Category: Nevin Manimala

J Mol Neurosci. 2026 Apr 27;76(2):71. doi: 10.1007/s12031-026-02515-y.

NO ABSTRACT

PMID:42043620 | DOI:10.1007/s12031-026-02515-y

Childs Nerv Syst. 2026 Apr 27;42(1):183. doi: 10.1007/s00381-026-07277-x.

ABSTRACT

BACKGROUND: Pediatric neuroradiology faces significant workforce shortages, with teleradiology emerging as a vital solution. However, studies investigating findings and their operational impact from teleradiology centers remain limited.

OBJECTIVES: To develop and validate structural equation models for identifying predictors of turnaround time and formulate recommendations for workflow optimization in pediatric tele-neuroradiology services.

DESIGN: A retrospective cohort study following STROBE guidelines.

SETTINGS: 107 hospitals across 17 states in the United States (US) via a teleradiology platform providing interpretation services through US board-certified radiologists.

PATIENTS AND METHODS: We analyzed 9985 pediatric neuroradiology scans from 7958 patients (January 2023-December 2024). We utilized confirmatory factor analysis to validate findings structures, followed by structural equation modeling to predict turnaround times. Binary logistic regression models were developed with area-under-the-curve (AUC) estimation for performance assessment. Bootstrap validation with 5000 samples ensured model stability.

MAIN OUTCOME MEASURES: Primary outcome was turnaround time. Secondary outcomes included requirements for multiple imaging studies, follow-up recommendations, and consultations.

SAMPLE SIZE: A total of 9985 studies providing over 99% statistical power for detecting significant relationships.

RESULTS: Factor analysis demonstrated a two-factor structure (trauma: α = 0.742, structural: α = 0.685). The structural model explained 7.8% of turnaround time variance, with computed tomography (CT) modality (β = -0.164), trauma score (β = 0.125), and structural score (β = 0.142) as significant predictors. Among immediate neurosurgical emergencies (n = 180, 1.8%), 89.4% achieved turnaround time within the 60-min benchmark for time-sensitive consultations. Prediction models demonstrated excellent discrimination: traumatic findings (AUC = 0.91), structural findings (AUC = 0.92), critical findings (AUC = 0.95), and a dedicated neurosurgical emergency model (AUC = 0.94, NPV = 0.996). A severity classification system showed strong validation against imaging needs (AUC = 0.76) and consultations (AUC = 0.89).

CONCLUSIONS: Our study establishes a validated SEM framework for pediatric tele-neuroradiology with excellent predictive performance (AUC = 0.91-0.95). Among immediate neurosurgical emergencies (n = 180, 1.8%), 89.4% met the 60-min benchmark, and a dedicated emergency prediction model achieved AUC = 0.94. However, translation to improved neurosurgical care delivery and patient outcomes remains unvalidated, representing the next investigational priorities.

LIMITATIONS: Retrospective design limits causal inference; a single platform may limit generalizability; the CT majority (96.8%) limits magnetic resonance imaging conclusions. Critically, post-diagnostic clinical outcomes, including neurosurgical consultations, interventions performed, and patient outcomes, were not tracked, precluding conclusions about whether documented operational efficiency translated to improved neurosurgical care delivery.

PMID:42043602 | DOI:10.1007/s00381-026-07277-x

J Mol Model. 2026 Apr 27;32(5):147. doi: 10.1007/s00894-026-06729-0.

