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15 pages, 3661 KiB  
Article
Development of a Real-Time Radiation Exposure Estimation Method Using a Depth Camera for Radiation Protection Education
by Toshioh Fujibuchi, Hiroyuki Arakawa and Choirul Anam
Radiation 2024, 4(3), 261-275; https://doi.org/10.3390/radiation4030021 (registering DOI) - 15 Sep 2024
Abstract
X-ray fluoroscopy causes relatively high radiation exposure to physicians, radiation professionals, and patients. Understanding the behavior of scattered radiation is crucial for reducing occupational exposure. We developed a system for estimating radiation exposure during fluoroscopy by monitoring the position of the physician using [...] Read more.
X-ray fluoroscopy causes relatively high radiation exposure to physicians, radiation professionals, and patients. Understanding the behavior of scattered radiation is crucial for reducing occupational exposure. We developed a system for estimating radiation exposure during fluoroscopy by monitoring the position of the physician using a depth camera for radiation protection education. The dose distribution of scattered radiation in an X-ray room was simulated using Monte Carlo code. The data were displayed using augmented reality markers, and the dose at each joint point location was estimated using body tracking. Additional functions were created, such as displaying arbitrary two-dimensional cross-sections. The system performance ranged from 9.0 to 11.0 FPS with or without motion and a protective apron. The estimated doses were 0.93 to 1.21 times the measured doses for all joint points, except for the chest and pelvis. The estimated doses for the chest and pelvis were lower than the measured dose, with the minimum values being 0.72 and 0.60 times lower for the chest and pelvis, respectively. The system provides valuable insight into the estimation of radiation dose at joint points based on the physician’s position and movements, the physician’s optimal fluoroscopy location, and warning of dangerous exposure doses. Full article
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Figure 1

Figure 1
<p>System components and overview. The AR marker information is captured using Azure Kinect’s color image and superimposed in virtual space with the scattered ray distribution in the X-ray room calculated in advance using a Monte Carlo simulation. Furthermore, the body tracking of the physician is performed using Azure Kinect’s depth image. These are integrated with Unity to estimate the radiation exposure of the physician in real time.</p>
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<p>Model geometry. The X-ray device is an over-couch X-ray tube type, with a 20 cm thick water phantom placed above the bed to simulate the patient.</p>
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<p>Equipment geometry and measurement positions. The upper field AR marker of the X-ray tube was fixed and placed. The Azure Kinect was placed at a height of 200 cm using a tripod. Numbers 1 to 6 are dose assessment points that assume the physician’s position at 100 cm intervals. Tripods were set up here and dosimeters were placed.</p>
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<p>Body tracking a physician wearing a protective apron.</p>
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<p>Screenshot of the developed system in use.</p>
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<p>Arrangement of equipment in the X-ray room when using the system.</p>
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<p>Ratio of simulated and measured values at each position and height in the X-ray room.</p>
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<p>Difference between the distance estimated by the system and the measured value of each joint point from the AR marker.</p>
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<p>Measured and estimated doses at seven joint points (right eye, left eye, neck, chest, pelvis, right hand, and left hand). (<b>a</b>) shows the dose at 1 in <a href="#radiation-04-00021-f003" class="html-fig">Figure 3</a>, (<b>b</b>) shows the dose at 2 in <a href="#radiation-04-00021-f003" class="html-fig">Figure 3</a>, and (<b>c</b>) shows the dose at 3 in <a href="#radiation-04-00021-f003" class="html-fig">Figure 3</a>. The vertical axis unit is the individual dose equivalent of each site per 1 mGy of the entrance surface dose to the patient.</p>
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<p>Variation in dose across the thickness at chest height. The red line shows the radiation dose at a position 90 cm away, and the light blue line shows the radiation dose at a position 90 cm away.</p>
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9 pages, 1969 KiB  
Article
Silver Nanoparticles Improve Fluorophore Photostability: Application to a Hypericin Study
by Grzegorz Wołąkiewicz, Monika Pietrzak and Mariusz Szabelski
Int. J. Mol. Sci. 2024, 25(18), 9963; https://doi.org/10.3390/ijms25189963 (registering DOI) - 15 Sep 2024
Abstract
Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible [...] Read more.
Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible light, which transform into chemical compounds harmful to health. Manufacturers often include information on the prohibition of exposure to sunlight on the packaging, but consumers often do not read the product leaflet. The solution to this problem may be the addition of silver particles to preparations. In the presented article, we proposed the use of silver nanoparticles to reduce the photobleaching and photoreaction of fluorophore, while increasing the fluorescence intensity. For our research, we used a compound that is particularly sensitive to radiation: hypericin. Full article
(This article belongs to the Collection Feature Papers in Molecular Nanoscience)
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Figure 1

Figure 1
<p>Absorption spectrum of a slide with silver nanoparticles.</p>
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<p>Fluorescence enhancement of hypericin on the layer of silver nanoparticles.</p>
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<p>Fluorescence intensity of hypericin in time on the glass and a layer of silver nanoparticles as a function of the fluorescence spectrum area in the 570–800 nm range.</p>
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<p>Normalized fluorescence signal of hypericin on silver (<b>a</b>) and glass (<b>b</b>) at different exposure times.</p>
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<p>Normalized absorption spectrum of hypericin before and after irradiation on glass.</p>
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12 pages, 1009 KiB  
Article
The Systemic Inflammation Response Index Efficiently Discriminates between the Failure Patterns of Patients with Isocitrate Dehydrogenase Wild-Type Glioblastoma Following Radiochemotherapy with FLAIR-Based Gross Tumor Volume Delineation
by Sukran Senyurek, Murat Serhat Aygun, Nulifer Kilic Durankus, Eyub Yasar Akdemir, Duygu Sezen, Erkan Topkan, Yasemin Bolukbasi and Ugur Selek
Brain Sci. 2024, 14(9), 922; https://doi.org/10.3390/brainsci14090922 (registering DOI) - 15 Sep 2024
Abstract
Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients [...] Read more.
Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients who received RT at a dose of 60 Gy to the GTV and 50 Gy to the clinical target volume (CTV) and had documented recurrence were retrospectively analyzed. Each patient’s maximum distance of recurrence (MDR) from the GTV was documented in whichever plane it extended the farthest. The failure patterns were described as intra-GTV, in-CTV/out-GTV, distant, and intra-GTV and distant. For analytical purposes, the failure pattern was categorized into two groups, namely Group 1, intra-GTV or in-CTV/out-GTV, and Group 2, distant or intra-GTV and distant. The SIRI was calculated before surgery and corticosteroid administration. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal SIRI cut-off that distinguishes between the different failure patterns. Results: Failure occurred as follows: intra-GTV in 40 (56.3%), in-CTV/out-GTV in 4 (5.6%), distant in 18 (25.4%), and intra-GTV + distant in 9 (12.7%) patients. The mean MDR was 13.5 mm, and recurrent lesions extended beyond 15 mm in only seven patients. Patients with an SIRI score ≥ 3 demonstrated a significantly higher incidence of Group 1 failure patterns than their counterparts with an SIRI score < 3 (74.3% vs. 50.0%; p = 0.035). Conclusions: The present results show that using the SIRI with a cut-off value of ≥3 significantly predicts failure patterns. Additionally, the margin for the GTV can be safely reduced to 15 mm when using FLAIR-based target delineation in patients with GB. Full article
(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy)
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Figure 1

Figure 1
<p>Examples of failure pattern definition. Intra-GTV (<b>a</b>,<b>b</b>), in-CTV/out-GTV (<b>c</b>), and distant (<b>d</b>). Red line: gross tumor volume (prescribed dose: 60 Gy/30 fr), blue line: clinical target volume (prescribed dose: 50 Gy/30 fr), cyan line: recurrent lesion.</p>
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<p>Receiver operating characteristic curve analyses outcomes. Area under curve: 71.8%; sensitivity: 71.8%; specificity: 70.3%; J-index: 0.421.</p>
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30 pages, 3287 KiB  
Article
GABA(A) Receptor Activation Drives GABARAP–Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors
by Debanjan Bhattacharya, Riccardo Barrile, Donatien Kamdem Toukam, Vaibhavkumar S. Gawali, Laura Kallay, Taukir Ahmed, Hawley Brown, Sepideh Rezvanian, Aniruddha Karve, Pankaj B. Desai, Mario Medvedovic, Kyle Wang, Dan Ionascu, Nusrat Harun, Subrahmanya Vallabhapurapu, Chenran Wang, Xiaoyang Qi, Andrew M. Baschnagel, Joshua A. Kritzer, James M. Cook, Daniel A. Pomeranz Krummel and Soma Senguptaadd Show full author list remove Hide full author list
Cancers 2024, 16(18), 3167; https://doi.org/10.3390/cancers16183167 (registering DOI) - 15 Sep 2024
Abstract
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. We find that a [...] Read more.
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. We find that a GABA(A) receptor activator, AM-101, impairs the viability and clonogenicity of NSCLC primary and brain-metastatic cells. Employing a human-relevant ex vivo ‘chip’, AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide-disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP–Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity. Full article
(This article belongs to the Special Issue The Emerging Role of Ion Channels in Cancer Treatment)
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Figure 1
<p>Activation of GABA(A) receptors triggers cell depolarization and death. (<b>A</b>) Type-A GABA (GABA(A)) receptors are ligand-gated chloride anion channels. Left, GABA(A) receptors move chloride anions (Cl<sup>−</sup>) out of the cell during embryonic stages of development but into the cell in mature or developed stages and are thereby depolarizing or hyperpolarizing, respectively. Right, GABA(A) receptors form hetero-pentameric structures with an α2β2γ1 stoichiometry. Two molecules of GABA (purple spheres) bind at the α-β interfaces to ‘activate’ receptor function (chloride anion transport). Commonly, one molecule of benzodiazepine (red sphere) binds at the α-γ interface to enhance flow of chloride anions. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a> (<b>B</b>) Left, GABRA5 or α5 protein in NSCLC patient-derived primary cell lines representing three histological subtypes (adenocarcinoma, A549, H1792; squamous cell, H1703; large cell, H460). Right, GABRA5 or α5 protein expression in patient-derived lung adenocarcinoma brain-metastatic cell line (UW-lung-16), and primary human lung adenocarcinoma cell line (H1792). The presence of protein confirmed by Western blotting of SDS (4–15% gradient) gels. GAPDH is used as a loading control. Cropped gel lanes from original blots, see <a href="#app1-cancers-16-03167" class="html-app">Figure S8</a>. (<b>C</b>) NSCLC primary (left) and brain-metastatic (right) patient tumor tissue from the same patient (or matched) stains for GABRA5 or α5 protein, as shown by immunohistochemistry staining at 30× magnification. Arrows show GABRA5 staining in large tumor cells within primary and brain-metastatic lung adenocarcinoma tissue sections. (<b>D</b>) AM-101 (QH-II-066) (274.32 g/mol) is a benzodiazepine analog (left). A representative single cell patch clamp electrophysiology trace of patient-derived adenocarcinoma lung cell line H1792 (right). Cells are responsive to GABA or electro-physiologically functional. Perfusion of cells with AM-101 plus GABA elicits an enhanced response, indicating that GABA(A) receptors are benzodiazepine-responsive or ‘activated’. Representative raw current trace recording with the following parameters: GABA, 1 µM; AM-101, 4 µM. (<b>E</b>) Lung adenocarcinoma (H1792) cells incubated with AM-101 are depolarized, as assessed by the TMRE assay and Fluorescence-Activated Cell Sorting (FACS) analysis. Shown is the degrees of depolarization relative to DMSO-alone treatment and FCCP, which provide negative and positive controls in this experiment, respectively. Parameters: AM-101, 2 µM; FCCP, 10 µM. (<b>F</b>) Half-maximal inhibitory concentration (IC<sub>50</sub>) values of patient-derived lung primary and brain-metastatic lines representative of three histological lung cancer subtypes, as measured using a viability (MTS) assay and AM-101. Indicated is the KRAS and TP53 mutational status of lines, where M represents mutant, and WT represents wild-type.</p>
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<p>GABA(A) receptor activation potentiates radiation. (<b>A</b>) Illustration of a human-relevant ex vivo ‘chip’ employed to test AM-101 and docetaxel (DTX) efficacy. Lung adenocarcinoma cancer cells (H1792-GFP, green) can be co-cultured with primary human alveolar and pulmonary endothelial cells and exposed to air (air–liquid interface) on-chip. Cancer cells form clusters that grow and spread through the epithelial compartment of the chip over time (<a href="#app1-cancers-16-03167" class="html-app">Figure S3</a>). (<b>B</b>) Testing of AM-101 and DTX ex vivo or ‘on-chip’ reveals that AM-101 is as cytotoxic as DTX but at a significantly lower concentration. The chip is a 3-D ex vivo model, and, to achieve the cytotoxicity that AM-101 generates in 5 μM concentration, DTX is required in 10 mM concentrations. To determine <span class="html-italic">p</span>-values between two groups, one-way ANOVA with Tukey’s multiple comparisons test was performed. ** <span class="html-italic">p</span> &lt; 0.001 and *** <span class="html-italic">p</span> &lt; 0.0001. Images acquired from chips were subjected to background signal removal and analysis using Fiji (Image J). To generate bar graphs, acquired images were evaluated through background subtraction and signal thresholding. Subsequently, particle analysis was performed using a Fiji plugin to estimate the number of GFP+ cells per field of view under each testing condition. (<b>C</b>) A clonogenic assay was employed to examine the radio-sensitizing effect of AM-101 in H1792 cells. The survival curves showing surviving fraction of H1792 cells following radiation exposure at two separate doses with and without AM-101. Cell cultures were treated with either AM-101 (2.5 μM) combined with two separate doses of radiation (3 Gy and 6 Gy) versus DMSO (vehicle) and two separate doses of radiation (3 Gy and 6 Gy). H1792 cells in culture were treated with AM-101 (2.5 μM) or DMSO (vehicle) 1 h before radiation and maintained in the medium after irradiation. According to the experimental design the media containing AM-101 or DMSO in all groups was replaced with fresh media 72 h after treatment. Colony-forming efficiency was determined 14 days later, and survival curves were generated. The vehicle in this experiment is DMSO, since DMSO is used as the solvent to solubilize AM-101. (<b>D</b>) Schematic of the efficacy experiment in H1792 subcutaneous heterotopic bilateral xenograft tumors generated in NSG mice. Mice in vehicle or drug treatment groups received i.p., vehicle, AM-101 (2.5 mg/kg), or DTX (8 mg/kg), on day 36 post-implantation and then six injections once per day. Mice in radiation (RT) or combo groups received a single fraction of radiation (5 Gy) to left flank only at 2 h before vehicle or drug on the first day of treatment. (<b>E</b>) At experimental endpoint, tumors from left (L) and right (R) flanks of each mouse were resected. H1792 subcutaneous xenograft tumor growth in NSG mice from different treatment groups: vehicle, radiation (RT), AM-101 ± RT, DTX ± RT. Number of mice per treatment group: <span class="html-italic">n</span> = 6 for vehicle, <span class="html-italic">n</span> = 4 for RT; <span class="html-italic">n</span> = 7 for AM-101 and <span class="html-italic">n</span> = 7 for AM-101 + RT, <span class="html-italic">n</span> = 5 for DTX + RT and <span class="html-italic">n</span> = 6 for DTX. (<b>F</b>) Tumor volume of left and right flank tumors was measured over time using Vernier calipers. The tumor growth delay curves show the tumor volumes of mice treated with a vehicle, radiation (RT), AM-101, and AM-101 plus RT. Each point on the curve represents the mean tumor volume after treatment, with error bars indicating the standard error (SE). Statistical significance is indicated by <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>GABA(A) receptor activation increases survival of mice bearing lung brain-metastatic tumors. (<b>A</b>) Bar graphs representing the number of colonies generated from clonogenic assay to determine the radiosensitizing effect of AM-101 when combined with radiation treatment (RT) versus AM-101 (2.5 μM) or RT (3 Gy) alone in patient-derived brain-metastatic UW-lung-16 cells. The combination of AM-101 plus RT (combo group) imparts the most significant impact on colony formation, a three-fold suppression of colony numbers than control and two-fold suppression of colony numbers than AM-101 and RT applied alone. Control is DMSO treated, as DMSO is the diluent of AM-101. Data are represented as mean ± S.E. One-way ANOVA with Tukey’s multiple comparisons test was performed to determine the <span class="html-italic">p</span>-values between two treatment groups. The one-way ANOVA <span class="html-italic">p</span> &lt; 0.0001. Based on Tukey’s multiple comparisons test, Control vs. AM-101, *** <span class="html-italic">p</span> = 0.0001; Control vs. RT ** <span class="html-italic">p</span> = 0.0019; Control vs. Combo **** <span class="html-italic">p</span> &lt; 0.0001; AM-101 vs. RT, ns (not significant), <span class="html-italic">p</span> = 0.308; AM-101 vs. Combo *** <span class="html-italic">p</span> = 0.0001; RT vs. Combo **** <span class="html-italic">p</span> &lt; 0.0001. (<b>B</b>) Schematic of efficacy experiment in intracranial xenograft tumors generated in athymic nude mice. Mice received a stereotaxic intracranial injection of cells (UW-lung-16) from a brain lesion of a patient with lung cancer. Mice (<span class="html-italic">n</span> = 21) were separated into three treatment groups (<span class="html-italic">n</span> = 7 per group). Ten days post-injection, mice received (1) vehicle, an i.p. injection of formulation; (2) radiation (RT), 2.5 Gy dose/day to the whole mouse brain for 5 consecutive days; (3) AM-101 plus RT, i.p. injection of formulated AM-101 (5 mg/kg) and RT (2.5 Gy dose/day/mouse for 5 days) to the whole mouse brain using a XenX irradiator (Xstahl Ltd.) and the supplied mouse gantry. The day of intracranial injection of tumor cells was assigned as day zero. Tumors were followed by bioluminescent imaging (BLI) over time. (<b>C</b>) BLI study of mice with brain metastatic lung tumors and treated with vehicle, radiation (RT), or RT plus AM-101. Mice were imaged at indicated time points post-intracranial injection of tumor cells. (<b>D</b>) Kaplan–Meier survival curve with <span class="html-italic">p</span>-value (log rank test) calculated for statistical significance. Kaplan–Meier curves were used to estimate the survival of mice in each group in mouse intracranial xenograft experiments. Statistical significance was determined by using the log-rank test.</p>
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<p>GABA(A) receptor activation enhances autophagic puncta and the flux and triggers multimerization of GABARAP and Nix. (<b>A</b>) Shown are confocal immunofluorescence microscopic images of H1792 cells under various treatments: DMSO or control; AM-101 (3 µM); radiation (RT); and AM-101 plus RT (combo) (scale bar, 20 µm). Radiation dose was 3 Gy. Cells were stained for DNA with DAPI (blue fluorescent) and LC3B (left) using LC3B antibody. LC3B puncta were quantified per 3 cells for each experimental group and plotted, as shown in the bar graph, where * <span class="html-italic">p</span> = 0.0108 (control vs. AM-101); ** <span class="html-italic">p</span> = 0.0037 (control vs. RT); **** <span class="html-italic">p</span> &lt; 0.0001 (control vs. combo) (right), which reveals a similar effect between AM-101 versus RT, but combining these two has a statistically pronounced impact on puncta formation. (<b>B</b>) Confocal immunofluorescence microscopic images of H1792 cells under various treatments that were then stained for DAPI and Nix to identify and quantify Nix puncta (left). Nix puncta were quantified per 3 cells for each experimental group and plotted, as shown in the bar graph, where *** <span class="html-italic">p</span> = 0.0008 (control vs. AM-101); ** <span class="html-italic">p</span> = 0.006 (control vs. RT); **** <span class="html-italic">p</span> &lt; 0.0001 (control vs. combo) (right), which reveals a pronounced effect of AM-101 on puncta formation and an increase in puncta when AM-101 is combined with radiation (RT) (combo treatment group). For statistical calculations, one-way ANOVA was performed and followed up with Dunnett’s multiple comparisons test. (<b>C</b>) Immunoblotting (using 4–15% gradient gel PAGE) demonstrates enhanced autophagic flux with LC3B-II as a marker in H1792 cells following co-treatment with AM-101 and bafilomycin A1. A representative immunoblot probed with an LC3B antibody shows the results from cell lysates of control (DMSO-treated) and three treatment groups: BafA1 alone, AM-101 alone, and AM-101 combined with BafA1. H1792 cells were treated with 3 μM AM-101 for 48 h, followed by either 50 nM bafilomycin A1 (AM-101 + BafA1) or DMSO (vehicle) for an additional 4 h. Control cells were treated with DMSO for 48 h and then with either 50 nM bafilomycin A1 or DMSO for 4 h. The right panel shows LC3B-II band intensities quantified using ImageJ, with bar graphs representing the fold increase in LC3B-II for each treatment group relative to the vehicle control (data shown as mean ± SEM, <span class="html-italic">n</span> = 2). Co-treatment of AM-101 and bafilomycin A1 significantly increased LC3B-II compared to AM-101 or bafilomycin A1 alone. GAPDH is used as loading control. To measure the statistical significance, ordinary one-way ANOVA (one-way ANOVA <span class="html-italic">p</span> &lt; 0.0006) with Tukey’s multiple comparison test was performed to compare the means of each group. ** <span class="html-italic">p</span> = 0.0051 (BafA1 vs. AM-101); ** <span class="html-italic">p</span> = 0.0029 (BafA1 vs. AM-101 + BafA1); and *** <span class="html-italic">p</span> = 0.0005 (AM-101 vs. AM-101 + BafA1). (<b>D</b>) Modified immunoblotting of SDS gels (4–15% gradient gel) showing the effect of AM-101 on monomeric GABARAP expression and its oligomeric state in H1792 cells. (<b>E</b>) Modified immunoblotting of SDS gels (4–15% gradient gel) showing the effect of AM-101 on monomeric Nix protein expression and its oligomeric state in H1792 cells. AM-101 (3.0 µM) triggers a multimerization of GABARAP and an apparent increase in abundance at 72 h (left). Nix abundance is also enhanced as well as formation of dimer by AM-101 (3 µM) in a concentration-dependent manner in H1792 cells. GAPDH is used as a loading control for both experiments in (<b>D</b>,<b>E</b>). D: dimer; M: monomer. Original western blots are presented in <a href="#app1-cancers-16-03167" class="html-app">Figure S9</a>.</p>
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<p>Change in abundance or utilization of autophagy biomarkers in response to GABA(A) activation. (<b>A</b>) ATG7 immunoblot (4–15% gradient polyacrylamide gel) of patient-derived lung adenocarcinoma primary (H1792) and brain-metastatic (UW-lung-16) cells following treatment with AM-101. Left, immunoblot showing increased expression of one isoform of ATG7 protein in primary H1792 cells of following treatment with 3.0 µM of AM-101 for 48 h compared to the control. Control: DMSO treated. Right, immunoblot showing change in ATG7 protein levels over time in lung cancer brain-metastatic UW-lung-16 cells treated with 3.0 µM AM-101 compared to the control. Significant increase in ATG7 protein is observed at 72 h. Control: DMSO treated. (<b>B</b>) Immunoblots showing the effect of in vitro AM-101 treatment on protein levels of ATG-12-ATG5 conjugate in primary H1792 cells (<b>left</b> panel) and patient-derived lung cancer brain metastatic UW-lung-16 (<b>right</b> panel) cells. In case of H1792 cells (<b>left</b> panel) sample was collected at 72 h after AM-101 treatment and in case of UW-lung-16 cells (<b>right</b> panel), samples were collected from both 48 h and 72 time points post treatment. (<b>C</b>) p62 immunoblots of SDS gels of lung adenocarcinoma primary (H1792) and brain-metastatic (UW-lung-16) cells following treatment with AM-101. Left, changes in expression of p62 protein as assessed by immunoblotting of lysates from H1792 cells treated with AM-101, radiation (3 Gy), and a combination of radiation (RT) plus AM-101 only. Control, DMSO. Middle, evaluation of the time-dependent utilization of p62 after AM-101 (3.0 µM) treatment in primary lung cancer cell (H1792). Right, patient-derived brain-metastatic lung adenocarcinoma cell line UW-lung-16 (right). Control, DMSO. GAPDH is used as a loading control. (<b>D</b>) Left, immunoblot showing Beclin-1 protein levels in control and AM-101 treated H1792 cells (treated for 72 h). Control, DMSO. Right, immunoblot shows Beclin-1 protein levels in patient-derived lung brain-metastatic UW-lung-16 cells treated with AM-101, radiation (3 Gy), and radiation (3 Gy) along with AM-101. Original western blots are presented in <a href="#app1-cancers-16-03167" class="html-app">Figure S10</a>.</p>
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<p>GABARAP–Nix abrogation inhibits AM-101 cytotoxicity. (<b>A</b>) Combined treatment of lung adenocarcinoma (H1792) cells with AM-101 plus Pen3-<span class="html-italic">ortho</span> (P3<span class="html-italic">o</span>), a stapled-peptide that binds to GABARAP and abrogates Nix binding, inhibits the cytotoxicity of AM-101. The inhibitory effect of P3<span class="html-italic">o</span> is enhanced with an increased concentration of the inhibitor. **** <span class="html-italic">p</span> &lt; 0.0001 [AM-101 vs. P3<span class="html-italic">o</span> (15 μM) + AM-101]; **** <span class="html-italic">p</span> &lt; 0.0001 [AM-101 vs. P3<span class="html-italic">o</span> (25 μM) + AM-101]; **** <span class="html-italic">p</span> &lt; 0.0001 [P3<span class="html-italic">o</span> (25 μM) vs. P3<span class="html-italic">o</span> (25 μM) + AM-101]. One-way ANOVA with Tukey’s multiple comparisons test was performed. (<b>B</b>) Treatment of H1792 cells with two different concentrations of P3<span class="html-italic">o</span> does not impact GABARAP protein abundance, as observed by immunoblot of SDS gel probed for GABARAP. (<b>C</b>) Treatment of H1792 cells with P3<span class="html-italic">o</span> reduces both Nix dimer and monomer protein levels, as observed by immunoblot of SDS gel probed for Nix. D: dimer, M: monomer. GAPDH is used as a loading control. Original western blots are presented in <a href="#app1-cancers-16-03167" class="html-app">Figure S11</a>.</p>
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<p>Model of GABA(A)-receptor-mediated autophagy. (<b>A</b>) NSCLC cells possess intrinsic GABA(A) receptors (chloride anion channels). (<b>B</b>) AM-101 activates GABA(A) receptors, which in turn depolarize mitochondria. Changes in the cancer cell by binding of AM-101 to the receptor in combination with radiation include (i) enhanced expression–abundance of key genes involved in autophagy, including <span class="html-italic">ATG7</span> and <span class="html-italic">BECLIN-1</span>; (ii) increased phosphorylation of the histone variant H2AX to generate γ-H2AX. (<b>C</b>) Depolarization induces key autophagic events in synergy with radiation: (i) enhanced expression and dimerization of GABA(A) receptor-associated protein, GABARAP; (ii) stabilization and dimerization of Nix, coupling GABARAP to mitochondria; (iii) enhanced expression of autophagy-associated proteins Beclin-1 and ATG7; (iv) utilization of ubiquitin-binding protein p62. Nix dimerization increases its stability and coordinates the nucleation of autophagosome formation. In this manner, GABA(A) receptor activation induces complex multimerization, activating autophagy. (<b>D</b>) Over time, GABARAP multimerizes commensurate with multimerization of the GABA(A) receptor, which enhances its activity. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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15 pages, 3249 KiB  
Article
The InterVision Framework: An Enhanced Fine-Tuning Deep Learning Strategy for Auto-Segmentation in Head and Neck
by Byongsu Choi, Chris J. Beltran, Sang Kyun Yoo, Na Hye Kwon, Jin Sung Kim and Justin Chunjoo Park
J. Pers. Med. 2024, 14(9), 979; https://doi.org/10.3390/jpm14090979 (registering DOI) - 15 Sep 2024
Abstract
Adaptive radiotherapy (ART) workflows are increasingly adopted to achieve dose escalation and tissue sparing under dynamic anatomical conditions. However, recontouring and time constraints hinder the implementation of real-time ART workflows. Various auto-segmentation methods, including deformable image registration, atlas-based segmentation, and deep learning-based segmentation [...] Read more.
