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Clinics (Sao Paulo, Brazil) Jun 2024Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral...
AIM
Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD.
METHODS
This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs).
RESULTS
The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust.
CONCLUSIONS
IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.
PubMed: 38943703
DOI: 10.1016/j.clinsp.2024.100421 -
Inorganic Chemistry Jun 2024We report on the detailed structural analysis of a series of 11 new quaternary rare earths containing thiosilicates, AkRESiS (Ak = Ca and Sr; RE = La, Ce, Pr, Nd, Sm,...
Crystal Growth of Quaternary AkRESiS (Ak = Ca and Sr; RE = La-Tb) Thiosilicates Using Flux-Assisted Boron Chalcogen Mixture Method: Exploring X-ray Scintillation, Luminescence, and Magnetic Properties.
We report on the detailed structural analysis of a series of 11 new quaternary rare earths containing thiosilicates, AkRESiS (Ak = Ca and Sr; RE = La, Ce, Pr, Nd, Sm, Gd, and Tb), synthesized using the flux-assisted boron chalcogen mixture method. High quality crystals were grown and used to determine their crystal structures by single crystal X-ray diffraction. All members of the AkRESiS series crystallize in the trigonal crystal system with space group 3̅ (space group no. 167). Polycrystalline powders were used for physical property measurements, including magnetic susceptibility, diffuse reflectance in the UV-visible range, and scintillation. Magnetic measurements indicated that CaRESiS (RE = Nd and Tb) exhibits paramagnetic behavior with a slightly negative Weiss constant. The band gaps of the materials were determined from diffuse reflectance data, and optical band gaps were estimated to be 2.5(1) and 2.9(1) eV for CaCeSiS and CaGdSiS, respectively. CaCeSiS, CaTbSiS, and SrCeSiS exhibited intense green luminescence upon irradiation with 375 nm ultraviolet light and, furthermore, scintillated when exposed to X-rays. Radioluminescence measurements of CaCeSiS powder revealed green emission with an intensity approximately 14% of that emitted by bismuth germanium oxide powder.
PubMed: 38943660
DOI: 10.1021/acs.inorgchem.4c01314 -
Analytical Chemistry Jun 2024Protein-based biopharmaceutical drugs, such as monoclonal antibodies, account for the majority of the best-selling drugs globally in recent years. For bioprocesses, key...
Protein-based biopharmaceutical drugs, such as monoclonal antibodies, account for the majority of the best-selling drugs globally in recent years. For bioprocesses, key performance indicators are the concentration and aggregate level for the product being produced. In water NMR (NMR), the use of the water transverse relaxation rate [(HO)] has been previously used to determine protein concentration and aggregate level; however, it cannot be used to separate between them without using an additional technique. This work shows that it is possible to "decouple" these two key characteristics by recording the water diffusion coefficient [(HO)] in conjunction with (HO), even in the event of overlap in either (HO) or (HO). This method is demonstrated on three different systems, following appropriate (HO) or (HO) calibration data acquisition for a protein of interest. Our method highlights the potential use of benchtop NMR as an at-line process analytical technique.
PubMed: 38943616
DOI: 10.1021/acs.analchem.3c05875 -
Epilepsia Open Jun 2024Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug-resistant epilepsy. Enhance...
OBJECTIVE
Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug-resistant epilepsy. Enhance diffusion-weighted imaging (eDWI) technique and tri-component model have been used in previous studies to calculate apparent diffusion coefficient from ultra high b-values (ADCuh). This study aimed to explore the alterations of ADCuh in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy.
METHODS
Twenty-nine patients with MRI-negative drug-resistant epilepsy and 18 healthy controls underwent eDWI scan with 15 b-values (0-5000 s/mm). The eDWI parameters including standard ADC (ADCst), pure water diffusion (D), and ADCuh were calculated from the 15 b-values. Regions-of-interest (ROIs) analyses were conducted in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus. ADCst, D, and ADCuh values were compared between the MRI-negative drug-resistant epilepsy patients and controls using multivariate generalized linear models. Inter-rater reliability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman (BA) analysis. False discovery rate (FDR) method was applied for multiple comparisons correction.
RESULTS
ADCuh values in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus in MRI-negative drug-resistant epilepsy were significantly higher than those in the healthy control subjects (all p < 0.05, FDR corrected).
SIGNIFICANCE
The alterations of the ADCuh values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy might reflect abnormal membrane water permeability in MRI-negative drug-resistant epilepsy. ADCuh might be a sensitive measurement for evaluating subcortical nuclei-related brain damage in epilepsy patients.
PLAIN LANGUAGE SUMMARY
This study aimed to explore the alterations of apparent diffusion coefficient calculated from ultra high b-values (ADCuh) in the subcortical nuclei such as the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. The bilateral thalamus and striatum showed higher ADCuh in epilepsy patients than healthy controls. These findings may add new evidences of subcortical nuclei abnormalities related to water and ion hemostasis in epilepsy patients, which might help to elucidate the underlying epileptic neuropathophysiological mechanisms and facilitate the exploration of therapeutic targets.
PubMed: 38943548
DOI: 10.1002/epi4.12990 -
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