Despite their recognized limitations, bibliometric assessments of scientific productivity have been widely adopted. We describe here an improved method to quantify the influence of a research article by making novel use of its co-citation network to field-normalize the number of citations it has received. Article citation rates are divided by an expected citation rate that is derived from performance of articles in the same field and benchmarked to a peer comparison group. The resulting Relative Citation Ratio is article level and field independent and provides an alternative to the invalid practice of using journal impact factors to identify influential papers. To illustrate one application of our method, we analyzed 88,835 articles published between 2003 and 2010 and found that the National Institutes of Health awardees who authored those papers occupy relatively stable positions of influence across all disciplines. We demonstrate that the values generated by this method strongly correlate with the opinions of subject matter experts in biomedical research and suggest that the same approach should be generally applicable to articles published in all areas of science. A beta version of iCite, our web tool for calculating Relative Citation Ratios of articles listed in PubMed, is available at https://icite.od.nih.gov.

Despite their recognized limitations, bibliometric assessments of scientific productivity have been widely adopted. We describe here an improved method to quantify the influence of a research article by making novel use of its co-citation network to field-normalize the number of citations it has received. Article citation rates are divided by an expected citation rate that is derived from performance of articles in the same field and benchmarked to a peer comparison group. The resulting Relative Citation Ratio is article level and field independent and provides an alternative to the invalid practice of using journal impact factors to identify influential papers. To illustrate one application of our method, we analyzed 88,835 articles published between 2003 and 2010 and found that the National Institutes of Health awardees who authored those papers occupy relatively stable positions of influence across all disciplines. We demonstrate that the values generated by this method strongly correlate with the opinions of subject matter experts in biomedical research and suggest that the same approach should be generally applicable to articles published in all areas of science. A beta version of iCite, our web tool for calculating Relative Citation Ratios of articles listed in PubMed, is available at https://icite.od.nih.gov. Author SummaryAcademic researchers convey their discoveries to the scientific community by publishing papers in scholarly journals. In the biomedical sciences alone, this process now generates more than one million new reports each year. The sheer volume of available information, together with the increasing specialization of many scientists, has contributed to the adoption of metrics, including journal impact factor and h-index, as signifiers of a researcher's productivity or the significance of his or her work. Scientists and administrators agree that the use of these metrics is problematic, but in spite of this strong consensus, such judgments remain common practice, suggesting the need for a valid alternative. We describe here an improved method to quantify the influence of a research article by making novel PLOS Biology |

Objective— Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells. The role of AQP1 in HPH pathogenesis has not been directly determined to date. To determine the possible roles of AQP1 in the pathogenesis of HPH and explore its possible mechanisms. Approach and Results— Aqp1 knockout mice were used, and HPH model was established in this study. Primary pulmonary artery smooth muscle cells, primary mouse lung endothelial cells, and lung tissue sections from HPH model were used. Immunohistochemistry, immunofluorescence and Western blot, cell cycle, apoptosis, and migration analysis were performed in this study. AQP1 expression was upregulated by chronic hypoxia exposure, both in pulmonary artery endothelia and medial smooth muscle layer of mice. Aqp1 deficiency attenuated the elevation of right ventricular systolic pressures and mitigated pulmonary vascular structure remodeling. AQP1 deletion reduced abnormal cell proliferation in pulmonary artery and accompanied with accumulation of HIF (hypoxia-inducible factor). In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration ability of primary cultured pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. Furthermore, Aqp1 deficiency protected lung endothelial cells from apoptosis in response to hypoxic injury. Conclusions— Our data showed that Aqp1 deficiency could attenuate hypoxia-induced vascular remodeling in the development of HPH. AQP1 may be a potential target for pulmonary hypertension treatment.

Unraveling the pathophysiological basis for the development of and recovery from depression is a unique challenge. Dendritic plasticity has been reported to be involved in the development of depression. We modeled an anxiety/depression-like phenotype by chronic corticosterone exposure in mice and reversed this anxiety/depression-like phenotype by long-term treatment with fluoxetine (FLX). Spine density in the hippocampus was detected by Golgi-Cox staining at five time points. The data showed that 35 days of corticosterone exposure led to a decrease in spine density in CA1, concomitant with the onset of depression. Following 25 days of treatment with FLX, the decrease in both the dendritic spine density in the hippocampus and the anxiety/depression-like phenotype induced by chronic corticosterone recovered to normal levels concomitantly. Interestingly, the total spine density changes are all mainly driven by changes in thin and stubby spines, not mushroom spines, following chronic corticosterone or FLX treatment. Our results suggest that the changes in dendritic spine density in the hippocampus may be one of the pathophysiological mechanisms underlying the development of and recovery from depression, and the neuronal plasticity of CA1 is first impaired during the development of depression.