Ongoing Laboratory Performance Study on Chemical Analysis of Hydrophobic and Hydrophilic Compounds in Three Aquatic Passive Samplers.

The quality of chemical analysis is an important aspect of passive sampling-based environmental assessments. The present study reports on a proficiency testing program for the chemical analysis of hydrophobic organic compounds in silicone and low-density polyethylene (LDPE) passive samplers and hydrophilic compounds in polar organic chemical integrative samplers. The median between-laboratory coefficients of variation (CVs) of hydrophobic compound concentrations in the polymer phase were 33% (silicone) and 38% (LDPE), similar to the CVs obtained in four earlier rounds of this program. The median CV over all rounds was 32%. Much higher variabilities were observed for hydrophilic compound concentrations in the sorbent: 50% for the untransformed data and a factor of 1.6 after log transformation. Limiting the data to the best performing laboratories did not result in less variability. Data quality for hydrophilic compounds was only weakly related to the use of structurally identical internal standards and was unrelated to the choice of extraction solvent and extraction time. Standard deviations of the aqueous concentration estimates for hydrophobic compound sampling by the best performing laboratories were 0.21 log units for silicone and 0.27 log units for LDPE (factors of 1.6 to 1.9). The implications are that proficiency testing programs may give more realistic estimates of uncertainties in chemical analysis than within-laboratory quality control programs and that these high uncertainties should be taken into account in environmental assessments.

A neurofunctional signature of subjective disgust generalizes to oral distaste and socio-moral contexts.

While disgust originates in the hard-wired mammalian distaste response, the conscious experience of disgust in humans strongly depends on subjective appraisal and may even extend to socio-moral contexts. Here, in a series of studies, we combined functional magnetic resonance imaging with machine-learning-based predictive modelling to establish a comprehensive neurobiological model of subjective disgust. The developed neurofunctional signature accurately predicted momentary self-reported subjective disgust across discovery (n = 78) and pre-registered validation (n = 30) cohorts and generalized across core disgust (n = 34 and n = 26), gustatory distaste (n = 30) and socio-moral (unfair offers; n = 43) contexts. Disgust experience was encoded in distributed cortical and subcortical systems, and exhibited distinct and shared neural representations with subjective fear or negative affect in interoceptive-emotional awareness and conscious appraisal systems, while the signatures most accurately predicted the respective target experience. We provide an accurate functional magnetic resonance imaging signature for disgust with a high potential to resolve ongoing evolutionary debates.

Sex differences in brain excitability revealed by concurrent iTBS/fNIRS.

Sex differences have been claimed an imperative factor in the optimization of psychiatric treatments. Intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation, is a promising non-invasive treatment option. Here, we investigated whether the real-time neural response to iTBS differs between men and women, and which mechanisms may mediate these differences. To this end, we capitalized on a concurrent iTBS/functional near-infrared spectroscopy setup over the left dorsolateral prefrontal cortex, a common clinical target, to test our assumptions. In a series of experiments, we show (1) a biological sex difference in absolute hemoglobin concentrations in the left dorsolateral prefrontal cortex in healthy participants; (2) that this sex difference is amplified by iTBS but not by cognitive tasks; and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity. These results inform future stimulation treatment optimizations towards precision psychiatry.

Computer-Aided Diagnosis of Maxillary Sinus Anomalies: Validation and Clinical Correlation.

OBJECTIVE: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. METHODS: This study uses Hamburg City Health Study (HCHS) a large, prospective, long-term, population-based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C-reactive protein, allergies). RESULTS: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. CONCLUSION: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Association between Medicaid Expansion and Cutaneous Melanoma Diagnosis and Outcomes: Does Where You Live Make a Difference?

BACKGROUND: Early detection and standardized treatment are crucial for enhancing outcomes for patients with cutaneous melanoma, the commonly diagnosed skin cancer. However, access to quality health care services remains a critical barrier for many patients, particularly the uninsured. Whereas Medicaid expansion (ME) has had a positive impact on some cancers, its specific influence on cutaneous melanoma remains understudied. METHODS: The National Cancer Database identified 87,512 patients 40-64 years of age with a diagnosis of non-metastatic cutaneous melanoma between 2004 and 2017. In this study, patient demographics, disease characteristics, and treatment variables were analyzed, and ME status was determined based on state policies. Standard univariate statistics were used to compare patients with a diagnosis of non-metastatic cutaneous melanoma between ME and non-ME states. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between ME and non-ME states. Multivariable Cox regression models were used to examine associations with OS. RESULTS: Overall, 28.6 % (n = 25,031) of the overall cohort was in ME states. The patients in ME states were more likely to be insured, live in neighborhoods with higher median income quartiles, receive treatment at academic/research cancer centers, have lower stages of disease, and receive surgery than the patients in non-ME states. Kaplan-Meier analysis found enhanced 5-year OS for the patients in ME states across all stages. Cox regression showed improved survival in ME states for stage II (hazard ratio [HR], 0.84) and stage III (HR, 0.75) melanoma. CONCLUSIONS: This study underscores the positive association between ME and improved diagnosis, treatment, and outcomes for patients with non-metastatic cutaneous melanoma. These findings advocate for continued efforts to enhance health care accessibility for vulnerable populations.

Patterns of neural activity in response to threatening faces are predictive of autistic traits: modulatory effects of oxytocin receptor genotype.

Autistic individuals generally demonstrate impaired emotion recognition but it is unclear whether effects are emotion-specific or influenced by oxytocin receptor (OXTR) genotype. Here we implemented a dimensional approach using an implicit emotion recognition task together with functional MRI in a large cohort of neurotypical adult participants (N = 255, male = 131, aged 17-29 years) to establish associations between autistic traits and neural and behavioral responses to specific face emotions, together with modulatory effects of OXTR genotype. A searchlight-based multivariate pattern analysis (MVPA) revealed an extensive network of frontal, basal ganglia, cingulate and limbic regions exhibiting significant predictability for autistic traits from patterns of responses to angry relative to neutral expression faces. Functional connectivity analyses revealed a genotype interaction (OXTR SNPs rs2254298, rs2268491) for coupling between the orbitofrontal cortex and mid-cingulate during angry expression processing, with a negative association between coupling and autistic traits in the risk-allele group and a positive one in the non-risk allele group. Overall, results indicate extensive emotion-specific associations primarily between patterns of neural responses to angry faces and autistic traits in regions processing motivation, reward and salience but not in early visual processing. Functional connections between these identified regions were not only associated with autistic traits but also influenced by OXTR genotype. Thus, altered patterns of neural responses to threatening faces may be a potential biomarker for autistic symptoms although modulatory influences of OXTR genotype need to be taken into account.

Procedural performance and outcome after pulsed field ablation for pulmonary vein isolation: comparison with a reference radiofrequency database.

Aims: Pulsed field ablation (PFA) is a promising ablation technique for pulmonary vein isolation (PVI) with appealing advantages over radiofrequency (RF) including speed, tissue selectivity, and the promise of enhanced durability. In this study, we determine the procedural performance, efficacy, safety, and durability of PFA and compare its performance with a dataset of optimized RF ablation. Methods and results: After propensity score matching, we compared 161 patients who received optimized RF-guided PVI in the PowerPlus study (CLOSE protocol) with 161 patients undergoing PFA-guided PVI for paroxysmal or persistent atrial fibrillation (AF; pentaspline basket catheter). The median age was 65 years with 78% paroxysmal AF in the PFA group (comparable characteristics in the RF group). Pulsed field ablation-guided PVI was obtained in all patients with a procedure time of 47 min (vs. 71 min in RF, P < 0.0001) and a fluoroscopy time of 15 min (vs. 11 min in RF, P < 0.0001). One serious adverse event [transient ischaemic attack] occurred in a patient with thrombocytosis (0.6 vs. 0% in RF). During the 6-month follow-up, 24 and 27 patients experienced a recurrence with 20 and 11 repeat procedures in the PFA and the RF groups, respectively (P = 0.6 and 0.09). High-density mapping revealed a status of 4 isolated veins in 7/20 patients in the PFA group and in 2/11 patients in the RF group (35 vs. 18%, P = 0.3). Conclusion: Pulsed field ablation fulfils the promise of offering a short and safe PVI procedure, even when compared with optimized RF in experienced hands. Pulmonary vein reconnection is the dominant cause of recurrence and tempers the expectation of a high durability rate with PFA.

Durable pulmonary vein isolation with optimized high-power and very high-power short-duration temperature-controlled ablation: A step-by-step guide.

INTRODUCTION: Through systematic scientific rigor, the CLOSE guided workflow was developed and has been shown to improve pulmonary vein isolation durability. However, this technique was developed at a time when using power-controlled ablation catheters with conventional power ranges was the norm. There has been increased adoption of a high-power and very high-power short-duration ablation practice propelled by the availability of the temperature-controlled radiofrequency QDOT MICRO catheter. METHODS: There are fundamental differences in biophysics between very high-powered temperature guided ablation and conventional ablation strategy that may impact patient outcomes. The catheter's design and ablation modes offer flexibility in technique while accommodating the individual operator's clinical discretion and preference to deliver a durable, transmural, and contiguous lesion set. RESULTS: Here, we provide recommendations for 3 different workflows using the QDOT MICRO catheter in a step-by-step manner for pulmonary vein isolation based on our cumulative experience as early adopters of the technology and the data available in the scientific literature. CONCLUSIONS: With standardization, temperature-controlled ablation with the QDOT MICRO catheter provides operators the flexibility of implementing different ablation strategies to ensure durable contiguous pulmonary vein isolation depending on patient characteristics.

