Epma Journal最新文献

Aim and background: Identifying risk factors for cancer initiation and progression is the cornerstone of the preventive approach to cancer management and control (EPMA J. 4(1):6, 2013). Tobacco smoking is a well-recognized risk factor for initiation and spread of several cancers. The predictive, preventive, and personalized medicine (PPPM) approach to cancer management and control focuses on smoking cessation as an essential cancer prevention strategy. Towards this end, this study examines the temporal patterns of cancer burden due to tobacco smoking in the last three decades at global, regional, and national levels.

Data and methods: The data pertaining to the burden of 16 cancers attributable to tobacco smoking at global, regional, and national levels were procured from the Global Burden of Disease 2019 Study. Two main indicators, deaths and disability-adjusted life years (DALYs), were used to describe the burden of cancers attributable to tobacco smoking. The socio-economic development of countries was measured using the socio-demographic index (SDI).

Results: Globally, deaths due to neoplasms caused by tobacco smoking increased from 1.5 million in 1990 to 2.5 million in 2019, whereas the age-standardized mortality rate (ASMR) decreased from 39.8/100,000 to 30.6/100,000 and the age-standardized DALY rate (ASDALR) decreased from 948.9/100,000 to 677.3/100,000 between 1990 and 2019. Males accounted for approximately 80% of global deaths and DALYs in 2019. Populous regions of Asia and a few regions of Europe account for the largest absolute burden, whereas countries in Europe and America have the highest age-standardized rates of cancers due to tobacco smoking. In 8 out of 21 regions, there were more than 100,000 deaths due to cancers attributable to tobacco smoking led by East Asia, followed by Western Europe in 2019. The regions of Sub-Saharan Africa (except southern region) had one of the lowest absolute counts of deaths, DALYs, and age-standardized rates. In 2019, tracheal, bronchus, and lung (TBL), esophageal, stomach, colorectal, and pancreatic cancer were the top 5 neoplasms attributable to tobacco smoking, with different burdens in regions as per their development status. The ASMR and ASDALR of neoplasms due to tobacco smoking were positively correlated with SDI, with pairwise correlation coefficient of 0.55 and 0.52, respectively.

Conclusion: As a preventive tool, tobacco smoking cessation has the biggest potential among all risk factors for preventing millions of cancer deaths every year. Cancer burden due to tobacco smoking is found to be higher in males and is positively associated with socio-economic development of countries. As tobacco smoking begins mostly at younger ages and the epidemic is unfolding in several parts of the world, more accelerated efforts are required towards tobacco cessation and preventing youth from entering this addiction.

Currently colorectal cancer (CRC) is the third most prevalent cancer worldwide. Body mass index (BMI) is frequently used in CRC screening and risk assessment to quantitatively evaluate weight. However, the impact of BMI on clinical strategies for CRC has received little attention. Within the framework of the predictive, preventive, and personalized medicine (3PM/PPPM), we hypothesized that BMI stratification would affect the primary, secondary, and tertiary care options for CRC and we conducted a critical evidence-based review. BMI dynamically influences CRC outcomes, which helps avoiding adverse treatment effects. The outcome of surgical and radiation treatment is adversely affected by overweight (BMI ≥ 30) or underweight (BMI < 20). A number of interventions, such as enhanced recovery after surgery and robotic surgery, can be applied to CRC at all levels of BMI. BMI-controlling modalities such as exercise, diet control, nutritional therapy, and medications may be potentially beneficial for patients with CRC. Patients with overweight are advised to lose weight through diet, medication, and physical activity while patients suffering of underweight require more focus on nutrition. BMI assists patients with CRC in better managing their weight, which decreases the incidence of adverse prognostic events during treatment. BMI is accessible, noninvasive, and highly predictive of clinical outcomes in CRC. The cost-benefit of the PPPM paradigm in developing countries can be advanced, and the clinical benefit for patients can be improved with the promotion of BMI-based clinical strategy models for CRC.

Background: Arterial stiffness is a major risk factor and effective predictor of cardiovascular diseases and a common pathway of pathological vascular impairments. Homocysteine (Hcy) and uric acid (UA) own the shared metabolic pathways to affect vascular function. Serum uric acid (UA) has a great impact on arterial stiffness and cardiovascular risk, while the mutual effect with Hcy remains unknown yet. This study aimed to evaluate the mutual effect of serum Hcy and UA on arterial stiffness and 10-year cardiovascular risk in the general population. From the perspective of predictive, preventive, and personalized medicine (PPPM/3PM), we assumed that combined assessment of Hcy and UA provides a better tool for targeted prevention and personalized intervention of cardiovascular diseases via suppressing arterial stiffness.

