Optimizing of a metal foam-assisted solar air heater performance: a thermo-hydraulic analysis of porous insert placement.

A numerical assessment of the heat transfer efficacy of a solar air heater (SAH) was carried out. The SAH is supplied with a porous metal foam layer to improve thermal mixing. Both the local thermal non-equilibrium (LTNE) and Darcy-extended Forchheimer (DEF) models were employed to forecast fluid and thermal transport within the partly filled SAH channel. The analysis was performed for various values of dimensionless foam layer lengths ( S = 0 - 1 ), pore densities ( ω = 10 - 40 PPI ), and Reynolds numbers ( R e = 4000 - 1 6 , 000 ) at a fixed value of layer thickness ( H f = 0.6 ). Based on the position of the porous layer, three distinct arrangements, marked as Case 1, Case 2, and Case 3, were explored. Regarding the parameters examined, the findings indicate a definite improvement in the average Nusselt number ( Nu ), but unfortunately, the friction factor also increases unfavorably. By reducing the length of the porous layer, a reasonable reduction in heat transfer rate and a significant decrease in pressure drop were noticed. The results showed about 26.64%, 48.73%, and 70.74% reductions in pressure drop by reducing the dimensionless foam length from 1 to 0.25, 0.5, and 0.75 respectively for ω = 10 at R e = 16 , 000 . On the other side, there are only about 11.05%, 23.11%, and 40.78% reductions in Nu . The exhaustive analysis of the thermal performance of SAH was conducted using the thermal performance factor (TPF), which considers the trade-off between the SAH channel's potential for improved heat transmission and its cost for pressure loss. The TPF may reach a maximum of 2.82 compared to the empty channel when the metal foam layer is inserted with S = 1 , for ω = 10 , and R e = 16 , 000 .

Efficacy of docetaxel, cisplatin, and 5-fluorouracil as an induction chemotherapy in oral squamous cell carcinoma in a tertiary hospital in Saudi Arabia.

Objective: To assess the efficacy and safety of the induction chemotherapy's combination of docetaxel, cisplatin, and 5-fluorouracil (TPF) in Oral Squamous Cell Carcinoma (OSCC) patients and its positive outcomes on tumor size and surgical resection. Method: A retrospective chart review of patient's medical records was conducted from 2018 to 2023. All patients diagnosed with OSCC and who received induction chemotherapy combination of TPF were included in the study. Patients with other conditions that affect chemotherapy tolerability, other primary malignancy, or incomplete medical records were excluded. Descriptive analysis was undertaken to summarize the data pertaining to tumors before and after administration of the TPF chemotherapy. Result: Five patients met the inclusion criteria. All five patients experienced a reduction in tumor size after receiving the TPF induction chemotherapy. Three patients showed a downstaging to [stage 0] after surgical resection. Specifically, one patient demonstrated a reduction in overall stage from [IVb] to [IVa] after receiving TPF induction chemotherapy, and two patients demonstrated a noteworthy improvement in N staging, reducing from [N2c] to [N2b]. In contrast, the fourth patient slightly improved after the induction chemotherapy and surgical resection procedures. However, the stage of the fifth patient remained unchanged before and after the treatment approach. Conclusion: The study shows that implementing TPF induction chemotherapy to surgical resection improves clinical outcomes in a subset of patients with advanced OSCC without any harmful consequences.

Oral administration of terpenoids and phenol fraction of Padina gymnospora stimulates the nonspecific immune response and expression of immune genes, and protects the common carp (Cyprinus carpio) from experimental Aeromonas hydrophila infection.

Common carp (Cyprinus carpio), a valuable aquaculture species susceptible to various infections, requires effective immune enhancement strategies. This study investigates the immunomodulatory effects of orally administered terpenoids and phenol fraction (TPF) from Padina gymnospora in C. carpio, focusing on stimulation of nonspecific immune response, immune gene expression, and protection against experimental infection. P. gymnospora is a brown seaweed species known for its bioactive compounds and medicinal properties. TPF was extracted using the Harborne fractionation method, and the presence of terpenoids and phenol compounds was confirmed by qualitative analysis and high-performance thin layer chromatography (HPTLC). TPF was administered orally in different doses to carp. Nonspecific immune responses were evaluated by measuring cellular ROS, RNI, and peroxidase production. The expression of immune genes (lysozyme and interleukin-1ß) was assessed by reverse transcriptase PCR. Furthermore, the protective efficacy of TPF was determined by infecting carp with a virulent pathogen, Aeromonas hydrophila, and monitoring mortality rates and disease symptoms. The results demonstrate that oral TPF administration significantly enhances nonspecific immune responses, with increased ROS, RNI, and peroxidase production, indicating improved immune function. Expression levels of lysozyme and interleukin-1ß were upregulated, suggesting immune system activation. Moreover, TPF exhibited significant protection against experimental infection, with lower mortality rates compared to the control group. These findings highlight TPF's potential as an effective immunostimulatory agent, enhancing immune responses and providing infection protection in carp. In conclusion, oral TPF administration stimulates nonspecific immune responses, modulates immune gene expression, and confers protection against experimental infection in carp, displaying its potential for enhancing immune responses and disease resistance in aquaculture species, and contributing to sustainable fish health management.

Mismatch between Clinical-Functional and Radiological Outcome in Tibial Plateau Fractures: A Retrospective Study.

BACKGROUND: The evaluation of tibial plateau fractures (TPF) encompasses the assessment of clinical-functional and radiological parameters. In this study, the authors aimed to investigate the potential correlation between these parameters by utilizing both the clinical-functional and the modified radiological Rasmussen score. METHODS: In this retrospective monocentric study conducted at a level-I trauma center, patients who underwent surgery between January 2014 and December 2019 due to a TPF were included. The clinical-functional Rasmussen score prior to the injury, at 1-year postoperatively, and during the last follow-up (minimum 18 months) was assessed using a standardized questionnaire. Additionally, the modified radiological Rasmussen score was determined at the 1-year postoperative mark using conventional radiographs in two planes. RESULTS: A total of 50 patients were included in this study, comprising 40% (n = 20) men, and 60% (n = 30) women, with an average age of 47 ± 11.8 years (range 26-73 years old). Among them, 52% (n = 26) had simple fractures (classified according to Schatzker I-III), while 48% (n = 24; according to Schatzker IV-VI) had complex fractures. The mean follow-up was 3.9 ± 1.6 years (range 1.6-7.5 years). The functional Rasmussen score assessed before the injury and at follow-up showed an "excellent" average result. However, there was a significant difference in the values of complex fractures compared to before the injury. One year postoperatively, both the clinical-functional score and the modified radiological score demonstrated a "good" average result. The "excellent" category was more frequently observed in the functional score, while the "fair" category was more common in the radiological score. There was no agreement between the categories in both scores in 66% of the cases. CONCLUSIONS: The data from this retrospective study demonstrated that patients with TPF are able to achieve a nearly equivalent functional level in the medium-term after a prolonged recovery period, comparable to their pre-injury state. However, it is important to note that the correlation between clinical-functional and radiological parameters is limited. Consequently, in order to create prospective outcome scores, it becomes crucial to objectively assess the multifaceted nature of TPF injuries in more detail, both clinically and radiologically.

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma.

OBJECTIVES: To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. METHODS: Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. RESULTS: Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. CONCLUSIONS: Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

Preoperative Mixed-Reality Visualization of Complex Tibial Plateau Fractures and Its Benefit Compared to CT and 3D Printing.

BACKGROUND: Various studies have shown the benefit of three-dimensional (3D) computed tomography (CT) reconstruction and especially 3D printing in the treatment of tibial plateau fractures (TPFs). This study aimed to investigate whether mixed-reality visualization (MRV) using mixed-reality glasses can provide a benefit for CT and/or 3D printing in planning treatment strategies for complex TPFs. METHODS: Three complex TPFs were selected for the study and processed for 3D imaging. Subsequently, the fractures were presented to specialists in trauma surgery using CT (including 3D CT reconstruction), MRV (hardware: Microsoft HoloLens 2; software: mediCAD MIXED REALITY) and 3D prints. A standardized questionnaire on fracture morphology and treatment strategy was completed after each imaging session. RESULTS: 23 surgeons from 7 hospitals were interviewed. A total of 69.6% (n = 16) of those had treated at least 50 TPFs. A change in fracture classification according to Schatzker was recorded in 7.1% of the cases and in 78.6% an adjustment of the ten-segment classification was observed after MRV. In addition, the intended patient positioning changed in 16.1% of the cases, the surgical approach in 33.9% and osteosynthesis in 39.3%. A total of 82.1% of the participants rated MRV as beneficial compared to CT regarding fracture morphology and treatment planning. An additional benefit of 3D printing was reported in 57.1% of the cases (five-point Likert scale). CONCLUSIONS: Preoperative MRV of complex TPFs leads to improved fracture understanding, better treatment strategies and a higher detection rate of fractures in posterior segments, and it thus has the potential to improve patient care and outcomes.

