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PubMed2026

Driving Under the Influence of Cannabis Among U.S. Young Adults Who Use Cannabis: Evidence From the 2021-2024 National Survey on Drug Use and Health.

PURPOSE: To estimate the prevalence of driving under the influence of cannabis (DUIC) and identify associated factors among U.S. young adult drivers reporting past-year cannabis use. METHODS: This cross-sectional study analyzed pooled 2021-2024 National Survey on Drug Use and Health. The analytic data were restricted to drivers aged 18-25 years who reported past-year cannabis use (N = unweighted 17,141; weighted N = 10,814,381). The outcome was self-reported past-year DUIC. Independent variables included demographics, substance use, mental health, cannabis-related perceptions, and driving behaviors. These relationships were assessed by modified Poisson regression. RESULTS: The weighted prevalence of DUIC was 28.0%, representing approximately over three million young adults. DUIC prevalence increased with cannabis use frequency, from 2.51 times higher among those using cannabis 12-49 days (adjusted prevalence ratio [APR]: 2.51; 95% confidence interval [CI]: 2.29-2.75) to 3.63 times higher among those reporting use on 300-365 days (APR: 3.63; 95% CI: 3.60-3.76), compared with those using cannabis 1-11 days. Cannabis use disorder (APR: 2.34; 95% CI: 2.06-2.65), simultaneous alcohol and cannabis use (APR: 1.29; 95% CI: 1.28-1.30), and perceived easy cannabis availability (APR: 2.36; 95% CI: 2.33-2.39) were also associated with higher prevalence of DUIC. Nonenrollment in school and living in a state with a medical cannabis law were associated with lower DUIC prevalence. DISCUSSION: DUIC is highly prevalent among U.S. young adults who use cannabis, with a clear graded association across categories of cannabis use frequency. Public health interventions should address frequent use, cannabis use disorder, alcohol-cannabis co-use, and perceived cannabis availability.

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PubMed2026

Rational design of high-productivity perfusion processes for CHO Cells: From growth inhibitory strategies to model-driven optimization.

While perfusion culture for Chinese hamster ovary (CHO) cells offers advantages such as continuous operation and flexibility, it suffers from product loss through cell bleeding and difficulties in reaching high productivity due to sustained rapid cell growth. Growth inhibitory strategies are widely used to enhance productivity in fed‑batch processes; however, their practical implementation and comparative effectiveness in perfusion processes remain insufficiently explored. Meanwhile, process development often relies on costly trial‑and‑error approaches. Here, we systematically compared three growth inhibitory strategies in perfusion culture-low cell‑specific perfusion rate (CSPR), sodium butyrate, and mild hypothermia-with respect to cell growth, metabolism, productivity, and product quality. Genome‑scale metabolic flux sampling analysis revealed that low‑CSPR and sodium butyrate induce a convergent up‑regulation of energy metabolism, correlating with greater gains in specific productivity (qp). Building on this insight, we developed a growth‑kinetic model for the combined low‑CSPR + butyrate strategy, incorporating parameter uncertainty. This model‑guided framework enabled the rational design of two distinct high‑productivity perfusion processes: a sustained mode that achieved robust long‑term stability alongside substantial productivity gains, and a high‑intensity mode that pushed qp and daily volumetric titer to their maxima, with increases of up to 108.94% and 190.36%, respectively, in a model CHO cell line with a moderate baseline productivity. Our study provides a proof‑of‑concept framework for perfusion intensification, from strategy selection to rational process design.

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PubMed2026

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60 °C and 80 °C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80 °C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

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PubMed2026

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples ≥ 10 to ≥ 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

PubMed2026

Novel non-contrast computed tomography parameters for predicting spontaneous stone passage and surgical requirement in ureteral stones: The role of ureteral wall thickness and dilatation ratio.

