Tag: pubmed

Biometrics. 2026 Jan 6;82(1):ujag013. doi: 10.1093/biomtc/ujag013.

ABSTRACT

Boundary estimates of random effects covariance matrices commonly arise when using maximum likelihood (ML) estimation in generalized linear mixed effects models, leading to numerical challenges and affecting statistical inference. To mitigate this, we introduce penalties to the likelihood function derived from conditionally conjugate priors for the covariance or precision matrices of the random effects. Our choice of penalties (priors) allows representation through pseudo-observations, enabling implementation of the proposed penalized estimator within the existing ML software by augmenting the original data. We derive a procedure for constructing these pseudo-observations, a non-trivial task because their likelihood contribution must match the functional form of the penalty and depend only on the covariance or precision matrix of the random effects. Our method includes penalty parameters that can be set using existing prior knowledge or, when no reliable prior information is available, via a novel fully data-driven procedure that eliminates the need for prior specification. Through simulation studies under realistic scenarios, we illustrate that the proposed approach can provide improved estimates of random-effects covariance matrices compared with competing methods in the settings considered. The approach is further illustrated on real-world data.

PMID:41657129 | DOI:10.1093/biomtc/ujag013

Diabetes Obes Metab. 2026 Feb 9. doi: 10.1111/dom.70524. Online ahead of print.

ABSTRACT

BACKGROUND: Since obesity and its associated metabolic dysregulation are recognized risk factors for cognitive decline, this study investigated whether semaglutide, a glucagon-like peptide-1 receptor agonist proven to have cardiometabolic benefits, could provide potential neuroprotective effects on brain structure and function.

METHODS: In a prospective, single-arm intervention study, 26 adults with overweight or obesity received 1.0 mg semaglutide weekly for 24 weeks. Multimodal assessments were performed pre- and post-intervention, including structural and functional MRI for analysing grey matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). Cognitive function was evaluated using standardized computerized tasks (the Flanker and N-back). Additionally, comprehensive metabolic profiles were assessed, including markers of glucose and lipid metabolism along with inflammatory cells.

RESULTS: Semaglutide treatment significantly improved systemic metabolic health, inducing weight loss and reducing glycolipid levels and leukocyte counts. Neuroimaging revealed targeted neurobiological effects in the left temporal lobe: specifically, increased GMV in the left inferior temporal gyrus and decreased fALFF in the left middle and superior temporal gyri alongside reduced ReHo in the left middle temporal gyrus. These neural changes occurred despite no significant improvement in cognitive task performance. Importantly, the alterations in brain structure and function were not statistically correlated with the degree of weight loss or metabolic improvement.

CONCLUSIONS: A 24-week semaglutide intervention induces significant neurobiological remodelling in the left temporal lobe of adults with overweight or obesity. These central effects are independent of the drug’s systemic metabolic improvements, offering new evidence for its potential neuroprotective role.

PMID:41657113 | DOI:10.1111/dom.70524

Arthritis Rheumatol. 2026 Feb 9. doi: 10.1002/art.70081. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluate performance of the Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) calculator in rheumatoid arthritis (RA).

METHODS: Patients with RA were matched up to 10 controls on age, sex, and enrollment year using national Veterans Health Administration (VHA), Medicare, and National Death Index data (2006-2020). Ten-year estimated cardiovascular disease (CVD) risk was calculated using PREVENT. Calibration (standardized incidence ratio [SIR]; observed:predicted events) and discrimination (sensitivity, Harrel’s C-statistics) were compared between RA cases and controls. PREVENT performance was compared with the Pooled Cohorts Equations (PCE) for atherosclerotic CVD (ASCVD) prediction in RA, including net reclassification index (NRI) calculation.

RESULTS: Among 30,687 RA and 231,752 non-RA patients, 28,061 ASCVD and 13,851 heart failure (HF) outcomes were identified over >2 million person-years. PREVENT underestimated overall CVD (SIR 1.83 [1.79-1.88]), ASCVD (SIR 2.25 [2.19-2.32]) and HF risk (SIR 1.41 [1.36-1.46]) to a greater degree in RA compared to controls and exhibited poor sensitivity for ASCVD (61.9%) and HF (63.2%) development. PREVENT performance was poorer for ASCVD prediction compared to the PCE (SIR 1.38 [1.34-1.41]; sensitivity 76.0%). NRI for PREVENT was modest (5.3%). Among 657 reclassified patients who experienced ASCVD, 626 were inappropriately reclassified as low/borderline risk. PREVENT performance significantly improved when including hemoglobin A1c (SIR Overall CVD 1.21 [1.18-1.24], ASCVD 1.45 [1.41-1.50], HF 0.79 [0.76-0.82]; sensitivity ASCVD 80.3%).

CONCLUSION: PREVENT underestimates CVD risk in RA, consistent with suboptimal performance of existing risk calculators. Preferential use of PREVENT including hemoglobin A1c should be considered. Improving CVD risk stratification in RA remains a high priority.

PMID:41657109 | DOI:10.1002/art.70081

Int J Methods Psychiatr Res. 2026 Mar;35(1):e70063. doi: 10.1002/mpr.70063.

