Predicting 3-month poor functional outcomes of acute ischemic stroke in young patients using machine learning.

BACKGROUND: Prediction of short-term outcomes in young patients with acute ischemic stroke (AIS) may assist in making therapy decisions. Machine learning (ML) is increasingly used in healthcare due to its high accuracy. This study aims to use a ML-based predictive model for poor 3-month functional outcomes in young AIS patients and to compare the predictive performance of ML models with the logistic regression model. METHODS: We enrolled AIS patients aged between 18 and 50 years from the Third Chinese National Stroke Registry (CNSR-III), collected between 2015 and 2018. A modified Rankin Scale (mRS) ≥ 3 was a poor functional outcome at 3 months. Four ML tree models were developed: The extreme Gradient Boosting (XGBoost), Light Gradient Boosted Machine (lightGBM), Random Forest (RF), and The Gradient Boosting Decision Trees (GBDT), compared with logistic regression. We assess the model performance based on both discrimination and calibration. RESULTS: A total of 2268 young patients with a mean age of 44.3 ± 5.5 years were included. Among them, (9%) had poor functional outcomes. The mRS at admission, living alone conditions, and high National Institutes of Health Stroke Scale (NIHSS) at discharge remained independent predictors of poor 3-month outcomes. The best AUC in the test group was XGBoost (AUC = 0.801), followed by GBDT, RF, and lightGBM (AUCs of 0.795, 0, 794, and 0.792, respectively). The XGBoost, RF, and lightGBM models were significantly better than logistic regression (P < 0.05). CONCLUSIONS: ML outperformed logistic regression, where XGBoost the boost was the best model for predicting poor functional outcomes in young AIS patients. It is important to consider living alone conditions with high severity scores to improve stroke prognosis.

Predictive etiological classification of acute ischemic stroke through interpretable machine learning algorithms: a multicenter, prospective cohort study.

BACKGROUND: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology. OBJECTIVE: We aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization. METHODS: This study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration. RESULTS: A total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%). CONCLUSIONS: The ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients' etiology and initiate optimal strategies for secondary prevention.

Modulating apoptosis as a novel therapeutic strategy against Respiratory Syncytial Virus infection: insights from Rotenone.

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infections, particularly in vulnerable populations such as neonates, infants, young children, and the elderly. Among infants, RSV is the primary cause of bronchiolitis and pneumonia, contributing to a notable proportion of child mortality under the age of 5. In this study, we focused on investigating the pathogenicity of a lethal RSV strain, GZ08-18, as a model for understanding mechanisms of hypervirulent RSV. Our findings indicate that the heightened pathogenicity of GZ08-18 stems from compromised activation of intrinsic apoptosis, as evidenced by aberration of mitochondrial membrane depolarization in host cells. We thus hypothesized that enhancing intrinsic apoptosis could potentially attenuate the virulence of RSV strains and explored the effects of Rotenone, a natural compound known to stimulate the intrinsic apoptosis pathway, on inhibiting RSV infection. Our results demonstrate that Rotenone treatment significantly improved mouse survival rates and mitigated lung pathology following GZ08-18 infection. These findings suggest that modulating the suppressed apoptosis induced by RSV infection represents a promising avenue for antiviral intervention strategies.

The role of AbaI quorum sensing molecule synthase in host cell inflammation induced by Acinetobacter baumannii and its effect on zebrafish infection model.

Acinetobacter baumannii is currently one of the most important opportunistic pathogens causing severe nosocomial infections worldwide. Quorum Sensing (QS) system is a widespread mechanism in bacteria to coordinate group behavior by sensing the density of bacterial populations and affect eukaryotic host cell. In Acinetobacter baumannii, AbaI protein is used as QS molecule synthetase to synthesize N- acyl homoserine lactones (AHLs). Currently, QS has made great progress in the study of drug resistance, but there is still a lack of complete understanding of its damage to host cells after adhesion and invasion. Thus, in this study, we examined the effects of abaI mutant (ΔabaI) on the functions of adhesion and invasion, cell viability, inflammation, apoptosis in A. baumannii infected A549 cells, to evaluate the effects of ΔabaI in a zebrafish model. We found the group infected with ΔabaI increased cell viability, reduced adhesion and invasion, cell injury, inflammatory cytokine production and apoptosis. By RNA-Seq, we explored the possibility that abaI stimulated A549 cells inflammation by A. baumannii infection via TLR4/MAPK signaling pathway. In addition, the ΔabaI significantly reduced pathogenicity and recruitment to neutrophils in zebrafish. These observations suggest that abaI plays a major role in A. baumannii infection.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

Generation and characterization of an induced pluripotent stem cell (iPSC) line SDQLCHi063-A from peripheral blood mononuclear cells of a patient with Maturity-onset diabetes of the young type 2 carrying GCK exon 1 deletion.

Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant disorder caused by mutations in the GCK gene. It is characterized by a non-progressive slight increase in glycosylated hemoglobin (HbA1c), and mildly raised fasting glucose. Here, we generated an induced pluripotent stem cell line SDQLCHi063-A from a five-year-old boy with MODY2 carrying exon 1 deletion of the GCK gene (OMIM*138079). The iPSC line carries original gene mutation, expresses pluripotency markers, has normal karyotype and differentiated spontaneously in the three germ layers.

PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness.

Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.

Health-promoting compounds in Amomum villosum Lour and Amomum tsao-ko: Fruit essential oil exhibiting great potential for human health.

The Zingiberaceae family serves as a diverse repository of bioactive phytochemicals, comprising approximately 52 genera and 1300 species of aromatic perennial herbs distinguished by their distinct creeping horizontal or tuberous rhizomes. Amomum villosum Lour. and Amomum tsao-ko Crevost & Lemaire., are the important plants of family Zingiberaceae that have been widely used in traditional medicine for the treatment of many ailments. The Amomum species are employed for their aromatic qualities and are valued as spices and flavorings. In the essential oils (EOs) of Amomum species, notable constituents include, camphor, methyl chavicol, bornyl acetate, trans-p-(1-butenyl) anisole, α-pinene, and ß-pinene. OBJECTIVE: The aim of this review is to present an overview of pharmacological studies pertaining to the extracts and secondary metabolites isolated from both species. The foremost objective of review is not only to increase the popularity of Amomum as a healthy food choice but also to enhance its status as a staple ingredient for the foreseeable future. RESULT: We endeavored to gather the latest information on antioxidant, antidiabetic, anticancer, antiobesity, antimicrobial, and anti-inflammatory properties of plants as well as their role in neuroprotective diseases. Research conducted through in-vitro studies, animal model, and compounds analysis have revealed that both plants exhibit a diverse array health promoting properties. CONCLUSION: the comprehensive review paper provides valuable insights into the diverse range of bioactive phytochemicals found in A. villosum and A. tsao-ko, showcasing their potential in preventing diseases and promoting overall human well-being. The compilation of information on their various health-enhancing properties contributes to the broader understanding of these plants and their potential applications in traditional medicine and beyond.

AI-Enabled Soft Sensing Array for Simultaneous Detection of Muscle Deformation and Mechanomyography for Metaverse Somatosensory Interaction.

Motion recognition (MR)-based somatosensory interaction technology, which interprets user movements as input instructions, presents a natural approach for promoting human-computer interaction, a critical element for advancing metaverse applications. Herein, this work introduces a non-intrusive muscle-sensing wearable device, that in conjunction with machine learning, enables motion-control-based somatosensory interaction with metaverse avatars. To facilitate MR, the proposed device simultaneously detects muscle mechanical activities, including dynamic muscle shape changes and vibrational mechanomyogram signals, utilizing a flexible 16-channel pressure sensor array (weighing ≈0.38 g). Leveraging the rich information from multiple channels, a recognition accuracy of ≈96.06% is achieved by classifying ten lower-limb motions executed by ten human subjects. In addition, this work demonstrates the practical application of muscle-sensing-based somatosensory interaction, using the proposed wearable device, for enabling the real-time control of avatars in a virtual space. This study provides an alternative approach to traditional rigid inertial measurement units and electromyography-based methods for achieving accurate human motion capture, which can further broaden the applications of motion-interactive wearable devices for the coming metaverse age.

Generation and characterization of PBMCs-derived human induced pluripotent stem cell (iPSC) line SDQLCHi055-A from a patient with NEDSDV carrying a heterozygote mutation in the CTNNB1 gene.

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, #615075), a rare autosomal dominant genetic disorder caused by heterozygous mutation in the CTNNB1 gene, is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Here, we established an iPSC line (SDQLCHi055-A) from a patient with NEDSDV carrying a heterozygote mutation (c.854 T > A, p.L285*) in the CTNNB1 gene. The iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

Generation of a human induced pluripotent stem cell line (SDQLCHi057-A) from an Isovaleric aciduria patient carrying novel compound heterozygous mutations in the IVD gene.

Isovaleric acidemia (IVA; OMIM ID#243500) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD). In this study, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi057-A from a 2-year-7-month old boy with IVA carrying two heterozygous missense mutations c.215A > G (p.N72S) and c.883A > G (p.M295V) of the IVD gene. Patient-specific hiPSCs provide a proper model for further understanding this rare disease.

Generation of an induced pluripotent stem cell line (SDQLCHi067-A) from a patient with subcortical band heterotopia harboring a heterozygous mutation in DCX gene.

Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.

Charged Fibrous Dressing to Promote Diabetic Chronic Wound Healing.

