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16 pages, 3231 KiB  
Article
Monovalent and Divalent Designs of Copper Radiotheranostics Targeting Fibroblast Activation Protein in Cancer
by Pawan Thapa, Sashi Debnath, Anjan Bedi, Madhuri Parashar, Paulina Gonzalez, Joshua Reus, Hans Hammers and Xiankai Sun
Cancers 2024, 16(24), 4180; https://doi.org/10.3390/cancers16244180 (registering DOI) - 15 Dec 2024
Viewed by 138
Abstract
Background: Fibroblast activation protein (FAP)-targeted theranostic radiopharmaceuticals have shown desired tumor-to-background organ selectivity due to the ubiquitous presence of FAP within the tumor microenvironment. However, suboptimal tumor retention and fast clearance have hindered their use to deliver effective cancer therapies. With well-documented [...] Read more.
Background: Fibroblast activation protein (FAP)-targeted theranostic radiopharmaceuticals have shown desired tumor-to-background organ selectivity due to the ubiquitous presence of FAP within the tumor microenvironment. However, suboptimal tumor retention and fast clearance have hindered their use to deliver effective cancer therapies. With well-documented FAP-targeting moieties and linkers appending them to optimal chelators, the development of copper radiopharmaceuticals has attracted considerable interest, given the fact that an ideal theranostic pair of copper radionuclides (64Cu: t1/2 = 12.7 h; 17.4% β+; Eβ+max = 653 keV and 67Cu: t1/2 = 2.58 d; 100% β; Eβmax = 562 keV) are available. Herein, we report our design, synthesis, and comparative evaluation of monovalent and divalent FAP-targeted theranostic conjugates constructed from our previously reported bifunctional chelator scaffold (BFS) based on 1,4,8,11-tetraaza-bicyclo [6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A), which forms the most stable complex with Cu(II). Methods: After synthesis and characterization, the monovalent and divalent conjugates were radiolabeled with 64Cu for in vitro cell assays, followed by in vivo positron emission tomography (PET) imaging evaluation in relevant mouse models. Results: Both 64Cu-labeled conjugates showed high in vitro stability and anticipated FAP-mediated cell binding and internalization. The divalent one showed significantly higher FAP-specific tumor uptake than its monovalent counterpart. Conclusions: Our results demonstrate that the BFS-based multivalent approach can be practically used to generate FAP-targeted radiotheranostic agents for effective cancer diagnosis and treatment. Full article
(This article belongs to the Section Cancer Drug Development)
Show Figures

Figure 1

Figure 1
<p>(<b>A</b>) UAMC1110, lead structure for FAPI development; (<b>B</b>) multivalent conjugate design for FAP-targeted copper radiotheranostics.</p>
Full article ">Figure 2
<p>Cell-based FAP-binding affinity and internalization assays of [<sup>64</sup>Cu]Cu-CB-TE2A-FAPI-04 (upper panel) and [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub> (lower panel). (<b>A</b>,<b>D</b>): FAP-specific binding assay using UAMC1110 as blockade; (<b>B</b>,<b>E</b>): Calculated ratios of total uptake vs. nonspecific uptake; (<b>C</b>,<b>F</b>): time-dependent internalization. Cell lines: RENCA-FAP (FAP<sup>+</sup>) and RENCA (FAP<sup>−</sup>).</p>
Full article ">Figure 3
<p>(<b>A</b>): Representative PET/CT images of [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub> in mice bearing RENCA-FAP (FAP<sup>+</sup>) tumors (yellow arrows indicate the tumors) at different time points. (<b>B</b>): Biodistribution of [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub> by quantitative imaging data analysis in the mice. Data presented as average %ID/g ± standard deviation (s.d.) (n = 3). (<b>C</b>): Tumor/muscle ratio at different time points. (<b>D</b>–<b>F</b>): Immunofluorescence staining assays of excised RENCA-FAP tumor tissues post imaging. The nuclei were stained with DAPI (<b>D</b>) and tumor cells with anti-FAP antibody (<b>E</b>). (<b>F</b>): Overlay of the FAP and DAPI staining.</p>
Full article ">Figure 4
<p>(<b>A</b>): Representative PET/CT images of XP-185 tumorgrafts in SCID/NOD mice (n = 4) with divalent [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub>. (<b>B</b>): Images obtained with co-injection of UAMC1110 with divalent [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub>. (<b>C</b>): Representative PET/CT images of XP-185 tumorgrafts in SCID/NOD mice (n = 4) with monovalent [<sup>64</sup>Cu]Cu-CB-TE2A-FAPI-04. Tumors are indicated with yellow arrows.</p>
Full article ">Figure 5
<p>Quantitative analysis of PET signals in tissues of interest in SCID/NOD mice bearing XP-185 tumorgrafts (n = 4). (<b>A</b>): [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub>. (<b>B</b>): [<sup>64</sup>Cu]Cu-CB-TE2A-(FAPI-04)<sub>2</sub> co-injected with UAMC1110 (tumor blocked vs. tumor unblocked at 4 h p.i., <span class="html-italic">p</span> = 0.0093.). (<b>C</b>): [<sup>64</sup>Cu]Cu-CB-TE2A-FAPI-04. Tumors are indicated with orange dotted boxes.</p>
Full article ">Scheme 1
<p>Synthetic route to monovalent and divalent FAPI-04 conjugates. Reagents and reaction condition for monovalent conjugate: FAPI-04 (1.2 equiv.), CB-TE2A(<span class="html-italic"><sup>t</sup></span>Bu)<sub>2</sub>-COOH (1 equiv.), HBTU (1 equiv.), DIPEA (5 equiv.), 24 h; TFA, 6 h. Reagents and reaction condition for divalent conjugate: FAPI-04 (3.5 equiv.), CB-TE2A(<span class="html-italic"><sup>t</sup></span>Bu)<sub>2</sub>-(COOH)<sub>2</sub> (1 equiv.), HBTU (2 equiv.), DIPEA (10 equiv.), 24 h; TFA, 3 h.</p>
Full article ">
11 pages, 1943 KiB  
Article
An Upcycling Strategy for Polyethylene Terephthalate Fibers: All-Polymer Composites with Enhanced Mechanical Properties
by Chiara Gnoffo, Rossella Arrigo and Alberto Frache
J. Compos. Sci. 2024, 8(12), 527; https://doi.org/10.3390/jcs8120527 (registering DOI) - 14 Dec 2024
Viewed by 164
Abstract
In this work, an effective route for achieving high-performance all-polymer materials through the proper manipulation of the material microstructure and starting from a waste material is proposed. In particular, recycled polyethylene terephthalate (rPET) fibers from discarded safety belts were used as reinforcing phase [...] Read more.
In this work, an effective route for achieving high-performance all-polymer materials through the proper manipulation of the material microstructure and starting from a waste material is proposed. In particular, recycled polyethylene terephthalate (rPET) fibers from discarded safety belts were used as reinforcing phase in melt-compounded high-density polyethylene (HDPE)-based systems. The formulated composites were subjected to hot- and cold-stretching for obtaining filaments at different draw ratios. The performed characterizations pointed out that the material morphology can be profitably modified through the application of the elongational flow, which was proven able to promote significant microstructural evolutions of the rPET dispersed domains, eventually leading to the obtainment of micro-fibrillated all-polymer composites. Furthermore, tensile tests demonstrated that hot-stretched and, especially, cold-stretched materials show significantly enhanced tensile modulus and strength as compared to the unfilled HDPE filaments, likely due to the formation of a highly oriented and anisotropic microstructure. Full article
(This article belongs to the Special Issue Mechanical Properties of Composite Materials and Joints)
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Figure 1

Figure 1
<p>SEM micrographs for HDPE/rPET extrudates processed at 220 (<b>a</b>,<b>b</b>), 240 (<b>c</b>) and 260 (<b>d</b>) °C.</p>
Full article ">Figure 2
<p>Trend of complex viscosity (η*) and of the storage modulus (G′) as a function of the frequency (ω) for HDPE/rPET processed at 220 (<b>a</b>,<b>d</b>), 240 (<b>b</b>,<b>e</b>) and 260 (<b>c</b>,<b>f</b>) °C. The rheological functions of the neat matrix are also reported.</p>
Full article ">Figure 3
<p>SEM micrographs for HDPE95/rPET5_260 °C hot-stretched filaments at DR<sub>H</sub> 4 (<b>a</b>) and 14 (<b>b</b>).</p>
Full article ">Figure 4
<p>Tensile modulus (<b>a</b>), tensile strength (<b>b</b>) and elongation at break (<b>c</b>) for HDPE and HDPE/rPET filaments as a function of DR<sub>H</sub>.</p>
Full article ">Figure 5
<p>Tensile modulus (<b>a</b>), tensile strength (<b>b</b>) and elongation at break (<b>c</b>) for HDPE and HDPE/rPET filaments as a function of DR<sub>C</sub>.</p>
Full article ">
18 pages, 2765 KiB  
Systematic Review
Comparing the Efficacy of CT, MRI, PET-CT, and US in the Detection of Cervical Lymph Node Metastases in Head and Neck Squamous Cell Carcinoma with Clinically Negative Neck Lymph Node: A Systematic Review and Meta-Analysis
by Ahmed Alsibani, Abdulwahed Alqahtani, Roaa Almohammadi, Tahera Islam, Mohammed Alessa, Saleh F. Aldhahri and Khalid Hussain Al-Qahtani
J. Clin. Med. 2024, 13(24), 7622; https://doi.org/10.3390/jcm13247622 (registering DOI) - 14 Dec 2024
Viewed by 234
Abstract
Background: Traditional imaging techniques have limited efficacy in detecting occult cervical lymph node (LN) metastases in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography/computed tomography (PET-CT) has demonstrated potential for assessing HNSCC, but the literature on its efficacy for detecting cervical [...] Read more.