Low p16 Cytoplasmic Staining Predicts Poor Treatment Outcome in Patients with p16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving TPF Induction Chemotherapy.

Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in HNSCC prognosis. A total of 195 HNSCC patients who received docetaxel, cisplatin, and 5-fluouracil (TPF) induction chemotherapy followed by chemoradiotherapy were enrolled. The status of p16 cytoplasmic staining was determined using immunohistochemistry. The median follow-up was 26.0 months for the whole study population and 90.3 months for 51 living survivors. p16 cytoplasmic staining was low in 108 patients and high in 87 patients. Low expression of p16 cytoplasmic staining and primary tumor location in the oral cavity were both independent factors indicating a worse response rate to TPF induction chemotherapy in the univariate and multivariate analyses. The logistic regression model also showed that low expression of p16 cytoplasmic staining and clinical N2-3 status were independent prognostic factors for worse progression-free survival and overall survival. Our study showed that p16 cytoplasmic staining could predict the treatment response to TPF induction chemotherapy and is an independent prognostic factor of survival in HNSCC.

Suppression of TLR signaling by IRAK-1 and -4 dual inhibitor decreases TPF-resistance-induced pro-oncogenic effects in HNSCC.

Combination of docetaxel, cisplatin and 5-FU, known as TPF, is an FDA-approved treatment for head and neck squamous cell carcinoma (HNSCC). Acquired chemo-resistance to TPF, a primary reason for non-responsiveness to the treatment and relapse of tumor is a major concern for treatment failure, especially in elder patients. In this study, we investigated the role of Interleukin-1 receptor-associated kinases (IRAK) mediated Toll-like receptor (TLR)-signaling in chemo-resistance using a cell line-based in-vitro TPF-resistant HNSCC model of laryngeal origin. TPF chemo-resistant state showed over-expression and phosphorylation of the active downstream kinases IRAK-1 and IRAK-4 along with enhanced proliferative potential, survival, stemness and metastatic capability as compared to the parent cell line. Pharmacological inhibition of IRAK-1 and -4 had a cytostatic effect on chemo-resistant cells and re-sensitized them to chemotherapy. The treatment also decreased the pro-oncogenic effects of the chemo-resistant cells. Our study provides insights into the pro-oncogenic role of amplified IRAK-1 and-4 mediated TLR signaling in TPF-resistant HNSCC. Pharmacological inhibition of IRAK-1 and-4 signaling is a promising therapeutic strategy for TPF-resistant HNSCC. It can also be used as a combination therapy or a chemo-drug sparing regimen in HNSCC.

Assessment of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with oral cavity cancer.

BACKGROUND: Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. METHODS: We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. RESULTS: A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p < 0.001) and clinical stage (p = 0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively. CONCLUSIONS: The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Treatment Outcomes and Prognostic Factors of Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and Fluorouracil in Advanced Head and Neck Cancer.

BACKGROUND/AIM: Although the efficacy of docetaxel, cisplatin, and 5-Fluorouracil (TPF) as induction chemotherapy has been confirmed, the therapeutic outcome and prognostic factors of concurrent chemoradiotherapy (CCRT) should be investigated. PATIENTS AND METHODS: Laboratory data of patients who underwent CCRT for advanced squamous cell carcinoma (SCC) of the head and neck were investigated to clarify the grade of side effects. Survival rates and prognostic scores were also calculated. Multivariate analysis was performed to examine the prognostic factors of the patients. RESULTS: Although there were significantly more advanced cases in the TPF group (n=72) than those in the cisplatin group (n=50), there were no significant differences in patient survival rates. In the TPF group, the lymphocyte count, albumin level, and C-reactive protein level of the patients before treatment were significantly correlated with patient outcomes. CONCLUSION: CCRT using the TPF regimen had remarkable treatment effects in advanced head and neck cancer.

