Correction For Multiple Comparisons Research Articles

Mechanical properties variation of samples fabricated by fused deposition additive manufacturing as a function of filler percentage and structure for different plastics.

One of the key factors in manufacturing products by fused deposition molding (FDM) or layer-by-layer printing technology is the material intensity of the product. The task of reducing the amount of material required to manufacture a product without significant loss of mechanical properties is one of the most practically important technological tasks. Material saving in FDM printing of products allows to reduce financial costs and increase the speed of manufacturing of the final product without reducing (or not significantly reducing) the quality properties of the product. In our work it is demonstrated that using Combs filling type and materials of poly lactic acid (PLA) and polyethylene terephthalate glycol (PETG) it is possible to achieve material savings of up to 23% at 50% filling for PLA and 17% at 75% filling for PETG without significant reduction of product strength in comparison with other filling types. Exceptions are PLA samples with 100% fill and Lateral fill. Application of Kruskal-Wallis criterion and Dunn's criterion with Bonferroni multiple comparison correction showed that there were no statistically significant differences within the strength limits of samples made by FDM printing technology from PLA and PETG plastics (p-value = 0.0514), as well as samples with Triangle and Grid filling type (p-value = 1). Based on this result, three groups of samples statistically significantly differing in ultimate strength were identified by methods of hierarchical cluster analysis; in each group (except for group 1, which included samples made of PLA plastic with Lateral filling type and 100% filling), correlation analysis was performed (Spearman correlation was used). The results of the correlation analysis showed a stable average correlation between the percentage of filling, modulus along the secant 0.05-0.2% strain, ultimate strength and strain corresponding to the yield stress. Analysis of the correlation graph showed that the main parameter correlating with all mechanical properties of the specimen is the 0.05-0.2% strain modulus. Based on this conclusion, robust regression equations predicting the 0.05-0.2% strain modulus as a function of the percentage of specimen filling were constructed for the two selected groups. Analysis of the equations showed that in the third group of specimens, the average modulus of 0.05-0.2% strain is more than twice the modulus of 0.05-0.2% strain in the second group. The detected statistical regularities can be explained by the mechanism of strain hardening, the actual value of which depends on the structure of the macrodefect (type of filling), properties and volume of the material (percentage of filling) used in the fabrication of samples using FDM printing technology.

Manipulating levels of uncertainty in a decision making task for obsessive-compulsive disorder.

The study aims to investigate whether manipulating levels of uncertainty would influence performance in a decision-making task in obsessive-compulsive disorder (OCD). This case-control study compares the performance in beads task (measuring reflection/decisional impulsivity) performance and trait impulsivity (Short Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (UPPS-P)) in patients with OCD (n=65) and non-clinical controls (n=45). Mann Whitney U test was carried out to assess between-group differences. The OCD group had significantly lesser draws to decision (U=1845 , p=.019) and subjective decisional-certainty (U=1518, p=0.00) in the low-uncertainty (85:15) condition , higher scores of negative urgency (U= 2163, p=<0.001) and lower scores on sensation-seeking (U= 907.5, p=.001) in the UPPS-P. However, the comparison of beads task performance does not survive correction for multiple comparisons. Patients with OCD engage in impulsive decision-making in the lower-uncertainty condition in comparison to healthy controls, despite low subjective certainty of the decision. They also had increased scores on the trait impulsivity factor of negative urgency. Future studies may explore the relationship between trait impulsivity as well as the contributions of symptom severity, anxiety and decisional certainty to impulsivity in OCD.

Differences in Physical Activity and Self-Rated Health Levels Based on Satisfaction with Physical Environment of Local Communities: From School to Lifelong Physical Education

