Development of machine learning-based personalized predictive models for risk evaluation of hepatocellular carcinoma in hepatitis B virus-related cirrhosis patients with low levels of serum alpha-fetoprotein.

INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.

OBJECTIVE: To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population. STUDY DESIGN: We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months). We investigated associations of growth velocities as well as their interactions with birthweight-for-gestational age on mid-childhood (mean age: 7.9 years) IQ, visual memory and learning, and visual motor ability. RESULTS: Greater overall height velocity was associated with modestly higher design memory score, (adjusted ß [95% CI] 0.19 [-0.01,0.38] P = .057])points per SD increase but lower verbal IQ (-0.88 [-1.76,0.00] P = .051). Greater early infancy height velocity was associated with higher visual motor score (1.92 [0.67,3.18]). Greater overall BMI velocity was associated with lower verbal IQ (-0.71 [-1.52,0.11] P = .090). Greater late infancy BMI velocity was associated with lower verbal IQ (-1.21 [-2.07,-0.34]), design memory score (-0.22 [-0.42,-0.03)], but higher picture memory score (0.22 [0.01,0.43]). Greater early infancy height velocity (-1.5 SD vs 1.5 SD) was associated with higher nonverbal IQ (margins [95% CI] 102.6 [98.9106.3] vs 108.2 [104.9111.6]) among small-for-gestational age infants (P-interaction = 0.04). CONCLUSIONS: Among generally well-nourished children, there might not be clear cognitive gains with faster linear growth except for those with lower birthweight-for-gestational age, revealing the potential importance of early infancy compensatory growth.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia.

OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia

SUMMARY OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

The heterogeneity of the COVID-19 pandemic and national responses: an explanatory mixed-methods study.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) has quickly spread to all corners of the world since its emergence in Wuhan, China in December of 2019. The disease burden has been heterogeneous across regions of the world, with Americas leading in cumulative cases and deaths, followed by Europe, Southeast Asia, Eastern Mediterranean, Africa and Western Pacific. Initial responses to COVID-19 also varied between governments, ranging from proactive containment to delayed intervention. Understanding these variabilities allow high burden countries to learn from low burden countries on ways to create more sustainable response plans in the future. METHODS: This study used a mixed-methods approach to perform cross-country comparisons of pandemic responses in the United States (US), Brazil, Germany, Australia, South Korea, Thailand, New Zealand, Italy and China. These countries were selected based on their income level, relative COVID-19 burden and geographic location. To rationalize the epidemiological variability, a list of 14 indicators was established to assess the countries' preparedness, actual response, and socioeconomic and demographic profile in the context of COVID-19. RESULTS: As of 1 April 2021, the US had the highest cases per million out of the nine countries, followed by Brazil, Italy, Germany, South Korea, Australia, New Zealand, Thailand and China. Meanwhile, Italy ranked first out of the nine countries' total deaths per million, followed by the US, Brazil, Germany, Australia, South Korea, New Zealand, China and Thailand. The epidemiological differences between these countries could be explained by nine indicators, and they were 1) leadership, governance and coordination of response, 2) communication, 3) community engagement, 4) multisectoral actions, 5) public health capacity, 6) universal health coverage, 7) medical services and hospital capacity, 8) demography and 9) burden of non-communicable diseases. CONCLUSION: The COVID-19 pandemic manifests varied outcomes due to differences in countries' vulnerability, preparedness and response. Our study rationalizes why South Korea, New Zealand, Thailand, Australia and China performed better than the US, Italy and Brazil. By identifying the strengths of low burden countries and weaknesses of hotspot countries, we elucidate factors constituting an effective pandemic response that can be adopted by leaders in preparation for re-emerging public health threats.

Effects of melanocortin 1 receptor (MC1R) gene polymorphisms on plumage color in mule ducks

The objective of the present study was to investigate the effect of single nucleotide polymorphism (SNP) of the melanocortin 1 receptor (MC1R) gene on plumage coloration in mule ducks. PCR-high-resolution melting analysis (PCR-HRM) and DNA sequencing were used to identify the SNP variability of the MC1R gene in white common ducks. Three non-synonymous SNP (MC1R gene exon 1, c.52G>A, c.376G>A, and c.409G>A) were identified in white Tsaiya ducks. Mating test (white Tsaiya ducks × white Muscovy drakes) in combination with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to investigate the effect of non-synonymous SNP of different maternal lines on plumage coloration in mule ducks. Genotyping results from 58 white Tsaiya ducks revealed the significant associations between genetic variations (c.52G>A, c.376A>G, and c.409G>A) and plumage color in two maternal populations. After genotyping of 266 mule ducks, these three non-synonymous SNP identified in white Tsaiya ducks were significantly associated with plumage color of mule ducks. Therefore, the polymorphisms of MC1R gene at c.52G>A, c.376A>G, and c.409G>A in white Tsaiya duck could be used in marker-assisted selection to improve the plumage color of mule ducks.(AU)

High-level expression of modified gene encoding human adiponectin in transgenic rice.

Adiponectin is a polypeptide specifically secreted from human adipocytes, and its deficiency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modified genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplification promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confirmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modified gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.

High-level expression of modified gene encoding human adiponectin in transgenic rice

Adiponectin is a polypeptide specifically secreted from human adipocytes, and its deficiency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modified genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplification promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confirmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modified gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.