Human Digital Twin: A Survey

Digital twin has recently attracted growing attention, leading to intensive research and applications. Along with this, a new research area, dubbed as "human digital twin" (HDT), has emerged. Similar to the conception of digital twin, HDT is referred to as the replica of a physical-world human in the digital world. Nevertheless, HDT is much more complicated and delicate compared to digital twins of any physical systems and processes, due to humans' dynamic and evolutionary nature, including physical, behavioral, social, physiological, psychological, cognitive, and biological dimensions. Studies on HDT are limited, and the research is still in its infancy. In this paper, we first examine the inception, development, and application of the digital twin concept, providing a context within which we formally define and characterize HDT based on the similarities and differences between digital twin and HDT. Then we conduct an extensive literature review on HDT research, analyzing underpinning technologies and establishing typical frameworks in which the core HDT functions or components are organized. Built upon the findings from the above work, we propose a generic architecture for the HDT system and describe the core function blocks and corresponding technologies. Following this, we present the state of the art of HDT technologies and applications in the healthcare, industry, and daily life domain. Finally, we discuss various issues related to the development of HDT and point out the trends and challenges of future HDT research and development

A nomogram combining thoracic CT and tumor markers to predict the malignant grade of pulmonary nodules ≤3 cm in diameter

BackgroundWith the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging.MethodsA retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors.ResultsA total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful.ConclusionThe nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery

Distinguishing EGFR mutant subtypes in stage IA non-small cell lung cancer using the presence status of ground glass opacity and final histologic classification: a systematic review and meta-analysis

BackgroundThe progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.MethodsA complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.ResultsA total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04–3.13; p = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95–3.44; p = 0.07).ConclusionThis meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes

Nomogram combining clinical and radiological characteristics for predicting the malignant probability of solitary pulmonary nodules measuring ≤ 2 cm

BackgroundAt present, how to identify the benign or malignant nature of small (≤ 2 cm) solitary pulmonary nodules (SPN) are an urgent clinical challenge. This retrospective study aimed to develop a clinical prediction model combining clinical and radiological characteristics for assessing the probability of malignancy in SPNs measuring ≤ 2 cm.MethodIn this study, we included patients with SPNs measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to December 2021. Clinical features, preoperative biomarker results, and computed tomography characteristics were collected. The enrolled patients were randomized at a ratio of 7:3 into a training cohort of 775 and a validation cohort of 331. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. The receiver operating characteristic (ROC) curve was used to evaluate the identification ability of the model. The calibration power was evaluated using the Hosmer–Lemeshow test and calibration curve. The clinical utility of the nomogram was also assessed by decision curve analysis (DCA).ResultA total of 1,106 patients were included in this study. Among them, the malignancy rate of SPNs was 85.08% (941/1,106). We finally identified the following six independent risk factors by logistic regression: age, carcinoembryonic antigen, nodule shape, calcification, maximum diameter, and consolidation-to-tumor ratio. The area under the ROC curve (AUC) for the training cohort was 0.764 (95% confidence interval [CI]: 0.714–0.814), and the AUC for the validation cohort was 0.729 (95% CI: 0.647–0.811), indicating that the prediction accuracy of nomogram was relatively good. The calibration curve of the predictive model also demonstrated a good calibration in both cohorts. DCA proved that the clinical prediction model was useful in clinical practice.ConclusionWe developed and validated a predictive model and nomogram for estimating the probability of malignancy in SPNs measuring ≤ 2 cm. With the application of predictive models, thoracic surgeons can make more rational clinical decisions while avoiding overtreatment and wasting medical resources

The Molecular Biology of Prostate Cancer Stem Cells: From the Past to the Future

Prostate cancer (PCa) continues to rank as the second leading cause of cancer-related mortality in western countries, despite the golden treatment using androgen deprivation therapy (ADT) or anti-androgen therapy. With decades of research, scientists have gradually realized that the existence of prostate cancer stem cells (PCSCs) successfully explains tumor recurrence, metastasis and therapeutic failure of PCa. Theoretically, eradication of this small population may improve the efficacy of current therapeutic approaches and prolong PCa survival. However, several characteristics of PCSCs make their diminishment extremely challenging: inherent resistance to anti-androgen and chemotherapy treatment, over-activation of the survival pathway, adaptation to tumor micro-environments, escape from immune attack and being easier to metastasize. For this end, a better understanding of PCSC biology at the molecular level will definitely inspire us to develop PCSC targeted approaches. In this review, we comprehensively summarize signaling pathways responsible for homeostatic regulation of PCSCs and discuss how to eliminate these fractional cells in clinical practice. Overall, this study deeply pinpoints PCSC biology at the molecular level and provides us some research perspectives