Background: In Korea, substantial disparities exist in physical environments across regions, exacerbating the polarization between metropolitan and provincial areas and urban and rural regions. Objectives: This study examines the differences in the physical activity and self-rated health of local communities in relation to satisfaction with the physical environment. By identifying and addressing these underlying causes of health disparities, the study provides foundational data to inform policy efforts. Methods: The study utilized data from the 2023 Community Health Survey conducted by the Korea Disease Control and Prevention Agency. It included 231,752 individuals aged 19 and older (105,754 men and 125,998 women) selected through a two-stage probability proportional systematic sampling method. One-on-one online interviews were conducted from 16 May to 31 July 2023. The physical environment was assessed based on public satisfaction with safety, natural and living environments, public transportation, and medical services. Study variables included subjective health status and physical activity, with subvariables for physical activity encompassing the duration of vigorous and moderate physical activity, walking, and flexibility exercises. For data analysis, MANOVA and ANOVA were conducted, with Bonferroni correction for multiple comparisons. Results: Considerable variations in physical activity were observed based on satisfaction with the local community environment. Regarding self-rated health, significant differences were found in safety levels, living environment, and medical services. Satisfaction with the physical environment positively influenced physical activity and self-rated health. Conclusion: Therefore, it is imperative to reduce disparities in the physical environment between regions and enhance residents’ satisfaction.

EPCO-43. DECONVOLUTION OF GLIOBLASTOMA RNA-SEQ REVEALS IMMUNE SUBPOPULATIONS PREDICTING THERAPEUTIC RESPONSE

Abstract Bulk RNA-seq is now among the standard of care for patients with newly diagnosed glioblastoma (GBM), but whether this data can predict therapeutic response is unclear. In silico deconvolution of bulk RNA-seq data allows for quantification of cell types comprising the tumor and its microenvironment. Our study tests whether cell type proportions predict therapeutic response in patients with GBM and high-grade glioma (HGG) enrolled in trials of investigational agents. 127 patients with GBM/HGG underwent post-resection/biopsy whole exome RNA-seq and reads were post-processed using standard computational pipelines. In silico deconvolution was performed using GBMDeconvoluteR, which generates cellular proportions comprising the RNA-seq reads. Multivariate Cox regression models were used to examine each cell proportion as a predictor of progression-free (PFS) and overall (OS) survival. Statistical significance was ascertained using Bonferroni correction for multiple comparisons. Among 54 patients treated with a PD-L1 inhibitor (nivolumab) and VEGF inhibitor (bevacizumab), the proportions of NK cells (p=0.0024), radial glial cells (p=0.0010), and mural cells (p=0.0025), was associated with increased PFS, while proportion of endothelial cells (p=0.0008) was associated with decreased PFS. Astrocyte (p=0.0022), macrophage (p=0.0015), NK cell (p&amp;lt;0.0001), and mural cell (p=0.0004) proportions were associated with longer OS, while endothelial cell proportion (p=0.0001) was associated with shorter OS. Among 21 patients treated with a tyrosine kinase inhibitor (ibrutinib) combined with radiation and temozolomide (RT/TMZ), cell proportions assessed at the time of diagnosis did not predict PFS or OS. In 52 patients with HGG treated with a JAK inhibitor (ruxolitinib) with RT/TMZ, only mural cell proportion was associated with a longer OS (p=0.0017). Our results highlight how bulk RNA-seq data can be used to predict therapeutic response. In GBM patients treated with immunotherapies, the proportion of NK cells may predict response. Further work will examine which gene programs are predictive of therapeutic response.

Free Water MRI of White Matter in Wilson's Disease.

Diffusion tensor imaging (DTI) is susceptible to partial volume effects from free water, which can be corrected by using bi-tensor free water imaging (FWI). This approach may improve the evaluation of microstructural changes associated with Wilson's disease (WD). To investigate microstructural changes in white matter of WD using DTI and FWI. Prospective. Nineteen neurological WD (7 female, 31.68 ± 7.89 years), 10 hepatic WD (3 female, 29.67 ± 13.37 years), and 25 healthy controls (13 female, 29.5 ± 7.7 years). 3-T, spin-echo echo-planar imaging diffusion-weighted imaging, T1-weighted, T2-weighted, fluid-attenuated inversion recovery. Various diffusion metrics, including mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy (FA), axial diffusivity (AD), free water, and free water-corrected metrics (MDT, RDT, FAT, and ADT) were estimated and compared across entire white matter skeleton among neurological WD, hepatic WD, and controls. Voxel-wise tract-based spatial statistics and region of interest (ROI) analysis based on white matter atlas were performed. Additionally, partial correlation analysis was conducted to assess the relationship between FWI indices in ROIs and clinical indicators. One-way analysis of variance, family-wise error correction for multiple comparisons, and Bonferroni correction for post hoc comparisons. A P-value <0.05, corrected for multiple comparisons, was considered statistically significant. Our study found significantly lower FA and higher MD, AD, and RD across most of white matter skeleton in neurological WD. Decreased FAT and increased MDT, ADT, and RDT were observed only in limited white matter areas compared to DTI indices. Additionally, a significant relationship was found between Unified WD Rating Scale neurological subscale of neurological WD and free water (r = 0.613) in middle cerebellar peduncle, ADT (r = -0.555) in superior cerebellar peduncle, RDT (r = 0.655), and FAT (r = -0.660) in posterior limb in internal capsule. FWI may allow a more precise evaluation of microstructural changes in WD than conventional DTI, with FWI metrics potentially correlating with clinical severity scores of WD patients. 2 TECHNICAL EFFICACY: Stage 2.

Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies.

This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve. Twenty-one percent of LLD and ND participants were Aβ positive and the groups did not differ on white matter hyperintensity volume (WMH (logscale); β = 0.12, p = 0.28). Compared to ND, the LLD group exhibited significantly lower bilateral volume in the lateral orbitofrontal cortex, hippocampus, accumbens area, superior temporal lobe, temporal pole, and amygdala after multiple comparison correction (p < 0.009 for all). Cortico-limbic volumes significantly improved classification of LLD beyond demographic characteristics, Aβ status, and WMH (AUCVol = 0.71, AUCWMH, Aβ = 0.62, AUC difference, 0.09 [0.03 to 0.15]). LLD exhibited poorer performance on measures of global cognition, set shifting, and verbal learning and memory relative to ND. Cognitive function was positively associated with cortico-limbic volumes and these relationships did not differ by group. Secondary analyses with an ND sample additionally matched for Mild Cognitive Impairment (MCI) diagnosis showed a similar but attenuated pattern of volume abnormalities. Overall, our results support LLD as being associated with cortico-limbic volume abnormalities that are distinct from Aβ and white matter pathologies and that these volume abnormalities are important factors associated with cognitive dysfunction in LLD.

Feasibility of Ultra-low Radiation and Contrast Medium Dosage in Aortic CTA Using Deep Learning Reconstruction at 60 kVp: An Image Quality Assessment

ObjectiveTo assess the viability of using ultra-low radiation and contrast medium (CM) dosage in aortic computed tomography angiography (CTA) through the application of low tube voltage (60kVp) and a novel deep learning image reconstruction algorithm (ClearInfinity, DLIR-CI). MethodsIodine attenuation curves obtained from a phantom study informed the administration of CM protocols. Non-obese participants undergoing aortic CTA were prospectively allocated into two groups and then obtained three reconstruction group. The conventional group (100kVp-CVgroup) underwent imaging at 100kVp and received 210 mg iodine/kg in combination with a hybrid iterative reconstruction algorithm (ClearView, HIR-CV). The experimental group was imaged at 60kVp with 105 mg iodine/kg, while images were reconstructed with HIR-CV (60 kVp-CV group) and with DLIR-CI (60 kVp-CI group). Student's t-test was used to compare differences in CM protocol and radiation dose. One-way ANOVA compared CT attenuation, image noise, SNR, and CNR among the three reconstruction groups, while the Kruskal-Wallis H test assessed subjective image quality scores. Post hoc analysis was performed with Bonferroni correction for multiple comparisons, and consistency analysis conducted in subjective image quality assessment was measured using Cohen's kappa. ResultsThe radiation dose (1.12±0.23 mSv vs. 2.03±0.82 mSv) and CM dosage (19.04±3.03 mL vs. 38.11±6.47 mL) provided the reduction of 45% and 50% in the experimental group compared to the conventional group. The CT attenuation, SNR and CNR of 60kVp-CI were superior to or equal to those of 100kVp-CV. Compared to the 60 kVp-CV group, images in 60kVp-CI showed higher SNR and CNR (all P < 0.001). There was no difference between the 60kVp-CI and 100kVp-CVgroup in terms of the subjective image quality of the aorta in various locations (all P > 0.05), with 60kVp-CI images were deemed diagnostically sufficient across all vascular segments. ConclusionsFor non-obese patients, the combined use of 60kVp and DLIR-CI algorithm can preserving image quality while enabling radiation dose and contrast medium savings for aortic CTA compared with 100kVp using HIR-CV.

Prospective associations between early adolescent reward functioning and later dimensions of psychopathology.

Individual differences in reward functioning have been associated with numerous disorders in adolescence. Given relations with multiple forms of psychopathology, it is unclear whether these associations are disorder specific or reflective of shared variance across multiple disorders. In a sample of adolescents (N = 418), we examined associations between neural and self-reported indices of early reward functioning (age 12) with different levels of a hierarchical psychopathology model assessed later in adolescence (age 18). We examined whether prospective relationships between reward functioning are specific to individual disorders or better explained by transdiagnostic dimensions. We found modest results for prospective associations between reward indices and different dimensions of psychopathology, with most significant associations not surviving correction for multiple comparisons. We discuss the benefits and limitations of the modeling approach used to examine dimension-specific associations that future work can build on. Overall, more work is needed to better understand how reward functioning is specifically associated with different forms of and hierarchical levels of psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Altered structural covariance of the cortex and hippocampal formation in patients with lung cancer after chemotherapy

ObjectiveIn this retrospective study, we aimed to investigate changes in brain morphology and structural topological networks in patients with lung cancer (LC) with or without chemotherapy. MethodsWe retrospectively recruited 191 participants for this cross-sectional study, including 113 patients with LC without chemotherapy (Ch-), 38 patients with LC with chemotherapy (Ch+), and 40 healthy controls (HC) matched for age, sex, and education. The gray matter volume (GMV) and cortical properties were compared among the three groups. We constructed the structural covariant network (SCN) based on cortical thickness, volumes of subcortical structures, and volumes of hippocampal subfields and the amygdala in all participants. The global and nodal topological properties of SCN were compared among groups. In addition, 23 patients with LC (8 Ch+ and 15 Ch-) who received two identical brain magnetic resonance scans were enrolled in the follow-up study. The paired t-test was used to compare group differences in brain morphology and topological properties in the structural network. ResultsThe GMV of the bilateral caudate and thalamus were smaller in the Ch- and Ch+ groups compared to the HC group using threshold-free cluster enhancement and permutation (P < 0.05, 5000 times permutations) for multiple comparison correction. The cortical SCN analysis suggested multiple enhanced nodal properties in several brain areas in Ch+ and Ch- compared to HC, mainly in the temporal gyrus, using permutations test and false discovery rate (FDR) (P < 0.05) corrections. Moreover, an increased sigma was found in the Ch+ compared with HC (P = 0.0238). The reduced nodal degree (P = 0.0002) and betweenness (P = 0.0008) in the right amygdala of Ch+ compared to HC were detected by subcortical SCN analysis. Furthermore, reduced gamma (P = 0.0342) and sigma (P < 0.0001) were found in Ch- compared with HC in the SCN analysis of subfields of the amygdala-hippocampal complex. In the follow-up study, reduced nodal degree (P < 0.0001) was found in the right anterior amygdala, and reduced clustering coefficient and local efficiency were found in patients with LC after the permutation test. ConclusionsOur study showed GMV defects and structural topological property abnormalities related to LC and chemotherapy. Such morphological changes associated with LC and chemotherapy could be used as imaging markers for clinical assessments and pathological indicators.

Differences in Fibromyalgia Characteristics by Mode of Commute and Age in Women: The Al-Ándalus Project.

This study aimed to test whether fibromyalgia-related characteristics differ by mode of commute and by age in women with fibromyalgia. A total of 450 women with fibromyalgia (aged 52.0 ± 8.0 years old) were included. Data on their body composition, socioeconomic factors, health-related quality of life (HRQoL), depressive symptoms, sleep quality, pain-related outcomes, fatigue, and mode of commute, as well as the impact of fibromyalgia on their lives, were obtained. We performed linear regression analyses to test the differences in fibromyalgia-related characteristics between the participants engaged in active/passive modes of commuting. To analyze in depth the differences, a one-way analysis of covariance with Bonferroni's correction for multiple comparisons was conducted. In the younger group, active commuters presented differences in fibromyalgia-related characteristics (all, p < 0.01): they were less impacted by having fibromyalgia, had lower levels of fatigue, and had a higher HRQoL than passive commuters. We observed no differences in symptoms between active and passive commuters in the older group (all, p > 0.05). The possible positive effect of active commuting on fibromyalgia-related characteristics might be reduced by age and by a decrease in total physical activity. Physical activity programs for women with fibromyalgia focused on improving fibromyalgia-related characteristics should consider active commuting behaviors to increase their effectiveness.

