Tag: pubmed

Psychophysiology. 2026 Jun;63(6):e70334. doi: 10.1111/psyp.70334.

ABSTRACT

Electroencephalography (EEG) has emerged as a key method for investigating the neural mechanisms through which oxytocin influences cognition and behavior. EEG is cost-effective, has excellent temporal precision, and may elucidate neural correlates of emotional and cognitive processes. EEG studies evaluating oxytocin’s electrophysiological effects have, however, yielded mixed results, which is likely driven by heterogeneity in EEG measures, study designs, dosages, and samples. To investigate the effect of oxytocin administration on EEG measures, we performed two multilevel random effects meta-analyses: The first meta-analysis synthesized studies investigating the effects of oxytocin administration on different neural correlates of social and cognitive processing; the second meta-analysis synthesized studies evaluating effects of oxytocin administration on exploratory, less task-specific neural activity measures, such as the modulation of microstates. Across both meta-analyses, we synthesized 161 effect sizes from 28 randomized controlled trials with a total of 1361 participants from different population groups. These multilevel meta-analyses yielded statistically significant, small effect sizes of oxytocin administration across different EEG measures reflecting social and cognitive processes (Hedges’ g = 0.14), and exploratory neural activity (Hedges’ g = 0.28) with significant heterogeneity estimates (p < 0.01 and p < 0.001, respectively). Moderator analyses revealed that the different EEG measurements of interest (e.g., event-related potentials) and the proportion of female participants were found to significantly moderate the effect of oxytocin on neural EEG activity. Altogether, these meta-analyses present tentative evidence for oxytocin administration modulating a wide range of EEG-based markers of neural activity. We observed substantial heterogeneity across studies-in terms of study designs, experimental paradigms and EEG measurements, and participant characteristics. More research is warranted to map out the context-specific effects of oxytocin administration on different neural markers, to better understand the neurobiological mechanisms of oxytocin.

PMID:42268581 | DOI:10.1111/psyp.70334

Clin Transl Oncol. 2026 Jun 10. doi: 10.1007/s12094-026-04442-1. Online ahead of print.

ABSTRACT

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression assessed by the combined positive score (CPS) is required for eligibility to first-line pembrolizumab-based therapy in metastatic triple-negative breast cancer (mTNBC). However, the predictive value of CPS beyond treatment eligibility, particularly for disease control, response kinetics and response durability in real-world practice, remains uncertain. This study evaluated the association between CPS analyzed as a continuous variable and clinical outcomes in a Polish real-world mTNBC population.

METHODS: This multicenter retrospective study included patients with PD-L1-positive (CPS ≥ 10) mTNBC treated with first-line pembrolizumab plus chemotherapy across 13 oncology centers in Poland (2022-2025). CPS was assessed locally and primarily analyzed as a continuous variable with exploratory categorical analyses performed for descriptive and visualization purposes. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression as best response. Secondary endpoints were time to best response (TTBR) and duration of response (DoR).

RESULTS: Seventy-two patients were eligible for analysis. Median age was 57 years (IQR 48-67) and median CPS was 20 (IQR 15-50). After a median follow-up of 11.6 months, ORR was 48.6% and DCR was 88.9%. CPS did not differ between patients achieving ORR versus no ORR (p = 0.58) or DCR versus no DCR (p = 0.56), nor was it associated with progression as best response. CPS showed no correlation with TTBR (ρ = 0.02, p = 0.9) or DoR (ρ = -0.33, p = 0.05). In univariable analysis, CPS was not associated with PFS. However, in multivariable Cox regression, CPS showed a statistically significant association with PFS, although the effect size was minimal (HR 1.01 per CPS unit).

CONCLUSIONS: In real-world PD-L1-positive mTNBC, CPS was not significantly associated with response outcomes. Although statistically linked to PFS, the effect was minimal and likely not clinically meaningful, supporting its role as a threshold-based rather than quantitative biomarker.

PMID:42268564 | DOI:10.1007/s12094-026-04442-1

Invest New Drugs. 2026 Jun 10. doi: 10.1007/s10637-026-01624-0. Online ahead of print.

