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PubMed2026

Maternal Intake of Vitamins A, C, D, and E During Pregnancy and Risk of Type 1 Diabetes in the Child: The Norwegian Mother, Father, and Child Cohort Study.

BACKGROUND: Dietary vitamins play a role in antioxidant defense and immunoregulation. However, prospective studies exploring the association between vitamin intakes during pregnancy and the child's risk of type 1 diabetes are limited. OBJECTIVES: This population-based prospective cohort study aimed to investigate the association between maternal intake of vitamins A, C, D, and E during pregnancy and risk of type 1 diabetes in children. METHODS: We included 85,244 children born between 2002 and 2009 in the Norwegian Mother and Child Cohort Study, with follow-up until 31 December, 2021. Maternal intake of vitamins from food and dietary supplements from conception to the 22nd week of pregnancy was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was used to estimate hazard ratios (HRs), adjusting for background factors. RESULTS: During follow-up, 529 (0.6%) children were diagnosed with type 1 diabetes at a mean age of 9.4 y (standard deviation: 4.1 y) No associations were observed between maternal pregnancy intake of vitamin A [HR: 0.993; 95% confidence interval (CI): 0.983, 1.003/100 μg], vitamin C (HR: 1.000; 95% CI: 0.993, 1.007/10 mg), vitamin D (HR: 0.991; 95% CI: 0.978, 1.003/1 μg), or vitamin E (HR: 0.999; 95% CI: 0.996, 1.004/10 mg) and risk of type 1 diabetes in the child when adjusted for potential confounders. The results were similar when intakes were assessed separately from food and dietary supplements and after restriction to children with human leukocyte antigen DQ2 and/or DQ8 risk haplotypes. CONCLUSIONS: This prospective cohort study does not support the hypothesis that higher maternal intake of vitamins A, C, D, and E during pregnancy would decrease risk of type 1 diabetes in the child. Corroborated with previous evidence, our findings support a general pattern of null associations.

Humans↗

PubMed2026

Functional and Nutritional Potential of Chickpea Protein Hydrolysates: A Systematic Review and Plant-protein Network Analysis.

Chickpea is a protein-rich legume increasingly explored as a substrate for functional plant-based ingredients. Chickpea protein hydrolysates (CPHs) and chickpea-derived peptides (CPs), obtained through enzymatic hydrolysis or simulated gastrointestinal digestion, may provide technological and biological properties while supporting the valorization of chickpea fractions and by-products. This review integrates a network analysis of title-abstract terms from 5,728 unique Scopus and PubMed records on plant protein hydrolysates with a systematic review of 72 studies focused on CPH production, peptide characterization, bioactivity, and translational gaps. The evidence indicates that CPHs and CPs show promising antioxidant, antihypertensive, antidiabetic, anti-inflammatory, lipid-lowering, immunomodulatory, antimicrobial, and anticancer-related activities, mainly supported by biochemical assays, cell models, and animal studies. However, heterogeneous hydrolysis protocols, incomplete peptide characterization, inconsistent bioactivity methods, limited scale-up evidence, and the absence of human intervention trials restrict translation. Future studies should prioritize standardized protocols, mechanistic validation, bioavailability, sensory and regulatory assessment, food-matrix validation, and clinical trials.

Cicer↗

PubMed2026

A 7-mm Covered TIPS Reduces Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters < 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n = 92) or 8-mm (n = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, p = 0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans↗

PubMed2025

Mediators of the Association Between a Parent's Experience of Trauma and Their Children's Well-Being: A Systematic Review.

At present, our understanding of trauma's complexity is underdeveloped, particularly with regard to intergenerational effects. In this paper, we review peer-reviewed literature on parental trauma and child well-being, focusing on mediating factors. We conducted a global systematic review of longitudinal, observational studies assessing mediators between a parent's traumatic exposure and their children's well-being. The primary outcome of the review was quantitative measures of child well-being (physical and psycho-social) assessed when the child was 18 years or under. We considered the following experiences as trauma exposures: intimate partner violence, rape, sexual assault, victimization during violent crime, childhood abuse, and exposure to direct, immediate threats to personal survival during war, political unrest, natural disasters, and sudden, critical injury/illness. Thirty-two studies met our inclusion criteria. The two most common mediator categories were caregiver mental health (n = 13) and parenting behavior (n = 10). Other studies measured aspects of the parent-child relationship (n = 9), maternal stress factors (n = 5), parental physical health (n = 2), and child-level factors (n = 6) as mediators. Almost all included studies (n = 28) detected a mediation effect. The majority of studies (n = 21) cited robust theoretical frameworks to support their mediator and outcome choices. Studies varied in quality, but most used appropriate, formal mediation analyses. Several study designs could be enhanced by methods to improve precision and reduce bias. Currently, there is little consistency in how similar constructs are measured between mediation studies. We did not locate any studies in low-income countries, and few studies examined aspects of family dynamics, physical health, environmental characteristics, or paternal factors.