Abnormal Granger causal connectivity based on altered gray matter volume and associated neurotransmitters of adolescents with internet gaming disorder revealed by a multimodal neuroimaging study

Although prior studies have revealed alterations in gray matter volume (GMV) among individuals with internet gaming disorder (IGD). The brain's multifaceted functions hinge crucially on the intricate connections and communication among distinct regions. However, the intricate interaction of information between brain regions with altered GMV and other regions, and how they synchronize with various neurotransmitter systems, remains enigmatic. Therefore, we aimed to integrate structural, functional and molecular data to explore the GMV-based Granger causal connectivity abnormalities and their correlated neurotransmitter systems in IGD adolescents. Voxel-based morphometry (VBM) analysis was firstly performed to investigate GMV differences between 37 IGD adolescents and 35 matched controls. Brain regions with altered GMV were selected as seeds for further Granger causality analysis (GCA). Two-sample t tests were performed using the SPM12 toolkit to compare the GMV and Granger causal connectivity between IGD and control groups (GRF corrected, Pvoxel<0.005, Pcluster<0.05). Then, GMV-based Granger causal connectivity was spatially correlated with PET- and SPECT-derived maps covering multifarious neurotransmitter systems. Multiple comparison correction was performed using false discovery rate (FDR). Compared with controls, IGD adolescents showed higher GMV in the caudate nucleus and lingual gyrus. For the GCA, IGD adolescents showed higher Granger causal connectivity from insula, putamen, supplementary motor area (SMA) and middle cingulum cortex (MCC) to the caudate nucleus, and lower Granger causal connectivity from superior/inferior parietal gyrus (SPG/IPG) and middle occipital gyrus (MOG) to the lingual gyrus. Besides, GMV-based Granger causal connectivity of IGD adolescents were associated with the dopaminergic, serotonergic, GABAergic and noradrenaline systems. This study revealed that the caudate nucleus and lingual gyrus may be the key sites of neuroanatomical changes in IGD adolescents, and whole-brain Granger causal connectivity abnormalities based on altered GMV involved large brain networks including reward, cognitive control, and visual attention networks, and these abnormalities are associated with a variety of neurotransmitter systems, which may be associated with higher reward sensitivity, cognitive control, and attention control dysfunction.

Vascular occlusion for optimising the functional improvement in patients with knee osteoarthritis: a randomised controlled trial.

Knee osteoarthritis (KOA) is a leading cause of global disability with conventional exercise yielding only modest improvements. Here we aimed to investigate the benefits of integrating blood flow restriction (BFR) into traditional exercise programmes to enhance treatment outcomes. The Vascular Occlusion for optimizing the Functional Improvement in patients with Knee Osteoarthritis randomised controlled trial enrolled 120 patients with KOA at Ghent University Hospital, randomly assigning them to either a traditional exercise programme or a BFR-enhanced programme over 24 sessions in 12 weeks. Assessments were conducted at baseline, 6 weeks, 12 weeks and 3 months postintervention using linear mixed models with Dunn-Sidak corrections for multiple comparisons. Primary outcome was the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire at 3 months follow-up with knee strength, Pain Catastrophizing Scale questionnaire and functional tests as secondary outcomes. Analysis followed an intention-to-treat approach (NCT04996680). The BFR group showed greater improvements in KOOS pain subscale (effect size (ES)=0.58; p=0.0009), quadriceps strength (ES=0.81; p<0.0001) and functional tests compared with the control group at 12 weeks. At 3 months follow-up, the BFR group continued to exhibit superior improvements in KOOS pain (ES=0.55; p=0.0008), symptoms (ES=0.59; p=0.0004) and quality of life (QoL) (ES=0.66; p=0.0001) with sustained benefits in secondary outcomes. Drop-out rates were similar in both groups. Incorporating BFR into traditional exercise programmes significantly enhances short-term and long-term outcomes for patients with KOA demonstrating persistent improvements in pain, symptoms, QoL and functional measures compared with conventional exercise alone. These findings suggest that BFR can provide the metabolic stimulus needed to achieve muscle strength and functional gains with lower mechanical loads. Reduced pain and increased strength support a more active lifestyle, potentially maintaining muscle mass, functionality and QoL even beyond the supervised intervention period. NCT04996680.

Proteome-wide associations of pulse pressure in the UK Biobank

Abstract Introduction Large artery stiffness (LAS) significantly contributes to the burden of cardiovascular morbidity and mortality, and is marked by an increased pulse pressure (PP)(1). Therapeutically targeting LAS may help in mitigating cardiovascular disease and other comorbidities. Purpose We aimed to investigate the proteomic associations of PP, and their putative causal role using Mendelian randomization (MR). Methods We first investigated associations between baseline circulating protein levels for 2,941 protein analytes measured using Olink technology, and PP in the UK Biobank (N=54,219). Regression analyses were adjusted for age, sex, mean arterial pressure, body mass index and stroke volume. Next, we conducted two-sample MR analyses to evaluate associations between genetically-predicted plasma protein levels and PP, for 1,820 proteins with available genetic instruments. We conducted inverse-variance weighted MR as our main analysis, and genetic colocalization analyses as sensitivity. We used a 5% false discovery rate (FDR) threshold to account for multiple comparisons. Results After correction for multiple comparisons, measured levels of 61 out of 2,923 proteins were significantly associated with PP (Figure 1). Genetically-predicted levels for 58 proteins were significantly associated with PP after FDR correction (Figure 2). At nominal significance, 31 proteins were concordantly associated with PP in both analyses, and 19 had consistent directions of effect, including natriuretic peptide B (NPPB, βobservational=0.04, Standard Error (SE)=0.009, PFDR&amp;lt;0.001), thrombospondin-2 (THBS2, βobservational=0.05, SE=0.009, PFDR&amp;lt;0.001), paraoxonase-2 (PON2, βobservational=-0.03, SE=0.008, PFDR&amp;lt;0.001), and sclerostin (SOST, βobservational=-0.03, SE=0.009, PFDR&amp;lt;0.001). NPPB was concordant in direction of effect and met an FDR-corrected significance threshold. Conclusions Our study identifies multiple novel proteins with a putative causal effect on PP. Our findings identify NPPB with a high level of statistical confidence, which could have important implications given the current availability of FDA-approved medications to boost NPPB effects. Our findings will lead to further investigations regarding the biology and clinical role of the identified candidate therapeutic targets.

Causal effect of gut microbiota on occurrence of herpes zoster and postherpetic neuralgia, and role of Tyzzerella 3

BackgroundPrevious research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN).MethodsA total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR–Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison.ResultsAmong the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174–1.718, p < 0.001, q = 0.039), as there is no heterogeneity or horizontal pleiotropy found.ConclusionsWith investigation of the causal association between gut microbiota, and herpes zoster/PHN, significant findings were identified in 22 different taxa. Among them, Tyzzerella 3 keeps significant after multiple comparison correction, and displays potential to facilitate the occurrence of herpes zoster.Graphical

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.

Disrupted gray matter connectome in vestibular migraine: a combined machine learning and individual-level morphological brain network analysis

BackgroundAlthough gray matter (GM) volume alterations have been extensively documented in previous voxel-based morphometry studies on vestibular migraine (VM), little is known about the impact of this disease on the topological organization of GM morphological networks. This study investigated the altered network patterns of the GM connectome in patients with VM.MethodsIn this study, 55 patients with VM and 57 healthy controls (HCs) underwent structural T1-weighted MRI. GM morphological networks were constructed by estimating interregional similarity in the distributions of regional GM volume based on the Kullback–Leibler divergence measure. Graph-theoretical metrics and interregional morphological connectivity were computed and compared between the two groups. Partial correlation analyses were performed between significant GM connectome features and clinical parameters. Logistic regression (LR), support vector machine (SVM), and random forest (RF) classifiers were used to examine the performance of significant GM connectome features in distinguishing patients with VM from HCs.ResultsCompared with HCs, patients with VM exhibited increased clustering coefficient and local efficiency, as well as reduced nodal degree and nodal efficiency in the left superior temporal gyrus (STG). Furthermore, we identified one connected component with decreased morphological connectivity strength, and the involved regions were mainly located in the STG, temporal pole, prefrontal cortex, supplementary motor area, cingulum, fusiform gyrus, and cerebellum. In the VM group, several connections in the identified connected component were correlated with clinical measures (i.e., symptoms and emotional scales); however, these correlations did not survive multiple comparison corrections. A combination of significant graph- and connectivity-based features allowed single-subject classification of VM versus HC with significant accuracy of 77.68%, 77.68%, and 72.32% for the LR, SVM, and RF models, respectively.ConclusionPatients with VM had aberrant GM connectomes in terms of topological properties and network connections, reflecting potential dizziness, pain, and emotional dysfunctions. The identified features could serve as individualized neuroimaging markers of VM.

Slowly expanding lesions are associated with disease activity and gray matter loss in relapse-onset multiple sclerosis.

Slowly expanding lesions (SELs) have been proposed as novel MRI markers of chronic active lesions in multiple sclerosis (MS). However, the mechanism through which SELs affect brain volume loss in patients with MS remains unknown. Additionally, the prevalence and significance of SELs in Asian patients with MS remain unclear. This study aimed to investigate the association between SELs and no evidence of disease activity (NEDA)-3 status as well as brain volume loss in Japanese patients. A total of 99 patients with relapse-onset MS were retrospectively evaluated. SELs were identified on brain MRI based on local deformation when consecutive scans were registered longitudinally. We developed a logistic regression model and generalized linear mixed models (GLMMs) to evaluate the association between the number of SELs and disease activity and changes in brain volume. During the observation period (2.0±0.22years), 35 patients developed at least one SEL. Multivariable logistic regression analysis showed that ≥2 SELs were associated with 0.2 times the risk of achieving a NEDA-3 status. GLMMs revealed that the number of SELs was negatively associated with volume changes in the cortex (p=.00169) and subcortical gray matter (p=.00964) after correction for multiple comparisons. SELs were identified in Japanese patients with MS during the 2-year observation period. The number of SELs is associated with disease activity and brain volume loss, suggesting that the number of SELs could be a biomarker of disease activity in MS.

Systematic evaluation of the correlation between serum metabolites and tinnitus

Objective: We performed a Mendelian randomisation (MR) analysis to explore the relationship between serum metabolites and tinnitus. Methods: In this study, 486 serum metabolites were considered as exposure factors, and single nucleotide polymorphisms (SNP) significantly associated with them were used as instrumental variables (IV). The serum metabolite data were obtained from a public database (http://metabolomips.org/gwas/index.php), while the genome-wide association study (GWAS) summary association statistics for tinnitus were obtained from a Finnish database (https://r10.finngen.fi/pheno/H8_TINNITUS). The inverse variance weighting (IVW) method was employed as the primary determination method for MR analysis, with corrections for multiple comparisons made using the false discovery rate (FDR). Sensitivity tests were conducted using the MR-Egger regression, Mendelian random polymorphism residuals and outliers (MR-PRESSO) methods. The identified serum metabolites were subjected to chained disequilibrium regression analysis (LDSC) and metabolic pathway analysis. Reverse MR analysis was performed to investigate the possibility of reverse causality. Analyses were performed in R software (version 4.3.1). Results: A total of 17 serum metabolites (including 10 known and 7 unknown metabolites) associated with tinnitus were identified. The known metabolites included protective metabolites such as acetylcarnitine, hydroxyisovaleryl carnitine, glycine, monounsaturated glycerol ester, and glycine-L-valine, and hazardous metabolites such as allantoin, glycerylphosphorylcholine 1-eicosatrienoate, myo-inositol, 15-methylpalmitate, and pseudouridine; the strongest causally protective metabolites were acetylcarnitine, the followed by hydroxyisopentanoyl carnitine and glycine; the hazardous metabolite with the strongest causal effect was pseudouridine, followed by inositol and 15-methylpalmitate; and only hydroxyisopentanoyl carnitine (PFDR=0.04) and glycerol monooleate (PFDR=0.04) reached significance values after FDR correction. The findings were free of heterogeneity, pleiotropy and reverse causal associations. The metabolic pathways were mainly enriched in pathways such as ascorbic acid and aldolac metabolism. Conclusions: The study suggests a causal relationship between serum metabolites and tinnitus risk. Serum metabolite levels may influence tinnitus-related metabolic pathways.

7912 Children's Neurodevelopmental Outcomes at School-Age After Conception with Hysterosalpingography Using Iodinated Contrast Media

Abstract Disclosure: S. Keestra: None. C. Kooper: None. N. van Welie: None. K. Dreyer: Grant Recipient; Self; research grants from Guerbet. Speaker; Self; travel and speaker fees Guerbet. R. van Eekelen: None. T. Roseboom: None. J. Oosterlaan: None. B. Mol: Consulting Fee; Self; Organon Laboratories, Norgine, Merck. Grant Recipient; Self; Merck. Stock Owner; Self; ObsEva. M. Finken: None. V. Mijatovic: Grant Recipient; Self; Guerbet, Merck, Ferring Pharmaceuticals. Speaker; Self; Guerbet, Merck, Ferring Pharmaceuticals. M. Königs: None. Thyroid hormone sufficiency in pregnancy is vital for children's neurodevelopment. Exposure to iodine excess can cause transient disruption of thyroid hormone synthesis through the Wolff-Chaikoff effect. Iodinated contrast media are commonly utilized in hysterosalpingography (HSG) as part of female fertility work-up. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone synthesis could jeopardize children's neurodevelopment. We compared the neurodevelopmental outcomes of 6-9-year-old children (n=69) conceived &amp;lt;6 months after HSG with 5-10 ml of oil-based contrast (iodine content: 480mg/ml) or water-based contrasts (iodine content: 250mg/ml) in the follow-up of a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). A community sample of naturally-conceived children (n=44) with similar age, sex and parental education was used as a comparison group (NTR9574). Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behaviour questionnaires for parents and teachers (Strengths and Difficulties Questionnaire (SDQ); Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN)), and academic performance. Secondary outcomes were neurocognitive domains assessed in computerized tasks focussing on Processing &amp; Control, Verbal Memory, Visual Memory, Verbal Working Memory, Visual Working Memory, and Visuomotor Integration (Emma Toolbox for Neurocognitive Functioning). We adjusted linear regression models for age, sex, and parental education, applying FDR correction for multiple comparisons. Additional analysis looked at children conceived within 4 weeks, 4-12 weeks, or &amp;gt;12 weeks after HSG. Children conceived &amp;lt;6 months after HSG had lower performance on intelligence tests (-6.81; 95%CI -10.97 to -2.65; p=0.02) and the neurocognitive domain Processing &amp; Control (-0.52; 95%CI-0.84 to -0.19; p=0.02), with processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. In comparison to naturally-conceived children, children conceived &amp;lt;4 weeks after HSG had lower performance on intelligence tests, but there was no difference for children conceived 4-12 weeks and &amp;gt;12 weeks after HSG. Replication studies with higher power are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children's neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Presentation: 6/1/2024

Low-field MRI lung opacity severity associated with decreased DLCO in post-acute Covid-19 patients

ObjectivesTo evaluate the clinical significance of low-field MRI lung opacity severity. MethodsRetrospective cross-sectional analysis of post-acute Covid-19 patients imaged with low-field MRI from 9/2020 through 9/2022, and within 1 month of pulmonary function tests (PFTs), 6-min walk test (6mWT), and symptom inventory (SI), and/or within 3 months of St. George Respiratory Questionnaire (SGRQ) was performed.Univariate and correlative analyses were performed with Wilcoxon, Chi-square, and Spearman tests. The association between disease and demographic factors and MR opacity severity, PFTs, 6mWT, SI, and SGRQ, and association between MR opacity severity with functional and patient-reported outcomes (PROs), was evaluated with mixed model analysis of variance, covariance and generalized estimating equations. Two-sided 5 % significance level was used, with Bonferroni multiple comparison correction. Results81 MRI exams in 62 post-acute Covid-19 patients (median age 57, IQR 41–64; 25 women) were included. Exams were a median of 8 months from initial illness. Univariate analysis showed lung opacity severity was associated with decreased %DLCO (ρ = −0.55, P = .0125), and lung opacity severity quartile was associated with decreased %DLCO, predicted TLC, FVC, and increased FEV1/FVC.Multivariable analysis adjusting for sex, initial disease severity, and interval from Covid-19 diagnosis showed MR lung opacity severity was associated with decreased %DLCO (P < .001). Lung opacity severity was not associated with PROs. ConclusionLow-field MRI lung opacity severity correlated with decreased %DLCO in post-acute Covid-19 patients, but was not associated with PROs.