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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury
|
|---|---|
| Published in |
BMC Medicine, August 2015
|
| DOI | 10.1186/s12916-015-0418-0 |
| Pubmed ID | |
| Authors |
Valentyn Usachov, Thomas J. Urban, Robert J. Fontana, Annika Gross, Sapna Iyer, M. Bishr Omary, Pavel Strnad, on behalf of the Drug-Induced Liver Injury Network |
| Abstract |
Keratin 8 and 18 (K8/K18) cytoskeletal proteins protect hepatocytes from undergoing apoptosis and their mutations predispose to adverse outcomes in acute liver failure (ALF). All known K8/K18 variants occur at relatively non-conserved residues and do not cause keratin cytoskeleton reorganization, whereas epidermal keratin-conserved residue mutations disrupt the keratin cytoskeleton and cause severe skin disease. The aim of our study was to identify keratin variants in idiosyncratic drug-induced liver injury (DILI). Genomic DNA was isolated from 800 patients enrolled in an ongoing US multicenter study, with DILI attributed to a wide range of drugs. Specific K8/K18 exonic regions were PCR-amplified and screened by denaturing HPLC followed by DNA sequencing. The functional impact of keratin variants was assessed using cell transfection and immune staining. Heterozygous and compound amino acid-altering K8/K18 variants were identified in 86 DILI patients and non-coding variants in 15 subjects. Five novel amino acid-altering (K8 Lys393Arg, K8 Ala351Val, K8 Ala358Val, K8 Ile346Val, K18 Asp89His) and two non-coding variants were observed. Several variants segregated with specific ethnic backgrounds but were found at similar frequencies in DILI subjects and ethnically matched population controls. Notably, variants in highly conserved residues of K8 Lys393Arg (ezetimibe/simvastatin-related) and K18 Asp89His (isoniazid-related) were found in patients with fatal DILI. These novel variants also led to keratin network disruption in transfected cells. Novel K8/K18 cytoskeleton-disrupting variants were identified in two patients and segregated with fatal DILI. Other non-cytoskeleton-disrupting keratin variants did not preferentially associate with DILI. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
| Members of the public | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 29% |
| Student > Doctoral Student | 4 | 17% |
| Student > Master | 2 | 8% |
| Other | 1 | 4% |
| Researcher | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 33% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Neuroscience | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2015.
All research outputs
#15,153,715
of 23,306,612 outputs
Outputs from BMC Medicine
#3,056
of 3,507 outputs
Outputs of similar age
#148,554
of 267,178 outputs
Outputs of similar age from BMC Medicine
#90
of 91 outputs
Altmetric has tracked 23,306,612 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,507 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 43.7. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,178 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 91 others from the same source and published within six weeks on either side of this one. This one is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.