Methods: This study consisted of 17,697 participants from Beijing Health Management Cohort, who underwent health examination between January 2012 and December 2019. Brachial-ankle pulse wave velocity (baPWV) was used as an index of arterial stiffness.

Results: Individuals with both high Hcy and UA had the highest baPWV, compared with those with low Hcy and low UA (β: 30.76, 95% CI: 18.36-43.16 in males; β: 53.53, 95% CI: 38.46-68.60 in females). In addition, these individuals owned the highest 10-year cardiovascular risk (OR: 1.49, 95% CI: 1.26-1.76 in males; OR: 7.61, 95% CI: 4.63-12.68 in females). Of note, males with high homocysteine and low uric acid were significantly associated with increased cardiovascular risk (OR: 1.30, 95% CI: 1.15-1.47), but not the high uric acid and low homocysteine group (OR: 1.02, 95% CI: 0.90-1.16).

Conclusions: This study found the significantly mutual effect of Hcy and UA on arterial stiffness and cardiovascular risk using a large population and suggested the clinical importance of combined evaluation and control of Hcy and UA for promoting cardiovascular health. The adverse effect of homocysteine on arteriosclerosis should be addressed beyond uric acid, especially for males. Monitoring of the level of both Hcy and UA provides a window opportunity for PPPM/3PM in the progression of arterial stiffness and prevention of CVD. Hcy provides a novel predictor beyond UA of cardiovascular health to identify individuals at high risk of arterial stiffness for the primary prevention and early treatment of CVD. In the progressive stage of arterial stiffness, active control of Hcy and UA levels from the aspects of dietary behavior and medication treatment is conducive to alleviating the level of arterial stiffness and reducing the risk of CVD. Further studies are needed to evaluate the clinical effect of Hcy and UA targeted intervention on arterial stiffness and cardiovascular health.

Supplementary information: The online version contains supplementary material available at 10.1007/s131

Background: Currently, the rate of recurrence or metastasis (ROM) remains high in rectal cancer (RC) patients treated with the standard regimen. The potential of diffusion-weighted imaging (DWI) in predicting ROM risk has been reported, but the efficacy is insufficient.

Aims: This study investigated the potential of a new sequence called readout-segmented echo-planar imaging (RS-EPI) DWI in predicting the ROM risk of patients with RC using machine learning methods to achieve the principle of predictive, preventive, and personalized medicine (PPPM) application in RC treatment.

Methods: A total of 195 RC patients from two centres who directly received total mesorectal excision were retrospectively enrolled in our study. Machine learning methods, including recursive feature elimination (RFE), the synthetic minority oversampling technique (SMOTE), and the support vector machine (SVM) classifier, were used to construct models based on clinical-pathological factors (clinical model), radiomic features from RS-EPI DWI (radiomics model), and their combination (merged model). The Harrell concordance index (C-index) and the area under the time-dependent receiver operating characteristic curve (AUC) were calculated to evaluate the predictive performance at 1 year, 3 years, and 5 years. Kaplan‒Meier analysis was performed to evaluate the ability to stratify patients according to the risk of ROM.

Findings: The merged model performed well in predicting tumour ROM in patients with RC at 1 year, 3 years, and 5 years in both cohorts (AUC = 0.887/0.813/0.794; 0.819/0.795/0.783) and was significantly superior to the clinical model (AUC = 0.87 [95% CI: 0.80-0.93] vs. 0.71 [95% CI: 0.59-0.81], p = 0.009; C-index = 0.83 [95% CI: 0.76-0.90] vs. 0.68 [95% CI: 0.56-0.79], p = 0.002). It also had a significant ability to differentiate patients with a high and low risk of ROM (HR = 12.189 [95% CI: 4.976-29.853], p < 0.001; HR = 6.427 [95% CI: 2.265-13.036], p = 0.002).

Conclusion: Our developed merged model based on RS-EPI DWI accurately predicted and effectively stratified patients with RC according to the ROM risk at an early stage with an individualized profile, which may be able to assist physicians in individualizing the treatment protocols and promote a meaningful paradigm shift in RC treatment from traditional reactive medicine to PPPM.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00303-3.

Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation o

Background: The N7-methylguanosine modification (m7G) of the 5' cap structure in the mRNA plays a crucial role in gene expression. However, the relation between m7G and tumor immune remains unclear. Hence, we intended to perform a pan-cancer analysis of m7G which can help explore the underlying mechanism and contribute to predictive, preventive, and personalized medicine (PPPM / 3PM).

Methods: The gene expression, genetic variation, clinical information, methylation, and digital pathological section from 33 cancer types were downloaded from the TCGA database. Immunohistochemistry (IHC) was used to validate the expression of the m7G regulator genes (m7RGs) hub-gene. The m7G score was calculated by single-sample gene-set enrichment analysis. The association of m7RGs with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. CellProfiler was used to extract pathological section characteristics. XGBoost and random forest were used to construct the m7G score prediction model. Single-cell transcriptome sequencing (scRNA-seq) was used to assess the activation state of the m7G in the tumor microenvironment.

Results: The m7RGs were highly expressed in tumors and most of the m7RGs are risk factors for prognosis. Moreover, the cellular pathway enrichment analysis suggested that m7G score was closely associated with invasion, cell cycle, DNA damage, and repair. In several cancers, m7G score was significantly negatively correlated with MSI and TMB and positively correlated with TIDE, suggesting an ICB marker potential. XGBoost-based pathomics model accurately predicts m7G scores with an area under the ROC curve (AUC) of 0.97. Analysis of scRNA-seq suggests that m7G differs significantly among cells of the tumor microenvironment. IHC confirmed high expression of EIF4E in breast cancer. The m7G prognostic model can accurately assess the prognosis of tumor patients with an AUC of 0.81, which was publicly hosted at https://pan-cancer-m7g.shinyapps.io/Panca-m7g/.

Conclusion: The current study explored for the first time the m7G in pan-cancer and identified m7G as an innovative marker in predicting clinical outcomes and immunotherapeutic efficacy, with the potential for deeper integration with PPPM. Combining m7G within the framework of PPPM will provide a unique opportunity for clinical intelligence and new approaches.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00305-1.

Aims: Computer-aided detection systems for retinal fluid could be beneficial for disease monitoring and management by chronic age-related macular degeneration (AMD) and diabetic retinopathy (DR) patients, to assist in disease prevention via early detection before the disease progresses to a "wet AMD" pathology or diabetic macular edema (DME), requiring treatment. We propose a proof-of-concept AI-based app to help predict fluid via a "fluid score", prevent fluid progression, and provide personalized, serial monitoring, in the context of predictive, preventive, and personalized medicine (PPPM) for patients at risk of retinal fluid complications.

Methods: The app comprises a convolutional neural network-Vision Transformer (CNN-ViT)-based segmentation deep learning (DL) network, trained on a small dataset of 100 training images (augmented to 992 images) from the Singapore Epidemiology of Eye Diseases (SEED) study, together with a CNN-based classification network trained on 8497 images, that can detect fluid vs. non-fluid optical coherence tomography (OCT) scans. Both networks are validated on external datasets.

Results: Internal testing for our segmentation network produced an IoU score of 83.0% (95% CI = 76.7-89.3%) and a DICE score of 90.4% (86.3-94.4%); for external testing, we obtained an IoU score of 66.7% (63.5-70.0%) and a DICE score of 78.7% (76.0-81.4%). Internal testing of our classification network produced an area under the receiver operating characteristics curve (AUC) of 99.18%, and a Youden index threshold of 0.3806; for external testing, we obtained an AUC of 94.55%, and an accuracy of 94.98% and an F1 score of 85.73% with Youden index.

Conclusion: We have developed an AI-based app with an alternative transformer-based segmentation algorithm that could potentially be applied in the clinic with a PPPM approach for serial monitoring, and could allow for the generation of retrospective data to research into the varied use of treatments for AMD and DR. The modular system of our app can be scaled to add more iterative features based on user feedback for more efficient monitoring. Further study and scaling up of the algorithm dataset could potentially boost its usability in a real-world clinical setting.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00301-5.

