Tag: pubmed

Ecol Lett. 2026 May;29(5):e70393. doi: 10.1111/ele.70393.

ABSTRACT

Understanding how plants influence each other’s spatial distribution is pivotal not only for interpreting current communities, but also for anticipating their responses to global changes. The combination of high-resolution, multi-scale sampling and novel statistical frameworks now enables us to identify species aggregations and segregations within their local co-occurrences. By applying this approach to approximately 800 plant species and their communities across the French Alps, we discovered that local species associations are dependent on soil acidity and nitrogen rather than climate. By building a regional network from these associations, we identified a centralised core comprising a few dominant, stress-tolerant graminoids and shrubs with high leaf dry matter content and no unique functional roles. Our findings demonstrate that plant community assembly is less dependent on random co-occurrence and more dependent on segregation around a few dominant, stress-tolerant species, with soil conditions modulating the outcome of local associations.

PMID:42068051 | DOI:10.1111/ele.70393

Med Sci Monit. 2026 May 2;32:e951712. doi: 10.12659/MSM.951712.

ABSTRACT

BACKGROUND Ankle arthritis is a chronic degenerative disease; its typical symptom is pain in the ankle joint. This retrospective study of 65 patients with mid-stage ankle osteoarthritis aimed to compare clinical outcomes from supramalleolar osteotomy (SMOT) and supramalleolar osteotomy combined with fibular osteotomy (SMOT+FO). MATERIAL AND METHODS Based on whether fibular osteotomy was performed during the procedure, the patients were categorized into the SMOT group (n=34) or the SMOT+FO group (n=31). Surgical outcomes were systematically assessed using the Visual Analogue Scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, range of motion (ROM), and complication rates. Radiographic parameters were compared between the 2 groups, including the distal tibial articular surface angle, talar tilt angle, tibiocrural angle, and tibial lateral surface angle. RESULTS The AOFAS scores, VAS scores, and imaging indicators in both patient groups showed significant improvement compared with preoperative levels (P<0.001). However, no statistically significant improvement was observed in the ROM. Compared to SMOT, the addition of fibular osteotomy demonstrated superior outcomes in terms of AOFAS scores and greater improvement in both the talar tilt and tibiocrural angles (P<0.001). The overall incidence of postoperative complications in the SMOT group was lower than that in the SMOT+FO group (2.9% vs 6.4%; OR, 0.44; 95% CI, 0.04 to 5.10). However, the difference did not reach statistical significance (P=0.500). CONCLUSIONS Combining fibular osteotomy with SMOT not only significantly enhances ankle joint function but also exhibits notable advantages in improving radiological parameters, so as to provide long-term clinical benefits for patients.

PMID:42068025 | DOI:10.12659/MSM.951712

J Hepatobiliary Pancreat Sci. 2026 May 1. doi: 10.1002/jhbp.70124. Online ahead of print.

ABSTRACT

BACKGROUND: The use of minimally invasive (MI) techniques for Hilar cholangiocarcinoma (HCCA) has increased in the last years, but high-quality evidence remains limited. This study aims to assess the safety of laparoscopic (LPS) and robotic (ROB) approaches compared to open surgery in the treatment of HCCA.

METHODS: After a systematic search, a frequentist network meta-analysis and a Trial sequential analysis were performed. Primary outcomes set for the study were major complications and R0 rate.

RESULTS: Fourteen studies including 1169 patients were found eligible, of which 403 were LPS (34.5%) and 137 operated with a ROB approach (11.7%). ROB and LPS techniques showed statistically similar rates of major complications (p = 0.251 and p = 0.143), while ROB was associated with a higher rate of negative resection margins (OR: 2.856, 95% CI: 1.585-5.144; p < 0.001). No differences were observed in the secondary outcomes assessed, except for the operative time, higher in both MI approaches, and length of stay, shorter in the ROB group.

CONCLUSIONS: Global experience in MI surgery for HCCA remains limited and subject to potential bias. Nevertheless, both LPS and ROB approaches seem to represent safe and viable options for carefully selected patients when performed by experienced surgeons in high-volume centers.

PMID:42068018 | DOI:10.1002/jhbp.70124

J Res Adolesc. 2026 Jun;36(2):e70193. doi: 10.1111/jora.70193.

ABSTRACT

Child maltreatment is a significant risk factor for mental and metabolic health, with negative effects that can persist into adulthood. Using data from a U.S.-nationwide study, the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examined the associations between child maltreatment, specifically childhood threat (i.e., harm or threat of harm) and deprivation (i.e., absence of expected environmental inputs), and young adult mental (i.e., depressive symptoms) and metabolic health (i.e., metabolic risk). The moderating effect of social support was also examined, focusing on both quality of different types of support (i.e., from teachers, friends, and other adults) and variety of support sources. Results showed that young adults who experienced more threat during childhood exhibited higher levels of depressive symptoms in young adulthood, and those exposed to more deprivation reported elevated levels of metabolic risk. This study also highlighted the protective-stabilizing role of quality of teacher support in buffering the impact of deprivation on depressive symptoms, and the protective-stabilizing role of high-quality other adult support in the link between childhood deprivation and metabolic risk, such that the benefits of social support remained stable across increasing levels of deprivation. Additionally, the variety of social support showed a protective-reactive pattern in moderating the link between deprivation and metabolic risk, wherein the benefits of variety of social support were released under low deprivation but not high deprivation conditions for metabolic risk. These findings underscore the importance of eliminating child maltreatment experiences and highlight potential interventions, such as enhancing teacher-student relationships and broadening adolescents’ access to diverse support networks, to buffer the long-term mental and metabolic health consequences associated with early experiences of threat and deprivation.

PMID:42068015 | DOI:10.1111/jora.70193

Drug Deliv. 2026 Dec 31;33(1):2665892. doi: 10.1080/10717544.2026.2665892. Epub 2026 May 1.

ABSTRACT

Cisplatin-induced hearing loss (CIHL) in pediatric cancer patients is an irreversible and highly prevalent adverse effect with a devastating impact on quality of life. Sodium thiosulfate (STS) has recently been approved for systemic administration as an otoprotective agent in children. However, implementation of systemic STS has its challenges, and there is currently limited evidence to support local STS for children. This review investigates the potential value of locally administered otoprotective agents other than STS with a focus on future pediatric implementation. We conducted a systematic review on the efficacy and safety of locally applied non-STS otoprotective agents in in vivo settings. This included a summary of investigated drug delivery methods and administration routes. We identified 70 preclinical and eight clinical studies. Agents were categorized based on their biological mechanisms: anti-inflammatory, chemical deactivators, calcium blockers, biologicals, and miscellaneous mechanisms. Preclinical studies investigated 45 different agents. Dexamethasone and N-acetylcysteine were identified as efficacious agents recurrently and progressed to clinical trials. Dexamethasone was investigated in three randomized clinical trials (RCTs) and three non-randomized clinical studies and showed statistically significant but not clinically relevant benefit in two trials. N-acetylcysteine was investigated in two clinical trials and one RCT and was minimally effective in the RCT and in one clinical study. Our review did not identify available studies of local alternative otoprotective agents that could reliably replace systemic STS in terms of safety and efficacy for pediatric patients. Further research on the optimal dosage, delivery method, and timing of otoprotective agents is needed.

PMID:42068011 | DOI:10.1080/10717544.2026.2665892

Pharm Stat. 2026 May-Jun;25(3):e70095. doi: 10.1002/pst.70095.

ABSTRACT

As Phase III trial costs and durations rise, pharmaceutical companies increasingly use quantitative methods to decide if a drug should progress beyond Phase II. A key method is the probability of success (PoS) for Phase III, calculated using the power function averaged across a treatment effect distribution estimated from Phase II. This paper explores PoS’s role, particularly in moving from Phase II trials with putative surrogate endpoints to Phase III trials with clinical endpoints. Since the relationship between these endpoints is often unknown, expert input is necessary (prior elicitation). We propose the bivariate meta-analysis and a copula-based extension to characterize their relationship, using visual tools to simplify parameter elicitation. Specifically, we begin by eliciting the marginal distributions of the two quantities of interest. Then, to assist in eliciting the concordance parameter, we use the distribution of the treatment effect on the clinical endpoint conditional on the treatment effect on the putative surrogate. Our approach is illustrated in prophylactic vaccine development, linking immunological and clinical endpoints.

PMID:42067960 | DOI:10.1002/pst.70095

Adv Simul (Lond). 2026 May 1. doi: 10.1186/s41077-026-00444-9. Online ahead of print.

ABSTRACT

BACKGROUND: In cardiac arrest management, cognitive aids provide prompts to encourage recall of critical information, which may improve clinical performance. Whether cognitive aids influence provider workload, cognitive load, teamwork dynamics, or leadership during cardiac arrest remains unknown. In this study, we evaluated the effect of using a multi-faceted decision support system with augmented reality-based cognitive aids (i.e. InterFACE-AR) vs. the American Heart Association (AHA) Pediatric Advanced Life Support (PALS) pocket card on provider workload and cognitive load, teamwork, and leadership during simulated pediatric cardiac arrest.

METHODS: We conducted secondary analysis of data collected from a prospective, randomized controlled trial comparing the use of the InterFACE-AR system to the AHA PALS pocket card during simulated pediatric cardiac arrest. Participants were recruited in groups of 3 to perform the roles of team leader, medication nurse, and documenting nurse. All teams completed a 12-min simulated cardiac arrest scenario. Provider workload (NASA-RTLX) and cognitive load (Paas score) were captured from participants after the scenario. Teamwork (TEAM score) and leadership performance (CALM score) were assessed via video review.

RESULTS: A total of 18 simulation sessions were analyzed (Control: n = 9; InterFACE-AR: n = 9), involving 54 participants in total. Team leaders using the InterFACE-AR system had lower RTLX (mean difference [MD]: -15.0; 95% confidence interval [CI]: -27.0 to -4.6, p = 0.022) and Paas score (MD: -2.4; 95%CI: -3.6 to -1.4, p < 0.001), while documenting nurses showed similar reductions (RTLX -13.7, 95%CI: -26.7 to -0.4, p = 0.049; Paas -1.6, 95%CI: -2.8 to -0.1, p = 0.046) compared with those using PALS pocket card. Medication nurses demonstrated no statistically significant differences in RTLX (p = 0.098) or Paas score (p = 0.194). Teams using the InterFACE-AR system achieved significantly higher TEAM scores compared to those using PALS pocket card only (39.2 vs 35.8, MD: 3.4, 95%CI: 0.8 – 5.9, p = 0.030). CALM scores did not differ significantly between groups.

CONCLUSION: Use of an AR-based decision support system during simulated pediatric cardiac arrest reduces workload and cognitive load for the team leader and documenting nurse, but does not affect workload or cognitive load of medication nurses. Use of the InterFACE-AR system seems to improve teamwork performance but does not influence leadership performance of team leaders.

TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT06376643.

PMID:42067953 | DOI:10.1186/s41077-026-00444-9

Alzheimers Res Ther. 2026 May 2. doi: 10.1186/s13195-026-02051-2. Online ahead of print.

ABSTRACT

BACKGROUND: Aging is the primary risk factor for sporadic Alzheimer’s disease (AD). While amyloid-beta oligomers (AβOs) accumulation is a key neuropathological process in AD, their specific effects in aged brains and how aging modulates brain response to AβOs remains poorly understood. We investigated how aging contributes to AβO-induced neurotoxicity and cognitive deficits in mice.

METHODS: After biochemical and in vitro characterizations on primary cultures of cortical neurons, AβOs or their vehicle were intracerebrally injected into both 3- and 18-month-old wild-type mice. A broad spectrum of assays including synaptic markers, neuroinflammation, apoptosis and cognitive functions was used to establish a preliminary characterization of the interplay between age and AβOs. In vivo data were analyzed using a multifactorial design (Treatment × Age), with two-way ANOVA or other appropriate statistical models.

RESULTS: Old mice had significantly reduced synaptic proteins SNAP-25 and PSD-95, elevated neuroinflammatory markers, and increased neuronal apoptosis in hippocampus and cortex, despite showing cognitive performances similar to young mice. All brain biomarkers were worsened after AβO injection in both young and old mice. Age and AβO effects either accumulated or interacted to promote neuroinflammation and apoptosis, depending on brain areas, whereas their effects on synaptic proteins were strictly additive. Moreover, AβO injection induced only mild spatial memory deficits in young mice, in contrast with those observed in old mice in both episodic and spatial memory tests.

DISCUSSION: Whereas the young brain showed resilience to maintain memory performances after AβO injection, the coping capacities of the aging brain were exceeded by AβO effects. At the neurobiological level, age and AβO effects were mainly additive, but also acted synergistically in a brain region-dependent vulnerability pattern. This study highlights the value of incorporating aging into preclinical models to improve their translational validity and enhance their relevance for drug testing targeting early stages of sporadic AD.

PMID:42067950 | DOI:10.1186/s13195-026-02051-2

Stem Cell Res Ther. 2026 May 1. doi: 10.1186/s13287-026-04915-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by loss of tear film homeostasis, inflammation, neurosensory abnormalities, and epithelial damage. Despite the availability of topical immunomodulators and procedural interventions, a substantial proportion of patients with moderate-to-severe or refractory DED experience persistent symptoms and inadequate ocular surface recovery. Stem cell-based therapies, particularly mesenchymal stem cells (MSCs) and MSC-derived exosomes, have emerged as regenerative and immunomodulatory strategies aimed at restoring epithelial integrity and tear film stability rather than providing solely symptomatic relief. We conducted a systematic review and meta-analysis to evaluate the clinical efficacy and safety of stem cell and stem cell-derived therapies in human DED.

METHODS: This study followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420251057372). Six databases were searched from inception to May 14, 2025. Eligible studies were peer-reviewed human clinical investigations evaluating stem cell-based interventions for DED and reporting objective efficacy outcomes such as Schirmer test, tear break-up time (TBUT), corneal fluorescein staining (CFS), or patient-reported outcomes including the Ocular Surface Disease Index (OSDI). Pooled mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Statistical heterogeneity was assessed using the I² statistic. Risk of bias was evaluated using RoB 2 for randomized controlled trials and ROBINS-I for non-randomized studies.

RESULTS: Six studies comprising 131 patients were included. Stem cell-based therapies demonstrated significant improvements in tear production, tear film stability, epithelial integrity, and symptom burden. Schirmer test improved by MD = 4.70 mm (95% CI, 4.18-5.22; p < 0.001; I² = 12.59%), indicating a consistent enhancement of aqueous tear secretion. TBUT showed a large standardized improvement with pooled SMD = 1.125 (95% CI, 0.821-1.428; p < 0.001), although randomized trials demonstrated smaller effect sizes than non-randomized studies. OSDI scores decreased by MD = -11.44 points (95% CI, -22.71 to -0.17; p = 0.047), reflecting symptomatic improvement but with substantial between-study variability. Corneal fluorescein staining decreased by MD = -1.04 (95% CI, -1.23 to -0.84; p < 0.001; I² = 0%), supporting epithelial recovery. No serious treatment-related adverse events were reported; however, safety reporting was heterogeneous and follow-up durations were limited.

CONCLUSION: Stem cell and stem cell-derived therapies are associated with significant improvements in both objective and subjective outcomes in DED and demonstrate a favorable short-term safety profile. Nevertheless, heterogeneity in cell source, delivery route, dosage, and study design limits generalizability. Larger, rigorously designed randomized trials with standardized protocols and longer follow-up are required to confirm efficacy and establish long-term safety.

PMID:42067941 | DOI:10.1186/s13287-026-04915-8

Respir Res. 2026 May 1. doi: 10.1186/s12931-026-03693-4. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous in vivo studies have demonstrated beta-2-adrenoceptor (β₂AR) -agonism as permissive in the development of allergic lung inflammation, and have implicated the arrestin-dependent signaling arm of the β₂AR in mediating this effect. However, the specific cell type(s) mediating β₂AR regulation of allergic lung inflammation remain unestablished.

METHODS: To explore the potential contribution of airway epithelia in this phenomenon, we compared the ability of ractopamine (RP), recently identified as a Gs-biased beta-agonist, to that of the unbiased/balanced beta-agonist albuterol (ALB), on IL-13-stimulated mucin and cytokine production in human airway epithelia cultures in air-liquid interface (HAE).

RESULTS: ALB, which activates both the β₂AR-arrestin and -Gs signaling pathways significantly augmented IL-13-induced mucin production in HAE. RP, which preferentially signals via Gs/PKA, did not. Although IL-13 stimulated production of numerous cytokines, including IL-1α, IL-1RA, MDC, TGF-α, and GROα, ALB-mediated augmentation of these cytokines was highly variable and not statistically significant. Similarly, RP did not augment the induction of cytokines stimulated by IL-13. Moreover, in contrast to previous studies that reported a requirement of concomitant β₂AR agonism for IL-13 to stimulate cytokine production, such a requirement was observed only in minority of the (12) cultures examined.

CONCLUSIONS: These data implicate arrestin-dependent β₂AR signaling augmenting airway epithelial mucin production as a contributor to the previously-demonstrated pro-inflammatory effects of β₂AR agonism in vivo. Moreover, they suggest that beta-agonist effects on the cytokine profile in the allergen-inflamed lung may be influenced by specific asthmatic endotypes and involve cooperativity among multiple cell types.

PMID:42067931 | DOI:10.1186/s12931-026-03693-4