Cardiometabolic and vascular disease, with their associated secondary complications, are the leading cause of morbidity and mortality in Western society. Chronic inflammation is a common theme that ...underlies initiation and progression of cardiovascular disease. In this regard, monocytes/macrophages are key players in the development of a chronic inflammatory state. Over the past decade, epigenetic modifications, such as DNA methylation and posttranslational histone processing, have emerged as important regulators of immune cell phenotypes. Accumulating studies reveal the importance of epigenetic enzymes in the dynamic regulation of key signaling pathways that alter monocyte/macrophage phenotypes in response to environmental stimuli. In this review, we highlight the current paradigms of monocyte/macrophage polarization and the emerging role of epigenetic modification in the regulation of monocyte/macrophage phenotype in obesity, diabetes mellitus, atherosclerosis, and abdominal aortic aneurysms.
Abstract Psychiatric symptoms are important non-motor features in PD, which occur at high frequency and have significant impact on health related quality of life. This review concentrates on the ...prevalence, pathophysiology, diagnosis and treatment of depression, anxiety, apathy and psychosis. The pathophysiology of these disorders is complex, reflecting the widespread brainstem and cortical pathology in PD, with involvement of several neurotransmitters, including dopaminergic, serotonergic, noradrenergic and cholinergic systems. The diagnosis of psychiatric conditions, in particular affective disorders, is challenging because of the overlap of somatic features of psychiatric disorders and underlying movement disorder. The pathogenesis is likely to differ considerably from non-PD patients, and treatments used in general psychiatry services may not be as effective in PD and will require clearer clarification in well-designed clinical studies. Management strategies include adjustment of dopaminergic medication, use of psychotropic treatments and behavioural and psychological approaches. However, the future challenge will be to develop treatments developed specifically for the pathogenesis of these disorders in PD.
The healing of cutaneous wounds is dependent on the progression through distinct, yet overlapping phases of wound healing, including hemostasis, inflammation, proliferation, and ...resolution/remodeling. The failure of these phases to occur in a timely, progressive fashion promotes pathologic wound healing. The macrophage (MΦ) has been demonstrated to play a critical role in the inflammatory phase of tissue repair, where its dynamic plasticity allows this cell to mediate both tissue-destructive and -reparative functions. The ability to understand and control both the initiation and the resolution of inflammation is critical for treating pathologic wound healing. There are now a host of studies demonstrating that metabolic and epigenetic regulation of gene transcription can influence MΦ plasticity in wounds. In this review, we highlight the molecular and epigenetic factors that influence MΦ polarization in both physiologic and pathologic wound healing, with particular attention to diabetic wounds.
Objectives
(1) To assess the methodological quality of radiomics studies investigating histological subtypes, therapy response, and survival in patients with renal cell carcinoma (RCC) and (2) to ...determine the risk of bias in these radiomics studies.
Methods
In this systematic review, literature published since 2000 on radiomics in RCC was included and assessed for methodological quality using the Radiomics Quality Score. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and a meta-analysis of radiomics studies focusing on differentiating between angiomyolipoma without visible fat and RCC was performed.
Results
Fifty-seven studies investigating the use of radiomics in renal cancer were identified, including 4590 patients in total. The average Radiomics Quality Score was 3.41 (9.4% of total) with good inter-rater agreement (ICC 0.96, 95% CI 0.93–0.98). Three studies validated results with an independent dataset, one used a publically available validation dataset. None of the studies shared the code, images, or regions of interest. The meta-analysis showed moderate heterogeneity among the included studies and an odds ratio of 6.24 (95% CI 4.27–9.12;
p
< 0.001) for the differentiation of angiomyolipoma without visible fat from RCC.
Conclusions
Radiomics algorithms show promise for answering clinical questions where subjective interpretation is challenging or not established. However, the generalizability of findings to prospective cohorts needs to be demonstrated in future trials for progression towards clinical translation. Improved sharing of methods including code and images could facilitate independent validation of radiomics signatures.
Key Points
•
Studies achieved an average Radiomics Quality Score of 10.8%. Common reasons for low Radiomics Quality Scores were unvalidated results, retrospective study design, absence of open science, and insufficient control for multiple comparisons.
•
A previous training phase allowed reaching almost perfect inter-rater agreement in the application of the Radiomics Quality Score.
•
Meta-analysis of radiomics studies distinguishing angiomyolipoma without visible fat from renal cell carcinoma show moderate diagnostic odds ratios of 6.24 and moderate methodological diversity.
A review of shark satellite tagging studies Hammerschlag, N.; Gallagher, A.J.; Lazarre, D.M.
Journal of experimental marine biology and ecology,
02/2011, Letnik:
398, Številka:
1-2
Journal Article
Recenzirano
Recent advances in satellite tagging technologies have provided scientists growing opportunities to resolve previously unknown spatial ecology of marine predators, including sharks. Such an ...understanding is particularly important at this time given recent declines in shark populations worldwide. Here we reviewed 48 studies published in the primary literature between 1984 and 2010, addressing the most basic questions regarding the use of satellite tagging for studying shark behavior and ecology. For each study, the following aspects were analyzed: tagging location; species tagged; study focus; technology employed; sample size; tag attachment and deployment technique; duration of tracking; tag failure rate; and study limitation. The potential impacts of tagging on shark behavior and physiology are considered. Finally, we discuss how satellite tagging has furthered our current knowledge of shark behavior and consider the possibility of new tag developments that can improve our ability to resolve the mechanisms underlying shark habitat use.
► In this article we review 48 studies that used satellite-tags to study sharks. ► We summarize aspects from each study to examine trends and identify knowledge gaps. ► Negative impacts of tagging on shark behavior and physiology are considered. ► Advances in tagging technology and its usage for conservation are discussed. ► Future tag developments are considered to determine mechanism underlying shark behavior.
To describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD ...Reaction Index for DSM-5 (RI-5) across 2 independent samples.
Study 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a "gold standard" structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version.
RI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94).
The developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health.
We set a framework for the study of Hardy spaces inherited by complements of analytic hypersurfaces in domains with a prior Hardy space structure. The inherited structure is a filtration, various ...aspects of which are studied in specific settings. For punctured planar domains, we prove a generalization of a famous rigidity lemma of Kerzman and Stein. A stabilization phenomenon is observed for egg domains. Finally, using proper holomorphic maps, we derive a filtration of Hardy spaces for certain power-generalized Hartogs triangles, although these domains fall outside the scope of the original framework.
Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. ...Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immunemediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.
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