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The circular RNAs (circRNAs) involved in competitive endogenous RNA (ceRNA) mechanism are critical modulators affecting pathogenesis of thyroid carcinoma (TC). The study's goal was to investigate the effects of circ 0003747 on the biological progression of papillary thyroid cancer (PTC). Normal thyroid cells Nthy-ori3-1 and TC derived cell lines were used in our study. Sanger sequencing and RNase R treatment were utilized for validating the circular structure of circ_0003747. In our work, circ_0003747 was found to be highly expressed in TC cells. Circ_0003747 knockdown reduced TC cell viability, proliferation, migration, and invasion while increasing cell apoptosis. Circ_0003747 targeted and negatively regulated miR-338-3p expression. Besides, miR-338-3p interacted with PLCD3 to repress its expression. Overexpression of miR-338-3p inhibited TC cell progression, and PLCD3 reversed these effects. Furthermore, PLCD3 overexpression reversed the effects of circ_0003747 knockdown on TC cells. Additionally, the knockdown of circ_0003747 remarkably suppressed tumour size and growth, restrained PLCD3 expression and promoted miR-338-3p expression in nude mice. In conclusion, circ_0003747 facilitated the biological progression of TC by modulating the miR-338-3p/PLCD3 axis, and it may be a new target for TC treatment. [Figure: see text] Abbreviations: TC: Thyroid carcinoma; PTC: Papillary thyroid carcinoma; CircRNAs: Circular RNAs; MiRNA: MicroRNA; EMT: Epithelial-mesenchymal transition; HCC: Hepatocellular carcinoma; PLCD3: Phospholipase C Delta 3; CeRNA: Competitive endogenous RNA.

Background: iPLEDGE is the mandatory regulatory program for isotretinoin in the United States, aimed to prevent isotretinoin-related teratogenicity. However, little is known about potential unintended impact of the program, including delay in isotretinoin initiation, course interruption, and premature termination, which may vary across sex and racial domains., Objective: To determine whether differences in isotretinoin start, interruption, and completion exist across sex and racial domains and whether iPLEDGE regulations contribute to such differences., Methods: Retrospective review of isotretinoin courses of patients prescribed isotretinoin for acne at the Brigham & Women's Hospital and Massachusetts General Hospital from 2008-2016., Results: 418 patients were included in analysis after being tightly matched across age and gender. 43.5% of non-white patients ended their course early compared to 30.1% of white patients (p = 0.010). iPLEDGE -related barriers were the most commonly specified reasons for delayed starting and interruption., Conclusion: iPLEDGE may disproportionately contribute to access barriers for non-white patients. Continued evaluation of iPLEDGE is needed to minimize unintended barriers to access., Competing Interests: The authors have declared that no competing interests exist.

Background: Treatments for early-stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband ultraviolet B (NBUVB), psoralen plus ultraviolet A (PUVA), and local radiation. The relative cost-effectiveness of each treatment given the differences in treatment failure, disease progression, and therapy escalation is not established., Objective: To compare the cost-effectiveness (CE) of treatment options for stage IA MF., Methods: A state-transition model was constructed with health states of stage IA to stage IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated by accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel., Results: The order of CE of the study treatments was determined to be as follows: local radiation, $225,399 for 15.40 life-years (LYs); NBUVB, $344,728 for 15.17 LYs; PUVA, $371,741 for 15.07 LYs; topical corticosteroids, $469,354 for 14.65 LYs; topical nitrogen mustard, $951,662 for 14.29 LYs; and topical bexarotene, 11,892,496 for 13.55 LYs. Sensitivity analyses confirmed the CE rankings., Limitations: We assumed a constant probability of response, relapse rates, and 3-month treatment intervals., Conclusions: Local radiation is the most cost-effective treatment for limited local disease, whereas phototherapy (NBUVB or PUVA) is cost-effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding selection of therapy for stage IA MF., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: We previously demonstrated that dermatology consultation substantially reduces the rates of misdiagnosis of cellulitis; however, broad implementation of dermatology consultation is impractical on account of existing practice patterns and reimbursement systems. Meanwhile, efforts to improve diagnostic accuracy have culminated in point-of-care tools, including the ALT-70 predictive model for lower extremity cellulitis and thermal imaging., Objective: To prospectively evaluate the performance of the ALT-70 predictive model and thermal imaging in diagnosing lower extremity cellulitis in a head-to-head comparison., Methods: We collected ALT-70 and thermal imaging data from patients with presumed lower extremity cellulitis and compared classification measures and accuracy for the ALT-70 predictive model, thermal imaging, and combination testing (ALT-70 predictive model plus thermal imaging)., Results: We enrolled 67 patients with ALT-70 and thermal imaging data. The ALT-70 predictive model conferred the highest sensitivity (97.8%) and negative predictive value (90.9%), whereas combination testing had the highest specificity (71.4%) and positive predictive value (86.6%). The ALT-70 predictive model had improved classification measures compared with thermal imaging. Combination testing conferred a marginal benefit compared with the ALT-70 predictive model alone., Limitations: Single-center design may limit generalizability., Conclusion: The ALT-70 predictive model outperformed thermal imaging in diagnosing lower extremity cellulitis. The accuracy of the ALT-70 predictive model was high and consistent with its performance in previously published literature. Broad implementation of the ALT-70 predictive model in clinical practice may decrease the rates of misdiagnosis of lower extremity cellulitis., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Variations in treatment modalities for skin growths contribute substantially to overall healthcare spending within dermatology. However, little is known regarding factors impacting patient decision-making when choosing a treatment modality. In this survey-based, cross-sectional study (n = 375, 81.9% response rate), we asked patients to rate the importance of different treatment parameters for a nonfacial skin growth, further classified into five domains: efficacy, appearance, financial impact, visit duration, and productivity. Although patients generally prioritized treatment efficacy when selecting a treatment modality, they emphasized different aspects of the treatment experience as a function of age, gender, race, insurance status, and history of malignancy. Patients over age 50 were less likely to consider treatment impact on finances as being "important", but more so efficacy and visit duration. Women were more likely to value efficacy and appearance. Patients without private insurance were more likely to cite efficacy and impact on productivity as being "important". While the underlying reasons for these variations differ across patients, these findings help explain variations in treatment selection among patients choosing between treatments for skin growths and may ultimately lead to improved shared decision-making.

