Identifying First-Trimester Risk Factors for SGA-LGA Using Weighted Inheritance Voting Ensemble Learning.

The classification of fetuses as Small for Gestational Age (SGA) and Large for Gestational Age (LGA) is a critical aspect of neonatal health assessment. SGA and LGA, terms used to describe fetal weights that fall below or above the expected weights for Appropriate for Gestational Age (AGA) fetuses, indicate intrauterine growth restriction and excessive fetal growth, respectively. Early prediction and assessment of latent risk factors associated with these classifications can facilitate timely medical interventions, thereby optimizing the health outcomes for both the infant and the mother. This study aims to leverage first-trimester data to achieve these objectives. This study analyzed data from 7943 pregnant women, including 424 SGA, 928 LGA, and 6591 AGA cases, collected from 2015 to 2021 at the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou, China. We propose a novel algorithm, named the Weighted Inheritance Voting Ensemble Learning Algorithm (WIVELA), to predict the classification of fetuses into SGA, LGA, and AGA categories based on biochemical parameters, maternal factors, and morbidity during pregnancy. Additionally, we proposed algorithms for relevance determination based on the classifier to ascertain the importance of features associated with SGA and LGA. The proposed classification solution demonstrated a notable average accuracy rate of 92.12% on 10-fold cross-validation over 100 loops, outperforming five state-of-the-art machine learning algorithms. Furthermore, we identified significant latent maternal risk factors directly associated with SGA and LGA conditions, such as weight change during the first trimester, prepregnancy weight, height, age, and obstetric factors like fetal growth restriction and birthing LGA baby. This study also underscored the importance of biomarker features at the end of the first trimester, including HDL, TG, OGTT-1h, OGTT-0h, OGTT-2h, TC, FPG, and LDL, which reflect the status of SGA or LGA fetuses. This study presents innovative solutions for classifying and identifying relevant attributes, offering valuable tools for medical teams in the clinical monitoring of fetuses predisposed to SGA and LGA conditions during the initial stage of pregnancy. These proposed solutions facilitate early intervention in nutritional care and prenatal healthcare, thereby contributing to enhanced strategies for managing the health and well-being of both the fetus and the expectant mother.

Endocytosis at the maternal-fetal interface: balancing nutrient transport and pathogen defense.

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, as well as fluid phase micropinocytosis and macropinocytosis, each demonstrating varying degrees of specificity and capacity. Collectively, these mechanisms facilitate the internalization of cargo into cellular vesicles. Pregnancy is one such physiological state during which endocytosis may play critical roles. A successful pregnancy necessitates ongoing communication between maternal and fetal cells at the maternal-fetal interface to ensure immunologic tolerance for the semi-allogenic fetus whilst providing adequate protection against infection from pathogens, such as viruses and bacteria. It also requires transport of nutrients across the maternal-fetal interface, but restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms remain less understood. A comprehensive understanding of endocytosis and its mechanisms not only enhances our knowledge of maternal-fetal interactions but is also essential for identifying the pathogenesis of pregnancy pathologies and providing new avenues for therapeutic intervention.

Integrative multi-omics analyses identify molecular subtypes of head and neck squamous cell carcinoma with distinct therapeutic vulnerabilities.

Substantial heterogeneity in molecular features, patient prognoses, and therapeutic responses in head and neck squamous cell carcinomas (HNSCC) highlights the urgent need to develop molecular classifications that reliably and accurately reflect tumor behavior and inform personalized therapy. Here, we leveraged the similarity network fusion bioinformatics approach to jointly analyze multi-omics datasets spanning copy number variations, somatic mutations, DNA methylation, and transcriptomic profiling and derived a prognostic classification system for HNSCC. The integrative model consistently identified three subgroups (IMC1-3) with specific genomic features, biological characteristics, and clinical outcomes across multiple independent cohorts. The IMC1 subgroup included proliferative, immune-activated tumors and exhibited a more favorable prognosis. The IMC2 subtype harbored activated EGFR signaling and an inflamed tumor microenvironment with cancer-associated fibroblast/vascular infiltrations. Alternatively, the IMC3 group featured highly aberrant metabolic activities and impaired immune infiltration and recruiting. Pharmacogenomics analyses from in silico predictions and from patient-derived xenograft model data unveiled subtype-specific therapeutic vulnerabilities including sensitivity to cisplatin and immunotherapy in IMC1 and EGFR inhibitors (EGFRi) in IMC2, which was experimentally validated in patient-derived organoid models. Two signatures for prognosis and EGFRi sensitivity were developed via machine learning. Together, this integrative multi-omics clustering for HNSCC improves current understanding of tumor heterogeneity and facilitates patient stratification and therapeutic development tailored to molecular vulnerabilities.

Gut-resident C. perfringens impedes rotavirus vaccine efficacy.

Background & Aims: The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy. Methods: We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.Influence of human microbiomes on RV vaccination was studied via administering germ-free mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to vaccination and challenge doses of RV. Results: SFB administration resulted in a phenotype reminiscent of RV vaccine failure, i.e. minimal generation of RV antigens and, consequently, lack of anti-RV antibodies resulting in proneness to RV challenge once SFB levels diminished. Transplant of microbiomes from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responding children exhibited high levels of fecal RV antigen shedding and RV antibodies in response to RV vaccination and, concomitantly, were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV challenge and, accordingly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested that RV vaccine failure might involve Clostridium perfringens . Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of previously-reported microbiome data found C. perfringens abundance in children associated with RV vaccine failure. Conclusion: Microbiota composition influences RV vaccine virus infection and, consequently, protective immunity. C. perfringens may be one, perhaps of many, bacterial species harbored in the intestine of RV-vaccine non-responders that influences RV vaccine outcomes.

Etiological analysis of ocular herpes virus infection.

OBJECTIVE: To do the etiological analysis of ocular herps virus infection, revealing the pathogen species and the distribution of different virus types within the eye. METHODS: Samples were collected from 2017 to 2021 at the Department of Ophthalmology, Peking University Third Hospital and tested using real-time PCR for common ocular viruses: herpes simplex virus 1 (HSV-1), cytomegalovirus (CMV), varicella-zoster virus (VZV) and Epstein-Barr virus (EBV). The pathogenesis of the different viruses was classified and analyzed according to the site of infection. RESULTS: Viral PCR detections were performed on 3627 samples collected over the 5-years and 649 (17.89%) samples contained one or more of the viruses tested. The overall detection rate of CMV was highest at 9.93%. Of all sample types, aqueous humor was the most common (1752 cases), of which 340 were positive (19.41% positive rate). Corneal samples were the next most common, with 1481 cases and 250 positive results (16.88% positive rate). CMV positivity was higher in aqueous humor and corneal samples than other viruses; vitreous body had the highest positive rate at 36.36% (20/55), among which 18 cases were VZV positive. CONCLUSIONS: Distribution of virus types differed among infection sites, with CMV the most common virus type detected in the cornea and aqueous humor, while VZV was the most common virus detected in the vitreous body.

Development of an Intelligent Risk Hierarchical Management System on Pulmonary Aspiration for the Elderly.

For the elderly, the risks associated with pulmonary aspiration are significant, and can severely impact their quality of life. Therefore, the management of pulmonary aspiration risk is crucial in promoting healthy aging, an aspect often overlooked in self-health management for the elderly. To enhance self-management of pulmonary aspiration risk among the elderly, we have organized a multidisciplinary team to develop an intelligent risk hierarchical management system on pulmonary aspiration for the elderly. This system tailors the assessment with different questionnaires based on the elderly individual's environment. Additionally, it utilizes elderly-friendly formats such as pictures, videos and animations, making it easier for seniors to comprehend the occurrence and hazards of pulmonary aspiration. This enables them to proactively take preventive measures to manage the risk, thus achieving self-management of pulmonary aspiration risk.

Development of an Intelligent Health Education System Based on Large Language Model for Elderly Pulmonary Aspiration Prevention.

As the aging process accelerates, the incidence of chronic diseases in the elderly is rising. As a result, it is crucial to optimize health education for the elderly. Pulmonary aspiration and aspiration pneumonia are significant concerns endangering the health of the elderly. The health education paradigm now in use to prevent pulmonary aspiration in the elderly has numerous flaws, including a lack of home-based health education and the digital divide. Large language model (LLM), an example of artificial intelligence technology, is anticipated to bring a chance to address these issues and offer easily comprehensible health information for the prevention of pulmonary aspiration in the elderly. Our multidisciplinary research team fully understood the needs from the perspective of physicians, nurses and patients, built a knowledge graph (KG), and developed an intelligent Health EducAtion system based on LLM for the prevention of elderly Pulmonary Aspiration (iHEAL-ePA system).

