Current State of Dermatology Mobile Applications With Artificial Intelligence Features.

Importance: With advancements in mobile technology and artificial intelligence (AI) methods, there has been a substantial surge in the availability of direct-to-consumer mobile applications (apps) claiming to aid in the assessment and management of diverse skin conditions. Despite widespread patient downloads, these apps exhibit limited evidence supporting their efficacy. Objective: To identify and characterize current English-language AI dermatology mobile apps available for download, focusing on aspects such as purpose, supporting evidence, regulatory status, clinician input, data privacy measures, and use of image data. Evidence Review: In this cross-sectional study, both Apple and Android mobile app stores were systematically searched for dermatology-related apps that use AI algorithms. Each app's purpose, target audience, evidence-based claims, algorithm details, data availability, clinician input during development, and data usage privacy policies were evaluated. Findings: A total of 909 apps were initially identified. Following the removal of 518 duplicates, 391 apps remained. Subsequent review excluded 350 apps due to nonmedical nature, non-English languages, absence of AI features, or unavailability, ultimately leaving 41 apps for detailed analysis. The findings revealed several concerning aspects of the current landscape of AI apps in dermatology. Notably, none of the apps were approved by the US Food and Drug Administration, and only 2 of the apps included disclaimers for the lack of regulatory approval. Overall, the study found that these apps lack supporting evidence, input from clinicians and/or dermatologists, and transparency in algorithm development, data usage, and user privacy. Conclusions and Relevance: This cross-sectional study determined that although AI dermatology mobile apps hold promise for improving access to care and patient outcomes, in their current state, they may pose harm due to potential risks, lack of consistent validation, and misleading user communication. Addressing challenges in efficacy, safety, and transparency through effective regulation, validation, and standardized evaluation criteria is essential to harness the benefits of these apps while minimizing risks.

Femoral neck stress fracture return to activity and the effect of metabolic dysfunction on recovery: A systematic review.

Background: Femoral neck stress fractures are rare fractures traditionally found in athletes and military personnel. There is limited literature on return to activity. Objectives: To report return to activity rates and times, and long-term outcomes for femoral neck stress fractures reported in the literature. To examine the effects of bone metabolic dysfunction and surgical management on return to activity following FNSF. Research design & methods: A systematic literature review of case reports and case series on adults with femoral neck stress fracture that were diagnosed by gross fracture line on X-ray or gold-standard diagnosis with MRI was conducted. Initial search was limited to articles published from January 1997 to Jan 2023 listed in Medline, Embase, and Scopus. Additional articles were manually added via search of retained paper sources. Patient demographics, fracture type, return to activity time, and surgical vs non-surgical treatment modality were collected. In addition, long-term outcomes and metabolic effects, if reported, were abstracted. Results: A total of 40 case reports or case series were retained. 123 stress fractures of the femoral neck from 103 patients were compiled. Of the 103 patients, data on return to activity at least one year following treatment was available for 53 patients. 71% (37/53) of those with long-term follow-up information returned to full pre-injury activity. 24% (13/53) at long-term follow-up had functional recovery but did not return to pre-injury activity due to residual pain. 4% (3/53) had disabling pain. Metabolic workup information was available for 36 patients. Conclusion: Long-term follow-up and return to activity information following FNSF treatment are not commonly reported. Based on the available data, outcomes appear benign with most returning to full activity. There is a clear need for standardization of follow-up periods and hip function measure after FNSF treatment. Additionally, a sizable proportion of FNSF occurred in a new population of low-activity individuals with abnormal bone metabolism, which warrants further exploration.

Pharmacokinetics of Orally Administered GS-441524 in Dogs.

Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury®) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations ~24-fold higher than the EC50 against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.

Why Great Mitotic Inhibitors Make Poor Cancer Drugs.

Chemotherapy is central to oncology, perceived to operate only on prolific cancerous tissue. Yet, many non-neoplastic tissues are more prolific compared with typical tumors. Chemotherapies achieve sufficient therapeutic windows to exert antineoplastic activity because they are prodrugs that are bioactivated in cancer-specific environments. The advent of precision medicine has obscured this concept, favoring the development of high-potency kinase inhibitors. Inhibitors of essential mitotic kinases exemplify this paradigm shift, but intolerable on-target toxicities in more prolific normal tissues have led to repeated failures in the clinic. Proliferation rates alone cannot be used to achieve cancer specificity. Here, we discuss integrating the cancer specificity of prodrugs from classical chemotherapeutics and the potency of mitotic kinase inhibitors to generate a class of high-precision cancer therapeutics.

Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.

Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of ENO1. Here, we describe the application of a nitroheterocycle phosphonoamidate pro-drug pair to capitalize on tumor hypoxia. This bioreducible prodrug exhibits greater-than 2-fold potency under hypoxic conditions compared to normoxia and exhibits robust stability in biological fluids. Our work provides strong in vitro proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition.