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Quinclorac is important precursor for pharmaceutical, agricultural, and synthetic chemistry. The state‐of‐art synthesis of quinclorac via condensation, chlorination and oxidative hydrolysis often uses homogeneous catalysts and strong acid oxidant agents to promote the catalytic oxidation, which requires huge manpower input for the late‐stage purification process and is usually environmentally unfriendly. In this work, we successfully fabricated a stable cobalt phthalocyanine (CoPc) Co‐based composite (CoPc/TiO2) by anchoring CoPc on the surface of TiO2 nanorods for the selective oxidation of 3,7‐dichloro‐8‐dichloro methyl quinoline (3,7‐D‐8‐DMQ) into quinclorac. More impressively, CoPc/TiO2‐2.5 %‐Mn‐Br exhibits a high selectivity of 91.9 % for the catalytic oxidation of 3,7‐D‐8‐DMQ to quinclorac in acetic acid, with a quinclorac yield of 86.4 %, which is approximately 2.43 times higher than that of pristine CoPc‐Mn‐Br. The obtained heterogeneous catalytic system shows good reusability. Detailed mechanistic investigations reveal that the system works through a free radical mechanism via the formation of Co2+/Co3+ redox cycles. This work provides a new understanding for the stabilization of reaction intermediates and facilitates the designs of catalysts for selective catalytic oxidation. [ABSTRACT FROM AUTHOR]

The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing among elderly (≥70 years) patients and the optimal treatment approach is not known. In this study, we aimed to determine disease and toxicity outcomes in an elderly HPV‐OPSCC population primarily treated with a chemoradiation (CRT) approach. We identified 70 elderly HPV‐OPSCC patients who were treated with either surgery, radiotherapy, or CRT between 2011 and 2021. Time‐to‐event analysis for overall survival (OS), progression‐free survival (PFS), and local control (LC) were conducted using the Kaplan–Meier method. Univariate and multivariable cox regression models were used to estimate the hazard ratio associated with covariates. The median follow‐up for our cohort was 43.9 months. Of the 70 elderly patients, 55 (78.6%) receive CRT and 15 (22.4%) received RT alone. Two patients underwent TORS resection. Of the 55 patients treated with CRT, the most common systemic agents were weekly carboplatin/taxol (n = 18), cetuximab (n = 17), and weekly cisplatin (n = 11). The 5‐year OS, PFS, and LC were 57%, 52%, and 91%, respectively. On univariate analysis, Eastern Cooperative Oncology Group performance status and Charlson Comorbidity Index (CCI) were significant predictors of OS, while on multivariate analysis only CCI was a significant predictor of OS (p = 0.006). The rate of late peg tube dependency, osteoradionecrosis, and aspiration was 10%, 4%, and 4%, respectively. Definitive local therapy in elderly HPV‐OPSCC patients is associated with excellent LC and a low rate of late toxicities. Prospective studies are needed to further stratify subgroups of elderly patients who may benefit from aggressive definitive local therapy. [ABSTRACT FROM AUTHOR]