ABSTRACT

CONTEXT: BRAF kinases are involved in cancer cell survival and metastasis. Mutations in BRAF are frequent in several types of cancer, occurring in more than 50% of melanomas, 50-70% of thyroid cancers, 15% of colorectal cancers, and 5-8% of non-small-cell lung cancers. The most prevalent mutation is V600E. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the FDA for clinical use. However, due to the increasing resistance to current kinase inhibitors, there is an urgent need to identify new molecular scaffolds with potential BRAF inhibitory activity. In this work, molecular docking, molecular dynamics, and metadynamics simulations were performed on twelve triterpenes to identify the best ligands with potential binding to BRAFWT and BRAFV600E. The interaction profiles of the selected triterpenes revealed key contacts with residues ILE463, THR529, GLN530, TRP531, CYS532, and PHE583, which contribute to stabilizing the conformation of both inhibitors and triterpenes within the catalytic binding site of the proteins. The ΔG of betulinic acid (-57.46 kcal/mol) in complex with BRAFWT is comparable to the BRAF inhibitors vemurafenib-OMe and dabrafenib reported in previous work, the ΔG of β-amyrin (-51.83 kcal/mol) showed a ΔG comparable to the inhibitors with BRAFV600E; moreover, the ΔG of lupeol (-62.43 kcal/mol) and moronic acid (-61.05 kcal/mol) are more favorable with BRAFV600E than vemurafenib-OMe and dabrafenib. These computational calculations allow us to consider these triterpenes as potential candidates for drug design cycles and to optimize the binding profile for the development of new selective inhibitors for BRAFV600E to cancer treatments.

METHODS: Molecular docking calculations using AutoGrid 4.2.6, AutoDockGPU 1.5.3, and AutoDockTools 1.5.6 were performed. Molecular dynamics and metadynamics simulations were performed in the Desmond module of the academic version of the Schrödinger-Maestro 2021-4 program, utilizing the OPLS-2005 force field. Finally, all the protein figures presented in this article were made in the PyMOL program and the RMSD graphics were made in the statistical package R and RStudio 2025.05.1.

PMID:42043592 | DOI:10.1007/s00894-026-06729-0

Eur J Pediatr. 2026 Apr 27;185(5):305. doi: 10.1007/s00431-026-06977-5.

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in early infancy, and the recent introduction of two novel immunoprophylaxis tools-maternal vaccination with the RSVpreF vaccine and infant protection with the long-acting monoclonal antibody nirsevimab-represents a major advancement in RSV prevention. The successful implementation of these strategies depends heavily on pediatricians’ awareness, confidence, and readiness to integrate them into routine clinical practice. Evidence from Southern Europe remains limited. This cross-sectional study assessed the knowledge, attitudes, and practices of pediatricians in Crete, Greece, regarding RSV infection and emerging prevention tools. A structured electronic questionnaire was distributed between April and July 2025 to all board-certified pediatricians and pediatric residents registered with the regional medical associations. Among 169 respondents (mean age 46 ± 12.5 years; 83.4% women), overall knowledge was high, with a mean score of 89.6 ± 10.0. Knowledge gaps were concentrated in areas related to newly introduced immunoprophylaxis tools, including awareness of RSV monoclonal antibody availability for infants, updated recommendations covering infants up to 6 months, and distinctions between palivizumab and nirsevimab. Attitudes toward vaccination were overwhelmingly positive: nearly all participants expressed strong vaccine confidence and adherence to national immunization guidelines. Most pediatricians (78.6%) felt adequately informed about RSV. These findings suggest that pediatricians in Crete possess a strong foundation for integrating new RSV prevention strategies, although targeted educational initiatives-particularly regarding nirsevimab-will be essential to ensure consistent and equitable implementation. The results provide timely insights to support national planning and optimize the rollout of RSV immunoprophylaxis in Greece and comparable settings. What is Known: • RSV is a leading cause of severe respiratory disease in early infancy. • New prevention tools (RSVpreF, nirsevimab) are being introduced into national programs. • Pediatricians’ knowledge and confidence strongly influence vaccine uptake. What is New: • Greek pediatricians show high overall RSV knowledge and strong vaccine confidence. • Specific gaps exist regarding nirsevimab and distinctions between immunoprophylaxis tools. • Findings highlight targeted education needs during early implementation of RSV prevention.

PMID:42043589 | DOI:10.1007/s00431-026-06977-5

Support Care Cancer. 2026 Apr 27;34(5):468. doi: 10.1007/s00520-026-10564-7.

ABSTRACT

PURPOSE: Patients with glioblastoma represent a highly vulnerable cohort as they often experience rapid health deterioration with severe symptom burden including neurological, (neuro)psychological, and psychiatric symptoms. The aim of this sub-analysis of the “Early Palliative Care for Patients with Glioblastoma” (EPCOG) trial was to investigate the specific challenges of conducting a multicenter, randomized, controlled, clinical trial in glioblastoma patients testing a specialized palliative care (PC) intervention.

METHODS: We analyzed screening protocols and protocol deviations with respect to number and reasons for non-participation, skipped/delayed visits and attrition using descriptive statistics and content analysis of free-text comments.

RESULTS: In total, 41.5% of 556 screened patients were enrolled. Main reasons for non-participation were lack of interest (25.7%) and low functional status (11.5%). Attrition due to death (57.6%) was higher than due to illness (5.2%) or other reasons (21.2%). Main reasons for visit deviations were structural issues (in > 50% of neurosurgical visits), health status, and patient request. Protocol deviations showed that specialized PC intervention visits were least frequently skipped (4.5%) compared to study-specific outcome assessment (10.1%) and neurosurgical (43.3%) visits. Further, only 11.0% of the specialized PC intervention visits were delayed compared to 22.3% of the outcome assessment and 56.4% of the neurosurgical visits.

CONCLUSION: In this clinical trial involving glioblastoma patients, a high level of motivation among the study participants could be reached, as reflected by low protocol deviations during the specialized PC intervention and study-specific outcome assessment visits. Reasons for this might be a close guidance as well as a patient and caregiver-oriented communication, e.g., by a personal contact of the PC team in the intervention group, personal outcome assessment visits at patients’ whereabouts, or the inclusion of a study nurse at each site. Considering the high vulnerability of glioblastoma patients is crucial when designing and conducting clinical trials.

PMID:42043583 | DOI:10.1007/s00520-026-10564-7

Acta Neurochir (Wien). 2026 Apr 27. doi: 10.1007/s00701-026-06880-w. Online ahead of print.

ABSTRACT

PURPOSE: Despite advances in endoscopic skull base surgery, postoperative sinonasal inflammation remains poorly characterized. In particular, sphenoid sinus osteitis has received little attention, as complications after endoscopic transsphenoidal surgery (ETS) have largely been assessed in terms of mucosal pathology. This study aims to determine the incidence of sphenoid sinus osteitis after ETS, describe its clinical and radiological features, and identify associated surgical and demographic risk factors.

METHODS: We retrospectively reviewed patients undergoing primary ETS for sellar or parasellar tumors between September 2021 and September 2024. Osteitis was assessed on high-resolution CT using the Lee and Kennedy classification. Clinical symptoms, particularly cacosmia, and surgical approach and reconstruction techniques were analyzed as potential risk factors.

RESULTS: Among 1,443 patients, sphenoid sinus osteitis was identified in 12 cases (0.83%). All cases occurred in patients who underwent sellar reconstruction, with no osteitis observed in those without reconstruction (p < 0.001). Regarding reconstruction techniques, the nasoseptal flap showed a borderline statistical significance (p = 0,045). Radiologically, osteitis was Grade 1 in 50%, Grade 2 in 25%, and Grade 3 in 25% of cases. Cacosmia was the presenting symptom in 75% of affected patients (p < 0.001). Surgical revision was required in 11 patients (91.7%), while medical treatment alone was sufficient in one case. At the 12-month follow-up, all of the patients were symptom-free; one patient required a second revision for recurrent sphenoid sinusitis at sixth months follow up.

CONCLUSION: Sphenoid sinus osteitis represents a rare but clinically relevant bone-centered complication following ETS, distinct from conventional rhinonasal morbidity. Its exclusive association with sellar reconstruction highlights the potential role of reconstruction-related bone contact and localized inflammatory responses in its pathogenesis. Recognizing sphenoid sinus osteitis as a distinct postoperative entity may improve diagnostic accuracy and guide more targeted management of postoperative rhinonasal symptoms. Surgical revision served as the primary intervention for the patient cohort, yielding favorable outcomes characterized by complete symptomatic resolution at the 12-month follow-up.