Adaptive radiotherapy (ART) workflows are increasingly adopted to achieve dose escalation and tissue sparing under dynamic anatomical conditions. However, recontouring and time constraints hinder the implementation of real-time ART workflows. Various auto-segmentation methods, including deformable image registration, atlas-based segmentation, and deep learning-based segmentation (DLS), have been developed to address these challenges. Despite the potential of DLS methods, clinical implementation remains difficult due to the need for large, high-quality datasets to ensure model generalizability. This study introduces an InterVision framework for segmentation. The InterVision framework can interpolate or create intermediate visuals between existing images to generate specific patient characteristics. The InterVision model is trained in two steps: (1) generating a general model using the dataset, and (2) tuning the general model using the dataset generated from the InterVision framework. The InterVision framework generates intermediate images between existing patient image slides using deformable vectors, effectively capturing unique patient characteristics. By creating a more comprehensive dataset that reflects these individual characteristics, the InterVision model demonstrates the ability to produce more accurate contours compared to general models. Models are evaluated using the volumetric dice similarity coefficient (VDSC) and the Hausdorff distance 95% (HD95%) for 18 structures in 20 test patients. As a result, the Dice score was 0.81 ± 0.05 for the general model, 0.82 ± 0.04 for the general fine-tuning model, and 0.85 ± 0.03 for the InterVision model. The Hausdorff distance was 3.06 ± 1.13 for the general model, 2.81 ± 0.77 for the general fine-tuning model, and 2.52 ± 0.50 for the InterVision model. The InterVision model showed the best performance compared to the general model. The InterVision framework presents a versatile approach adaptable to various tasks where prior information is accessible, such as in ART settings. This capability is particularly valuable for accurately predicting complex organs and targets that pose challenges for traditional deep learning algorithms. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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<p>The proposed InterVision framework. (1) illustrates the general model training using the original dataset, the training set and the validation set is divided using the original dataset. (2) illustrates the progress of the general fine-tuning model. The general fine-tuning model is using 1 personalized patient data for the training. For the evaluation, other fraction of the personalized patient data will be used. (3) shows the workflow of the InterVision framework. (3-1), (3-2) and (3-3) show the process of generating InterVision dataset.</p>
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<p>Conceptual representation of generating the InterVision dataset. A deformable vector is created by comparing each slide. Utilizing this deformable vector, we generate intermediate images between each slide. Consequently, we nearly doubled the size of the personalized dataset.</p>
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<p>Concept of calculating deformation vectors using control points. Images within the original image are repositioned based on the deformation vectors derived from each control point. The degree of deformation applied to a voxel increases as its proximity to the control point decreases.</p>
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<p>The architecture of Swin-Unet comprises an encoder, bottleneck, decoder, and skip connections. All components—the encoder, bottleneck, and decoder—are constructed using Swin Transformer blocks.</p>
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<p>Overview of the Swim Transformer block structure.</p>
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<p>Visual results of the optic chiasm (<b>a</b>), L cochlea (<b>b</b>) and L parotid (<b>c</b>) achieved by the general model, the general fine-tuning model and the InterVision model comparing with the manual contours in yellow.</p>
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23 pages, 7362 KiB  
Article
Thermal Efficiency Analysis of a 1 kW ORC System with a Solar Collection Stage and R-245fa Working Fluid: A Case Study
by Raúl Alejandro Martínez-Sánchez, José M. Álvarez-Alvarado, Gerardo I. Pérez-Soto, Idalberto Macías-Socarrás, Karla A. Camarillo-Gómez and Juvenal Rodríguez-Reséndiz
Fluids 2024, 9(9), 217; https://doi.org/10.3390/fluids9090217 (registering DOI) - 15 Sep 2024
Abstract
A thermal efficiency analysis of an organic Rankine cycle (ORC) system enables its performance to be evaluated; for this purpose, critical system components, including the turbine and the boiler, must be scrutinized. ORC plants can operate under various regimes, such as simple, regeneration, [...] Read more.
A thermal efficiency analysis of an organic Rankine cycle (ORC) system enables its performance to be evaluated; for this purpose, critical system components, including the turbine and the boiler, must be scrutinized. ORC plants can operate under various regimes, such as simple, regeneration, and reheat work modes. Organic fluids such as R-245fa integrate low-temperature sources such as solar radiation. However, a literature review revealed limited research on the impact of a solar collection system on the overall thermal efficiency of an ORC system during the regeneration stage. In this study, we examined the thermal efficiency behavior of an ORC plant with a 1 kW generator operating in simple and regeneration modes with a solar collection stage. The results show that the thermal efficiency in simple mode was 35.27%, while in regeneration mode with solar collection it reached 51.30%. Improving the thermal efficiency of a thermodynamic cycle system can reduce CO2 emissions. The operating temperature ranges facilitate the development of a methodology for industries to implement ORC systems in their manufacturing processes, thereby utilizing waste heat from industrial operations. Full article
(This article belongs to the Special Issue Evaporation, Condensation and Heat Transfer)
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<p>(<b>a</b>) The stages and equipment of an ideal Rankine cycle. (<b>b</b>) A T–s diagram of an ideal Rankine cycle.</p>
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<p>(<b>a</b>) The stages and equipment of an ideal Rankine cycle with a regeneration stage. (<b>b</b>) A T–s diagram of an ideal regenerative Rankine cycle.</p>
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<p>ORC prototype plant.</p>
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<p>Diagram of equipment, field instrumentation, and piping.</p>
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<p>Process flow diagram.</p>
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<p>Pressure control strategy.</p>
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<p>Solar collector coupled to regeneration stage in ORC plant.</p>
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<p>ORC plant instrumentation diagram.</p>
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<p>Solar irradiation measured at solarimetric station.</p>
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<p>Thermal efficiency obtained from solar collector.</p>
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<p>(<b>a</b>) Values measured with temperature sensor TT-01. (<b>b</b>) Values measured with temperature sensor TT-02.</p>
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<p>(<b>a</b>) Values measured with temperature sensor TT-03. (<b>b</b>) Values measured with temperature sensor TT-04.</p>
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<p>(<b>a</b>) Values measured with temperature sensor TT-05. (<b>b</b>) Enthalpy values obtained from analysis of thermodynamic states.</p>
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12 pages, 9997 KiB  
Article
Molecular Characterization of the MoxR AAA+ ATPase of Synechococcus sp. Strain NKBG15041c
by Kota Mano, Kentaro Noi, Kumiko Oe, Takahiro Mochizuki, Ken Morishima, Rintaro Inoue, Masaaki Sugiyama, Keiichi Noguchi, Kyosuke Shinohara, Masafumi Yohda and Akiyo Yamada
Int. J. Mol. Sci. 2024, 25(18), 9955; https://doi.org/10.3390/ijms25189955 (registering DOI) - 15 Sep 2024
Abstract
We isolated a stress-tolerance-related gene from a genome library of Synechococcus sp. NKBG15041c. The expression of the gene in E. coli confers resistance against various stresses. The gene encodes a MoxR AAA+ ATPase, which was designated SyMRP since it belongs to the MRP [...] Read more.
We isolated a stress-tolerance-related gene from a genome library of Synechococcus sp. NKBG15041c. The expression of the gene in E. coli confers resistance against various stresses. The gene encodes a MoxR AAA+ ATPase, which was designated SyMRP since it belongs to the MRP subfamily. The recombinant SyMRP showed weak ATPase activity and protected citrate synthase from thermal aggregation. Interestingly, the chaperone activity of SyMRP is ATP-dependent. SyMRP exists as a stable hexamer, and ATP-dependent conformation changes were not detected via analytical ultracentrifugation (AUC) or small-angle X-ray scattering (SAXS). Although the hexameric structure predicted by AlphaFold 3 was the canonical flat-ring structure, the structures observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM) were not the canonical ring structure. In addition, the experimental SAXS profiles did not show a peak that should exist in the symmetric-ring structure. Therefore, SyMRP seems to form a hexameric structure different from the canonical hexameric structure of AAA+ ATPase. Full article
(This article belongs to the Section Molecular Microbiology)
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<p>Amino acid sequence alignment (<b>a</b>) and phylogenetic tree of SyMRP (<b>b</b>). Amino acid sequence alignments were performed via ClustalOmega. A phylogenetic tree was generated by iTOL.</p>
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<p>Effects of SyMRP on the growth of <span class="html-italic">E. coli</span> under various stress conditions. (<b>a</b>–<b>d</b>) Growth curves under various stress conditions. (<b>a</b>) Nonstress condition. (<b>b</b>) Salt stress condition (1.0 M NaCl). (<b>c</b>) Acid stress condition (pH 4.0). (<b>d</b>) Thermal stress condition (45 °C). Red circle: pSK-SyMRP; blue circle: pSK-BAA10517; black: vector control. (<b>e</b>–<b>g</b>) Spot tests. 1: pSK-SyMRP, 2: pSK-BAA10517, 3: vector control. (<b>e</b>) Nonstress condition. (<b>f</b>) Salt stress condition (0.8 M NaCl). (<b>g</b>) Thermal stress condition (50 °C, 30 min).</p>
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<p>Effects of SyMRP on the growth of <span class="html-italic">E. coli</span> under various stress conditions. (<b>a</b>–<b>d</b>) Growth curves under various stress conditions. (<b>a</b>) Nonstress condition. (<b>b</b>) Salt stress condition (1.0 M NaCl). (<b>c</b>) Acid stress condition (pH 4.0). (<b>d</b>) Thermal stress condition (45 °C). Red circle: pSK-SyMRP; blue circle: pSK-BAA10517; black: vector control. (<b>e</b>–<b>g</b>) Spot tests. 1: pSK-SyMRP, 2: pSK-BAA10517, 3: vector control. (<b>e</b>) Nonstress condition. (<b>f</b>) Salt stress condition (0.8 M NaCl). (<b>g</b>) Thermal stress condition (50 °C, 30 min).</p>
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<p>Chaperone function of SyMRP. The thermal aggregation of CS from the porcine heart was monitored by measuring light scattering at 500 nm with a spectrofluorometer at 43 °C. CS (0.1 µM, monomer) was incubated in assay buffer with or without SyMRP and BSA at the specified concentration. To examine their effects, 1 mM ATP (<b>a</b>) or ADP (<b>b</b>) was added.</p>
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<p>AUC results of SyMRP solutions at 25 °C. The red and blue lines show the concentration distributions of molecules as a function of the sedimentation coefficient for the solutions without and with ATP, respectively.</p>
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<p>SAXS profiles of SyMRP solutions at 25 °C. The red and blue circles show the SAXS profiles of the solutions without and with ATP, respectively. The solid black line indicates the calculated scattering profile for the hexameric model predicted by AlphaFold 3. The arrow represents the peak for the calculated scattering profile at <span class="html-italic">q</span> ~ 0.2 Å<sup>−1</sup>.</p>
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<p>Hexameric structure of SyMRP predicted by AlphaFold 3. (<b>a</b>) Top view, (<b>b</b>) side view.</p>
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<p>AFM and TM images of SyMRP. (<b>a</b>) Images of small oligomers observed by AFM. (<b>b</b>) Image of probable hexamers observed by TEM (<b>top</b>) and AFM (<b>bottom</b>).</p>
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16 pages, 3332 KiB  
Review
Complex Diagnostic Challenges in Glioblastoma: The Role of 18F-FDOPA PET Imaging
by David Sipos, Zsanett Debreczeni-Máté, Zsombor Ritter, Omar Freihat, Mihály Simon and Árpád Kovács
Pharmaceuticals 2024, 17(9), 1215; https://doi.org/10.3390/ph17091215 (registering DOI) - 15 Sep 2024
Viewed by 70
Abstract
Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterized by rapid proliferation and diffuse infiltration into the surrounding brain tissues. Despite advancements in therapeutic approaches, the prognosis for GBM patients is poor, with median survival times [...] Read more.
Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterized by rapid proliferation and diffuse infiltration into the surrounding brain tissues. Despite advancements in therapeutic approaches, the prognosis for GBM patients is poor, with median survival times rarely exceeding 15 months post-diagnosis. An accurate diagnosis, treatment planning, and monitoring are crucial for improving patient outcomes. Core imaging modalities such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are indispensable in the initial diagnosis and ongoing management of GBM. Histopathology remains the gold standard for definitive diagnoses, guiding treatment by providing molecular and genetic insights into the tumor. Advanced imaging modalities, particularly positron emission tomography (PET), play a pivotal role in the management of GBM. Among these, 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-FDOPA) PET has emerged as a powerful tool due to its superior specificity and sensitivity in detecting GBM and monitoring treatment responses. This introduction provides a comprehensive overview of the multifaceted role of 18F-FDOPA PET in GBM, covering its diagnostic accuracy, potential as a biomarker, integration into clinical workflows, impact on patient outcomes, technological and methodological advancements, comparative effectiveness with other PET tracers, and its cost-effectiveness in clinical practice. Through these perspectives, we aim to underscore the significant contributions of 18F-FDOPA PET to the evolving landscape of GBM management and its potential to enhance both clinical and economic outcomes for patients afflicted with this formidable disease. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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<p>The chemical structure of <sup>18</sup>F-FDOPA.</p>
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<p>Left frontal post craniotomy status. Inhomogeneous, mainly centrally, moderate enhancement of contrast material is observed on T1-weighted post-contrast MRI images. The lesion in the left hemisphere is surrounded by edema (<b>C</b>,<b>D</b>). Irregularly shaped intense, focal <sup>18</sup>F-FDOPA accumulation can be detected on the left side of the brain frontally, above the level of lateral ventricles (<b>A</b>,<b>B</b>). Pink line—GTV, green line—BTV 1.7 (<b>A</b>,<b>C</b>), green line—BTV 2.0 (<b>B</b>,<b>D</b>), red line—PTV, and yellow line—recurrence [<a href="#B42-pharmaceuticals-17-01215" class="html-bibr">42</a>].</p>
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17 pages, 3437 KiB  
Article
Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment
by Eva Schmidt, Luitpold Distel, Ramona Erber, Maike Büttner-Herold, Marie-Charlotte Rosahl, Oliver J. Ott, Vratislav Strnad, Carolin C. Hack, Arndt Hartmann, Markus Hecht, Rainer Fietkau and Sören Schnellhardt
Cancers 2024, 16(18), 3160; https://doi.org/10.3390/cancers16183160 (registering DOI) - 15 Sep 2024
Viewed by 123
Abstract
Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage [...] Read more.
Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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<p>Representative images of sections of breast cancer tissue microarray cores with immunohistochemical CD66b staining. (<b>A</b>) Invasive front sample with stromal neutrophil infiltration (brown). Example of intraepithelial compartment segmentation (green) via BIOMAS software. (<b>B</b>) Tissue microarray core of lymph node sample with an example of stained neutrophils (brown) among other inflammatory cells (blue). (<b>C</b>) Normal tissue sample with immunohistochemical CD66b staining of neutrophils (brown) in between adipose tissue. (<b>D</b>) Box plots of stromal and intraepithelial CD66b+ cell density distribution in different locations. Horizontal black bars signify <span class="html-italic">p</span> &lt; 0.05 in Student’s <span class="html-italic">t</span>-test. The central line indicates median values while the box represents the interquartile range (IQR). Whiskers represent 1.5 × IQR or minimum/maximum. Outliers are represented by dots (up to 3 × IQR) or asterisks (&gt;3 IQR). Outliers not visible in this diagram are depicted as a caret.</p>
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<p>(<b>A</b>) Disease-free survival of the studied patient cohort analyzed with the Kaplan–Meier method and log-rank test. (<b>B</b>) Disease-free survival according to stromal CD66b+ neutrophil density in lymph nodes. (<b>C</b>,<b>D</b>) Disease-free survival according to stromal CD66b+ neutrophil density in normal tissue from tumor proximity (<b>C</b>) and normal tissue from the periphery of the resection (<b>D</b>).</p>
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<p>(<b>A</b>,<b>B</b>) Disease-free survival rate according to stromal (<b>A</b>) and intraepithelial (<b>B</b>) CD66b+ neutrophil density in central breast tumor samples analyzed with the Kaplan–Meier method and log-rank test. (<b>C</b>,<b>D</b>) Disease-free survival rate according to stromal (<b>C</b>) and intraepithelial (<b>D</b>) CD66b+ neutrophil density in invasive front samples.</p>
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<p>(<b>A</b>) Box plots of stromal (blue) and intraepithelial (red) CD66b+ cell density distribution in patients with high versus low M1/M2 ratio. Carets signify outliers. (<b>B</b>,<b>C</b>) Disease-free survival rate according to stromal (<b>B</b>) and intraepithelial (<b>C</b>) CD66b+ neutrophil density in central breast tumor samples in patients with a high M1/M2 ratio analyzed with the Kaplan–Meier method and log-rank test. (<b>D</b>,<b>E</b>) Disease-free survival according to stromal (<b>D</b>) and intraepithelial (<b>E</b>) CD66b+ neutrophil density in central tumor samples in patients with a low M1/M2 ratio.</p>
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<p>Proposed model of cellular mechanisms of immunosuppression in early luminal breast cancer. Type A tumors are capable of polarizing tumor-associated macrophages (TAMs) towards the immunosuppressive M2-like state (low M1/M2 ratio), resulting in inactivation of anti-tumor elements like cytotoxic T cells. Tumor-associated neutrophils (TANs) are numerous but play a subordinate role, possibly due to the contrary effects of anti-tumor N1-like TANs and suppressive N2-like TANs in this scenario. Type B tumors are not capable of macrophage repolarization (high M1/M2 ratio) and utilize the immunosuppressive properties of TANs which are most likely polarized towards the N2-like state. Figure created with Biorender.com.</p>
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15 pages, 9533 KiB  
Article
Photo-Crosslinked Pro-Angiogenic Hydrogel Dressing for Wound Healing
by Wang Zhang, Shuyi Qian, Jia Chen, Tianshen Jian, Xuechun Wang, Xianmin Zhu, Yixiao Dong and Guoping Fan
Int. J. Mol. Sci. 2024, 25(18), 9948; https://doi.org/10.3390/ijms25189948 (registering DOI) - 15 Sep 2024
Viewed by 148
Abstract
Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and [...] Read more.
Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF–Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing. Full article
(This article belongs to the Special Issue Advanced Research on Wound Healing 2.0)
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<p>Fabrication of an injectable HA-P hydrogel wound dressing. (<b>A</b>) Schematic illustration of the synthesis of MeHA and in situ crosslinking with cysteine-modified PR1P to form a hydrogel wound dressing. (<b>B</b>) Real-time crosslinking rheological measurements of HA and HA-P hydrogels (0.5% <span class="html-italic">w</span>/<span class="html-italic">v</span>) with 30 s exposure to UV radiation. (<b>C</b>) Compressive modulus of HA hydrogels with different material concentrations (gelation with 30 s exposure to UV radiation). (<b>D</b>) Compressive modulus of HA and HA-P hydrogels (0.5% <span class="html-italic">w</span>/<span class="html-italic">v</span>, with 30 s exposure to UV radiation) (mean ± SD, n = 6, <span class="html-italic">** p &lt;</span> 0.01, <span class="html-italic">**** p &lt;</span> 0.0001, ns, not statistically significant).</p>
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<p>Characterization of HA and HA-P hydrogels. (<b>A</b>,<b>B</b>) SEM micrographs and quantification of the average pore size of freeze-dried HA hydrogels (0.5% <span class="html-italic">w</span>/<span class="html-italic">v</span>) with 30 s, 60 s, and 90 s of UV exposure. (<b>C</b>,<b>D</b>) SEM micrographs and quantification of the average pore size of HA and HA-P hydrogels (0.5% <span class="html-italic">w</span>/<span class="html-italic">v</span>, with 30 s of UV exposure). (<b>E</b>,<b>F</b>) Swelling ratios of HA hydrogels with various UV exposure times and material concentrations. (<b>G</b>) Swelling ratios of HA and HA-P hydrogels (0.5% <span class="html-italic">w</span>/<span class="html-italic">v</span>, with 30 s of UV exposure) (mean ± SD, n = 3, *** <span class="html-italic">p</span> &lt; 0.001, <span class="html-italic">**** p</span> &lt; 0.0001, ns, not statistically significant, scale bar, 100 μm).</p>
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<p>VEGF recruitment and in vitro angiogenic effect of HA-P hydrogels. (<b>A</b>) Schematic illustration of VEGF recruitment assay. (<b>B</b>) Quantitative analysis of the maintained VEGF within hydrogels shows the HA-P hydrogel binds more VEGF than HA hydrogel does (n = 8). (<b>C</b>) Representative images of cell migration in a scratch wound healing assay after 0, 6, 12, and 24 h. (<b>D</b>) Quantitative analysis of the migration ratio shows HA-P hydrogel loaded with VEGF significantly promotes cell migration compared with the other groups. (<b>E</b>) Representative images of the tube formation of HUVECs. (<b>F</b>,<b>G</b>) Quantitative analysis of capillary length and the number of branch points of the tubule network. The capillary length and branch points in HA-P hydrogels are significantly higher than in the other groups (mean ± SD, n = 3, <span class="html-italic">** p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, scale bar, 200 μm).</p>
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<p>HA-P hydrogel dressing promotes wound regeneration in burns. (<b>A</b>) Representative photos exhibit the wound healing process. (<b>B</b>) Quantitative analysis of residual wound area (%) up to 14 days. HA-P hydrogel treatment shows significant acceleration of healing compared to the control group after day 6. (<b>C</b>) Representative images of H&amp;E staining and (<b>D</b>) Masson’s trichrome staining of the wounds at 14 days post-wounding (scale bar, 500 μm). (<b>E</b>) Quantitative analysis of epithelium thickness and (<b>F</b>) collagen density indicates less epidermis hyperplasia and increased collagen deposition in the HA-P hydrogel treatment group (mean ± SD, n = 8–10, <span class="html-italic">* p</span> &lt; 0.05, <span class="html-italic">** p</span> &lt; 0.01, ns, not statistically significant).</p>
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<p>HA-P hydrogel dressing enhances angiogenesis and reduces myofibroblasts in burns. (<b>A</b>) Representative images of the CD31<sup>+</sup> staining (green) of different groups at day 14 post-wounding. The nucleus was stained with DAPI (blue). (<b>B</b>,<b>C</b>) Stereological quantification of the surface area and length density of vasculature demonstrates a significant enhancement in angiogenesis for HA-P hydrogel compared with the control group. (<b>D</b>) Representative images of α-SMA<sup>+</sup> staining (red) at day 14 post-wounding. The nucleus was stained with DAPI (blue). (<b>E</b>) Quantitative analysis of the positive area of α-SMA shows the HA-P hydrogel treatment significantly reduces myofibroblasts’ regeneration (mean ± SD, n = 8–10, <span class="html-italic">** p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001, ns, not statistically significant, scale bar, 100 μm).</p>
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<p>HA-P hydrogel dressing promoted angiogenesis via activation of the VEGF–Akt signaling pathway. (<b>A</b>) Schematic illustration of the molecular mechanism for HA-P hydrogel dressing which activates the VEGF–Akt signaling pathway in wound healing. (<b>B</b>) Representative images of Western blotting of Akt, p-Akt, and VEGFA in wounds at day 14 post-wounding. (<b>C</b>,<b>D</b>) Quantitative results of Western blotting show that the HA-P hydrogel treatment significantly increases the relative protein expression level of VEGFA and the relative expression ratio of p-Akt/Akt (mean ± SD, n = 8–10, <span class="html-italic">* p</span> &lt; 0.05, ns, not statistically significant).</p>
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<p>HA-P hydrogel dressing promotes wound healing in a full-thickness excisional wound model. (<b>A</b>) Representative images of the healing process up to 14 days post-wounding. (<b>B</b>) Wound closure curves of different groups show a significant acceleration of healing with the HA-P hydrogel treatment compared to the HA hydrogel and control group from day 4. (<b>C</b>) Representative images of CD31<sup>+</sup> (green) and α-SMA<sup>+</sup> (red) staining at day 14 post-wounding. The nucleus was stained with DAPI (blue). (<b>D</b>,<b>E</b>) Quantitative analysis indicates the HA-P hydrogel treatment significantly improves the angiogenesis and (<b>F</b>) reduces myofibroblasts’ regeneration (mean ± SD, n = 6, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001, ns, not statistically significant, scale bar, 100 μm).</p>
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36 pages, 7438 KiB  
Article
New Geometric Theorems Derived from Integral Equations Applied to Radiative Transfer in Spherical Sectors and Circular Segments
by Joseph Cabeza-Lainez
Mathematics 2024, 12(18), 2875; https://doi.org/10.3390/math12182875 (registering DOI) - 14 Sep 2024
Viewed by 288
Abstract
Semicircles and circular sectors are both ubiquitous in the natural realm. However, mathematically speaking they have represented an enigma since antiquity. In recent years, the author has worked in integral equations with sections of spheres as related to radiative heat transfer and their [...] Read more.
Semicircles and circular sectors are both ubiquitous in the natural realm. However, mathematically speaking they have represented an enigma since antiquity. In recent years, the author has worked in integral equations with sections of spheres as related to radiative heat transfer and their associated form factors, to the point of defining new postulates. The main theorems thus far enunciated refer to the radiative exchange between circles and half disks, but recently the possibility to treat circular sectors has arrived, thanks to the research already conducted. As is known, to find the exact expression of the configuration factor by integration is complex. In the above mentioned problem of the circular sectors, the author reached the first two steps of the basic formulation for radiant exchange. Subsequently, the novelty of the procedure lies in introducing a finite differences approach for the third and fourth integrals which still remain unsolved, once we have been able to find the preliminary integrals. This possibility had not been identified by former research and the output provides us with an ample variety of unexpected scenarios. As a consequence, we are able to analyze with more precision the spatial transference of radiant heat for figures composed of circular sectors. We already know that spherical shapes cannot be discretized with any accuracy. Therefore, we would be able to reduce a considerable amount of hindrance in the progress of thermal radiation science. Important sequels will be derived for radiation in the entrance to tunnels, aircraft design and lighting as well. Full article
(This article belongs to the Section Engineering Mathematics)
30 pages, 9406 KiB  
Article
Potential Use and Chemical Analysis of Some Natural Plant Extracts for Controlling Listeria spp. Growth In Vitro and in Food
by Abdul-Raouf Al-Mohammadi, Seham Abdel-Shafi, Ahmed H. Moustafa, Nehal Fouad, Gamal Enan and Rehab A. Ibrahim
Foods 2024, 13(18), 2915; https://doi.org/10.3390/foods13182915 (registering DOI) - 14 Sep 2024
Viewed by 343
Abstract
Listeria are Gram-negative intracellular foodborne pathogens that can cause invasive infections with high mortality rates. In this work, the antibacterial activity of ten essential oils, infusion extracts, and decoction extracts of some medicinal plants was tested against Listeria monocytogenes and listeria ivanovii strains. [...] Read more.
Listeria are Gram-negative intracellular foodborne pathogens that can cause invasive infections with high mortality rates. In this work, the antibacterial activity of ten essential oils, infusion extracts, and decoction extracts of some medicinal plants was tested against Listeria monocytogenes and listeria ivanovii strains. The effects of different physical conditions including temperature, pH, sodium chloride, and some organic acids were studied. The results showed that the water extracts gave the maximum bacterial inhibition, while ethanolic extract was inactive against the tested Listeria spp. The antibiotic sensitivity of L. monocytogenes LMG10470 and L. ivanovii LMZ11352 was tested against five antibiotics including imipenem, levofloxacin, amikacin, ampicillin, and amoxicillin. Imipenem was the most effective antibiotic, resulting in inhibition zones of 40 mm and 31 mm for L. monocytogenes and L. ivanovii, respectively. When imipenem mixed with Syzygium aromaticum oil, Salvia officinalis oil, Pimpinella anisum infusion, and Mentha piperita infusion each, the water extract of Moringa oleifera leaves and seeds against LMG10470 and LMZ11352 resulted in broader antibacterial activity. The antimicrobial activity of both Pimpinella anisum and Mentha piperita plant extracts is related to a variety of bioactive compounds indicated by gas chromatography–mass spectrometry analysis of these two plant extracts. These two plant extracts seemed to contain many chemical compounds elucidated by gas chromatography–mass spectrometry (GC-MS) and infrared radiation spectra. These compounds could be classified into different chemical groups such as ethers, heterocyclic compounds, aromatic aldehydes, condensed heterocyclic compounds, ketones, alicyclic compounds, aromatics, esters, herbicides, saturated fatty acids, and unsaturated fatty acids. The use of these natural compounds seems to be a useful technological adjuvant for the control of Listeria spp. in foods. Full article
(This article belongs to the Special Issue Detection and Control of Food-Borne Pathogens)
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Figure 1

Figure 1
<p>Thermal death point of <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 after 15 min of exposure to different temperatures different temperature exposure.</p>
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<p>Effect of different pH values on <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 growth.</p>
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<p>Effect of different NaCl concentrations on <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 growth.</p>
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<p>Effect of citric acid concentration on <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 growth.</p>
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<p>Effect of oxalic acid concentrations on <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 growth.</p>
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<p>Effect of salicylic acid concentrations on <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 growth.</p>
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<p>Antibacterial activity of different concentrations of infusion extracts of <span class="html-italic">Mentha piperita</span> and <span class="html-italic">Pimpinella anisum</span> against <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 by the disc assay method. The numbers 1, 2, 3, 4, and 5 show inhibition zone diameters of 10%, 25%, 50%, 75%, and 100%.</p>
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<p>Growth curves of (<b>A</b>) Pimpinella anisum, (<b>B</b>) Mentha piperita, (<b>C</b>) Zingiber officinalis, (<b>D</b>) Rosemarinus officinalis, (<b>E</b>) Salvia officinalis, and (<b>F</b>) Martricaria chamomilla against L. monocytogenes LMG10470 in nutrient broth incubated at 37 °C for 24 h.</p>
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<p>Growth curves of (<b>A</b>) Pimpinella anisum, (<b>B</b>) Mentha piperita, (<b>C</b>) Zingiber officinalis, (<b>D</b>) Rosemarinus officinalis, (<b>E</b>) Salvia officinalis, and (<b>F</b>) Martricaria chamomilla against L. monocytogenes LMG10470 in nutrient broth incubated at 37 °C for 24 h.</p>
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<p>Growth curves of (<b>A</b>) <span class="html-italic">Pimpinella anisum</span>, (<b>B</b>) <span class="html-italic">Mentha piperita</span>, (<b>C</b>) <span class="html-italic">Zingiber officinalis</span>, (<b>D</b>) <span class="html-italic">Rosemarinus officinalis</span>, (<b>E</b>) <span class="html-italic">Salvia officinalis</span>, and (<b>F</b>) <span class="html-italic">Martricaria chamomilla</span> against <span class="html-italic">L. ivanovii</span> LMZ11352 in nutrient broth incubated at 37 °C for 24 h.</p>
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<p>Growth curves of (<b>A</b>) <span class="html-italic">Pimpinella anisum</span>, (<b>B</b>) <span class="html-italic">Mentha piperita</span>, (<b>C</b>) <span class="html-italic">Zingiber officinalis</span>, (<b>D</b>) <span class="html-italic">Rosemarinus officinalis</span>, (<b>E</b>) <span class="html-italic">Salvia officinalis</span>, and (<b>F</b>) <span class="html-italic">Martricaria chamomilla</span> against <span class="html-italic">L. ivanovii</span> LMZ11352 in nutrient broth incubated at 37 °C for 24 h.</p>
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<p>Quantitative inhibition of decoction extract of the test medicinal plants against <span class="html-italic">L. monocytogenes</span> LMG10470. (<b>A</b>) <span class="html-italic">Pimpinella anisum</span>, (<b>B</b>) <span class="html-italic">Rosemarinus officinalis</span>, (<b>C</b>) <span class="html-italic">Cinnamum zeylanieum</span>, and (<b>D</b>) <span class="html-italic">Syzygium aromaticum</span>.</p>
Full article ">Figure 10 Cont.
<p>Quantitative inhibition of decoction extract of the test medicinal plants against <span class="html-italic">L. monocytogenes</span> LMG10470. (<b>A</b>) <span class="html-italic">Pimpinella anisum</span>, (<b>B</b>) <span class="html-italic">Rosemarinus officinalis</span>, (<b>C</b>) <span class="html-italic">Cinnamum zeylanieum</span>, and (<b>D</b>) <span class="html-italic">Syzygium aromaticum</span>.</p>
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<p>Quantitative inhibition of decoction extract of test medicinal plants against <span class="html-italic">L. ivanovii</span> LMZ11352. (<b>A</b>) <span class="html-italic">Pimpinella anisum</span>, (<b>B</b>) <span class="html-italic">Rosemarinus officinalis</span>, (<b>C</b>) <span class="html-italic">Cinnamum zeylanieum</span>, and (<b>D</b>) <span class="html-italic">Syzygium aromaticum</span>.</p>
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<p>Antibacterial activity of <span class="html-italic">Moringa oleifera</span> extracts (leaves) against <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 using disc assay and agar well diffusion methods. WE: water extract of leaves. ME: methanol extract of leaves.</p>
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<p>Antibacterial activity of <span class="html-italic">Moringa oleifera</span> extracts (Seeds) against <span class="html-italic">L. monocytogenes</span> LMG10470 and <span class="html-italic">L. ivanovii</span> LMZ11352 using disc assay and agar well diffusion methods. WE: water extract of seeds. ME: methanol extract of seeds.</p>
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<p>Antibacterial activity of mixed combinations of natural extracts and an antibiotic (imipenem) against <span class="html-italic">L. monocytogenes</span> by the disc assay method. (<b>A</b>) imipenem against <span class="html-italic">L. monocytogenes</span>. (<b>B</b>) (imipenem–natural extract) mixture combination against <span class="html-italic">L. monocytogenes</span>. (<b>C</b>) natural extract against <span class="html-italic">L. monocytogenes</span>.</p>
Full article ">Figure 14 Cont.
<p>Antibacterial activity of mixed combinations of natural extracts and an antibiotic (imipenem) against <span class="html-italic">L. monocytogenes</span> by the disc assay method. (<b>A</b>) imipenem against <span class="html-italic">L. monocytogenes</span>. (<b>B</b>) (imipenem–natural extract) mixture combination against <span class="html-italic">L. monocytogenes</span>. (<b>C</b>) natural extract against <span class="html-italic">L. monocytogenes</span>.</p>
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<p>Antibacterial activity of mixed combinations of natural extracts and an antibiotic (imipenem) against <span class="html-italic">L. ivanovii</span> by the disc assay method. (<b>A</b>): imipenem against <span class="html-italic">L. ivanovii</span>. (<b>B</b>): (imipenem—natural extract) mixture combination against <span class="html-italic">L. ivanovii.</span> (<b>C</b>): natural extract against <span class="html-italic">L. ivanovii</span>.</p>
Full article ">Figure 15 Cont.
<p>Antibacterial activity of mixed combinations of natural extracts and an antibiotic (imipenem) against <span class="html-italic">L. ivanovii</span> by the disc assay method. (<b>A</b>): imipenem against <span class="html-italic">L. ivanovii</span>. (<b>B</b>): (imipenem—natural extract) mixture combination against <span class="html-italic">L. ivanovii.</span> (<b>C</b>): natural extract against <span class="html-italic">L. ivanovii</span>.</p>
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<p>IR spectrum of <span class="html-italic">Pimpinella anisum.</span> Growth of <span class="html-italic">L. monocytogenes</span> LMG10470 (CFU/mL) in the presence of <span class="html-italic">L. delbreukii</span> subsp. <span class="html-italic">bulgaricus</span> Z55, <span class="html-italic">E. faecium</span> NM2, and <span class="html-italic">L. plantarum</span> LPS10 in vitro.</p>
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<p>IR spectrum of <span class="html-italic">Mentha pipertia</span>.</p>
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21 pages, 19820 KiB  
Article
Evaluation of the Surface Downward Longwave Radiation Estimation Models over Land Surface
by Yingping Chen, Bo Jiang, Jianghai Peng, Xiuwan Yin and Yu Zhao
Remote Sens. 2024, 16(18), 3422; https://doi.org/10.3390/rs16183422 (registering DOI) - 14 Sep 2024
Viewed by 239
Abstract
Surface downward longwave radiation (SDLR) is crucial for maintaining the global radiative budget balance. Due to their ease of practicality, SDLR parameterization models are widely used, making their objective evaluation essential. In this study, against comprehensive ground measurements collected from more than 300 [...] Read more.
Surface downward longwave radiation (SDLR) is crucial for maintaining the global radiative budget balance. Due to their ease of practicality, SDLR parameterization models are widely used, making their objective evaluation essential. In this study, against comprehensive ground measurements collected from more than 300 globally distributed sites, four SDLR parameterization models, including three popular existing ones and a newly proposed model, were evaluated under clear- and cloudy-sky conditions at hourly (daytime and nighttime) and daily scales, respectively. The validation results indicated that the new model, namely the Peng model, originally proposed for SDLR estimation at the sea surface and applied for the first time to the land surface, outperformed all three existing models in nearly all cases, especially under cloudy-sky conditions. Moreover, the Peng model demonstrated robustness across various land cover types, elevation zones, and seasons. All four SDLR models outperformed the Global Land Surface Satellite product from Advanced Very High-Resolution Radiometer Data (GLASS-AVHRR), ERA5, and CERES_SYN1de-g_Ed4A products. The Peng model achieved the highest accuracy, with validated RMSE values of 13.552 and 14.055 W/m2 and biases of −0.25 and −0.025 W/m2 under clear- and cloudy-sky conditions at daily scale, respectively. Its superior performance can be attributed to the inclusion of two cloud parameters, total column cloud liquid water and ice water, besides the cloud fraction. However, the optimal combination of these three parameters may vary depending on specific cases. In addition, all SDLR models require improvements for wetlands, bare soil, ice-covered surfaces, and high-elevation regions. Overall, the Peng model demonstrates significant potential for widespread use in SDLR estimation for both land and sea surfaces. Full article
(This article belongs to the Special Issue Earth Radiation Budget and Earth Energy Imbalance)
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Figure 1
<p>Spatial distribution of the 318 sites in nine surface radiation observing networks. Detailed information about the nine observing networks is provided in <a href="#remotesensing-16-03422-t002" class="html-table">Table 2</a>.</p>
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<p>Validation accuracy of the Prata, Carmona2, and Peng models with the original and calibrated coefficients at daily scales under clear-sky conditions. The color bar indicates the number of samples.</p>
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<p>The same as <a href="#remotesensing-16-03422-f002" class="html-fig">Figure 2</a>, but for the K-C, Carmona2, and Peng models under cloudy-sky conditions.</p>
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<p>Validation accuracies of the four evaluated SDLR models at a daily scale for eight land cover types under clear- and cloudy-sky conditions. The dashed boxes indicate the results under a cloudy sky.</p>
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<p>The same as <a href="#remotesensing-16-03422-f004" class="html-fig">Figure 4</a>, but for six elevation zones (&lt;300 m, 300–1000 m, 1000–1500 m, 1500–2500 m, 2500–3500 m, 3500–4500 m). The results under cloudy-sky conditions are added to the gray background.</p>
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<p>The same as <a href="#remotesensing-16-03422-f005" class="html-fig">Figure 5</a>, but for four seasons: Spring (Mar.–May), Summer (Jun.–Aug.), Autumn (Sep.–Nov.), and Winter (Dec.–Feb.).</p>
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<p>Overall validation accuracy of the four SDLR models and three products (ERA5, CERES4, and GLASS-AVHRR) at daily scales under clear- (<b>a</b>–<b>f</b>) and (<b>g</b>–<b>l</b>) cloudy-sky conditions.</p>
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<p>The spatial distribution of the validated RRMSE at site scale for (<b>a</b>) Peng model and (<b>b</b>–<b>d</b>) three products (GLASS-AVHRR, ERA5, CERES4).</p>
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<p>The time series of the daily SDLR from the Peng model and other three products at two sites (<b>a</b>) SF_GCM (34.25°N, 89.87°W, Grassland) and (<b>b</b>) PM-QAS_M (61.100°N, −46.833°W, ICE).</p>
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<p>Differences in the validated RMSE (ΔRMSE) between the Peng models with different combinations of the five input variables and the original one (all five variables).</p>
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<p>The same as <a href="#remotesensing-16-03422-f010" class="html-fig">Figure 10</a>, but on a daily scale under cloudy-sky conditions for the four seasons. The red box indicates the smallest ΔRMSE. Note that a negative ΔRMSE indicates that the corresponding combination of variables in the Peng model performed better than the original one.</p>
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15 pages, 5740 KiB  
Article
Dynamic Deformation in Nuclear Graphite and Underlying Mechanisms
by Melonie Thomas, Hajin Oh, Ryan Schoell, Stephen House, Miguel Crespillo, Khalid Hattar, William Windes and Aman Haque
Materials 2024, 17(18), 4530; https://doi.org/10.3390/ma17184530 (registering DOI) - 14 Sep 2024
Viewed by 173
Abstract
Time-dependent deformation in nuclear graphite is influenced by the creation and migration of radiation-induced defects in the reactor environment. This study investigates the role of pre-existing defects such as point defect clusters and Mrozowski cracks in nuclear graphite IG-110. Separate specimens were irradiated [...] Read more.
Time-dependent deformation in nuclear graphite is influenced by the creation and migration of radiation-induced defects in the reactor environment. This study investigates the role of pre-existing defects such as point defect clusters and Mrozowski cracks in nuclear graphite IG-110. Separate specimens were irradiated with a 2.8 MeV Au2+ beam with a fluence of 4.38 × 1014 cm−2 and an 8 MeV C2+ beam with a fluence of 1.24 × 1016 cm−2. Microscopic specimens were either mechanically loaded inside a transmission electron microscope (TEM) or subjected to ex situ indentation-based creep loading. In situ TEM tests showed significant plasticity in regions highly localized around the Mrozowski cracks, resembling slip or ripplocation bands. Slip bands were also seen near regions without pre-existing defects but at very high stresses. Ex situ self-ion irradiation embrittled the specimens and decreased the creep displacement and rate, while heavy ion irradiation resulted in the opposite behavior. We hypothesize that the large-sized gold ions (compared to the carbon atoms) induced interplanar swelling as well as cross-plane channels for increased defect mobility. These findings illustrate the role of pre-existing defects in the dynamic relaxation of stresses during irradiation and the need for more studies into the radiation environment’s impact on the mechanical response of nuclear graphite. Full article
(This article belongs to the Section Carbon Materials)
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Figure 1
<p>Stopping and Range of Ions in Matter simulation results for the displacement per atom (dpa) in (<b>a</b>) Au<sup>2+</sup>- and (<b>b</b>) C<sup>2+</sup>-ion-irradiated specimens.</p>
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<p>(<b>a</b>) Focused-ion-beam-milled specimens for in situ TEM mechanical testing. (<b>b</b>) Schematic diagram of a conical-punch-based micro-pillar specimen compression. (<b>c</b>) An example of a time-dependent deformation test at constant force.</p>
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<p>(<b>a</b>) Contact depth vs. time data showing the lower, average, and upper limits of the load–displacement response in carbon-irradiated IG-110 graphite. (<b>b</b>) Average data trend for pristine and carbon-irradiated specimens.</p>
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<p>Snapshots taken from in situ TEM dynamic micro-pillar compression tests on pristine IG-110 nuclear graphite. (<b>a</b>) Unloaded specimen showing three deformation bands identified with dashed paralellograms. (<b>b</b>) Loaded to 150 μN in 60 s. (<b>c</b>–<b>f</b>) Images acquired at 100, 150, 200, and 250 s of loading at a constant value of 150 μN. Arrows in <a href="#materials-17-04530-f004" class="html-fig">Figure 4</a>e show extensive cross-slip.</p>
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<p>(<b>a</b>–<b>c</b>) TEM micrographs of a collection of buckled ligaments separated by nanoscale cracks showing extensive dislocation and point defect clusters. Ligaments are shown in white arrows.</p>
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<p>Snapshots taken from in situ TEM dynamic micro-pillar compression tests on 2.8 MeV Au<sup>2+</sup>-ion-irradiated IG-110 nuclear graphite. (<b>a</b>) Unloaded specimen showing filler-binder interface with yellow arrows and deformation ligaments with black arrows. (<b>b</b>) Loaded to 150 μN in 60 s. (<b>c</b>–<b>f</b>) Constant load maintained over time. Yellow circles in <a href="#materials-17-04530-f006" class="html-fig">Figure 6</a>d indicate areas with newly formed deformation bands.</p>
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<p>Repeated experiment on Au<sup>2+</sup>-ion-irradiated IG-110 nuclear graphite at higher load. (<b>a</b>) Before loading, (<b>b</b>) after 300 s at 200 μN load, showing a newly developed deformation band with the dashed line parallelogram and (<b>c</b>) after 500 s at the same load, showing two new cross-slip deformation bands with solid line parallelograms. The circle denotes active deformation but without a prismatic band structure.</p>
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<p>(<b>a</b>,<b>b</b>) Fracture surface showing failure by creep deformation at the base of the micro-pillar specimen. Inset shows the specimen before the fracture with arrows indicating the stress concentration.</p>
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<p>Ex situ indentation creep results for (<b>a</b>) creep displacement and (<b>b</b>) stress rate over time while the load is kept constant.</p>
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<p>Ex situ indentation creep displacements at constant load for pristine and ion irradiated specimens.</p>
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28 pages, 2208 KiB  
Review
Flap Monitoring Techniques: A Review
by Ignacy Rogoń, Agnieszka Rogoń, Mariusz Kaczmarek, Adam Bujnowski, Jerzy Wtorek, Filip Lachowski and Jerzy Jankau
J. Clin. Med. 2024, 13(18), 5467; https://doi.org/10.3390/jcm13185467 (registering DOI) - 14 Sep 2024
Viewed by 162
Abstract
Postoperative tissue flap vitality monitoring enables early detection of clinical complications, allowing for intervention. Timely re-operation can prevent the need for extensive correction procedures, thus reducing healthcare costs and hospitalization time. Statistics show that monitoring can increase the success rate of flap survival [...] Read more.
Postoperative tissue flap vitality monitoring enables early detection of clinical complications, allowing for intervention. Timely re-operation can prevent the need for extensive correction procedures, thus reducing healthcare costs and hospitalization time. Statistics show that monitoring can increase the success rate of flap survival to 95% or higher. However, despite the significant progress in monitoring techniques, major and minor complications, leading to the loss of the flap, still occur. This clinical application review aims to provide a comprehensive overview of the recent advancements and findings in flap surgery reconstructions, transplants, and systems for their postoperative assessment. The literature from the years 1925 to 2024 has been reviewed to capture previous and current solutions for monitoring flap vitality. Clinically acclaimed methods and experimental techniques were classified and reviewed from a technical and clinical standpoint. Physical examination, metabolism change, ultrasound method, and electromagnetic (EM) radiation-based measurement methods were carefully evaluated from the perspective of their considered applications. Guidelines aiding engineers in the future design and development process of monitoring systems were proposed. This paper provides a comprehensive overview of the monitoring techniques used in postoperative flap vitality monitoring. It also gives an overview of each approach and potential ways for future development. Full article
(This article belongs to the Special Issue Breast Reconstruction: Current Challenges and Future Perspectives)
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Figure 1

Figure 1
<p>Overview of postoperative flap vitality monitoring techniques.</p>
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<p>(<b>A</b>) A summary of free flap reconstruction methods comparing them by the amount of muscle involved is presented. Red blocks show an illustrative model of the transverse rectus abdominis muscle. Dark color represents amount of muscle removed (Free TRAM or MS-TRAM) or incised (in DIEP). (<b>B</b>) An example of pedicled flap: pedicled TRAM method employed in breast reconstruction surgery (<b>C</b>) An example of free flap: free TRAM method of breast reconstruction surgery.</p>
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<p>Complications after TRAM breast reconstruction. (<b>A</b>) Marginal ischemic necrosis. (<b>B</b>) Severe ischemic necrosis caused by vessel thrombosis.</p>
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<p>Electromagnetic (EM) radiation-based methods classification based on the wavelength.</p>
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