Development of an Online Training System on Pulmonary Aspiration for Clinical Nurses.

Pulmonary aspiration is a particularly problematic condition in patients in hospitals and nursing home. To promote patient safety and prevent serious complications, the nurse's role in preventing and caring for patient at high risk of pulmonary aspiration is crucial. Our team has developed an online training system on pulmonary aspiration for nurses to improve their ability to identify early risk factors, scientifically assess the risk of aspiration, and effectively intervene and manage when pulmonary aspiration occurs. This system was developed via WeChat app, the most popular social media application in China. It has four main functions, such as online training, online assessment, announcement interaction, and learning record. This online training systems offer the benefits of flexible learning time with anytime access, rich resources that are easy to update, and greater cost-effectiveness. This paper presents and discusses the development process of this system.

Nurses' Experiences of Internet + Nursing Service Based on Service Quality: A Qualitative Study.

Internet + Nursing Services began operating from 2019 in China. The Internet+Nursing Service offers convenience to patients with limited mobility. As the application gains traction and order volume increases, guaranteeing service quality becomes the next challenge. Nonetheless, there is still a dearth of study on service quality assurance. In order to investigate nurses' experiences in the service process, this study used a qualitative research approach from the perspectives of the nurses. It is intended to serve as a guide for the creation of Internet+ nursing services. Two primary topics emerged from the analysis: Factors influencing service motivation (Getting Returns, Discontent, Concerns) and Experience of the service process (Trust contributes to smooth service delivery, Nurses' competence affects service quality, Correct assessment of whether the service is available or not, Shortcomings existing in the service process).

ChatGPT Research in Healthcare is Increasing Dramatically: A Bibliometric Analysis Based on VOSviewer.

The ChatGPT (Chat Generative Pretrained Transformer), an AI-based chatbot, has garnered significant attention in healthcare. We methodically extracted two significant English databases (PubMed and Web of Science) to examine the current state of research and potential future directions for ChatGPT in the healthcare field. Following screening, 921 publications were included in the analysis, demonstrating a sharp rise in the previous year and a peak number of publications released in October 2023. Meanwhile, we obtained 88 items and categorized them into 10 clusters, of which artificial intelligence, ChatGPT, and humans ranked among the top three in terms of frequency.

Parental knowledge, attitudes, and practices toward vaccinating their children against influenza: a cross-sectional study from China.

Aims: Influenza infection is a health burden in children, and the influenza vaccine is an important prevention strategy for flu illness. Parents play a crucial role in children's influenza vaccination. The study aimed to assess parental knowledge, attitudes, and practices (KAP) related to influenza illness for their children and explore factors that may impact their decisions. Methods: This cross-sectional study was conducted in a tertiary hospital in Guangzhou from November 2022 to April 2023. Answers to KAP questions regarding influenza illness and vaccination were summed, with a total KAP score of 20. Univariate and multivariate logistic regression models and linear regression models were conducted to explore the factors associated with influenza vaccination. The results were presented as odds ratios (ORs), ß, and 95% confidence intervals (CIs). Results: Overall, 530 parents were respondents, of whom 162 (30.56%) had vaccinated their children during the past year. The mean KAP score (standard deviation) was 13.40 (3.57). Compared to parents who reported non-vaccinated for their children in the past year, the parents who reported an influenza vaccination have higher knowledge scores, attitude scores, practice scores, and total scores. Child body mass index, parental education level (under college), parental work (part-time), and more than two family members over 60 years old were negatively correlated with knowledge score. Child health condition and knowledge score were positively correlated with attitude score. Parental age was negatively associated with attitude score. Conclusion: Though high awareness about influenza illness and vaccination for parents, the coverage rate of influenza vaccination in children was lower in Guangzhou. Implementing public health policies is necessary to spread knowledge about influenza illness and vaccination and to promote the practice of receiving the influenza vaccine in children. Education campaigns would help change the attitudes of parents toward vaccinating their children against the flu.

Super-Stable Mineralization of Metal Ions from Smelting Wastewater by In Situ Synthesis of NiFe-Based Layered Double Hydroxides for Catalytic Phenol Hydroxylation.