PMID:42043579 | DOI:10.1007/s00701-026-06880-w

Psychol Med. 2026 Apr 27;56:e113. doi: 10.1017/S0033291726103614.

ABSTRACT

BACKGROUND: Insomnia is commonly seen in opioid use disorder (OUD) patients receiving methadone maintenance treatment (MMT) and might be related to high heroin relapse risk. This study aims to identify potential mediation pathways among peripheral cytokines, neuroimaging characteristics, and insomnia in MMT patients, and explore diagnostic markers and therapeutic targets for MMT-related insomnia.

METHODS: A total of 121 OUD individuals (OUDs) and 109 healthy controls were recruited, including MMT individuals (MMT group, N = 53), short-term abstinent (median: 30 days) heroin users at baseline (OUD1, N = 68), and around 10-month follow-up (OUD2, N = 61) without MMT, healthy controls-cohort 1 (HC1, N = 53, age/gender/education match MMT), and healthy controls-cohort 2 (HC2, N = 56, age/gender match OUD1). Multimodal datasets, including cerebral diffusion tensor imaging (DTI), peripheral hematologic indicators, and neuropsychological assessments, were collected from the MMT group and HC1. Within the MMT group, we revealed relationships among cytokines, DTI metrics, and neuropsychological assessments via partial correlation and mediation analyses. Mendelian randomization (MR) analyses between OUD and white matter (WM)-related imaging-derived phenotypes were used to further confirm Tract-Based Spatial Statistics (TBSS) results. Besides, the results of TBSS among OUD1, OUD2, and HC2 hypothetically served as baseline WM alteration before MMT.

RESULTS: Through comparisons among OUD1, OUD2, and HC2, WM aberrances could return to normal after 10-month abstinence, and we used the results as baseline alterations before MMT. MMT patients exhibited a broad imbalance in peripheral immune cells and cytokines, as well as presented insomnia, anxiety, and depression symptoms. After Bonferroni correction, mean diffusivity and radial diffusivity in extensive WM regions were higher in MMT patients than those of HC1. Ultimately, through multimodal correlation analysis, the ‘Interferon-γ (IFN-γ)-WM aberrance-insomnia’ axis was discovered in the MMT group.

CONCLUSIONS: Together, these results primarily link cytokines and WM injury for OUDs with MMT to insomnia, implicating pharmacological IFN-γ target as a latent strategy to improve the insomnia of MMT patients.

PMID:42037510 | DOI:10.1017/S0033291726103614

J Orthop Res. 2026 Apr;44(5):e70208. doi: 10.1002/jor.70208.

ABSTRACT

Anterior cruciate ligament (ACL) injury and subsequent changes in the magnitude and distribution of contact stress about the articular surfaces of the knee are associated with post-traumatic osteoarthritis. Soon after ACL injury, changes in tibial articular cartilage thickness occur that can be explained, in part, by abnormal positioning of the tibia relative to the femur. However, little is known about the effects of ACL injury on the positions of the menisci. The purpose of this case-control study was to determine the effect of ACL injury on posterior horn meniscus centroid (PHMC) position relative to the tibia in males and females. ACL-injured and matched control subjects with normal knees underwent bilateral magnetic resonance imaging soon after the index injury and prior to ACL reconstruction. The PHMC position was defined in three dimensions at the point of maximal tibial articular cartilage concavity in the lateral and medial compartments of the knee. In control subjects, there were no significant differences in PHMC position between knees in the lateral and medial compartments. In ACL-injured knees, there were significant posterior-directed changes in PHMC position in both compartments for males and females when compared to their contralateral normal knees. These changes in PHMC position may alter the distribution of articular cartilage contact stress and explain a portion of the changes in knee biomechanics and cartilage thickness that occur following ACL injury. In addition, these findings suggest that the menisci should not be used as landmarks to establish regions of interest when measuring cartilage thickness and matrix components.

