This comprehensive exploration delves into the pivotal role of microRNAs (miRNAs) within the intricate tapestry of cellular regulation. As potent orchestrators of gene expression, miRNAs exhibit diverse functions in cellular processes, extending their influence from the nucleus to the cytoplasm. The complex journey of miRNA biogenesis, involving transcription, processing, and integration into the RNA-induced silencing complex, showcases their versatility. In the cytoplasm, mature miRNAs finely tune cellular functions by modulating target mRNA expression, while their reach extends into the nucleus, influencing transcriptional regulation and epigenetic modifications. Dysregulation of miRNAs becomes apparent in various pathologies, such as cancer, autoimmune diseases, and inflammatory conditions. The adaptability of miRNAs to environmental signals, interactions with transcription factors, and involvement in intricate regulatory networks underscore their significance. DNA methylation and histone modifications adds depth to understanding the dynamic regulation of miRNAs. Mechanisms like competition with RNA-binding proteins, sponging, and the control of miRNA levels through degradation and editing contribute to this complex regulation process. In this review, we mainly focus on how dysregulation of miRNA expression can be related with skin-related autoimmune and autoinflammatory diseases, arthritis, cardiovascular diseases, inflammatory bowel disease, autoimmune and autoinflammatory diseases, and neurodegenerative disorders. We also emphasize the multifaceted roles of miRNAs, urging continued research to unravel their complexities. The mechanisms governing miRNA functions promise advancements in therapeutic interventions and enhanced insights into cellular dynamics in health and disease.

Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues. Calcific aortic valve disease, vascular calcification, gallstones, kidney stones, and abnormal mineralization in arthritis are common examples of ectopic mineralization. They are debilitating diseases and exhibit excess mortality, disability, and morbidity, which impose on patients with limited social or financial resources. Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields. In the present review, we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization. The current knowledge of inflammatory milieu in pathological mineralization is reviewed, including how immune cells, pro-inflammatory mediators, and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells, providing nucleating sites and assembly of aberrant minerals. Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.

OBJECTIVE: Biosimilars were introduced to decrease biologic-related expenditures, but their uptake in inflammatory bowel disease (IBD) remains suboptimal. Herein, we review biosimilar concepts, current products available for IBD treatment, and resources to support biosimilar utilization.
RESULTS: Although a cornerstone of IBD treatment, biologics are costly due to their development. Biosimilars, which are biologic products highly similar to a reference product, aim to decrease these expenditures. Infliximab, adalimumab, and ustekinumab biosimilars are approved for IBD, but uptake remains low due to biosimilar efficacy and safety concerns and delayed market entry. Clinicians can effectively address some of these barriers and help patients and healthcare systems reap the benefits of decreased costs and increased treatment access. Data shows comparable efficacy and safety outcomes with biosimilars in IBD. Several biosimilar products are available and in the pipeline, but efforts are needed from various stakeholders to bolster utilization and generate benefits.

OBJECTIVE: This study aimed to assess the psychometric properties of two widely used fatigue scales in a sample of patients with inflammatory conditions.
METHODS: Rasch analysis was used to examine scale reliability, item bias, unidimensionality and overall fit to the Rasch model. Sub-test methodology was utilised to attempt to improve model fit for the CFQ and BRAF-MDQ.
RESULTS: Initial analysis displayed strong reliability (PSI=0.89 0.96), alongside a lack of item bias in both scales. However, evidence for unidimensionality was not found for either scale. Overall fit to the Rasch model was marginal for the CFQ, and misfitting for the BRAF-MDQ. Local dependency was observed, as well as significant item misfit for both scales. Sub-test modifications resulted in the best model fit for the BRAF-MDQ (χ2(16)=15.77, p=0.469) and the CFQ (χ2(25)=15.49, p=0.929). Modifications resulted in improved fit, reductions in measurement error, and the production of ordinal-to-interval conversion tables for both scales. Conversion tables apply the benefits of enhanced measurement accuracy, valid comparison of BRAF-MDQ and CFQ scores to other interval-level data, appropriate use in parametric statistics, and enhanced precision in clinical cut-off scores-without the need to change administration format.
CONCLUSIONS: The BRAF-MDQ and CFQ are valid, reliable tools for fatigue assessment. Psychometric indices and content factors suggest the CFQ is suited to measuring general fatigue, particularly when response burden is a concern, while the BRAF-MDQ should be used in clinical presentations where other symptoms are severe and the impact of fatigue on daily living, emotional, and social well-being is of interest.

Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies.
An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the \'Think Aloud\' method with patient advisory group members and Research Nurses to assess the usability of the system.
Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials.
By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development.
ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.
More and more patients tell clinicians how they feel by completing questionnaires electronically. Therefore, it is important to assess how easy it is for patients to do this. In this study, we describe how we developed an electronic platform for patients to report their symptoms and how we tested the usability of this platform with patient partners and research nurses. Once the electronic platform was developed, quality of life and symptoms questionnaires were programmed onto it. Alerts were sent to the clinical team if specific scores were obtained on the symptoms questionnaires. Although two patient partners were not able to finish the testing session because of technical issues, the ones who completed the session liked its simplicity and responsiveness. The research nurses also liked the system and only suggested minor modifications. Following this testing, we refined the electronic platform to test it further in a larger study which investigates the safety and use of a drug. We hope that thanks to this electronic platform, we will obtain useful information on the safety and efficacy of treatment.

This paper describes the synthesis of some heteroaryl compounds and compositions comprising an effective amount of one or more such compounds and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway, comprising administering an adequate amount of a heteroaryl compound to a patient in need thereof. These compounds are mTOR/PI3K/Akt pathway inhibitors.

