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Gaudet MM Falk RT Stevens RD Gunter MJ Bain JR Pfeiffer RM Potischman N Lissowska J Peplonska B Brinton LA Garcia-Closas M Newgard CB Sherman ME 《The Journal of clinical endocrinology and metabolism》2012,97(9):3216-3223
Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. Design: This was the Polish Endometrial Cancer Study (2001-2003). Setting: This study was a population-based case-control study. Patients: Patients included 250 cases and 250 controls. Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. Main Outcome Measure: The main outcome measure was endometrial cancer. Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer. 相似文献
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Shlush LI Chapal-Ilani N Adar R Pery N Maruvka Y Spiro A Shouval R Rowe JM Tzukerman M Bercovich D Izraeli S Marcucci G Bloomfield CD Zuckerman T Skorecki K Shapiro E 《Blood》2012,120(3):603-612
Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia. 相似文献
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Perceptions towards disability among social work students in Israel: Development and validation of a new scale 下载免费PDF全文
Over the last decades, the disability movement has been advocating for a paradigmatic shift in how disability is perceived and managed: from a medical or individual perspective focusing on the person's body and mind to a social perspective emphasizing the context and barriers of disability. However, we still know little about the perceptions of helping professionals, particularly social workers who work closely with disabled people. Thus, the aim of the current study is to develop and validate a scale—Perceptions Toward Disability Scale (PTDS)—to measure how social workers view disability: as an individual or social category. This paper describes the three phases of the scale's construction. First, scale items were formulated and its content validity was examined. Next, a pilot of 30 social workers completed a questionnaire and an initial exploratory factor analysis was conducted. In the third and main phase, the final draft was completed in 2016 by 565 Israeli social work students to assess its psychometric properties. Both exploratory and confirmatory factorial validity and discriminant validity analyses were conducted. The results of a confirmatory factor analysis revealed two distinct factors: an individual perspective of disability comprised of eight items (α = 0.77) and a social perspective of disability comprised of ten (α = 0.66). Subsequent analyses supported the scale's discriminant validity as indicated by the lack of an association between the Attitude Toward Disabled Persons Scale (ATDP) and the social model subscale (r = .13, p = .19) and by the weak negative relation with the individual model subscale (r = ?.25, p = .01). These findings show that the PTDS possesses promising construct validity and provide support for its utility. This easy‐to‐administer instrument offers several practical benefits and can serve as a framework for further empirical research regarding social work practice with disabled people. 相似文献
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ABSTRACTThis article discusses and illustrates the role and impact of the intersection of supervisors’ and supervisees’ social identities and the associated power and privilege within the context of supervision for trauma-informed practice. Based on current theoretical, empirical, and practice literature, challenges related to the supervisor’s and supervisee’s racial, ethnicity, gender, social class, and additional social affiliations are identified, as are strategies for addressing them within supervision for trauma-informed practice. A case example drawn from the authors’ experiences illustrates the importance of attending to intersectionality in trauma-informed supervision Suggestions for future research efforts are offered. 相似文献
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The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus’ onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO’s response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts. 相似文献
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Justin Taylor Mark T.A. Donoghue Caleb Ho Kseniya Petrova-Drus Hikmat A. Al-Ahmadie Samuel A. Funt Yanming Zhang Umut Aypar Pavitra Rao Shweta S. Chavan Michael Haddadin Roni Tamari Sergio Giralt Martin S. Tallman Raajit K. Rampal Priscilla Baez Rajya Kappagantula Satyajit Kosuri Ahmet Dogan Satish K. Tickoo Victor E. Reuter George J. Bosl Christine A. Iacobuzio-Donahue David B. Solit Barry S. Taylor Darren R. Feldman Omar Abdel-Wahab 《The Journal of clinical investigation》2020,130(12):6668