A finite element analysis of the supportive effect of a new type of rotary support plate on lateral tibial plateau fractures.

Background: Tibial plateau fractures (TPFs) are a challenging type of fracture in orthopedic traumatology. We previously designed a plate (Patent Number: CN201520195596.5) for posterolateral TPF combined with posterior lateral collapse.. In this study, finite element analysis was used to compare the biomechanical characteristics of two internal fixation methods for posterolateral TPF. We investigated the support effect of the new steel plate on lateral TPFs combined with posterior TPFs. Methods: Two models of complex TPF were established. Model A was fixed with the new type of plate, and model B was fixed without the plate. Three axial loads of 500, 1,000, and 1,500 N were applied using FEA on the two fracture models (A and B) to analyze the data. Results: In model A, the maximum displacement at 500, 1,000, and 1,500 N was 0.085797, 0.17043, and 0.25465 mm, respectively; the maximum stress of the bone block was 11.285, 20.648, and 29.227 MPa, respectively; and the maximum strain of the bone block was 0.0012474, 0.007435, and 0.0035769 mm, respectively. The maximum displacement of the internal fixation was 0.096932, 0.18682, and 0.27655 mm, respectively; the maximum stress was 69.54, 112.1, and 155.71 MPa, respectively; and the maximum strain was 0.00066228, 0.0010676, and 0.0014829 mm, respectively. In model B, the maximum displacement of fractures at 500, 1,000, and 1,500 N was 0.15675, 0.29868, and 0.44017 mm, respectively; the maximum stress of the bone block was 6.5519, 12.575, and 18.842 MPa, respectively; and the maximum strain of the bone block was 0.0032554, 0.0074357, and 0.012146 mm, respectively. The maximum displacement of the screw was 0.14177, 0.27109, and 0.39849 mm, respectively; the maximum stress was 48.916, 92.251, and 135.27 MPa, respectively; and the maximum strain was 0.00046608, 0.00087893, and 0.0012887 mm, respectively. Conclusions: The fixation method using this type of plates and screws can replace other methods using two plates to fix complex TPF.

Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer.

OBJECTIVES: Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT. MATERIALS AND METHODS: This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of < 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL). RESULTS: Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153). CONCLUSION: Noninferiority of cet+RT over cis+RT was not demonstrated.

Induction chemotherapy regimen of docetaxel plus cisplatin versus docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Preliminary results of an open-label, noninferiority, multicentre, randomised, controlled phase 3 trial.

Background: Induction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen. Methods: We performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337. Findings: Between June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death. Interpretation: The preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC. Funding: This study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].

Study of Mechanical Behavior in Epiphyseal Fracture Treated by Reduction and Cement Injection: No Immediate Post-Operative Weight-Bearing but Only Passive and Active Mobilization Should be Advised.

The development of new percutaneous treatment techniques using a balloon for the reduction and cement for the stabilization for tibial plateau fractures (TPF) are promising. The biomechanical changes brought by the cement in the periarticular fracture are unknown. The objective of this study was to provide elements of understanding of the bone behavior in an epiphyseal fracture treated with cementoplasty and to define the modifications brought about by the presence of this cement in the bone from both an architectural and biomechanical point of view. In vitro animal experimentation was conducted. Bones samples were prepared with a cavity created with or without cancellous compaction, aided by balloon expansion following the same protocol as in the treatment of TPF. A uniaxial compression test was performed with various speeds and by using Heaviside Digital Image Correlation to measure mechanical fields. Preliminary finite element models were constructed with various boundary conditions to be compared to our experimental results. The analysis of the images permits us to obtain a representative load vs. time response, the displacement fields, and the strain distribution for crack initiation for each sample. Microcracks and discontinuity began very early at the interface bone/cement. Even when the global behavior was linear, microcracks already happened. There was no strain inside the cement. The finite element model that matched our experiments had no link between the two materials. In this work, the use of a novel correlation process highlighted the biomechanical role of the cement inside the bone. This demonstrated that there is no load transfer between bone and cement. After the surgery, the cement behaves like a rigid body inside the cancellous bone (same as a screw or plate). The cement provides good reduction and primary stabilization (mini-invasive approach and good stress distribution), permitting the patient to undergo rehabilitation with active and passive mobilization, but no weight-bearing should be authorized while the cortical bone is not consolidated or stabilized.

