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Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2.

We present a precision medical perspective to assist in the definition, diagnosis, and management of Post Treatment Lyme Disease Syndrome (PTLDS)/chronic Lyme disease. PTLDS represents a small subset of patients treated for an erythema migrans (EM) rash with persistent or recurrent symptoms and functional decline. The larger population with chronic Lyme disease is less understood and well defined. Multiple Systemic Infectious Disease Syndrome (MSIDS) is a multifactorial model for treating chronic disease(s), which identifies up to 16 overlapping sources of inflammation and their downstream eff

The TITAN-X Platform Integrates Big Data, Artificial Intelligence, Bioinformatics, and Advanced Computational Modeling to Understand Immune Responses and Develop the Next Wave of Precision Medicines.

The TITAN-X Precision Medicine Platform was engineered to rapidly, fully, and efficiently utilize large-scale immunology datasets, including public data, in drug discovery and development. TITAN-X integrates big data with artificial intelligence (AI), bioinformatics, and advanced computational modeling to seamlessly transition from early target discovery to clinical testing of new therapeutics, developing biomarker-driven precision medicines tailored to specific patient populations. We illustrate the capabilities of TITAN-X through four case studies, demonstrating its use in computationally dr…

A Novel Mecp2Y120D Knock-in Model Displays Similar Behavioral Traits But Distinct Molecular Features Compared to the Mecp2-Null Mouse Implying Precision Medicine for the Treatment of Rett Syndrome.

MeCP2 is a fundamental protein associated with several neurological disorders, including Rett syndrome. It is considered a multifunctional factor with a prominent role in regulating chromatin structure; however, a full comprehension of the consequences of its deficiency is still lacking. Here, we characterize a novel mouse model of Mecp2 bearing the human mutation Y120D, which is localized in the methyl-binding domain. As most models of Mecp2, the Mecp2Y120D mouse develops a severe Rett-like phenotype. This mutation alters the interaction of the protein with chromatin, but surprisingly, it als

Buprenorphine Initiation in the Era of High-potency Synthetic Opioids: A Call for Community-based Participatory Research to Help Learning Health Systems Provide Precision Medicine for Opioid Use Disorder.

High-potency synthetic opioids and adulterants have saturated the US opioid supply, heightening risk to people who use drugs and creating ch … information. Successful conduct of these efforts in learning health systems can help us move toward precision medicine for opioid use disorder.

Precision Medicine Approach to Develop and Internally Validate Optimal Exercise and Weight-Loss Treatments for Overweight and Obese Adults With Knee Osteoarthritis: Data From a Single-Center Randomized Trial.

OBJECTIVE: To apply a precision medicine approach to determine the optimal treatment regime for participants in an exercise (E), dietary weight loss (D), and D + E trial for knee osteoarthritis that would maximize their expected outcomes. METHODS: Using data from 343 participants of the Intensive Diet and Exercise for Arthritis (IDEA) trial, we applied 24 machine-learning models to develop individualized treatment rules on 7 outcomes: Short Form 36 physical component score, weight loss, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/function/stiffness scores, comp…

Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: prospective cohort study before and after implementation of personalized bleeding risks.

OBJECTIVE: To examine whether prospective bleeding risk estimates for patients undergoing percutaneous coronary intervention could improve the use of bleeding avoidance strategies and reduce bleeding. DESIGN: Prospective cohort study comparing the use of bleeding avoidance strategies and bleeding rates before and after implementation of prospective risk stratification for peri-procedural bleeding. SETTING: Nine hospitals in the United States. PARTICIPANTS: All patients undergoing percutaneous coronary intervention for indications other than primary reperfusion for ST elevation myocardial in

Update on research and clinical translation on specific clinical areas: From bench to bedside: How insight in immune pathogenesis can lead to precision medicine of severe juvenile idiopathic arthritis.

Despite the enormous progress in the treatment of juvenile idiopathic arthritis (JIA), innovations based on true bench-to-bedside research, performed in JIA patients, are still scarce. This chapter describes novel developments in which clinical innovations go hand in hand with basic discoveries. For the purpose of this review, we will mainly focus on developments in severe forms of JIA, most notably systemic JIA and polyarticular JIA. However, also in less severe forms of JIA, such as oligoarticular JIA, better insight will help to improve diagnosis and treatment. Facilitating the transition f

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, such as sarcomas, access to patient samples is limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up <1% of all human cancers, sarcomas represent 15% of cancers in dogs. Because dogs have similar im

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… This latter aspect addresses a key pitfall in precision medicine approaches to treat human cancers—the effect of a selected therapy may not be clear for many years. … This experience illustrates the gaps that will need to be bridged if precision medicine is to be utilized in the treatment of soft tissue sarcoma and other challenging solid tumors. …

Multicentre randomised comparative effectiveness trial of cleavage-stage versus blastocyst-stage embryo transfer in patients with few embryos (PRECISE): implementation of a study protocol in reproductive medicine.

