The significance of machine learning in neonatal screening for inherited metabolic diseases

BackgroundNeonatal screening for inherited metabolic diseases (IMDs) has been revolutionized by tandem mass spectrometry (MS/MS). This study aimed to enhance neonatal screening for IMDs using machine learning (ML) techniques.MethodsThe study involved the analysis of a comprehensive dataset comprising 309,102 neonatal screening records collected in the Ningbo region, China. An advanced ML system model, encompassing nine distinct algorithms, was employed for the purpose of predicting the presence of 31 different IMDs. The model was compared with traditional cutoff schemes to assess its diagnostic efficacy. Additionally, 180 suspected positive cases underwent further evaluation.ResultsThe ML system exhibited a significantly reduced positive rate, from 1.17% to 0.33%, compared to cutoff schemes in the initial screening, minimizing unnecessary recalls and associated stress. In suspected positive cases, the ML system identified 142 true positives with high sensitivity (93.42%) and improved specificity (78.57%) compared to the cutoff scheme. While false negatives emerged, particularly in heterozygous carriers, our study revealed the potential of the ML system to detect asymptomatic cases.ConclusionThis research provides valuable insights into the potential of ML in pediatric medicine for IMD diagnosis through neonatal screening, emphasizing the need for accurate carrier detection and further research in this domain

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.National Natural Science Foundation of China [32022078]; National Key R&D Program of China [2022YFF1000900]; Local Innovative and Research Teams Project of Guangdong Province [2019BT02N630]; China Agriculture Research System [CARS-35]. Funding for open access charge: National Natural Science Foundation of China [32022078].Peer reviewe

Research on Initial Model Construction of Seismic Inversion Based on Velocity Spectrum and Siamese Network

The initial model plays an important role in seismic inversion. Generally, the initial model is constructed by lateral extrapolation of parameters under horizons constraints. However, without horizon data, initial modeling becomes a challenging task. Velocity spectrum is a 2D image that can reflect the characteristics of the formations. We regard the problem of establishing the initial model as the problem of similarity analysis of seismic lateral characteristics and propose a method of establishing the initial inversion model based on velocity spectrum and Siamese network. Firstly, the lateral variation of formation characteristics is tracked on velocity spectra generated by common depth point (CDP) gathers. Then, the target tracking results at different CDP positions are obtained with the triple Siamese network. Finally, the discrete inversion parameters are extrapolated along the tracking paths to obtain the initial inversion model. The Siamese network can quickly obtain the similarity of 2D images and does not need manual labels. The theoretical and practical results show that our method can efficiently generate the initial model that conforms to the seismic structure and stratigraphic characteristics without the constraint of interpreted horizon data

Research on Initial Model Construction of Seismic Inversion Based on Velocity Spectrum and Siamese Network

The initial model plays an important role in seismic inversion. Generally, the initial model is constructed by lateral extrapolation of parameters under horizons constraints. However, without horizon data, initial modeling becomes a challenging task. Velocity spectrum is a 2D image that can reflect the characteristics of the formations. We regard the problem of establishing the initial model as the problem of similarity analysis of seismic lateral characteristics and propose a method of establishing the initial inversion model based on velocity spectrum and Siamese network. Firstly, the lateral variation of formation characteristics is tracked on velocity spectra generated by common depth point (CDP) gathers. Then, the target tracking results at different CDP positions are obtained with the triple Siamese network. Finally, the discrete inversion parameters are extrapolated along the tracking paths to obtain the initial inversion model. The Siamese network can quickly obtain the similarity of 2D images and does not need manual labels. The theoretical and practical results show that our method can efficiently generate the initial model that conforms to the seismic structure and stratigraphic characteristics without the constraint of interpreted horizon data