ABSTRACT

A common, often unstated paradigm in T-cell engager (TCE) translation assumes that target-antigen density and drug exposure are the main efficacy drivers, with effector context secondary. This paradigm is visible in dose-escalation strategies and in the use of high-E:T screens as principal preclinical assays. We tested whether an alternative, receptor-saturation framework better organizes the published AMG 330 record in acute myeloid leukemia (AML). Receptor-saturation arguments motivate two qualitative expectations: at sufficiently high CD33 densities, EC $_{50}^{}$ should show little systematic dependence on additional antigen density, and response should become increasingly constrained by effector availability and functional state. We tested these expectations using two statistical reanalyses of published AMG 330 data-log-linear regression of EC $_{50}^{}$ on CD33 density across 11 AML cell lines, and a comparative effect-size analysis of effector-to-target (E:T) ratio versus CD33 expression in 38 primary AML samples-integrated with clinical exposure-response findings and effector-augmenting rescue studies. Both expectations were supported. CD33 density did not significantly predict EC $_{50}^{}$ across the 3.9-fold range tested ( $p=0.13$ ; bootstrap 95% CI on slope includes zero). In primary samples, E:T ratio dominated sustained lysis by approximately an order of magnitude over CD33 expression (92.4 vs. 8.5 percentage points; CD33 effect $p=0.7$ , not significant). Clinical exposure-response analyses identified baseline E:T ratio and T-cell PD-1 expression as response correlates. A similar target-effector dissociation has been reported in several other TCE programs. The AMG 330 record is more coherently organized by an effector-context framework than by the conventional target-density-and-exposure paradigm. These findings indicate that endogenous-effector assays, paired target-effector biomarkers, and rational effector-support strategies are likely to be clinically informative complements to conventional cell-line potency and dose-escalation approaches in future CD33 TCE development.

PMID:42268556 | DOI:10.1007/s10637-026-01624-0

Neuroinformatics. 2026 Jun 10;24(2):35. doi: 10.1007/s12021-026-09792-3.

ABSTRACT

Dynamic functional connectivity (dFC) analysis in functional magnetic resonance imaging (fMRI) faces a fundamental challenge: conventional sliding-window methods must trade temporal resolution against statistical reliability, while rare transient neural events risk becoming undetectable when included in training data. We introduce HESREN (Hermite-Enhanced Software Reservoir Network), a novel framework integrating echo state networks with derivative-informed Hermite-type neural operators to enable windowless dFC estimation and leakage-free transient detection. HESREN employs a leaky-integrator reservoir that projects multivariate fMRI time series into high-dimensional state spaces, augmented with Gaussian-smoothed temporal derivatives to form enhanced feature vectors encoding value, velocity, and acceleration. Strict temporal partitioning trains all components exclusively on baseline segments while evaluating on complete time series, preserving transient events as out-of-distribution signals. Teacher-student distillation transfers the temporal precision of micro-window connectivity estimates into stable windowless operators via ridge-regularised linear readout; all hyperparameters and initialisation procedures are fully specified to ensure reproducibility. Validation on the NEBULA101 resting-state fMRI dataset across [Formula: see text] participants demonstrates consistent and substantial improvements over conventional methods. Transient event detection achieves AUC[Formula: see text] and average precision AP[Formula: see text], compared to AUC[Formula: see text] for raw-derivative baselines (Wilcoxon [Formula: see text], [Formula: see text], Cohen’s [Formula: see text]), with phase-randomised surrogate testing confirming statistical robustness in all participants ([Formula: see text], [Formula: see text] surrogates). Comparison against mainstream dFC alternatives shows that HESREN statistically significant performance gains Gaussian Hidden Markov Models (AUC[Formula: see text]), temporal convolutional networks (AUC[Formula: see text]), LSTM autoregressive predictors (AUC[Formula: see text]), and conventional sliding-window correlation (AUC[Formula: see text]), with all advantages statistically significant ([Formula: see text]). Windowless dFC trajectories attain lag-corrected correlation [Formula: see text] with micro-window teachers while providing 3-[Formula: see text] finer temporal resolution than 25-TR sliding windows. Network-level analysis reveals that HESREN detects transient events an average of 4.5 TR (9 s) earlier than sliding-window methods, selectively amplifies within-language-network coupling by [Formula: see text] and default-mode-network coupling by [Formula: see text] during detected events, and is the only evaluated method to yield a positive network segregation index ([Formula: see text]), consistent with the known modular organisation of resting-state brain networks. HESREN overcomes fundamental limitations of sliding-window dFC through derivative-aware reservoir dynamics, offering a computationally efficient, mathematically principled framework for capturing transient neural reconfigurations with temporal precision previously improved in fMRI connectivity analysis. The modular architecture facilitates adaptation to diverse neuroimaging applications, from basic neuroscience to real-time clinical monitoring systems.

