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PubMed2026

Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.

AIMS: To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity. MATERIALS AND METHODS: The phase 3a, 68-week REDEFINE 1 trial randomised adults without diabetes with BMI ≥ 30 kg/m2, or ≥ 27 kg/m2 with ≥ 1 obesity-related complication, to once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention. This secondary, post hoc analysis assessed the proportions of participants achieving BMI < 27 kg/m2 and/or WHtR < 0.53 targets, and percentage weight loss by anthropometric target. The association between the proportion of participants maintaining or achieving normalisation of four cardiometabolic outcomes: normoglycemia (glycated haemoglobin < 5.7% and fasting plasma glucose < 5.6 mmol/L); blood pressure (< 130/80 mmHg); triglycerides (< 1.7 mmol/L); lipids (high-density lipoprotein cholesterol ≥ 1.3 mmol/L [female] or ≥ 1.0 mmol/L [male]) and reaching anthropometric targets or change in body weight (%) was also assessed. RESULTS: The proportion of participants achieving both BMI < 27 kg/m2 and WHtR < 0.53 targets at week 68 was 30.3%, 19.1%, 9.0%, and 3.3% in participants who received CagriSema, semaglutide, cagrilintide, or placebo respectively. Both BMI and WHtR performed similarly as indicators for all four cardiometabolic outcomes. At more stringent cut-off values, anthropometric targets were better measures than percentage weight loss. CONCLUSIONS: The proportion of participants achieving anthropometric targets was greater with CagriSema Versus other treatments. These findings support further validation of BMI and WHtR anthropometric treatment targets and indicate a potential for indicating amelioration of clinical outcomes in obesity and a greater emphasis on target-based treatment strategies.

Humans↗

PubMed2026

Evaluation of pilocarpine effects on sweat proteome.

BACKGROUND: Sweat is increasingly recognized as a valuable, non-invasive biofluid for biomarker discovery, yet its composition depends on the stimulation method. This study aimed to determine how pharmacological induction with pilocarpine compares to physiologically induced sweat through exercise in shaping the sweat proteome. RESULTS: We analyzed thermoregulatory sweat from exercise, pilocarpine-induced sweat, and combined pilocarpine plus exercise sweat. Total protein concentrations were similar across conditions, but pilocarpine markedly increased proteomic diversity, with combined pilocarpine plus exercise sweat showing the highest number of identifications. The core sweat proteome remained stable, while pilocarpine selectively enriched low-abundance proteins involved in vesicular trafficking, cytoskeletal remodelling, and metabolism. Proteins linked to the canonical M3-Gq-PLC-Ca2+ pathway, including AQP5, CALML5, and CLIC1, were consistently enriched, confirming cholinergic activation. Pilocarpine-induced sweat also contained plasma-derived and immune-related proteins, reflecting enhanced secretion and reduced ductal reabsorption. CONCLUSIONS: Exercise yields a physiologically relevant but less complex proteome, pilocarpine-induced sweat produces a pharmacologically enriched yet biased profile, and combined pilocarpine plus exercise sweat maximizes protein detection at the expense of interpretability. These findings highlight the critical impact of stimulation paradigm on sweat proteomics and provide a reference framework for biomarker research. SIGNIFICANCE: This study employed LC-MS/MS to systematically characterize eccrine sweat and delineate how stimulation paradigms-exercise, pilocarpine, and their combination-shape its proteomic landscape. By demonstrating that pharmacological induction profoundly alters protein diversity and composition compared to physiologically induced sweat, these findings establish a critical benchmark for sweat-based biomarker research and highlight the need for paradigm-aware sampling strategies in clinical and translational contexts. Nonetheless, several methodological constraints warrant consideration: the limited sample size (five individuals per group), the exclusive inclusion of women under combined oral contraceptive treatment (21 active pills followed by 7 pill-free days), which restricts extrapolation to naturally cycling women, and the focus on healthy young adults (18-25 years), limiting generalizability to older or clinically heterogeneous populations. Despite these limitations, this work provides a foundational framework for optimizing sweat collection protocols and advancing precision approaches in non-invasive diagnostics.

Pilocarpine↗

PubMed2026

Comparison of paralog identification methods and their impact on species tree topologies in target capture phylogenomics within the Sindora clade (Detarioideae: Leguminosae).

Target capture is a common method of generating high throughput DNA sequencing data for phylogenetic reconstruction of species relationships, for which single copy genes are usually most informative. However, a pervasive problem with target capture is that putatively single copy genes may in fact be paralogs resulting from gene duplication, which are problematic for phylogenetic inference because their evolutionary history may differ from the divergence history of species. Here, we use as a case study a target enrichment dataset of 88 species of Detarioideae (Leguminosae) with a focus on the Sindora clade to examine approaches for handling paralogs, including the built-in paralog handling functions in HybPiper and CAPTUS, plus subsequent steps using Putative Paralog Detection and the tree-based Yang & Smith orthology inference approach. We compare the paralogs flagged using these methods and verify their performance with BLAST mapping against a reference genome sequence of Sindora glabra, and then subsequently compare the species tree topologies produced across these methods. Our comparisons of paralogs flagged across the Sindora clade show that the Putative Paralog Detection pipeline was the most accurate in identifying paralogs in terms of its similarity to the BLAST mapping, followed by the built-in paralog identification function of CAPTUS. However, the results we recovered for the Detarioideae subfamily suggest that the largest differences in species tree topology resulted from the use of paralog-filtered alignments (such as with the Putative Paralog Detection pipeline and the Yang & Smith orthology inference approaches) rather than just by removing the sequences of identified paralogous genes. This was the true for HybPiper-assembled datasets but was not seen in CAPTUS-assembled datasets. In all comparisons, the topological differences caused by different paralog handling methods tended to be confined to clades where processes such as hybridisation and introgression are prevalent. Our study provides a roadmap to establish the best approach to identify, eliminate or separate paralogs in the absence of a chromosomally contiguous reference genome for a study group, and highlights the importance of careful data inspection and processing in addition to understanding the extent of paralogy and paralog characteristics (e.g. sequence divergence between copies) for their study group.

Phylogeny↗

PubMed2026

Impact of oxytocin discontinuation on fetal heart rate and uterine contractility: A pre-specified ancillary analysis embedded within a randomized trial.

INTRODUCTION: Oxytocin is widely used to augment uterine contractions during labor. However, its use has been associated with fetal heart rate (FHR) abnormalities and neonatal morbidity, which may be reduced by discontinuing oxytocin during labor. We aimed to assess the impact of oxytocin discontinuation at the onset of the active phase of labor on FHR patterns and uterine contractility. MATERIAL AND METHODS: This study is a pre-specified ancillary analysis of the STOPOXY trial, a multicenter, randomized, open-label, controlled superiority trial conducted in 21 French maternity units between January 2020 and January 2022, which aimed to assess the impact of oxytocin discontinuation during active labor on neonatal morbidity. Participants who received oxytocin before 4 cm dilation were randomly assigned (1:1) to either oxytocin discontinuation or oxytocin continuation. For the present analysis, we included women from the per-protocol discontinuation group of the parent trial. Inclusion was restricted to the six centers with electronic cardiotocography storage where valid cardiotocography recordings were available for at least 1 h before and 1 h after oxytocin discontinuation. Using a paired before-and-after design, FHR parameters (classified according to FIGO criteria) and uterine activity were compared during the 60 min preceding versus the 60 min following oxytocin discontinuation by independent obstetricians blinded to neonatal outcomes. Changes in FHR pattern were categorized as no change, improvement, or deterioration. RESULTS: 284 women fulfilled the eligibility criteria. Following oxytocin discontinuation, mean FHR increased (135 vs. 137.5 bpm; p < 0.002) and FHR variability significantly changed (p = 0.010), with a lower rate of reduced variability (3.9% vs. 2.5%) and a higher rate of normal variability (48.2% vs. 53.3%). The proportion of tracings with decelerations significantly decreased (64.1% vs. 48.6%; p < 0.001). Uterine activity decreased, with fewer uterine contractions (4.0 vs. 3.5 contractions per 10 min; p < 0.001). CONCLUSIONS: Among women receiving oxytocin during early labor, discontinuation at the onset of the active phase was associated with improved FHR patterns and reduced uterine activity, suggesting a lower fetal stress and tachysystole. Further studies are needed to assess whether these changes affect labor management or maternal experience.

Humans↗

PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗

PubMed2026

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p < 0.01), all-cause mortality (OR 0.62; p < 0.01;) and stroke (OR 0.67; p < 0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans↗

PubMed2026

Spore-forming Clostridia as overlooked determinants of microbial risk in wastewater reuse systems.

Using treated municipal wastewater for crop irrigation is a key strategy to combat drought-induced water scarcity. However, current wastewater reclamation standards systematically underestimate risks from spore-forming pathogens. As highlighted in a recent minireview by A. Mrozinski, C. Le Maréchal, and E. Topp in Applied and Environmental Microbiology (92:e00173-26, 2026, https://doi.org/10.1128/aem.00173-26), Clostridioides difficile and Clostridium perfringens survive conventional disinfection, persist indefinitely in agricultural soils, and harbor critical antibiotic resistance genes. To safeguard the food supply and protect public health, regulatory frameworks must shift from relying solely on standard vegetative bacterial indicators and include monitoring resilient, spore-forming pathogens.

Clostridium↗

PubMed2026

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the β - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher β values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed2026

The landscape of pruning for large language models: A systematic review and unified taxonomy.

Confronting the inherent tension between the exceptional capabilities and the immense computational costs of Large Language Models (LLMs), pruning has become a crucial technique for achieving efficient deployment. However, a systematic analytical framework dedicated specifically to LLM pruning remains absent. In this paper, we aim to bridge this gap. We first elucidate the theoretical foundations that underpin the effectiveness of pruning, namely overparameterization and redundancy, and then propose a multidimensional taxonomy that organizes existing approaches along the axes of granularity, timing, and criteria. Building upon this unified perspective, we further analyze performance recovery mechanisms and the broader evaluation ecosystem, while also exploring forward-looking challenges such as interpretability, automation, and hardware-algorithm co-design. Through this comprehensive synthesis, we seek to provide an integrated and coherent analytical lens for advancing both research and practice in LLM pruning.

Large Language Models↗

PubMed2026

Comment on "Large-scale whole-genome sequencing of animal clinical Salmonella enterica demonstrates relatedness to human cases".

Explore the source record for details and available documents.

Letter↗

PubMed2026

Efficient homologous replacement and deletion of large genomic fragments through template-jumping prime editing in rice.

Homologous replacement of genomic sequences with large DNA fragments (> 100 bp) holds great potential for crop breeding, yet an efficient method to achieve such edits is lacking in plants. Here, in rice, we developed template-jumping prime editing (TJ-PE), a recently reported PE strategy for large targeted insertion, as an efficient tool for homologous replacement with DNA fragments ranging from dozens to hundreds of base pairs, and using TJ-PE, we replaced genomic fragments of up to 340 bp with homologous fragments of the same length. In addition, our TJ-PE tool also enabled precise deletion of 944- to 2024-bp fragments in rice, with efficiencies of up to 34.6% for c. 2000-bp precise deletions. Collectively, this study expands the editing scope of PE in rice and establishes TJ-PE as a generalist tool for precise deletion and replacement of large DNA fragments.

Oryza↗

PubMed2026

An individualized nomogram for predicting progression-free survival in systemic anaplastic large cell lymphoma: a multicenter, retrospective, and internally validated study.

OBJECTIVES: To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS: Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum β2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION: This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.

Humans↗

PubMed2026

Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals↗

PubMed2026

Evaluation of a cornea-specialized large language model for diagnostic and management accuracy in complex corneal cases.

PURPOSE: To evaluate whether a cornea-specialized large language model (LLM) enhanced with retrieval-augmented generation (RAG) improves clinicians' diagnostic and management accuracy in complex corneal cases compared to a general-purpose GPT-4o model and unaided clinician performance. METHODS: This prospective, randomized, masked evaluation study involved three cornea trainees who each independently reviewed 39 real-world corneal cases under three experimental conditions: unaided, GPT-4o-assisted, and assisted by a cornea-specialized GPT-4o model. The cornea-specialized model was constructed by embedding over 200 publicly available Wikipedia articles into GPT-4o's RAG framework. Participants provided open-ended diagnoses and selected the next-step management options (multiple choice). They were allowed up to three GPT-4o queries per case, and the AI-assisted arms were randomized to minimize bias. Accuracy for both tasks was compared against expert reference standards using McNemar's test. RESULTS: Diagnostic accuracy was 48.7%, 20.5%, and 38.5% unaided, improving to 69.2%, 46.2%, and 59.0% with general GPT-4o (p<0.04). The cornea-specialized GPT-4o further improved accuracy to 71.8%, 48.7%, and 74.4%, with improvements over unaided performance for all clinicians (p<0.01). For next-step decisions, unaided accuracy was 76.9%, 87.2%, and 59.0%. With the specialized model, Ophthalmologist 3 improved to 71.8% (p<0.05), Ophthalmologist 1 remained high at 82.1%, and Ophthalmologist 2 declined to 64.1% (p<0.05). CONCLUSIONS: A cornea-specialized LLM enhanced with RAG improved diagnostic accuracy in complex corneal cases, particularly among clinicians with lower baseline performance. Effects on management accuracy were inconsistent. Future studies should explore the use of open-ended management tasks and examine whether smaller, curated retrieval corpora yield better model performance.

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

RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD+/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

AKT/mTOR signaling pathway↗

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↗