Humans↗

PubMed2026

Integrated analysis uncovers exogenous induction and molecular regulation of erinacine A accumulation in Hericium erinaceus.

Erinacine A, a cyathane-type diterpenoid mainly from Hericium erinaceus mycelia, exhibits prominent neurotrophic and neuroprotective activities, making it a promising candidate for managing neurodegenerative diseases. However, its low abundance and unclear genetic regulatory mechanisms hinder its application as a nutraceutical. This study aimed to decipher its regulatory mechanisms and enhance production. Four exogenous inducers were screened, with salicylic acid (SA) and ergosterol (ERG) significantly increasing erinacine A content by 62.21% and 146.70% at 20 days, respectively. Transcriptome and WGCNA of inducer-treated sample identified darkorange and magenta modules associated with erinacine A biosynthesis, with the eri gene cluster enriched in the darkorange module and eriG and eriF as hub genes. Forward genetic analysis via QTL mapping of the HeD127 dikaryon population revealed significant phenotypic variation in erinacine A content (0.341-13.085 mg/g) and identified two loci (erA-1 and erA-2) explaining 18.63% of phenotypic variation. Integrating these forward and reverse genetic analyses revealed that salicylic acid and ergosterol synergistically regulate core carbon metabolic pathways to augment acetyl-CoA supply for the mevalonate pathway, suppressed competitive metabolism, enhanced diterpene skeleton construction and structural modification. These results deepen our understanding of the genetic and molecular basis governing accumulation of erinacine A, and facilitate its application in neuroprotective pharmaceuticals.

Diterpenes↗

PubMed2026

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum↗

PubMed2026

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses↗

PubMed2026

Decoding bipotency: a transient regulatory state bridging totipotency and lineage commitment.

Early mammalian embryogenesis entails a coordinated transition from totipotency to the first lineage bifurcation, giving rise to embryonic lineages and the extra-embryonic trophectoderm. The mechanisms by which totipotency is resolved into lineage-primed states remain incompletely understood. Emerging evidence supports a non-binary model in which cells traverse a continuum of potency states, passing through a transient bipotent intermediate that retains both embryonic and extra-embryonic potential while exiting totipotency. Here, we synthesize recent advances in the mechanisms that establish, maintain, and resolve bipotency. We emphasize the coordinated roles of transposable elements, transcription factors, and signaling pathways in regulating this transition. We also highlight newly developed bipotent stem cell models and their implications in generating advanced embryo models in vitro. Notably, current insights are largely derived from mouse systems; given key differences between mouse and human early embryogenesis, extending these findings to human models remains a critical next step.

Animals↗

PubMed2026

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals↗

PubMed2026

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult↗

PubMed2026

Artificial Intelligence Cannot Replace Peer Reviewers but May Help Editors Triage: A Comparative Analysis of a Large Language Model and Human Reviewer Recommendations at the American Journal of Sports Medicine.

BACKGROUND: The peer review system faces increasing strain from rising manuscript volumes, reviewer fatigue, and well-documented interreviewer disagreement. Large language models (LLMs) have shown potential to support the peer review process, but their ability to replicate editorial decisions at high-impact medical journals and their utility as manuscript screening tools remain unknown. PURPOSE: To compare the agreement between an LLM and the final editorial decision on manuscripts submitted to the American Journal of Sports Medicine and to evaluate the potential of LLMs as a manuscript screening tool. STUDY DESIGN: Cross-sectional agreement study. METHODS: Fifty-four manuscripts randomly selected from submissions to the American Journal of Sports Medicine (September 2024-October 2024) were reviewed by a locally deployed LLM (Ministral 3 14B; Mistral AI) using a standardized prompt. The artificial intelligence (AI) produced a categorical recommendation (reject, cascade, revision, or accept) and a numerical score (0-100) for each manuscript. Agreement with the final editorial decision was assessed by Cohen kappa (4-category model) for pooled human reviewers (n = 139 reviews) and the AI (n = 54). Screening performance was evaluated by positive predictive value (PPV), sensitivity, and specificity. RESULTS: Pooled human reviewers demonstrated fair agreement with the final decision (κ = 0.181 [P < .001]; 42.4% agreement), while the AI demonstrated slight, nonsignificant agreement (κ = 0.126 [P = .099]; 37.0% agreement). The AI recommended revision for 61.1% of manuscripts, of which 72.7% were ultimately rejected or cascaded, demonstrating systematic "revision bias." When the AI recommended rejection, 54.5% of those manuscripts were ultimately rejected and 27.3% were cascaded; when the AI recommended cascade, 50% were rejected and 50% were cascaded. However, when the AI recommended rejection or cascade (n = 21), 90.5% received a final decision of rejection or cascade (PPV, 90.5%; specificity, 81.8%). Manuscripts with an AI score <70 were rejected or cascaded 88.0% of the time (PPV, 88.0%). CONCLUSION: AI cannot replicate the nuanced judgment of human peer reviewers at a high-impact sports medicine journal. When AI recommended rejection or cascade, 90.5% of manuscripts received that final decision (descriptive PPV, 90.5%; 95% CI, 71.1%-97.3%), suggesting potential utility as an exploratory first-pass screening tool warranting further validation in larger cohorts. However, AI could not reliably distinguish manuscripts destined for outright rejection from those that would be cascaded to a sister journal-an important limitation for editorial triage applications.

Sports Medicine↗

PubMed2026

The association between normalized creatinine-to-cystatin C ratio and incident circadian syndrome in middle-aged and older adults: a national cohort study.

BACKGROUND: Evidence on the association between the normalized creatinine-to-cystatin C ratio (NCCR) and Circadian Syndrome (CircS) in the general population remains scarce. This study aimed to investigate this relationship using data from middle-aged and elderly participants in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We conducted a cross-sectional analysis of 5,981 participants (2011 wave) and a prospective cohort analysis of 2,053 participants (2015 wave, median follow-up 4.0 years). CircS was defined as a cluster including elevated blood pressure, dyslipidemia, hyperglycemia, abdominal obesity, depression, and abnormal sleep duration. RESULTS: During follow-up, 552 participants developed incident CircS. A significant inverse association was observed: the risk of new-onset CircS progressively decreased with higher baseline NCCR levels. After adjusting for multiple confounders, each standard deviation increase in NCCR was associated with a 40% reduced odds of CircS (adjusted odds ratio = 0.60, 95% confidence interval: 0.48 to 0.75). Subgroup and dose-response analyses confirmed the robustness of this inverse relationship. CONCLUSIONS: In conclusion, a lower NCCR is independently associated with an elevated risk of developing CircS. These findings support NCCR's role as a practical serum indicator of sarcopenia and implicate muscle loss as a potentially key underlying pathway in the pathogenesis of Circadian Syndrome.

Humans↗

PubMed2026

Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5 mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5 mg or Val/Aml 80/5 mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25 mg or Val/Aml 160/5 mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean ± SE change in MSSBP was -19.70 ± 1.31 mmHg in the Val/Aml/CTD group versus -8.71 ± 1.26 mmHg in the control group, yielding a statistically significant between-group difference of -10.99 ± 1.81 mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

Humans↗

PubMed2026

A flipped classroom approach compared with low-interactive online learning for pediatric pain management knowledge and instructional motivation in nursing students: A randomized controlled study.

AIM: This study aimed to compare a flipped classroom approach with low-interactive online learning in terms of nursing students' questionnaire-assessed pediatric pain management knowledge and instructional motivation. BACKGROUND: Pain management in children is a critical and multidimensional nursing responsibility. However, limited curricular time and opportunities for applied learning may restrict nursing students' preparedness in this area. Structured and interactive instructional formats, such as the flipped classroom, may support knowledge acquisition and motivation in pediatric nursing education. METHODS: This study employed a parallel-group randomized controlled trial design with a 1:1 allocation ratio. Eighty-eight third-year prelicensure nursing students were randomized to either the flipped classroom group (n = 44) or the low-interactive online learning group (n = 44). Due to attrition (2 intervention, 2 control), analyses included 42 participants per group (n = 84 in total). Data were collected between February and July 2022 using the Pediatric Pain Management Knowledge Scale for Nursing Students and the Instructional Materials Motivation Survey. This study was prospectively registered at ClinicalTrials.gov (Identifier: NCT07129044). RESULTS: At baseline, the groups were comparable in terms of knowledge and learning motivation. Following the intervention, the flipped classroom group demonstrated greater improvements in questionnaire-assessed pediatric pain management knowledge and instructional motivation than the low-interactive online learning group. Although scores declined from post-test to the three-month follow-up, they remained above baseline in the flipped classroom group. CONCLUSIONS: Within the context of this course, the flipped classroom approach was associated with greater improvement in questionnaire-assessed pediatric pain management knowledge and instructional motivation than low-interactive online learning. The findings should be interpreted as proximal educational outcomes rather than evidence of improved clinical competence or durable long-term effectiveness. Further studies using objective performance-based outcomes and longer follow-up periods are needed.

Humans↗

PubMed2026

Identification of CD55 as a downstream factor of EP4 receptor signaling in colorectal cancer cells.

Prostaglandin E2 (PGE2) signaling through the E-type prostanoid 4 (EP4) receptor has been implicated in the pathophysiology of colorectal cancer (CRC). We herein identified decay-accelerating factor, also known as CD55, as a novel CRC-associated downstream factor of the EP4 receptor. The integration of transcriptomic profiling of PGE2-stimulated HCA-7 human colon cancer cells with analyses of cancer genomic databases predicted CD55 as a potential EP4 receptor-regulated target. Inhibitor-based experiments showed the induction of CD55 after a PGE2 stimulation required the EP4 receptor and Gi protein in HCA-7 cells, whereas protein kinase A signaling was dispensable. In combination with a toxicogenomic database analysis, p38 mitogen-activated protein kinase (MAPK) was identified as the predominant effector connecting the EP4 receptor to CD55 upregulation. A single-cell RNA-seq re-analysis of human CRC tissues revealed CD55 upregulation and p38 MAPK-related gene set enrichment in epithelial cells expressing the EP4 receptor, suggesting that this induction mechanism may operate in a subset of epithelial cells in clinical specimens. Collectively, these results delineate a PGE2/EP4 receptor/Gi protein/p38 MAPK signaling axis that induces CD55 expression in HCA-7 cells and epithelial tumor cells, provide new mechanistic clues for understanding the regulation of complement regulatory molecule CD55 expression by prostaglandin signaling.

Humans↗

PubMed2026

A bimodal large language model reduces misalignment in patient education: A double-blinded randomized trial.

BACKGROUND: Effective patient education requires accurate communication aligned with patients' emotional and semantical needs. Text-based large language models (LLMs) lack access to non-verbal cues, which may contribute to misaligned responses. METHODS: We evaluated emotional and semantic misalignment in a text-based LLM using 64,200 utterances from 16,583 patient education cases across six departments and three centers. Dolphin was developed integrating text and audio cues and evaluated through emotion recognition, semantic consistency assessment, branch-level ablations, and a double-blinded randomized trial against a matched text-based LLM comparator (Chinese Clinical Trial Registry: (ChiCTR2500095933). FINDINGS: The text-based LLM showed emotional misalignment in 36.7% of responses and semantic misalignment in 28.3% of cases, with higher misalignment under greater burden. Dolphin outperformed the text-based LLM in emotion recognition accuracy (0.886 vs. 0.713) and semantic consistency (84.9% vs. 82.1%; both adjusted p < 0.001). Ablations supported contribution of audio branches. Dolphin received higher expert ratings than the text-based LLM and human educators (all p < 0.001). In 555 patients, Dolphin was associated with greater patient satisfaction (98.6% vs. 93.8%), suggestion acceptance (76.1% vs. 58.9%; p < 0.001), proactive disclosure (44.6% vs. 26.5%; p < 0.001), and fewer 7-day unplanned recontact (12.9% vs. 22.9%; p = 0.002). No unsafe recommendations or safety events were identified. CONCLUSIONS: Compared with text-based LLM, Dolphin improved emotional-semantic alignment and patient-education outcomes, supporting bimodal alignment as a strategy for reducing misalignment-driven communication failures. FUNDING: National Natural Science Foundation of China, State Key Laboratory Special Fund, and Chinese Academy of Medical Sciences Innovation Fund.

