Artificial intelligence guided physician directive improves head and neck planning quality and practice Uniformity: A prospective study.

•AI dose predictor was fully integrated with treatment planning system and used as a physicain decision support tool to improve uniformity of practice.•Model was trained based on our standard of practice, but implemented at the time of expansion with 3 new physicians join the practice.•Phase 1 retrospective evaluation demonstrated the non-uniform practice among 3 MDs and only 52.9% frequency planner can achieve physicians' directives.•Significant improvement in practice uniformity of practice was observed after utilizing AI as DST and 80.4% frequency clinical plan can achieve AI-guided physician directives.

EMG-driven fatigue-based self-adapting admittance control of a hand rehabilitation robot.

Upper-limb rehabilitation therapy sessions for post-stroke people generally contain rhythmic hand movements in a tiresome manner to rebuild the injured neural circuits. Fatigue formation causes breaks in the training and limits the therapy duration. Therefore, it is essential to establish a correlation between the patient's muscle condition and the rehabilitation exercises to improve the physiotherapy sessions. A self-adapting control method based on online fatigue detection in rhythmic arm movements is presented. Experimental tests were performed on twenty healthy subjects to validate the method's feasibility. Electromyography (EMG) and force signals considered the interfaces between users and the robot. In the first stage of the experiment, utilizing the frequency features from EMG signals, a neural network for fatigue detection trained; however, in the end, it substituted with a simple function as a refinement in the time-consuming aspect for the online employment. The initiation of the fatigue process is followed by reducing the admittance controller damping term based on the EMG signal processing. Trajectory tracking with the robot employs the self-adapting admittance controller (SAAC) method and the non-adapting admittance controller (NAAC). Movement accuracy and smoothness were measured and showed a better performance of the SAAC method related to the NAAC. Simulations with two different stiffness levels were performed on an upper-limb OpenSim model to study a stroke-injured arm and evaluate the proposed method's proficiency. The metabolic cost indicated the movement's superiority in a fatigue situation for reduced environment stiffness.

Site-agnostic 3D dose distribution prediction with deep learning neural networks.

PURPOSE: Typically, the current dose prediction models are limited to small amounts of data and require retraining for a specific site, often leading to suboptimal performance. We propose a site-agnostic, three-dimensional dose distribution prediction model using deep learning that can leverage data from any treatment site, thus increasing the total data available to train the model. Applying our proposed model to a new target treatment site requires only a brief fine-tuning of the model to the new data and involves no modifications to the model input channels or its parameters. Thus, it can be efficiently adapted to a different treatment site, even with a small training dataset. METHODS: This study uses two separate datasets/treatment sites: data from patients with prostate cancer treated with intensity-modulated radiation therapy (source data), and data from patients with head-and-neck cancer treated with volumetric-modulated arc therapy (target data). We first developed a source model with 3D UNet architecture, trained from random initial weights on the source data. We evaluated the performance of this model on the source data. We then studied the generalizability of the model to the new target dataset via transfer learning. To do this, we built three more models, all with the same 3D UNet architecture: target model, adapted model, and combined model. The source and target models were trained on the source and target data from random initial weights, respectively. The adapted model fine-tuned the source model to the target domain by using the target data. Finally, the combined model was trained from random initial weights on a combined data pool consisting of both target and source datasets. We tested all four models on the target dataset and evaluated quantitative dose-volume histogram metrics for the planning target volume (PTV) and organs at risk (OARs). RESULTS: When tested on the source treatment site, the source model accurately predicted the dose distributions with average (mean, max) absolute dose errors of (0.32%±0.14, 2.37%±0.93) (PTV) relative to the prescription dose, and highest mean dose error of 1.68%±0.76, and highest max dose error of 5.47%± 3.31 for femoral head right. The error in PTV dose coverage prediction is 3.21%±1.51 for D98 , 3.04%±1.69 for D95 , and 1.83%±1.01 for D02 . Averaging across all OARs, the source model predicted the OAR mean dose within 1.38% and the OAR max dose within 3.64%. For the target treatment site, the target model average (mean, max) absolute dose errors relative to the prescription dose for the PTV were (1.08%±0.95, 2.90%±1.35). Left cochlea had the highest mean and max dose errors of 5.37%±5.82 and 8.33%±8.88, respectively. The errors in PTV dose coverage prediction for D98 and D95 were 2.88%±1.59 and 2.55%±1.28, respectively. The target model can predict the OAR mean dose within 2.43% and the OAR max dose within 4.33% on average across all OARs. CONCLUSION: We developed a site-agnostic model for three-dimensional dose prediction and tested its adaptability to a new target treatment site via transfer learning. Our proposed model can make accurate predictions with limited training data.