Acute aortic dissection (AAD) is a severe aortic injury disease, which is often life-threatening at the onset. However, its early prevention remains a challenge. Therefore, in the context of predictive, preventive, and personalized medicine (PPPM), it is particularly important to identify novel and powerful biomarkers. This study aimed to identify the key markers that may contribute to the predictive early risk of AAD and analyze their role in immune infiltration. Three datasets, including a total of 23 AAD and 20 healthy control aortic samples, were retrieved from the Gene Expression Omnibus (GEO) database, and a total of 519 differentially expressed genes (DEGs) were screened in the training set. Using the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) algorithm, FERMT1 (AUC = 0.886) and SGCD (AUC = 0.876) were identified as key markers of AAD. A novel AAD risk prediction model was constructed using an artificial neural network (ANN), and in the validation set, the AUC = 0.920. Immune infiltration analysis indicated differential gene expression in regulatory T cells, monocytes, γδ T cells, quiescent NK cells, and mast cells in the patients with AAD and the healthy controls. Correlation and ssGSEA analysis showed that two key markers' expression in patients with AAD was correlated with many inflammatory mediators and pathways. In addition, the drug-gene interaction network identified motesanib and pyrazoloacridine as potential therapeutic agents for two key markers, which may provide personalized medical services for AAD patients. These findings highlight FERMT1 and SGCD as key biological targets for AAD and reveal the inflammation-related potential molecular mechanism of AAD, which is helpful for early risk prediction and targeted prevention of AAD. In conclusion, our study provides a new perspective for developing a PPPM method for managing AAD patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00302-4.

In the current era of medical revolution, genomic testing has guided the healthcare fraternity to develop predictive, preventive, and personalized medicine. Predictive screening involves sequencing a whole genome to comprehensively deliver patient care via enhanced diagnostic sensitivity and specific therapeutic targeting. The best example is the application of whole-exome sequencing when identifying aberrant fetuses with healthy karyotypes and chromosomal microarray analysis in complicated pregnancies. To fit into today's clinical practice needs, experimental system biology like genomic technologies, and system biology viz., the use of artificial intelligence and machine learning is required to be attuned to the development of preventive and personalized medicine. As diagnostic techniques are advancing, the selection of medical intervention can gradually be influenced by a person's genetic composition or the cellular profiling of the affected tissue. Clinical genetic practitioners can learn a lot about several conditions from their distinct facial traits. Current research indicates that in terms of diagnosing syndromes, facial analysis techniques are on par with those of qualified therapists. Employing deep learning and computer vision techniques, the face image assessment software DeepGestalt measures resemblances to numerous of disorders. Biomarkers are essential for diagnostic, prognostic, and selection systems for developing personalized medicine viz. DNA from chromosome 21 is counted in prenatal blood as part of the Down's syndrome biomarker screening. This review is based on a detailed analysis of the scientific literature via a vigilant approach to highlight the applicability of predictive diagnostics for the development of preventive, targeted, personalized medicine for clinical application in the framework of predictive, preventive, and personalized medicine (PPPM/3 PM). Additionally, targeted prevention has also been elaborated in terms of gene-environment interactions and next-generation DNA sequencing. The application of 3 PM has been highlighted by an in-depth analysis of cancer and cardiovascular diseases. The real-time challenges of genome sequencing and personalized medicine have also been discussed.

Lung cancer has a very high mortality in females and males. Most (~ 85%) of lung cancers are non-small cell lung cancers (NSCLC). When lung cancer is diagnosed, most of them have either local or distant metastasis, with a poor prognosis. In order to achieve better outcomes, it is imperative to identify the molecular signature based on genetic and epigenetic variations for different NSCLC subgroups. We hypothesize that DNA and histone modifications play significant roles in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Epigenetics has a significant impact on tumorigenicity, tumor heterogeneity, and tumor resistance to chemotherapy, targeted therapy, and immunotherapy. An increasing interest is that epigenomic regulation is recognized as a potential treatment option for NSCLC. Most attention has been paid to the epigenetic alteration patterns of DNA and histones. This article aims to review the roles DNA and histone modifications play in tumorigenesis, early detection and diagnosis, and advancements and therapies of NSCLC, and also explore the connection between DNA and histone modifications and PPPM, which may provide an important contribution to improve the prognosis of NSCLC. We found that the success of targeting DNA and histone modifications is limited in the clinic, and how to combine the therapies to improve patient outcomes is necessary in further studies, especially for predictive diagnostics, targeted prevention, and personalization of medical services in the 3P medicine approach. It is concluded that DNA and histone modifications are potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.