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PubMed2026

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals↗

PubMed2026

The Acute Effects of Blood Flow Restriction on Ankle Muscle Reaction Time and Proprioception in Healthy Individuals.

Blood flow restriction (BFR) induces hypoxic and metabolic stress, which may alter afferent feedback and neuromuscular control. However, its acute effects on ankle sensorimotor function remain unclear. The aim of the study was to investigate the acute effects of lower-limb BFR on multidimensional ankle sensorimotor function in healthy adults. Twenty-four participants (12 females, 12 males) completed two conditions in randomized order and a crossover design: BFR at 60% arterial occlusion pressure (AOP) and a control condition (20 mmHg). All measurements were performed during occlusion. Outcomes included joint position sense (active and passive), kinesthesia, static and dynamic balance, lower-limb muscle activation (surface electromyography), and muscle reaction time during sudden ankle inversion. BFR impaired active joint position sense at 20 degrees of inversion (p = 0.011), with no changes at other angles or in kinesthesia. Static balance deteriorated, with increases in sway area (p = 0.017), sway distance (p = 0.029), and sway velocity (p < 0.001), particularly under eyes-closed single-leg stance. Posterolateral reach distance decreased (p = 0.023), accompanied by reduced lower-limb muscle activation. Tibialis anterior muscle reaction time during 30 degrees of inversion in the ankle neutral position was shortened (p < 0.001), whereas peroneus longus muscle responses were unchanged. Acute lower-limb BFR impairs ankle sensorimotor control by reducing proprioceptive accuracy, balance performance, and muscle activation, while shortening reaction time. These findings suggest caution when applying BFR during tasks that require high postural demands or end-range control. Registration number and date: NCT07307339, 12/26/2025.

Humans↗

PubMed2026

Age-related differences in motor unit behaviours and maximal strength: A systematic review and meta-analysis.

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD = -0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Aging↗

PubMed2026

Development and protective efficacy of a live attenuated vaccine candidate against goose astrovirus.

Goose astrovirus (GAstV) is a significant pathogen affecting goslings by inducing visceral gout, yet no commercial vaccine is currently available. This study involved the serial passaging of the GAstV-GXNN strain in LMH cells to investigate alterations in viral replication, genomic stability, and pathogenicity, as well as to assess the potential of a vaccine candidate. The findings indicated that the viral titer increased progressively with each passage, reaching 107.35 TCID50/mL by the 120th passage (GAstV-GXNNP120). Whole-genome sequencing revealed the presence of 6, 19, 26, and 28 nucleotide mutations at the 30th, 60th, 90th, and 120th passages, respectively. Pathogenicity assays demonstrated a reduction in virulence with successive passages, culminating in the complete attenuation of GAstV-GXNNP120, which did not induce clinical signs or lesions in one-day-old goslings. Following five successive passages in goslings, the attenuated strain exhibited stable genetic characteristics without any reversion to virulence. Goslings aged one day, inoculated with GAstV-GXNNP120 at dosages ranging from 102.0 to 105.0 TCID50, developed neutralizing antibodies by the third day post-vaccination. Antibody levels increased in a dose-dependent manner, peaking at day 21 and remaining elevated through day 42. Challenge experiments utilizing the virulent GAstV-GXNN strain revealed that groups vaccinated with doses of 103.0 TCID50 and above achieved complete protection. These groups exhibited no clinical symptoms or pathological damage post-challenge, and both tissue viral loads and virus shedding levels were significantly reduced compared to the control group. Consequently, the minimum effective vaccination dose was established at 103.0 TCID50. These results provide a crucial foundation for the development of a live attenuated GAstV vaccine.

Animals↗

PubMed2026

Novel histopathologic findings in abdominoscrotal hydrocele: Clues to pathogenesis.

PURPOSE: To evaluate whether underlying histological alterations in hydrocele sac wall can provide an explanation of difference in abdominoscrotal hydrocele (ASH) and communicating hydrocele (CH) behavior. The aim of this study is to assess the immunohistopathologic characteristics of CH and ASH sac walls in pediatric patients. METHODS: In a retrospective case-control study, patients diagnosed with ASH or CH underwent surgical management at a tertiary pediatric center. Samples of ASH or CH wall sac were obtained for histopathologic evaluations, especially for contractile units and fibromuscular components. These assessments comprised Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining for smooth muscle actin (SMA), Myogenin and Caldesmon (H-CALD) to identify and quantify the presence of cells with striated or smooth muscle origins. All patient's imaging, clinical and demographic data were evaluated. All statistical analysis performed using SPSS software and p-value of <0.05 considered as the level of significance. RESULTS: Among 38 patients in our case-control study, 14 (36.84%) patients referred with bilateral hydrocele. The intra-operative observation of all ASH cases indicated no patent processus vaginalis. The IHC evaluations of ASH and CH specimens demonstrated that there is a significantly higher expression of SMA (median 5.73% versus 0.56%, P-Value <0.001), H-CALD (median 9.28% versus 0.18%, P-Value <0.001) in comparison to those of CH. CONCLUSION: The higher expression of smooth muscle and myofibroblast origins in the ASH wall suggests the potential of consistent contractility, which likely affects the secretion-reabsorption imbalance. Performing histologic studies can enhance our understanding of ASH pathogenesis and clinical characteristics.