Serum Levels of Stromal Cell-Derived Factor-1α and Vascular Endothelial Growth Factor Predict Clinical Outcomes in Head and Neck Squamous Cell Carcinoma Patients Receiving TPF Induction Chemotherapy.

Chemokines, such as stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF), are associated with clinical outcomes in several cancer types. This study aimed to investigate the role of SDF-1α and VEGF in the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) who underwent TPF induction chemotherapy (docetaxel, cisplatin, and 5-fluorouracil). A total of 77 HNSCC patients were enrolled and circulating SDF-1α and VEGF values were examined at two time points for each patient, including pre-TPF treatment (treatment-naïve) and post-TPF treatment but before chemoradiotherapy. The median progression-free survival (PFS) and overall survival (OS) were 18.1 and 32.9 months, respectively. Decreased SDF-1α and VEGF levels after TPF treatment, post-TPF SDF-1α < 1500 pg/mL and VEGF value < 150 pg/mL were independent prognostic factors for better PFS and OS in univariate and multivariate analyses. A combination of SDF-1α and VEGF values may predict clinical outcomes significantly. Our study confirmed the role of SDF-1α and VEGF in the disease progression of HNSCC, and that decreased SDF-1α and VEGF after TPF treatment and lower post-TPF SDF-1α and VEGF values were associated with better prognosis in HNSCC patients who received induction chemotherapy with TPF followed by chemoradiotherapy.

Imaging Sub-Cellular Methionine and Insulin Interplay in Triple Negative Breast Cancer Lipid Droplet Metabolism.

Triple negative breast cancer (TNBC) is a particularly aggressive cancer subtype that is difficult to diagnose due to its discriminating epidemiology and obscure metabolome. For the first time, 3D spatial and chemometric analyses uncover the unique lipid metabolome of TNBC under the tandem modulation of two key metabolites - insulin and methionine - using non-invasive optical techniques. By conjugating heavy water (D2O) probed Raman scattering with label-free two-photon fluorescence (TPF) microscopy, we observed altered de novo lipogenesis, 3D lipid droplet morphology, and lipid peroxidation under various methionine and insulin concentrations. Quantitative interrogation of both spatial and chemometric lipid metabolism under tandem metabolite modulation confirms significant interaction of insulin and methionine, which may prove to be critical therapeutic targets, and proposes a powerful optical imaging platform with subcellular resolution for metabolic and cancer research.

A proof-of-concept study on the use of a fluorescein-based 18F-tracer for pretargeted PET.

BACKGROUND: Pretargeted immuno-PET tumor imaging has emerged as a valuable diagnostic strategy that combines the high specificity of antibody-antigen interaction with the high signal and image resolution offered by short-lived PET isotopes, while reducing the irradiation dose caused by traditional 89Zr-labelled antibodies. In this work, we demonstrate proof of concept of a novel 'two-step' immuno-PET pretargeting approach, based on bispecific antibodies (bsAbs) engineered to feature dual high-affinity binding activity for a fluorescein-based 18F-PET tracer and tumor markers. RESULTS: A copper(I)-catalysed click reaction-based radiolabeling protocol was developed for the synthesis of fluorescein-derived molecule [18F]TPF. Binding of [18F]TPF on FITC-bearing bsAbs was confirmed. An in vitro autoradiography assay demonstrated that [18F]TPF could be used for selective imaging of EpCAM-expressing OVCAR3 cells, when pretargeted with EpCAMxFITC bsAb. The versatility of the pretargeting approach was showcased in vitro using a series of fluorescein-binding bsAbs directed at various established cancer-associated targets, including the pan-carcinoma cell surface marker EpCAM, EGFR, melanoma marker MCSP (aka CSPG4), and immune checkpoint PD-L1, offering a range of potential future applications for this pretargeting platform. CONCLUSION: A versatile pretargeting platform for PET imaging, which combines bispecific antibodies and a fluorescein-based 18F-tracer, is presented. It is shown to selectively target EpCAM-expressing cells in vitro and its further evaluation with different bispecific antibodies demonstrates the versatility of the approach.