Background: Traditional imaging techniques have limited efficacy in detecting occult cervical lymph node (LN) metastases in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography/computed tomography (PET-CT) has demonstrated potential for assessing HNSCC, but the literature on its efficacy for detecting cervical LN metastases is scarce and exhibits varied outcomes, hindering comparisons. Aim: To compare the efficacy of CT, MRI, PET-CT, and US for detecting LN metastasis in HNSCC with clinically negative neck lymph nodes. Methods: A systematic search was performed using Web of Science, PubMed, Scopus, Embase, and Cochrane databases. Studies comparing CT, MRI, PET-CT, or US to detect cervical metastases in HNSCC were identified. The quality of the studies was assessed using the QUADAS-2 instrument. The positive likelihood ratios (+LR) and negative likelihood ratios (−LR), sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR), with 95% confidence intervals (C.I.), were calculated. Analysis was stratified according to lymph node and patient basis. Results: Fifty-seven studies yielded 3791 patients. At the patient level, PET-CT exhibited the highest diagnostic performance, with a SEN of 74.5% (95% C.I.: 65.4–81.8%) and SPE of 83.6% (95% C.I.: 77.2–88.5%). PET-CT also demonstrated the highest +LR of 4.303 (95% C.I.: 3.082–6.008) and the lowest −LR of 0.249 (95% C.I.: 0.168–0.370), resulting in the highest DOR of 15.487 (95% C.I.: 8.973–26.730). In the evaluation of diagnostic parameters for various imaging modalities on node-based analysis results, MRI exhibited the highest SEN at 77.4%, and PET demonstrated the highest SPE at 96.6% (95% C.I.: 94.4–98%). PET-CT achieved the highest DOR at 24.353 (95% C.I.: 10.949–54.166). Conclusions: PET-CT outperformed other imaging modalities across the majority of studied metrics concerning LN metastasis detection in HNSCC. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
Show Figures

Figure 1

Figure 1
<p>PRISMA flow chart.</p>
Full article ">Figure 2
<p>Forest plot of estimates of sensitivity and specificity for different imaging modalities in the Detection of Lymph Node Metastasis with Node as a Unit of Analysis. Included studies [<a href="#B4-jcm-13-07622" class="html-bibr">4</a>,<a href="#B13-jcm-13-07622" class="html-bibr">13</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B20-jcm-13-07622" class="html-bibr">20</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B27-jcm-13-07622" class="html-bibr">27</a>,<a href="#B28-jcm-13-07622" class="html-bibr">28</a>,<a href="#B30-jcm-13-07622" class="html-bibr">30</a>,<a href="#B31-jcm-13-07622" class="html-bibr">31</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B41-jcm-13-07622" class="html-bibr">41</a>,<a href="#B42-jcm-13-07622" class="html-bibr">42</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B53-jcm-13-07622" class="html-bibr">53</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B57-jcm-13-07622" class="html-bibr">57</a>,<a href="#B58-jcm-13-07622" class="html-bibr">58</a>,<a href="#B60-jcm-13-07622" class="html-bibr">60</a>,<a href="#B61-jcm-13-07622" class="html-bibr">61</a>,<a href="#B64-jcm-13-07622" class="html-bibr">64</a>,<a href="#B66-jcm-13-07622" class="html-bibr">66</a>,<a href="#B68-jcm-13-07622" class="html-bibr">68</a>].</p>
Full article ">Figure 3
<p>Forest plot of estimates of negative likelihood ratio and positive likelihood ratio for different imaging modalities in the Detection of Lymph Node Metastasis with Node as a Unit of Analysis. Included studies [<a href="#B4-jcm-13-07622" class="html-bibr">4</a>,<a href="#B13-jcm-13-07622" class="html-bibr">13</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B20-jcm-13-07622" class="html-bibr">20</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B27-jcm-13-07622" class="html-bibr">27</a>,<a href="#B28-jcm-13-07622" class="html-bibr">28</a>,<a href="#B30-jcm-13-07622" class="html-bibr">30</a>,<a href="#B31-jcm-13-07622" class="html-bibr">31</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B41-jcm-13-07622" class="html-bibr">41</a>,<a href="#B42-jcm-13-07622" class="html-bibr">42</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B53-jcm-13-07622" class="html-bibr">53</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B57-jcm-13-07622" class="html-bibr">57</a>,<a href="#B58-jcm-13-07622" class="html-bibr">58</a>,<a href="#B60-jcm-13-07622" class="html-bibr">60</a>,<a href="#B61-jcm-13-07622" class="html-bibr">61</a>,<a href="#B64-jcm-13-07622" class="html-bibr">64</a>,<a href="#B66-jcm-13-07622" class="html-bibr">66</a>,<a href="#B68-jcm-13-07622" class="html-bibr">68</a>].</p>
Full article ">Figure 4
<p>Forest plot of estimates of diagnostic odds ratio for different imaging modalities in the Detection of Lymph Node Metastasis with Node as a Unit of Analysis. Included studies [<a href="#B4-jcm-13-07622" class="html-bibr">4</a>,<a href="#B13-jcm-13-07622" class="html-bibr">13</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B20-jcm-13-07622" class="html-bibr">20</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B27-jcm-13-07622" class="html-bibr">27</a>,<a href="#B28-jcm-13-07622" class="html-bibr">28</a>,<a href="#B30-jcm-13-07622" class="html-bibr">30</a>,<a href="#B31-jcm-13-07622" class="html-bibr">31</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B41-jcm-13-07622" class="html-bibr">41</a>,<a href="#B42-jcm-13-07622" class="html-bibr">42</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B47-jcm-13-07622" class="html-bibr">47</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B53-jcm-13-07622" class="html-bibr">53</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B57-jcm-13-07622" class="html-bibr">57</a>,<a href="#B58-jcm-13-07622" class="html-bibr">58</a>,<a href="#B60-jcm-13-07622" class="html-bibr">60</a>,<a href="#B61-jcm-13-07622" class="html-bibr">61</a>,<a href="#B64-jcm-13-07622" class="html-bibr">64</a>,<a href="#B66-jcm-13-07622" class="html-bibr">66</a>,<a href="#B68-jcm-13-07622" class="html-bibr">68</a>].</p>
Full article ">Figure 5
<p>Forest plot of estimates of sensitivity and specificity for different imaging modalities in the Detection of Lymph Node Metastasis with Patient as a Unit of Analysis. Included studies [<a href="#B1-jcm-13-07622" class="html-bibr">1</a>,<a href="#B12-jcm-13-07622" class="html-bibr">12</a>,<a href="#B14-jcm-13-07622" class="html-bibr">14</a>,<a href="#B15-jcm-13-07622" class="html-bibr">15</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B21-jcm-13-07622" class="html-bibr">21</a>,<a href="#B22-jcm-13-07622" class="html-bibr">22</a>,<a href="#B23-jcm-13-07622" class="html-bibr">23</a>,<a href="#B24-jcm-13-07622" class="html-bibr">24</a>,<a href="#B25-jcm-13-07622" class="html-bibr">25</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B29-jcm-13-07622" class="html-bibr">29</a>,<a href="#B32-jcm-13-07622" class="html-bibr">32</a>,<a href="#B33-jcm-13-07622" class="html-bibr">33</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B36-jcm-13-07622" class="html-bibr">36</a>,<a href="#B37-jcm-13-07622" class="html-bibr">37</a>,<a href="#B38-jcm-13-07622" class="html-bibr">38</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B40-jcm-13-07622" class="html-bibr">40</a>,<a href="#B43-jcm-13-07622" class="html-bibr">43</a>,<a href="#B44-jcm-13-07622" class="html-bibr">44</a>,<a href="#B45-jcm-13-07622" class="html-bibr">45</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B48-jcm-13-07622" class="html-bibr">48</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B50-jcm-13-07622" class="html-bibr">50</a>,<a href="#B51-jcm-13-07622" class="html-bibr">51</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B55-jcm-13-07622" class="html-bibr">55</a>,<a href="#B56-jcm-13-07622" class="html-bibr">56</a>,<a href="#B59-jcm-13-07622" class="html-bibr">59</a>,<a href="#B62-jcm-13-07622" class="html-bibr">62</a>,<a href="#B63-jcm-13-07622" class="html-bibr">63</a>,<a href="#B65-jcm-13-07622" class="html-bibr">65</a>,<a href="#B67-jcm-13-07622" class="html-bibr">67</a>,<a href="#B69-jcm-13-07622" class="html-bibr">69</a>].</p>
Full article ">Figure 6
<p>Forest plot of estimates of negative likelihood ratio and positive likelihood ratio for different imaging modalities in the Detection of Lymph Node Metastasis with Patient as a Unit of Analysis. Included studies [<a href="#B1-jcm-13-07622" class="html-bibr">1</a>,<a href="#B12-jcm-13-07622" class="html-bibr">12</a>,<a href="#B14-jcm-13-07622" class="html-bibr">14</a>,<a href="#B15-jcm-13-07622" class="html-bibr">15</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B21-jcm-13-07622" class="html-bibr">21</a>,<a href="#B22-jcm-13-07622" class="html-bibr">22</a>,<a href="#B23-jcm-13-07622" class="html-bibr">23</a>,<a href="#B24-jcm-13-07622" class="html-bibr">24</a>,<a href="#B25-jcm-13-07622" class="html-bibr">25</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B29-jcm-13-07622" class="html-bibr">29</a>,<a href="#B32-jcm-13-07622" class="html-bibr">32</a>,<a href="#B33-jcm-13-07622" class="html-bibr">33</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B36-jcm-13-07622" class="html-bibr">36</a>,<a href="#B37-jcm-13-07622" class="html-bibr">37</a>,<a href="#B38-jcm-13-07622" class="html-bibr">38</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B40-jcm-13-07622" class="html-bibr">40</a>,<a href="#B43-jcm-13-07622" class="html-bibr">43</a>,<a href="#B44-jcm-13-07622" class="html-bibr">44</a>,<a href="#B45-jcm-13-07622" class="html-bibr">45</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B48-jcm-13-07622" class="html-bibr">48</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B50-jcm-13-07622" class="html-bibr">50</a>,<a href="#B51-jcm-13-07622" class="html-bibr">51</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B55-jcm-13-07622" class="html-bibr">55</a>,<a href="#B56-jcm-13-07622" class="html-bibr">56</a>,<a href="#B59-jcm-13-07622" class="html-bibr">59</a>,<a href="#B62-jcm-13-07622" class="html-bibr">62</a>,<a href="#B63-jcm-13-07622" class="html-bibr">63</a>,<a href="#B65-jcm-13-07622" class="html-bibr">65</a>,<a href="#B67-jcm-13-07622" class="html-bibr">67</a>,<a href="#B69-jcm-13-07622" class="html-bibr">69</a>].</p>
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<p>Forest plot of estimates of diagnostic odds ratio for different imaging modalities in the Detection of Lymph Node Metastasis with Patient as a Unit of Analysis. Included studies [<a href="#B1-jcm-13-07622" class="html-bibr">1</a>,<a href="#B12-jcm-13-07622" class="html-bibr">12</a>,<a href="#B14-jcm-13-07622" class="html-bibr">14</a>,<a href="#B15-jcm-13-07622" class="html-bibr">15</a>,<a href="#B19-jcm-13-07622" class="html-bibr">19</a>,<a href="#B21-jcm-13-07622" class="html-bibr">21</a>,<a href="#B22-jcm-13-07622" class="html-bibr">22</a>,<a href="#B23-jcm-13-07622" class="html-bibr">23</a>,<a href="#B24-jcm-13-07622" class="html-bibr">24</a>,<a href="#B25-jcm-13-07622" class="html-bibr">25</a>,<a href="#B26-jcm-13-07622" class="html-bibr">26</a>,<a href="#B29-jcm-13-07622" class="html-bibr">29</a>,<a href="#B32-jcm-13-07622" class="html-bibr">32</a>,<a href="#B33-jcm-13-07622" class="html-bibr">33</a>,<a href="#B34-jcm-13-07622" class="html-bibr">34</a>,<a href="#B35-jcm-13-07622" class="html-bibr">35</a>,<a href="#B36-jcm-13-07622" class="html-bibr">36</a>,<a href="#B37-jcm-13-07622" class="html-bibr">37</a>,<a href="#B38-jcm-13-07622" class="html-bibr">38</a>,<a href="#B39-jcm-13-07622" class="html-bibr">39</a>,<a href="#B40-jcm-13-07622" class="html-bibr">40</a>,<a href="#B43-jcm-13-07622" class="html-bibr">43</a>,<a href="#B44-jcm-13-07622" class="html-bibr">44</a>,<a href="#B45-jcm-13-07622" class="html-bibr">45</a>,<a href="#B46-jcm-13-07622" class="html-bibr">46</a>,<a href="#B48-jcm-13-07622" class="html-bibr">48</a>,<a href="#B49-jcm-13-07622" class="html-bibr">49</a>,<a href="#B50-jcm-13-07622" class="html-bibr">50</a>,<a href="#B51-jcm-13-07622" class="html-bibr">51</a>,<a href="#B52-jcm-13-07622" class="html-bibr">52</a>,<a href="#B54-jcm-13-07622" class="html-bibr">54</a>,<a href="#B55-jcm-13-07622" class="html-bibr">55</a>,<a href="#B56-jcm-13-07622" class="html-bibr">56</a>,<a href="#B59-jcm-13-07622" class="html-bibr">59</a>,<a href="#B62-jcm-13-07622" class="html-bibr">62</a>,<a href="#B63-jcm-13-07622" class="html-bibr">63</a>,<a href="#B65-jcm-13-07622" class="html-bibr">65</a>,<a href="#B67-jcm-13-07622" class="html-bibr">67</a>,<a href="#B69-jcm-13-07622" class="html-bibr">69</a>].</p>
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15 pages, 1527 KiB  
Article
Decision Analysis Approaches on the Collection Methods of Polyethylene Terephthalate Waste
by Johnson A. Oyewale, Lagouge K. Tartibu and Imhade P. Okokpujie
Recycling 2024, 9(6), 124; https://doi.org/10.3390/recycling9060124 - 13 Dec 2024
Viewed by 278
Abstract
The rising challenge of polyethylene terephthalate (PET) waste necessitates efficient collection methods to mitigate environmental impacts. The Analytic Hierarchy Process (AHP) is one of the Multi-Criteria Decision Analysis (MCDA) approaches utilized in this study. The Technique for Order of Preference by Similarity to [...] Read more.
The rising challenge of polyethylene terephthalate (PET) waste necessitates efficient collection methods to mitigate environmental impacts. The Analytic Hierarchy Process (AHP) is one of the Multi-Criteria Decision Analysis (MCDA) approaches utilized in this study. The Technique for Order of Preference by Similarity to the Ideal Solution (TOPSIS) was used to rank each alternative according to the objective weight that AHP had produced. Also, sensitivity analysis was performed to determine how robust the findings were when considering equal weights and entropy weights to maximize PET waste collection techniques. The alternative achieved the objective of obtaining the best collection method, Threshold Plastic Bottle Waste Collection (Tpbw), out of all the three alternatives considered. Another MCDA approach, VIseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR), was used to compare the results and validate the ranking result achieved by the TOPSIS method. The VIKOR technique’s validation of the TOPSIS approach showed that the outcomes were highly consistent. Data for the study were gathered from the archives of waste management companies on possible practices of plastic waste collection, addressing costs, environmental impacts, social acceptance, feasibility, and efficiency. The findings provide a prioritized framework for enhancing PET waste collection strategies, contributing to sustainable waste management. Many criteria are considered when deciding the best collecting method for PET waste recycling, making it challenging. By using criteria importance, MCDA was applied in this study, and the objective weight of the criteria was determined using the AHP. The five criteria considered in this study are Initial investment cost, operational cost, transportation cost, environmental risk, employment potential, and the objective weights allocated to them. AHP results 0.4952, 0.1997, 0.1565, 0.0870, and 0.0616 are, respectively, determined. Full article
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<p>Euclidean distance for two points between two axes.</p>
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<p>The Euclidean ranking positions the three alternatives.</p>
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<p>Sensitivity analysis of decision-making matrices.</p>
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<p>The hierarchal framework of PET waste collection for maximum recycling.</p>
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<p>Criteria weights of AHP, and entropy weights methods.</p>
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13 pages, 837 KiB  
Article
Reduced Homogeneous Myocardial [18F]FDG Uptake in Routine PET/CT Studies as an Early Indicator of Chemotherapy-Induced Cardiotoxicity
by David Palomino-Fernández, Héctor Bueno, Carmen Jiménez-López-Guarch, Guillermo Moreno, Alexander P. Seiffert, Enrique J. Gómez, Adolfo Gómez-Grande and Patricia Sánchez-González
Appl. Sci. 2024, 14(24), 11653; https://doi.org/10.3390/app142411653 - 13 Dec 2024
Viewed by 297
Abstract
Cardiotoxicity refers to the damage induced by antineoplastic treatments, leading to various cardiovascular conditions. [18F]FDG PET radiomics analysis could provide relevant information on early onset changes occurring in cardiac metabolism of chemotherapy-induced cardiotoxicity. Patients’ sociodemographic data, cardiovascular risk factors, laboratory parameters, [...] Read more.
Cardiotoxicity refers to the damage induced by antineoplastic treatments, leading to various cardiovascular conditions. [18F]FDG PET radiomics analysis could provide relevant information on early onset changes occurring in cardiac metabolism of chemotherapy-induced cardiotoxicity. Patients’ sociodemographic data, cardiovascular risk factors, laboratory parameters, and left ventricle [18F]FDG PET radiomic features are analyzed. The HRad index for the quantification of the heterogeneity of the metabolic uptake patterns is proposed. Statistical analysis is performed by separating patients according to the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Baseline, intermediate, and end-of-treatment scans are evaluated as separate groups. Overall, CTRCD+ patients show lower overall mean standardized uptake values (SUVmean) compared to CTRCD− patients, with statistically significant differences between groups only observed in the intermediate PET study (p = 0.025). A total of 34 radiomic features show statistically significant differences between the CTRCD+ and CTRCD− groups in the intermediate imaging studies. In the CTRCD− group, greater overall heterogeneity of metabolic uptake is observed in the intermediate PET image compared to the CTRCD+ groups (p = 0.025). The assessment of CTRCD through [18F]FDG PET radiomics analysis could be a potential tool for the identification of a predisposition to the later development of cardiac complications after cardiotoxic treatment. Full article
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<p>Comparison of value distribution and change over time (baseline, intermediate, and EOT) in the mean [<sup>18</sup>F]FDG PET/CT scan SUV values between the CTRCD+ and CTRCD− groups. The vertical axis is expressed in log scale to evidence the differences between groups. Statistically significant differences between CTRCD groups after multiple-testing correction are indicated with their respective <span class="html-italic">p</span>-values. (<b>a</b>) <span class="html-italic">SUV<sub>max</sub></span>. (<b>b</b>) <span class="html-italic">SUV<sub>mean</sub></span>. SUV: standardized uptake value; EOT: end-of-treatment.</p>
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<p><span class="html-italic">H<sub>Rad</sub></span> index distribution and trends in median values for the CTRCD+ and CTRCD− groups in the baseline, intermediate, and EOT image studies. The vertical axis is expressed in log scale to evidence the differences between groups. Statistically significant differences between CTRCD groups after multiple-testing correction are indicated with their respective <span class="html-italic">p</span>-values. CTRCD: cancer therapy-related cardiac dysfunction; EOT: end-of-treatment.</p>
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12 pages, 3168 KiB  
Article
A Photothermal-Responsive Soft Actuator Based on Biomass Carbon Nanosheets of Synergistic Bilateral Polymers
by Jianze Chen, Quanzhong Wei, Honglin Wang, Wenjia Cui, Xuewei Zhang and Yuanyuan Wang
Polymers 2024, 16(24), 3476; https://doi.org/10.3390/polym16243476 - 13 Dec 2024
Viewed by 301
Abstract
Currently, polymer actuators capable of photothermal response are being developed to be more sensitive and repeatable. In this work, a three-layered structured soft film actuator (NA/PET/NI-3) was designed by combining poly(N-isopropylacrylamide) (PNIPAM), poly(N-(2-aminoethyl)-acrylamide) (PANGA) and poly(ethylene glycol-co-terephthalate) (PET) film. Coconut water and PEI [...] Read more.
Currently, polymer actuators capable of photothermal response are being developed to be more sensitive and repeatable. In this work, a three-layered structured soft film actuator (NA/PET/NI-3) was designed by combining poly(N-isopropylacrylamide) (PNIPAM), poly(N-(2-aminoethyl)-acrylamide) (PANGA) and poly(ethylene glycol-co-terephthalate) (PET) film. Coconut water and PEI were used to synthesize a new kind of carbon nanosheet (PEI-CCS), which, when triggered by near-infrared light, will enable photothermal bending behavior in the micrometer-scale NA/PET/NI-n film, while PET served as the supporting and heat conducting layer. This three-layered actuator utilized the synergistic effects of two kind of polymers, PNIPAM and PNAGA, on either side of PET, with the upper critical solution temperatures and lower critical solution temperatures when subjected to temperature changes. This bilateral polymer design exhibited a rapid response under near-infrared light stimulation, bending to 180° within 4 s and recovering to its original shape within 30 s. When the bending process was set to 90° as in the standard experiment, NA/PET/NI-3 responded within 2 s and recovered within 8 s. NA/PET/NI-3 also demonstrated good reversibility and repeatability, capable of undergoing reversible driving over 120 times. The design and preparation of this actuator provided new ideas for the development of polymer soft actuators. Full article
(This article belongs to the Section Polymer Applications)
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<p>The synthesis of PEI-CCS carbon nanosheets. (<b>a</b>) TEM image of PEI-CCS after a microwave carbonization time of 3.5 min. (<b>b</b>) AFM image of the PEI-CCS solution after a microwave carbonization time of 3.5 min. (<b>c</b>) Fourier transform infrared (FTIR) spectra of coconut water and PEI-CCS. (<b>d</b>) The temperature–time variation curves of deionized water and PEI-CCS solution with a carbonization time of 3.0, 3.5 and 4.0 min under near-infrared light irradiation.</p>
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<p>The XPS of PEI-CCS and CCD. (<b>a</b>) The wide scan XPS spectra of PEI-CCS and CCD. (<b>b</b>) C1s spectra of CCD. (<b>c</b>) C1s spectra of PEI-CCS. (<b>d</b>) N1s spectra of PEI-CCS.</p>
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<p>The synthesis and photothermal response properties of the NA/PET/NI-3 soft actuator. (<b>a</b>) An illustration and SEM image of the section of the NA/PET/NI-3 soft actuator. (<b>b</b>) The stress–strain curves of the PET film and the NA/PET/NI-3 soft actuator. (<b>c</b>) The responsive and recovery behavior of NA/PET/NI-3 actuator. (<b>d</b>) The actuation performance of soft actuators with different thicknesses.</p>
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<p>The application of NA/PET/NI-3 photothermal actuator. (<b>a</b>) Repeated testing cycles of the photothermal response driving for the NA/PET/NI-3 soft actuator film. The red lines represent conditions under near-infrared light irradiation, while the blue lines represent conditions with near-infrared light turned off. (<b>b</b>) The NA/PET/NI-3 soft actuator mimics the flapping motion of butterfly wings. (<b>c</b>) Comparison of this work with other photothermal-responsive soft actuators.</p>
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<p>The photothermal response mechanism of the NA/PET/NI-3 soft actuator.</p>
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26 pages, 1207 KiB  
Article
Behavior Coding of Adolescent and Therapy Dog Interactions During a Social Stress Task
by Seana Dowling-Guyer, Katie Dabney, Elizabeth A. R. Robertson and Megan K. Mueller
Vet. Sci. 2024, 11(12), 644; https://doi.org/10.3390/vetsci11120644 - 12 Dec 2024
Viewed by 266
Abstract
Youth mental health interventions incorporating trained therapy animals are increasingly popular, but more research is needed to understand the specific interactive behaviors between participants and therapy dogs. Understanding the role of these interactive behaviors is important for supporting both intervention efficacy and animal [...] Read more.
Youth mental health interventions incorporating trained therapy animals are increasingly popular, but more research is needed to understand the specific interactive behaviors between participants and therapy dogs. Understanding the role of these interactive behaviors is important for supporting both intervention efficacy and animal welfare and well-being. The goal of this study was to develop ethograms to assess interactive behaviors (including both affiliative and stress-related behaviors) of participants and therapy dogs during a social stress task, explore the relationship between human and dog behaviors, and assess how these behaviors may vary between experimental conditions with varying levels of physical contact with the therapy dog. Using video data from a previous experimental study (n = 50 human–therapy dog interactions, n = 25 control group), we successfully developed behavioral ethograms that could be used with a high degree of interrater reliability. Results indicated differences between experimental conditions in dog and human behaviors based on whether participants were interacting with a live or a stuffed dog, and whether they were allowed to touch the dog. These findings suggest that physically interacting with a live dog may be an important feature of these interventions, with participants demonstrating increased positive behaviors such as laughing and smiling in these conditions. Dog behaviors also varied based on whether they were in the touching/petting condition of the study which could indicate reactions to the session and has potential welfare implications for the dogs. Future research should focus on identifying specific patterns of interactive behaviors between dogs and humans that predict anxiolytic outcomes. Full article
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<p>Original experimental conditions and study timeline/tasks.</p>
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<p>Human behaviors by experimental condition (<span class="html-italic">N</span> = 75). Note: * indicates difference of <span class="html-italic">p</span> &lt; .05 between conditions based on mean rank testing, indicated by brackets.</p>
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<p>Dog behaviors by experimental condition (<span class="html-italic">n</span> = 50). Note: * indicates difference of <span class="html-italic">p</span> &lt; .05 between conditions based on mean rank testing.</p>
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17 pages, 4384 KiB  
Case Report
Surgical Treatment and Targeted Therapy for a Large Metastatic Malignant Peripheral Nerve Sheath Tumor: A Case Report and Literature Review
by Patryk Skórka, Dawid Kordykiewicz, Andrzej Ilków, Konrad Ptaszyński, Janusz Wójcik, Wiktoria Skórka and Małgorzata Edyta Wojtyś
Life 2024, 14(12), 1648; https://doi.org/10.3390/life14121648 - 12 Dec 2024
Viewed by 268
Abstract
Neurofibromatosis type 1 (NF1) significantly increases the risk of malignant peripheral nerve sheath tumors (MPNST), a rare and aggressive malignancy for which treatment is clinically challenging. This paper presents the case of a 24-year-old male with an NF1 who developed MPNST with lung [...] Read more.
Neurofibromatosis type 1 (NF1) significantly increases the risk of malignant peripheral nerve sheath tumors (MPNST), a rare and aggressive malignancy for which treatment is clinically challenging. This paper presents the case of a 24-year-old male with an NF1 who developed MPNST with lung metastases. Due to the limited effectiveness of systemic therapy in the treatment of MPNST, the patient underwent radical surgical resection and radiotherapy. Pathological evaluation confirmed high-grade MPNST, and PET-CT imaging revealed further metastatic progression. The treatment results for our patient are compared with those of other patients with NF1 who also developed MPNST with lung metastases in the literature. The findings suggest the need for further research into personalized treatment strategies that may improve prognosis and overall survival in patients with NF1 and MPNST, with immunotherapy being a promising therapeutic option. Full article
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<p>Patient’s current café au lait spot in the trunk (<b>A</b>,<b>B</b>).</p>
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<p>Preoperative image showing a tumor in the left retroperitoneal space infiltrating adjacent structure (<b>A</b>). Tumor in the left lumbar region visualized during surgery, showing extensive neoplastic tissue (<b>B</b>). Postoperative image showing significantly reduced tumor masses in the lumbar region after the initial resection (<b>C</b>). Image confirming the presence of a new tumor in the left retroperitoneal space, requiring further surgical intervention (<b>D</b>). Cross-sectional images of removed tumors from the left lumbar region and retroperitoneal space (<b>E</b>,<b>F</b>). Post-operative wound with the drainage system (<b>G</b>,<b>H</b>).</p>
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<p>PET/CT axial plane. (<b>A</b>) Showing no lung lesions April 2024. (<b>B</b>) Lung metastasis July 2024 (white arrows).</p>
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<p>Intraoperative view showing the left lateral retroperitoneal tumor during exposure. The tumor is partially visible within the surgical field (<b>A</b>). Close-up of the left retroperitoneal tumor during resection, highlighting its dense and fibrotic structure (<b>B</b>). Advanced stage of dissection in the left retroperitoneal region, revealing tumor adherence to adjacent tissues (<b>C</b>). Completely resected tumor mass from the left retroperitoneal space, with irregular margins visible (<b>D</b>). Post-resection surgical field showing the cavity left by the removed tumor (<b>E</b>). Resected tumor mass (<b>F</b>).</p>
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<p>Chest X-Rays performed a one-month interval showing progression of lung metastasis. (<b>A</b>,<b>B</b>).</p>
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<p>Chest CT: axial plane (<b>A</b>,<b>C</b>,<b>D</b>), coronal plane (<b>B</b>) heterogeneous density lesion of the right lung lobule with displacement of mediastinal structures.</p>
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<p>The initial phase of right thoracotomy reveals the metastatic MPNST mass in the thoracic cavity (<b>A</b>). The tumor during partial separation from the surrounding tissues, demonstrating anatomical infiltration (<b>B</b>). Post-thoracotomy view showing the space left after the complete resection of the metastatic tumor from the right lung (<b>C</b>). Final operative field view after the complete tumor resection, illustrating the area cleared of the mass (<b>D</b>).</p>
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<p>Histopathological specimens (representative hematoxylin–eosin stained histological images): (<b>A</b>) Spindle- and oval-shaped cells display a vague fascicular growth pattern with some perivascular accentuation. A moderate number of mitotic figures are present (original magnification ×200). (<b>B</b>) A high-power view of the spindle- and oval-shaped cells reveals a vague fascicular growth pattern (original magnification ×400). (<b>C</b>) A paratracheal nodule shows histological features of neurofibroma (original magnification ×200).</p>
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12 pages, 1780 KiB  
Article
Do Not Throw Pet Faeces Away: Composted Manures Obtained from Dog and Cat Faeces Contain High Nutrients and Effectively Cultivate Plants
by Suwit Wuthisuthimethavee, Jindarha Prempramote, Worakan Boonhoh, Athakorn Promwee, Orachun Hayakijkosol and Tuempong Wongtawan
Recycling 2024, 9(6), 123; https://doi.org/10.3390/recycling9060123 - 12 Dec 2024
Viewed by 627
Abstract
Dog and cat faeces are a globally neglected issue that demands proper management. The poor handling of pet waste not only impacts environmental health but also contributes to community conflicts due to insufficient waste management practices. The objectives were to investigate the properties [...] Read more.
Dog and cat faeces are a globally neglected issue that demands proper management. The poor handling of pet waste not only impacts environmental health but also contributes to community conflicts due to insufficient waste management practices. The objectives were to investigate the properties of pet wastes compared to livestock wastes (pigs, hens, and cattle) with the intention of formulating an efficient compost product suitable for agricultural applications. Faeces from dogs and cats were collected from the community, while faeces from livestock (pigs, cattle, and hens) were collected from farms. Faeces were mixed with probiotics, rice bran, and rice husk to make compost and used to grow sweet corn plants. The nutrient content was compared between fresh and composted faeces. Composted manure from different animal sources was compared for its effectiveness in promoting sweet corn growth. The results showed that fresh and composted dog and cat manures contained higher levels of nutrients (p < 0.05) compared to livestock manures. Additionally, composted pet manure accelerated (p < 0.05) the growth of the plants compared to composted livestock manures and control groups. This is the first study to conclude that composted pet faeces surpass livestock manure in their higher nutrients and enhance plant growth. The findings could help reduce pet waste and transform it into a valuable recycled resource. However, the safety of composted manure, especially concerning toxoplasmosis from cat faeces, remains a significant concern and requires further investigation. Full article
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<p>Colour of control (rice bran and rice husk), fresh manures from dogs, cats, pigs, cows, and hens mixed with rice bran and rice husk (day 0), and composted manure on day 14.</p>
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<p>Temperature change during composting process.</p>
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<p>Growth of sweet corn after treatment with different composts including control 1 (soil only), control 2 (rice brand and husk compost), composted dog manure, composted cattle manure, composted pig manure, composted cat manure, and composted hen manure.</p>
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13 pages, 5489 KiB  
Article
CT-Free Attenuation Correction in Paediatric Long Axial Field-of-View Positron Emission Tomography Using Synthetic CT from Emission Data
by Maria Elkjær Montgomery, Flemming Littrup Andersen, René Mathiasen, Lise Borgwardt, Kim Francis Andersen and Claes Nøhr Ladefoged
Diagnostics 2024, 14(24), 2788; https://doi.org/10.3390/diagnostics14242788 - 12 Dec 2024
Viewed by 332
Abstract
Background/Objectives: Paediatric PET/CT imaging is crucial in oncology but poses significant radiation risks due to children’s higher radiosensitivity and longer post-exposure life expectancy. This study aims to minimize radiation exposure by generating synthetic CT (sCT) images from emission PET data, eliminating the [...] Read more.
Background/Objectives: Paediatric PET/CT imaging is crucial in oncology but poses significant radiation risks due to children’s higher radiosensitivity and longer post-exposure life expectancy. This study aims to minimize radiation exposure by generating synthetic CT (sCT) images from emission PET data, eliminating the need for attenuation correction (AC) CT scans in paediatric patients. Methods: We utilized a cohort of 128 paediatric patients, resulting in 195 paired PET and CT images. Data were acquired using Siemens Biograph Vision 600 and Long Axial Field-of-View (LAFOV) Siemens Vision Quadra PET/CT scanners. A 3D parameter transferred conditional GAN (PT-cGAN) architecture, pre-trained on adult data, was adapted and trained on the paediatric cohort. The model’s performance was evaluated qualitatively by a nuclear medicine specialist and quantitatively by comparing sCT-derived PET (sPET) with standard PET images. Results: The model demonstrated high qualitative and quantitative performance. Visual inspection showed no significant (19/23) or minor clinically insignificant (4/23) differences in image quality between PET and sPET. Quantitative analysis revealed a mean SUV relative difference of −2.6 ± 5.8% across organs, with a high agreement in lesion overlap (Dice coefficient of 0.92 ± 0.08). The model also performed robustly in low-count settings, maintaining performance with reduced acquisition times. Conclusions: The proposed method effectively reduces radiation exposure in paediatric PET/CT imaging by eliminating the need for AC CT scans. It maintains high diagnostic accuracy and minimises motion-induced artifacts, making it a valuable alternative for clinical application. Further testing in clinical settings is warranted to confirm these findings and enhance patient safety. Full article
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<p>Illustrative sample patient with banana artifact presented. Panels (<b>a</b>,<b>b</b>) show the normal CT and corresponding PET. The synthetic CT (sCT) and corresponding sPET are seen in (<b>c</b>,<b>d</b>). PET is fused on top of the CT scan in (<b>e</b>), illustrating the mismatch between CT and emission data. The blue line represents the superior part of the liver at the time of CT scanning. Panel (<b>f</b>) shows the sPET fused on top of the sCT.</p>
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<p>Sample patient with metal implant exhibiting streaking artefacts in the CT image (<b>a</b>), which are absent in the sCT image (<b>b</b>). The corresponding PET images are seen for PET and sPET, respectively (<b>c</b>,<b>d</b>). The zoom panels have been magnified by a factor of 2.3.</p>
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<p>Representation of a 1-year-old patient featuring the CT, sCT, and corresponding PET images PET and sPET (<b>a</b>–<b>d</b>). Additionally, a relative percent difference map between the PET and sPET images (<b>e</b>) highlights that the discrepancies in the PET images are localised in the patient’s cranium and left arm.</p>
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<p>Relative max difference (<b>a</b>) and mean difference (<b>b</b>) between the PET and sPET for lesions found in the examinations. The colour and size of each point represent the lesion type and size, respectively.</p>
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<p>Violin-plot showing the mean relative percent difference between PET and sPET for selected organs. The white dot in each presents the median value, and the solid black box represents the interquartile range, whereas the line extends to 1.5 times the interquartile range.</p>
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<p>Violin-plot showing the mean relative difference between PET, PET<sub>60</sub>, sPET<sub>90</sub>, and sPET<sub>60LC</sub> for selected organs.</p>
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<p>Flowchart for the proposed method. In the first step, we pretrain just the generator using paired NAC-PET and CT data from adult patients. This resulting generator is identical to the pre-trained generator from [<a href="#B47-diagnostics-14-02788" class="html-bibr">47</a>]. Next, we train a cGAN where the generator is initialised with weights from the pretraining step. The cGAN is optimized with data from n = 172 paediatric examinations. Finally, in the test phase, we use the trained generator to predict synthetic CT (sCT) images from NAC-PET patches, which are combined into full volumes.</p>
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12 pages, 5594 KiB  
Article
Automated Supraclavicular Brown Adipose Tissue Segmentation in Computed Tomography Using nnU-Net: Integration with TotalSegmentator
by Kasper Jørgensen, Frederikke Engel Høi-Hansen, Ruth J. F. Loos, Christian Hinge and Flemming Littrup Andersen
Diagnostics 2024, 14(24), 2786; https://doi.org/10.3390/diagnostics14242786 - 11 Dec 2024
Viewed by 352
Abstract
Background/Objectives: Brown adipose tissue (BAT) plays a crucial role in energy expenditure and thermoregulation and has thus garnered interest in the context of metabolic diseases. Segmentation in medical imaging is time-consuming and prone to inter- and intra-operator variability. This study aims to develop [...] Read more.
Background/Objectives: Brown adipose tissue (BAT) plays a crucial role in energy expenditure and thermoregulation and has thus garnered interest in the context of metabolic diseases. Segmentation in medical imaging is time-consuming and prone to inter- and intra-operator variability. This study aims to develop an automated BAT segmentation method using the nnU-Net deep learning framework, integrated into the TotalSegmentator software, and to evaluate its performance in a large cohort of patients with lymphoma. Methods: A 3D nnU-Net model was trained on the manually annotated BAT regions from 159 lymphoma patients’ CT scans, employing a 5-fold cross-validation approach. An ensemble model was created using these folds to enhance segmentation performance. The model was tested on an independent cohort of 30 patients. The evaluation metrics included the DICE score and Hausdorff Distance (HD). Additionally, the mean standardized uptake value (SUV) in the BAT regions was analyzed in 7107 FDG PET/CT lymphoma studies to identify patterns in the BAT SUVs. Results: The ensemble model achieved a state-of-the-art average DICE score of 0.780 ± 0.077 and an HD of 29.0 ± 14.6 mm in the test set, outperforming the individual fold models. Automated BAT segmentation revealed significant differences in the BAT SUVs between the sexes, with higher values in women. The morning scans showed a higher BAT SUV compared to the afternoon scans, and seasonal variations were observed, with an increased uptake during the winter. The BAT SUVs decreased with age. Conclusions: The proposed automated BAT segmentation tool demonstrates robust performance, reducing the need for manual annotation. The analysis of a large patient cohort confirms the known patterns of BAT SUVs, highlighting the method’s potential for broader clinical and research applications. Full article
(This article belongs to the Special Issue AI as a Tool to Improve Hybrid Imaging in Cancer—2nd Edition)
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<p>Violin plots show the distribution of DICE and HD metrics for each individual fold model in the CV, with a combined plot for full CV results. The last violin plots represent the ensemble model’s performance on the independent test set.</p>
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<p>Comparison of BAT segmentation across four test patients. Each column shows the CT images, ground truth BAT annotations, model-predicted BAT segmentations, and agreement analysis showing true positive pixels (green), false negative pixels (red), and false positive pixels (blue).</p>
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<p>Example of manual (blue) and predicted (red) BAT regions with 3D views showing discrepancies, including unannotated predictions near the shoulders (green arrows).</p>
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<p>Mean values across different subject groups in the LymphBAT–7107 cohort with 95% con–fidence intervals (mean <math display="inline"><semantics> <mrow> <mo>±</mo> <mo> </mo> </mrow> </semantics></math>1.96 SEM) shown.</p>
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<p>Application of the BAT segmentation model for SUV PET analysis on two test patients from the LymphBAT-7007 cohort, for which ground truth BAT annotations are unavailable. First column displays the model-inferred BAT regions, while the second shows the CT with PET overlay.</p>
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14 pages, 1604 KiB  
Article
Identification of the Compounds Used in Waste Bottle Caps Using Terahertz Radiation for Sustainable Resource Recycling to Benefit International Cooperation
by Gaku Manago, Kazuaki Okubo, Jeongsoo Yu, Tadao Tanabe and Tetsuo Sasaki
Sustainability 2024, 16(24), 10864; https://doi.org/10.3390/su162410864 - 11 Dec 2024
Viewed by 502
Abstract
In Japan, when people take their waste bottle caps to designated recycling companies, JPY 5/kg is donated to developing countries for polio vaccine dissemination activities. The waste volume of plastic bottles and caps is increasing every year, and there is not a day [...] Read more.
In Japan, when people take their waste bottle caps to designated recycling companies, JPY 5/kg is donated to developing countries for polio vaccine dissemination activities. The waste volume of plastic bottles and caps is increasing every year, and there is not a day that goes by that we do not see more bottles and caps. PET bottles are more easily recycled, as the bottle body is made of a single material. However, bottle caps are made of two different materials (PP and PE), which are difficult to identify perfectly when utilising the existing NIR technology in the recycling field. This is because the designs and colours of PP and PE bottle caps are becoming more diverse, with black and dark-coloured caps being difficult to sort using NIR technology. In addition, their specific gravity is almost the same; therefore, it is difficult to separate them by their water-based specific gravity, which is an approach commonly used by recyclers. Unidentified caps are sent for thermal recycling, which runs counter to the need for decarbonisation. They may also be mixed with identified caps and sold as recycled raw material, resulting in a reduction in the purity of the recycled plastic. If PP and PE caps can be identified using simple technology, it is expected to promote high resource recycling. Therefore, in order to develop such a sorting process, this study proposes a new method for the material identification of waste caps using terahertz waves. Therefore, this research aims to identify a new identification method for waste plastic caps, which has been a challenge both domestically and internationally. Specifically, we describe the limitations of the conventional methods for identifying PP and PE bottle caps according to their weight, specific gravity, and melting point and propose an identification method using terahertz waves, demonstrating its measurement-related merits and high identification accuracy. Full article
(This article belongs to the Section Waste and Recycling)
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<p>Research target.</p>
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<p>Collected samples of waste bottle caps.</p>
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<p>Measuring method using terahertz device.</p>
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<p>FTIR spectra of PP and PE bottle caps.</p>
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<p>THz transmittance spectra of PP and PE bottle caps.</p>
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<p>Result of waste bottle caps’ transmittance parameter.</p>
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12 pages, 6805 KiB  
Article
Development of a PET Probe Targeting Bromodomain and Extra-Terminal Proteins for In Vitro and In Vivo Visualization
by Yongle Wang, Yanli Wang, Yulong Xu, Hua Cheng, Tewodros Mulugeta Dagnew, Leyi Kang, Darcy Tocci, Iris Z. Shen, Can Zhang and Changning Wang
Pharmaceuticals 2024, 17(12), 1670; https://doi.org/10.3390/ph17121670 - 11 Dec 2024
Viewed by 286
Abstract
Background: Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to [...] Read more.
Background: Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to develop and evaluate a novel C-11 labeled PET radiotracer, [11C]YL10, for imaging the BD1 bromodomain of BRD4 in vivo. Methods: [11C]YL10 was synthesized and evaluated for its ability to bind to the BD1 bromodomain selectively. PET imaging studies were conducted in mice to assess brain penetration, pharmacokinetics, and selectivity. In vitro autoradiography and blocking experiments were performed to confirm the tracer’s specificity for the BD1 domain. Results: [11C]YL10 demonstrated good brain penetration, high selectivity for the BD1 bromodomain, and favorable pharmacokinetics in initial PET imaging studies. In vitro autoradiography and blocking experiments confirmed the specific binding of [11C]YL10 to the BD1 domain of BRD4, further validating its potential as a targeted radiotracer. Conclusions: The development of [11C]YL10 provides a new tool for studying BRD4 bromodomains using PET imaging technology. This radiotracer offers potential advancement in the diagnosis and research of neurodegenerative diseases and related disorders involving BRD4 dysregulation. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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<p>Chemical structures of BET inhibitors and C-11 and F-18 radiotracers.</p>
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<p>Chemical design of YL10 and [<sup>11</sup>C]YL10.</p>
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<p>In vitro inhibitory activity of compound YL10 against BRD4 (BD1/BD2), with <span class="html-italic">K<sub>d</sub></span> values of 0.48 μM for BRD4 BD1 and 1.65 μM for BRD4 BD2, respectively, as determined by a BROMOscan bromodomain competition binding assay. Curve Images: The amount of bromodomain measured by qPCR (Signal; <span class="html-italic">y</span>-axis) is plotted against the corresponding compound concentration in nM in log10 scale (<span class="html-italic">x</span>-axis).</p>
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<p>Molecular docking of YL10 to BRD4 protein (PDB ID: 3ZYU), (<b>A</b>) Molecular interactions of YL10 with BRD4 highlighting key hydrogen bonds and hydrophobic contacts within the binding pocket. (<b>B</b>) YL10 docked within the (acetyl lysine binding) hydrophobic pocket of BRD4 illustrating its favorable binding conformation [<a href="#B23-pharmaceuticals-17-01670" class="html-bibr">23</a>,<a href="#B24-pharmaceuticals-17-01670" class="html-bibr">24</a>].</p>
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<p>(<b>A</b>) Standard in vitro autoradiographic imaging of sagittal mouse brain slices; (<b>B</b>) a comparison of radiotracer binding in the baseline versus a blocking condition. In the baseline, slices were treated only with [<sup>11</sup>C]YL10, while in the blocking experiment, slices were incubated with 10 µM of compound YL10 as a competitor. Quantitative analysis in grayscale is shown as the mean ± standard deviation across four samples. Statistical significance is indicated by asterisks: ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>The radioligand [<sup>11</sup>C]YL10 exhibits ideal binding specificity. (<b>A</b>) PET/CT images of mouse brains obtained after intravenous (i.v.) injection of our radioligand (total acquisition time of 20–60 min). (<b>B</b>) Area under the curve (AUC) of the TACs from (<b>D</b>). (<b>C</b>) Whole-brain baseline and self-blockade (4.0 mg/kg unlabeled YL10) time-activity curves (TACs) (n = 3). (<b>D</b>) Normalized TACs of baseline and blockade conditions. * Indicates statistical significance: **** <span class="html-italic">p</span> ≤ 0.0001.</p>
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<p>Time-activity curves of [<sup>11</sup>C]YL10 in various brain regions. (<b>A</b>) Representative PET/CT images of [<sup>11</sup>C]YL10 focusing on the mouse brain under baseline conditions, acquired 20 to 60 min post intravenous (i.v.) injection. (<b>B</b>) Baseline TACs of [<sup>11</sup>C]YL10 in various brain regions, including the cortex, cerebellum, thalamus, hypothalamus, striatum, hippocampus, and amygdala.</p>
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<p>(<b>A</b>) PET-CT imaging of [<sup>11</sup>C]YL10 in a mouse brain at 5, 15, 30, and 60 min after the intravenous administration of radioligand. (<b>B</b>) the biodistribution of [<sup>11</sup>C]YL10 in mice at 5, 15, 30, and 60 min after the intravenous administration of radioligand (3 for each time point).</p>
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<p>Reagents and conditions: (<b>1</b>) LiOH·H<sub>2</sub>O, THF, 20–80 °C, 3 h; (<b>2</b>) CH<sub>3</sub>NO<sub>2</sub>, NaOH, H<sub>2</sub>O, 0–20–45 °C, 1.5 h; 2-amino-4-bromo-5-methoxy-benzoic acid, 12 M HCl; H<sub>2</sub>O, 35 °C, 5 h; (<b>3</b>) Ac<sub>2</sub>O, KOAc, 90 °C, 2 h; (<b>4</b>) POCl<sub>3</sub>, Et<sub>3</sub>N, 0–100 °C, 5 h; (<b>5</b>) (R)-1-phenylethan-1-amine, DMF, 30 °C, 4 h; (<b>6</b>) NH<sub>4</sub>Cl, Fe, EtOH, H<sub>2</sub>O, 90 °C, 5 h; (<b>7</b>) CDI, CH<sub>3</sub>COOH, KOAc, 100 °C, 5 h; (<b>8</b>) 1,4-dioxane, Pd(dppf)Cl<sub>2</sub>, KOAc, H<sub>2</sub>O, 20–100 °C, 20 min, 2 h. (<b>9</b>) NaH, THF, 0 °C, 15 min, CH<sub>3</sub>I, 0-RT, overnight.</p>
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<p>Radiolabeling [<sup>11</sup>C]YL10. Reagents and conditions: [<sup>11</sup>C]CH<sub>3</sub>I, KOH, DMF, 100 °C, 3 min, Radiochemical yield (RCY): 21–29% (decay-corrected). Specific activity of [<sup>11</sup>C]YL10 is 62.5–64.3 GBq/μmol at the end of bombardment (EOB).</p>
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15 pages, 3226 KiB  
Opinion
Nurturing Futures: The Role of Veterinary Nurses in Promoting the Healthy Development of Puppies and Kittens
by Tabitha Hookey, Brianne Morrow, Georgiana R. T. Woods, Franck Péron, John Flanagan and Virginie Gaillard
Pets 2024, 1(3), 443-457; https://doi.org/10.3390/pets1030031 - 11 Dec 2024
Viewed by 491
Abstract
The health of adult dogs and cats is affected positively or negatively by their development in utero and throughout postnatal growth. Preventive veterinary care is particularly important when animals are physiologically immature and sensitive to modifiable environmental factors. Veterinary nurses/technicians are often at [...] Read more.
The health of adult dogs and cats is affected positively or negatively by their development in utero and throughout postnatal growth. Preventive veterinary care is particularly important when animals are physiologically immature and sensitive to modifiable environmental factors. Veterinary nurses/technicians are often at the forefront of promoting healthy development, reinforcing the work of veterinarians and using their knowledge, experience, and passion to lead initiatives with breeders and pet guardians. This opinion article considers the role of qualified veterinary nurses/technicians in the care of puppies and kittens throughout their developmental life stages—gestation, the suckling period, growth post-weaning to puberty or neutering, and late growth to adulthood. Much of their influence is through the education of pet carers; they provide trustworthy information relevant to the individual pet and focused on the practicalities of best husbandry practices. These include practical advice on recognizing dystocia, neonatal care, weaning, introduction to the new home, the prevention and management of infectious diseases, socialization with conspecifics and humans, habituation to potential environmental stresses, nutrition, oral hygiene, and grooming. The veterinary nurse’s goal is not only to see young pets develop into healthy, well-adjusted adults but also to see pet guardians developing sustainable human–animal bonds. Full article
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<p>Overview of the role of veterinary nurses in the development of puppies and kittens.</p>
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16 pages, 3768 KiB  
Article
Effect of Hydrolyzed Frozen Meat on Diet Palatability, Apparent Digestibility, Immune Response, Fecal Microbiota, and Metabolome in British Shorthair Cats
by Shibin Ye, Zhihao Cao, Shiyan Jian, Limeng Zhang, Baichuan Deng and Jinping Deng
Pets 2024, 1(3), 427-442; https://doi.org/10.3390/pets1030030 - 10 Dec 2024
Viewed by 594
Abstract
Frozen meat is an important source of protein in pet food, and has attracted much attention in recent years. In this study, we compared the effect of meat meal (MM), frozen meat (FM), and hydrolyzed frozen meat (HFM) as ingredients in extruded pet [...] Read more.
Frozen meat is an important source of protein in pet food, and has attracted much attention in recent years. In this study, we compared the effect of meat meal (MM), frozen meat (FM), and hydrolyzed frozen meat (HFM) as ingredients in extruded pet food on its palatability and apparent digestibility, as well as its effects on the immune response, fecal microbiota, and metabolome of British shorthair cats. A total of 24 British shorthair cats were allocated to the MM, FM, and HFM groups according to body weight and gender. The palatability test lasted 4 days and the feeding test lasted 45 days. The results showed that the FM and HFM diets had better palatability than the MM diet (p < 0.05) and significantly improved dry matter and crude protein digestibility (p < 0.05). The serum IL-10 level was significantly higher in the HFM group compared to the MM and FM groups (p < 0.05). The serum IgM levels were also found to be significantly higher in the FM group compared to the MM and HFM groups (p < 0.05). The blood urea nitrogen/creatinine ratio was significantly lower in the HFM and FM groups than in the MM group (p < 0.05). Cats fed HFM had a higher abundance of fecal Actinobacteria and Bifidobacterium and a lower content of Bacteroidota (p < 0.05). Furthermore, serum metabolomics analysis revealed that the tryptophan (Trp) metabolism and bile acid metabolism were affected by HFM. Overall, FM and HFM were better for the cat’s health than meat meal, but they also have some potential risks. Full article
(This article belongs to the Topic Research on Companion Animal Nutrition)
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<p>Schematic representation of the study design. Group1 was fed MM and FM (<span class="html-italic">n</span> = 8), Group2 was fed MM and HFM (<span class="html-italic">n</span> = 8), and Group3 was fed FM and HFM (<span class="html-italic">n</span> = 8).</p>
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<p>Intake ratio (%) (<b>A</b>) and first consumption choice (%) (<b>B</b>) of cats (MM: <span class="html-italic">n</span> = 8; FM: <span class="html-italic">n</span> = 8; HFM: <span class="html-italic">n</span> = 8) fed experimental diets containing MM, FM, and HFM. The symbol (*) indicates statistically significant differences between two groups (* <span class="html-italic">p</span>&lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Gut microbial composition and structure of cats (MM: <span class="html-italic">n</span> = 6; FM: <span class="html-italic">n</span> = 6; HFM: <span class="html-italic">n</span> = 8) fed experimental diets containing MM, FM, and HFM. Venn diagram of fecal samples in each group (<b>A</b>); alpha diversity (<b>B</b>); principal co-ordinate analysis (PCoA) based on weighted UniFrac distances (<b>C</b>). The symbol (*) indicates statistically significant differences between two groups (* <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span>&lt; 0.01).</p>
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<p>Predominant fecal microbial communities and different bacteria at the phylum (<b>A</b>) and genus levels (<b>B</b>) in cats (MM: <span class="html-italic">n</span> = 6; FM: <span class="html-italic">n</span> = 6; HFM: <span class="html-italic">n</span> = 8) fed experimental diets containing MM, FM, and HFM. The symbol (*) indicates statistically significant differences between two groups (* <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span>&lt; 0.01), and the symbol (<sup>#</sup>) represents the difference tendency (<sup>#</sup> <span class="html-italic">p</span> &lt; 0.10).</p>
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<p>The linear discriminant analysis effect size (LEfSe) analysis identified the most differential microbiota in cats fed experimental diets containing MM, FM, and HFM.</p>
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<p>Multivariate statistical analysis of metabolites in cats fed experimental diets containing MM, FM, and HFM. Score plots from the principal component analysis (PCA) model among the three groups (<b>A</b>). Score plots from the partial least-squares discriminant analysis (PLS-DA) model among the three groups (<b>B</b>).</p>
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<p>Bar charts of the metabolic pathway analysis of differential serum metabolites between the MM and FM groups (<b>A</b>) and between the FM and HFM groups (<b>B</b>).</p>
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