Tetrahydroquinoline units in flexible heteroarotinoids (Flex-Hets) convey anti-cancer properties in A2780 ovarian cancer cells.

SHetA2 (NSC 721689), our lead Flex-Het anti-cancer agent, consists of a thiochroman (Ring A) and a 4-nitrophenyl (Ring B) linked by a thiourea bridge. In this work, several series of new analogs having a tetrahydroquinoline (THQ, Ring A) unit connected by a urea or thiourea linker to a 4-substituted phenyl (Ring B) have been prepared and evaluated relative to SHetA2 in terms of binding affinity with mortalin and inhibition of A2780 ovarian cancer cells. Six of the derivatives equaled or exceeded the efficacy shown by SHetA2. Compounds 1a-d (series 1), lacking a methyl on the Ring A nitrogen and the gem-dimethyls on the adjacent carbon, showed only weak activity. Salt 2, the quaternized N,N-dimethyl iodide salt analog of 1a, also possessed very modest growth inhibition in the cell line studied. Series 3 compounds, which had a C3 ketone and an N-methyl replacing the sulfur in Ring A, were most successful. Compound 3a [Ring A = 1,2,2,4,4-pentamethyl-3-oxo-1,2,3,4-tetrahydroquinolin-6-yl; urea linker; Ring B = 4-nitrophenyl] had slightly lower potency (IC50 3.8 µM), but better efficacy (94.8%) than SHetA2 (IC50 3.17 µM, efficacy 84.3%). In addition, 3c and 3d [urea and thiourea linkers, respectively; Ring B = 4-(trifluoromethyl)phenyl] and 3e and 3f [urea and thiourea linkers, respectively; Ring B = 4-(trifluoromethoxy)phenyl] were also evaluated since these agents possessed electron-withdrawing groups with H-bonding capability. All displayed good activity. Compounds 3c and 3e showed improvement in both potency and efficacy compared to SHetA2. In general, when the linker group between Rings A and B was a urea, efficacy values slightly exceeded those with a thiourea linker in the carbonyl-containing THQ systems 3a-g. In contrast, when Ring A possessed the 1,2,2,4,4-pentamethyl-3-hydroxytetrahydroquinolin-6-yl unit (4a-f, series 4), very modest potency and efficacy was observed. Model compound 5, an exact N-methyl THQ analog of SHetA2, demonstrated less potency (IC50 4.5 µM), but improved efficacy (91.7%). Modeling studies were performed to rationalize the observed results.

Comparing the effect of dexmedetomidine and labetalol on hemodynamic variables in patients undergoing microlaryngoscopy.

INTRODUCTION: This study was conducted to compare the effect of dexmedetomidine and labetalol on hemodynamic variables in patients undergoing microlaryngoscopy. MATERIAL AND METHODS: In this randomized clinical trial study 70 patients undergoing microlaryngoscopy were involved. The patients were randomly assigned into two groups. Patients in dexmedetomidine group received 0.5 µg/kg of dexmedetomidine diluted in 100 ml of saline solution and the patients in the second group received 0.25 mg/kg of labetalol before anesthesia induction. At the beginning of the surgery, dexmedetomidine was infused at the dose of 0.4 µg/kg/h in the dexmedetomidine group, and labetalol at the dose of 1.8 mg/kg/h in the labetalol group. Patients' systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and heart rate at different times and anesthesia and surgery duration, recovery time and dose of prescribed propofol were recorded and compared between two groups. RESULTS: There was a significant difference in mean systolic blood pressure, mean diastolic blood pressure, mean arterial blood pressure and mean heart rate between two groups at different times (p value < 0.05). CONCLUSION: The results of this study indicated that dexmedetomidine had higher efficacy, compared to labetalol, in reducing diastolic blood pressure, systolic blood pressure, heart rate, and mean arterial blood pressure following microlaryngoscopy.

Activity of oxygen-versus sulfur-containing analogs of the Flex-Het anticancer agent SHetA2.

Five series of chromans with urea and thiourea linkers connecting a chroman unit (ring A) and a 4-substituted benzene unit (ring B) have been prepared and evaluated relative to SHetA2 (NSC 721689) for activity against the human A2780 ovarian cancer cell line. The lead compound SHetA2 had a sulfur in place of the oxygen in ring A and a thiourea linker to ring B. The 2-Me-4-Me series (two sets of geminal dimethyl groups at C2 and at C4 on the ring A unit) permitted direct comparison with SHetA2. Ring B in this series was evaluated with specific functional groups at C4 on the ring, including NO2, CO2Et, CF3, OCF3, CN and SO2NH2. The 2-H-4-Me series (only one geminal dimethyl group at the C4 position on ring A) permitted structure-activity relationship analysis to assess the importance of the hydrophobic geminal dimethyl groups on ring A to the activity of SHetA2. The remaining three series 2-Et-4-Me, 2-Me-4-Et and 2-Et-4-Et (ring A methyl groups replaced with ethyls at C2, at C4 and at both C2 and C4, respectively) offered the opportunity to modulate the hydrophobicity of the chroman moiety. Additionally, in all these series, the influence of a urea versus a thiourea linker was also investigated. The results of these modifications are summarized below. The exact analog of SHetA2 with oxygen substituted for sulfur in ring A (2a) showed comparable efficacy but a significantly lower IC50 against the ovarian cancer cell line. The urea linked analogs bearing CN, CF3 and OCF3 at C4 of ring B (3c,d and f) showed greater efficacy than SHetA2, but also had lower IC50 values. Removing the geminal dimethyl group at C2 (4a-c, 5a-c) caused a significant lowering of the efficacy and percent growth inhibition, indicating that the hydrophobic geminal dimethyl group at C2 in ring A is crucial for activity. Finally, replacing the geminal dimethyl groups with geminal diethyls on ring A in the urea derivatives gave 6b-c, 7c-d and 8b, all of which outperformed SHetA2 with respect to efficacy and IC50. The results for compounds 4-8 are in concurrence with modeling studies, which predicted that greater hydrophobicity in ring A would be beneficial. Binding energies were determined for compounds docked in silico to mortalin, the protein identified as a receptor of SHetA2. The urea linker promoted activity comparable to or, in some cases, greater than compounds with a thiourea linker. Several compounds achieved 94% efficacy and an IC50 of 2 µM, which were better than SHetA2 (84%, 3 µM).

Facile fabrication of sulfated alginate electrospun nanofibers.

Mass fabrication of sodium alginate nanofibers using single-nuzzle electrospinning process is an open challenge mainly due to its inter- and intramolecular hydrogen bonding, rigid chain conformation and low solubility. In this regards, we synthesized sodium sulfated alginate (SSA) through sulfation of hydroxyl functional groups of alginate. Not only decreases the hydrogen bonding density through the sulfation reaction, but the sulfated alginate also demonstrates more solubility in aqueous media compared to the pristine alginate. Beside the sulfation of alginate, its electrospinnability in combination with polyvinyl alcohol (PVA) significantly improves. In contrast to the neat alginate, concentrated aqueous solutions of sulfated alginate, 10 wt%, can be easily prepared and electrospun to obtain nanofibers of sulfated alginate. In this regards, facile fabrication of electrospun nanofibers of alginate derivatives with 50 wt% content in dry electrospun mat of SSA/PVA using single-nuzzle electrospinning and flow rate of 5 mL h-1 was developed for the first time.

ß-Adrenoceptors in the dorsal hippocampus are involved in ethanol-induced state-dependent retrieval in mice.

This study was designed to investigate the involvement of ß-adrenoceptors of the dorsal hippocampus (DH) in ethanol-induced state-dependent retrieval. We used a step-down type of inhibitory avoidance (IA) task to assess retrieval in male NMRI mice. Bilateral guide cannulae were implanted in the DH. The results showed that in the animals with pre-training injections of ethanol (1g/kg, i.p.) and pre-test saline treatment memory retrieval was impaired. Pre-test injections of ethanol (0.5 and 1g/kg, i.p.) also impaired memory retrieval in the animals that received saline before training. Ethanol (1g/kg, i.p.), when injected in both time points of pre-training and pre-test, induced state-dependent retrieval. The results also revealed that intra-DH infusions of a ß-adrenoceptor agonist salbutamol (0, 0.0025, 0.005, 0.01 and 0.02 µg/mouse) by itself had no significant effect, however, along with an ineffective dose of ethanol (0.25 g/kg) significantly improved memory retrieval. On the other hand, pre-test intra-DH infusions of different doses of a non-selective ß-adrenoceptor antagonist propranolol (0, 0.1, 0.3 and 0.5 µg/mouse) by itself had no effect on memory retrieval. But, pre-test intra-DH infusions of the same doses of propranolol (0, 0.1, 0.3 and 0.5 µg/mouse) disrupted ethanol-induced state-dependent retrieval. Interestingly, intra-DH infusions of propranolol (0.05, 0.75 and 0.1 µg/mouse) inhibited the improving effect of salbutamol on state-dependent retrieval. In conclusion, the results support the existence of a functional involvement of ß-adrenoceptors in the DH in ethanol-induced state-dependent retrieval.