1.Analysis of the current status of red blood cell transfusion in very preterm infants from Chinese Neonatal Network in 2022
Yan MO ; Aimin QIAN ; Ruimiao BAI ; Shujuan LI ; Xiaoqing YU ; Jin WANG ; K. Shoo LEE ; Siyuan JIANG ; Qiufen WEI ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(1):55-61
Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.
2.Lantana camara alleviating TNBS-induced ulcerative colitis in rats: regulating TNF-α/EGFR/STAT3/Bcl-2 signaling pathways
Manoj S. Magre ; Pooja A. Bhalerao ; Satish K. Mandlik ; Deepa S. Mandlik
Digital Chinese Medicine 2025;8(2):234-253
[Objective]:
To investigate the therapeutic potential and underlying mechanism of Lantana camara ethanolic extract (LCEE) in ulcerative colitis (UC).
[Methods] :
Phytochemical analysis of LCEE was conducted using qualitative analysis, liquid chromatography-mass spectrometry (LC-MS), and high-performance thin-layer chromatography (HPTLC). The active constituents of LCEE were identified through network pharmacology analysis, followed by molecular docking. The therapeutic mechanism was validated in a UC rat model using 42 male Wistar rats (200 – 250 g) induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rats were randomly divided into seven groups (n = 6 per group): normal control (NC), ethanol control (EC), disease control (DC), three doses of LCEE treatment [low dose LCEE (100 mg/kg), medium dose LCEE (200 mg/kg), and high dose LCEE (400 mg/kg), p.o.], and dexamethasone (DEX, 2 mg/kg, p.o.) groups. Following TNBS-induced UC (120 mg/kg, intrarectally), rats were treated orally for 28 d. Disease severity was assessed through body weight changes, disease activity index (DAI), colon weight, colon length, and morphological scores. Haematological parameters, enzymatic antioxidants, nitric oxide (NO), myeloperoxidase (MPO), and inflammatory cytokines were measured in the serum and colon tissues. Gene expressions of tumor necrosis factor (TNF)-α, epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and B-cell lymphoma 2 (Bcl-2) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Histopathological alterations in the colon tissues were evaluated using hematoxylin and eosin (HE), Giemsa, and periodic acid-schiff staining (PAS).
[Results] :
LC-MS analysis identified 13 phytoconstituents in LCEE, and HPTLC analysis confirmed the presence of ursolic acid, geniposide, and chlorogenic acid. Network pharmacological analysis identified 152 potential therapeutic targets with TNF, STAT3, Bcl-2, albumin (ALB), and EGFR as the top 5 hub targets. Molecular docking revealed strong binding affinities of LCEE phytoconstituents with key inflammatory and apoptotic targets: linaroside with TNF-α (– 6.1 kcal/mol), ursolic acid with STAT3 (– 6.8 kcal/mol) and Bcl-2 (– 8.7 kcal/mol), and cirsiliol with EGFR (– 8.2 kcal/mol), comparable to DEX. LCEE treatment significantly increased body weights and thymus weight, while significantly reducing colon weight, spleen weight, and DAI scores. Haematological parameters showed significant improvements with increased haemoglobin, red blood cells, and platelet count, and decreased white blood cells counts. Antioxidants markers were significantly improved with increased glutathione, superoxide dismutase, and catalase levels, and decreased malondialdehyde levels. LCEE significantly reduced NO and MPO levels and inflammatory cytokines including TNF-α, interleukin (IL)-1β, nuclear factor kappa-B (NF-κB), IL-6, and IL-12 compared with TNBS treated rats. LCEE downregulated the gene expression levels of TNF-α, EGFR, and STAT3, while upregulating Bcl-2 expression level, indicating modulation of inflammation and apoptosis pathways. Histological evaluation confirmed that after LECC treatment, mucosal ulcers and inflammatory cell infiltration decreased.
[Conclusion]
The findings suggest that Lantana camara may serve as a medicinal plant to alleviate UC and offer an investigational basis for the clinical utilization of Lantana camara.
5.Etiome Study Using Molecular Epigenetic Markers and Lung Organoid in Korean School Meal Service Workers (Etiome Study in S-meal Workers): Study Protocol
Sungji MOON ; Soseul SUNG ; Sue K. PARK
Journal of Preventive Medicine and Public Health 2025;58(3):231-240
School meal service workers may face an increased risk of lung cancer due to the nature of their work. This study aims to assess environmental exposure levels during occupational cooking among these workers in Seoul, Korea, and to examine the associations with carcinogen-associated biomarkers. Additionally, the study seeks to verify lung carcinogenesis through experiments using lung organoids treated with carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and particulate matter. Here, we introduce the study protocol and outline our research strategies. This etiome study employs molecular epidemiological approaches involving at least 200 school meal service workers from 25-30 school cafeterias in Seoul, as well as in vitro lung organoid experiments. The study includes a questionnaire survey to analyze workers’ occupational environments, focusing on exposure to hazardous substances such as cooking oil fumes and assessing the use of personal protective equipment (e.g., masks) and the presence of ventilation systems. We measure molecular epigenomic biomarkers, including PAH adducts and metabolites along with methylation markers, in the exposure and control groups. Additionally, lung organoid experiments are performed to investigate the potential for lung cancer development due to respiratory carcinogen exposure in cooks. This study is expected to contribute to health risk assessments and the establishment of preventive strategies for meal service workers.
