-
Neuro-oncology Jun 2024IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically...
BACKGROUND
IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear.
METHODS
We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling.
RESULTS
We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion.
CONCLUSIONS
Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.
PubMed: 38943513
DOI: 10.1093/neuonc/noae102 -
Advanced Materials (Deerfield Beach,... Jun 2024Films and patterns of 3D-oriented metal-organic frameworks (MOFs) afford well-ordered pore structures extending across centimeter-scale areas. These macroscopic domains...
Films and patterns of 3D-oriented metal-organic frameworks (MOFs) afford well-ordered pore structures extending across centimeter-scale areas. These macroscopic domains of aligned pores are pivotal to enhance diffusion along specific pathways and orient functional guests. The anisotropic properties emerging from this alignment are beneficial for applications in ion conductivity and photonics. However, the structure of 3D-oriented MOF films and patterns can rapidly degrade under humid and acidic conditions. Thus, more durable 3D-ordered porous systems are desired for practical applications. Here, oriented porous polymer films and patterns are prepared by using heteroepitaxially oriented N-functionalized MOF films as precursor materials. The film fabrication protocol utilizes an azide-alkyne cycloaddition on the Cu(AzBPDC)DABCO MOF. The micropatterning protocol exploits the X-ray sensitivity of azide groups in Cu(AzBPDC)DABCO, enabling selective degradation in the irradiated areas. The masked regions of the MOF film retain their N-functionality, allowing for subsequent cross-linking through azide-alkyne coupling. Subsequent acidic treatment removes the Cu ions from the MOF, yielding porous polymer micro-patterns. The polymer has high chemical stability and shows an anisotropic fluorescent response. The use of 3D-oriented MOF systems as precursors for the fabrication of oriented porous polymers will facilitate the progress of optical components for photonic applications. This article is protected by copyright. All rights reserved.
PubMed: 38943469
DOI: 10.1002/adma.202404384 -
Cancer Imaging : the Official... Jun 2024This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
OBJECTIVE
This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
METHODS
Clinical, pathological, and imaging data of 102 patients with surgically and pathologically confirmed meningiomas were retrospectively analyzed. Patients were divided into recurrence and non-recurrence groups based on follow-up. Tumor-infiltrating CD8 + T cells in tissue samples were quantitatively assessed with immunohistochemical staining. Apparent diffusion coefficient (ADC) histogram parameters from preoperative MRI were quantified in MaZda. Considering the high correlation between ADC histogram parameters, we only chose ADC histogram parameter that had the best predictive efficacy for COX regression analysis further. A visual nomogram was then constructed and the recurrence probability at 1- and 2-years was determined. Finally, subgroup analysis was performed with the nomogram.
RESULTS
The risk factors for meningioma recurrence were ADCp1 (hazard ratio [HR] = 0.961, 95% confidence interval [95% CI]: 0.937 ~ 0.986, p = 0.002) and CD8 + T cells (HR = 0.026, 95%CI: 0.001 ~ 0.609, p = 0.023). The resultant nomogram had AUC values of 0.779 and 0.784 for 1- and 2-years predicted recurrence rates, respectively. The survival analysis revealed that patients with low CD8 + T cells counts or ADCp1 had higher recurrence rates than those with high CD8 + T cells counts or ADCp1. Subgroup analysis revealed that the AUC of nomogram for predicting 1-year and 2-year recurrence of WHO grade 1 and WHO grade 2 meningiomas was 0.872 (0.652) and 0.828 (0.751), respectively.
CONCLUSIONS
Preoperative ADC histogram parameters and tumor-infiltrating CD8 + T cells may be potential biomarkers in predicting meningioma recurrence risk.
CLINICAL RELEVANCE STATEMENT
The findings will improve prognostic accuracy for patients with meningioma and potentially allow for targeted treatment of individuals who have the recurrent form.
Topics: Humans; Meningioma; Nomograms; Male; Female; Neoplasm Recurrence, Local; Middle Aged; CD8-Positive T-Lymphocytes; Retrospective Studies; Meningeal Neoplasms; Lymphocytes, Tumor-Infiltrating; Aged; Adult; Magnetic Resonance Imaging; Risk Factors; Prognosis
PubMed: 38943200
DOI: 10.1186/s40644-024-00731-6 -
BMC Oral Health Jun 2024Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly...
BACKGROUND
Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly because the absence of objective and quantitative methods for diagnosing nerve damage renders treatment and compensation ambiguous while often leading to medico-legal disputes. The aim of this study was to examine discriminating factors of traumatic mandibular nerve within a specific magnetic resonance imaging (MRI) protocol and to suggest tangible diagnostic criteria for peripheral trigeminal nerve injury.
METHODS
Twenty-six patients with ipsilateral mandibular nerve trauma underwent T2 Flex water, 3D short tau inversion recovery (STIR), and diffusion-weighted imaging (DWI) acquired by periodically rotating overlapping parallel lines with enhanced reconstruction (PROPELLER) pulse sequences; 26 injured nerves were thus compared with contra-lateral healthy nerves at anatomically corresponding sites. T2 Flex apparent signal to noise ratio (FSNR), T2 Flex apparent nerve-muscle contrast to noise ratio (FNMCNR) 3D STIR apparent signal to noise ratio (SSNR), 3D STIR apparent nerve-muscle contrast to noise ratio (SNMCNR), apparent diffusion coefficient (ADC) and area of cross-sectional nerve (Area) were evaluated.
RESULTS
Mixed model analysis revealed FSNR and FNMCNR to be the dual discriminators for traumatized mandibular nerve (p < 0.05). Diagnostic performance of both parameters was also determined with area under the receiver operating characteristic curve (AUC for FSNR = 0.712; 95% confidence interval [CI]: 0.5660, 0.8571 / AUC for FNMCNR = 0.7056; 95% confidence interval [CI]: 1.011, 1.112).
CONCLUSIONS
An increase in FSNR and FNMCNR within our MRI sequence seems to be accurate indicators of the presence of traumatic nerve. This prospective study may serve as a foundation for sophisticated model diagnosing trigeminal nerve trauma within large patient cohorts.
Topics: Humans; Male; Female; Adult; Middle Aged; Magnetic Resonance Imaging; Mandibular Nerve Injuries; Imaging, Three-Dimensional; Diffusion Magnetic Resonance Imaging; Mandibular Nerve; Aged; Young Adult; Trigeminal Nerve Injuries; Signal-To-Noise Ratio
PubMed: 38943102
DOI: 10.1186/s12903-024-04514-0 -
Scientific Reports Jun 2024The Philippines are central to understanding the expansion of the Austronesian language family from its homeland in Taiwan. It remains unknown to what extent the...
The Philippines are central to understanding the expansion of the Austronesian language family from its homeland in Taiwan. It remains unknown to what extent the distribution of Malayo-Polynesian languages has been shaped by back migrations and language leveling events following the initial Out-of-Taiwan expansion. Other aspects of language history, including the effect of language switching from non-Austronesian languages, also remain poorly understood. Here we apply Bayesian phylogenetic methods to a core-vocabulary dataset of Philippine languages. Our analysis strongly supports a sister group relationship between the Sangiric and Minahasan groups of northern Sulawesi on one hand, and the rest of the Philippine languages on the other, which is incompatible with a simple North-to-South dispersal from Taiwan. We find a pervasive geographical signal in our results, suggesting a dominant role for cultural diffusion in the evolution of Philippine languages. However, we do find some support for a later migration of Gorontalo-Mongondow languages to northern Sulawesi from the Philippines. Subsequent diffusion processes between languages in Sulawesi appear to have led to conflicting data and a highly unstable phylogenetic position for Gorontalo-Mongondow. In the Philippines, language switching to Austronesian in 'Negrito' groups appears to have occurred at different time-points throughout the Philippines, and based on our analysis, there is no discernible effect of language switching on the basic vocabulary.
Topics: Philippines; Bayes Theorem; Phylogeny; Language; Humans; Taiwan; Polynesia; Human Migration; Pacific Island People
PubMed: 38942799
DOI: 10.1038/s41598-024-65810-x -
Scientific Reports Jun 2024Older adults (OAs) are typically slower and/or less accurate in forming perceptual choices relative to younger adults. Despite perceptual deficits, OAs gain from...
Older adults (OAs) are typically slower and/or less accurate in forming perceptual choices relative to younger adults. Despite perceptual deficits, OAs gain from integrating information across senses, yielding multisensory benefits. However, the cognitive processes underlying these seemingly discrepant ageing effects remain unclear. To address this knowledge gap, 212 participants (18-90 years old) performed an online object categorisation paradigm, whereby age-related differences in Reaction Times (RTs) and choice accuracy between audiovisual (AV), visual (V), and auditory (A) conditions could be assessed. Whereas OAs were slower and less accurate across sensory conditions, they exhibited greater RT decreases between AV and V conditions, showing a larger multisensory benefit towards decisional speed. Hierarchical Drift Diffusion Modelling (HDDM) was fitted to participants' behaviour to probe age-related impacts on the latent multisensory decision formation processes. For OAs, HDDM demonstrated slower evidence accumulation rates across sensory conditions coupled with increased response caution for AV trials of higher difficulty. Notably, for trials of lower difficulty we found multisensory benefits in evidence accumulation that increased with age, but not for trials of higher difficulty, in which increased response caution was instead evident. Together, our findings reconcile age-related impacts on multisensory decision-making, indicating greater multisensory evidence accumulation benefits with age underlying enhanced decisional speed.
Topics: Humans; Aged; Adult; Middle Aged; Female; Male; Aged, 80 and over; Decision Making; Adolescent; Reaction Time; Young Adult; Auditory Perception; Aging; Visual Perception; Photic Stimulation; Acoustic Stimulation
PubMed: 38942761
DOI: 10.1038/s41598-024-65549-5 -
The Journal of Physical Chemistry. B Jun 2024The ability of small lipophilic molecules to penetrate the blood-brain barrier through transmembrane diffusion has enabled researchers to explore new diagnostics and...
The ability of small lipophilic molecules to penetrate the blood-brain barrier through transmembrane diffusion has enabled researchers to explore new diagnostics and therapies for brain disorders. Until now, therapies targeting the brain have mainly relied on biochemical mechanisms, while electrical treatments such as deep brain stimulation often require invasive procedures. An alternative to implanting deep brain stimulation probes could involve administering small molecule precursors intravenously, capable of crossing the blood-brain barrier, and initiating the formation of conductive polymer networks in the brain through polymerization. This study examines the aggregation behavior of five water-soluble conducting polymer precursors sharing the same conjugate core but differing in side chains, using spectroscopy and various computational chemistry tools. Our findings highlight the significant impact of side chain composition on both aggregation and spectroscopic response.
PubMed: 38942741
DOI: 10.1021/acs.jpcb.4c02891 -
Journal of Chemical Theory and... Jun 2024The optimal interaction of drugs with plasma membranes and membranes of subcellular organelles is a prerequisite for desirable pharmacology. Importantly, for drugs...
Application of Generative Artificial Intelligence in Predicting Membrane Partitioning of Drugs: Combining Denoising Diffusion Probabilistic Models and MD Simulations Reduces the Computational Cost to One-Third.