Cyclodextrin-Based Nanoplatforms for Tumor Phototherapy: An Update

Tumor phototherapies are light-mediated tumor treatment modalities, which usually refer to tumor photothermal therapy (PTT) and photodynamic therapy (PDT). Due to the outstanding spatial-temporal control over treatment through light irradiation, tumor phototherapies display extremely low side effects during treatment and are believed to be a tumor treatment method with a clinical translation potential. However, current tumor phototherapy nanoplatforms face obstacles, including light irradiation-induced skin burning, tumor hypoxia microenvironments, limited light penetration depth, et al. Therefore, one important research direction is developing a tumor phototherapy nanoplatform with multifunctionality and enhanced pharmacological effects to overcome the complexity of tumor treatment. On the other hand, cyclodextrins (CDs) are starch-originated circular oligosaccharides with negligible toxicity and have been used to form supermolecular nanostructures through a host–guest interaction between the inner cavity of CDs and functional biomolecules. In the past few years, numerous studies have focused on CD-based multifunctional tumor phototherapy nanoplatforms with an enhanced photoeffect, responsive morphological transformation, and elevated drug bioavailability. This review focuses on the preparation methods of CD-based tumor phototherapy nanoplatforms and their unique physiochemical properties for improving anti-tumor pharmacological efficacy

Multiple Roles of Black Raspberry Anthocyanins Protecting against Alcoholic Liver Disease

This study aimed to investigate the protective effect of black raspberry anthocyanins (BRAs) against acute and subacute alcoholic liver disease (ALD). Network analysis and docking study were carried out to understand the potential mechanism. Thereafter, the serum biochemical parameters and liver indexes were measured, the histopathological changes of the liver were analyzed in vivo. The results showed that all tested parameters were ameliorated after the administration of BRAs with alcohol. Meanwhile, there was increased protein expression of NF-κB and TGF-β in extracted livers, which was associated with hepatitis and hepatic fibrosis. Furthermore, BRAs and cyanidin-3-O-rutinoside exhibited cytotoxic effects on t-HSC/Cl-6, HepG2, and Hep3B and induced the apoptosis of HepG2 cells; downregulated the protein expression level of Bcl-2; upregulated the level of Bax; and promoted the release of cytochrome C, cleaved caspase-9, cleaved caspase-3, and cleaved PARP in HepG2 cells. In addition, the antioxidant activity of BRAs was tested, and the chemical components were analyzed by FT-ICR MS. The results proved that BRAs exert preventive effect on ALD through the antioxidant and apoptosis pathways

Evaluation of Cognitive Impairment in Patients with Minimal Hepatic Encephalopathy Based on Degree Centrality of Resting-state Blood Oxygenation Level-dependent Functional Magnetic Resonance Imaging

