Ethics of artificial intelligence in dermatology.

The integration of artificial intelligence (AI) in dermatology holds promise for enhancing clinical accuracy, enabling earlier detection of skin malignancies, suggesting potential management of skin lesions and eruptions, and promoting improved continuity of care. AI implementation in dermatology, however, raises several ethical concerns. This review explores the current benefits and challenges associated with AI integration, underscoring ethical considerations related to autonomy, informed consent, and privacy. We also examine the ways in which beneficence, nonmaleficence, and distributive justice may be impacted. Clarifying the role of AI, striking a balance between security and transparency, fostering open dialogue with our patients, collaborating with developers of AI, implementing educational initiatives for dermatologists and their patients, and participating in the establishment of regulatory guidelines are essential to navigating ethical and responsible AI incorporation into dermatology.

Photodynamic Therapy in Treating a Subset of Basal Cell Carcinoma: Strengths, Shortcomings, Comparisons with Surgical Modalities, and Potential Role as Adjunctive Therapy.

Basal cell carcinoma (BCC) is the most common skin cancer, for which there are multiple treatment options, including the gold standard Mohs micrographic surgery (MMS), surgical excision, electrodesiccation and curettage, radiation therapy, cryosurgery, and photodynamic therapy (PDT). While PDT is currently approved for treating actinic keratosis, it has been used off-label to treat BCC patients who may not tolerate surgery or other treatment modalities. We present a review of the efficacy of these modalities and describe important considerations that affect the usage of PDT and MMS. ALA-PDT and MAL-PDT are both efficacious treatment options for lower-risk BCC that can serve as non-invasive alternatives to surgical excision with favorable cosmetic outcomes in patients unsuitable to undergo surgery. In particular, PDT may be considered an adjuvant for the prevention and treatment of BCC lesions in patients with some genetic syndromes such as Gorlin syndrome, and in combination with surgical excision in lesions presenting in certain locations. Limitations to PDT include lack of margin control to prevent recurrence, pain, and cost of certain photosensitizers. Future studies should investigate the role of PDT as adjunctive therapy, standardization of protocols, and causes and ways to address recurrence following PDT treatment.

Improved Electrochemical Performance in an Exfoliated Tetracyanonickelate-Based Metal-Organic Framework.

Tetracyanonickelate (TCN)-based metal-organic frameworks (MOFs) show great potential in electrochemical applications such as supercapacitors due to their layered morphology and tunable structure. This study reports on improved electrochemical performance of exfoliated manganese tetracyanonickelate (Mn-TCN) nanosheets produced by the heat-assisted liquid-phase exfoliation (LPE) technique. The structural change was confirmed by the Raman frequency shift of the C≡N band from 2177 to 2182 cm-1 and increased band gap from 3.15 to 4.33 eV in the exfoliated phase. Statistical distribution obtained from atomic force microscopy (AFM) shows that 50% of the nanosheets are single-to-four-layered and have an average lateral size of ∼240 nm2 and thickness of ∼1.2-4.8 nm. High-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) patterns suggest that the material maintains its crystallinity after exfoliation. It exhibits an almost 6-fold improvement in specific capacitance (from 13.0 to 72.5 F g-1) measured at a scan rate of 5 mV s-1 in 1 M KOH solution. Galvanostatic charge-discharge (GCD) measurement shows a capacity enhancement from ∼18 F g-1 in the bulk phase to ∼45 F g-1 in the exfoliated phase at a current density of 1 A g-1. Bulk crystals exhibit an increasing trend of capacitance retention by ∼125% over 1000 charge-discharge cycles attributed to electrochemical exfoliation. Electrochemical impedance spectroscopy (EIS) demonstrates a 5-fold reduction in the total equivalent series resistance (ESR) from 4864 Ω (bulk) to 1089 Ω (exfoliated). The enhanced storage capacity in the exfoliated phase results from the combined effect of the electrochemical double-layer charge storage mechanism at the nanosheet-electrolyte interface and the Faradic process characteristic of the pseudocapacitive charge storage behavior.

Potential mechanisms of multimodal prehabilitation effects on surgical complications: a narrative review.

Continuous advances in prehabilitation research over the past several decades have clarified its role in improving preoperative risk factors, yet the evidence demonstrating reduced surgical complications remains uncertain. Describing the potential mechanisms underlying prehabilitation and surgical complications represents an important opportunity to establish biological plausibility, develop targeted therapies, generate hypotheses for future research, and contribute to the rationale for implementation into the standard of care. In this narrative review, we discuss and synthesize the current evidence base for the biological plausibility of multimodal prehabilitation to reduce surgical complications. The goal of this review is to improve prehabilitation interventions and measurement by outlining biologically plausible mechanisms of benefit and generating hypotheses for future research. This is accomplished by synthesizing the available evidence for the mechanistic benefit of exercise, nutrition, and psychological interventions for reducing the incidence and severity of surgical complications reported by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). This review was conducted and reported in accordance with a quality assessment scale for narrative reviews. Findings indicate that prehabilitation has biological plausibility to reduce all complications outlined by NSQIP. Mechanisms for prehabilitation to reduce surgical complications include anti-inflammation, enhanced innate immunity, and attenuation of sympathovagal imbalance. Mechanisms vary depending on the intervention protocol and baseline characteristics of the sample. This review highlights the need for more research in this space while proposing potential mechanisms to be included in future investigations.

Lateral mammillary body neurons in mouse brain are disproportionately vulnerable in Alzheimer's disease.

The neural circuits governing the induction and progression of neurodegeneration and memory impairment in Alzheimer's disease (AD) are incompletely understood. The mammillary body (MB), a subcortical node of the medial limbic circuit, is one of the first brain regions to exhibit amyloid deposition in the 5xFAD mouse model of AD. Amyloid burden in the MB correlates with pathological diagnosis of AD in human postmortem brain tissue. Whether and how MB neuronal circuitry contributes to neurodegeneration and memory deficits in AD are unknown. Using 5xFAD mice and postmortem MB samples from individuals with varying degrees of AD pathology, we identified two neuronal cell types in the MB harboring distinct electrophysiological properties and long-range projections: lateral neurons and medial neurons. lateral MB neurons harbored aberrant hyperactivity and exhibited early neurodegeneration in 5xFAD mice compared with lateral MB neurons in wild-type littermates. Inducing hyperactivity in lateral MB neurons in wild-type mice impaired performance on memory tasks, whereas attenuating aberrant hyperactivity in lateral MB neurons ameliorated memory deficits in 5xFAD mice. Our findings suggest that neurodegeneration may be a result of genetically distinct, projection-specific cellular dysfunction and that dysregulated lateral MB neurons may be causally linked to memory deficits in AD.

Vancomycin area under the curve/minimum inhibitory concentration and trough level concordance-evaluation on an urban health unit.

Background: A vancomycin AUC/MIC (area under the curve/minimum inhibitory concentration) of 400-600 mg•h/L is associated with improved clinical outcomes for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. Currently, there are still limited studies evaluating the relationship between vancomycin trough and AUC. Objectives: To evaluate the correlation between vancomycin trough and AUC/MIC and determine if trough-guided monitoring is an adequate predictor of AUC/MIC in the Urban Health population at St Paul's Hospital. Methods: This was a retrospective chart review of 29 patients from November 2019 to February 2021. Patient demographics and laboratory data were collected from electronic medical records. The two-level equation-based approach was used to calculate AUC/MIC. The proportion of AUC/MIC values within target (400-600 mg•h/L) despite subtherapeutic troughs, and the proportion of AUC/MIC values supratherapeutic when trough is within target (15-20 mg/L) were the primary endpoints. Main Results: Fifty-seven sets of levels were collected and 75% of vancomycin troughs and AUC24 were found to be discordant. When trough was 10-14.9 mg/L, AUC24 was > 400 mg•h/L in 94% of cases and when trough was 15-20 mg/L, AUC24 was > 600 mg•h/L in 69% of cases. There was a moderate correlation between vancomycin trough and AUC24h (R 2 = 0.57; p < 0.001). Conclusion: A vancomycin trough between 15 and 20 mg/L may result in an AUC/MIC greater than necessary for clinical efficacy. Considering these findings and the practical concerns of AUC-guided monitoring, a modest reduction in target troughs to prevent vancomycin toxicity warrants clinical consideration and further evaluation.

Senescence mechanisms and targets in the heart.

Cellular senescence is a state of irreversible cell cycle arrest associated with ageing. Senescence of different cardiac cell types can direct the pathophysiology of cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and cardiac fibrosis. While age-related telomere shortening represents a major cause of replicative senescence, the senescent state can also be induced by oxidative stress, metabolic dysfunction, and epigenetic regulation, among other stressors. It is critical that we understand the molecular pathways that lead to cellular senescence and the consequences of cellular senescence in order to develop new therapeutic approaches to treat CVD. In this review, we discuss molecular mechanisms of cellular senescence, explore how cellular senescence of different cardiac cell types (including cardiomyocytes, cardiac endothelial cells, cardiac fibroblasts, vascular smooth muscle cells, and valve interstitial cells) can lead to CVD, and highlight potential therapeutic approaches that target molecular mechanisms of cellular senescence to prevent or treat CVD.

Multifaceted Regulation of Akt by Diverse C-Terminal Post-translational Modifications.

Akt is a Ser/Thr protein kinase that regulates cell growth and metabolism and is considered a therapeutic target for cancer. Regulation of Akt by membrane recruitment and post-translational modifications (PTMs) has been extensively studied. The most well-established mechanism for cellular Akt activation involves phosphorylation on its activation loop on Thr308 by PDK1 and on its C-terminal tail on Ser473 by mTORC2. In addition, dual phosphorylation on Ser477 and Thr479 has been shown to activate Akt. Other C-terminal tail PTMs have been identified, but their functional impacts have not been well-characterized. Here, we investigate the regulatory effects of phosphorylation of Tyr474 and O-GlcNAcylation of Ser473 on Akt. We use expressed protein ligation as a tool to produce semisynthetic Akt proteins containing phosphoTyr474 and O-GlcNAcSer473 to dissect the enzymatic functions of these PTMs. We find that O-GlcNAcylation at Ser473 and phosphorylation at Tyr474 can also partially increase Akt's kinase activity toward both peptide and protein substrates. Additionally, we performed kinase assays employing human protein microarrays to investigate global substrate specificity of Akt, comparing phosphorylated versus O-GlcNAcylated Ser473 forms. We observed a high similarity in the protein substrates phosphorylated by phosphoSer473 Akt and O-GlcNAcSer473 Akt. Two Akt substrates identified using microarrays, PPM1H, a protein phosphatase, and NEDD4L, an E3 ubiquitin ligase, were validated in solution-phase assays and cell transfection experiments.

Bitbow Enables Highly Efficient Neuronal Lineage Tracing and Morphology Reconstruction in Single Drosophila Brains.

Identifying the cellular origins and mapping the dendritic and axonal arbors of neurons have been century old quests to understand the heterogeneity among these brain cells. Current Brainbow based transgenic animals take the advantage of multispectral labeling to differentiate neighboring cells or lineages, however, their applications are limited by the color capacity. To improve the analysis throughput, we designed Bitbow, a digital format of Brainbow which exponentially expands the color palette to provide tens of thousands of spectrally resolved unique labels. We generated transgenic Bitbow Drosophila lines, established statistical tools, and streamlined sample preparation, image processing, and data analysis pipelines to conveniently mapping neural lineages, studying neuronal morphology and revealing neural network patterns with unprecedented speed, scale, and resolution.

Comparing the reporting and conduct quality of exercise and pharmacological randomised controlled trials: a systematic review.

OBJECTIVE: Evaluate the quality of exercise randomised controlled trial (RCT) reporting and conduct in clinical populations (ie, adults with or at risk of chronic conditions) and compare with matched pharmacological RCTs. DESIGN: Systematic review. DATA SOURCES: Embase (Elsevier), PubMed (NLM) and CINAHL (EBSCO). STUDY SELECTION: RCTs of exercise in clinical populations with matching pharmacological RCTs published in leading clinical, medical and specialist journals with impact factors ≥15. REVIEW METHODS: Overall RCT quality was evaluated by two independent reviewers using three research reporting guidelines (ie, Consolidated Standards of Reporting Trials (CONSORT; pharmacological RCTs)/CONSORT for non-pharmacological treatments; exercise RCTs), CONSORT-Harms, Template for Intervention Description and Replication) and two risk of bias assessment (research conduct) tools (ie, Cochrane Risk of Bias, Jadad Scale). We compared research reporting and conduct quality within exercise RCTs with matched pharmacological RCTs, and examined factors associated with quality in exercise and pharmacological RCTs, separately. FINDINGS: Forty-eight exercise RCTs (11 658 patients; median sample n=138) and 48 matched pharmacological RCTs were evaluated (18 501 patients; median sample n=160). RCTs were conducted primarily in cardiovascular medicine (43%) or oncology (31%). Overall quality score (composite of all research reporting and conduct quality scores; primary endpoint) for exercise RCTs was 58% (median score 46 of 80; IQR: 39-51) compared with 77% (53 of 68; IQR: 47-58) in the matched pharmacological RCTs (p≤0.001). Individual quality scores for trial reporting and conduct were lower in exercise RCTs compared with matched pharmacological RCTs (p≤0.03). Factors associated with higher overall quality scores for exercise RCTs were journal impact factor (≥25), sample size (≥152) and publication year (≥2013). CONCLUSIONS AND RELEVANCE: Research reporting and conduct quality within exercise RCTs is inferior to matched pharmacological RCTs. Suboptimal RCT reporting and conduct impact the fidelity, interpretation, and reproducibility of exercise trials and, ultimately, implementation of exercise in clinical populations. PROSPERO REGISTRATION NUMBER: CRD42018095033.

COVID-19 vaccine trust among clients in a sample of California residential substance use treatment programs.

