Antibiotic adherence in dermatologic surgery: a Multicenter prospective cohort study.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583-0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.

Epigenetic modulation through BET bromodomain inhibitors as a novel therapeutic strategy for progranulin-deficient frontotemporal dementia.

Frontotemporal dementia (FTD) is a debilitating neurodegenerative disorder with currently no disease-modifying treatment options available. Mutations in GRN are one of the most common genetic causes of FTD, near ubiquitously resulting in progranulin (PGRN) haploinsufficiency. Small molecules that can restore PGRN protein to healthy levels in individuals bearing a heterozygous GRN mutation may thus have therapeutic value. Here, we show that epigenetic modulation through bromodomain and extra-terminal domain (BET) inhibitors (BETi) potently enhance PGRN protein levels, both intracellularly and secreted forms, in human central nervous system (CNS)-relevant cell types, including in microglia-like cells. In terms of potential for disease modification, we show BETi treatment effectively restores PGRN levels in neural cells with a GRN mutation known to cause PGRN haploinsufficiency and FTD. We demonstrate that BETi can rapidly and durably enhance PGRN in neural progenitor cells (NPCs) in a manner dependent upon BET protein expression, suggesting a gain-of-function mechanism. We further describe a CNS-optimized BETi chemotype that potently engages endogenous BRD4 and enhances PGRN expression in neuronal cells. Our results reveal a new epigenetic target for treating PGRN-deficient forms of FTD and provide mechanistic insight to aid in translating this discovery into therapeutics.

Entropy for q-rung linear diophantine fuzzy hypersoft set with its application in MADM.

A notable advancement in fuzzy set theory is the q-rung linear diophantine fuzzy set. The soft set theory was expanded into the hypersoft set theory. By combining both the q-rung linear diophantine fuzzy set and hypersoft set, this study describes the notion of q-rung linear diophantine fuzzy hypersoft set that can handle multi sub-attributed q-rung linear diophantine fuzzy situations in the real world. Furthermore, some of its algebraic operations such as union, intersection and complement are described in this study. In addtion, the entropy measure of the q-rung linear diophantine fuzzy hypersoft set is established as it is helpful in determining the degree of fuzziness of q-rung linear diophantine fuzzy hypersoft sets. A multi-attribute decision making algorithm based on suggested entropy is presented in this study along with a numerical example of selecting a suitable wastewater treatment technology to demonstrate the effectiveness of the proposed algorithm in real-life situations. A comparative study was undertaken that describes the validity, robustness and superiority of the proposed algorithm and notions by discussing the advantages and drawbacks of existing theories and algorithms. Overall, this study describes a novel fuzzy extension that prevails over the existing ones and contributes to the real world with a valid real-life multi-attribute decision making algorithm that can cover many real-world problems that are unable to be addressed by the existing methodology.

Patient Preferences for Pain Control After Mohs Micrographic Surgery: A Single-Center Discrete Choice Experiment.