Humans↗

PubMed2026

Comparative analysis of lipopolysaccharide lipid A structure and its biosynthetic genes in the plant-associated bacteria Brucella cytisi and Brucella lupini.

The genus Brucella comprises important human and animal pathogens, as well as numerous environmental and symbiotic species. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, plays a crucial role in bacterial physiology and host interactions. In this study, the structures of lipid A, the hydrophobic anchor of lipopolysaccharide, isolated from two plant-associated strains, Brucella cytisi ESC1ᵀ and Brucella lupini LUP21ᵀ, were presented. Lipid A preparations were structurally characterized using chemical methods, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The obtained results indicated that both lipid A molecules have almost identical structures. Their sugar backbones consist exclusively of 2,3-diamino-2,3-dideoxy-d-glucose (d-GlcpN3N). Phosphate residues were connected to distal and proximal GlcpN3N in approximately half of the lipid A molecules. Fatty acid analysis revealed the presence of C14:0 (3-OH), C16:0 (3-OH), and traces of C18:0 (3-OH). All of these were primary fatty substituents of the sugar backbone and were amide-linked residues. Lactobacillic acid C19:0cyc and 27-hydroxyoctacosanoic acid (C28:0 (27-OH)) were found as ester-linked secondary acyl residues. In turn, C28:0 (27-OH) was partly esterified by a 3-hydroxybutyroyl residue. Two unsubstituted 3-hydroxyfatty acids were linked exclusively to the proximal d-GlcpN3N residue. It was pointed out that sequences of putative genes encoding enzymes required for lipid A biosynthesis and genes encoding specific enzymes involved in structural modifications of lipid A occurring in the genomes of both bacterial species are almost identical. The high sequence similarity of these proteins reflects the observed similarities in the lipid A structures in both investigated Brucella species.

Brucella↗

PubMed2026

Anatomy and Biomechanics of the Deltoid Ligament Complex in Healthy Ankles: Protocol for a Systematic Review and Meta-Analysis.

INTRODUCTION: Up to one in two individuals who have a history of an ankle injury will develop chronic ankle instability, which subsequently increases the risk of osteoarthritis development. Although lateral ankle ligament injuries are the most common, recent research shows that concomitant injuries to the deltoid (medial collateral) ligament complex may be more prevalent than previously recognised. However, the anatomy and biomechanics of the deltoid ligament complex are reported inconsistently in the literature. This systematic review will summarise current evidence on the anatomy and biomechanics of the deltoid ligament complex in healthy adult ankles. METHODS: Searches will be conducted in Scopus, MEDLINE, Embase, CINAHL and SPORTDiscus. Our search strategy will cover terms associated with 'deltoid ligament', 'anatomy' and 'biomechanics'. We will only include dissection and imaging studies published in English that report any of the listed clinically relevant properties of the deltoid ligament in healthy adult human ankles. Two reviewers will independently perform screening and assess study quality using the anatomical quality assessment (AQUA) tool. One reviewer will extract relevant data, which will be independently verified by co-authors. Primary outcomes include band prevalence, length, width, cross-sectional area, maximum and/or failure load and elastic modulus. If three or more studies report a primary outcome, we will conduct a meta-analysis and report findings as pooled means with 95% confidence intervals. If a meta-analysis is not feasible, outcomes will be summarised as a narrative analysis. Measures will be taken during data synthesis to address anticipated methodological heterogeneity across included studies, and pooled estimates will be interpreted with caution. DISCUSSION: This protocol details a systematic review that aims to summarise the anatomy and biomechanics of the deltoid ligament complex. Our findings will inform computational modelling, clinical management and biomechanics for ankle pathologies, as well as identifying research gaps and directions for future research. TRIAL REGISTRATION: PROSPERO: CRD420251142867.

Humans↗