BACKGROUND: We previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.
METHODS: Using our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.
RESULTS: C4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions.
CONCLUSIONS: We have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.

Microorganisms have been used in nutrition and medicine for thousands of years worldwide, long before humanity knew of their existence. It is now known that the gut microbiota plays a key role in regulating inflammatory, metabolic, immune and neurobiological processes. This text discusses the importance of microbiota-based precision nutrition in gut permeability, as well as the main advances and current limitations of traditional probiotics, new-generation probiotics, psychobiotic probiotics with an effect on emotional health, probiotic foods, prebiotics, and postbiotics such as short-chain fatty acids, neurotransmitters and vitamins. The aim is to provide a theoretical context built on current scientific evidence for the practical application of microbiota-based precision nutrition in specific health fields and in improving health, quality of life and physiological performance.

This review presents a comprehensive exploration of gene editing technologies and their potential applications in the treatment of liver fibrosis, a condition often leading to serious complications such as liver cancer. Through an in-depth review of current literature and critical analysis, the study delves into the intricate signaling pathways underlying liver fibrosis development and examines the promising role of gene editing in alleviating this disease burden. Gene editing technologies offer precise, efficient, and reproducible tools for manipulating genetic material, holding significant promise for basic research and clinical practice. The manuscript highlights the challenges and potential risks associated with gene editing technology. By synthesizing existing knowledge and exploring future perspectives, this study aims to provide valuable insights into the potential of precision gene editing to combat liver fibrosis and its associated complications, ultimately contributing to advances in liver fibrosis research and therapy.

Breast cancer, a prevalent disease with significant mortality rates, often presents treatment challenges due to its complex genetic makeup. This review explores the potential of combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene knockout strategies with immunotherapeutic approaches to enhance breast cancer treatment. The CRISPR/Cas9 system, renowned for its precision in inducing genetic alterations, can target and eliminate specific cancer cells, thereby minimizing off-target effects. Concurrently, immunotherapy, which leverages the immune system\'s power to combat cancer, has shown promise in treating breast cancer. By integrating these two strategies, we can potentially augment the effectiveness of immunotherapies by knocking out genes that enable cancer cells to evade the immune system. However, safety considerations, such as off-target effects and immune responses, necessitate careful evaluation. Current research endeavors aim to optimize these strategies and ascertain the most effective methods to stimulate the immune response. This review provides novel insights into the integration of CRISPR/Cas9-mediated knockout strategies and immunotherapy, a promising avenue that could revolutionize breast cancer treatment as our understanding of the immune system\'s interplay with cancer deepens.

Microbial therapies have promising applications in the treatment of a broad range of diseases. However, effective colonization of the target region by therapeutic microorganisms remains a significant challenge owing to the complexity of the intestinal system. Here, we developed surface nanocoating-based universal platform (SNUP), which enabled the manipulation of controlled release and targeted colonization of therapeutic microbes in the digestive tract without the utilization of any targeting molecules. The system controlled the decomposition time of SNUP in the gut by regulating different modification layers and modification sequences on the microorganism\'s surface, so that the microorganism was released at a predetermined time and space. With the SNUP nanomodification technology, we could effectively deliver therapeutic microorganisms to specific complex intestinal regions such as the small intestine and colon, and protect the bioactivity of therapeutic microorganisms from destruction by both strong acids and digestive enzymes. In this study, we found that two layers SNUP-encapsulated Liiliilactobacillus salivarius (LS@CCMC) could efficiently colonize the small intestine and significantly improve the symptoms of a mouse model of Parkinson\'s disease through sustained secretion of γ-aminobutyric acid (GABA). This surface nanocoating-based universal platform system does not require the design of specific targeting molecules, providing a simple and universal method for colonized microbial therapy, target theranostics, precision medicine, and personalized medicine.

UNASSIGNED: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling.
UNASSIGNED: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes.
UNASSIGNED: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed.
UNASSIGNED: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009-2019 at a single-center academic children\'s hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs (p < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively (p < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.

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UNASSIGNED: More recently approved drugs have significantly fewer indications than drugs approved many years ago. One possible reason for this may be that, controlling for the number of years since approval or launch, more recently approved drugs have fewer indications (e.g. at the time of launch). The role of precision and personalised medicine has increased, and the goal of precision medicine is to provide a more precise approach for the prevention, diagnosis and treatment of disease. Drugs that have fewer indications may be \'more precise\' than drugs that have many indications.
UNASSIGNED: We use different kinds of data from two countries - France and the U.S. - to analyze the relationship across many drugs between the number of indications of a drug, the drug\'s vintage - i.e. the year in which the drug was first marketed or approved - and its age - the number of years it has been marketed.
UNASSIGNED: All the evidence from both countries indicates that, controlling for drug age, more recently approved drugs tend to have fewer indications than drugs approved many years ago. In the U.S., a 10-year increase in vintage is associated with a 10.7% decline in the effective number of indications of all drugs, and a 19.4% decline in the effective number of indications of drugs approved after 1989. In France, the positive effect on the number of indications of the increase in drug age was more than offset by the negative effect of the increase in drug vintage.
UNASSIGNED: More recently approved drugs are less likely to be \'general-purpose technologies\' (or even multi-purpose technologies) than older drugs. The relative importance of \'precision medicine\' has increased in recent decades. Drugs that have fewer indications may be \'more precise\' than drugs that have many indications.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms\' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients\' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.