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Transcriptomic responses of Porphyrophora sophorae larvae during licorice root colonization reveal coordinated remodeling of translation, mitochondrial energy metabolism and defense-related genes.

BACKGROUND: Porphyrophora sophorae is a subterranean piercing-sucking scale insect that damages licorice (Glycyrrhiza uralensis) roots, but the molecular responses associated with larval root colonization remain insufficiently defined. METHODS: We compared non-parasitic larvae (NP) and root-colonizing larvae (RC) using six RNA-seq libraries, de novo transcriptome assembly, DESeq2-based differential expression analysis, GO/KEGG enrichment, annotation-based candidate gene screening, and RT-qPCR validation of selected genes. RESULTS: Sequencing yielded 260.91 million clean reads, and de novo assembly produced 60,794 non-redundant transcripts. DESeq2 identified 703 FDR-significant DEGs, including 49 upregulated and 654 downregulated genes in RC larvae. Upregulated genes were mainly associated with translation- and ribosome-related processes, whereas downregulated genes were enriched in mitochondrial, oxidation-reduction, energy metabolism, and oxidative phosphorylation-related functions. Annotation-based screening identified 75 FDR-significant candidate genes associated with chemosensation, defense-related responses, and energy metabolism, with mitochondrial energy metabolism-related genes forming the largest module. RT-qPCR validation based on the raw Ct data showed concordant expression directions for ten selected transcript targets. CONCLUSIONS: Root colonization in P. sophorae larvae was associated with coordinated transcriptional remodeling involving selective activation of translation-related processes, adjustment of mitochondrial energy metabolism, and changes in defense-related gene expression. These results provide candidate molecular targets for future functional studies of host contact, feeding establishment, and physiological adjustment in this subterranean scale insect.

Animals

The global potential of freshwater microbes for plastic degradation.

Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.

Plastics

Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a meta-analysis.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score ≤10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

Humans

Safety and efficacy of recombinant botulinum toxin type A (Eveotox®) in patients with post-stroke upper limb spasticity: Results from a Phase Ib/II clinical trial.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

BACKGROUND: Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear. PURPOSE: The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health. METHODS: In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5&#x2009;&#xb1;&#x2009;14 years, 76.2&#x2009;&#xb1;&#x2009;14 kg) ingested a PLA (PLA, 2 &#xd7; 6 g/d maltodextrin), GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;PLA (2 &#xd7; 5 g/d), or GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;CrM (2 &#xd7; 5 g/d) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p&#x2009;>&#x2009;0.05-p&#x2009;<&#x2009;0.10). RESULTS: GAA supplementation tended to improve overall reaction time (-241.8&#x2009;ms [-533, 50], p&#x2009;=&#x2009;0.10) while significant interaction effects were observed in overall reaction time (p&#x2009;=&#x2009;0.031-330 ms [-629, -31]) and YES reaction time (-290&#x2009;ms [-484, -96], p&#x2009;=&#x2009;0.004) while recalled correct reaction time (-178&#x2009;ms [-374, 21], p&#x2009;=&#x2009;0.078) and recalled correct YES (7.4 % [-1, 15.8], p&#x2009;=&#x2009;0.084) approached significance compared to PLA. Limited to no effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test. The amount of time engaged in moderate physical activity was significantly greater (p&#x2009;<&#x2009;0.05) in the GAA group compared to PLA. Participants in the GAA group reported a lower frequency of controlling irritations (p&#x2009;=&#x2009;0.036), and feeling like difficulties are mounting (p&#x2009;=&#x2009;0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that participants in the GAA group reported less frequent feelings of being worn out (p&#x2009;=&#x2009;0.068) and that their health was excellent (p&#x2009;=&#x2009;0.092) while those in the GAA&#x2009;+&#x2009;CrM group reported more frequent limitations when bending, kneeling, or stooping (p&#x2009;=&#x2009;0.053), more often feeling full of life (p&#x2009;=&#x2009;0.081), and less frequency in feeling downhearted and depressed (p&#x2009;=&#x2009;0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups. CONCLUSION: Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d&#x2009;+&#x2009;GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Humans

Post-trial 12-month follow-up of TRACE (targeted research on addictive and compulsive eating) randomised controlled trial participants: A brief report.

Few treatment interventions for addictive eating have evaluated long-term effectiveness. This post-trial follow-up study evaluates secondary changes in addictive eating symptoms and quality of life at 12-months in a sample of individuals who participated in the TRACE (Targeted Research for Addictive and Compulsive Eating) RCT. Thirty-three adults out of possible 144 (82% female), median age 53 years, randomised to either the active intervention (five telehealth sessions delivered over 3-months), passive intervention (self-guided workbook) or control group completed an online post-trial survey. Pre- and immediate post-intervention (3-months) outcomes were compared to 12-months post-trial outcomes. Positive effects reported in the short term showed a rebound effect at post-trial follow-up in &#x223c;50% of participants. The findings suggest that longer term support is needed to maintain changes in addictive eating behaviours and improve quality of life. Future research is needed to identify optimal intervention durations and support options for sustained change. Australian New Zealand Clinical Trials Registry (ACTRN12621001079831).

Humans

Dispositional optimism and open-label placebo responses in hair cortisol concentrations and psychological distress-A randomized controlled trial.

Open-label placebo (OLP) treatments show beneficial effects on various health-related outcomes, but studies investigating OLP effects on physiological measures remain scarce. This randomized controlled trial examined the effect of a 4-week OLP intervention on psychological distress and hair cortisol concentrations (HCC) in 202 healthy university students preparing for mandatory oral exams and whether dispositional optimism moderates the OLP effects. Participants were randomly assigned to an OLP or control group. Psychological distress was repeatedly assessed via negative affect, test anxiety, and subjective stress. HCC was measured before and within the intervention. Treatment expectations were additionally examined in interaction with optimism. Results show that OLPs significantly reduced psychological distress and HCC compared to the controls. Optimism moderated the OLP effect on HCC, with less optimistic individuals demonstrating the strongest reduction, independent of expectation. Optimism did not moderate OLP effects in psychological distress. However, the OLP effect on psychological distress depended on the three-way interaction of group, optimism, and expectation. The results suggest that OLPs alleviate the psychophysiological impact of a real-life stressor and indicate that optimism and expectation differently shape psychological and physiological OLP responses. These findings are discussed within the framework of the interactionist perspective.

Humans

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (&#x3b2;&#x2009;=&#x2009;5.272, 95% CI: 2.707, 7.837), albumin (&#x3b2;&#x2009;=&#x2009;3.675, 95% CI: 1.854, 5.496), prealbumin (&#x3b2;&#x2009;=&#x2009;11.835, 95% CI: 6.623, 17.047), body mass index (&#x3b2;&#x2009;=&#x2009;1.719, 95% CI: 0.868, 2.569), the GCS (&#x3b2;&#x2009;=&#x2009;0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p&#x2009;<&#x2009;0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans

Recovery of polysaccharides from marc and pomace through sequential extractions assisted by ultrasound, enzymes and acid maceration.

This study evaluated the pilot-scale recovery of polysaccharides from Vitis vinifera pomace/marc using sequential extraction strategies combining high-power ultrasound (UAE), enzymes (EAE), and acid maceration (AAE). Laboratory-scale trials identified optimal conditions for enzyme dosage and liquid/solid ratio (L/S). Pilot-scale trials demonstrated that the extraction sequence and the processing byproducts influenced extraction efficiency, total soluble polysaccharide in the extract (TSP), and polysaccharide composition. Post-maceration at pH&#xa0;3.2, with/without the maximum enzyme dose after UAE in a L/S of 1.3/1, improved structural polysaccharide extraction from Viura pomace, while Tempranillo marc showed better recovery of pectic families and TSP with UAE&#xa0;+&#xa0;EAE. Separating grape pomace extract (UAE) from the post-maceration stage at pH&#xa0;3.2 produced two extracts: E1, with higher yield (19.9%), enriched in structural polysaccharides and oligosaccharides, and E2, enriched in high and medium molecular weight pectic polysaccharides (58.03%), a low degree of esterification (17.1%) and more complex rhamnogalacturan structures.

Polysaccharides

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans

A Sentiment-Based Comparison of AI- and Physician-Generated Empathic Statements in Palliative Care.