A neural signature for the subjective experience of threat anticipation under uncertainty.

Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining an uncertainty-variation threat anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we train a brain model that accurately predicts subjective anxious arousal intensity during anticipation and test it across 9 samples (total n = 572, both gender). Using publicly available datasets, we demonstrate that the whole-brain signature specifically predicts anxious anticipation and is not sensitive in predicting pain, general anticipation or unspecific emotional and autonomic arousal. The signature is also functionally and spatially distinguishable from representations of subjective fear or negative affect. We develop a sensitive, generalizable, and specific neuroimaging marker for the subjective experience of uncertain threat anticipation that can facilitate model development.

Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures.

AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.

Neurocognitive mechanisms of mental imagery-based disgust learning.

Disgust imagery represents a potential pathological mechanism for disgust-related disorders. However, it remains controversial as to whether disgust can be conditioned with disgust-evoking mental imagery serving as the unconditioned stimulus (US). Therefore, we examined this using a conditioned learning paradigm in combination with event-related potential (ERP) analysis in 35 healthy college students. The results indicated that the initial neutral face (conditioned stimulus, CS+) became more disgust-evoking, unpleasant, and arousing after pairing with disgust-evoking imagery (disgust CS+), compared to pairing with neutral (neutral CS+) and no (CS-) imagery. Moreover, we observed that mental imagery-based disgust conditioning was resistant to extinction. While the disgust CS + evoked larger P3 and late positive potential amplitudes than CS- during acquisition, no significant differences were found between disgust CS+ and neutral CS+, indicating a dissociation between self-reported and neurophysiological responses. Future studies may additionally acquire facial EMG as an implicit index of conditioned disgust. This study provides the first neurobiological evidence that associative disgust learning can occur without aversive physical stimuli, with implications for understanding how disgust-related disorders may manifest or deteriorate without external perceptual aversive experiences, such as in obsessive-compulsive disorder (OCD).

Mothers and fathers show different neural synchrony with their children during shared experiences.

Parent-child shared experiences has an important influence on social development in children although contributions of mothers and fathers may differ. Neural synchronicity occurs between mothers and fathers and their children during social interactions but it is unclear whether they differ in this respect. We used data from simultaneous fNIRS hyperscanning in mothers (n = 33) and fathers (n = 29) and their children (3-4 years) to determine different patterns and strengths of neural synchronization in the frontal cortex during co-viewing of videos or free-play. Mothers showed greater synchrony with child than fathers during passive viewing of videos and the synchronization was positively associated with video complexity and negatively associated with parental stress. During play interactions, mothers showed more controlling behaviors over their child and greater evidence for joint gaze and joint imitation play with child whereas fathers spent more time gazing at other things. In addition, different aspects of child communication promoted neural synchrony between mothers and fathers and child during active play interactions. Overall, our findings indicate greater neural and behavioral synchrony between mothers than fathers and young children during passive or active shared experiences, although for both it was weakened by parental distress and child difficulty.

Ultra-low-dose photon-counting CT of paranasal sinus: an in vivo comparison of radiation dose and image quality to cone-beam CT.

PURPOSE: This study investigated the differences in subjective and objective image parameters as well as dose exposure of photon-counting CT (PCCT) compared to cone-beam CT (CBCT) in paranasal sinus imaging for the assessment of rhinosinusitis and sinonasal anatomy. METHODS: This single-centre retrospective study included 100 patients, who underwent either clinically indicated PCCT or CBCT of the paranasal sinus. Two blinded experienced ENT radiologists graded image quality and delineation of specific anatomical structures on a 5-point Likert scale. In addition, contrast-to-noise ratio (CNR) and applied radiation doses were compared among both techniques. RESULTS: Image quality and delineation of bone structures in paranasal sinus PCCT was subjectively rated superior by both readers compared to CBCT (P < .001). CNR was significantly higher for photon-counting CT (P < .001). Mean effective dose for PCCT examinations was significantly lower than for CBCT (0.038 mSv ± 0.009 vs. 0.14 mSv ± 0.011; P < .001). CONCLUSION: In a performance comparison of PCCT and a modern CBCT scanner in paranasal sinus imaging, we demonstrated that first-use PCCT in clinical routine provides higher subjective image quality accompanied by higher CNR at close to a quarter of the dose exposure compared to CBCT.

The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in the regulation of cognition and behavior as well as in the neuropathology of neurological and mental disorders. The angiotensin II type 1 receptor (AT1R) mediates most functional and neuropathology-relevant actions associated with the central RAS. However, an overarching comprehension to guide translation and utilize the therapeutic potential of the central RAS in humans is currently lacking. We conducted a comprehensive characterization of the RAS using an innovative combination of transcriptomic gene expression mapping, image-based behavioral decoding, and pre-registered randomized controlled discovery-replication pharmacological resting-state functional magnetic resonance imaging (fMRI) trials (N = 132) with a selective AT1R antagonist. The AT1R exhibited a particular dense expression in a subcortical network encompassing the thalamus, striatum, and amygdalo-hippocampal formation. Behavioral decoding of the AT1R gene expression brain map showed an association with memory, stress, reward, and motivational processes. Transient pharmacological blockade of the AT1R further decreased neural activity in subcortical systems characterized by a high AT1R expression, while increasing functional connectivity in the cortico-basal ganglia-thalamo-cortical circuitry. Effects of AT1R blockade on the network level were specifically associated with the transcriptomic signatures of the dopaminergic, opioid, acetylcholine, and corticotropin-releasing hormone signaling systems. The robustness of the results was supported in an independent pharmacological fMRI trial. These findings present a biologically informed comprehensive characterization of the central AT1R pathways and their functional relevance on the neural and behavioral level in humans.

A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge.

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional near-infrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural self-regulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.

Brain Structural Connectivity Guided Vision Transformers for Identification of Functional Connectivity Characteristics in Preterm Neonates.

Preterm birth is the leading cause of death in children under five years old, and is associated with a wide sequence of complications in both short and long term. In view of rapid neurodevelopment during the neonatal period, preterm neonates may exhibit considerable functional alterations compared to term ones. However, the identified functional alterations in previous studies merely achieve moderate classification performance, while more accurate functional characteristics with satisfying discrimination ability for better diagnosis and therapeutic treatment is underexplored. To address this problem, we propose a novel brain structural connectivity (SC) guided Vision Transformer (SCG-ViT) to identify functional connectivity (FC) differences among three neonatal groups: preterm, preterm with early postnatal experience, and term. Particularly, inspired by the neuroscience-derived information, a novel patch token of SC/FC matrix is defined, and the SC matrix is then adopted as an effective mask into the ViT model to screen out input FC patch embeddings with weaker SC, and to focus on stronger ones for better classification and identification of FC differences among the three groups. The experimental results on multi-modal MRI data of 437 neonatal brains from publicly released Developing Human Connectome Project (dHCP) demonstrate that SCG-ViT achieves superior classification ability compared to baseline models, and successfully identifies holistically different FC patterns among the three groups. Moreover, these different FCs are significantly correlated with the differential gene expressions of the three groups. In summary, SCG-ViT provides a powerfully brain-guided pipeline of adopting large-scale and data-intensive deep learning models for medical imaging-based diagnosis.

Early atrial fibrillation recurrence post catheter ablation: Analysis from insertable cardiac monitor in the era of optimized radiofrequency ablation.

BACKGROUND: Early recurrence of atrial tachyarrhythmia (ERAT) is associated with ablation-induced proarrhythmogenic inflammation; however, existing studies used intermittent monitoring or nonoptimized radiofrequency (RF) applications (noncontiguous or without ablation index target value). OBJECTIVE: The purpose of this study was to investigate the relationship between ERAT and late recurrence based on insertable cardiac monitor (ICM) data. METHODS: We compiled data from Close-To-Cure and Close Maze studies, which enrolled patients who underwent RF ablation for paroxysmal or persistent atrial fibrillation (AF). All patients were implanted with an ICM 2-3 months before ablation. RESULTS: We studied 165 patients (104 with paroxysmal AF, 61 with persistent AF). Over the 1-year follow-up period, 41 of the patients experienced late recurrence. The risk of late recurrence was higher in patients experiencing ERAT (hazard ratio [HR] 6.2; 95% confidence interval [CI] 3.0-13.0), with negative and positive predictive values of 90.5% and 45.7%, respectively. Median burden of AF during the blanking period was significantly higher in patients with late recurrence (7.9% [0.0%-99.6%]) compared to those without recurrence (0.0% [0.0%-6.0]; P <.001). For each 1% increase in AF burden during the blanking period, late recurrence increased by 4.6% (HR 1.046; 95% CI 1.035-1.059). The best tradeoff for predicting AF from ERAT occurrence was AF burden of 0.6% and last ERAT at 64 days. CONCLUSION: In patients ablated for paroxysmal and persistent AF with a durable RF lesion set and implanted with a continuous monitoring device, postablation early AF recurrence and burden significantly predict late recurrence. The post-AF ablation blanking period should be reduced to 2 months.