Background Minimal hepatic encephalopathy has atypical clinical symptoms but mild neuropsychiatric deficits, which are easily neglected by patients and their family members as a specific type of hepatic encephalopathy. The degree centrality (DC) analysis method based on resting-state blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) is a data analysis method derived from graph-theoretic approach reflecting whole-brain network connectivity, which can provide a more complete, faster and better representation of brain function. Objective To explore the effects of abnormal changes in the brain functional network connectivity properties and functional brain regions on cognitive function in patients with minimal hepatic encephalopathy and their neuroimaging mechanisms. Methods A total of 65 patients with hepatitis B cirrhosis hospitalized in the department of infectious diseases in General Hospital of Ningxia Medical University from October 2020 to February 2022 and 40 healthy volunteers recruited during the same period were selected as the study subjects. Gender, age, education level, number connection test A (NCT-A) score, digit symbol test (DST) score and Montreal cognitive assessment (MoCA) score of the study subjects were collected. Finally, patients with hepatitis B cirrhosis were divided into cirrhosis group (n=30) and MHE group (n=28) according to NCT-A and DST scores, and the recruited healthy volunteers were considered as the healthy control group (n=34) . The DC values of brain regions in each group were calculate, the differences in DC values of brain image between MHE group and cirrhosis group, cirrhosis group and healthy control group, MHE group and healthy control group were compared, respectively. The correlations between the DC values of brain regions with the scores of NCT-A, DST and MoCA in MHE patients was analyzed by using person correlation analysis, the distribution of brain regions with DC values correlated with the scores of above scales and the corresponding scatter plots were drawn. Results The NCT-A score in the healthy control and cirrhotic group was lower than MHE group, DST score and MoCA score in the healthy control and cirrhotic group were higher than MHE group (P&lt;0.05) . Compared with healthy control group, the MHE group had increased DC values in right middle frontal gyrus, left middle temporal gyrus, right inferior parietal lobule and decreased DC values in left angular gyrus, right middle occipital gyrus, right precentral gyrus (voxel cluster&gt;18, P&lt;0.05) . Compared with healthy control group, cirrhotic group had increased DC values in the bilateral middle temporal gyrus and decreased DC values in the left angular gyrus (voxel cluster&gt;18, P&lt;0.05) ; compared with cirrhotic group, MHE group had decreased values in the right middle temporal gyrus and left precuneus (voxel cluster&gt;18, P&lt;0.05) . The results of correlation analysis showed that in the MHE group, the DST score was correlated with DC values in the left superior temporal gyrus (r=0.639, P&lt;0.001) , and the NCT-A score was negatively correlated with the DC values in the right inferior temporal gyrus (r=-0.722, P&lt;0.001) ; MoCA scale score was positively correlated with DC values in the right inferior frontal gyrus and left inferior frontal gyrus (r=0.437, P=0.020; r=0.549, P=0.002) and negatively correlated with DC values in the left inferior temporal gyrus (r=-0.591, P=0.001) . Conclusion The abnormal functional connectivity of several brain regions and the correlation of DC values in some brain regions with NCT-A, DST and MoCA scale scores in MHE patients suggest that DC value may be a potential neuroimaging marker to quantify the severity of cognitive changes in MHE patients

Prognostic value of systemic immune-inflammation index/ albumin for transcatheter arterial chemoembolization treatment

Background and objective: In the process of tumor occurrence, evolution and development, immune, inflammation and nutrition are principal elements. The purpose of this study was to assess the prognostic value of systemic immune-inflammation index/albumin (SII/ALB) for patients with HBV-related hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE). Methods: A total of 125 HBV-related HCC patients met inclusion criteria and were all enrolled in this research. The survminer R package. was used to calculate the best SII/ALB cutoff values. Chi-square test was used to analyze the relationship between SII/ALB and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards models were used to investigate the effect of SII/ALB on overall survival (OS). Results: The cutoff value of SII/ALB was 2.992. In the derivation cohort, the patients were divided into SII/ALB-low (SII/ALB≤2.992) and SII/ALB-high (SII/ALB >2.992) groups. SII/ALB-high was found in patients with tumor size ≥3 (cm), white blood cell ≥3.5 (109/L), platelet ≥100 (109/L), neutrophils ≥1.8 (109/L), PT ≥ 14(s), SII ≥100, NLR ≥1.50 and PLR ≥60, (P < 0.05). The Kaplan–Meier curves showed that elevated SII/ALB were associated with decreased OS. OS rate of SII/ALB-low and SII/ALB-high groups at 1 and 2 years were 96.6% vs. 70.3% and 87.8% vs. 48.5%, respectively (C2 = 9.804, P = 0.002). The BCLC stage, tumor number, tumor size, vascular invasion, AST, SII/ALB, SII, NLR and PNI were all significant prognostic indicators of OS. The SII/ALB (HR: 17.98; 95%CI: 1.82–177.32) and tumor size (HR: 3.26; 95%CI: 1.27–8.35) were all independent prognostic factors for OS, (p < 0.05).Conclusion: we found that SII/ALB could be an important prognostic parameter for HBV-related HCC patients after TACE treatment

Comparative Study of the Short-Term Efficacy and Safety between DEB-TACE and C-TACE in the Treatment of Unresectable Hepatocellular Carcinoma, a Retrospective Study

Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups’ progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant ( P  > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group ( P  < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group ( P  < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference ( P  < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. Conclusion: DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma