The assessment of seismic hazard and risk requires a catalogue of earthquakes (both historical and recorded during the instrumental era), where the location and magnitude of events affecting the study area are reported. Mw is commonly used for this aim, but it is a static measure of earthquake size and it cannot capture the full extent of earthquake source complexity. Other magnitude scales connected to the rupture kinematics and dynamics should complement Mw in hazard studies, but this required efforts in re-analyzing catalogs of intensity data. To this aim, we developed a high-frequency magnitude (m3Hz) estimated using a random or log-averaged horizontal component of ground motion from frequencies above the highest corner frequency of the earthquake source spectrum. Here, we apply the novel procedure to the intensity data from the Parametric Catalogue of Italian Earthquakes (CPTI15). We derive m3Hz for 1,951 earthquakes (from 1117 to 2020). The new earthquake catalog is defined by the acronym ICEM. For all earthquakes a quality index based on the variance-to-mean ratio (VMR) has been assigned.
Exoskeletons have the potential to augment balance and decrease fall risk. However, existing balance-augmenting wearable robotic controllers have only been tested in single planes of motion during either standing or walking. Thus, it is unclear whether a single control scheme can generalize across perturbations with varying spatial properties or from standing to walking. Inspired by the nervous system's generalizable balance control strategy across perturbation types and conditions, we propose a novel torque control framework that modulates multi-joint reactive torques based on center of mass (CoM) deviation. We evaluated the generalizability of our delayed CoM feedback controller to predict multi-joint torque responses to perturbations of varying magnitudes, directions, and across movement contexts. In nine healthy young adults, we tested the ability of a delayed CoM feedback scheme to predict multi-joint torque responses to (1) ramp-and-hold support surface perturbations at three magnitudes in 8 directions, (2) a continuous sinusoidal movement, resulting in a cyclical movement of the CoM with similar periodic features as walking, and (3) a sinusoidal motion with random perturbations superimposed to mimic perturbations during cyclic tasks. We trained the model on single ramp-and-hold conditions and evaluated its ability to generalize across directions, magnitudes, movement contexts, and subjects. The delayed CoM feedback controller trained on a single ramp-and-hold condition generalized to all ramp-and-hold perturbations for all joints, predicting the joint torques for perturbations of varying directions and magnitudes with high fidelity (average R2 > 0.84 and RMSE < 0.08 Nm/kg). However, generalization from standing to cyclic movement only occurred for hip and knee flexion. The CoM feedback parameters from ramp-and-hold perturbations generalized to the continuous sinusoidal movement (cyclic movement) and the sinusoidal movement with superimposed perturbations (unexpected perturbations) for hip flexion and knee flexion (average R²>0.70 and RMSE < 0.13 Nm/kg), but not for ankle plantarflexion and hip adduction (R²>0.20 and RMSE < 0.22 Nm/kg). Our findings show that a physiologically-inspired CoM feedback controller can robustly predict balance-correcting torques appropriate for driving a hip or knee wearable robotic device during standing and movement, and an ankle device during standing only. The goodness-of-fit of joint torque is comparable to top machine learning algorithms, yet requires orders of magnitude less training data, enabling rapid implementation to reduce fall risk.