The super-stable mineralization of metal ions from industrial wastewater by in situ synthesis of layered double hydroxides (LDHs) has been regarded as a sustainable approach from environmental protection and resource utilization perspectives. Herein, the study reports a super-stable mineralization of metal ions including Ni, Fe, Cr, Mn, Cu, Ca, Al, etc. from smelting wastewater by in situ synthesis of NiFe-based LDHs through facile coprecipitation. Such approach exhibits superior mineralization efficiency of metal ions simultaneously that can remove hundreds, thousands, or even tens of thousands mg/L of multiple metal ions to below the values of the Chinese National Emission Standards of Pollutants. Furthermore, the obtained NiFe-based LDHs exhibit excellent catalytic performance of phenol hydroxylation due to the mineralization of multiple metals on the laminates, where 48.24% conversion of phenol and 71.58% selectivity of dihydroxybenzenes are realized under room temperature for 3 h. This work paves a sustainable strategy for hazardous material disposal and resource utilization.

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Ophthalmic Artery Morphology and Hemodynamics Associated with White Matter Hyperintensity.

Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.

TFEB safeguards trophoblast syncytialization in humans and mice.

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation.

High-Performance Refractive Index and Temperature Sensing Based on Toroidal Dipole in All-Dielectric Metasurface.

This article shows an all-dielectric metasurface consisting of "H"-shaped silicon disks with tilted splitting gaps, which can detect the temperature and refractive index (RI). By introducing asymmetry parameters that excite the quasi-BIC, there are three distinct Fano resonances with nearly 100% modulation depth, and the maximal quality factor (Q-factor) is over 104. The predominant roles of different electromagnetic excitations in three distinct modes are demonstrated through near-field analysis and multipole decomposition. A numerical analysis of resonance response based on different refractive indices reveals a RI sensitivity of 262 nm/RIU and figure of merit (FOM) of 2183 RIU-1. This sensor can detect temperature fluctuations with a temperature sensitivity of 59.5 pm/k. The proposed metasurface provides a novel method to induce powerful TD resonances and offers possibilities for the design of high-performance sensors.

MYCT1 controls environmental sensing in human haematopoietic stem cells.

The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs1-3. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of MYCT1 prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which MYCT1 was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.

Commensal bacterial outer membrane protein A induces interleukin-22 production.

Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that exposing Peyer's patch cells (PPCs), ex vivo, to fecal supernatants (FSs) recapitulates fermentable fiber- and microbiota-dependent IL-22 production, and cellular sources thereof, thus supporting the use of this model. An interrogation of FSs generated from mice fed the fermentable fiber inulin (FS-Inu) revealed that its IL-22-inducing activity is mediated by heat-labile protein. Fractionation of FS-Inu by ion-exchange chromatography, and subsequent proteomic analysis of IL-22-inducing fractions, indicates that outer membrane protein A (OmpA) might be a microbial driver of IL-22 expression. Concomitantly, recombinant OmpA from Parabacteroides goldsteinii, which is enriched by an inulin diet, induces IL-22 production and expression of the IL-22-dependent genes REG3γ and -ß, in PPCs and mice. Thus, OmpA is one bacterial inducer of IL-22 expression, potentially linking diet, mucosal immune homeostasis, and gut health.

Proteins linking APOE ɛ4 with Alzheimer's disease.

INTRODUCTION: The ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for Alzheimer's disease (AD), but the mechanisms connecting APOE ɛ4 to AD are not clear. METHODS: Participants (n = 596) were from two clinical-pathological studies. Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry to obtain amyloid beta (Aß) load and tau tangle density. RESULTS: In separate models, APOE ɛ4 was associated with 18 proteins, which were associated with Aß and tau tangles. Examining the proteins in a single model identified Netrin-1 and secreted frizzled-related protein 1 (SFRP1) as the two proteins linking APOE ɛ4 with Aß with the largest effect sizes and Netrin-1 and testican-3 linking APOE ɛ4 with tau tangles. DISCUSSION: We identified Netrin-1, SFRP1, and testican-3 as the most promising proteins that link APOE ɛ4 with Aß and tau tangles. HIGHLIGHTS: Of 8425 proteins extracted from prefrontal cortex, 18 were related to APOE ɛ4. The 18 proteins were also related to amyloid beta (Aß) and tau. The 18 proteins were more related to APOE ɛ4 than other AD genetic risk variants. Netrin-1 and secreted frizzled-related protein 1 were the two most promising proteins linking APOE ɛ4 with Aß. Netrin-1 and testican-3 were two most promising proteins linking APOE ɛ4 with tau.