We investigated the predictive value of standard non-contrast computed tomography (NCCT) measurements, the ureteral dilatation ratio (DDR) and intraluminal urine stasis markers, for spontaneous stone passage (SSP) versus surgical intervention in patients with ureteral stones. We also evaluated ureteral wall thickness (UWT) as a practical clinical marker. This retrospective study included 461 patients diagnosed with ureteral stones via NCCT. Patients were categorised into two groups based on clinical outcomes: the spontaneous passage group (MET; n = 229) and the endoscopic surgery group (URS; n = 232). Stone volume, stone density (HU), UWT, DDR and intraluminal urine attenuation values were measured for all patients. Independent risk factors were identified using a multivariate logistic regression model and clinical cut-off values were determined via ROC curve analysis. Stone volume, density, UWT and hydronephrosis grade were all significantly higher in the URS group. Multivariate regression analysis revealed that increased UWT (OR: 5.03, 95% CI: 3.66-6.90; p < 0.001) was the strongest independent predictor of surgery. Higher DDR (OR: 1.88; p = 0.003), advanced hydronephrosis, stone volume, and density also increased surgical risk. A UWT cut-off ≥ 2.97 mm predicted surgery with 84.8% sensitivity and 84.3% specificity (AUC: 0.872). A DDR cut-off > 1.79 yielded 81.7% specificity and 40.4% sensitivity. UWT weakly correlated with stone volume (r = 0.145), indicating wall thickening reflects an inflammatory response rather than a mere mechanical consequence. UWT is a superior predictor of SSP failure, supported by increased DDR as a highly specific complementary risk factor. These parameters could help clinicians to identify patients who would benefit from early surgical counselling and intervention rather than prolonged conservative management.

Humans↗

PubMed2026

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Early diagnosis of cholangiocarcinoma (CCA) remains challenging because existing diagnostic approaches often lack sufficient sensitivity for reliable detection of early-stage disease. Circulating tumor cells (CTCs) in blood and exfoliated tumor cells (ETCs) in bile represent valuable targets for liquid biopsy-based detection; however, their low abundance and the complexity of clinical sample analysis pose substantial technical challenges for reliable enrichment and identification. Herein, we present a reproducible workflow for isolating and identifying CCA tumor cells from blood for CTCs and bile for ETCs using synthetic cell-surface heparan sulfate (HS) octasaccharide-functionalized magnetic beads (MBs) on integrated microfluidic systems. The method combined sample pre-processing, magnetic bead-based enrichment, controlled low-shear mixing and immunofluorescence-based identification into a unified workflow compatible with distinct clinical sample types. Key operational parameters, including MB concentration, mixing frequency, and pressure settings, were detailed to facilitate consistent performance. Using this workflow, tumor cell capture rates of approximately 70% in bile (for ETCs) and blood (for CTCs) were achieved, with a total processing time of 60-90 min per sample under clinically relevant low-abundance conditions. The platform enables reliable detection of as few as 1 tumor cell per mL of blood or bile. This method provides a practical and adaptable strategy for glycosaminoglycan-mediated liquid biopsy applications and may be extended to other tumor-cell enrichment workflows involving heterogeneous cell-surface interactions.

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PubMed2026

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans↗

PubMed2026

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA ≥85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans↗

PubMed2026

Postoperative Curvature Loss in Three-Level Anterior Cervical Discectomy and Fusion With Zero-Profile Device.

PURPOSE: Cervical curvature loss is a frequent complication following 3-level anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device. Consequently, the capacity of this device to maintain cervical sagittal alignment in 3-level ACDF remains highly controversial. This study aimed to identify potential predictors for postoperative curvature loss (PCL) and evaluate its impact on clinical outcomes. METHODS: A total of 113 patients who underwent ACDF for 3-level cervical degenerative disc disease (CDDD) between January 2021 and December 2023 were retrospectively reviewed. Demographic data, radiological parameters, and clinical outcomes were analyzed. Radiographic measures included cervical curvature, T1 slope, C2-7 sagittal vertical axis, and titanium plate and endplate (TPE) distance. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Statistical analyses were performed using paired and independent t-tests, as well as Pearson correlation coefficients. RESULTS: The average curvature loss was 6.82° from 1 week postoperatively to the final follow-up (p < 0.001). However, the final curvature (11.65°) was maintained, representing a 4.33° improvement compared to preoperative values. Significant correlations were observed between PCL and preoperative curvature (r = -0.368, p = 0.013), preoperative T1 slope (r = -0.546, p < 0.001), ∆T1 slope (r = 0.443, p = 0.002), and ∆TPE distance (r = 0.417, p = 0.004). PCL did not correlate with Japanese Orthopaedic Association (JOA) scores or arm VAS scores at the final follow-up. Nevertheless, patients with a PCL ≥ 6° exhibited significantly higher neck VAS (p = 0.028) and NDI scores (p = 0.041). CONCLUSION: Although contiguous 3-level ACDF with a Zero-Profile device may result in PCL, it preserves an improved cervical lordosis compared to the preoperative baseline. Low preoperative curvature and a low preoperative T1 slope are potentially predictive factors for PCL. Postoperative changes in TPE distance and T1 slope are significantly associated with PCL, suggesting a potential biomechanical link that requires direct validation. Furthermore, PCL may lead to higher neck VAS and NDI scores. Consequently, the Zero-Profile device may require careful consideration in 3-level CDDD patients presenting with low preoperative curvature and a low T1 slope. Importantly, the 6° PCL threshold identified is preliminary and requires prospective validation before clinical application.

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

Safety and efficacy of distal versus conventional radial artery cannulation for invasive blood pressure monitoring: a systematic review and meta-analysis.

To compare the safety and effectiveness of distal radial artery (DRA) versus conventional radial artery (CRA) catheterization for invasive arterial blood pressure monitoring. This meta-analysis followed PRISMA guidelines. Randomized controlled trials published up to December 30, 2025 were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, CNKI, Wanfang, VIP, and SinoMed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were conducted using Review Manager 5.4 and Stata 18.0, and evidence quality was evaluated with the GRADE system. 12 randomized controlled trials (RCTs) involving 1,790 participants were included. For the primary outcomes, compared with CRA, DRA was associated with lower incidences of haematoma (RR = 0.42, 95% CI: 0.24-0.73), catheter blockage (RR = 0.33, 95% CI: 0.14-0.81), and bleeding (RR = 0.25, 95% CI: 0.11-0.59), but a longer catheter insertion time (MD = 26.89, 95% CI: 5.28-48.50). For the secondary outcomes, DRA was associated with a shorter haemostasis time and reduced waveform instability, with no significant differences in first-attempt success rate or pain scores. Subgroup analysis showed a higher first-attempt success rate in patients aged ≤ 65 years (RR = 1.14, 95% CI: 1.02-1.28). DRA catheterization for invasive arterial blood pressure monitoring appears to be associated with fewer complications and more stable arterial waveform acquisition than CRA catheterization, despite a longer insertion time. DRA may represent a feasible alternative in surgical and intensive care settings; however, further high-quality studies are needed to confirm its long-term safety and generalizability.

Humans↗

PubMed2026

Impaired toilet training and bladder and bowel dysfunction in children with developmental coordination disorder - an underreported issue.

BACKGROUND & OBJECTIVE: Children with Developmental Coordination Disorder (DCD) face significant, yet often overlooked, challenges beyond motor impairments, including difficulties with toilet training and bladder and bowel dysfunctions (BBD). This study aims to explore whether children with DCD exhibit greater difficulties in these areas compared to typically developing children (TDC). METHOD: This cross-sectional case-control study included 84 children aged 5-8 years (42 DCD, 42 TDC), matched by school-grade and sex (33 boys and 9 girls per group). Parents completed the Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) to assess BBD symptoms, the Dutch DCD-questionnaire (DCD-Q) to evaluate motor coordination, and additional questions regarding toilet training, elimination diagnosis, and co-occurring conditions. Correlations and exploratory group differences were analysed. RESULTS: Parents of children with DCD reported significantly more toilet training difficulties than parents of controls (p < 0.001), including persistent accidents (47.6% vs. 9.5%), prolonged training (45.2% vs. 4.8%), and difficulties recognizing urination urgency (40.5% vs. 2.4%). The parental report of delayed attainment of bowel and bladder control (p < 0.05) and BBD rates (p < 0.001) was also significantly higher in children with DCD. Exploratory analyses indicated that the prevalence of these outcomes was not significantly different between children with DCD with and without co-occurring ADHD or autism, suggesting a possible primary association with DCD. Additionally, across both children with DCD and TDC, poorer motor skills were associated with more BBD symptoms (r = -0.474, p < 0.001). CONCLUSION: Children with DCD have a higher prevalence of toilet training difficulties and BBD compared to TDC, potentially affecting their psychosocial well-being. Greater awareness is crucial for timely and targeted care. Notably, the study's design, directly comparing children diagnosed with DCD to matched TDC, provides new insights into the prevalence of elimination difficulties in this population.

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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

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans↗

PubMed2026

Beyond multidimensionality: a systematic review of recurrent frailty archetypes in community-dwelling older adults.

BACKGROUND: Frailty is a clinically heterogeneous geriatric syndrome commonly summarised using physical or multidomain severity scores. Whether person-centred analyses identify recurring within-frailty configurations has not been systematically examined in community-dwelling older adults. METHODS: We searched PubMed, Embase, MEDLINE, and CINAHL (January 2000-November 2025) for cross-sectional studies using latent class, latent profile, or analogous clustering methods to derive frailty subgroups. Quality was assessed using the AHRQ checklist and a purpose-built appraisal of person-centred model reporting. Study-derived classes were mapped in duplicate to a structured archetype framework developed through comparison of class-defining features across studies. RESULTS: Fourteen reports representing 12 independent datasets from eight countries were included. Six configurations were identified: minimally impaired reference, mobility-physical, nutritional-metabolic, cognitive-predominant, combined cognitive-physical, and psychosocial/mood-predominant. Convergence was measurement-dependent. The reference and mobility-physical configurations recurred across physical-only and multidomain indicator sets, while the combined cognitive-physical configuration appeared across several multidomain frameworks but required cognition to be measured. The remaining configurations emerged only when their defining domains were included. Evidence of prognostic value beyond aggregate frailty severity came from one deficit-index study. Collapsing shared-provenance reports and excluding the boundary-eligible study did not alter recurrence; excluding the Croatian dataset left five configurations recurrent, with the cognitive-predominant configuration supported by one independent dataset. CONCLUSIONS: Person-centred analyses identify recurring within-frailty configurations, but their apparent stability is partly measurement-dependent. A five-configuration core persisted after exclusion of the Croatian dataset, whereas the cognitive-predominant configuration remained weakly replicated. Harmonised indicators and rigorous external validation are needed before clinical application.

Humans↗

PubMed2026

Presentation, management, and outcomes of anterior inferior cerebellar artery dissecting and fusiform aneurysms: a systematic review and institutional case series.

Dissecting and fusiform aneurysms of the anterior inferior cerebellar artery (AICA) are rare and poorly characterized lesions. This study provides a comprehensive patient-level synthesis to date, combining a systematic review with institutional data to describe their clinical presentation, diagnostic workup, management strategies, and outcomes. A systematic review was conducted according to PRISMA guidelines. Studies were included if they reported on dissecting or fusiform AICA aneurysms. Individual patient data were extracted and supplemented with a single-institution case series. Outcomes, complications, and radiological evolution were analyzed descriptively. Forty-nine patients from 36 studies and 6 patients from our institution were included in this study. In the systematic review cohort, most aneurysms presented with subarachnoid hemorrhage (n = 38/49, 77.6%). Compressive cranial neuropathies, particularly including the vestibulocochlear system, were common in patients with unruptured aneurysms. Diagnosis often required digital subtraction angiography after the initial non-invasive imaging. Endovascular treatment, most commonly parent artery occlusion, was employed in 61.2% (n = 30/49) of cases. However, ischemic complications occurred in 23.3% (n = 7/30), especially in proximal (A1-A2) lesions. Bypass surgery was reported selectively for proximal aneurysms with inadequate collateral flow. As an alternative surgical approach, decompression or trapping was pursued based on aneurysm morphology or clinical context. Conservative management was typically reserved for select patients with poor-grade SAH, high procedural risk, or patient refusal of intervention. Overall, 81.4% (n = 35/43) of patients with available follow-up achieved good functional outcomes. Management of AICA dissecting and fusiform aneurysms is highly individualized. Endovascular approaches were frequently used to secure ruptured lesions or lesions considered at high risk, but periprocedural ischemic risk in perforator-rich segments remains a notable concern. Bypass procedures were reported in selected proximal aneurysms with limited collateralization. Conservative management was reserved for highly selected high-risk or anatomically inaccessible cases. Clinical trial registration: This study is not a clinical trial.

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PubMed2026

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