Tag: nevin manimala

J Gerontol A Biol Sci Med Sci. 2026 Jun 10:glag143. doi: 10.1093/gerona/glag143. Online ahead of print.

ABSTRACT

BACKGROUND: Physical activity (PA), sedentary behavior (SB), and sleep are modifiable lifestyle factors linked to cognitive health. Prior research has largely relied on self-report to measure these constructs or ignored the compositional nature of these data. We applied compositional data analysis (CoDA) to quantify the association between accelerometry-derived measures of time in major activity domains and cognitive outcomes among older adults.

METHODS: Participants were 927 older adults (M age = 82.71 years, SD = 3.99, range = 76-95) from the Atherosclerosis Risk in Communities (ARIC) study who wore wrist-worn accelerometers and completed cognitive assessments. Major activity domains were time in bed and time out of bed, which were divided into four categories: sedentary behavior (SB), low-light (low-LIPA), high-light (high-LIPA), and moderate-to-vigorous physical activity (MVPA). Cognitive outcomes included global cognition, memory, executive function, and language performance.

RESULTS: Across all cognitive domains, greater time spent in MVPA relative to other activity domains, including out-of-bed time, sedentary behavior, and low-LIPA, was associated with better cognitive performance. In contrast, greater time spent in low-LIPA relative to other activity domains was consistently associated with poorer performance across all cognitive domains, and these associations were attenuated, but remained statistically significant, after adjustment for gait speed. Sedentary behavior was negatively associated with executive function only.

CONCLUSIONS: The trade-off between time spent in MVPA and in low-LIPA is the objectively measured physical activity that was most strongly associated with cognitive abilities. Time spent in low-LIPA may be an important biomarker of physical health and cognitive impairment.

PMID:42268661 | DOI:10.1093/gerona/glag143

JAMA Dermatol. 2026 Jun 10. doi: 10.1001/jamadermatol.2026.1527. Online ahead of print.

ABSTRACT

IMPORTANCE: In Germany, a population-based skin cancer screening (SCS) program was implemented in 2008. The benefit of the intervention is unclear.

OBJECTIVE: To determine whether the German SCS program was associated with reduced melanoma mortality.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, ecological comparative effectiveness study compared trends in melanoma mortality from 2009 to 2022 in Germany with those in neighboring countries without population-based SCS using data on melanoma mortality from the official cause-of-death statistics. The total populations of 15 federal states of Germany and 9 neighboring countries were examined. The German federal state of Schleswig-Holstein was excluded from the analysis due to a potential lasting effect of a preceding pilot project, conducted in 2003 and 2004. Data were analyzed from November 7, 2025, to February 11, 2026.

EXPOSURE: The German SCS program entitles men and women aged 35 years and older to a visual skin examination every 2 years, regardless of their individual skin cancer risk. The 2-year participation rate was estimated at approximately 32%.

MAIN OUTCOMES AND MEASURES: Pooled estimates of annual percentage changes (APCs) in age-standardized melanoma mortality rates in German and non-German control regions were calculated using a random-effects model.

RESULTS: Data include a mean of 79.1 million inhabitants in Germany and 164.8 million inhabitants in 9 neighboring countries. Between 2009 and 2022, age-standardized melanoma mortality rates decreased in each included region. In Germany, APCs ranged from -3.8% (95% CI, -5.5% to -2.2%) to -0.1% (95% CI, -1.7% to 1.5%). In the control regions, mortality rates decreased between -3.8% (95% CI, -4.9% to -2.7%) and -1.0% (95% CI, -1.9% to -0.2%) per year. Pooled APC estimates are -1.8% (95% CI, -2.3% to -1.4%) for Germany and -2.2% (95% CI, -2.8% to -1.6%) for the non-German control regions; the difference was not statistically significant (P = .42).

CONCLUSIONS AND RELEVANCE: The findings of this ecological study are in line with previous studies that failed to show a melanoma mortality benefit associated with the German SCS program. To enable a well-founded decision on the future of the program, the causes of its poor performance should be investigated.