Diabetic chronic wounds cause a significant amount of pain to patients because of their low cure rates and high recurrence rates. Traditional approaches to treating diabetic chronic wounds often involve the delivery of drugs or cytokines that regulate the microenvironment and eliminate bacterial infection in the wound area, but they are passive in controlling cell behaviors and may lead to drug resistance. Emerging drug-free wound treatments are important for convenient, effective, and safe treatment strategies. However, the current approaches cannot fully promote tissue regeneration or prevent bacterial infections. Here, the efficacy of a negatively charged fiber dressing in promoting diabetic chronic wound healing is investigated. The negatively charged fiber dressing can generate reactive oxygen species to inhibit bacterial reproduction with the assistance of ultrasound during the inflammatory phase. Furthermore, the dressing provides an electrostatic field that regulates cellular behavior during the inflammatory and proliferative phases. In particular, the dressing can promote fibroblast migration and induce macrophage polarization and neovascularization without any additional drugs. It is demonstrated that this strategy enables the healing of diabetic chronic wounds in a mouse model, achieving effective wound closure over a 12-day treatment cycle and providing a drug-free therapeutic strategy for diabetic chronic wound care.

Generation and characterization of PBMCs-derived human induced pluripotent stem cell (iPSC) line SDQLCHi050-A from a healthy donor.

The human induced pluripotent stem cell (iPSC) line SDQLCHi050-A was derived from the PBMCs of a healthy 5-year-old male child. The karyotyping, pluripotency, and trilineage differentiation characteristics were verified in the SDQLCHi050-A line.

Efficacy of a WeChat-Based Multimodal Digital Transformation Management Model in New-Onset Mild to Moderate Hypertension: Randomized Clinical Trial.

BACKGROUND: The advantages of multimodal digitally transformed mobile health management for patients diagnosed with mild to moderate hypertension are not yet established. OBJECTIVE: We aim to evaluate the therapeutic benefits of a novel WeChat-based multimodal digital transforming management model in mobile health blood pressure (BP) management. METHODS: This randomized controlled clinical trial included 175 individuals with new-onset mild to moderate hypertension who were admitted to our center between September and October 2022. The patients were randomly assigned to either the multimodal intervention group (n=88) or the usual care group (n=87). The primary composite outcome was home and office BP differences after 6 months. The major secondary outcomes were 6-month quality-of-life scores, including the self-rating anxiety scale, self-rating depression scale, and Pittsburgh Sleep Quality Index. RESULTS: The mean home BP decreased from 151.74 (SD 8.02)/94.22 (SD 9.32) to 126.19 (SD 8.45)/82.28 (SD 9.26) mm Hg in the multimodal intervention group and from 150.78 (SD 7.87)/91.53 (SD 9.78) to 133.48 (SD 10.86)/84.45 (SD 9.19) mm Hg in the usual care group, with a mean difference in systolic blood pressure and diastolic blood pressure of -8.25 mm Hg (95% CI -11.71 to -4.78 mm Hg; P<.001) and -4.85 mm Hg (95% CI -8.41 to -1.30 mm Hg; P=.008), respectively. The mean office BP decreased from 153.64 (SD 8.39)/93.56 (SD 8.45) to 127.81 (SD 8.04)/ 82.16 (SD 8.06) mm Hg in the multimodal intervention group and from 151.48 (SD 7.14)/(91.31 (SD 9.61) to 134.92 (SD 10.11)/85.09 (SD 8.26) mm Hg in the usual care group, with a mean difference in systolic blood pressure and diastolic blood pressure of -9.27 mm Hg (95% CI -12.62 to -5.91 mm Hg; P<.001) and -5.18 mm Hg (95% CI -8.47 to -1.89 mm Hg; P=.002), respectively. From baseline to 6 months, home BP control <140/90 mm Hg was achieved in 64 (72.7%) patients in the multimodal intervention group and 46 (52.9%) patients in the usual care group (P=.007). Meanwhile, home BP control <130/80 mm Hg was achieved in 32 (36.4%) patients in the multimodal intervention group and 16 (18.4%) patients in the usual care group (P=.008). After 6 months, there were significant differences in the quality-of-life total and graded scores, including self-rating anxiety scale scores (P=.04), self-rating depression scale scores (P=.03), and Pittsburgh Sleep Quality Index scores (P<.001), in the multimodal intervention group compared with the usual care group. CONCLUSIONS: The WeChat-based multimodal intervention model improved the BP control rates and lowered the BP levels more than the usual care approach. The multimodal digital transforming management model for hypertension represents an emerging medical practice that utilizes the individual's various risk factor profiles for primary care and personalized therapy decision-making in patients with hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200063550; https://www.chictr.org.cn/showproj.html?proj=175816.

Geographic differences and variation of functional components of brown rice in 690 mini-core collections from global germplasms.