PMID:42268529 | DOI:10.1007/s12021-026-09792-3

Breast Cancer. 2026 Jun 10. doi: 10.1007/s12282-026-01876-x. Online ahead of print.

ABSTRACT

BACKGROUND: Although taxanes are a mainstay treatment for locally advanced or metastatic breast cancer (LABC/MBC), they often impair quality of life (QoL). Treatments that avoid taxane-related QoL deteriorations would be valuable.

METHODS: The JBCRG-M06/EMERALD trial (NCT03264547, UMIN000027938) compared eribulin with a taxane, each combined with trastuzumab and pertuzumab, in patients with human epidermal growth factor receptor type 2 (HER2)-positive LABC/MBC. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) version 3.0. QoL deterioration was defined as a decrease in the Global Health Status (GHS) score by ≥ 10 points (minimum clinically important difference), disease progression, or death.

RESULTS: QoL data were available for 210 (of 224 randomized) and 205 (of 222 randomized) patients in the eribulin and taxane groups, respectively. The median (95% confidence interval) time to QoL deterioration was 7.16 (6.28-8.34) months in the eribulin group versus 4.57 (4.17-6.14) months in the taxane group, with a hazard ratio of 0.80 (95% confidence interval 0.65-0.98; log-rank P = 0.08). QoL was maintained at 6 and 12 months in greater proportions of the eribulin group (62.7% and 30.5%) compared with the taxane group (43.5% and 25.5%). GHS scores remained stable over time in the eribulin group. GHS deteriorated between weeks 9 and 27 in the taxane group (i.e. during treatment) with subsequent recovery toward baseline.

CONCLUSIONS: Eribulin could help avoid the early deteriorations in QoL that occur during taxane therapy and maintain QoL for longer in patents with HER2-positive LABC/MBC receiving trastuzumab and pertuzumab.

PMID:42268523 | DOI:10.1007/s12282-026-01876-x

Saudi Dent J. 2026 Jun 10;38(6):85. doi: 10.1007/s44445-026-00195-3.

ABSTRACT

To investigate the effect of Psidium guajava fruit suspension in preventing orthodontic treatment relapse in a Wistar rat model. Twenty-four male Wistar rats (aged 8-12 weeks) underwent orthodontic treatment on the left maxillary side for 48 days. After space creation, orthodontic appliances were removed, and a 35-day retention phase was initiated. Meanwhile, the rats were randomly allocated to two groups. The control group received normal saline, and the intervention group received a suspension of 250 mg/kg P. guajava via oral gavage. After retention, the resin retainers were removed to allow for a 7-day relapse phase. Polyvinyl siloxane impressions were obtained at the start (T0) and end (T1) of the relapse phase and scanned for analysis using OrthoCad software. Of the 24 rats initially recruited, 20 rats successfully completed the experiment and were included in the statistical analysis. The mean orthodontic tooth movement (T0) and relapse measurements (T1) in the intervention group were 0.570 ± 0.125 mm and 0.515 ± 0.094 mm, respectively. In the control group, the corresponding mean values were 0.630 ± 0.194 mm and 0.410 ± 0.204 mm, respectively. The intervention group demonstrated significantly lower mean orthodontic relapse (T1-T0) than that of the control group (-0.055 ± 0.089 mm and -0.220 ± 0.058 mm, respectively, P < 0.001). Orally administered P. guajava fruit suspension may reduce orthodontic relapse and improve treatment outcomes. Further studies are required to validate these findings and elucidate the underlying mechanisms before considering human trials.

PMID:42268518 | DOI:10.1007/s44445-026-00195-3

Drugs Real World Outcomes. 2026 Jun 10. doi: 10.1007/s40801-026-00560-y. Online ahead of print.

ABSTRACT

BACKGROUND: Antidepressants are widely prescribed, with increasing use among older adults. However, evidence on their association with dementia remains inconsistent.

OBJECTIVE: This study examines the association between long-term antidepressant use and dementia risk in older adults using a propensity score-matched design, with a separate analysis of long-term tricyclic antidepressant (TCAs) use, given their anticholinergic properties.

METHODS: A retrospective cohort study was conducted using Swiss healthcare claims data (2013-2023) from older adults aged 65 years and above. Long-term antidepressant users (> 2 years) and long-term TCAs users were separately matched to nonusers using variable ratio propensity score matching. The primary outcome was incident dementia, defined by a recorded dementia diagnosis or antidementia drug prescription. Covariates were derived from inpatient and/or outpatient records, depending on the respective variable.

RESULTS: A final sample of 19,155 long-term antidepressant users were compared with 20,648 propensity score matched nonusers. After adjusting for covariates, long-term antidepressant use was significantly associated with dementia (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.72-2.15, p < 0.001). Long-term TCAs users also had higher odds of developing dementia compared with nonusers (OR 1.73, 95% CI 1.33-2.25, p < 0.001). Sensitivity analyses largely confirmed these results: long-term antidepressant users had higher odds of developing dementia compared with short-term users (OR 1.23, 95% CI 1.11-1.35, p < 0.001), but for TCA, the difference between long-term and short-term users was not statistically significant (OR 1.25, 95% CI 0.99-1.57, p = 0.059).

CONCLUSIONS: These findings suggest that long-term antidepressant and long-term TCAs use is associated with an increased risk of dementia in older adults, even after accounting for various comorbidities. This study adds to the ongoing debate on the link between antidepressants and dementia. Future research is needed to further clarify underlying mechanisms and guide clinical practice.

PMID:42268515 | DOI:10.1007/s40801-026-00560-y

Ann Biomed Eng. 2026 Jun 10. doi: 10.1007/s10439-026-04213-7. Online ahead of print.

ABSTRACT

PURPOSE: This study investigates the dynamic regulation of cerebral oxygenation in individuals with mild cognitive impairment (MCI) compared to healthy controls, using a novel pseudorandom binary sequence (PRBS) gas challenge. Traditional assessments often overlook frequency-dependent features of cerebrovascular control; this work aims to uncover latent deficits through broadband perturbations and nonparametric dynamic modeling.

METHODS: Seventeen ApoE4-negative participants (9 controls, 8 MCI) underwent a three-session supine protocol involving PRBS-modulated inhalation of hypoxic and hypercapnic gas mixtures. Physiological signals-including near-infrared spectroscopy (TOI), arterial pressure (ABP), and end-tidal CO₂ (PETCO₂)-were recorded. Laguerre-based Volterra modeling and Principal Dynamic Mode (PDM) decomposition were used to analyze the dynamic response of cerebral oxygenation to ABP and CO₂ stimuli. Group differences were statistically assessed using Welch’s t-tests and repeated measures ANOVA.

RESULTS: Controls showed significant increases in ventilation and TOI from baseline to stimulation ( $p<0.01$ ), while MCI did not. Gain of the first CO₂ PDM increased in controls during PRBS (p = 0.016) but decreased in MCI. A low-frequency ABP-derived PDM ( $\sim$ 0.014 Hz), consistent with endothelial-dependent vasodilation, was elevated only in controls during stimulation. Persistent differences in spectral recovery, kernel profiles, and PDM Gains suggested impaired baroreflex and chemoreflex regulation, and possible disruption of cholinergic-linked neurovascular coupling in MCI.

CONCLUSION: PRBS gas modulation combined with dynamic modeling revealed subtle but significant cerebrovascular control impairments in MCI. This methodology enables mechanistic insights into early pathophysiology and may aid future physiomarker development.

