The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex.

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology.

The transient receptor potential ion channel TRPA1 is a Ca2+-permeable nonselective cation channel widely expressed in sensory neurons, but also in many nonneuronal tissues typically possessing barrier functions, such as the skin, joint synoviocytes, cornea, and the respiratory and intestinal tracts. Here, the primary role of TRPA1 is to detect potential danger stimuli that may threaten the tissue homeostasis and the health of the organism. The ability to directly recognize signals of different modalities, including chemical irritants, extreme temperatures, or osmotic changes resides in the characteristic properties of the ion channel protein complex. Recent advances in cryo-electron microscopy have provided an important framework for understanding the molecular basis of TRPA1 function and have suggested novel directions in the search for its pharmacological regulation. This chapter summarizes the current knowledge of human TRPA1 from a structural and functional perspective and discusses the complex allosteric mechanisms of activation and modulation that play important roles under physiological or pathophysiological conditions. In this context, major challenges for future research on TRPA1 are outlined.

Deep learning based bilateral filtering for edge-preserving denoising of respiratory-gated PET.

BACKGROUND: Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations. The only broadly used approach for noise reduction in PET imaging has been the application of low-pass filters, usually Gaussians, which however leads to loss of spatial resolution and increased partial volume effects affecting detectability of small lesions and quantitative data evaluation. The bilateral filter (BF) - a locally adaptive image filter - allows to reduce image noise while preserving well defined object edges but manual optimization of the filter parameters for a given PET scan can be tedious and time-consuming, hampering its clinical use. In this work we have investigated to what extent a suitable deep learning based approach can resolve this issue by training a suitable network with the target of reproducing the results of manually adjusted case-specific bilateral filtering. METHODS: Altogether, 69 respiratory-gated clinical PET/CT scans with three different tracers ( [ 18 F ] FDG, [ 18 F ] L-DOPA, [ 68 Ga ] DOTATATE) were used for the present investigation. Prior to data processing, the gated data sets were split, resulting in a total of 552 single-gate image volumes. For each of these image volumes, four 3D ROIs were delineated: one ROI for image noise assessment and three ROIs for focal uptake (e.g. tumor lesions) measurements at different target/background contrast levels. An automated procedure was used to perform a brute force search of the two-dimensional BF parameter space for each data set to identify the "optimal" filter parameters to generate user-approved ground truth input data consisting of pairs of original and optimally BF filtered images. For reproducing the optimal BF filtering, we employed a modified 3D U-Net CNN incorporating residual learning principle. The network training and evaluation was performed using a 5-fold cross-validation scheme. The influence of filtering on lesion SUV quantification and image noise level was assessed by calculating absolute and fractional differences between the CNN, manual BF, or original (STD) data sets in the previously defined ROIs. RESULTS: The automated procedure used for filter parameter determination chose adequate filter parameters for the majority of the data sets with only 19 patient data sets requiring manual tuning. Evaluation of the focal uptake ROIs revealed that CNN as well as BF based filtering essentially maintain the focal SUV max values of the unfiltered images with a low mean ± SD difference of δ SUV max CNN , STD = (-3.9 ± 5.2)% and δ SUV max BF , STD = (-4.4 ± 5.3)%. Regarding relative performance of CNN versus BF, both methods lead to very similar SUV max values in the vast majority of cases with an overall average difference of δ SUV max CNN , BF = (0.5 ± 4.8)%. Evaluation of the noise properties showed that CNN filtering mostly satisfactorily reproduces the noise level and characteristics of BF with δ Noise CNN , BF = (5.6 ± 10.5)%. No significant tracer dependent differences between CNN and BF were observed. CONCLUSIONS: Our results show that a neural network based denoising can reproduce the results of a case by case optimized BF in a fully automated way. Apart from rare cases it led to images of practically identical quality regarding noise level, edge preservation, and signal recovery. We believe such a network might proof especially useful in the context of improved motion correction of respiratory-gated PET studies but could also help to establish BF-equivalent edge-preserving CNN filtering in clinical PET since it obviates time consuming manual BF parameter tuning.

Data driven surrogate signal extraction for dynamic PET using selective PCA: time windows versus the combination of components.

