UNASSIGNED: The impact of intrafractional motion and deformations on clinical radiotherapy delivery has so far only been investigated by simulations as well as point and planar dose measurements. The aim of this study was to combine anthropomorphic 3D dosimetry with a deformable abdominal phantom to measure the influence of intra-fractional motion and gating in photon radiotherapy and evaluate the applicability in proton therapy.
UNASSIGNED: An abdominal phantom was modified to hold a deformable anthropomorphic 3D dosimeter shaped as a human liver. A liver-specific photon radiotherapy and a proton pencil beam scanning therapy plan were delivered to the phantom without motion as well as with 12 mm sinusoidal motion while using either no respiratory gating or respiratory gating.
UNASSIGNED: Using the stationary irradiation as reference the local 3 %/2 mm 3D gamma index pass rate of the motion experiments in the planning target volume (PTV) was above 97 % (photon) and 78 % (proton) with gating whereas it was below 74 % (photon) and 45 % (proton) without gating.
UNASSIGNED: For the first time a high-resolution deformable anthropomorphic 3D dosimeter embedded in a deformable abdominal phantom was applied for experimental validation of both photon and proton treatments of targets exhibiting respiratory motion. It was experimentally shown that gating improves dose coverage and the geometrical accuracy for both photon radiotherapy and proton therapy.

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In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

Adipocyte characterization and assessing membrane proteins using flow cytometry has been proven to be challenging as adipocytes are fragile, especially in subjects with high BMI. We overcame these challenges through a protocol optimizing tissue digestion time by reducing intermediate steps to minimize adipocyte friction and breakage. We avoided requirement for specialized instrument configuration and used a modified gating strategy to prevent inclusion of lipid droplets during analysis. Up to 90% of the cell population were available in the gating area. We checked the expression level of ABCA1, a membrane protein reaffirming adipocyte selection. In summary, this protocol requires lesser tissue sample improving feasibility and cost efficiency. Thus, our flow cytometry method is an improvement for studying adipocyte membrane characteristics.

OBJECTIVE: Flow cytometry is a widely used technique for identifying cell populations in patient-derived fluids, such as peripheral blood (PB) or cerebrospinal fluid (CSF). Despite its ubiquity in research and clinical practice, the process of gating, i.e., manually identifying cell types, is labor-intensive and error-prone. The objective of this study is to address this challenge by introducing GateNet, a neural network architecture designed for fully end-to-end automated gating without the need for correcting batch effects.
METHODS: For this study a unique dataset is used which comprises over 8,000,000 events from N = 127 PB and CSF samples which were manually labeled independently by four experts. Applying cross-validation, the classification performance of GateNet is compared to the human experts performance. Additionally, GateNet is applied to a publicly available dataset to evaluate generalization. The classification performance is measured using the F1 score.
RESULTS: GateNet achieves F1 scores ranging from 0.910 to 0.997 demonstrating human-level performance on samples unseen during training. In the publicly available dataset, GateNet confirms its generalization capabilities with an F1 score of 0.936. Importantly, we also show that GateNet only requires ≈10 samples to reach human-level performance. Finally, gating with GateNet only takes 15 microseconds per event utilizing graphics processing units (GPU).
CONCLUSIONS: GateNet enables fully end-to-end automated gating in flow cytometry, overcoming the labor-intensive and error-prone nature of manual adjustments. The neural network achieves human-level performance on unseen samples and generalizes well to diverse datasets. Notably, its data efficiency, requiring only ∼10 samples to reach human-level performance, positions GateNet as a widely applicable tool across various domains of flow cytometry.

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.

(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.

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.

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.

OBJECTIVE: Target positions should be acquired during beam delivery for accurate lung stereotactic body radiotherapy. We aimed to perform kilovoltage (kV) imaging during beam irradiation (intra-irradiation imaging) under phase-gated conditions and evaluate its performance.
METHODS: Catphan 504 and QUASAR respiratory motion phantoms were used to evaluate image quality and target detectability, respectively. TrueBeam STx linac and the Developer Mode was used. The imaging parameters were 125 kVp and 1.2 mAs/projection. Flattened megavoltage (MV) X-ray beam energies 6, 10 and 15 MV and un-flattened beam energies 6 and 10 MV were used with field sizes of 5 × 5 and 15 × 15 cm2 and various frame rates for intra-irradiation imaging. In addition, using a QUASAR phantom, intra-irradiation imaging was performed during intensity-modulated plan delivery. The root-mean-square error (RMSE) of the CT-number for the inserted rods, image noise, visual assessment, and contrast-to-noise ratio (CNR) were evaluated.
RESULTS: The RMSEs of intra-irradiation cone-beam computed tomography (CBCT) images under gated conditions were 50-230 Hounsfield Unit (HU) (static < 30 HU). The noise of the intra-irradiation CBCT images under gated conditions was 15-35 HU, whereas that of the standard CBCT images was 8.8-27.2 HU. Lower frame rates exhibited large RMSEs and noise; however, the iterative reconstruction algorithm (IR) was effective at improving these values. Approximately 7 fps with the IR showed an equivalent CNR of 15 fps without the IR. The target was visible on all the gated intra-irradiation CBCT images.
CONCLUSIONS: Several image quality improvements are required; however, intra-irradiated CBCT images showed good visual target detection.