PMID:42268486 | DOI:10.1007/s10439-026-04213-7

Metab Brain Dis. 2026 Jun 10;41(1):132. doi: 10.1007/s11011-026-01895-9.

ABSTRACT

Alzheimer’s disease (AD) is characterized by progressive cognitive decline accompanied by profound disturbances in cerebral energy metabolism. Mitochondrial dysfunction has long been implicated in AD pathophysiology; however, the specific contribution of mitochondrial enzymes in human disease remains fragmented across heterogeneous studies. Enzymes regulating carbon entry into the tricarboxylic acid cycle, oxidative phosphorylation, and redox balance represent key metabolic control points whose dysfunction may contribute to neuronal vulnerability. To systematically synthesize human evidence on mitochondrial enzyme alterations in Alzheimer’s disease and to evaluate the feasibility of quantitative meta-analysis based on current reporting practices. A systematic literature search was conducted in PubMed, Scopus, and Web of Science from database inception through January 2026 in accordance with PRISMA 2020 guidelines. Studies were included if they investigated mitochondrial enzymes in human postmortem brain tissue, human-derived cellular models, or peripheral biospecimens. Risk of bias was assessed using the ROBINS-I tool. The feasibility of meta-analysis was evaluated based on the availability and comparability of group-level summary statistics. Fifteen studies met the eligibility criteria and were included in the final synthesis. Mitochondrial enzymes involved in carbon entry into the tricarboxylic acid cycle, oxidative phosphorylation, redox regulation, and neurotransmitter-linked mitochondrial metabolism were the most frequently investigated targets. Direct enzyme-activity evidence most consistently implicated selected metabolic control points, particularly PDHC and αKGDHC, whereas additional studies supported mitochondrial impairment through protein or post-translational modification changes, respiratory dysfunction, redox alterations, or RNA-regulatory mechanisms. Quantitative meta-analysis was not feasible due to heterogeneous assay methodologies, variable normalization strategies, and inconsistent reporting of group-level summary statistics. Human evidence consistently implicates mitochondrial enzyme dysfunction as a central metabolic feature of Alzheimer’s disease. However, progress toward cumulative quantitative synthesis remains limited by methodological heterogeneity and incomplete reporting of enzyme activity outcomes. Standardized measurement and reporting of mitochondrial enzyme alterations will be essential to advance mechanistic understanding and enable future meta-analytic integration.

PMID:42268484 | DOI:10.1007/s11011-026-01895-9

Daru. 2026 Jun 10;34(2):33. doi: 10.1007/s40199-026-00609-x.

ABSTRACT

BACKGROUND: Growing evidence supports the therapeutic role of nutraceuticals as complementary and alternative therapies in patients with type 2 diabetes mellitus (T2DM). Resveratrol, a natural polyphenol compound has been shown to modulate metabolically disturbances include insulin resistance and lipid profile disturbances.

OBJECTIVES: This umbrella review and meta-analysis study conducted to assess the effect of resveratrol on glycemic indices and lipid profile in T2DM.

METHODS: The study was performed by using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines (PRISMA) checklist. The PubMed, Web of Sciences, and Google Scholar databases were used to search the published papers up to 2025. The AMSTAR questionnaire was used for assessing the quality of eligible studies. Additionally, The Cochran Q test and I² statistics were used for examining heterogeneity.

RESULTS: Of 10 meta-analyses evaluating the resveratrol effects on glycemic indices and lipid profile showed no significant effects on fasting blood sugar, glycosylated hemoglobin A1c (HbA1c), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), despite significant heterogeneity. Nevertheless, based on SMD analyses, resveratrol supplementation showed only significant effects on LDL-C reduction. Also, significant decline in serum insulin level was observed for sample size ≥ 500 and study number ≥ 10.

CONCLUSION: Given the high heterogeneity and limitations attributed to the study, resveratrol supplementation was not considered as a beneficial agent in declining glycemic indices and lipid profile in patients with T2DM.

PMID:42268476 | DOI:10.1007/s40199-026-00609-x