Distinct Features of Plasma Ultrashort Single-Stranded Cell-Free DNA as Biomarkers for Lung Cancer Detection.

BACKGROUND: Using broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection. METHODS: Using BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC). In comparison to mncfDNA, we assessed whether functional element (FE) peaks, fragmentomics, end-motifs, and G-Quadruplex (G-Quad) signatures could be useful features of uscfDNA for NSCLC determination. RESULTS: In noncancer participants, compared to mncfDNA, uscfDNA fragments showed a 45.2-fold increased tendency to form FE peaks (enriched in promoter, intronic, and exonic regions), demonstrated a distinct end-motif-frequency profile, and presented with a 4.9-fold increase in G-Quad signatures. Within NSCLC participants, only the uscfDNA population had discoverable FE peak candidates. Additionally, uscfDNA showcased different end-motif-frequency candidates distinct from mncfDNA. Although both cfDNA populations showed increased fragmentation in NSCLC, the G-Quad signatures were more discriminatory in uscfDNA. Compilation of cfDNA features using principal component analysis revealed that the first 5 principal components of both cfDNA subtypes had a cumulative explained variance of >80%. CONCLUSIONS: These observations indicate that the distinct biological processes of uscfDNA and that FE peaks, fragmentomics, end-motifs, and G-Quad signatures are uscfDNA features with promising biomarker potential. These findings further justify its exploration as a distinct class of biomarker to augment pre-existing liquid biopsy approaches.

Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.

Negative symptoms and cognitive deficits contribute strongly to disability in schizophrenia, and are resistant to existing medications. Recent drug development has targeted enhanced NMDA function by increasing mGluR2/3 signaling. However, the clinical utility of such agents remains uncertain, and markers of brain circuit function are critical for clarifying mechanisms and understanding individual differences in efficacy. We conducted a double-blind, placebo-controlled, randomized cross-over (14 day washout) pilot study evaluating adjunctive use of the mGluR2 positive allosteric modulator AZD8529 (80 mg daily for 3 days), in chronic stable patients with schizophrenia (n = 26 analyzed). We focused on 3 T fMRI response in frontostriatal regions during an n-back working memory task, testing the hypothesis that AZD8529 produces fMRI changes that correlate with improvement in negative symptoms and cognition. We found that AZD8529 did not produce significant group-average effects on symptoms or cognitive accuracy. However, AZD8529 did increase n-back fMRI activation in striatum (p < 0.0001) and anterior cingulate/paracingulate (p = 0.002). Greater drug-versus-placebo effects on caudate activation significantly correlated with greater reductions in PANSS negative symptom scores (r = -0.42, p = 0.031), and exploratory correlations suggested broader effects across multiple symptom domains and regions of interest. These findings demonstrate that fMRI responses to mGluR2 positive modulation relate to individual differences in symptom reduction, and could be pursued for future biomarker development. Negative clinical results at the group level should not lead to premature termination of investigation of this mechanism, which may benefit an important subset of individuals with schizophrenia. Imaging biomarkers may reveal therapeutic mechanisms, and help guide treatment toward specific populations.

Predictors of sentinel lymph node metastasis in very thin invasive melanomas.

BACKGROUND: Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients. OBJECTIVES: To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas. METHODS: The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses. RESULTS: Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively. CONCLUSIONS: Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB.

Treatment Options and Outcomes for Squamous Cell Carcinoma of the Nail Unit: A Systematic Review.

BACKGROUND: Nail squamous cell carcinoma (nSCC) is the most common nail unit malignancy. However, no studies to date have evaluated treatment options for nSCC based on recurrence data while controlling for invasion. OBJECTIVE: To identify temporal trends in nSCC treatment modalities and compare treatment outcomes based on invasion. METHODS AND MATERIALS: The authors performed a systematic review of articles published on PubMed, MEDLINE, and Scopus from inception to April 2020 reporting treatment of nSCC. The primary outcome was disease recurrence. RESULTS: Reports of nSCC treatments have increased in the past decade. Mohs micrographic surgery (MMS) is the most common treatment reported overall. The lowest recurrence rates for in situ nSCC were seen with wide surgical excision (WSE) and MMS. For invasive disease, the recurrence rates were lowest with amputation, MMS, and WSE. CONCLUSION: Complete surgical excision of nSCC with either WSE or MMS is associated with lower recurrence rates than limited excision and nonsurgical therapies, regardless of degree of invasion. The prognostic significance of in situ versus invasive disease remains unclear. Confirmation of complete excision may improve outcomes. Digital amputation is indicated for nSCC with bone invasion. Prospective studies and randomized controlled trials are needed to directly compare surgical modalities for nSCC.

Delayed medical care due to transportation barriers among US children with atopic dermatitis.

Our objective was to examine the prevalence and predictors of delayed medical care due to transportation barriers among children with atopic dermatitis (AD) living in the United States (US). We analyzed data from the 1998-2018 National Health Interview Survey, a nationally representative survey of US households. In 2018, transport-delayed care was reported for 3.4% of US children with AD, representing approximately 279,000 children annually given the National Health Interview Survey's weighted survey design, and was more common among patients of lower socioeconomic status. Targeted interventions aimed at reducing transportation barriers to healthcare among at-risk AD patients may reduce health disparities related to AD.

A Multimetric Readability Analysis of Online Patient Educational Materials for Submental Fat Reduction.