Small differences between females and males in cognitive abilities have been consistently reported, but the factors underlying these sex differences remain unclear. Social and cultural factors are thought to play a key role, but studies on this topic have been inconclusive. Examination of genetic factors may shed some light on the mechanisms underlying cognitive sex differences. Using data from the Philadelphia Neurodevelopmental Cohort, a large, general population sample of individuals aged 8 to 21 years old (N = 4,694), we tested for sex differences in the genetic factors (i.e., Gene × Sex interactions) underlying cognitive ability. Participants completed the Penn Computerized Neurocognitive Battery, which consists of 14 tests designed to capture accuracy and speed in five domains: 1) executive function (abstraction and mental flexibility, attention, working memory), 2) episodic memory (verbal, facial, spatial), 3) complex cognition (verbal reasoning, nonverbal reasoning, spatial processing), 4) social cognition (emotion identification, emotion differentiation, age differentiation), and 5) speed (motor, sensorimotor). Composite domain scores were derived using confirmatory factor analysis, and general accuracy (g) and speed (gs) using principal component analysis. Small sex differences were observed on most cognitive measures (standardized mean difference (SMD) = 0.061-0.182). Males showed significantly higher genetic variance and lower environmental variance in executive (female σ2g = 0.301 v. male σ2g = 0.598, p = 0.001, female σ2e = 0.243 v. male σ2e = 0.024, p = 0.007), and complex (female σ2g = 0.291 v. male σ2g = 0.610, p = 0.001, female σ2e = 0.259 v. male σ2e = 0.023, p = 0.006) accuracy. Females showed significantly higher genetic and lower environmental variance on complex (female σ2g = 0.575 v. male σ2g = 0.135, p = 0.009, female σ2e = 0.222 v. male σ2e = 0.641, p = 0.012) and social (female σ2g = 0.589 v. male σ2g = 0.129, p = 0.009, female σ2e = 0.236 v. male σ2e = 0.672, p = 0.012) speed. Genetic correlations between females and males were not significantly different from 1 on any cognitive measure. Altogether, our results suggest that while the same genetic factors influence cognition in females and males, the magnitude of effect of these genetic factors differs. We observed small differences between females and males on most cognitive measures, as well as sex differences in heritability on some measures. Future studies are needed to delineate how environmental, genetic, and other biological factors jointly influence cognition. Small differences in cognition between females and males have been consistently reported across abilities, cultures, and decades. However, the factors underlying these cognitive sex differences remain unclear. Social and cultural factors are thought to play a key role, but there has been less examination of potential genetic factors. We tested for sex differences in the genetic factors underlying a range of cognitive abilities in a large, general population sample of individuals aged 8 to 21 years old. Small sex differences were observed across most cognitive domains, with female advantages in memory and social cognition, and male advantages in executive and complex cognition. Moreover, differences between females and males in the magnitude of genetic factors underlying cognition were observed for executive, complex, and social cognition, suggesting that some cognitive sex differences are partly driven by sex differences in underlying genetic factors. Most research on the underlying causes of sex differences in cognitive abilities has focused on social and cultural factors, but our findings highlight the importance of considering genetic factors, as well as how these genetic factors act jointly with social and cultural factors to impact cognition. Given the impact of cognition on social, emotional, and health outcomes, further work is needed to delineate the interplay between environmental and genetic factors that underlie cognitive sex differences.
The aim of this study was to quantify postoperative regional condylar remodeling and its role in skeletal relapse after bimaxillary surgery using CBCT scans. 40 patients with mandibular hypoplasia who underwent bimaxillary surgery were analyzed. CBCT scans were acquired preoperatively, one-week postoperatively and two-years postoperatively. Deep-learning based 3D regional condylar volume analysis was performed and skeletal relapse was quantified through voxel-based matching. The maxilla and mandible were advanced by a mean of 2.87 mm and 8.37 mm, respectively, with a corresponding mean sagittal relapse of .57 mm and 1.62 mm. Postoperative volume loss was observed in 78% of condyles (mean loss = 242 mm3; 16%). Linear regression analyses identified age, gender and magnitude of advancement as significant predictors of relapse. Condylar volume loss significantly mediated the relationship between surgical advancement and skeletal relapse, accounting for 29.1% of the total effect. No statistically significant correlation was found between specific condylar regional sub-volumes and directions of surgical movement. These findings underline the importance of condylar volume stability in predicting long-term skeletal stability among patients who undergo bimaxillary surgery with large advancements. The results also indicated that condylar remodeling is a generalized phenomenon related to surgical movements rather than a localized process restricted to specific anatomical regions of condyles.
This work introduces the Hierarchical Neighborhood of Atoms (HNA) partitioning, a recursive classification of chemically equivalent atoms that enables ultrafast computation of exact symmetry-corrected atomic correspondence and RMSD for molecular conformers. By decomposing the assignment problem hierarchically, the algorithm reduces the number of evaluated combinations from the product of branch possibilities to their sum, yielding reductions of up to 16 orders of magnitude for systems such as myoglobin. Topology-unaware approaches based on linear assignment produce chemically invalid atomic correspondences in over 89% of protein conformer pairs, while topology-aware graph isomorphism methods time out on 51-66% of biologically relevant molecules. In contrast, the proposed method achieves 100% topologically correct assignments without timeouts across all 1.4 million pairs tested, with millisecond-scale mean execution times (1.3-3.8 ms for the CCD data set, 2.7-16.5 ms for the BIRD data set) and 11-42× speedups over polynomial-time methods on protein conformer ensembles. Beyond RMSD, the HNA framework can be used for symmetry-consistent comparison of atomic properties, canonical atom labeling, and force field parametrization.
We demonstrate that anisotropic magnetoresistance (AMR) in metal-ferromagnet bilayers can arise entirely from interfacial scattering, without invoking bulk spin Hall or inverse spin Hall effects. Using a minimal boundary-value formulation of the Boltzmann equation with interfacial exchange and Rashba spin-orbit coupling, we identify a resonant spin-filtering mechanism whereby one spin projection becomes immune to backscattering at a clean interface. This mechanism quantitatively reproduces the magnitude (Δρ/ρ∼10^{-4}-10^{-3}), thickness dependence, and angular symmetry conventionally attributed to spin Hall magnetoresistance in Pt/YIG. Crucially, the maximal AMR scales linearly in the smaller of the interfacial exchange or spin-orbit coupling: a parametric behavior forbidden in any spin-Hall-based theory. The effect is intrinsically sensitive to interface quality, charge transfer, and disorder, providing clear signatures that can be experimentally tested. Our results establish interfacial spin filtering as an essential and previously overlooked origin of AMR in metal-ferromagnet heterostructures, calling for a fundamental reassessment of magnetotransport mechanisms in spin-orbit-coupled metals.
The comparative superiority among the triglyceride-glucose (TyG) index and its obesity-related composite indicators in identifying hypertension and carotid atherosclerosis (CAS) remains unknown. This study aims to evaluate and compare the discriminative ability of these indices in a large-scale population to identify the optimal marker for cardiovascular risk assessment. This cross-sectional study included 154,873 participants who underwent routine physical examinations and carotid ultrasonography. Binary logistic regression, restricted cubic spline (RCS), receiver operating characteristic (ROC) analyses, and mediation analyses were used to evaluate the associations of TyG, TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), and TyG-body mass index (TyG-BMI) with hypertension and CAS. The mean age of participants was 45.7 ± 12.5 years, with 42.1% being female and 91.0% being married. A total of 16,235(10.5%) participants had hypertension, and 81,337 (52.5%) had CAS. Comparing the highest to the lowest quartile, TyG-WHtR demonstrated the strongest association with hypertension (OR = 8.644, 95% CI: 7.927-9.426) and CAS (OR = 2.173, 95% CI: 2.086-2.263). RCS analyses revealed monotonic increases for hypertension and complex nonlinear patterns for CAS. Stratified analyses revealed distinct phenotypic signatures. For hypertension, risk magnitudes were markedly amplified in younger adults (≤ 60 years) (P for interaction < 0.001 for all indices). For CAS, a significant interaction between sex and the indices was observed (P for interaction < 0.05 for TyG, TyG-WHtR, and TyG-BMI): TyG-WHtR exhibited the strongest association in women (OR = 1.504), whereas in men, the isolated TyG index was inversely associated with CAS, and only TyG-BMI showed a significant positive association (OR = 1.091). Mediation analyses revealed that obesity indicators (WHtR, BMI) demonstrated substantial direct associations with on outcomes, with TyG providing negligible or partial mediation, which may account for the stronger associations observed with composite indices. TyG-obesity composite indices are strongly associated with hypertension and CAS, particularly in younger adults. TyG-WHtR is optimal for women and the general population, while TyG-BMI is superior for men. These easily accessible and cost-effective metrics can serve as practical tools for early cardiovascular risk screening in primary care. Implementing such age-targeted and sex-specific risk stratification could facilitate more precise and timely preventive interventions.
The coupled normal-mode model is a fundamental tool for simulating underwater sound propagation in range-dependent environments, but its cost is high because the modal Sturm-Liouville problem must be solved repeatedly for every segment. This paper proposes an accelerated coupled normal-mode model based on physics-informed neural networks. Empirical orthogonal function analysis compresses the input sound-speed profiles, and a dual-branch physics-informed neural network predicts the horizontal wavenumbers and modal depth functions. The training loss combines a data-driven term with physics constraints from the modal equation and boundary conditions. On the 2015 Shallow Water Sound Fluctuation experiment dataset, the surrogate reaches a mode-averaged relative error of 1.52 × 10-3% for the wavenumbers and 6.7% for the depth functions, one orders of magnitude smaller than first-order modal perturbation theory, and cuts the online modal-solving time by 85% relative to a finite difference solver. The reconstructed field is evaluated against KRAKENC for idealized internal solitary wave environments, measured 2015 Shallow Water Sound Fluctuation experiment sound-speed sections, and piecewise-linear sloping bathymetry. Transmission loss errors stay within 3 dB and the complex pressure normalized mean squared error remains on the order of 10-5, with comparable accuracy in the measured and sloping environments. The framework offers practical accuracy and computational efficiency for shallow water environments with combined sound-speed and bathymetric range dependence.
We propose a novel coherent freeze-out mechanism where a weakly interacting massive particle (WIMP) is quadratically coupled to a light axionlike particle (ALP). Although the coupling is too feeble to thermalize the ALP, coherent forward scattering induces medium-dependent mass shifts that significantly modify both WIMP freeze-out and ALP misalignment dynamics. The symmetry of the ALP potential is broken at high temperatures and restored through either a first-order transition or a crossover. In the former, WIMPs alone compose dark matter with annihilation cross sections enhanced by up to 3 orders of magnitude relative to the standard scenario; in the latter, a Planck-suppressed coupling naturally yields an ALP abundance of the order of the observed dark matter density, largely independent of its initial displacement and mass.
We evaluated the effectiveness, adherence, and safety of preservative-free (PF) lubricants in adults with dry eye disease (DED) under real-world clinical conditions. The ENRICHED-PF trial (NCT06162442) was a single-arm, prospective interventional study conducted in Cali, Colombia. A total of 120 adults with mild-to-moderate DED initiated PF propylene glycol 0.3% / polyethylene glycol 0.4% drops for six months. Longitudinal analyses were performed using linear mixed-effects models, with multiple imputation applied under a Missing at Random assumption to handle missing data. At baseline, the median Ocular Surface Disease Index (OSDI) score was 31.2 [19.2-47.4]. Longitudinal model-based estimates showed an OSDI estimated marginal mean (EMM) of 33.9 at baseline, 23.1 at 3 months, and 16.8 at 6 months in the mITT population, corresponding to an estimated change of - 17.1 points at month six (p < 0.001), with 65.4% of the modified intention-to-treat (mITT) population and 58% of the per-protocol (PP) population achieving a clinically meaningful response (≥ 10-point improvement). Tear break-up time increased and corneal staining scores decreased (both p < 0.001), while Schirmer I values remained stable. Additionally, NEI VFQ-25 composite scores improved by 8.9±3.1 points (p<0.001). These findings suggest clinically meaningful improvements in symptoms, tear film stability, and ocular surface integrity over time, which were associated with treatment using PF lubricants. However, given the single-arm design, the absence of a comparator group, and loss to follow-up during the study period, the magnitude of these effects should be interpreted with caution and confirmed in controlled comparative studies.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT06162442.
Individual microbes often respond differently to the same environment, yet the magnitude of such niche variation inherent to individuals remains unresolved and is anticipated to differ substantially from community-level average responses. We conducted metagenomic binning on monthly time-series soil samples from three sites across seasonal cycles. By considering 440,571 genes as dimensions of the fundamental individualised niche (FIN), we traced FIN trajectories of archaea and bacteria during warming, cooling, and turning periods. We found that neither mean temperature nor temperature difference had a significant effect on FIN breadth or overlap. Instead, we discovered a temporally constant, stepwise gradient of niche differentiation across taxonomic categories. At the interdomain level (Archaea vs. Bacteria), niche overlap is approximately 25%, rising to ~40% at the interphylum level and ~60% at the interorder level. This discontinuous gradient likely marks the limit boundaries of niche variation, is closely linked to functional synergy within FINs, and provides a preliminary comparable ecological carrying capacity for each niche step, particularly regarding the interdomain balance.
Immune responses elicited by natural infection of the coronavirus SARS-CoV-2 (COVID-19) show significant heterogeneity in the magnitude and quality of memory T and B cell responses. However, little is known about the contributing factors. In this study, we investigated the early immune factors that contribute to this variability using RNA-seq, targeted proteomics, and flow cytometry analyses. Specifically, we sought to investigate associations between early immune responses and SARS-CoV-2 memory immunity in a longitudinal cohort of 46 individuals hospitalized for COVID-19 from May 2020 to March 2021. These participants returned for follow-up visits up to one-year post-hospitalization where we characterized antibody titers, antibody neutralization, antibody durability, and cellular memory T and B cell responses with multiple assays. Additionally, using integration analysis of Omic measurements, we identified common genes, proteins, and cellular pathways associated with differential memory response outcomes. Our data suggests that high levels of inflammatory proteins, and co-stimulatory molecules during the early stages of COVID-19 lead to enhanced memory T and B cell responses and improved durability. Alternatively, molecules that have a negative effect on dendritic cell maturation including TNFSF11 and FLT3LG correlated with suboptimal memory immune responses. Importantly, we were able to identify early markers that are positively and negatively associated with durable antibody responses in infected participants. This study provides a unique and thorough examination of both innate and memory immunity in the same patients over time, offering valuable insights into the long-term durability of SARS-CoV-2 immunity.
The energy landscapes and electronic properties of non-polar and polar nanofilms of silicon carbide are studied using periodic hybrid density functional calculations. Relative energies and electronic properties are reported as a function of film thickness for a set of structures derived from those of wurtzite, zinc blende and graphite. The energy landscape of the films is complex with pronounced nano-polymorphism. Across polar films different mechanisms in different cases remove or reduce the dipole moment, including charge transfer and phase transitions to the graphitic-like structures which are stable for the thinnest films. Graphitic structures are lowest in energy for the thinnest films. For ten layers non-polar films - zinc blende (110) and wurtzite (101bar0 ) - with tetrahedrally-coordinated Si and C in Si3C3 rings in chair conformations - are lowest in energy, followed, ∼0.1 eV per formula unit higher in energy, by a body-centred tetragonal structure containing Si3C3 rings in boat conformations. In the planar graphene structure the energy of the anti-site defect CSi-SiC (∼0.3 eV)) is more than an order of magnitude lower than in the bulk, suggesting a much higher degree of disorder in such films. One staggered graphitic-like structure with ABC stacking, a local minimum in the energy landscape, is of particular interest, since it lies in a regime of uncompensated polarity and possesses a direct band gap that decreases linearly with film thickness., from ∼2 eV (3 layers) to zero (6 layers).
Genotoxic anticancer therapies exploit the heightened DNA replication stress of cancer cells. Members of the phosphoinositide-3-kinase-related kinase (PIKK) family, including ATR, ATM and DNA-PKcs, orchestrate the DNA damage response at stalled and broken replication forks, triggering complex signaling cascades that dictate cell fate. p53 plays a pivotal role in regulating the processes of cell cycle, DNA repair and programmed cell death, although p53-independent regulatory mechanisms are also evident. Genotoxic drugs often induce therapy-induced senescence, a state of dynamic and reversible cytostasis that promotes drug resistance and unfavorable patient outcomes. Conversely, severe replication stress culminates in DNA replication catastrophe, a manifestation of irreversible fork collapse with extensive single-stranded DNA accumulation that ultimately results in cell death. Therefore, the magnitude of DNA replication damage and engaged signal transduction pathways determine the outcome of genotoxic therapy. Understanding the molecular basis of the replication stress response that drives therapy-induced senescence versus cell death has far-reaching implications for enhancing the cytotoxic efficacy of anticancer regimens. Here we review the mechanisms of the DNA replication stress response, focusing on pharmacological interventions designed to shift the balance from survival to cell death.
We investigated how causal attributions-that is, individuals' beliefs about what caused their obesity-are associated with weight loss in a digital lifestyle intervention. Data were collected from Healthy Weight Coaching, a 12-month real-world online intervention. Weight and height were self-reported. Body mass index (BMI) was calculated using interpolated weights at 3, 6, 9, and 12 months. At baseline, participants completed an eight-item questionnaire on causal attributions, rating each as playing no role, some role, or a major role. TwoStep cluster analysis grouped individuals with similar response profiles. Data were available for 1834 participants (1524 83.1% women, median age 52 years, median BMI 39.1 kg/m2). Participants most frequently attributed obesity to unhealthy dietary habits and lack of physical activity, whereas genetics, family lifestyle habits, and medication were least endorsed. Attributing obesity to stress (somewhat, standardized B=0.156 95% CI, 0.051-0.262; very much, B=0.204 95% CI, 0.100-0.307), fatigue (very much, B=0.154 95% CI, 0.073-0.235), adversities in life (somewhat, B=0.112 95% CI, 0.041-0.184; very much, B=0.100 95% CI, 0.024-0.176), or medication (somewhat, B=0.089 95% CI, 0.022-0.155; very much, B=0.108 95% CI, 0.025-0.192) were associated with lower weight loss compared with those not endorsing these attributions. However, only stress ("very much") reached a small effect size according to Cohen's criteria, whereas the remaining associations were negligible in magnitude despite statistical significance. Cluster analysis revealed four clusters. Compared to those Behaviourally focused, particularly endorsing dietary habits and physical activity, all other clusters showed higher endorsement of stress, fatigue, and adversities in life, with a cluster labelled Multifactorial fully endorsing all eight items. Relative to Behaviourally focused, all other clusters had lower odds of 5% weight loss and lost less weight (Broad lifestyle oriented, B=0.104 95% CI, 0.032-0.177, p=0.004; Psychologically burdened, B=0.144 95% CI, 0.063-0.225, p<0.001; Multifactorial, B=0.222 95% CI, 0.136-0.308, p<0.001). Only the Multifactorial cluster reached a small effect size. Strong endorsement of stress as a cause of obesity and membership in the Multifactorial cluster were associated with less favourable weight loss outcomes. However, effect sizes were small, suggesting limited standalone impact but potential relevance within broader behavioural and psychological treatment contexts.
Nitrogen management and harvest timing are critical determinants of fresh bean (Phaseolus vulgaris L.) pod quality; however, their combined effects on morphological, colorimetric and biochemical characteristics during pod development remain insufficiently characterized. This study evaluated the effects of four nitrogen top-dressing fertilizers (ammonium sulfate [AS], slow-release fertilizer [SRF], nitropower [NP], and urea) and five pod development stages (BBCH 72-81) on pod morphology, color parameters, antioxidant capacity, phenolic compounds, flavonoids, and protein content under field conditions. Nitrogen top-dressing significantly prolonged days to 50% flowering and pod setting times, with the latest flowering observed under urea treatment compared to basal fertilization. Pod length and width increased with advancing development stages, while pod water content declined from early stages to physiological maturity. Colorimetric analysis revealed a marked increase in lightness (L*), yellowness (b*) and chroma values with maturation, accompanied by a decrease in hue angle, indicating reduction in greenness and increase in yellowness. Antioxidant capacity exhibited a stage-dependent pattern, with lower values at intermediate stages and higher values at late development stages, particularly under urea treatment. Total phenolic, flavonoid and protein content increased significantly at the final development stage. Strong positive correlations were detected between antioxidant capacity, phenolic, flavonoid and protein content, whereas pod water content showed significant negative correlations with these quality traits. Overall, the results demonstrate that development stage plays a key role in determining pod quality, while nitrogen source influences the magnitude of these responses. Late harvest stages (BBCH 79-81), together with stable nitrogen sources such as SRF and AS, could be employed to improve nutritional and antioxidant properties of fresh bean pods.
Although developmental language delays affect approximately 10% of children in the general population, the neurodevelopmental mechanisms that support normative language acquisition, and atypicalities that may predict later language delay, across the first year of life are poorly understood. Here, resting-state fMRI data from the Baby Connectome Project was used to first evaluate age-related changes in language network functional connectivity and alterations associated with suboptimal language development. Additionally, a data-driven machine learning algorithm was used to partition our sample into three groups who showed Typical, Advanced, or Lagging trajectories of language development. These groups reliably differed on several assessments of language ability during infancy and toddlerhood. Using a priori brain regions involved in adult language processing, a seed-based functional connectivity analysis showed broad age-related increases in functional synchrony and specialization throughout the infant language network. Additionally, the Lagging group showed several distinct patterns of functional connectivity with language regions. Importantly, the magnitude of connectivity differences consistently predicted later language scores at two-year outcome across several different language assessments. These findings add to our understanding of normative neurodevelopmental patterns underlying language acquisition, and identify several potential biomarkers associated with language heterogeneity that could serve as future targets to inform diagnoses and clinical interventions.
It remains unclear whether trimming sharp edges from scan body library files improves automatching accuracy, what magnitude of trimming is optimal, and whether any benefits are consistent across different scan body geometries. The purpose of this in vitro study was to evaluate the effect of scan body geometry and the edge trimming of scan body library files on the accuracy of matching between intraoral scans and library files. Two scan body geometries (angular and rounded) were evaluated with 3 library file designs: unmodified (U), 0.1-mm edge removal (E01), and 0.3-mm edge removal (E03). Ten scan bodies per geometry were scanned using a desktop scanner and an intraoral scanner. Library files were matched to the intraoral scan data in a computer-aided design software program to generate implant positions that were compared with reference positions derived from desktop scans. Deviations were measured as the linear distance between implant apices, angular difference between long axes, and root mean square surface deviation (n=10 per group). The data were analyzed by using mixed 2-way analysis of variance (α=.05). Edge trimming improved accuracy. For the angular geometry, linear deviation decreased from 118.4 ±21.7 µm (U) to 93.6 ±20.9 µm (E03; P=.001), angular deviation decreased from 0.33 ±0.12 degrees (U) to 0.24 ±0.11 degrees (E03; P=.043), and surface deviation decreased from 56.4 ±4.8 µm (U) to 44.0 ±6.9 µm (E03; P<.001). For the rounded geometry, linear deviation decreased from 91.2 ±12.1 µm (U) to 73.6 ±11.0 µm (E03; P=.020), and surface deviation decreased from 51.7 ±4.9 µm (U) to 39.1 ±5.1 µm (E03; P<.001). The rounded scan body showed lower linear deviation than the angular across all library designs (all P<.05). Edge removal in library files and the use of simpler rounded scan body geometry enhanced the accuracy of library automatching between intraoral implant scans and scan body library files.
Chlorobenzenediols are a class of emerging aromatic disinfection byproducts (DBPs) that were identified in chlor(am)inated drinking water and exhibit great developmental toxicity. However, data on their cytotoxicity are lacking. This study updated their quantitative method, cytotoxicity, and quantitative structure-activity relationship (QSAR) modeling. The limits of quantification (LOQs) for chlorobenzenediols were 0.1-1 ng/L, which are 10-100 times lower than previously reported values (1-50 ng/L), enabling the quantification of chlorobenzenediols at trace levels. The LC50 values of the 15 chlorobenzenediols for CHO cells ranged from 6.1 to 1742.0 μM, with a median value of 19.0 μM, suggesting that their overall cytotoxicity was lower than that of chloroketones (median: 6.6 μM), but was higher than chloroacetaldehydes (median: 29.2 μM), chlorobenzoquinones (median: 31.1 μM), chloronitrophenols (median: 67.3 μM), chloroacetonitriles (median: 68.3 μM), chlorophenols (median: 244 μM), chloronitromethanes (median: 529 μM), chlorohydroxybenzonitriles (mean: 558 μM), chlorohydroxybenzoic acids (median: 447 μM), chloroacetamides (median: 1920 μM), chloroacetic acids (median: 2400 μM), and trichloromethane (9620 μM). 2,5-Dichlorobenzene-1,4-diol and 2‑chloro-1,4-benzenediol were the key drivers in drinking water leveraging the TIC-Tox method. The QSAR model revealed that the cytotoxicity of chlorobenzenediols was closely related to molecular parameters, especially EHOMO. The cytotoxicity of chlorobenzenediols is enhanced when hydroxyl group is substituted at the 2‑ or 4‑position of the benzene ring, but is reduced when a chlorine atom is located at the 2‑position. Although chlorobenzenediols are a class of highly cytotoxic aromatic DBPs compared to other DBPs, this study found their actual concentrations in drinking water to be orders of magnitude lower than their LC50 values (typically by a factor of 106 to 109), indicating a low probability of significant short-term health risks to the population.
Transcranial direct current stimulation (tDCS) has been proposed to modulate neural circuits involved in reward processing. However, the optimal electrode placement and area of interest for maximum electrical field strength remain unclear. This pre-registered systematic review and meta-analysis aimed to synthesize current evidence on the modulation of reward processing by tDCS and to relate behavioral outcomes to modeled electric field distributions in healthy subjects. We systematically analyzed studies combining tDCS with reward-processing tasks in healthy subjects. Effect sizes were computed for each behavioral outcome. In addition, the magnitude and normal component of the electric field were calculated. For the normal component, positive values indicate an inward current (entering the cortex), whereas negative values indicate an outward current (exiting the cortex). Finally, behavioral outcomes were correlated with the magnitude and normal component of the electric field, yielding the performance-electric field index (PEI). For the normal component of the electrical field we found positive correlations in the anterior parts of gyri in the fronto-to-parietal cortex, with a maximum PEI of 0.482 (p < .00001). Negative values were observed in the posterior banks of gyri in the same cortical region, with a minimum PEI of -0.477 (p < .00001). Only marginal associations were found for electric field strength in the right anterior prefrontal cortex (PEI=0.228; p = 0.035). Anodal stimulation over the right prefrontal cortex with a cathode over the right parietal cortex was associated with enhanced reward processing performance in healthy subjects.