PMID:42037506 | DOI:10.1002/jor.70208

Eur J Neurol. 2026 May;33(5):e70568. doi: 10.1111/ene.70568.

ABSTRACT

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), yet the application of diagnostic frameworks of Neurocognitive Disorders (NCDs) is limited. Additionally, the integration of multimodal data for predicting cognitive outcomes using artificial intelligence (AI) remains underexplored. This study aimed to characterize NCDs in MS and predict cognitive worsening using an explainable deep learning model trained on MRI and clinical data.

METHODS: Two-hundred twenty-four MS patients and 115 healthy controls (HC) underwent 3.0 T MRI and clinical assessment at baseline. MS patients also completed neuropsychological testing, including estimation of z-cognitive reserve, at baseline and after a median follow-up of 3.4 (interquartile range = [2.0; 6.1]) years. MS patients were classified as Mild or Major NCD according to the Diagnostic and Statistical Manual of Mental Disorders criteria at baseline, and as “stable” or “worsened” based on cognitive changes at follow-up. A deep learning model was trained on baseline T1-weighted MRI, demographic, clinical, and brain volumetric data to predict cognitive decline, with explainability methods used to interpret the model’s decisions.

RESULTS: At baseline, 4% of patients had Mild and 11% Major NCD. At follow-up, 12% showed cognitive decline. The deep learning model predicted follow-up cognitive status with 90% accuracy. Explainability models identified the most relevant predictors, in order of importance: cortical gray matter volume, age, thalamic and hippocampal volumes, T2 lesion volume, and z-cognitive reserve.

CONCLUSIONS: The proposed multimodal AI approach demonstrated robust performance and highlighted relevant brain regions associated with cognitive worsening, underscoring its potential for personalized cognitive assessment and monitoring in MS.

PMID:42037489 | DOI:10.1111/ene.70568

Psychol Med. 2026 Apr 27;56:e115. doi: 10.1017/S0033291726103985.

ABSTRACT

Parental severe mental illnesses (SMIs), including schizophrenia, bipolar disorder, and major depressive disorder (MDD), can impact children’s well-being, yet existing meta-analyses are limited in scope and methodology and do not comprehensively assess cognitive and academic performance in offspring across SMIs. This meta-analysis aimed to synthesize the existing evidence on the association between parental SMIs and offspring cognitive and academic performance. MEDLINE, EMBASE, PsycINFO, and CINAHL were searched from their inception to December 2025. We included studies assessing associations between parental SMIs and offspring cognitive/academic performance at any age, including attention, memory, language, executive function, processing speed, IQ, social cognition, and academic performance. Standardized mean differences (SMDs) between offspring of parents with SMIs and controls were calculated. Differences in cognitive performance between affected offspring and controls were pooled using random-effects meta-analyses, with robust variance estimation. The meta-analysis included 109 studies (1,586,339 participants). Parental schizophrenia was strongly associated with several cognitive domains, including general cognition (SMD = -1.07, 95% CI: -1.92, -0.22), language (-0.70; -1.20, -0.20), and IQ (-0.53; -0.72, -0.34). Parental bipolar disorder was associated with general cognition (SMD = -0.45, 95% CI = -0.79, -0.12), memory (-0.40; -0.60, -0.19), executive function (-0.34; -0.51, -0.16), IQ (-0.32; -0.48, -0.17), and language (-0.18, 95% CI -0.34, -0.02). Parental MDD showed weaker but statistically significant associations with executive function, general cognition, and language development. Children of parents with SMIs, particularly schizophrenia or bipolar disorder, are at increased risk of cognitive difficulties. Population-level early intervention strategies targeting these families may improve offspring’s cognitive performance.

PMID:42037487 | DOI:10.1017/S0033291726103985