Tag: pubmed

J Dent Res. 2024 Dec 19:220345241291528. doi: 10.1177/00220345241291528. Online ahead of print.

ABSTRACT

Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children (N = 6,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI] = 0.42-0.79) among monozygotic twins and 0.44 (95% CI = 0.34-0.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci (P < 5 × 10^-8) and 1 genome-wide significant gene (TAAR6) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate immunity in the oral cavity, was strongly associated with ECC. While no locus remained significant after studywise multiple-testing correction, 3 loci were nominally significant (P < 0.05) and directionally consistent in external cohorts of 285,248 adults (rs1442369, DLGAP1 and rs74606067, RP11-856F16.2) and 18,994 children (rs71327750, SLC41A3). Meanwhile, the strongest marker known to be associated with adult caries (rs1122171, tagging the long noncoding RNA PITX1-AS1) was nominally significant (P = 0.01) and directionally consistent with ECC in our study. Taken together, the results of this study add to the genomics knowledge base for early childhood caries, offer several plausible candidates for future mechanistic studies, and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations.

PMID:39698793 | DOI:10.1177/00220345241291528

Adv Clin Exp Med. 2024 Dec 19. doi: 10.17219/acem/189851. Online ahead of print.

ABSTRACT

BACKGROUND: Dysphagia, prevalent in 90% of children with neurological disorders, poses risks of medical complications and is associated with cognitive and psychosocial challenges. The absence of the sucking-swallowing reflex and variations in the gag reflex contribute to feeding difficulties.

OBJECTIVES: This study focuses on examining the impact of the gag reflex on the masticatory system structure in children with cerebral palsy, aiming to assess its significance.

MATERIAL AND METHODS: This observational study investigated the gag reflex and soft palate shape in 25 children with cerebral palsy (average age: 14 years). Inclusion criteria considered specific levels of the Eating and Drinking Ability Classification System (EDACS) and the Gross Motor Function Classification System (GMFCS). Exclusion criteria comprised hypotension, inflammation and tumors. The Castillo-Morales questionnaire assessed variables and statistical analysis (Spearman’s rank correlation and non-parametric tests) utilizing PQStat v. 1.8.6.120 software.

RESULTS: Findings did not reveal an association between the absence of the gag reflex and abnormal palate structure in children. Our results showed a correlation between higher tension of the buccinator muscles and mobility of the tongue on the structure of the palate.

CONCLUSIONS: Children with neurological disorders, such as cerebral palsy, are a diverse group requiring specialized orthodontic treatment and close interdisciplinary collaboration.

PMID:39698777 | DOI:10.17219/acem/189851

Intern Med J. 2024 Dec 19. doi: 10.1111/imj.16612. Online ahead of print.

ABSTRACT

BACKGROUND: Optimal heart failure (HF) pharmacotherapy (guideline-directed medical therapy and diuretics) in older people with frailty is uncertain due to limited evidence.

AIMS: To evaluate utilisation of HF pharmacotherapy and prevalence of polypharmacy, adverse drug events (ADEs), falls, delirium, renal impairment and duration of hospitalisation in older inpatients, according to frailty.

METHODS: A retrospective cross-sectional study of the TO HOME cohort of 2000 inpatients ≥75 years admitted for ≥48 h to rehabilitation, geriatric or general medicine from 1 July 2016 to 30 June 2017 across six hospitals in Sydney, Australia. Data were collected from electronic medical records. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification identified HF diagnosis, ADEs and frailty using hospital frailty risk score. Outcomes included utilisation of HF pharmacotherapy; polypharmacy; ADEs, falls, delirium, renal and impairment; and duration of hospitalisation.

RESULTS: Among 439 (22.0% of TO HOME cohort) patients with undifferentiated HF, 284 (69.5%) had intermediate or high risk of frailty, and 412 (94%) took ≥1 HF pharmacotherapy, with 357 (81.3%) patients on loop diuretics. Patients with high frailty risk frequently continued beta-blockers (70%) and discontinued renin-angiotensin system inhibitors (57%). Most patients experienced polypharmacy (n = 426, 97.0%). Renal impairment prevalence was 67%-76% across frailty groups. Increasing frailty risk (low, intermediate and high) was associated with increasing prevalence of ADEs (31%, 56% and 84%), falls (12%, 25% and 46%) and delirium (8%, 27% and 49%) and longer hospitalisation.

CONCLUSIONS: Frailty, HF-pharmacotherapy changes in hospital and ADEs were common among older inpatients with HF. The association of adverse outcomes according to frailty needs further investigation. Poor documentation of HF phenotype may be a barrier to medication optimisation in older inpatients.

PMID:39698760 | DOI:10.1111/imj.16612

Med Vet Entomol. 2024 Dec 19. doi: 10.1111/mve.12782. Online ahead of print.

ABSTRACT

Aedes albopictus (Diptera: Culicidae), commonly known as the Asian tiger mosquito, is an important vector transmitting dangerous arboviruses to humans. This study investigated the phenotypic and genetic variation of this species in Thailand through wing geometric morphometric (GM) and mitochondrial cytochrome c oxidase subunit I (COI) gene sequence analyses. A total of 236 Ae. albopictus specimens from 12 populations in Thailand and 89 specimens from invasive populations in Florida, Hawaii and Brazil underwent wing GM analysis. The centroid size (CS) of Ae. albopictus populations in Thailand ranged from 2.00 mm in Bangkok to 2.36 mm in Chanthaburi, while in invasive populations, CS varied from 2.25 mm in Brazil to 2.47 mm in Florida. Pairwise comparisons of wing shape revealed significant differences for most population pairs, with distances ranging from 1.63 to 10.02. The clustering tree indicated distant relationships in wing shape between native and invasive populations. Additionally, partial COI gene sequences were amplified from 108 specimens, revealing a mean haplotype diversity of 0.842 ± 0.025 and a mean nucleotide diversity of 0.002 ± 0.001. The results from neutral Tajima’s D and Fu’s Fs tests indicated negative and statistically significant values (-2.159 and -33.846, respectively), suggesting population expansion. Further examination of haplotype relationships between Thailand and other countries identified two distinct groups: a Southeast Asia group, with Thai haplotypes clustered exclusively within it, and a non-Southeast Asia group. These findings highlight the phenotypic and genetic variation of Ae. albopictus in Thailand, providing essential insights for disease control strategies and tracing the mosquito’s origins across regions.

PMID:39698758 | DOI:10.1111/mve.12782

Biom J. 2025 Feb;67(1):e70016. doi: 10.1002/bimj.70016.

ABSTRACT

Gene set analysis, a popular approach for analyzing high-throughput gene expression data, aims to identify sets of genes that show enriched expression patterns between two conditions. In addition to the multitude of methods available for this task, users are typically left with many options when creating the required input and specifying the internal parameters of the chosen method. This flexibility can lead to uncertainty about the “right” choice, further reinforced by a lack of evidence-based guidance. Especially when their statistical experience is scarce, this uncertainty might entice users to produce preferable results using a “trial-and-error” approach. While it may seem unproblematic at first glance, this practice can be viewed as a form of “cherry-picking” and cause an optimistic bias, rendering the results nonreplicable on independent data. After this problem has attracted a lot of attention in the context of classical hypothesis testing, we now aim to raise awareness of such overoptimism in the different and more complex context of gene set analyses. We mimic a hypothetical researcher who systematically selects the analysis variants yielding their preferred results, thereby considering three distinct goals they might pursue. Using a selection of popular gene set analysis methods, we tweak the results in this way for two frequently used benchmark gene expression data sets. Our study indicates that the potential for overoptimism is particularly high for a group of methods frequently used despite being commonly criticized. We conclude by providing practical recommendations to counter overoptimism in research findings in gene set analysis and beyond.

PMID:39698741 | DOI:10.1002/bimj.70016

Biom J. 2025 Feb;67(1):e70023. doi: 10.1002/bimj.70023.

ABSTRACT

In a longitudinal clinical registry, different measurement instruments might have been used for assessing individuals at different time points. To combine them, we investigate deep learning techniques for obtaining a joint latent representation, to which the items of different measurement instruments are mapped. This corresponds to domain adaptation, an established concept in computer science for image data. Using the proposed approach as an example, we evaluate the potential of domain adaptation in a longitudinal cohort setting with a rather small number of time points, motivated by an application with different motor function measurement instruments in a registry of spinal muscular atrophy (SMA) patients. There, we model trajectories in the latent representation by ordinary differential equations (ODEs), where person-specific ODE parameters are inferred from baseline characteristics. The goodness of fit and complexity of the ODE solutions then allow to judge the measurement instrument mappings. We subsequently explore how alignment can be improved by incorporating corresponding penalty terms into model fitting. To systematically investigate the effect of differences between measurement instruments, we consider several scenarios based on modified SMA data, including scenarios where a mapping should be feasible in principle and scenarios where no perfect mapping is available. While misalignment increases in more complex scenarios, some structure is still recovered, even if the availability of measurement instruments depends on patient state. A reasonable mapping is feasible also in the more complex real SMA data set. These results indicate that domain adaptation might be more generally useful in statistical modeling for longitudinal registry data.

PMID:39698740 | DOI:10.1002/bimj.70023

Quant Imaging Med Surg. 2024 Dec 5;14(12):9323-9334. doi: 10.21037/qims-24-1230. Epub 2024 Nov 29.

ABSTRACT

BACKGROUND: Quantitative assessment of cortical bone microstructure is crucial for the evaluation of osteoporosis, yet current clinical methods such as dual-energy X-ray absorptiometry (DXA) have many limitations. The in vivo quantitative assessment without radiation can be achieved by ultrashort echo time (UTE) magnetic resonance imaging (MRI), where double-echo UTE has high clinical feasibility. However, related studies have mainly focused on distal extremities, and there is a lack of in vivo studies on the proximal femur. This cross-sectional study, as a preliminary study for in vivo quantitative assessment of proximal femoral cortical bone in healthy adults by double-echo UTE MRI, aimed to evaluate the repeatability and explore the impact of potential influencing factors on UTE measurements, thereby providing a reference for the further clinical application of this technique.

METHODS: Healthy volunteers without osteoporosis risk factors were enrolled and underwent double-echo UTE MRI of the proximal femur. Porosity index (PI) and cortical bone thickness (CbTh) were obtained manually by two radiologists independently on double-echo UTE images using image processing software. Repeatability of PI and CbTh measurements were evaluated using intra-class correlation coefficient (ICC) analysis. PI and CbTh of different limbs and sexes were compared, and P<0.05 indicated statistical significance for these analyses. Correlations of PI and CbTh with age and body mass index (BMI) were assessed by Pearson or Spearman correlation coefficient as well as the partial Pearson correlation coefficient. Curve estimation was used to assess non-monotonic variable correlations in scatterplots. For these analyses, P<0.025 indicated statistical significance according to the Bonferroni correction.

RESULTS: A total of 52 healthy cases (33 males, 19 females) aged 22-55 years were included for analysis, where no statistical difference in age was found between sexes (P=0.586) and BMI of males was greater than that of females (P=0.007). The repeatability of PI and CbTh measurements was excellent (ICC 0.985 and 0.943, respectively). The proximal femoral cortical PI was greater on the non-dominant side (P<0.001). PI was greater in males than in females (non-dominant: P<0.001, dominant: P=0.032) and CbTh was greater on the non-dominant side in males than in females (P=0.036) after excluding the effect of confounding factor (BMI). PI on the dominant side was positively correlated with BMI in males (r=0.535, P=0.001), and CbTh on the non-dominant side was positively correlated with BMI in males (r=0.482, P=0.005). There was a U-shaped curve trend between dominant side cortical PI and age in females (y = 65.32 – 1.88x + 0.02x², R²=0.348, P=0.033), although there was no statistical significance after Bonferroni correction.

CONCLUSIONS: Double-echo UTE MRI enables in vivo quantitative assessment of proximal femoral cortical microarchitecture with excellent repeatability. We identified the effects of limb dominance, sex, age, and BMI on UTE measurements in healthy adults, which can serve as a reference for future in vivo studies on proximal femoral cortical bone and is essential before clinical application.

PMID:39698732 | PMC:PMC11652011 | DOI:10.21037/qims-24-1230

Quant Imaging Med Surg. 2024 Dec 5;14(12):8601-8613. doi: 10.21037/qims-24-1035. Epub 2024 Nov 24.

ABSTRACT

BACKGROUND: Currently, the activity of juvenile dermatomyositis (JDM) is mainly assessed based on clinical manifestations, creatine kinase (CK) level, and magnetic resonance imaging (MRI), but certain limitations arise in these approaches for children. Thus, this cross-sectional study aimed to explore the value of ultrasound in evaluating muscle inflammation via the dynamic analysis of muscle ultrasound characteristics in children with active or stable JDM.

METHODS: The data of a group of children who were diagnosed with JDM and admitted to the Rheumatology and Immunology Department of the Capital Pediatric Research Institute Children’s Hospital between June 2022 and November 2023, and a normal control group were collected. The clinical, ultrasound, and laboratory data of the children with active and stable JDM were collected and compared with those of a normal control group. Muscle thickness (MT), fascia thickness (FT), muscle echo intensity (EI), muscle microvascular flow imaging (MVFI) distribution, and the blood flow resistance index (RI) were measured via ultrasound for the comparative analysis. A Spearman correlation analysis was conducted to assess the correlation between the ultrasound parameters in the JDM patients, and muscle scores and laboratory indicators of disease activity. Receiver operating characteristic (ROC) curves were generated for the ultrasound parameters. Five active JDM children were dynamically followed up.

RESULTS: The data of 26 children with active JDM, 29 with stable JDM, and 31 normal control children were collected. The patients with active JDM had significantly greater EI (median 68.9 vs. 47.4, P<0.01), increased FT (median 0.25 vs. 0.15, P<0.01), and an increased MVFI distribution (P<0.01). The Spearman correlation analysis revealed a negative correlation between increased EI, FT, and MVFI distribution, and the Childhood Myositis Assessment Scale (CMAS) score (R=-0.662, -0.673, -0.667, all P<0.05). There was a statistically significant difference in EI between the stable JDM children and healthy children (median 47.4 vs. 39.0, P<0.05). During the follow-up period, two children with slow fasciitis resolution developed soft tissue calcification.

CONCLUSIONS: EI, FT, and MVFI distribution can be used to assess the activity status of individuals with JDM, and are correlated with clinical activity indices. EI may be abnormal even in children with a stable clinical condition, which suggests that ultrasound may more accurately reflect muscle status. Children with long-term unresolved fasciitis may be at risk of developing calcification.

PMID:39698728 | PMC:PMC11651955 | DOI:10.21037/qims-24-1035

Quant Imaging Med Surg. 2024 Dec 5;14(12):8520-8537. doi: 10.21037/qims-24-941. Epub 2024 Oct 24.

ABSTRACT

BACKGROUND: Given the limited capacity and suboptimal sensitivity of ultrasonography (US), gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) demonstrates good diagnostic performance for hepatocellular carcinoma (HCC). Some researchers have proposed that the abbreviated MRI (AMRI) protocols have potential as a surveillance tool. However, few studies have compared multiple AMRI protocols with complete Gd-EOB-DTPA contrast-enhanced MRI for HCC surveillance. We aimed to explore and compare the diagnostic performance of 3 AMRI protocols as HCC surveillance in high-risk patients.

METHODS: This multi-center, retrospective, blinded reader study conducted in China consecutively enrolled 339 patients with hepatitis and/or cirrhosis who underwent complete Gd-EOB-DTPA contrast-enhanced MRI for HCC surveillance from 2020 to 2023. We extracted 3 additional AMRI protocols: noncontrast-AMRI [NC-AMRI: T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)]; dynamic-AMRI (Dyn-AMRI: early and late arterial phases, portal venous phase, and DWI); and hepatobiliary phase-AMRI (HBP-AMRI: T2WI, DWI, and HBP). Then, 2 independent radiologists assessed the AMRI and complete Gd-EOB-DTPA contrast-enhanced MRI protocols. Patients were classified as HCC positive/HCC negative based on the reference standard. Agreement was assessed using Kappa statistics. The acquisition time differences of the 4 MRI protocols were analyzed by analysis of variance (ANOVA). Per-lesion HCC diagnostic performances were compared by Cochran’s Q test. Receiver operating characteristic (ROC) curves for the 3 AMRI protocols were evaluated, and the area under the ROC curve (AUROC) was calculated and compared by DeLong’s test.

RESULTS: A total of 353 lesions were detected in the 339 included patients, and 21/339 patients were diagnosed with HCC (prevalence, 6.2%). The inter-observer agreement was good for all 4 MRI protocols (k>0.75). Acquisition times differed significantly (P<0.001), from the shortest to the longest: NC-AMRI (263.44±5.05 s) < HBP-AMRI (269.18±4.93 s) < Dyn-AMRI (307.71±4.93 s) < complete Gd-EOB-DTPA contrast-enhanced MRI (582.03±3.59 s). The sensitivity (Cochran’s Q=14.667, P=0.002) and specificity (Cochran’s Q=59.682, P<0.001) of 4 MRI protocols were statistically significant. HBP-AMRI showed the highest sensitivity (84.00%), whereas Dyn-AMRI exhibited the highest specificity (99.39%) among 3 AMRI protocols. The per-lesion positive predictive value (PPV) for the NC-AMRI, Dyn-AMRI, and HBP-AMRI was 41.66%, 88.89%, and 47.72%, the corresponding negative predictive value (NPV) was 96.21%, 97.31%, and 98.70%, and the number needed to diagnose (NND) for the NC-AMRI, Dyn-AMRI, HBP-AMRI, and complete Gd-EOB-DTPA contrast-enhanced MRI was: 1.865, 1.577, 1.234, and 1.569, respectively. DeLong’s test showed the AUROC value of either Dyn-AMRI or HBP-AMRI was significantly higher than that of NC-AMRI (Z=2.330, P=0.019; Z=2.680, P=0.007, respectively), but no significant difference between HBP-AMRI and Dyn-AMRI (Z=1.643, P=0.100).

CONCLUSIONS: AMRI protocols can be implemented in clinical practice as a patient-centered and tailored regimen for HCC surveillance in China. NC-AMRI might become an optional tool due to its minimal scanning time, lower cost, and exemption from contrast agents. Dyn-AMRI, achieving the highest specificity, is a reliable surveillance strategy. HBP-AMRI as a favorable alternative showed a high sensitivity and NPV while maintaining considerable specificity and NND.

PMID:39698720 | PMC:PMC11651963 | DOI:10.21037/qims-24-941

Quant Imaging Med Surg. 2024 Dec 5;14(12):9220-9233. doi: 10.21037/qims-24-318. Epub 2024 Nov 14.

ABSTRACT

BACKGROUND: Gut microbiota are associated with brain imaging-derived phenotypes (IDPs); however, the specific causal relationship between the gut microbiota and brain iron-related IDPs remains unclear. Thus, we sought to analyze the potential causal effects of gut microbiota on brain iron-related IDPs using Mendelian randomization (MR).

METHODS: We obtained the data of 196 gut microbiota from a genome-wide association study (GWAS) from the MiBioGen database, as well as the data of 18 quantitative susceptibility mapping (QSM) IDPs and 10 T2* IDPs from the United Kingdom Biobank (UKB). We then conducted one-way two-sample MR analyses to examine their causal interactions. To guarantee the robustness of the results, we performed two independent analysis processes by selecting statistically significant instrumental variables (IVs) with a distinct level of statistical strictness, and derived the intersection of these two analyses.

RESULTS: Our results showed that the genus Howardella was positively correlated with the median susceptibility in the right caudate [β: 0.0935, 95% confidence interval (CI): 0.0601, 0.1269, P_{inverse variance weighting (IVW)}=4.00E-08]; the genus Dialister was positively correlated with the median susceptibility in the right accumbens (β: 0.0949, 95% CI: 0.0575, 0.1324, P_IVW=6.90E-07); the genus Butyricicoccus was positively associated with the median T2* in the left hippocampus with the additional deconfounding of the background field gradient (β: 0.1543, 95% CI: 0.0959, 0.2127, P_IVW=2.20E-07); the genus Desulfovibrio was positively related to the T2* white matter hyperintensity (WMH) IDP with WMH volume regressed out (β: 0.1168, 95% CI: 0.0697, 0.1639, P_IVW=1.20E-06). Notably, both the family Defluviitaleaceae (β: -0.1215, 95% CI: -0.1604, -0.0827, P_IVW=8.40E-10) and genus DefluviitaleaceaeUCG011 (β: -0.1142, 95% CI: -0.1614, -0.0670, P_IVW=2.10E-06) were negatively correlated with the median T2* in the right accumbens with the additional deconfounding of the background field gradient.

CONCLUSIONS: This study found genetic evidence that gut microbiota dysbiosis has causal effects on brain iron-related IDPs. Our findings provide novel insights into the diagnosis and therapeutic management of central nervous system (CNS) diseases.

PMID:39698716 | PMC:PMC11652028 | DOI:10.21037/qims-24-318