BACKGROUND: Patients often utilize the Internet to seek information related to their care. This study assesses the readability of online patient educational materials for submental fat reduction. METHODS: Patient educational materials from the 12 most popular websites related to submental fat reduction were downloaded and assessed for readability grade level using 10 unique scales. RESULTS: Analysis of the 12 most popular websites (and corresponding 47 articles) revealed that patient educational materials were written, on average, at an 11th grade reading level. The Flesch Reading Ease score was 48.9 (range 39.8-59.2), representing a "difficult" level of reading. Mean readability grade levels (range 9-13th grade for individual websites) were as follows: Coleman-Liau, 11.1; Flesch-Kincaid, 10.8; FORCAST, 10.8; Fry Graph, 10.1; Gunning Fog, 12.7; New Dale-Chall, 10.1; New Fog Count, 11.8; Simple Measure of Gobbledygook, 11.7; Raygor, 6.7. No website was at the 6th grade reading level for patient educational materials recommended by the American Medical Association and National Institutes of Health. CONCLUSIONS: Online patient educational materials for submental fat reduction are written well above the recommended reading level. Recognition of disparities in health literacy is necessary to enable patients to make informed decisions and become active participants in their own care. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

Labiaplasty: Analysis of the National Surgical Quality Improvement Program Database.

BACKGROUND: Labiaplasty is an increasingly popular procedure performed for both cosmetic and pathologic etiologies. Questions have been raised regarding the efficacy of the procedure, especially for cosmetic etiologies. OBJECTIVES: The aim of this study was to examine the complication profiles of labiaplasties for both cosmetic and pathologic etiologies. METHODS: The 2005 to 2017 National Surgical Quality Improvement Program database was analyzed for patients who, according to the relevant Current Procedural Terminology code, had undergone labiaplasties. Our cohort was further separated into cosmetic and pathologic groups based on International Classification of Diseases codes. Information was collected on patient demographic characteristics, patient comorbidities, and operative variables. Outcomes of interest included surgical complications and delayed length of stay (DLOS). A univariate analysis and multivariate logistic regression were applied to determine statistically significant predictors of our outcomes of interest for both etiologies. RESULTS: There were 640 patients in the cosmetic cohort and 1919 patients in the pathologic cohort. There were no significant differences in rates of surgical complications between the 2 groups, but there was a statistically significant increase in length of stay for the pathologic group. Univariate analysis revealed operative time and plastic surgeon specialty to be predictive of DLOS in the cosmetic cohort. No covariates were implicated with multivariate analysis for either surgical complications or for DLOS in the cosmetic cohort. CONCLUSIONS: Our findings suggest that cosmetic labiaplasty is a safe and efficacious procedure with low complication rates and no predictors of adverse outcomes.

Tumor primary site as a prognostic factor for Merkel cell carcinoma disease-specific death.

BACKGROUND: Merkel cell carcinoma (MCC) primary site has not been fully investigated as a potential prognostic factor. OBJECTIVE: To determine the incidence by tumor primary site of death due to MCC. METHODS: We undertook a retrospective analysis of the Survival, Epidemiology, and End Results database. MCC patients treated between 1973 and 2016 were grouped by tumor primary site and a competing risks analysis was performed to test the impact of primary site on disease-specific death. Cumulative incidence of Merkel cell carcinoma-specific mortality (CMMI) at 5 years was estimated for each primary site. RESULTS: Of 9407 MCC patients identified, 6305 (67.0%) had localized disease, 2397 (25.5%) had regional metastasis, and 705 (7.5%) had distant metastasis. Tumor primary site was predictive of CMMI and varied by stage at diagnosis. Tumors involving the scalp/neck carried the highest CMMI among localized MCC (26.0%). Tumors involving the lip had the highest CMMI among MCC with regional metastasis (56.7%) and distant metastasis (82.1%). LIMITATIONS: Tumor size data were missing for a large proportion of patients, precluding stratification by stage according to current American Joint Committee on Cancer guidelines. CONCLUSIONS: Probability of MCC disease-specific death varies by primary site. The primary site of the tumor may be useful as a prognostic indicator for MCC.

Acne and social media: A cross-sectional study of content quality on TikTok.

Our objective was to assess the quality of acne-related medical information present on TikTok, the world's fastest growing social media platform. We queried the TikTok mobile application for videos tagged with "#acne" on May 1, 2020, and assessed the top 100 videos meeting inclusion criteria for content quality using DISCERN, a validated and reliable instrument for evaluating consumer health information. The mean content quality rating of videos was 2.03 (SD 0.47) which, according to the DISCERN instrument, indicates information with serious to potentially important shortcomings. Dermatologists should be aware that adolescents are using TikTok to gather acne-related information, and should prioritize acne education in this patient demographic due to the generally low content quality of such information.

Customizable live-cell imaging chambers for multimodal and multiplex fluorescence microscopy.

Using multiple imaging modalities while performing independent experiments in parallel can greatly enhance the throughput of microscopy-based research, but requires the provision of appropriate experimental conditions in a format that meets the optical requirements of the microscope. Although customized imaging chambers can meet these challenges, the difficulty of manufacturing custom chambers and the relatively high cost and design inflexibility of commercial chambers has limited the adoption of this approach. Herein, we demonstrate the use of 3D printing to produce inexpensive, customized, live-cell imaging chambers that are compatible with a range of imaging modalities, including super-resolution microscopy. In this approach, biocompatible plastics are used to print imaging chambers designed to meet the specific needs of an experiment, followed by adhesion of the printed chamber to a glass coverslip, producing a chamber that is impermeant to liquids and that supports the growth and imaging of cells over multiple days. This approach can also be used to produce moulds for casting microfluidic devices made of polydimethylsiloxane. The utility of these chambers is demonstrated using designs for multiplex microscopy, imaging under shear, chemotaxis, and general cellular imaging. Together, this approach represents an inexpensive yet highly customizable approach for producing imaging chambers that are compatible with modern microscopy techniques.