PMID:42268621 | DOI:10.1001/jamadermatol.2026.1527

JAMA Netw Open. 2026 Jun 1;9(6):e2617684. doi: 10.1001/jamanetworkopen.2026.17684.

ABSTRACT

IMPORTANCE: Effectiveness of seasonal influenza vaccine must be assessed annually as influenza viruses evolve, requiring updated vaccine components. Evidence is limited for direct vaccine benefit in lowering risk of death following influenza virus infection.

OBJECTIVE: To evaluate the association between current-season influenza vaccination and laboratory-confirmed influenza virus infection and, among persons with laboratory-confirmed influenza, the association with influenza-associated death.

DESIGN, SETTING, AND PARTICIPANTS: A case-control analysis of California residents aged 6 months or older with influenza diagnostic testing ordered between October 1, 2024, and May 31, 2025, with data on diagnostic test result and 2024 to 2025 influenza vaccination. Influenza-associated deaths within 30 days of testing among persons with laboratory-confirmed influenza were identified from vital statistics records.

EXPOSURES: Influenza vaccination from October 1, 2024, to May 31, 2025.

MAIN OUTCOMES AND MEASURES: Associations were evaluated between 2024 to 2025 influenza vaccination and (1) laboratory-confirmed influenza, in which case individuals tested positive and control individuals tested negative for laboratory confirmed influenza; and (2) influenza-associated death, in which deaths were compared with surviving cases among persons with laboratory-confirmed influenza. Associations were assessed with mixed-effects logistic regression.

RESULTS: Among 1 106 628 persons tested for laboratory-confirmed influenza (610 093 female participants [55.1%]), 234 715 were case individuals with laboratory-confirmed influenza (median [IQR] age, 28 [10-52] years) and 871 913 were control individuals (median [IQR] age, 42 [19-67] years); 45 441 influenza cases (19.4%) and 255 605 control individuals (29.3%) had received 2024 to 2025 influenza vaccination. Vaccination was significantly associated with decreased likelihood of laboratory-confirmed influenza (estimated vaccine effectiveness, 40%; 95% CI, 39%-41%). Among persons with laboratory confirmed influenza, there were 801 influenza-associated deaths. Influenza-associated death among persons aged 65 years or older was associated with lower likelihood of influenza vaccination (adjusted odds ratio, 0.71; 95% CI, 0.60-0.84) compared with persons with nonfatal infection.

CONCLUSIONS AND RELEVANCE: In this case-control study of estimated vaccine effectiveness, influenza vaccination was associated with decreased likelihood of laboratory-confirmed influenza and influenza-associated deaths among those with laboratory-confirmed influenza. Electronic laboratory reporting linked to immunization registry and vital statistics provide tools to assess vaccine effectiveness and risk of death, a rare influenza-associated outcome.

PMID:42268610 | DOI:10.1001/jamanetworkopen.2026.17684

FASEB J. 2026 Jun 30;40(12):e71993. doi: 10.1096/fj.202600816RR.

ABSTRACT

Biological noise is ubiquitous in living systems; yet, it is often neglected in cell-based experiments, potentially biasing data interpretation. We provide a quantitative characterization of single-cell equivalent diameter distributions in six human cell types using cell counting. By analyzing thousands of cells over passage number, we show that cell size is phenotype dependent and varies significantly with passage, with most cell types exhibiting a progressive reduction in median diameter. This variability is structured: When diameters are converted to masses, the distributions obey scaling laws, revealing conserved statistical properties of human cells in culture. Because key physiological processes such as metabolism scale with cell mass, passage-dependent shifts in diameter distributions can propagate into functional readouts. We show that changes in cell size are sufficient to bias estimates of construct-level metabolic rate, potentially confounding the interpretation of size-normalized assays and treatment effects. Our results highlight that biological noise in vitro is a source of statistical structure that enables scaling analyses and a dynamic property that, if ignored, can lead to systematic misinterpretation of experimental outcomes. Accounting for size distributions and their evolution over passages may therefore improve experimental design, data interpretation, and, ultimately, the translatability of in vitro models.

PMID:42268592 | DOI:10.1096/fj.202600816RR

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