BACKGROUND: With improvements in in vitro culture techniques, there has been a steady shift in practice to transfer in vitro fertilisation (IVF) embryos at the blastocyst-stage to increase pregnancy rates per embryo transfer (ET) and reduce the risk of multiple pregnancy. In patients with fewer embryos (≤5 zygotes), fresh cleavage-stage ET is still commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst-stage in vitro. However, evidence for improved outcomes with cleavage-stage embryo transfer in this subgroup of patients is lacking. We will compare

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut mi

Cohort profile: the PRIMETIME 1 (PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy) cohort - a longitudinal Danish nationwide study of individuals with diabetes and a performed kidney biopsy.

PURPOSE: Individuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and management of complications. The PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy (PRIMETIME) 1 cohort is designed to study clinical characteristics, diagnostic accuracy and prognostic markers in a population with diabetes and kidney disease classified by biopsy. PARTICIPANTS: This retrospective Danish nationwide cohort includes 2586 individua…

A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study.

INTRODUCTION: The search for drugs to treat Alzheimer's disease (AD) has failed to yield effective therapies. Here we report the first genome-wide search for biomarkers associated with therapeutic response in AD. Blarcamesine (ANAVEX2-73), a selective sigma-1 receptor (SIGMAR1) agonist, was studied in a 57-week Phase 2a trial (NCT02244541). The study was extended for a further 208 weeks (NCT02756858) after meeting its primary safety endpoint. METHODS: Safety, clinical features, pharmacokinetic, and efficacy, measured by changes in the Mini-Mental State Examination (MMSE) and the Alzheimer's D

Integrating real-world data with gold-standard longitudinal clinical and genomic data to advance precision medicine for the Alzheimer's Disease Research Center Program and beyond: a proof-of-concept data platform.

INTRODUCTION: Integrating real-world data (RWD) with clinical research datasets creates more complete, context-rich resources to drive discovery and enable precision medicine in Alzheimer's disease and related dementias. The National Alzheimer's Coordinating Center conducted a proof-of-concept (POC) project to link its longitudinal Uniform Data Set (UDS) with electronic health records (EHRs), Medicare claims, and genomic data. METHODS: In partnership with three Alzheimer's Disease Research Centers (ADRCs), we developed scalable data pipelines and a governance framework to collect, harmonize, …

Correction: Lee, T.-S. Intracellular Crosstalk of the Gasotransmitter Trio (NO, CO, H2S) in Cardiovascular Health and Disease: From Molecular Signaling to Precision Gas Medicine. Int. J. Mol. Sci. 2026, 27, 6248.

Text Correction [...].

Epigenetic precision diagnostics of traditional Chinese medicine (TCM) syndrome differentiation: a pilot study of atrial fibrillation with qi-yin deficiency syndrome based on 5-hydroxymethylcytosine signatures in extracellular vesicle DNA from plasma.

BACKGROUND: Syndrome differentiation in Traditional Chinese Medicine (TCM) is pivotal to clinical practice and dictates the efficacy of medicinal treatments. However, precision diagnostic models for TCM syndromes, constructed from biomarkers such as metabolites and proteins, have failed to achieve high precision. Recent studies have highlighted a strong link between TCM and epigenetics, an area that remains largely unexplored in TCM diagnosis. Taking atrial fibrillation (AF) with Qi-Yin deficiency syndrome (QYDS) as an example, we utilized a type of epigenetic sequencing technology called 5hmC

Ultrasound-Guided Synovial Biopsy Can Be Effectively and Safely Performed in Different Clinical Settings Favouring a Widespread Application of Precision Medicine in Rheumatoid Arthritis: A Post-hoc Analysis of Three Clinical Trials.

Objectives: In the perspective of an increasingly widespread application of precision medicine in rheumatoid arthritis (RA), this study aimed to compare efficacy and safety of ultrasound-guided synovial biopsy (US-SB) performed in an experienced rheumatology and community hospital setting. Methods: A post hoc analysis of R4RA, STRAP and STRAP-EU trials was performed, comparing US-SB performed in a radiology department of a community hospital without experience in RA (n = 14), versus a rheumatology academic centre with a high expertise in RA management and US-SB (n = 16). Suitability of specime…

Associations of Vitamin D Receptor (ApaI, FokI, TaqI, BsmI) Polymorphisms with Neurodegenerative Diseases in the Middle East, North Africa and Turkiye (MENA&T) Region: A Systematic Review and Meta-Analysis Toward Population-Specific Precision Medicine.

Background: Vitamin D receptor (VDR) polymorphisms have been widely investigated as genetic determinants of neurodegenerative diseases, yet … lation-specific genetic associations underscore the importance of incorporating VDR genotyping into precision medicine frameworks for neurodegenerative disease risk stratification in MENA&T populations, where vitamin D deficiency is highly prevalent.

Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response.This study will test the hypothesis, within an open-label paralle

[Re-evaluating ALS Medical Care in Japan: An International Comparison of Japan, Europe, the United States, and Canada-Insights from Mechanical Ventilation, Support for Social Participation, End-of-Life Care Options, Approved Drugs, and Precision Medicine].

Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the … challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.