ABSTRACT

OBJECTIVES: Adjustment disorder (AjD) is a highly prevalent diagnosis in the U.S. military. Psychometric evaluation of the AjD assessment tool, the Adjustment Disorder New Module-Military (ADNM-20-MIL), improves the accuracy of AjD assessment for military service members.

METHODS: This study investigated the internal reliability, convergent, and divergent validity of the ADNM-20-MIL as well as its factor structure. U.S. active duty service members (N = 149) with and without a recent AjD diagnosis completed the ADNM-20-MIL, Depression Anxiety Stress Scales 21 (DASS-21), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and General Well-Being Schedule (GWB).

RESULTS: ADNM-20-MIL scores were significantly worse in the AjD-positive group; there were no AjD severity differences by sex, military rank, or past recent deployment status. The ADNM-20-MIL demonstrated robust internal reliability (Cronbach’s α = 0.96, 95% CI [0.95-0.97]). It had strong positive associations with with the PCL-5 (rs (145) = 0.81, p < 0.001) and the DASS-21 (rs (146) = 0.83, p < 0.001), indicating convergent validity; and moderately negative associations with the GWB subdomains that reflect positive health (rs ranging from -0.5 to -0.63), p < 0.001, indicating divergent validity. Confirmatory Factor Analysis indicated a unidimensional structure for AjD symptoms.

CONCLUSIONS: Longitudinal studies are needed to evaluate the effectiveness of the ADNM-20-MIL in assessing the trajectory of AjD in the military.

PMID:41657071 | DOI:10.1002/mpr.70063

Pediatr Pulmonol. 2026 Feb;61(2):e71492. doi: 10.1002/ppul.71492.

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia is one of the most common complications of preterm birth and has lifelong repercussions in respiratory health.

OBJECTIVE: To examine lung function and exercise capacity and assess potential differences in exertional respiratory pattern and ventilatory and gas exchange responses in school-aged children with a history of prematurity and/or BPD.

METHODS: Prospective observational study including children and adolescents born preterm, with and without BPD, and healthy term-born controls without a known history of asthma. Participants performed spirometry and cardiopulmonary exercise testing.

RESULTS: Eighty-two children aged 6-18 years (mean: 11.9 years, SD: 3.1) were enrolled and examined in three groups: preterm-born with BPD (gestational age < 32 weeks), preterm-born without BPD (GA < 37 weeks), and term-born controls (GA ≥ 37 weeks). FVC, FEV₁, FEF_{25% -75%}, and FEV₁/FVC were normal and comparable among the three groups. V̇O₂peak% was reduced in the BPD group and was significantly lower than the control group (mean difference: -14.4, CI: -28 to -0.7, adjusted p = 0.04), but the difference was not significant when adjusting for height. The BPD group had the highest mean VE/VCO₂ adjusted for height (32.7), followed by the preterm (30.3) and the control group (29.5), and the difference between the BPD and control group was statistically significant (p = 0.015). Moreover, BPD status was significantly associated with increased VE/VCO₂ (β = +3.2, CI: 1-5.4, p = 0.005). The rest of the CPET parameters were within normal limits and comparable among groups.

CONCLUSIONS: Children with BPD have normal lung function but reduced exercise capacity and decreased ventilatory efficiency during exercise.

PMID:41657058 | DOI:10.1002/ppul.71492

BJOG. 2026 Mar;133(4):867-868. doi: 10.1111/1471-0528.70062. Epub 2025 Oct 20.

NO ABSTRACT

PMID:41657048 | DOI:10.1111/1471-0528.70062

Acta Otolaryngol. 2026 Feb 9:1-8. doi: 10.1080/00016489.2025.2609294. Online ahead of print.

ABSTRACT

BACKGROUND: The symptoms of chronic rhinosinusitis (CRS) are common. Diagnosis with computed tomography (CT) and endoscopy is not possible in all patients. Nasal nitric oxide (nNO) detects the obstruction of paranasal sinus ostia, but its clinical relevance is unknown.

AIMS/OBJECTIVES: We assessed whether nNO, Sinonasal Outcome Test 22 (SNOT-22) and Zinreich modified Lund-Mackay (ZL-M) CT-scores are associated with subsequent surgery among CRS or recurrent acute rhinosinusitis (RARS) patients.

MATERIAL AND METHODS: Sixty-six CRS (with/without nasal polyps) or RARS patients were included in this prospective study. Appropriate medical therapy was used for at least 2 months. Patients were assessed during three consecutive visits: on current prescriptions, after a medication pause, and after intranasal fluticasone propionate. The clinician was unaware of the nNO results during subsequent treatment decisions.

RESULTS: The positive predictive value (PPV) of nNO for the decision to proceed with surgical intervention “after fluticasone” was 76%, and the negative predictive value (NPV) was 80%. These results were not statistically significantly different from those of the ZL-M (PPV 76%; NPV 82%).