Objective: To understand the geographic differences and variations in the functional components of brown rice cores collected from global rice germplasms. Methods: Four functional components, γ-aminobutyric acid (GABA), resistant starch (RS), total flavonoids, and alkaloids, in brown rice from 690 mini-core collections from 31 countries from five continents and the International Rice Research Institute, were analyzed using a spectrophotometry colorimetric method, and the results were statistically validated. Conclusion: The highest average amounts of functional components were obtained in Asian germplasms, except for GABA, and total flavonoids were highest in brown rice from Europe and Oceania, followed by Asia. The highest coefficient of variation for GABA was observed in Asia; that for RS and total flavonoids was observed in Africa, followed by Asia; and that for alkaloids was observed in America, followed by Asia. Overall, Asian countries were the most prominent and representative zones with the highest genotypic potential for functional components of brown rice. Forty-one rice accessions with enriched functional components originated mostly from biodiversity-rich areas in China, followed by those in the Philippines. Late sowing favored the enrichment of these components in brown rice. The current study provides a reference for rice breeding with enriched functional constituents, and guidelines for screening functional rice that could be used for human chronic disease research.

Prevalence and Prognostic Value of Atrial Cardiopathy in Embolic Stroke of Undetermined Source.

INTRODUCTION: We utilized data from the Third China National Stroke Registry to investigate the prevalence of atrial cardiopathy markers in patients with embolic stroke of undetermined source (ESUS) and to assess their association with death and stroke recurrence. METHODS: In China, patients experiencing transient ischemic attack or ischemic stroke were recruited consecutively by the Third China National Stroke Registry. We compared atrial cardiopathy markers, such as left atrial (LA) enlargement, increased P-wave terminal force in lead V1 (PTFV1), premature atrial contractions, paroxysmal supraventricular tachycardia, advanced interatrial block, prolonged PR interval, prolonged P-wave dispersion, and prolonged P-wave duration between ESUS patients and those with small vessel disease and large artery atherosclerosis strokes. The association between these markers and the recurrence of stroke as well as mortality risk in ESUS patients was evaluated using Cox regression analysis. RESULTS: Of 8528 ischemic stroke patients who underwent a standard diagnostic work-up, 2415 were identified as having ESUS. Multivariable analysis revealed a significant association between elevated PTFV1 and an increased risk of stroke recurrence (HR: 2.50; 95% CI: 1.53-4.09; p < 0.01) as well as mortality (HR: 3.76; 95% CI: 1.58-8.91; p < 0.01) at 1 year in patients with ESUS. Furthermore, we observed that moderate-severe LA enlargement slightly increased the risk of stroke recurrence in patients with ESUS (HR: 1.95; 95% CI: 0.90-4.26; p = 0.09). Both LA diameter (HR: 1.03; 95% CI: 1.00-1.06; p = 0.03) and the top quartile of the LA diameter index (HR: 1.56; 95% CI: 1.03-2.40; p = 0.04) were associated with stroke recurrence in patients with ESUS. CONCLUSIONS: PTFV1 was independently associated with an elevated risk of stroke recurrence and mortality in ESUS patients. Additionally, a trend toward a correlation between LA enlargement and high stroke recurrence risk after ESUS was observed.

[Analysis of clinical features and ATRX gene variants in a Chinese pedigree affected with X-linked alpha thalassemia mental retardation (ATR-X) syndrome].

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION: The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.

An induced pluripotent stem cell line (SDQLCHi062-A) from a patient carrying a mutation in the PAX2 gene.

Focal segmental glomerulosclerosis 7 (FSGS7, # 616002) is a condition marked by significant proteinuria with or without features of nephrotic syndrome. Heterozygous mutations in the PAX2 gene on chromosome 10q24 can cause FSGS7. Here, we generated an induced pluripotent stem cell line SDQLCHi062-A from a thirteen -years-old boy with FSGS7 caused by heterozygous mutation (c.226 G>A, p.G76S) in the PAX2 gene (OMIM * 167409). The established iPSC line was validated by pluripotency markers expression, original gene mutation and demonstrated trilineage differentiation potential in vitro.

Establishment of human induced pluripotent stem cell line (SDQLCHi060-A) from a patient with AUTS2 syndrome carrying a heterozygous mutation in AUTS2 gene.

AUTS2 syndrome is a neurodevelopmental disorder caused by pathogenic variants and deletions of the AUTS2 gene, resulting in intellectual disability, microcephaly, and other phenotypes. Here, we generated a human induced pluripotent stem cell (iPSC) line from a 21-month-old boy with AUTS2 syndrome caused by a heterozygous mutation (c.1486C > T, p.Q496X) in the AUTS2 gene. The iPSCs had normal morphology and karyotype, expressed pluripotency markers, showed differentiation potential in vitro, and carried the AUTS2 gene mutation.