Importance: Patient preferences for pain medications after Mohs micrographic surgery are important to understand and have not been fully studied. Objective: To evaluate patient preferences for pain management with only over-the-counter medications (OTCs) or OTCs plus opioids after Mohs micrographic surgery given varying levels of theoretical pain and opioid addiction risk. Design, Setting, and Participants: This prospective discrete choice experiment was conducted in a single academic medical center from August 2021 to April 2022 among patients undergoing Mohs surgery and their accompanying support persons (≥18 years). A prospective survey was administered to all participants using the Conjointly platform. Data were analyzed from May 2022 to February 2023. Main outcome and measure: The primary outcome was the pain level at which half of the respondents chose OTCs plus opioids equally to only OTCs for pain management. This pain threshold was determined for varying opioid addiction risk profiles (low, 0%; low-moderate, 2%; moderate-high, 6%; high, 12%) and measured via a discrete choice experiment and linear interpolation of associated parameters (pain levels and risk of addiction). Results: Of the 295 respondents (mean [SD] age, 64.6 [13.1] years; 174 [59%] were female; race and ethnicity were not considered) who completed the discrete choice experiment, 101 (34%) stated that they would never consider opioids for pain management regardless of the pain level experienced, and 147 (50%) expressed concern regarding possible opioid addiction. Across all scenarios, 224 respondents (76%) preferred only OTCs vs OTCs plus opioids after Mohs surgery for pain control. When the theoretical risk of addiction was low (0%), half of the respondents expressed a preference for OTCs plus opioids given pain levels of 6.5 on a 10-point scale (90% CI, 5.7-7.5). At higher opioid addiction risk profiles (2%, 6%, 12%), an equal preference for OTCs plus opioids and only OTCs was not achieved. In these scenarios, patients favored only OTCs despite experiencing high levels of pain. Conclusion and relevance: The findings of this prospective discrete choice experiment indicate that the perceived risk of opioid addiction affects the patient's choice of pain medications after Mohs surgery. It is important to engage patients undergoing Mohs surgery in shared decision-making discussions to determine the optimal pain control plan for each individual. These findings may encourage future research on the risks associated with long-term opioid use after Mohs surgery.

Patient-Reported Nasal Function and Appearance After Interpolation Flap Repair Following Skin Cancer Resection: A Multicenter Prospective Cohort Study.

Objective: Among patients undergoing two-stage interpolated flap repair of nasal defects, nasal function, and appearance before surgery and at 16 weeks after flap takedown were compared using the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ). Design: Multicenter prospective cohort study. Methods: Adult patients with a nasal skin cancer anticipated to require two-stage interpolation flap repair completed the NAFEQ before surgery, at 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Results: One hundred sixty-nine patients were enrolled, with 138 patients completing both presurgical and 16-week post-takedown NAFEQs. Overall NAFEQ score increased by 1.09 points (1.91% improvement, confidence interval [95% CI -0.34 to 2.53]). NAFEQ functional subscale increased by 0.72 points (2.58% increase; 95% CI [0.10-1.35]) and appearance subscale increased by 0.37 points (1.28% improvement, 95% CI [-0.65 to 1.39]). Conclusion: At 16 weeks after flap takedown, patients' perceptions of their nasal function and appearance are similar to or slightly improved when compared with their presurgical assessments.

Artificial Neurons on Flexible Substrates: A Fully Printed Approach for Neuromorphic Sensing.

Printed electronic devices have demonstrated their applicability in complex electronic circuits. There is recent progress in the realization of neuromorphic computing systems (NCSs) to implement basic synaptic functions using solution-processed materials. However, a fully printed neuron is yet to be realised. We demonstrate a fully printed artificial neuromorphic circuit on flexible polyimide (PI) substrate. Characteristic features of individual components of the printed system were guided by the software training of the NCS. The printing process employs graphene ink for passive structures and In2O3 as active material to print a two-input artificial neuron on PI. To ensure a small area footprint, the thickness of graphene film is tuned to target a resistance and to obtain conductors or resistors. The sheet resistance of the graphene film annealed at 300 °C can be adjusted between 200 Ω and 500 kΩ depending on the number of printed layers. The fully printed devices withstand a minimum of 2% tensile strain for at least 200 cycles of applied stress without any crack formation. The area usage of the printed two-input neuron is 16.25 mm2, with a power consumption of 37.7 mW, a propagation delay of 1 s, and a voltage supply of 2 V, which renders the device a promising candidate for future applications in smart wearable sensors.

The think aloud paradigm reveals differences in the content, dynamics and conceptual scope of resting state thought in trait brooding.