Effects of Neoadjuvant Radiotherapy on Survival in Patients with Stage IIIA-N2 Non-Small-Cell Lung Cancer Following Pneumonectomy

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan–Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients

Effect of MSTN Mutation on Growth and Carcass Performance in Duroc × Meishan Hybrid Population

The Meishan pig is a traditional Chinese native breed, known for its excellent reproduction performance that is widely used in commercial pig production through two-way or three-way crossbreeding systems. However, the lean meat yield of Meishan crossbred pigs is still very low and cannot meet the market demand. To evaluate the lean meat yield of Meishan crossbred pigs, six wild-type Meishan sows were artificially inseminated by using the MSTN+/− Duroc boar semen in this experiment. Some reproductive performance-related traits of Meishan sows were recorded to ensure that semen from MSTN knockout Duroc boar did not affect offspring production, including total births, live births, sex, and litter weight. In total, 73 piglets were obtained and 63 were alive. Male to female ratio was close to 1: 1. because of factors such as disease, only 43 pigs were utilized, including 28 MSTN mutant pigs (MSTN+/−) and 15 MSTN homozygous pigs (MSTN+/+). We compared the growth performance and carcass performance of these full or half-sib populations and found that there were no differences between MSTN+/− and MSTN+/+ genotypes for live animal measures including average daily gain (ADG), body dimensions, or ultrasonic measurement of fat thickness when pigs were harvested after 120 days of feeding. Conversely, the MSTN+/− pigs had higher dressing percentage and lean meat percentage, lower level of carcass fat, larger longissimus muscle area, less percentage of skin and skeleton, thinner average backfat thickness, and lower intramuscular fat (IMF) content than MSTN+/+ pigs. In conclusion, the production of MSTN+/− mutant progeny from Meishan females resulted in improved carcass composition, providing a feasible solution to improve the lean meat yield of Chinese local fat-type pig breeds

A Review on Serious Games for Dementia Care in Ageing Societies

Dementia is a severe disease threatening ageing societies, which not only causes great harm to patients both physically and psychologically but also places a heavy burden on patients' families. Medications have been used for the treatment of dementia but with little success. However, serious games, as a new form of dementia therapy, stand out from various therapeutic methods and pave the way for dementia treatment. In the field of serious games for dementia care (SGDC) in ageing societies, there exists abundant research related to this topic. While, a detailed review of the development route and a category framework for characteristics of dementia are still needed. Besides, due to the large number of games, it is difficult to select out effective ones. Yet, there is no unified and comprehensive assessment methods for SGDC. So a reliable assessment model is worth studying. In this paper, we review these existing research work on SGDC from two perspectives: (1) the development of SGDC; (2) the different symptoms in different dementia stages. We also propose a comprehensive and professional assessment model of the therapeutic effectiveness of SGDC to compensate for the simplicity of existing assessment methods. Finally, a discussion related to SGDC is presented

Comprehensive Analysis of Porcine Prox1 Gene and Its Relationship with Meat Quality Traits

Prox1 is involved in muscle fiber conversion, adult-onset obesity, and type 2 diabetes. However, information regarding porcine Prox1 and its relationship with meat quality traits is still unknown. In this study, we characterized the full-length cDNA and proximal promoter of two transcript variants of porcine Prox1. Moreover, Prox1 was expressed abundantly in the skeletal muscle and its expression was higher in the soleus muscle than that in the biceps femoris muscle. Its expression pattern in the high and low meat color (redness) value a* groups was similar to that of myoglobin and MyHC I, but opposed to that of MyHC IIB. Importantly, there was a significant positive correlation between Prox1 expression and meat color (redness) value a* (r = 0.3845, p = 0.0394), and a significant negative correlation between Prox1 expression and drip loss (r = −0.4204, p = 0.0232), as well as the ratio of MyHC IIB to MyHC I expression (r = −0.3871, p = 0.0380). In addition, we found that the polymorphisms of three closely linked SNPs in Prox1 promoter 1 were significantly associated with pH24h in a pig population. Taken together, our data provide valuable insights into the characteristics of porcine Prox1 and indicate that Prox1 is a promising candidate gene affecting meat quality traits

A Key Gene, PLIN1, Can Affect Porcine Intramuscular Fat Content Based on Transcriptome Analysis

Intramuscular fat (IMF) content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs) between the higher (H) and lower (L) IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the DEG perilipin-1 (PLIN1) was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR) signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG) level and lipid droplet (LD) size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation