Nevin ManimalaStat Probab Lett. 2025 Mar;218:110295. doi: 10.1016/j.spl.2024.110295. Epub 2024 Nov 22.
ABSTRACT
We introduce a generalized Bayesian credible set that can achieve any preassigned credible level, addressing a limitation of the current credible sets. This is achieved by exploiting a connection between the highest posterior density set and the Neyman-Pearson lemma.
PMID:39803594 | PMC:PMC11722005 | DOI:10.1016/j.spl.2024.110295
bioRxiv [Preprint]. 2024 Dec 30:2024.12.30.630778. doi: 10.1101/2024.12.30.630778.
ABSTRACT
A significant advancement in synthetic biology is the development of synthetic gene circuits with predictive Boolean logic. However, there is no universally accepted or applied statistical test to analyze the performance of these circuits. Many basic statistical tests fail to capture the predicted logic (OR, AND, etc.) and most studies neglect statistical analysis entirely. As synthetic gene circuits shift toward advanced applications, primarily in computing, biosensing, and human health, it is critical to standardize the statistical methods used to evaluate gate success. Here, we propose the application of a linear mixed effects model to analyze and quantify genetic Boolean logic gate performance. First, we analyzed 144 currently published Boolean logic gates for trends and used unsupervised machine learning (k-means clustering) to validate the statistical model. Next, we utilized the model to generate estimates for the fixed effect of the ON state, β, as a general descriptor of the Boolean nature of a circuit and used Monte Carlo simulations to recommend sample sizes for evaluating gate performance. Finally, we examined β as a holistic metric for circuit performance using a series of nested repressor OR gates with intentionally degraded performance. We observed a linear correlation between β and the predicted translation rate, highlighting the use of β for the forward design of new Boolean gates. In summary, we utilized a linear mixed effects model to describe synthetic gene circuits and determined that the fixed effect, β, is an appropriate descriptor of gate behavior that can be used to statistically evaluate performance.
PMID:39803539 | PMC:PMC11722350 | DOI:10.1101/2024.12.30.630778
bioRxiv [Preprint]. 2025 Jan 2:2023.03.02.530774. doi: 10.1101/2023.03.02.530774.
ABSTRACT
Neural cell types have classically been characterized by their anatomy and electrophysiology. More recently, single-cell transcriptomics has enabled an increasingly fine genetically defined taxonomy of cortical cell types, but the link between the gene expression of individual cell types and their physiological and anatomical properties remains poorly understood. Here, we develop a hybrid modeling approach to bridge this gap. Our approach combines statistical and mechanistic models to predict cells’ electrophysiological activity from their gene expression pattern. To this end, we fit biophysical Hodgkin-Huxley-based models for a wide variety of cortical cell types using simulation-based inference, while overcoming the challenge posed by the mismatch between the mathematical model and the data. Using multimodal Patch-seq data, we link the estimated model parameters to gene expression using an interpretable sparse linear regression model. Our approach recovers specific ion channel gene expressions as predictive of biophysical model parameters including ion channel densities, directly implicating their mechanistic role in determining neural firing.
PMID:39803528 | PMC:PMC11722265 | DOI:10.1101/2023.03.02.530774
bioRxiv [Preprint]. 2025 Jan 4:2025.01.03.631258. doi: 10.1101/2025.01.03.631258.
ABSTRACT
Sensory stimuli vary across a variety of dimensions, like contrast, orientation, or texture. The brain must rely on population representations to disentangle changes in one dimension from changes in another. To understand how the visual system might extract separable stimulus representations, we recorded multiunit neuronal responses to texture images varying along two dimensions: contrast, a property represented as early as the retina, and naturalistic statistical structure, a property that modulates neuronal responses in V2 and V4, but not in V1. We measured how sites in these 3 cortical areas responded to variation in both dimensions. Contrast modulated responses in all areas. In V2 and V4, the presence of naturalistic structure both modulated responses and increased contrast sensitivity. Tuning for naturalistic structure was strongest in V4; tuning in both dimensions was most heterogeneous in V4. We measured how well populations in each area could support the linear readout of both dimensions. Populations in V2 and V4 could support the linear readout of naturalistic structure, but only in V4 did we find evidence for a robust representation that was contrast-invariant.
SIGNIFICANCE STATEMENT: Single neurons in visual cortex respond selectively to multiple stimulus dimensions, so signals from single neurons cannot distinguish changes in one dimension from changes in another. We measured responses from simultaneously recorded neural populations in three hierarchically linked visual areas – V1, V2, and V4 – using texture stimuli that varied in two dimensions, contrast and naturalistic image structure. We used linear decoding methods to extract information about each dimension. In all three areas, contrast could be decoded independently of image structure. Only in V4, however, could image structure be decoded independently of contrast. The reason is that selectivity for texture and contrast in V4 was much more diverse than in V1 or V2. This heterogeneity allows V4 to faithfully represent naturalistic image structure independent of contrast.
PMID:39803474 | PMC:PMC11722230 | DOI:10.1101/2025.01.03.631258
J Adv Prosthodont. 2024 Dec;16(6):348-357. doi: 10.4047/jap.2024.16.6.348. Epub 2024 Dec 19.
ABSTRACT
PURPOSE: This pilot study investigated the effect of surface roughness on osseointegration by comparing two types of commercial SLA-treated dental implants with different surface roughness levels: moderately rough (Sa = 1 – 2 µm) and rough surfaces (Sa > 2 µm).
MATERIALS AND METHODS: Two implant groups were studied: TS (rough surface) and ADD (moderately rough surface) groups. Surface characteristics were analyzed using optical profilometry and SEM. In vitro studies using BRITER cells assessed cell adhesion, proliferation, and osteogenic differentiation through CCK-8 assay and qRT-PCR for osteopontin (OPN), osteocalcin (OCN), and alkaline phosphatase (ALP) expression. The in vivo study involved 12 implants (six per group) placed in mandibular defects of two beagle dogs. After 8 weeks, histomorphometric analysis evaluated bone to implant contact (BIC) and inter-thread bone density (ITBD). Statistical analysis used Student’s t-test and two-way ANOVA for in vitro data, and Mann-Whitney U test for in vivo data.
RESULTS: Surface analysis revealed Sa values of 2.50 ± 0.27 µm for the TS group and 1.80 ± 0.06 µm for the ADD group. In vitro studies showed no significant differences in cell adhesion and proliferation between the groups (P > .05). However, gene expression patterns differed, with ADD group showing higher OPN expression (P < .001) and TS group showing higher ALP expression (P < .01). The in vivo study revealed no statistically significant differences in BIC and ITBD between the two groups (P > .05).
CONCLUSION: Surface roughness influenced osteoblast differentiation in vitro, but did not significantly affect osseointegration outcomes in vivo. Both moderately rough and rough surfaces appeared to support comparable levels of osseointegration. Larger studies are needed to confirm these findings and determine optimal implant surface characteristics.
PMID:39803382 | PMC:PMC11711448 | DOI:10.4047/jap.2024.16.6.348
J Adv Prosthodont. 2024 Dec;16(6):328-335. doi: 10.4047/jap.2024.16.6.328. Epub 2024 Dec 19.
ABSTRACT
PURPOSE: Proper tooth alignment directs occlusal forces along the long axis, supporting optimal masticatory function and periodontal health. Deviations that lead to non-axial forces are common; however, teeth with such deviations often maintain optimal health. This study aims to assess various occlusal and periodontal parameters in teeth experiencing non-axial forces to better understand the underlying reasons and mechanisms that contribute to their maintained health status.
MATERIALS AND METHODS: Fifty subjects, each with one normally aligned posterior tooth (Group A) and a malaligned contralateral tooth (Group B), were recruited for this study. Clinical assessments were conducted to measure relative occlusal load, gingival status, and alveolar bone levels in both groups. Statistical analyses were performed to compare findings between normally aligned and malaligned teeth.
RESULTS: Seventy two percent of malaligned teeth (9.33 ± 6.38%) exhibited reduced relative occlusal force compared to normally aligned teeth (12.05 ± 8.39%). No significant differences in gingival status or alveolar bone levels were observed between the two groups.
CONCLUSION: This study demonstrates that malaligned teeth can adapt to non-axial occlusal forces while preserving their structural integrity, which could imply the presence of adaptive mechanisms within the stomatognathic system. Further research is needed to differentiate the types and directions of occlusal forces and to explore the broader clinical implications of these findings across diverse populations.
PMID:39803381 | PMC:PMC11711452 | DOI:10.4047/jap.2024.16.6.328
J Adv Prosthodont. 2024 Dec;16(6):319-327. doi: 10.4047/jap.2024.16.6.319. Epub 2024 Dec 19.
ABSTRACT
PURPOSE: This study aimed to compare the accuracy of an alternative scan path with that of traditional scan paths to obtain a more accurate method for complete arch scans.
MATERIALS AND METHODS: A mandibular stone cast, including tooth preparations for the inlay, crown, and fixed prosthesis, was scanned 10 times using four different scan paths (A, B, C, and D). The scans were converted into stereolithography files, resized, and superimposed onto a control file obtained from a desktop scanner. The scan time, total surface deviation, and local deviation of the mandibular teeth were measured. One-way analysis of variance (ANOVA) and Welch ANOVA were used for statistical analyses (α = .05). The relative standard deviation and standard error of the mean were calculated to evaluate accuracy.
RESULTS: The total surface deviation differed significantly according to the scanning path despite a similar scan time. Path D had the highest accuracy and the most uniform color maps, showing minimal deformation of the digital model. Meanwhile, no significant differences were found in the local deviations in the individual tooth assessments, likely owing to issues with the superimposition method.
CONCLUSION: Among all scan paths, the scan path with the shortest distance from the starting point to the end point showed the smallest total surface deviation and the highest accuracy. No differences were observed in the deviations of specific teeth based on the scan path.
PMID:39803380 | PMC:PMC11711450 | DOI:10.4047/jap.2024.16.6.319
Addiction. 2025 Jan 12. doi: 10.1111/add.16755. Online ahead of print.
ABSTRACT
AIM: We applied the Institute of Medicine (IOM) definition of racial and ethnic disparities in healthcare to estimate disparities in alcohol-related problems. This estimation involved adjusting for drinking patterns, gender and age, with observed disparities further explained by socioeconomic status (SES). We compared results of five statistical approaches which use different methods for adjusting covariates.
DESIGN AND SETTING: We conducted analysis of the repeated cross-sectional data from the US National Alcohol Surveys (NAS) from 2000 to 2020, comparing traditional regression, rank-and-replacement, propensity score weighting, G-computation and the double-robust methods.
PARTICIPANTS: 39 239 respondents aged 18 + across five NAS surveys oversampling Black and Hispanic/Latino/a populations.
MEASUREMENTS: Our primary analysis examined the dichotomous outcomes of the three alcohol problem measures: occurrence of negative consequences, alcohol dependence (using DSM-IV criteria) and alcohol use disorder (AUD, using DSM-5 criteria). The drinking pattern variables encompassed past year total alcohol volume and measures of heavy drinking, including the number of days consuming 12+, 8-11 and 5-7 drinks.
FINDINGS: After adjusting for age, alcohol volume and heavy drinking days, statistically significantly higher prevalence of DSM-IV dependence and DSM-5 AUD were observed for Black and Hispanic men who drank in the past year compared with White men who drank. For instance, the Black-White difference in AUD prevalence ranged from 3.7% (95% confidence interval = 1.1%, 6.2%) to 4.9% (2.1%, 7.8%)-, while the HispanicWhite difference ranged from 2.3% (0.1%, 4.4%) to 3.4% (1.1%, 5.6%), using different adjustment methods. Further adjusting for SES factors only moderately explained the observed disparities. We found consistent results in the estimation of disparities across all five methods.
CONCLUSIONS: There appear to be racial and ethnic disparities in alcohol-related problems between Black and Hispanic men in the United States relative to White men after alcohol drinking patterns and age are adjusted. The findings also exhibit overall consistency across the five different methods or measurement applied.
PMID:39800864 | DOI:10.1111/add.16755
Pediatr Dermatol. 2025 Jan 12. doi: 10.1111/pde.15850. Online ahead of print.
ABSTRACT
BACKGROUND/OBJECTIVES: Anaplastic large cell lymphomas (ALCLs) present unique challenges due to their clinical and genetic heterogeneity. This study investigated the clinical characteristics of children diagnosed with systemic ALCL.
METHODS: Retrospective data from 14 pediatric patients diagnosed with systemic ALCL at Valme University Hospital were studied. Demographic, clinical, and treatment data were collected and statistically analyzed.
RESULTS: The mean age at diagnosis was 8.5 years, with a male predominance (78.6%). Cutaneous presentation occurred in 35.7% of cases, with characteristic rapidly growing subcutaneous nodules. B symptoms were present in 57.1% of patients, while 100% exhibited nodal involvement. Visceral and bone marrow involvement was observed in 71.4% and 7.1% of patients, respectively. Central nervous system (CNS) involvement was absent. Anaplastic lymphoma kinase (ALK) rearrangement was positive in all cases. Anthracycline-based chemotherapy resulted in 100% 5- and 10-year overall survival rates.
CONCLUSIONS: Systemic ALCL in children often presents with advanced-stage disease, with cutaneous involvement in a significant proportion of cases. Prompt recognition of skin lesions is vital to expedite diagnosis and treatment initiation, ultimately improving patient outcomes. This study underscores the importance of vigilance and early intervention in managing pediatric ALCL.
PMID:39800860 | DOI:10.1111/pde.15850
Aust J Rural Health. 2025 Feb;33(1):e13214. doi: 10.1111/ajr.13214.
ABSTRACT
OBJECTIVE: To measure current levels and experiences of food and water security in Walgett to guide a community-led program and to provide a baseline measure.
DESIGN: A community-led cross-sectional survey conducted in April 2022 by trained local researchers.
SETTING: Walgett, a regional town in NSW, Australia.
PARTICIPANTS: A total of 251 Aboriginal adults.
MAIN OUTCOME MEASURED: Food and water security levels and experiences were measured using the Household Food Insecurity Access Scale (HFIAS) and Household Water InSecurity Experiences (HWISE) Scale. The relationship between food and water insecurity was determined through linear regression analysis.
RESULTS: Almost half of the respondents experienced food insecurity (46%) or water insecurity (44%) in the last 12 months. Most participants attributed food insecurity to difficulties with food affordability (71%) and availability (63%). More than four in five participants reported relying on purchased or donated bottled water due to main water source interruption (83%) or quality concerns (86%). Water insecurity was associated with food insecurity; HFIAS score increased by 0.43 points for every point higher on the HWISE scale.
CONCLUSIONS: This study is the first to measure levels and experiences of food and water security in an Aboriginal community in Australia using validated tools. The results highlight the interconnectedness of food and water insecurity and provide evidence of levels far higher than Australian national level estimates and comparable to low- and middle-income countries. A holistic government response alongside community-led efforts are needed to increasefood and water security to improve health and well-being in remote Aboriginal communities.
PMID:39800851 | DOI:10.1111/ajr.13214