Although central to well-being, functional and dysfunctional thoughts arise and unfold over time in ways that remain poorly understood. To shed light on these mechanisms, we adapted a "think aloud" paradigm to quantify the content and dynamics of individuals' thoughts at rest. Across two studies, external raters hand coded the content of each thought and computed dynamic metrics spanning duration, transition probabilities between affective states, and conceptual similarity over time. Study 1 highlighted the paradigm's high ecological validity and revealed a narrowing of conceptual scope following more negative content. Study 2 replicated Study 1's findings and examined individual difference predictors of trait brooding, a maladaptive form of rumination. Across individuals, increased trait brooding was linked to thoughts rated as more negative, past-oriented and self-focused. Longer negative and shorter positive thoughts were also apparent as brooding increased, as well as a tendency to shift away from positive conceptual states, and a stronger narrowing of conceptual scope following negative thoughts. Importantly, content and dynamics explained independent variance, accounting for a third of the variance in brooding. These results uncover a real-time cognitive signature of rumination and highlight the predictive and ecological validity of the think aloud paradigm applied to resting state cognition.

Rates of Opioid Prescriptions Obtained After Mohs Surgery: A Claims Database Analysis From 2009 to 2020.

IMPORTANCE: To curtail the opioid epidemic, physicians have been advised to limit opioid prescriptions. OBJECTIVE: To characterize the frequency and changes over time (2009-2020) of opioid prescriptions following Mohs micrographic surgery. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study using Optum Clinformatics DataMart (Optum CDM), a nationally representative insurance claims database, included patients aged 18 years and older who had Mohs micrographic surgery insurance claims in the Optum CDM database from 2009 to 2020. Data were analyzed from November 11, 2020, to March 30, 2021. EXPOSURES: Opioid prescription following Mohs surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery. Secondary outcomes included type and opioid quantity prescribed. RESULTS: Among 358 012 patients with Mohs micrographic surgery claims (mean [SD] age, 69 [13] years; 205 609 [57.4%] were men), the proportion of patients obtaining an opioid prescription after Mohs micrographic surgery increased from 2009 (34.6%) to 2011 (39.6%). This proportion then declined each year, reaching a low of 11.7% in 2020 (27.9% absolute decrease from 2011 to 2020). Hydrocodone, codeine, oxycodone, and tramadol were the 4 most commonly prescribed opioids. By 2020, hydrocodone was obtained less (2009: 47.5%; 2011: 67.1%; 2020: 45.4%; 21.7% absolute decrease from 2011 to 2020) and tramadol was obtained more (2009: 1.6%; 2020: 27.9%; 26.3% absolute increase from 2009 to 2020). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Mohs micrographic surgery claims, patients obtained fewer postsurgery opioid prescriptions over the study period, suggesting responsiveness of patients and dermatologic surgeons to public health concerns regarding the opioid epidemic. During this decline, prescriptions for hydrocodone decreased and tramadol increased.

High-content image-based analysis and proteomic profiling identifies Tau phosphorylation inhibitors in a human iPSC-derived glutamatergic neuronal model of tauopathy.

Mutations in MAPT (microtubule-associated protein tau) cause frontotemporal dementia (FTD). MAPT mutations are associated with abnormal tau phosphorylation levels and accumulation of misfolded tau protein that can propagate between neurons ultimately leading to cell death (tauopathy). Recently, a p.A152T tau variant was identified as a risk factor for FTD, Alzheimer's disease, and synucleinopathies. Here we used induced pluripotent stem cells (iPSC) from a patient carrying this p.A152T variant to create a robust, functional cellular assay system for probing pathophysiological tau accumulation and phosphorylation. Using stably transduced iPSC-derived neural progenitor cells engineered to enable inducible expression of the pro-neural transcription factor Neurogenin 2 (Ngn2), we generated disease-relevant, cortical-like glutamatergic neurons in a scalable, high-throughput screening compatible format. Utilizing automated confocal microscopy, and an advanced image-processing pipeline optimized for analysis of morphologically complex human neuronal cultures, we report quantitative, subcellular localization-specific effects of multiple kinase inhibitors on tau, including ones under clinical investigation not previously reported to affect tau phosphorylation. These results demonstrate the potential for using patient iPSC-derived ex vivo models of tauopathy as genetically accurate, disease-relevant systems to probe tau biochemistry and support the discovery of novel therapeutics for tauopathies.