CONCLUSIONS AND SIGNIFICANCE: Low nNO in patients with CRS symptoms was associated with a later decision for surgery. The applicability of nNO to guide ENT referrals from primary care should be further evaluated.

PMID:41657044 | DOI:10.1080/00016489.2025.2609294

Anal Chem. 2026 Feb 9. doi: 10.1021/acs.analchem.5c07536. Online ahead of print.

ABSTRACT

The detection of related substances in both active pharmaceutical ingredients (APIs) and dosage forms, especially via process analytical technology (PAT), is of crucial importance for the assurance of pharmaceutical quality and clinical safety. However, this process remains a formidable challenge because related substances are structurally similar to APIs, resulting in severe spectral overlap. Herein, we present a host-guest doping room-temperature phosphorescence (RTP) sensing strategy that facilitates rapid detection of impurities in naproxen APIs and dosage forms. Leveraging the low luminescence efficiency at minimal host content, the platform can sensitively detect trace impurities, 2-acetyl-6-methoxynaphthalene (MANAP), in naproxen APIs, achieving a limit of detection (LOD) of 0.05% (w/w), which satisfies the pharmacopeial threshold of 0.1% (w/w). The method demonstrates statistical equivalency to HPLC, with average recovery rates of 98.03%-103.38%. Furthermore, both spectral analysis and real-time visualization inspection were successfully achieved for the limit test of MANAP in naproxen granules and tablets. This work introduces a novel RTP-based PAT approach for impurity testing in pharmaceutical manufacturing.

PMID:41657036 | DOI:10.1021/acs.analchem.5c07536

J Neurol Sci. 2026 Feb 5;482:125795. doi: 10.1016/j.jns.2026.125795. Online ahead of print.

ABSTRACT

INTRODUCTION: Nusinersen improves motor outcomes in SMA, but reliable biomarkers for treatment monitoring, especially in adults, are still lacking. We investigated cerebrospinal fluid (CSF) and plasma levels of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF), exploring their potential as biomarkers in disease progression.

METHODS: This single-centre observational study included adults with type 3 SMA treated with nusinersen over 30 months. GFAP and VEGF levels in CSF and plasma were measured using ELISA at baseline, 14 and 30 months. Functional evaluation included Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and respiratory tests. Longitudinal data were evaluated using generalized linear mixed-effects models. A significance level of α = 0.05 was used in all analyses.

RESULTS: Eleven patients were included (63.6% male, aged 19-60 at baseline). Improvements were observed in motor function, with an estimated non-linear increase of 9.02% (CI95%: 5.13-8.79) for RULM and an estimated average increase of 6.96 points (CI95%: 5.44-8.48) for HFMSE over 30 months of treatment. However, both CSF and plasma GFAP and VEGF levels changes at 14 and 30 months did not reach statistical significance, respectively (all p > 0.05).

CONCLUSION: CSF and plasma GFAP and VEGF trajectories over a 30-month period under nusinersen treatment were nonsignificant. This study confirms sustained motor function improvements in adult type 3 SMA patients treated with nusinersen. Future research in larger, multicentric, and internationally collaborative cohorts are essential to fully understand the role of these potential biomarkers in SMA pathogenesis.

PMID:41655361 | DOI:10.1016/j.jns.2026.125795

Radiography (Lond). 2026 Feb 7;32(3):103352. doi: 10.1016/j.radi.2026.103352. Online ahead of print.

ABSTRACT

INTRODUCTION: A standardised Medical Imaging Suite (MIS) request form was developed as an educational tool to simulate real-world clinical documentation and improve radiography students’ ability to interpret and communicate medical imaging requests. This form was integrated into the radiography curriculum to support learning outcomes related to clinical reasoning, documentation, and communication. This study evaluates student perceptions of the MIS request form and its influence on their preparedness following their first clinical placement.

METHODS: A closed-ended survey was administered to second-year undergraduate (n = 73) and first-year postgraduate (n = 75) diagnostic radiography students at an Australian tertiary institution. The survey captured demographic data; perceived preparedness; communication confidence; usability of the MIS form; and its impact on critical thinking. Quantitative data were analysed descriptively. Optional open-ended questions allowed participants to expand on their responses, and the frequency of each issue was counted and reported as descriptive statistics.

RESULTS: Of 148 eligible students, 137 completed the survey (92.6 % response rate; 48 % undergraduate, 52 % postgraduate). Most respondents were female (78.1 %) and aged 18-25 (84.7 %). Over 75 % agreed that the standardised MIS request form improved their understanding of clinical requests, confidence in interpreting information, and overall preparedness for placement. The redesigned MIS request form was rated clearer and more complete by 84.7 % of students, with 94.5 % recommending its continued use in X-ray practical classes.

CONCLUSION: Embedding a standardised imaging request form into the radiography curriculum appears to enhance student’s clinical preparedness. The form supports the development of critical thinking, documentation accuracy, and interprofessional communication.

IMPLICATIONS FOR PRACTICE: Continued evaluation and refinement of the MIS request form will help maintain strong alignment between university teaching and clinical expectations.

PMID:41655338 | DOI:10.1016/j.radi.2026.103352