6.Temporalis Fascia and Free Post‐Aural Soft Tissue Graft in Sub‐Centimeter Skull Base Defect Repair
Journal of Rhinology 2025;32(1):55-59
Skull base defects often manifest as meningocele/meningoencephalocele or cerebrospinal fluid (CSF) leaks. Ventral and lateral skull base defects are effectively treated endoscopically and microscopically using various approaches. This case series study analyzes the utility and efficacy of post-aural soft tissue and temporalis fascia grafts in repairing small (<1 cm) skull base defects. Five out of six patients (83.33%) achieved successful defect closure. Patients were followed for donor site morbidity, postoperative CSF leak, and/or recurrent meningocele. One patient experienced reconstruction failure and developed a CSF leak eight months after surgery. The results suggest that TF grafts combined with post-aural soft tissue may be effectively used to repair small skull base defects without significant donor site morbidity.
7.Non-Inferiority Trials in Stroke Research: What Are They, and How Should We Interpret Them?
Linxin LI ; Vasileios-Arsenios LIOUTAS ; Ralph K. AKYEA ; Stefan GERNER ; Kui Kai LAU ; Emily RAMAGE ; Aristeidis H. KATSANOS ; George HOWARD ; Philip M. BATH
Journal of Stroke 2025;27(1):41-51
Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.
8.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
9.Developing an Explainable Artificial Intelligence System for the Mobile-Based Diagnosis of Febrile Diseases Using Random Forest, LIME, and GPT
Kingsley F. ATTAI ; Constance AMANNAH ; Moses EKPENYONG ; Daniel E. ASUQUO ; Oryina K. AKPUTU ; Okure U. OBOT ; Peterben C. AJUGA ; Jeremiah C. OBI ; Omosivie MADUKA ; Christie AKWAOWO ; Faith-Michael UZOKA
Healthcare Informatics Research 2025;31(2):125-135
Objectives:
This study proposes a mobile-based explainable artificial intelligence (XAI) platform designed for diagnosing febrile illnesses.
Methods:
We integrated the interpretability offered by local interpretable model-agnostic explanations (LIME) and the explainability provided by generative pre-trained transformers (GPT) to bridge the gap in understanding and trust often created by machine learning models in critical healthcare decision-making. The developed system employed random forest for disease diagnosis, LIME for interpretation of the results, and GPT-3.5 for generating explanations in easy-to-understand language.
Results:
Our model demonstrated robust performance in detecting malaria, achieving precision, recall, and F1-scores of 85%, 91%, and 88%, respectively. It performed moderately well in detecting urinary tract and respiratory tract infections, with precision, recall, and F1-scores of 80%, 65%, and 72%, and 77%, 68%, and 72%, respectively, maintaining an effective balance between sensitivity and specificity. However, the model exhibited limitations in detecting typhoid fever and human immunodeficiency virus/acquired immune deficiency syndrome, achieving lower precision, recall, and F1-scores of 69%, 53%, and 60%, and 75%, 39%, and 51%, respectively. These results indicate missed true-positive cases, necessitating further model fine-tuning. LIME and GPT-3.5 were integrated to enhance transparency and provide natural language explanations, thereby aiding decision-making and improving user comprehension of the diagnoses.
Conclusions
The LIME plots revealed key symptoms influencing the diagnoses, with bitter taste in the mouth and fever showing the highest negative influence on predictions, and GPT-3.5 provided natural language explanations that increased the reliability and trustworthiness of the system, promoting improved patient outcomes and reducing the healthcare burden.
10.Interactive Engagement with Self-Paced Learning Content in a Didactic Course
Nazlee SHARMIN ; Shahram HOUSHYAR ; Thomas R. STEVENSON ; Ava K. CHOW
Healthcare Informatics Research 2025;31(1):96-106
Objectives:
A growing number of health professional institutions around the world are embracing innovative technologies to increase student engagement, primarily to improve clinical and simulated learning experiences. Didactic learning is an essential component of dental and medical curricula. However, limited research is available regarding the implementation of technology-infused teaching in classroom settings. We developed self-paced interactive learning content using the HTML5 Package (H5P) to promote student engagement in a didactic course within a dental hygiene program.
Methods:
A total of 52 interactive artifacts were created and administered to students as supplementary learning material. A descriptive study was conducted to explore student perceptions and engagement with the H5P content, as well as to evaluate the impact of these artifacts on academic performance.
Results:
Students performed significantly better on exam questions associated with interactive H5P content posted in the learning management system compared to other questions. Most students were highly engaged with the H5P content during the week leading up to each summative assessment. However, two of the three students with the highest course grades demonstrated consistent engagement with this content throughout the course.
Conclusions
Our results highlight the effectiveness of interactive content created using the H5P platform in fostering student engagement. The development of self-paced interactive materials may benefit various aspects of didactic teaching, including both synchronous and asynchronous online learning.


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