Purpose: To implement an outcome‐driven frequency filter for improving radiomics‐based modeling of human papillomavirus (HPV) for patients with oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: One hundred twenty‐eight OPSCC patients with known HPV status (60‐HPV+ and 68‐HPV–, confirmed by immunohistochemistry‐P16 protein testing) were retrospectively studied. A 3D Discrete Fourier Transform was applied on contrast‐enhanced computed tomography (CE‐CT) images of patient gross tumor volumes (GTVs) to transform intensity distributions to the frequency domain and estimate frequency power spectrums of HPV– and HPV+ patient cohorts. Statistical analyses were performed to rank frequency bands contributing toward the prediction of HPV status. An outcome‐driven frequency filter was designed accordingly and applied to GTV frequency information. A 3D inverse discrete Fourier transform was applied to reconstruct HPV‐related frequency‐filtered images. Radiomics features (11 feature‐categories) were extracted from pre‐ and post‐frequency filtered images using our previously published "ROdiomiX" software. Least‐absolute‐shrinkage‐and‐selection‐operation (Lasso) combined with a generalized linear model (Lasso‐GLM) was developed to identify and rank feature subsets with the optimal information for prediction of HPV+/–. Radiomics‐based Lasso‐GLM classifiers (pre‐ and post‐frequency filtered) were constructed and validated using random permutation sampling and nested cross‐validation (CV) techniques. Average area under the receiver operating characteristic (AUC), and positive and negative predictive values (PPV and NPV) were computed to estimate generalization error and prediction performance. Results: Among 192 radiomic features, 15 features were found to be statistically significant discriminators between HPV+/– cohorts on post‐frequency filtered CE‐CT images. Fourteen such radiomic features were observed on pre‐frequency filtered datasets. Discriminant features included tumor morphology and intensity contrast. Performances for prediction of HPV for the pre‐ and post‐frequency filtered Lasso‐GLM classifiers were as follows: AUC/PPV/NPV = 0.789/0.755/0.805 and 0.850/0.808/0.877, respectively. Nested CV performances for prediction of HPV for the pre‐ and post‐frequency filtered Lasso‐GLM classifiers were as follows: AUC/PPV/NPV = 0.814/0.725/0.877 and 0.890/0.820/0.911, respectively. Conclusion: Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results on the importance of frequency analysis prior to radiomic feature extraction toward enhancement of model performance for characterizing HPV in patients with OPSCC. [ABSTRACT FROM AUTHOR]

Background and Purpose: Nicotinic ACh receptors containing the α7 sub-unit (α7-nAChRs) suppress inflammation through a wide range of pathways in immune cells. These receptors are thus potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying the anti-inflammatory effects of α7-nAChRs remain to be described.Experimental Approach: Anti-inflammatory effects of α7-nAChR agonists were assessed in both murine macrophages (RAW 264.7) and bone marrow-derived macrophages (BMDM), stimulated with LPS, using immunoblotting, RT-PCR and luciferase reporter assays. The role of adenylyl cyclase-6 in the degradation of Toll-like receptor 4 (TLR4) following endocytosis, was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease (COPD) induced by porcine pancreatic elastase was used to confirm key findings.Results: Anti-inflammatory effects of α7-nAChRs were largely dependent on adenylyl cyclase-6 activation, as knockdown of adenylyl cyclase-6 considerably reduced the effects of α7-nAChR agonists while adenylyl cyclase-6 overexpression promoted them. We found that α7-nAChRs and adenylyl cyclase-6 are co-localized in lipid rafts of macrophages and directly interact. Activation of adenylyl cyclase-6 led to increased degradation of TLR4. Administration of the α7-nAChR agonist PNU-282987 attenuated pathological and inflammatory end points in a mouse model of COPD.Conclusion and Implications: The α7-nAChRs inhibit inflammation through activating adenylyl cyclase-6 and promoting degradation of TLR4. The use of α7-nAChR agonists may represent a novel therapeutic approach for treating COPD and possibly other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Purpose: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low‐field MRIs acquired on an MR‐linac via image registration to further enable cardiac substructure sparing on TPCTs. Methods: Sixteen upper thoracic patients treated at various breathing states (7 end‐exhalation, 7 end‐inhalation, 2 free‐breathing) on a 0.35T MR‐linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three‐dimensional (3D) U‐Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re‐optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV‐V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches. Results: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re‐optimized plans reduced left anterior descending artery (LADA) mean and LADA0.03cc (0.0–63.9% and 0.0 to 17.3 Gy, respectively). LV0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV‐V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D0.03cc. One patient exhibited >10 Gy reduction in D0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re‐optimization. Four patients benefited from new beam arrangements, leading to further dose reductions. Conclusions: By introducing 0.35T MRIs acquired on an MR‐linac to verify cardiac substructure segmentations for CT‐based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation‐related cardiotoxicities. [ABSTRACT FROM AUTHOR]