Humans↗

PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4 Hz and 30 Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0 Hz), low-frequency (4 Hz), or high-frequency (30 Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4 Hz and 29 at 30 Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

Animals↗

PubMed2026

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6 weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6 weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1α expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα)) and lower TGF-β1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-β-Gal, 53BP1, and p16, with SA-β-Gal reduction comparable to that of TGF-β1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-β1.

Humans↗

PubMed2026

Is ophthalmology a pain-free career? A systematic review and meta-analysis of musculoskeletal pain among ophthalmologists.

OBJECTIVE: To estimate the pooled prevalence, anatomical distribution, and occupational impact of work-related musculoskeletal (MSK) pain among ophthalmologists, and to identify modifiable ergonomic risk factors. DESIGN: A systematic review and meta-analysis of published data. The protocol was preregistered (PROSPERO CRD42023422368) and reported in accordance with PRISMA. PARTICIPANTS: The participants were 6691 ophthalmologists from 21 studies. METHODS: Electronic databases (MEDLINE, Embase, Cochrane, and PubMed) were searched for peer-reviewed quantitative studies reporting MSK pain prevalence in ophthalmologists. Pooled estimates with 95% CI were calculated using random-effects models; heterogeneity was quantified using I². MAIN OUTCOME MEASURES: Prevalence of overall and site-specific MSK pain; effects on workload and productivity; prevalence of treatment or mitigation strategies. RESULTS: The pooled prevalence of any MSK pain was 70% (95% CI: 65%-75%; I² = 92%); neck (41%; 95% CI: 35%-47%; I² = 95%), lower back (36%; 95% CI: 32%-39%; I² = 87%), and shoulder pain (28%; 95% CI: 22%-35%; I² = 91%) were most common. Pain led to workload modification in up to 44% and contributed to reduced clinical volume, sick leave, or contemplation of early retirement. Forty-six percent (95% CI: 22%-71%) pursued no treatment; 39% (95% CI: 30%-49%) used medical therapy; and 29% (95% CI: 20%-41%) sought physiotherapy. Heterogeneity was high across studies, reflecting differing case definitions and self-reported measures. CONCLUSIONS: MSK pain affects most ophthalmologists, particularly in the cervical and lumbar regions and frequently alters practice patterns. These findings underscore the need for early ergonomic training, structured micro-breaks, and workspace redesign. Prospective intervention trials are required to establish causality and quantify benefit.

Humans↗

PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗

PubMed2026

The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games↗

PubMed2026

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000 Hz, 95 dB SPL, 2 h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2 weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1 day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1 day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals↗

PubMed2026

Randomized study of the effects of testosterone administration on severity of asthma in horses.

BACKGROUND: Low testosterone concentrations are associated with poor lung function in human asthmatics, and androgen administration improves airway obstruction in women with asthma. HYPOTHESIS/OBJECTIVES: Testosterone improves clinical scores, lung function, airway neutrophilia, and airway remodeling in horses with severe asthma. ANIMALS: Ten horses affected by severe asthma from a research herd. METHODS: In a randomized, blinded, crossover study, horses received dexamethasone (0.06 mg/kg PO q24h for 10 days) or a single intramuscular injection of testosterone cypionate (0.35 mg/kg), with a 2-week washout period. Clinical respiratory scores were assessed at days 0, 2, 5, and 10; lung function was evaluated at days 0, 5, and 10; and bronchoalveolar lavage fluid cytology and central airway remodeling at days 0 and 10. Mixed linear models were used for analysis. RESULTS: The respiratory clinical scores improved with dexamethasone administration (median [95% CI], from 12 (9-13) to 5 (3-6), P < .001), and remained unchanged with testosterone administration (from 10 [8-12] to 9 [8-11], P = .6). Pulmonary elastance improved with both treatments, but the effect was more pronounced with dexamethasone administration (from 5.1 cm H2O/L [2.4-5.8] to 0.5 [0.4-0.8], P < .001) than with testosterone administration (from 4.5 cm H2O/L [1.6-8.5] to 3.0 [1.0-4.1], P = .04). Pleural pressure and pulmonary resistance decreased only with dexamethasone. Neither treatment altered airway neutrophilia or bronchial remodeling. CONCLUSIONS AND CLINICAL IMPORTANCE: Testosterone is less effective than dexamethasone and only mildly improves pulmonary elastance in horses with severe asthma.

Animals↗

PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans↗

PubMed2026

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article↗

PubMed2026

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals↗

PubMed2026

The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p = 0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p = 0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

Humans↗