and stimulation parameters of acupuncture is analyzed to propose an appropriate acupuncture protocol. Results: Current experiments have shown that acupuncture can play a significant role to improve inflammation reaction and reduce mortality in infectious animal and patients with sepsis and its mechanisms are mainly achieved by stimulating the vagus?cholinergic anti?inflammatory pathways.Applying acupuncture in treating COVID-19 patients with sepsis hasfour aspects of advantages. Moreover, a simple and convenient clinical acupuncture protocol including point selection and appropriate stimulation parameters is proposed. Conclusion: Acupuncture, especially electroacupuncture, has shown potentials in effectively treating infectious sepsis of animal models and critically ill patients in small sample studies by stimulating the nervous system, but has been largely overlooked in the clinic so far. It is advised that acupuncture should be integrated into the existing medical guidelines in dealing with COVID-19 complicated with sepsis.  相似文献   
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Background:Workplace hazards are a significant source of health impairment for workers and of financial losses for firms. EU directives on workers’ health and safety standards significantly contributed to reduce reported occupational injuries, yet the incidence and prevalence of work-related mental illness is still very high.Objectives:We investigated the association between work-related hazards and individuals’ perceived mental health. We reviewed the existing evidence on the channels through which task-related factors, adverse agents and psychosocial factors are expected to affect workers’ health, with specific regard to mental health.Methods:We used data from the fifth wave of the European Working Conditions Survey, covering over 40,000 face-to-face interviews with workers in 34 countries, which includes information on socio-demographic characteristics, firms and jobs attributes, employment status, as well as working conditions and health status. We carried out an empirical analysis with multivariate regression models in order to estimate the relationship between workers’ mental health problems and workplace risk factors.Results:21,020 interviews were used in the multivariate analysis. We found strong correlations between hazards and various indicators of mental health. Among hazardous agents, low temperatures (β=0.0287) and contact with infectious materials (β=0.0394) were positively associated with mental health outcomes. Among task/sequence-related factors, tiring or painful positions (β=0.0713), repetitive hand/arm movements (β=0.0255), working with VDUs (β=0.0301), repetitive tasks <10 min (β=0.0859) and working in evenings (β=0.00754) were positively associated with mental health. Various psychosocial risk factors related to both the content of the job (for example, frequent disruptive interruptions: β=0.219, working in free time: β=0.0759, poor work-life balance: β=0.228) as well as the job context (for example, bad employment prospects: β=0.177, low decisional autonomy: β=0.245, bad social relations: β=0.186, workplace violence: β=0.411) were positively associated with mental health. The main results of the decomposition show that an important contribution to workers’ overall mental distress at work is associated with psychosocial risk factors (up to 60% for depression/anxiety symptoms and sleep disorders), while the contribution of somatic factors is on average lower (up to 20% for overall fatigue).Conclusions:We argue that action is needed to improve workers’ mental well-being, and reduce the economic costs for both the national health system and employers. Regulations and traditional economic measures are unlikely to prove successful in providing adequate standards of primary and secondary preventive measures in the work place without an appropriate and reliable Risk Assessment Procedure.Key words: Work hazards, risk assessment, job content, mental health  相似文献   
9.

Objective

To evaluate the cost-effectiveness of financial incentives for human immunodeficiency virus (HIV) viral suppression compared to standard of care.

Study Design

Mathematical model of 2-year intervention offering financial incentives ($70 quarterly) for viral suppression (<400 copies/ml3) based on the HPTN 065 clinical trial with HIV patients in the Bronx, NY and Washington, D.C.

Methods

A disease progression model with HIV transmission risk equations was developed following guidelines from the Second Panel on Cost-Effectiveness in Health and Medicine. We used health care sector and societal perspectives, 3% discount rate, and lifetime horizon. Data sources included trial data (baseline N = 16,208 patients), CDC HIV Surveillance data, and published literature. Outcomes were costs (2017 USD), quality-adjusted life years (QALYs), HIV infections prevented, and incremental cost-effectiveness ratio (ICER).

Results

Financial incentives for viral suppression were estimated to be cost-saving from a societal perspective and cost-effective ($49,877/QALY) from a health care sector perspective. Compared to the standard of care, financial incentives gain 0.06 QALYs and lower discounted lifetime costs by $4210 per patient. The model estimates that incentivized patients transmit 9% fewer infections than the standard-of-care patients. In the sensitivity analysis, ICER 95% credible intervals ranged from cost-saving to $501,610/QALY with 72% of simulations being cost-effective using a $150,000/QALY threshold. Modeling results are limited by uncertainty in efficacy from the clinical trial.

Conclusions

Financial incentives, as used in HTPN 065, are estimated to improve quality and length of life, reduce HIV transmissions, and save money from a societal perspective. Financial incentives offer a promising option for enhancing the benefits of medication in the United States.  相似文献   
10.
PurposeThe purpose of this study was to compare morphologic assessment and relaxometry of patellar hyaline cartilage between conventional sequences (fast spin-echo [FSE] T2-weighted fat-saturated and T2-mapping) and synthetic T2 short-TI inversion recovery (STIR) and T2 maps at 1.5 T magnetic resonance imaging (MRI).MethodThe MRI examinations of the knee obtained at 1.5 T in 49 consecutive patients were retrospectively studied. There were 21 men and 28 women with a mean age of 45 ± 17.7 (SD) years (range: 18–88 years). Conventional and synthetic acquisitions were performed, including T2-weighted fat-saturated and T2-mapping sequences. Two radiologists independently compared patellar cartilage T2-relaxation time on conventional T2-mapping and synthetic T2-mapping images. A third radiologist evaluated the patellar cartilage morphology on conventional and synthetic T2-weighted images. The presence of artifacts was also assessed. Interobserver agreement for quantitative variables was assessed using intraclass correlation coefficient (ICC).ResultsIn vitro, conventional and synthetic T2 maps yielded similar mean T2 values 58.5 ± 2.3 (SD) ms and 58.8 ± 2.6 (SD) ms, respectively (P = 0.414) and 6% lower than the expected experimental values (P = 0.038). Synthetic images allowed for a 15% reduction in examination time compared to conventional images. On conventional sequences, patellar chondropathy was identified in 35 patients (35/49; 71%) with a mean chondropathy grade of 4.8 ± 4.8 (SD). On synthetic images, 28 patients (28/49; 57%) were diagnosed with patellar chondropathy, with a significant 14% difference (P = 0.009) and lower chondropathy scores (3.7 ± 4.9 [SD]) compared to conventional images. Motion artifacts were more frequently observed on synthetic images (18%) than on conventional ones (6%). The interobserver agreement was excellent for both conventional and synthetic T2 maps (ICC > 0.83). Mean cartilage T2 values were significantly greater on synthetic images (36.2 ± 3.8 [SD] ms; range: 29-46 ms) relative to conventional T2 maps (31.8 ± 4.1 [SD] ms; range: 26-49 ms) (P < 0.0001).ConclusionDespite a decrease in examination duration, synthetic images convey lower diagnostic performance for chondropathy, greater prevalence of motion artifacts, and an overestimation of T2 values compared to conventional MRI sequences.  相似文献   
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