Citations

Abstract This retrospective study from Jiangsu Province Hospital elucidates the prevalence and impact of pediatric androgenetic alopecia (AGA). Over a period of 14 years, 133 patients under the age of 18 were studied, with manifestations appearing as early as 8 years of age. Of note, 39.8% had an overweight/obese and 78.2% reported a family history of AGA. Comorbidities included seborrhoeic dermatitis (51.9%), acne (42.9%) and sleep disorders (28.6%). In addition, 4.5% had polycystic ovarian syndrome. Hormonal imbalances such as low sex hormone-binding globulin (47.1%) and vitamin D deficiency (61%) were common, as was low ferritin (23.6%). Male AGA patterns were characterised by crown thinning and temporal variations, whereas females showed crown thinning with frontal hair retention. Trichoscopic differences were observed between genders and age groups. This study highlights the importance of individualised, stepwise and comprehensive treatment, prioritising hormonal disorders and comorbidities when treating hair loss with topical minoxidil. Encouraging patients to adhere to regular medication and follow-up appointments can lead to favourable outcomes.

AbstractPurposeRural populations are disproportionately affected by the COVID‐19 pandemic. We characterized urban‐rural disparities in patient portal messaging utilization for COVID‐19, and, of those who used the portal during its early stage in the Midwest.MethodsWe collected over 1 million portal messages generated by midwestern Mayo Clinic patients from February to August 2020. We analyzed patient‐generated messages (PGMs) on COVID‐19 by urban‐rural locality and incorporated patients’ sociodemographic factors into the analysis.FindingsThe urban‐rural ratio of portal users, message senders, and COVID‐19 message senders was 1.18, 1.31, and 1.79, indicating greater use among urban patients. The urban‐rural ratio (1.69) of PGMs on COVID‐19 was higher than that (1.43) of general PGMs. The urban‐rural ratios of messaging were 1.72‐1.85 for COVID‐19‐related care and 1.43‐1.66 for other health care issues on COVID‐19. Compared with urban patients, rural patients sent fewer messages for COVID‐19 diagnosis and treatment but more messages for other reasons related to COVID‐19‐related health care (eg, isolation and anxiety). The frequent senders of COVID‐19‐related messages among rural patients were 40+ years old, women, married, and White.ConclusionsIn this Midwest health system, rural patients were less likely to use patient online services during a pandemic and their reasons for its use differ from urban patients. Results suggest opportunities for increasing equity in rural patient engagement in patient portals (in particular, minority populations) for COVID‐19. Public health intervention strategies could target reasons why rural patients might seek health care in a pandemic, such as social isolation and anxiety.

AbstractObjectiveThe study sought to describe the literature related to the development of methods for auditing the Unified Medical Language System (UMLS), with particular attention to identifying errors and inconsistencies of attributes of the concepts in the UMLS Metathesaurus.Materials and MethodsWe applied the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach by searching the MEDLINE database and Google Scholar for studies referencing the UMLS and any of several terms related to auditing, error detection, and quality assurance. A qualitative analysis and summarization of articles that met inclusion criteria were performed.ResultsEighty-three studies were reviewed in detail. We first categorized techniques based on various aspects including concepts, concept names, and synonymy (n = 37), semantic type assignments (n = 36), hierarchical relationships (n = 24), lateral relationships (n = 12), ontology enrichment (n = 8), and ontology alignment (n = 18). We also categorized the methods according to their level of automation (ie, automated systematic, automated heuristic, or manual) and the type of knowledge used (ie, intrinsic or extrinsic knowledge).ConclusionsThis study is a comprehensive review of the published methods for auditing the various conceptual aspects of the UMLS. Categorizing the auditing techniques according to the various aspects will enable the curators of the UMLS as well as researchers comprehensive easy access to this wealth of knowledge (eg, for auditing lateral relationships in the UMLS). We also reviewed ontology enrichment and alignment techniques due to their critical use of and impact on the UMLS.