The impact of the market entry of adalimumab biosimilars on clinical practices and specialty pharmacies is explained. A roadmap is also provided for how pharmacists can successfully navigate this landscape.
Biosimilars have previously been introduced as a mechanism to help curb biologic expenditures, with biosimilars undergoing an abbreviated regulatory approval process that focuses on biosimilarity and generating product competition. Adalimumab is currently the leading product in the biologics market, generating approximately $20 to $30 billion in sales worldwide consecutively from 2019 to 2021. Many adalimumab biosimilars are slated to enter the market in 2023 and become available for patient use. However, compared to other biosimilars, adalimumab biosimilars have several unique considerations, such as interchangeability and concentration, that will impact pharmacy practices and workflows. Because pharmacists embedded in clinical practices and specialty pharmacies will be significantly involved in the processes relating to adalimumab biosimilar implementation, adoption, and use, a primer on understanding the various adalimumab biosimilar products available and considerations surrounding these products with regard to workflow and patient use is critical. Several resources are also provided to help pharmacists successfully navigate the adalimumab biosimilar landscape.
The biosimilar landscape continues to evolve, and 2023 will see the launch of several adalimumab biosimilar products, which vary with regard to formulation, concentration, and interchangeability status. Pharmacists are well positioned to educate providers and patients about this landscape and help implement an efficient workflow to support adalimumab biosimilar adoption and use.

UNASSIGNED: Combined oral contraceptive pills (COCs) are safe and effective therapies for females with acne vulgaris. Data is lacking regarding dermatology residents\' COCs use. We aimed to evaluate dermatology residents\' knowledge, comfort level, and prescribing practices of COCs in the management of acne vulgaris.
UNASSIGNED: A cross-sectional survey study was emailed to current dermatology residents in approved training programs and descriptive statistics were performed.
UNASSIGNED: Most residents reported that COCs are an effective treatment for acne (160/170, 94.1%) but, less felt adequately trained on efficacy (105/170, 61.8%) and safety (72/170, 42.4%). 30 percent (51/170) of residents\' attending physicians regularly prescribed COCs for acne. Half were comfortable counseling patients on adverse effects of COCs (86/170, 50.6%) while fewer were comfortable counseling on how to properly take COCs (66/170, 38.8%). 60 percent (102/170) felt comfortable prescribing COCs to healthy adolescents while 66.5 percent (113/170) were comfortable prescribing to adults.
UNASSIGNED: Limitations include a small sample size, response bias, and inability to calculate an accurate response rate.
UNASSIGNED: This data suggests most residents recognize COCs are an effective treatment for acne vulgaris, but less feel adequately trained. Several knowledge gaps and potential educational interventions regarding COCs, including safety, efficacy, adverse effects, and contraindications, are highlighted.

OBJECTIVE: To investigate the changes in the m6A methylation modification profile of human periodontal ligament cells (hPDLCs) in response to inflammatory conditions.
BACKGROUND: Periodontitis is an infectious disease of the periodontal support tissue that leads to the loss of alveolar bone. HPDLCs are primary cells that can repair periodontal tissue defects caused by periodontitis. However, the inflammatory conditions induce inflammatory damage and decrease ossification of hPDLCs. This inflammatory response depends on genetic and epigenetic mechanisms, including m6A methylation.
METHODS: HPDLCs were cultured with osteogenic induction medium (NC group), while TNF-α (10 ng/mL) and IL-1β (5 ng/mL) were added to simulate inflammatory conditions (Inflam group). Then RNA-seq and MeRIP-seq analyses were performed to identify m6A methylation modification in the transcriptome range of hPDLCs.
RESULTS: The results showed that the osteogenic differentiation of hPDLCs was inhibited under inflammatory conditions. RNA-seq analysis also revealed that the decreased genes in response to inflammatory conditions were primarily annotated in processes associated with ossification. Compared with the NC group, differentially m6A-methylated genes were primarily enriched in histone modification processes. Among 145 histone modification genes, 25 genes have been reported to be involved in the regulation of osteogenic differentiation, and they include KAT6B, EP300, BMI1, and KDMs (KDM1A, KDM2A, KDM3A, KDM4B, and KDM5A).
CONCLUSIONS: This study demonstrated that the m6A landscape of hPDLCs was changed in response to inflammation. M6A methylation differences among histone modification genes may act on the osteogenic differentiation of hPDLCs.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disorder characterized by recurring painful and suppurating lesions, with the disease disproportionately affecting black populations in the United States. Ethnoracial representation in clinical trials is vital to ensuring results are generalizable. The purpose of this study is to examine whether ethnic or racial disparities exist in HS clinical trials.
METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify HS clinical trials. Trials that did not present ethnic or racial data on either the website or publication were not considered.
RESULTS: A total of 57 HS trials were identified. Of these, 23 trials, containing 2530 patients, included racial or ethnic data (Table 1). White patients made up 76.1% (1435/1886) of the study population, followed by Blacks or African Americans (13.7% (238/1732)), Hispanics or Latinos (7.2% (20/279), Asians (2.6% (26/1016)), American Indians or Alaska Natives (1.3% (14/1051)), and Native Hawaiians or Other Pacific Islanders (0.4% (4/926)).
CONCLUSIONS: Our results establish a significant lack of minority ethnoracial representation in HS clinical trials. Since HS prevalence is highest among Blacks or African Americans, it is imperative that future clinical trials are conducted with a larger proportion of this population. Furthermore, clinical trials that did not report racial or ethnic information were conducted in countries with predominantly White populations, which likely skewed the results of this study and caused underreporting of these patients.