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Institution

University of Pittsburgh

EducationPittsburgh, Pennsylvania, United States
About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.


Papers
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Journal ArticleDOI
TL;DR: Although phototherapy successfully reduces serum bilirubin levels, patients are again at risk for kernicterus around the time of puberty, when phototherapy becomes less effective, and liver transplantation is the only definitive treatment.
Abstract: Crigler–Najjar syndrome type I is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia beginning at birth. The syndrome results from an absence of hepatic uridine diphosphoglucuronate (UDP) glucuronosyltransferase activity, which is essential for the conjugation and excretion of bilirubin. Because of the accumulation of unconjugated bilirubin in plasma, patients are at risk for kernicterus.1 Although phototherapy successfully reduces serum bilirubin levels, patients are again at risk for kernicterus around the time of puberty, when phototherapy becomes less effective.2 The necessary daily duration of phototherapy often approaches 14 to 16 hours. At present, liver transplantation is the only definitive treatment. . . .

982 citations

Book ChapterDOI
01 Dec 1988
TL;DR: In their everyday life, the authors must constantly make choices concerning what tasks to do or not to do, when to do them, and whether toDo them at all.
Abstract: In our everyday life, we must constantly make choices concerning what tasks to do or not to do, when to do them, and whether to do them at all.

982 citations

Journal ArticleDOI
TL;DR: In this article, the authors suggest that productive disciplinary engagement can be fostered by designing learning environments that support problematizing subject matter, giving students authority to address such problems, holding students accountable to others and to shared disciplinary norms, and providing students with relevant resources.
Abstract: This article suggests that productive disciplinary engagement can be fostered by designing learning environments that support (a) problematizing subject matter, (b) giving students authority to address such problems, (c) holding students accountable to others and to shared disciplinary norms, and (d) providing students with relevant resources. To provide empirical support for this suggestion, we use these 4 guiding principles to explain a case of productive disciplinary engagement from a Fostering Communities of Learners classroom. We use the principles to understand 1 group of students' emergent and sustained controversy over a species' classification. The students became passionately engaged, used evidence in scholarly ways, developed several arguments, and generated questions regarding biological classification. We propose the controversy as an example of productive disciplinary engagement, and show how it was supported by: the treatment of the classification as a legitimate problem by the students and...

982 citations

Journal ArticleDOI
23 Jan 2020-Nature
TL;DR: Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.
Abstract: Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases. Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.

981 citations

Journal ArticleDOI
22 Sep 2010-JAMA
TL;DR: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly inThose with a TSH concentration of 10 mIU/L or greater.
Abstract: Context Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. Objective To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. Data Sources and Study Selection The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. Data Extraction Individual data on 55 287 participants with 542 494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25 977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. Results Among 55 287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51 837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P Conclusions Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.

981 citations


Authors

Showing all 87737 results

NameH-indexPapersCitations
JoAnn E. Manson2701819258509
Graham A. Colditz2611542256034
Yi Chen2174342293080
David J. Hunter2131836207050
David Miller2032573204840
Rakesh K. Jain2001467177727
Lewis C. Cantley196748169037
Dennis W. Dickson1911243148488
Terrie E. Moffitt182594150609
Dennis S. Charney179802122408
Ronald C. Petersen1781091153067
David L. Kaplan1771944146082
Jasvinder A. Singh1762382223370
Richard K. Wilson173463260000
Deborah J. Cook173907148928
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023260
20221,089
202111,151
202010,407
20199,333
20188,577