Objectives Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features. Methods Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes. Results Analyses of both CL and NCL monocytes demonstrated that many genes had a lower expression rate in SLE monocytes than in controls. Unsupervised hierarchical clustering of the CL and NCL data sets demonstrated independent clusters of cells from the patients with SLE that were related to disease activity, type I interferon (IFN) and medication use. Thus, each of these factors exerted a different impact on monocyte gene expression that could be identified separately, and a number of genes correlated uniquely with disease activity. We found within-cell correlations between genes directly induced by type I IFN-induced and other non–IFN-induced genes, suggesting the downstream biological effects of type I IFN in individual human SLE monocytes which differed between CLs and NCLs. Conclusions In summary, single-cell gene expression in monocytes was associated with a wide range of clinical and biological features in SLE, providing much greater detail and insight into the cellular biology underlying the disease than previous mixed-cell population studies.

Prohibitin 1 (PHB1) is best known as a mitochondrial chaperone, and its role in cancer is conflicting. Mice lacking methionine adenosyltransferase α1 (MATα1) have lower PHB1 expression, and we reported that c‐MYC interacts directly with both proteins. Furthermore, c‐MYC and MATα1 exert opposing effects on liver cancer growth, prompting us to examine the interplay between PHB1, MATα1, and c‐MYC and PHB1's role in liver tumorigenesis. We found that PHB1 is highly expressed in normal hepatocytes and bile duct epithelial cells and down‐regulated in most human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). In HCC and CCA cells, PHB1 expression correlates inversely with growth. PHB1 and MAT1A positively regulate each other's expression, whereas PHB1 negatively regulates the expression of c‐MYC, MAFG, and c‐MAF. Both PHB1 and MATα1 heterodimerize with MAX, bind to the E‐box element, and repress E‐box promoter activity. PHB1 promoter contains a repressive E‐box element and is occupied mainly by MAX, MNT, and MATα1 in nonmalignant cholangiocytes and noncancerous tissues that switched to c‐MYC, c‐MAF, and MAFG in cancer cells and human HCC/CCA. All 8‐month‐old liver‐specific Phb1 knockout mice developed HCC, and one developed CCA. Five‐month‐old Phb1 heterozygotes, but not Phb1 flox mice, developed aberrant bile duct proliferation; and one developed CCA 3.5 months after left and median bile duct ligation. Phb1 heterozygotes had a more profound fall in the expression of glutathione synthetic enzymes and higher hepatic oxidative stress following left and median bile duct ligation. Conclusion: We have identified that PHB1, down‐regulated in most human HCC and CCA, heterodimerizes with MAX to repress the E‐box and positively regulates MAT1A while suppressing c‐MYC, MAFG, and c‐MAF expression; in mice, reduced PHB1 expression predisposes to the development of cholestasis‐induced CCA. (Hepatology 2017;65:1249‐1266).

c‐Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice, and induction of Maf proteins (MafG and c‐Maf) contributes to cholestatic liver injury, whereas S‐adenosylmethionine (SAMe) administration is protective. Here, we determined whether there is interplay between c‐Myc, Maf proteins, and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in the liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh‐28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein‐protein interactions, molecular mechanisms, and functional outcomes. We found that c‐Myc, MATα1 (encoded by MAT1A), MafG, and c‐Maf interact with one another directly. MAT1A expression fell in hepatocytes and bile duct epithelial cells during chronic cholestasis and in murine and human CCA. The opposite occurred with c‐Myc, MafG, and c‐Maf expression. MATα1 interacts mainly with Mnt in normal liver, but this switches to c‐Maf, MafG, and c‐Myc in cholestatic livers and CCA. Promoter regions of these genes have E‐boxes that are bound by MATα1 and Mnt in normal liver and benign bile duct epithelial cells that switched to c‐Myc, c‐Maf, and MafG in cholestasis and CCA cells. E‐box positively regulates c‐Myc, MafG, and c‐Maf, but it negatively regulates MAT1A. MATα1 represses, whereas c‐Myc, MafG, and c‐Maf enhance, E‐box‐driven promoter activity. Knocking down MAT1A or overexpressing MafG or c‐Maf enhanced CCA growth and invasion in vivo. Conclusion: There is a novel interplay between MATα1, c‐Myc, and Maf proteins, and their deregulation during chronic cholestasis may facilitate CCA oncogenesis. (Hepatology 2016;64:439‐455)