Background: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss. The lack of a definitive biomarker or formal diagnostic criteria for AA limits our ability to define the epidemiology of the disease. In this study, we developed and tested the Alopecia Areata Assessment Tool (ALTO) in an academic medical center to validate the ability of this questionnaire in identifying AA cases., Methods: The ALTO is a novel, self-administered questionnaire consisting of 8 closed-ended questions derived by the Delphi method. This prospective pilot study was administered during a 1-year period in outpatient dermatology clinics. Eligible patients (18 years or older with chief concern of hair loss) were recruited consecutively. No patients declined to participate. The patient's hair loss diagnosis was determined by a board-certified dermatologist. Nine scoring algorithms were created and used to evaluate the accuracy of the ALTO in identifying AA., Results: 239 patients (59 AA cases and 180 non-AA cases) completed the ALTO and were included for analysis. Algorithm 5 demonstrated the highest sensitivity (89.8%) while algorithm 3 demonstrated the highest specificity (97.8%). Select questions were also effective in clarifying disease phenotype., Conclusion: In this study. we have successfully demonstrated that ALTO is a simple tool capable of discriminating AA from other types of hair loss. The ALTO may be useful to identify individuals with AA within large populations., Competing Interests: The authors have declared that no competing interests exist.

Importance: Many inflammatory skin dermatoses mimic cellulitis (pseudocellulitis) and are treated with antibiotics and/or hospitalization, leading to unnecessary patient morbidity and substantial health care spending., Objective: To evaluate the impact of early dermatology consultation on clinical and economic outcomes associated with misdiagnosed cellulitis., Design, Setting, and Participants: This prospective cohort study enrolled patients with presumed diagnosis of cellulitis in the emergency department, in the emergency department observation unit, or within 24 hours of admission to an inpatient unit of a large urban teaching hospital between February and September 2017. Patients were provided with telephone and clinic follow-up during the 30-day postdischarge period. We screened 165 patients with the primary concern of cellulitis. Of these, we excluded 44 who required antibiotics for cutaneous, soft-tissue, and deeper-tissue and/or bone infections irrespective of cellulitis status, and 5 who were scheduled to be discharged by the emergency department., Interventions: Early dermatology consultation for presumed cellulitis., Main Outcomes and Measures: Primary outcomes were patient disposition and rates of antibiotic use., Results: Of 116 patients (63 [54.3%] women; 91 [78.4%] non-Hispanic white; mean [SD] age, 58.4 [19.1] years), 39 (33.6%) were diagnosed with pseudocellulitis by dermatologists. Of these, 34 (87.2%) had started using antibiotics for presumed cellulitis as prescribed by the primary team at the time of enrollment. The dermatology team recommended antibiotic discontinuation in 28 of 34 patients (82.4%), and antibiotics were stopped in 26 of 28 cases (92.9%). The dermatologists also recommended discharge from planned observation or inpatient admission in 20 of 39 patients with pseudocellulitis (51.3%), and the primary team acted on this recommendation in 17 of 20 cases (85.0%). No patients diagnosed with pseudocellulitis experienced worsening condition after discharge based on phone and clinic follow-up (30 of 39 [76.9%] follow-up rate). Extrapolating the impact of dermatology consultation for presumed cellulitis nationally, we estimate 97 000 to 256 000 avoided hospitalization days, 34 000 to 91 000 patients avoiding unnecessary antibiotic exposure, and $80 million to $210 million in net cost savings annually., Conclusions and Relevance: Early consultation by dermatologists for patients with presumed cellulitis represents a cost-effective intervention to improve health-related outcomes through the reduction of inappropriate antibiotic use and hospitalization.