CONTEXT: Empathic communication promotes trust in patient-provider relationships. As healthcare integrates artificial intelligence (AI) into patient communication, we have yet to understand how these models' communication compares to that of physicians. OBJECTIVES: Our primary objectives were to examine patient preferences for AI-generated vs. palliative care physician-generated empathic statements addressing fear and anxiety around cancer treatment, and to analyze associations between linguistic features and patient preferences. METHODS: We conducted a secondary analysis of the PALL-AI trial, a randomized controlled survey comparing cancer patients' preferences of AI- to physician-generated empathic statements. Physicians and AI were provided the same prompt with a maximum sentence length. Patient preferences for each statement were measured in blinded surveys. We analyzed sentiment of the statements using the Valence Aware Dictionary and Sentiment Reasoner (VADER) and the National Research Council Canada (NRC) Emotion Lexicon. We evaluated associations between sentiment scores and patient preferences using Spearman's correlation coefficients. RESULTS: A total of 105 patients completed blinded surveys, preferring the AI-generated statement 72.4% of the time. VADER sentiment analysis showed all three AI statements displayed positive sentiment, while all three physician statements displayed negative sentiment. Controlling for statement length, AI statements used twice as many positive words as human statements. However, they contained a similar number of negative words. Of the eight NRC emotions, "trust" and "joy" demonstrated the strongest correlations with patient preference. CONCLUSION: Patients preferred AI-generated statements around cancer care over those from palliative care physicians when standardized for prompt and statement length. Analysis shows AI-generated statements contain more positive language which may be the factor driving patient preference toward AI.

Humans

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n&#xa0;=&#xa0;53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

Humans

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals

Patient-reported outcomes in pediatric regional anesthesia trials: current use and limitations.

PURPOSE OF REVIEW: This review examines the current use and limitations of patient-reported outcome measures (PROMs) in pediatric regional anesthesia research. Despite the increasing emphasis on patient-centered outcomes, existing pediatric outcome assessment frameworks may inadequately capture the pain experience and interference with daily living. RECENT FINDINGS: Across 17 identified randomized controlled trials and 15 ongoing studies, PROM use remains highly variable, with consistent reliance on observational pain scales such as the Face, Legs, Activity, Cry, and Consolability scale and limited incorporation of standardized, longitudinal health-related quality-of-life measures. SUMMARY: Current pediatric PROM frameworks remain fragmented, limiting comprehensive evaluation of recovery. Greater standardization and incorporation of developmentally appropriate, longitudinal outcome measures are needed to better align clinical research with meaningful patient-centered endpoints and to improve assessment of functional and psychosocial recovery.

Humans

Incidence and risk factors for malignancy in patients with incidental solitary pulmonary nodules: a systematic review and meta-analysis.

BACKGROUND: The increasing use of chest imaging has led to a higher detection rate of incidental solitary pulmonary nodules (SPNs), often causing patient anxiety. Determining the malignancy rate and associated risk factors is crucial for developing appropriate follow-up strategies to prevent overdiagnosis, overtreatment, or missed diagnoses. This meta-analysis aims to investigate the malignancy rate and risk factors in patients with incidental SPNs. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to June 30, 2025. Data on malignancy rates and potential risk factors were extracted from eligible studies. All pooled analyses were performed using a random-effects model. RESULTS: Fifty-four studies involving 19,985 patients were included. The pooled malignancy rate for incidental SPNs was 56.7% (95% CI: 51.5-62.0), with significant between-study heterogeneity (I2 = 98.5%, p&#x2009;<&#x2009;0.001). The pooled effect size showed a minimal change after adjustment for potential publication bias using the non-parametric Trim-and-Fill method (54.7%; 95%CI: 50.9-58.8). Risk factor analysis identified that older age, history of cancer, cigarette smoker, larger nodule diameter, spiculation, upper lobe location, lobulation, pleural indentation, vascular convergence, solid nodules, family history of cancer, and irregular or ill-defined margins were significantly associated with an increased risk of malignancy. Conversely, male sex, presence of calcification, and clear borders were significantly associated with a reduced risk of malignancy. CONCLUSION: This meta-analysis provides a comprehensive assessment of malignancy rates and risk factors in incidental SPNs. The high pooled malignancy rate should be interpreted considering the significant heterogeneity and the inclusion of a high proportion of retrospective studies and populations from high-risk regions. Nonetheless, these findings offer essential evidence for clinical risk stratification, supporting optimized follow-up and informed decision-making.

Humans