Respiratory motion correction is beneficial in PET, as it can reduce artefacts caused by motion and improve quantitative accuracy. Methods of motion correction are commonly based on a respiratory trace obtained through an external device (like the Real Time Position Management System) or a data driven method, such as those based on dimensionality reduction techniques (for instance PCA). PCA itself being a linear transformation to the axis of greatest variation. Data driven methods have the advantage of being non-invasive, and can be performed post-acquisition. However, their main downside being that they are adversely affected by the tracer kinetics of the dynamic PET acquisition. Therefore, they are mostly limited to static PET acquisitions. This work seeks to extend on existing PCA-based data-driven motion correction methods, to allow for their applicability to dynamic PET imaging. The methods explored in this work include; a moving window approach (similar to the Kinetic Respiratory Gating method from Schleyer et al.), extrapolation of the principal component from later time points to earlier time points, and a method to score, select, and combine multiple respiratory components. The resulting respiratory traces were evaluated on 22 data sets from a dynamic 18FFDG study on patients with Idiopathic Pulmonary Fibrosis. This was achieved by calculating their correlation with a surrogate signal acquired using a Real Time Position Management System. The results indicate that all methods produce better surrogate signals than when applying conventional PCA to dynamic data (for instance, a higher correlation with a gold standard respiratory trace). Extrapolating a late time point principal component produced more promising results than using a moving window. Scoring, selecting, and combining components held benefits over all other methods. This work allows for the extraction of a surrogate signal from dynamic PET data earlier in the acquisition and with a greater accuracy than previous work. This potentially allows for numerous other methods (for instance, respiratory motion correction) to be applied to this data (when they otherwise could not be previously used).

Revealing molecular determinants governing mambalgin-3 pharmacology at acid-sensing ion channel 1 variants.

Acid-sensing ion channels (ASICs) are trimeric proton-gated cation channels that play a role in neurotransmission and pain sensation. The snake venom-derived peptides, mambalgins, exhibit potent analgesic effects in rodents by inhibiting central ASIC1a and peripheral ASIC1b. Despite their distinct species- and subtype-dependent pharmacology, previous structure-function studies have focussed on the mambalgin interaction with ASIC1a. Currently, the specific channel residues responsible for this pharmacological profile, and the mambalgin pharmacophore at ASIC1b remain unknown. Here we identify non-conserved residues at the ASIC1 subunit interface that drive differences in the mambalgin pharmacology from rat ASIC1a to ASIC1b, some of which likely do not make peptide binding interactions. Additionally, an amino acid variation below the core binding site explains potency differences between rat and human ASIC1. Two regions within the palm domain, which contribute to subtype-dependent effects for mambalgins, play key roles in ASIC gating, consistent with subtype-specific differences in the peptides mechanism. Lastly, there is a shared primary mambalgin pharmacophore for ASIC1a and ASIC1b activity, with certain peripheral peptide residues showing variant-specific significance for potency. Through our broad mutagenesis studies across various species and subtype variants, we gain a more comprehensive understanding of the pharmacophore and the intricate molecular interactions that underlie ligand specificity. These insights pave the way for the development of more potent and targeted peptide analogues required to advance our understating of human ASIC1 function and its role in disease.

A Tunable Graphene Superlattice with Deformable Periodical Nano-Gating.

Graphene superlattices have simple and controllable electronic band structures, which can also be electrostatically tuned. They have been widely studied for band engineering and strong correlated physics, and have led to the discovery of a variety of exciting phenomena. To experimentally study the physics of graphene superlattices in a systematic way, it is desirable to control the structure parameters, which barely exist at the moment, onsite. Here, a tunable superlattice with graphene and a deformable gating structure is demonstrated. The period and duty cycle of the nano-gating, and furthermore of the superlattice potential, can be tuned through altering the shape of the gating structure with piezo-actuators, offering a tunable band structure. The tuning of the electronic band structures of both a two-dimensional and a one-dimensional superlattice is demonstrated with numerical simulations, offering a new approach for tunable electronic and photonic devices.

Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.