Background: The risk of postoperative pyoderma gangrenosum (PG) in patients with a known history of PG is unknown., Objective: To quantify risk and identify patient- and/or procedure-related risk factors for postsurgical recurrence or exacerbation of PG in patients with a known history of PG., Methods: We retrospectively evaluated the likelihood of postsurgical recurrence or exacerbation of PG for all patients with a confirmed diagnosis of PG at Brigham and Women's Hospital and Massachusetts General Hospital from 2000 to 2015., Results: In all, 5.5% of procedures (n = 33) led to recurrence of PG in 15.1% of patients (n = 25). Compared with skin biopsy, small open surgical procedures had an adjusted odds ratio (aOR) of 8.65 (95% confidence interval [CI], 1.55-48.33) for PG recurrence or exacerbation; large open surgical procedures had an aOR of 5.97 (95% CI, 1.70-21.00); and Mohs micrographic surgery/skin excision had an aOR of 6.47 (95% CI, 1.77-23.61). PG chronically present at the time of the procedure had an aOR of 4.58 (95% CI, 1.72-12.22). Immunosuppression, time elapsed since the original PG diagnosis, and procedure location did not significantly influence risk., Limitations: Our study is limited by its retrospective nature and relatively small sample size., Conclusion: There is a small but clinically meaningful risk for postsurgical recurrence or exacerbation of PG in patients with a known history of PG; higher risks occur with more invasive procedures and chronically present PG., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Anetoderma is an elastolytic skindisorder that has been associated with the presenceof antiphospholipid antibodies (aPL). Patients withantiphospholipid antibody-positive anetoderma havebeen reported to develop symptoms of Graves disease,antiphospholipid syndrome, and other autoimmuneconditions. The temporal relationship, however,between anetoderma onset and the emergence ofaPL remains unclear, a clarification of which may haveimplications for the screening and monitoring ofpatients with anetoderma., Case: Herein we report acase of a patient with systemic lupus erythematosuspresenting with anetoderma that preceded thedevelopment of aPL. The patient was found to havesubsequently developed IgM cardiolipin antibodiesat a serology follow-up approximately two years later.Conclusion and Relevance: This finding suggests thatanetoderma can precede aPL seroconversion andthat patients with anetoderma may require continuedserology monitoring. Such long-term monitoring willbe important for identifying laboratory indicationsthat may portend the development of furtherautoimmune symptoms associated with anetoderma.

Importance: Though there have been significant shifts in US demographic data over the past 50 years, research cohorts lack full racial and ethnic representation. There is little data available regarding the diversity of dermatology research cohorts with respect to sex, race, and ethnicity., Objective: To characterize and assess the representation of racial and ethnic minorities and women in randomized controlled trials across a range of dermatologic conditions., Evidence Review: All randomized clinical trials (RCTs) were identified between July 2010 and July 2015 within the PubMed database using the following keywords: "psoriasis," "atopic dermatitis," "acne," "vitiligo," "seborrheic dermatitis," "alopecia areata," and "lichen planus." Diverse study populations were defined as including a greater than 20% racial or ethnic minority participants based on US census data. The distributions of sex and race groups in studies were compared by journal type, disease type, and funding source., Findings: Of the 626 articles reporting RCTs included in this analysis, 532 (85.0%) reported the sex of study participants. Overall, 52 of 626 international (11.3%) studies and 58 of 97 studies (59.8%) conducted exclusively within the United States reported on the racial or ethnic demographics of study participants. Across all RCTs exclusively recruited within the United States that reported race, 74.4% of study participants were white. Disease type was significantly associated with the degree of racial diversity (P < .001) within a study cohort: 30.0% of US-based psoriasis had more than 20% racially or ethnically diverse research participants as compared with 73.9% of acne studies and 91.7% of eczema studies., Conclusion and Relevance: Dermatologic clinical trials within the United States reflect the growing diversity of the US population. Reporting of both sex and racial/ethnic diversity of research cohorts is still lacking, especially among studies conducted outside of the United States.

Group B Streptococcus (GBS) is an asymptomatic colonizer of human mucosal surfaces that is responsible for sepsis and meningitis in neonates. Bacterial persistence and pathogenesis often involves biofilm formation. We previously showed that biofilm formation in medium supplemented with glucose is mediated by the PI-2a pilus. Here, biofilm formation was tested in cell culture medium supplemented with human plasma. GBS strains were able to form biofilms in these conditions unlike Group A Streptococcus (GAS) or Staphylococcus aureus. Analysis of mutants impaired for various surface components revealed that the GBS capsule is a key component in this process., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes., Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis., Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189)., Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.