Paclitaxel plus cisplatin and 5-fluorouracil induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: a phase II clinical trial.

PURPOSE: This phase II trial aimed to assess the safety and efficacy of paclitaxel in combination with cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). METHODS: Patients with primary tumor or bulky lymph nodes that might invade nearby organs were eligible. Treatment started with 2-3 cycles of TPF induction chemotherapy, followed by surgery if the tumor was assessed resectable, or by radical concurrent chemoradiotherapy if unresectable. The primary endpoint was pathologically proven complete resection (R0) rate. RESULTS: From July 2014 to February 2019, a total of 47 patients were enrolled. After TPF chemotherapy, 27 patients (57.4%) received surgery and 11 patients (23.4%) received radical concurrent chemoradiotherapy. R0 resection was confirmed in 25 patients (53.2%, 95% confidence interval (CI) 38.9-67.5%). Pathologic complete response was confirmed in four patients (8.5%). The median overall survival (OS) and progression-free survival (PFS) for all patients were 33.3 months and 20.3 months, respectively. The median OS was significantly more favorable in surgery group than in chemoradiotherapy and chemotherapy alone group [33.3 months vs 14.1 months, hazard ratio 0.32 (95% CI 0.12-0.88), p = 0.027]. During induction chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (29.8%), leucopenia (21.3%) and stomatitis (4.3%). No serious postoperative complications were observed in patients undergoing surgery. CONCLUSIONS: The treatment strategy of induction chemotherapy followed by surgery is promising for patients with locally advanced BR-ESCC. To further improve the R0 resection rate, more effective induction chemotherapy regimens need to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02976909.

Intelligent Trigonometric Particle Filter for visual tracking.

Visual tracking is one of the pre-eminent tasks in several computer vision applications. Particle filter (PF) is extensively used in visual tracking for intelligent surveillance system applications, hugely significant. But the re-sampling procedure of PF will result in sample impoverishment, which will affect the precision of tracking simultaneously. In this paper, a new tracking technique, called Trigonometric Particle Filter (TPF), based on PF optimized by Sine Cosine Algorithm (SCA), which contains trigonometric sine and cosine functions, is proposed. An enhanced method for improving the number of target particles used in a Sine Cosine Algorithm for trigonometric particle filter includes SCA ahead of the re-sampling step. This step ensures a more extensive particle set Achievement of the proposed TPF tracker is inspected and assessed on Visual Tracker Benchmark (VOT) databases. The proposed TPF tracker is compared with evolutionary-based methods like the Spider monkey optimization assisted PF (SMO-PF), Firefly algorithm-based PF (FAPF) method, Particle swarm optimization-based PF (PSO-PF) and Particle filter, recent four correlation filter-based trackers, and also with other ten state-of-the-art tracking methods. We demonstrate that visual tracking using TPF delivers additional consistent and proficient tracking outcomes than compared trackers.

Treponema pallidum (Syphilis) Antigen TpF1 Induces Activation of Macrophages and Accelerates P2X7R-Induced NLRP3-Dependent Release of IL-1ß.

BACKGROUND: Syphilis is a chronic infectious disease caused by Treponema pallidum (Tp) infection, which causes local inflammation in the host. TpF1 is an oligomeric protein expressed by the Tp-infected host that can induce the host immune response. There are few studies regarding the role of TpF1 in macrophage activation and the subsequent release of cytokines. OBJECTIVE: The objective of this study is to elucidate the effects of TpF1 on the pathological process of Syphilis. In addition, we explored how purinergic 2X7 (P2X7R) induced NOD-like receptor family protein 3 (NLRP3) -dependent release of interleukin-1ß (IL-1ß) and the underlying mechanisms. METHODS: We explored the influence of TpF1 on cytokine release by macrophages using qRT-PCR and ELISA. The specific phenotype of activated macrophages was determined by flow cytometry. RESULTS: TpF1 was able to activate macrophages and induce the M1 macrophage phenotype. Moreover, TpF1 activated the NLRP3 inflammasome in macrophages, which was mediated by P2X7R. CONCLUSION: The Tp-induced protein TpF1 is able to induce macrophage activation and P2X7R-induced NLRP3-dependent release of IL-1ß. Our findings provide a theoretical basis for clarifying the clinical symptoms and pathogenesis of syphilis.