Together with its ß-subunit OSTM1, ClC-7 performs 2Cl-/H+ exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis and lysosomal storage. CLCN7 variants can cause recessive or dominant disease. Different variants entail different sets of symptoms. Loss of ClC-7 causes osteopetrosis and mostly neuronal lysosomal storage. A recently reported de novo CLCN7 mutation (p.Tyr715Cys) causes widespread severe lysosome pathology (hypopigmentation, organomegaly, and delayed myelination and development, "HOD syndrome"), but no osteopetrosis. We now describe two additional HOD individuals with the previously described p.Tyr715Cys and a novel p.Lys285Thr mutation, respectively. Both mutations decreased ClC-7 inhibition by PI(3,5)P2 and affected residues lining its binding pocket, and shifted voltage-dependent gating to less positive potentials, an effect partially conferred to WT subunits in WT/mutant heteromers. This shift predicts augmented pH gradient-driven Cl- uptake into vesicles. Overexpressing either mutant induced large lysosome-related vacuoles. This effect depended on Cl-/H+-exchange, as shown using mutants carrying uncoupling mutations. Fibroblasts from the p.Y715C patient also displayed giant vacuoles. This was not observed with p.K285T fibroblasts probably due to residual PI(3,5)P2 sensitivity. The gain of function caused by the shifted voltage-dependence of either mutant likely is the main pathogenic factor. Loss of PI(3,5)P2 inhibition will further increase current amplitudes, but may not be a general feature of HOD. Overactivity of ClC-7 induces pathologically enlarged vacuoles in many tissues, which is distinct from lysosomal storage observed with the loss of ClC-7 function. Osteopetrosis results from a loss of ClC-7, but osteoclasts remain resilient to increased ClC-7 activity.

Auditory Sensory Gating: Effects of Noise.

Cortical auditory evoked potentials (CAEPs) indicate that noise degrades auditory neural encoding, causing decreased peak amplitude and increased peak latency. Different types of noise affect CAEP responses, with greater informational masking causing additional degradation. In noisy conditions, attention can improve target signals' neural encoding, reflected by an increased CAEP amplitude, which may be facilitated through various inhibitory mechanisms at both pre-attentive and attentive levels. While previous research has mainly focused on inhibition effects during attentive auditory processing in noise, the impact of noise on the neural response during the pre-attentive phase remains unclear. Therefore, this preliminary study aimed to assess the auditory gating response, reflective of the sensory inhibitory stage, to repeated vowel pairs presented in background noise. CAEPs were recorded via high-density EEG in fifteen normal-hearing adults in quiet and noise conditions with low and high informational masking. The difference between the average CAEP peak amplitude evoked by each vowel in the pair was compared across conditions. Scalp maps were generated to observe general cortical inhibitory networks in each condition. Significant gating occurred in quiet, while noise conditions resulted in a significantly decreased gating response. The gating function was significantly degraded in noise with less informational masking content, coinciding with a reduced activation of inhibitory gating networks. These findings illustrate the adverse effect of noise on pre-attentive inhibition related to speech perception.

Molecular and Evolution In Silico Studies Unlock the h4-HPPD C-Terminal Tail Gating Mechanism.

The enzyme 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) is involved in the catabolism of the amino acid tyrosine in organisms such as bacteria, plants, and animals. It catalyzes the conversion of 4-hydroxyphenylpyruvate to a homogenisate in the presence of molecular oxygen and Fe(II) as a cofactor. This enzyme represents a key step in the biosynthesis of important compounds, and its activity deficiency leads to severe, rare autosomal recessive disorders, like tyrosinemia type III and hawkinsinuria, for which no cure is currently available. The 4-HPPD C-terminal tail plays a crucial role in the enzyme catalysis/gating mechanism, ensuring the integrity of the active site for catalysis through fine regulation of the C-terminal tail conformation. However, despite growing interest in the 4-HPPD catalytic mechanism and structure, the gating mechanism remains unclear. Furthermore, the absence of the whole 3D structure makes the bioinformatic approach the only possible study to define the enzyme structure/molecular mechanism. Here, wild-type 4-HPPD and its mutants were deeply dissected by applying a comprehensive bioinformatics/evolution study, and we showed for the first time the entire molecular mechanism and regulation of the enzyme gating process, proposing the full-length 3D structure of human 4-HPPD and two novel key residues involved in the 4-HPPD C-terminal tail conformational change.

Clinical Outcomes of Online Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Adrenal Metastases from a Single Institution.

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT.

