Purpose Sleep aids derived from traditional plant medicines are strong candidates for safely improving insomnia but require wider validation in patient populations. Methods We conducted an open label trial of the impact of a compound, Sip2Sleep ® , containing Montmorency tart cherry ( prunus cerasus ) extract and Venetron ® ( apocynum venetum ) on subjective sleep quality, subjective daytime alertness, sleep duration, sleep latency, anxiety, and insomnia in 43 adults with moderate to severe insomnia. Participants collected data over four weeks, with the sleep aid consumed prior to bed during weeks two and four. Results The Montmorency tart cherry and Venetron ® mixture statistically improved subjective sleep quality, daytime alertness, insomnia symptoms, and anxiety without impacting sleep duration and latency. Subjective improvements in sleep quality exhibited a statistical upward trend across the entire study window, suggesting potential persistence of the compounds days after consumption and greater improvement with longer-term consumption. Conclusions The combination of Montmorency tart cherry and Venetron ® in this commercially available tincture is a promising sleep aid warranting further investigation in larger trials. ### Competing Interest Statement RPP is the founder/CEO of (Lakshmi Nutraceuticals LLC), the maker of Sip2Sleep and an expert sleep physician. He contributed to study design and manuscript review and was not involved in the preparation of results. All other authors are employed by People Science Inc., a contract research & participatory research organization that conducts trials of alternative and adjunctive therapies. ### Clinical Trial NCT06299488 ### Clinical Protocols ### Funding Statement This study was funded by Lakshmi Nutraceuticals. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study and all procedures were approved by the Advarra Institutional Review Board (IRB) under Pro00068483. All participants gave informed consent. All research was performed in accordance with relevant guidelines and regulations. This protocol was registered at [clinicaltrials.gov][1] under [NCT06299488][2], 07/03/2024. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06299488&atom=%2Fmedrxiv%2Fearly%2F2024%2F04%2F25%2F2024.04.24.24306307.atom

Supplementary Figure 1 from A Critical Role for GRP78/BiP in the Tumor Microenvironment for Neovascularization during Tumor Growth and Metastasis

Supplementary Tables 1-2 from Enhanced Antitumor Activity Induced by Adoptive T-Cell Transfer and Adjunctive Use of the Histone Deacetylase Inhibitor LAQ824

Supplementary Figure Legend from A Critical Role for GRP78/BiP in the Tumor Microenvironment for Neovascularization during Tumor Growth and Metastasis

Background CJM112 is a potent anti-IL-17A monoclonal antibody, whose clinical efficacy in psoriasis was recently documented. This study aimed to assess the effect of IL-17A blockade, using CJM112, in patients with moderate to severe acne.Methods A randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study was conducted on patients with moderate to severe acne. Patients received CJM112 300 mg, 75 mg, or placebo subcutaneously during Treatment Period 1 (0–12 weeks). Patients receiving placebo were re-randomized to receive CJM112 300 mg or 75 mg during Treatment Period 2 (12–24 weeks). The primary endpoint was the number of inflammatory facial lesions at Week 12.Results As the futility criterion was met during the interim analysis, only 52/75 (69.3%) patients were recruited. In total, 48/52 (92.3%) and 26/41 (63.4%) completed Treatment Periods 1 and 2, respectively. All groups exhibited a reduction in facial inflammatory lesions, with no difference observed between CJM112 and placebo (CJM112 300 mg 27.6 ± 20.7; CJM112 75 mg 30.4 ± 34.8; placebo 23.6 ± 13.6; primary endpoint). Additionally, no differences were observed between groups in other secondary and exploratory endpoints at Week 12.Conclusions Anti-IL-17A therapy was not significantly different compared to the placebo in reducing inflammatory lesions in patients with moderate to severe acne.

To the Editor: Atopic dermatitis (AD) profoundly affects quality of life because of unrelenting pruritus, sleep disturbance, infections, and stigma.1,2 Treatment options are limited. Telemedicine-enabled, decentralized clinical trials may accelerate clinical trials and bring new treatments to market faster.3 To use these tools with confidence, it is important to ensure that telemedicine-based clinical outcome assessments are scientifically reliable in comparison with conventional in-person assessments.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.

