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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Dongbing Lai Emma C. Johnson Sarah Colbert Gayathri Pandey Grace Chan Lance Bauer Meredith W. Francis Victor Hesselbrock Chella Kamarajan John Kramer Weipeng Kuang Sally Kuo Samuel Kuperman Yunlong Liu Vivia McCutcheon Zhiping Pang Martin H. Plawecki Marc Schuckit Jay Tischfield Leah Wetherill Yong Zang Howard J. Edenberg Bernice Porjesz Arpana Agrawal Tatiana Foroud 《Alcoholism, clinical and experimental research》2022,46(3):374-383
2.
Juan D. Gonzalez‐Sanz 《Nursing philosophy》2020,21(4)
The current situation in which the humanities are disparaged affects all university disciplines, including nursing, in whose historical evolution the humanities have always been present in one form or another. Looking beyond this disrepute, this study proposes that nursing renew its attention to classical philosophy. Specifically, it invites a close reading of Xenophon's Anabasis and Plato's Meno, to get three related goals: to show how the use of ancient texts are very valuable tools for the philosophical initiation of nursing students and can help them reflect on their choice of nursing as a practical activity; to reflect on the problem of virtue and the nature of the good life; and to show how the interaction with ancient texts allows students to reflect on questions and issues of life, theirs and others, that are not open to investigation through a purely scientific method. Consequently, both Anabasis and Meno readings strengthen the intellectual relationship between philosophy and nursing, enabling the latter to delve deeper into the key questions of its own thought as a discipline. 相似文献
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4.
Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
5.
Julia Thornton Snider Jesse Sussell Mahlet Gizaw Tebeka Alicia Gonzalez Joshua T. Cohen Peter Neumann 《Value in health》2019,22(3):332-339
Background
Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.Objective
We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).Study Design
Retrospective analysis of pharmaceutical sales data.Methods
From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).Results
Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.Conclusions
This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results. 相似文献6.
Toshiro Hara Rony Chanoch-Myers Nathan D. Mathewson Chad Myskiw Lyla Atta Lillian Bussema Stephen W. Eichhorn Alissa C. Greenwald Gabriela S. Kinker Christopher Rodman L. Nicolas Gonzalez Castro Hiroaki Wakimoto Orit Rozenblatt-Rosen Xiaowei Zhuang Jean Fan Tony Hunter Inder M. Verma Kai W. Wucherpfennig Itay Tirosh 《Cancer cell》2021,39(6):779-792.e11
7.
8.
Alexander C. Egbe Rosalyn Adigun Vidhu Anand Collin P. West Victor M. Montori Hassan M. Murad Emmanuel Akintoye Karim Osman Heidi M. Connolly 《The Canadian journal of cardiology》2019,35(12):1784-1790
BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem. 相似文献
9.
Marlen Z. Gonzalez Lane Beckes Joanna Chango Joseph P. Allen James A. Coan 《Social cognitive and affective neuroscience》2015,10(7):921-928
Neuroimaging studies using the social-exclusion paradigm Cyberball indicate increased dorsal anterior cingulate cortex (dACC) and right insula activity as a function of exclusion. However, comparatively less work has been done on how social status factors may moderate this finding. This study used the Cyberball paradigm with 85 (45 females) socio-economically diverse participants from a larger longitudinal sample. We tested whether neighborhood quality during adolescence would predict subsequent neural responding to social exclusion in young adulthood. Given previous behavioral studies indicating greater social vigilance and negative evaluation as a function of lower status, we expected that lower adolescent neighborhood quality would predict greater dACC activity during exclusion at young adulthood. Our findings indicate that young adults who lived in low-quality neighborhoods in adolescence showed greater dACC activity to social exclusion than those who lived in higher quality neighborhoods. Lower neighborhood quality also predicted greater prefrontal activation in the superior frontal gyrus, dorsal medial prefrontal cortex and the middle frontal gyrus, possibly indicating greater regulatory effort. Finally, this effect was not driven by subsequent ratings of distress during exclusion. In sum, adolescent neighborhood quality appears to potentiate neural responses to social exclusion in young adulthood, effects that are independent of felt distress. 相似文献