Patient Quality of Life After Interpolated Flap Repair of Nasal Mohs Surgery Defects: A Multicenter Prospective Cohort Study.

IMPORTANCE: Single-center studies have shown that patients report better skin cancer-specific quality of life (QOL) after Mohs micrographic surgery (MMS), but it is unclear whether this improved QOL applies to patients after MMS and complex reconstruction in cosmetically sensitive areas. OBJECTIVE: To evaluate patient QOL after MMS and interpolation flap reconstruction for patients with nasal skin cancers. DESIGN, SETTING AND PARTICIPANTS: This multicenter prospective survey study used the Skin Cancer Index (SCI), a validated, 15-question QOL questionnaire administered at 4 time points: before MMS, 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Patients age 18 years or older with a nasal skin cancer who presented for MMS and were anticipated to undergo 2-stage interpolated flap repair by a Mohs surgeon were recruited from August 9, 2018, to February 2, 2020, at 8 outpatient MMS locations across the United States, including both academic centers and private practices. MAIN OUTCOMES AND MEASURES: Mean difference in overall SCI score before MMS vs 16 weeks after flap takedown. RESULTS: A total of 169 patients (92 men [54.4%]; mean [SD] age, 67.7 [11.4] years) were enrolled, with 147 patients (75 men [51.0%]; mean [SD] age, 67.8 [11.7] years) completing SCI surveys both before MMS and 16 weeks after flap takedown. Total SCI scores improved significantly 16 weeks after flap takedown compared with pre-MMS scores, increasing by a mean of 13% (increase of 7.11 points; 95% CI, 5.48-8.76; P < .001). All 3 SCI subscale scores (emotion, appearance, and social) improved significantly (emotion subscale, increase of 3.27 points; 95% CI, 2.35-4.18; P < .001; appearance subscale, increase of 1.65 points; 95% CI, 1.12-2.18; P < .001; and social subscale, increase of 2.10 points; 95% CI, 1.55-2.84; P < .001) 16 weeks after flap takedown compared with pre-MMS. CONCLUSIONS AND RELEVANCE: Removal of a nasal skin cancer and repair of the resulting defect can be distressing for patients. However, this cohort study suggests that physicians referring patients for MMS can be reassured that their patient's QOL will improve on average after surgery, even when a complex reconstruction is required.

Supporting Underrepresented in Medicine (UIM) and non-UIM Trainees Applying into Dermatology: A Qualitative Analysis.

BACKGROUND: Recently, there have been calls to improve diversity among the dermatology workforce, with emphasis placed on the resident selection process and trainee pipeline. However, there is limited data on the perspectives of dermatology applicants, especially among UIM trainees, and the support that they need and want to successfully apply in dermatology. METHODS: To assess trainee perspectives, we disseminated a survey to medical students, interns (matched into dermatology), and dermatology residents asking how dermatology residency programs can best support trainees through the dermatology application process. We developed a codebook drawing upon grounded theory methodology, and consensus coded all qualitative responses. RESULTS: We received 224 qualitative responses from underrepresented in medicine (UIM) (65, 29.0%) and non-UIM trainees (159, 70.9%). UIM trainees were more likely to mention diversity and inclusion initiatives (46.2% vs 3.8%, P<0.001), transparency in program information (40.0% vs 24.5%, P=0.021), holistic review (30.8% vs 6.3%, P<0.001), UIM student outreach/pipeline programs (23.1% vs 0.6%, P<0.001), and mentorship (21.5% vs 8.2%, P=0.009). CONCLUSION: Improving programmatic efforts to address unique challenges UIM trainees face when applying into dermatology is instrumental to mitigating barriers. We highlight opportunities for dermatology residency programs to create a more fair and equitable dermatology application process and support a more diverse pipeline of future dermatologists. J Drugs Dermatol. 2021;20(7):795-797. doi:10.36849/JDD.6043.