BACKGROUND: Individuals with a substance use disorder (SUD) are at a significantly higher risk for coronavirus disease-19 (COVID-19) and have higher rates of COVID-19 related hospitalization and death than those without SUD. This study assessed COVID-19 vaccine trust, transmission awareness, risk and protective behaviors, and effects of COVID-19 on mental health and smoking among a sample of clients in California residential SUD treatment programs and identified factors associated with vaccine trust. METHODS: A multi-site sample of SUD treatment clients (n = 265) completed a cross-sectional survey. Multivariable logistic regression was used to identify factors associated with COVID-19 vaccine trust. RESULTS: Participants were predominantly male (82.3 %) and racially/ethnically diverse (33.3 % Non-Hispanic White). Most participants were aware of COVID-19 modes of transmission, however, only 39.5 % trusted a COVID-19 vaccine would be safe and effective. Factors independently associated with trust in a COVID-19 vaccine included age (AOR = 1.03, 95 % CI = 1.02, 1.05, p = 0.0001) and wearing a mask all the time (AOR = 2.48, 95 % CI = 1.86, 3.31, p = 0.0001). African Americans were less likely than White participants to trust that a COVID-19 vaccine is safe and effective (AOR = 0.41, 95 % CI = 0.23, 0.70, p = 0.001). CONCLUSION: SUD treatment clients were aware of COVID-19 modes of transmission; however, fewer than half trusted that a COVID-19 vaccine would be safe and effective. Health communication about COVID-19 for people with SUD should use a multipronged approach to address COVID-19 vaccine mistrust and transmission risk behaviors.

Synthesis of Printable Polyvinyl Alcohol for Aerosol Jet and Inkjet Printing Technology.

Polyvinyl Alcohol (PVA) is a promising polymer due to its high solubility with water, availability in low molecular weight, having short polymer chain, and cost-effectiveness in processing. Printed technology is gaining popularity to utilize processible solution materials at low/room temperature. This work demonstrates the synthesis of PVA solution for 2.5% w/w, 4.5% w/w, 6.5% w/w, 8.5% w/w and 10.5% w/w aqueous solution was formulated. Then the properties of the ink, such as viscosity, contact angle, surface tension, and printability by inkjet and aerosol jet printing, were investigated. The wettability of the ink was investigated on flexible (Kapton) and non-flexible (Silicon) substrates. Both were identified as suitable substrates for all concentrations of PVA. Additionally, we have shown aerosol jet printing (AJP) and inkjet printing (IJP) can produce multi-layer PVA structures. Finally, we have demonstrated the use of PVA as sacrificial material for micro-electro-mechanical-system (MEMS) device fabrication. The dielectric constant of printed PVA is 168 at 100 kHz, which shows an excellent candidate material for printed or traditional transistor fabrication.

High Permeability Photosintered Strontium Ferrite Flexible Thin Films.

The paper is focused on the development and optimization of strontium ferrite nanomaterial and photosintered flexible thin films. These magnetic thin films are characterized with direct current (DC) and high frequency measurements. For photosintered strontium ferrite samples, we achieved relative complex permeability of about 29.5-j1.8 and relative complex permittivity of about 12.9-j0.3 at a frequency of 5.9 GHz.

Emerging Approaches to Functionalizing Cell Membrane-Coated Nanoparticles.

There has been significant interest in developing cell membrane-coated nanoparticles due to their unique abilities of biomimicry and biointerfacing. As the technology progresses, it becomes clear that the application of these nanoparticles can be drastically broadened if additional functions beyond those derived from the natural cell membranes can be integrated. Herein, we summarize the most recent advances in the functionalization of cell membrane-coated nanoparticles. In particular, we focus on emerging methods, including (1) lipid insertion, (2) membrane hybridization, (3) metabolic engineering, and (4) genetic modification. These approaches contribute diverse functions in a nondisruptive fashion while preserving the natural function of the cell membranes. They also improve on the multifunctional and multitasking ability of cell membrane-coated nanoparticles, making them more adaptive to the complexity of biological systems. We hope that these approaches will serve as inspiration for more strategies and innovations to advance cell membrane coating technology.

Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics.

The adenosine analogue remdesivir has emerged as a front-line antiviral treatment for SARS-CoV-2, with preliminary evidence that it reduces the duration and severity of illness1.Prior clinical studies have identified adverse events1,2, and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments7, yet little is known about the specific genetic pathways involved in cellular remdesivir metabolism and cytotoxicity. Through genome-wide CRISPR-Cas9 screening and RNA sequencing, we show that remdesivir treatment leads to a repression of mitochondrial respiratory activity, and we identify five genes whose loss significantly reduces remdesivir cytotoxicity. In particular, we show that loss of the mitochondrial nucleoside transporter SLC29A3 mitigates remdesivir toxicity without a commensurate decrease in SARS-CoV-2 antiviral potency and that the mitochondrial adenylate kinase AK2 is a remdesivir kinase required for remdesivir efficacy and toxicity. This work elucidates the cellular mechanisms of remdesivir metabolism and provides a candidate gene target to reduce remdesivir cytotoxicity.