Nevin Manimala

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

BMC Med Educ. 2026 May 2. doi: 10.1186/s12909-026-09332-2. Online ahead of print.

ABSTRACT

BACKGROUND: Strengthening professional identity is crucial to mitigate nursing students’ attrition and ensure a sustainable workforce. While the hidden curriculum and learning engagement are believed to influence this identity, their interrelationships remain unclear.

AIMS: This study aims to explore the relationship between hidden curriculum and professional identity and examine whether learning engagement mediates the relationship between hidden curriculum and professional identity.

METHODS: A cross-sectional study was conducted among 623 undergraduate nursing students from two medical colleges in China. The general information questionnaire, Hidden Curriculum Evaluation Scale in Nursing Education, Utrecht Work Engagement Scale-Student, and Professional Identity Scale for Nursing Students were used for data collection, and IBM SPSS 26.0 and PROCESS macro (Model 4) were used for statistical analysis.

RESULTS: Hidden curriculum, learning engagement, and professional identity were significantly positively correlated. Learning engagement partially mediated the relationship between hidden curriculum and professional identity, accounting for 44.13% of the total effect.

CONCLUSIONS: Nursing educators should proactively develop the hidden curriculum and implement strategies to boost learning engagement, thereby fostering students’ professional identity and reducing future workforce attrition.

PMID:42067930 | DOI:10.1186/s12909-026-09332-2

BMC Oral Health. 2026 May 2. doi: 10.1186/s12903-026-08511-3. Online ahead of print.

ABSTRACT

BACKGROUND: The popularity of white teeth among patients has led to the introduction of various restorative materials with bleach shades. However, color change in these materials remains a drawback to the long-term success of such restorations. The aim of this study was to compare the effects of different light-curing intensities on the color change of three Resin-Based Composite types in two shades after immersion in coffee.

METHODS: In this in vitro study, 120 samples of three types of Resin-Based Composite were prepared, including Vit-l-escence in two shades (PN and OS), Gradia in two shades (A2 and XBW), and Filtek Z350 XT in two shades (A2 and XW). They were polymerized at intensities of 1000 mW/cm² and 1400 mW/cm² using a Valo light-curing device for 20 s. All specimens were incubated in distilled water at 37 °C for 24 h. After measuring the initial color, all specimens were immersed in a coffee solution at 50 °C for 7 days. The final color of the specimens was re-evaluated, and ΔE₀₀ was calculated. Data were analyzed using One and Three-way ANOVA, and Post hoc Tukey HSD test in SPSS 26. P < 0.05 was considered statistically significant.

RESULTS: Resin-Based Composite type (P < 0.001), Resin-Based Composite shade (P < 0.001), and light-curing intensity (P < 0.001) had a significant effect on color change. The greatest color change was observed in Vit-l-escence (bleach shade, light-curing intensity of 1000 mW/cm²) and the lowest color change was in Gradia Direct (normal shade, light-curing intensity of 1400 mW/cm²). The higher light-curing intensity (1400 mW/cm²) significantly reduced color change in Gradia for both bleach and normal shades, as well as in Vit-l-escence for both bleach and normal shades.

CONCLUSIONS: Gradia Direct and Vit-l-escence showed less significant color change at a light-curing intensity of 1400 mW/cm² compared to 1000 mW/cm²; however, Filtek Z350 did not exhibit this result. The color change of bleach shade Resin-Based Composites was also greater than that of the normal shades. Thus, light-curing intensity may influence the color stability of Resin-Based Composites, and this effect likely depends on multiple factors, such as Resin-Based Composite shade and type.

PMID:42067920 | DOI:10.1186/s12903-026-08511-3

BMC Oral Health. 2026 May 1. doi: 10.1186/s12903-026-08495-0. Online ahead of print.

ABSTRACT

AIM: The aim of this study is to assess whether coloured resin composites undergo greater colour changes following exposure to a colouring solution after the use of a whitening mouthwash.

MATERIALS AND METHODS: Sixty composite discs (2 × 8 mm) were prepared and divided into three groups (n = 20). Each group was then randomly assigned to one of two different mouthwash groups (n = 10). The samples were then immersed in a coffee solution for 6 days. The samples were immersed in a whitening mouthwash solution for 24 h. The samples were then immersed in the coffee solution again for 6 days. ∆E values were calculated according to the CIEDE2000 color system. For statistical analysis, the Kolmogorov-Smirnov test, one-way ANOVA, and the LSD Post Hoc test were performed. The significance level was taken as P < 0.05.

RESULTS: For both ΔE_{00 (1-0)}, and ΔE_{00 (3-2)}; the highest colour difference values were observed in the OMN group, whilst the lowest values were observed in the EST group (P < 0.001). For ΔE_{00 (2-1)}, the values for the OMN group were found to be significantly higher than those for both the EST and PAL groups (P < 0.001).

CONCLUSION: In this study, which investigated whether coloured composite resins undergo further colour changes following exposure to a whitening mouthwash, varying degrees of colour change were observed in the composite resin samples. Re-exposure of the composite resins, which had changed colour following the use of a whitening mouthwash, to the colouring solution did not result in further colour change.

PMID:42067918 | DOI:10.1186/s12903-026-08495-0

BMC Psychol. 2026 May 1. doi: 10.1186/s40359-026-04611-5. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescence is a critical developmental stage characterized by heightened vulnerability in psychological and behavioral domains. During this period, adverse experiences such as social ostracism, anhedonia, and behavioral problems are more prevalent and can significantly disrupt individual well-being. Interventions that fail to account for adolescents’ developmental characteristics often remain ineffective. This study aims to contribute to the literature by examining the interrelationships among these variables through an integrated and holistic framework.

METHODS: The research employed a correlational survey design and was conducted with high school students. Advanced statistical techniques were used to analyze the data, allowing for a comprehensive exploration of the complex associations among the study variables.

RESULTS: The findings revealed that adolescents’ resilience negatively and indirectly influenced ostracism through anhedonia, and further affected both externalizing and internalizing behaviors indirectly and negatively through anhedonia and ostracism. Conversely, anhedonia was found to have an indirect and positive effect on externalizing and internalizing behaviors via ostracism.

CONCLUSIONS: The study demonstrated that resilience serves as a protective factor, buffering adolescents against adverse emotional and social experiences. However, anhedonic tendencies were shown to weaken social relationships and exacerbate behavioral difficulties. These findings underscore the importance of strengthening protective factors such as psychological resilience in interventions designed for adolescents.

PMID:42067911 | DOI:10.1186/s40359-026-04611-5

BMC Psychol. 2026 May 1. doi: 10.1186/s40359-026-04035-1. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigates how emotional intelligence mediates the link between future temporal orientation and depressive symptoms in university students and explores whether physical activity moderates this connection.

METHOD: Data were collected from 1,014 undergraduate students (490 males and 524 females) across three universities in Fujian Province, China, between 1 March and 5 July 2024. Participants were selected via random sampling and completed the Future Time Perspective Scale, Emotional Intelligence Scale, Physical Activity Rating Scale, and Epidemiologic Studies Depression Scale. Statistical analyses included Pearson’s correlation, linear regression, and moderated mediation analysis (PROCESS Model 7) using SPSS 22.0.

RESULTS: (1) Future time perspective significantly and negatively predicted depression (β = -0.32, p < 0.001). (2) Emotional intelligence partially mediated the association between future time perspective and depression (indirect effect = -0.11, SE = 0.02, 95% CI [-0.15, -0.08]). (3) Physical exercise moderated the first-stage path of the mediation model (FTP → EI). Simple slope analyses showed that the FTP-EI association was significant at both low (M – 1 SD) and high (M + 1 SD) levels of physical exercise, but was stronger at high physical exercise (simple slope: β = 0.41, p < 0.01) than at low physical exercise (simple slope: β = 0.25, p < 0.01).

CONCLUSION: Future time perspective influences depression both directly and indirectly through emotional intelligence. Additionally, physical exercise enhances the predictive effect of future time perspective on emotional intelligence, suggesting that active individuals exhibit a stronger link between future-oriented thinking and emotion regulation.

PMID:42067909 | DOI:10.1186/s40359-026-04035-1