Importance:Teledermatology has undergone exponential growth in the past 2 decades. Many technological innovations are becoming available without necessarily undergoing validation studies for specific dermatologic applications.Objective:To determine whether patient-taken photographs of acne using Network Oriented Research Assistant (NORA) result in similar lesion counts and Investigator's Global Assessment (IGA) findings compared with in-person examination findings.Design, Setting, and Participants:This pilot reliability study enrolled consecutive patients with acne vulgaris from a single general dermatology practice in Los Angeles, California, who were able to use NORA on an iPhone 6 to take self-photographs. Patients were enrolled from January 1 through March 31, 2016. Each individual underwent in-person and digital evaluation of his or her acne by the same dermatologist. A period of at least 1 week separated the in-person and digital assessments of acne.Interventions:All participants were trained on how to use NORA on the iPhone 6 and take photographs of their face with the rear-facing camera.Main Outcomes and Measures:Reliability of patient-taken photographs with NORA for acne evaluation compared with in-person examination findings. Acne assessment measures included lesion count (total, inflammatory, noninflammatory, and cystic) and IGA for acne severity.Results:A total of 69 patients (37 male [54%] and 32 female [46%]; mean [SD] age, 22.7 [7.7] years) enrolled in the study. The intraclass correlation coefficients of in-person and photograph-based acne evaluations indicated strong agreement. The intraclass correlation coefficient for total lesion count was 0.81; for the IGA, 0.75. Inflammatory lesion count, noninflammatory lesion count, and cyst count had intraclass correlation coefficients of 0.72, 0.72, and 0.82, respectively.Conclusions and Relevance:This study found agreement between acne evaluations performed in person and from self-photographs with NORA. As a reliable telehealth technology for acne, NORA can be used as a teledermatology platform for dermatology research and can increase access to dermatologic care.

Background . Mobile medical software applications (apps) are used for clinical decision-making at the point of care. Objectives . To determine (1) the usage, reliability, and popularity of mobile medical apps and (2) medical students’ perceptions of app usage effect on the quality of patient-provider interaction in healthcare settings. Methods . An anonymous web-based survey was distributed to medical students. Frequency of use, type of app used, and perceptions of reliability were assessed via univariate analysis. Results . Seven hundred thirty-one medical students responded, equating to a response rate of 29%. The majority (90%) of participants thought that medical apps enhance clinical knowledge, and 61% said that medical apps are as reliable as textbooks. While students thought that medical apps save time, improve the care of their patients, and improve diagnostic accuracy, 53% of participants believed that mobile device use in front of colleagues and patients makes one appear less competent. Conclusion . While medical students believe in the utility and reliability of medical apps, they were hesitant to use them out of fear of appearing less engaged. Higher levels of training correlated with a greater degree of comfort when using medical apps in front of patients.

Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.

In child sexual exploitation offenses, the collected evidence images often show the skin of nonfacial body parts of the criminals and victims. For identification in this scenario, "relatively permanent pigmented or vascular skin marks," abbreviated as RPPVSM, were recently introduced as the basis for a novel biometric trait. This pilot study evaluated the interexaminer variability of RPPVSM identification. Four dermatology physicians were recruited to examine RPPVSM from 75 skin images collected from a total of 51 Caucasian and Asian subjects. The images were separated into 50 reference ("suspect") images and 25 evaluation ("evidence") images. The examiners were asked to perform identification by annotating RPPVSM in each of the 25 evaluation images and matching them with the reference images. The rate of misidentification was 0% while the mean rate at which examiners failed to find a match was 6%, indicating the potential of dermatology physicians performing the role of RPPVSM examiners.

Correction to: The ISME Journal (2015) 9, 2092–2107; doi:10.1038/ismej.2015.47; published online 7 April 2015 Since the publication of this article, the authors have noticed errors in Figures 4a and 6, where one Propionibacterium acnes strain, HL103PA1, was mislabeled in Figure 4a, and the CRISPR spacers were shown incorrectly in Figure 6.

Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B-12 biosynthesis pathway in the skin bacterium Propionibacterium acnes was significantly down-regulated in acne patients. We hypothesized that host vitamin B-12 modulates the activities of the skin microbiota and contributes to acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B-12. We found that the supplementation repressed the expression of vitamin B-12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the 10 subjects studied developed acne 1 week after vitamin B-12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B-12 supplementation in P. acnes cultures promoted the production of porphyrins, which have been shown to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B-12 supplementation leads to acne development in a subset of individuals. Our study discovered that vitamin B-12, an essential nutrient in humans, modulates the transcriptional activities of skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development.

Background: The ability to reliably recognize and classify a range of skin signs and symptoms remains a necessary skill across most clinical disciplines but one that is traditionally mastered via nonsystematic experience over long periods.Objective: We investigated whether online Perceptual and Adaptive Learning Modules (PALMs) could efficiently train preclerkship medical students to identify and discriminate primary skin lesion morphologies, configurations, and anatomic distributions.Methods: Medical students completed an online skin lesion morphology PALM voluntarily in year 1 and by requirement, along with configuration and anatomic distribution PALMs, in year 2. In controlled before-and-after studies, multiple-choice pretests and posttests using previously unused images, assessed PALM-induced learning. In prospective cohort studies, differences in year-2 performance between students who had and had not completed the morphology PALM in year 1 were also assessed.Results: Multiple-choice tests, used to evaluate PALM effectiveness, demonstrated large (effect sizes of 1.1 [+/- 0.1 SE] to 2.2 [+/- 0.1 SE]) and statistically significant (P < .0001) improvements after PALM training, with learning retention when tested after 1 year.Limitations: Results are from self-selected groups and a single class at 1 institution.Conclusion: PALMs are a useful tool for efficient development of the core clinical skills of pattern recognition and classification of skin lesion characteristics.

ABSTRACT Propionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1.