The optimal interaction of drugs with plasma membranes and membranes of subcellular organelles is a prerequisite for desirable pharmacology. Importantly, for drugs targeting the transmembrane lipid-facing sites of integral membrane proteins, the relative affinity of a drug to the bilayer lipids compared to the surrounding aqueous phase affects the partitioning, access, and binding of the drug to the target site. Molecular dynamics (MD) simulations, including enhanced sampling techniques such as steered MD, umbrella sampling (US), and metadynamics, offer valuable insights into the interactions of drugs with the membrane lipids and water in atomistic detail. However, these methods are computationally prohibitive for the high-throughput screening of drug candidates. This study shows that applying denoising diffusion probabilistic models (DDPMs), a generative AI method, to US simulation data reduces the computational cost significantly. Specifically, the models used only partial (one-third) data from the US simulations and reproduced the complete potential of mean force (PMF) profiles for three FDA-approved drugs (β2-adrenergic agonists) and ∼20 biologically relevant chemicals with known experimentally characterized bilayer locations. Intriguingly, the model can predict the solvation-free energies for partitioning and crossing the bilayer, preferred bilayer locations (low-energy well), and orientations of the ligands with high accuracy. The results indicate that DDPMs can be used to characterize the complete membrane partitioning profile of drug molecules using fewer umbrella sampling simulations at select positions along the bilayer normal (-axis), irrespective of their amphiphilic-lipophilic-cephalophilic characteristics.
PubMed: 38942732
DOI: 10.1021/acs.jctc.4c00315 -
International Journal of Biological... Jun 2024Controlled drug delivery systems offer numerous advantages. This research evaluates Opuntia leaf mucilage grafted with polyacrylamide (OPM-g-PAM) as a promising...
Evaluation of microwave irradiated Polyacrylamide grafted Opuntia leaf mucilage graft copolymer (OPM-g-PAM) as effective controlled release polymer for release of Rosuvastastin as model drug.
Controlled drug delivery systems offer numerous advantages. This research evaluates Opuntia leaf mucilage grafted with polyacrylamide (OPM-g-PAM) as a promising controlled-release polymer. PAM chains were grafted onto the backbone of OPM using a microwave-assisted method. Optimization of the best grade was based on % grafting efficiency and intrinsic viscosity, followed by extensive physical and analytical characterizations. Analytical characterizations revealed semicrystalline nature of the biomaterial. SEM and AFM observations revealed rough and porous surfaces, indicating effective grafting. Swelling behavior showed maximum sensitivity at pH 7, with reduced swelling at higher sodium chloride concentrations. A comparative study of % drug release of Rosuvastatin over 24 h showed that the optimized grade controlled drug release effectively, achieving 78.5 % release compared to 98.8 % for GF-3. The release data fitted the Korsmeyer-Peppas model, with an "n" value of 0.8334, indicating non-Fickian (anomalous) diffusion. Bacterial biodegradability studies confirmed the high biodegradability of the graft copolymer. In vitro acute toxicity tests showed no toxicity, as confirmed by histopathological studies of heart, liver, and kidney. Overall, the results indicate that OPM-g-PAM is a highly promising material for use in drug delivery systems, demonstrating potential as a novel controlled-release polymer.
PubMed: 38942673
DOI: 10.1016/j.ijbiomac.2024.133200 -
Neuroimaging Clinics of North America Aug 2024Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease of the central nervous system, commonly featuring disability and cognitive impairment. The... (Review)
Review
Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease of the central nervous system, commonly featuring disability and cognitive impairment. The pathologic hallmark of MS lies in demyelination and hence impaired structural and functional neuronal pathways. Recent studies have shown that MS shows extensive structural disconnection of key network hub areas like the thalamus, combined with a functional network reorganization that can mostly be related to poorer clinical functioning. As MS can, therefore, be considered a network disorder, this review outlines recent innovations in the field of network neuroscience in MS.
Topics: Humans; Multiple Sclerosis; Brain; Nerve Net; Magnetic Resonance Imaging; Neuroimaging
PubMed: 38942522
DOI: 10.1016/j.nic.2024.03.008