Calcium Regulation of Connexin Hemichannels.

Connexin hemichannels (HCs) expressed at the plasma membrane of mammalian cells are of paramount importance for intercellular communication. In physiological conditions, HCs can form gap junction (GJ) channels, providing a direct diffusive path between neighbouring cells. In addition, unpaired HCs provide conduits for the exchange of solutes between the cytoplasm and the extracellular milieu, including messenger molecules involved in paracrine signalling. The synergistic action of membrane potential and Ca2+ ions controls the gating of the large and relatively unselective pore of connexin HCs. The four orders of magnitude difference in gating sensitivity to the extracellular ([Ca2+]e) and the cytosolic ([Ca2+]c) Ca2+ concentrations suggests that at least two different Ca2+ sensors may exist. While [Ca2+]e acts as a spatial modulator of the HC opening, which is most likely dependent on the cell layer, compartment, and organ, [Ca2+]c triggers HC opening and the release of extracellular bursts of messenger molecules. Such molecules include ATP, cAMP, glutamate, NAD+, glutathione, D-serine, and prostaglandins. Lost or abnormal HC regulation by Ca2+ has been associated with several diseases, including deafness, keratitis ichthyosis, palmoplantar keratoderma, Charcot-Marie-Tooth neuropathy, oculodentodigital dysplasia, and congenital cataracts. The fact that both an increased and a decreased Ca2+ sensitivity has been linked to pathological conditions suggests that Ca2+ in healthy cells finely tunes the normal HC function. Overall, further investigation is needed to clarify the structural and chemical modifications of connexin HCs during [Ca2+]e and [Ca2+]c variations. A molecular model that accounts for changes in both Ca2+ and the transmembrane voltage will undoubtedly enhance our interpretation of the experimental results and pave the way for developing therapeutic compounds targeting specific HC dysfunctions.

Visual Recalibration and Gating Enhancement Network for Radiology Report Generation.

Automatic radiology medical report generation is a necessary development of artificial intelligence technology in the health care. This technology serves to aid doctors in producing comprehensive diagnostic reports, alleviating the burdensome workloads of medical professionals. However, there are some challenges in generating radiological reports: (1) visual and textual data biases and (2) long-distance dependency problem. To tackle these issues, we design a visual recalibration and gating enhancement network (VRGE), which composes of the visual recalibration module and the gating enhancement module (gating enhancement module, GEM). Specifically, the visual recalibration module enhances the recognition of abnormal features in lesion areas of medical images. The GEM dynamically adjusts the contextual information in the report by introducing gating mechanisms, focusing on capturing professional medical terminology in medical text reports. We have conducted sufficient experiments on the public datasets of IU X-Ray to illustrate that the VRGE outperforms existing models.

Individualized Closed-Loop Acoustic Stimulation Suggests an Alpha Phase Dependence of Sound Evoked and Induced Brain Activity Measured with EEG Recordings.

Following repetitive visual stimulation, post hoc phase analysis finds that visually evoked response magnitudes vary with the cortical alpha oscillation phase that temporally coincides with sensory stimulus. This approach has not successfully revealed an alpha phase dependence for auditory evoked or induced responses. Here, we test the feasibility of tracking alpha with scalp electroencephalogram (EEG) recordings and play sounds phase-locked to individualized alpha phases in real-time using a novel end-point corrected Hilbert transform (ecHT) algorithm implemented on a research device. Based on prior work, we hypothesize that sound-evoked and induced responses vary with the alpha phase at sound onset and the alpha phase that coincides with the early sound-evoked response potential (ERP) measured with EEG. Thus, we use each subject's individualized alpha frequency (IAF) and individual auditory ERP latency to define target trough and peak alpha phases that allow an early component of the auditory ERP to align to the estimated poststimulus peak and trough phases, respectively. With this closed-loop and individualized approach, we find opposing alpha phase-dependent effects on the auditory ERP and alpha oscillations that follow stimulus onset. Trough and peak phase-locked sounds result in distinct evoked and induced post-stimulus alpha level and frequency modulations. Though additional studies are needed to localize the sources underlying these phase-dependent effects, these results suggest a general principle for alpha phase-dependence of sensory processing that includes the auditory system. Moreover, this study demonstrates the feasibility of using individualized neurophysiological indices to deliver automated, closed-loop, phase-locked auditory stimulation.

Author's response to Letter-to-the-Editor from Chang JS. concerning: "Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial".

We appreciate Chang JS.'s interest in the article: "Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial". The author's response corroborates the statements and comments of Chang JS.

Clinical Implementation and Initial Validation of Respiratory-Gated Stereotactic Body Radiotherapy for Thoracoabdominal Tumors Under Abdominal Compression Using an Anzai Laser-Based Gating Device With Visual Guidance on an Elekta Linear Accelerator.

We have clinically implemented gated stereotactic body radiotherapy under abdominal compression using an Anzai laser-based gating device with visual guidance in combination with an Elekta linear accelerator. To ensure accuracy, we configured the gating window for each patient by correlating the respiratory curve from the laser sensor and the tumor positions from the 4D computed tomography (CT) images reconstructed with the aid of the respiratory curve. This allowed us to define a patient-specific gating window to keep the tumor displacement below 5 mm from the end-expiration, assuming the reproducibility of the tumor trajectories and the laser-based body surface measurements. Results are summarized as follows: 1) A patient-specific gating window internal target volume (ITV) with a prespecified maximum tumor displacement relative to the end-expiration was obtained by acquiring a 4D CT consisting of 20 phase CT sets and a respiratory curve from the Anzai system. 2) Respiratory hysteresis was managed by setting two different thresholds on the respiratory curve based on the predetermined maximum tumor displacement relative to end-expiration. 3) Abdominal compression increased gating window width, thereby presumably leading to faster gated-beam delivery. 4) Gamma index pass rates in sliding-window gated intensity-modulated radiotherapy (IMRT) were superior to those in gated volumetric modulated arc therapy (VMAT). 5) Intrafraction gated cone-beam computed tomography (CBCT) demonstrated that the tumor appeared to remain within the gating window ITV during the stereotactic gated sliding-window IMRT. In conclusion, we have successfully implemented gated stereotactic body radiotherapy at our clinic and achieved a favorable clinical validation result. More cases need to be evaluated to increase the validity.

Motion robust coronary MR angiography using zigzag centric ky-kz trajectory and high-resolution deep learning reconstruction.

PURPOSE: To develop a new MR coronary angiography (MRCA) technique by employing a zigzag fan-shaped centric ky-kz k-space trajectory combined with high-resolution deep learning reconstruction (HR-DLR). METHODS: All imaging data were acquired from 12 healthy subjects and 2 patients using two clinical 3-T MR imagers, with institutional review board approval. Ten healthy subjects underwent both standard 3D fast gradient echo (sFGE) and centric ky-kz k-space trajectory FGE (cFGE) acquisitions to compare the scan time and image quality. Quantitative measures were also performed for signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as sharpness of the vessel. Furthermore, the feasibility of the proposed cFGE sequence was assessed in two patients. For assessing the feasibility of the centric ky-kz trajectory, the navigator-echo window of a 30-mm threshold was applied in cFGE, whereas sFGE was applied using a standard 5-mm threshold. Image quality of MRCA using cFGE with HR-DLR and sFGE without HR-DLR was scored in a 5-point scale (non-diagnostic = 1, fair = 2, moderate = 3, good = 4, and excellent = 5). Image evaluation of cFGE, applying HR-DLR, was compared with sFGE without HR-DLR. Friedman test, Wilcoxon signed-rank test, or paired t tests were performed for the comparison of related variables. RESULTS: The actual MRCA scan time of cFGE with a 30-mm threshold was acquired in less than 5 min, achieving nearly 100% efficiency, showcasing its expeditious and robustness. In contrast, sFGE was acquired with a 5-mm threshold and had an average scan time of approximately 15 min. Overall image quality for MRCA was scored 3.3 for sFGE and 2.7 for cFGE without HR-DLR but increased to 3.6 for cFGE with HR-DLR and (p < 0.05). The clinical result of patients obtained within 5 min showed good quality images in both patients, even with a stent, without artifacts. Quantitative measures of SNR, CNR, and sharpness of vessel presented higher in cFGE with HR-DLR. CONCLUSION: Our findings demonstrate a robust, time-efficient solution for high-quality MRCA, enhancing patient comfort and increasing clinical throughput.

Neto proteins differentially modulate the gating properties of Drosophila NMJ glutamate receptors.

The formation of functional synapses requires co-assembly of ion channels with their accessory proteins which controls where, when, and how neurotransmitter receptors function. The auxiliary protein Neto modulates the function of kainate-type glutamate receptors in vertebrates as well as at the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse widely used for genetic studies on synapse development. We previously reported that Neto is essential for the synaptic recruitment and function of glutamate receptors. Here, using outside-out patch-clamp recordings and fast ligand application, we examine for the first time the biophysical properties of recombinant Drosophila NMJ receptors expressed in HEK293T cells and compare them with native receptor complexes of genetically controlled composition. The two Neto isoforms, Neto-α and Neto-ß, differentially modulate the gating properties of NMJ receptors. Surprisingly, we found that deactivation is extremely fast and that the decay of synaptic currents resembles the rate of iGluR desensitization. The functional analyses of recombinant iGluRs that we report here should greatly facilitate the interpretation of compound in vivo phenotypes of mutant animals.

Deep generative denoising networks enhance quality and accuracy of gated cardiac PET data.

BACKGROUND: Cardiac positron emission tomography (PET) can visualize and quantify the molecular and physiological pathways of cardiac function. However, cardiac and respiratory motion can introduce blurring that reduces PET image quality and quantitative accuracy. Dual cardiac- and respiratory-gated PET reconstruction can mitigate motion artifacts but increases noise as only a subset of data are used for each time frame of the cardiac cycle. AIM: The objective of this study is to create a zero-shot image denoising framework using a conditional generative adversarial networks (cGANs) for improving image quality and quantitative accuracy in non-gated and dual-gated cardiac PET images. METHODS: Our study included retrospective list-mode data from 40 patients who underwent an 18F-fluorodeoxyglucose (18F-FDG) cardiac PET study. We initially trained and evaluated a 3D cGAN-known as Pix2Pix-on simulated non-gated low-count PET data paired with corresponding full-count target data, and then deployed the model on an unseen test set acquired on the same PET/CT system including both non-gated and dual-gated PET data. RESULTS: Quantitative analysis demonstrated that the 3D Pix2Pix network architecture achieved significantly (p value<0.05) enhanced image quality and accuracy in both non-gated and gated cardiac PET images. At 5%, 10%, and 15% preserved count statistics, the model increased peak signal-to-noise ratio (PSNR) by 33.7%, 21.2%, and 15.5%, structural similarity index (SSIM) by 7.1%, 3.3%, and 2.2%, and reduced mean absolute error (MAE) by 61.4%, 54.3%, and 49.7%, respectively. When tested on dual-gated PET data, the model consistently reduced noise, irrespective of cardiac/respiratory motion phases, while maintaining image resolution and accuracy. Significant improvements were observed across all gates, including a 34.7% increase in PSNR, a 7.8% improvement in SSIM, and a 60.3% reduction in MAE. CONCLUSION: The findings of this study indicate that dual-gated cardiac PET images, which often have post-reconstruction artifacts potentially affecting diagnostic performance, can be effectively improved using a generative pre-trained denoising network.

Electrostatic Control of Nonlinear Photonic-Crystal Polaritons in a Monolayer Semiconductor.

Integration of 2D semiconductors with photonic crystal slabs provides an attractive approach to achieving strong light-matter coupling and exciton-polariton formation in a chip-compatible geometry. However, for the development of practical devices, it is crucial that polariton excitations are easily tunable and exhibit a strong nonlinear response. Here we study neutral and charged exciton-polaritons in an electrostatically gated photonic crystal slab with an embedded monolayer semiconductor MoSe2 and experimentally demonstrate a novel approach to optical control based on polariton nonlinearity. We show that spatial modulation of the dielectric environment within the photonic crystal unit cell results in the formation of two distinct excitonic species with significantly different nonlinear responses of the corresponding charged exciton-polaritons under optical pumping. This behavior enables optical switching with ultrashort laser pulses and can be sensitively controlled via an electrostatic gate voltage. Our results open new avenues toward the development of active polaritonic devices in a compact chip-compatible implementation.

Lung sparing in MR-guided non-adaptive SBRT treatment of peripheral lung tumors.

Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.