Navigating therapeutic strategies: HPV classification in head and neck cancer.

The World Health Organisation recognised human papillomavirus (HPV) as the cause of multiple cancers, including head and neck cancers. HPV is a double-stranded DNA virus, and its viral gene expression can be controlled after infection by cellular and viral promoters. In cancer cells, the HPV genome is detected as either integrated into the host genome, episomal (extrachromosomal), or a mixture of integrated and episomal. Viral integration requires the breakage of both viral and host DNA, and the integration rate correlates with the level of DNA damage. Interestingly, patients with HPV-positive head and neck cancers generally have a good prognosis except for a group of patients with fully integrated HPV who show worst clinical outcomes. Those patients present with lowered expression of viral genes and limited infiltration of cytotoxic T cells. An impediment to effective therapy applications in the clinic is the sole testing for HPV positivity without considering the HPV integration status. This review will discuss HPV integration as a potential determinant of response to therapies in head and neck cancers and highlight to the field a novel therapeutic avenue that would reduce the cancer burden and improve patient survival.

Efficacy of fosaprepitant combined with tropisetron plus dexamethasone in preventing nausea and emesis during fractionated radiotherapy with weekly cisplatin chemotherapy: interim analysis of a randomized, prospective, clinical trial using competing risk analysis.

PURPOSE: There are no well-recognized guidelines for antiemesis during concurrent chemoradiotherapy (CCRT) for cervical cancer (CC) and nasopharyngeal cancer (NPC) until now. The study was designed to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low-dose cisplatin chemotherapy in patients with CC or NPC. METHODS: Patients with CC or NPC were scheduled to receive fractionated radiotherapy and weekly cisplatin (25-40 mg/m2) chemotherapy for at least 5 weeks. Patients stratified by tumor type and induction chemotherapy were 1:1 randomly assigned to receive fosaprepitant, tropisetron, and dexamethasone or tropisetron plus dexamethasone as an antiemetic regimen. Efficacy was assessed primarily by the cumulative incidence of emesis after 5 weeks of treatment, and safety by adverse events (AEs). RESULTS: Between July 2020 and July 2022, 116 patients consented to the study of whom 103 were included in this interim analysis (fosaprepitant group [N = 52] vs control group [N = 51]). The cumulative incidence of emesis at 5 weeks (competing risk analysis) was 25% (95% CI 14.2-37.4) for the fosaprepitant group compared with 59% (95% CI 43.9-71.0) for the control group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group (HR 0.35 [95% CI 0.19-0.64]; p < 0.001). Fosaprepitant was well tolerated as the incidences of adverse events in the two groups were comparable. CONCLUSION: The addition of fosaprepitant to tropisetron plus dexamethasone significantly reduced the risk of nausea and vomiting during 5 weeks of CCRT in patients with CC or NPC, and fosaprepitant was well tolerated. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on October 3, 2022, number NCT05564286.

A corpus-assisted discourse study of Chinese university students' perceptions of sustainability.

Education for sustainable development (ESD) in the higher education context plays a critical role in advancing the cause of sustainable development. However, previous research on university students' perceptions of sustainable development is limited. This study used a corpus-assisted eco-linguistic approach to investigate students' perceptions of sustainability issues and responsible actors to address these issues. This quantitative and qualitative study is based on a corpus of 501 collaborative essays on sustainability written by ~2,000 Chinese university students collected with their permission. The results show that the students had a comprehensive perception of the three dimensions of sustainable development. Environmental issues have received the most attention from students, followed by economic and social issues. With regard to perceived actors, students were inclined to view themselves as active participants in the cause of sustainable development, rather than as observers. They called for coordinated action of all relevant parties, such as the government, business sectors, institutions, and individuals. On the other hand, the author also noticed a tendency toward superficial green talk and anthropocentrism in students' discourse. This study aims to contribute to sustainability education by integrating findings into English as a foreign language (EFL) classes. Implications for sustainability education in the context of higher education are also discussed.

Analyzing national parks visitor activities using geotagged social media photos.

Visitor activities within national parks are important information for park management. Currently, national parks and nature-based recreation area worldwide have no systematic visitor activity data collection schemes. Traditional visitor movement or activity data collection methods used in tourism studies are often costly in money and time and difficult to implement. This paper presents a framework and formal procedure that uses geotagged photos crowdsourced from social media platforms to uncover visitor activities within national parks. First, the daily individual space-time paths are constructed from the photo geotags and timestamps for all visitors. Then the following information is derived from the space-time paths: 1) four activity types including stationary, walking, vehicle riding, and flying; 2) the total time of various visitor activities in a park; 3) visitor flow directions aggregated to a grid; 4) a graph constructed from space-time paths and the directed and undirected connections (flows) between POIs; and 5) the centrality of POIs derived from the graph. A case study of four highly visited U.S. national park units from 2008 to 2021 demonstrates the process and capabilities of the method. It also reveals a trend of increased walking time and decreased stationary time in the case study parks over the years. Although this study is only based on Flickr photos, the method can be implemented with data derived from any social media platforms as long as geotags and timestamps are available. The method may be used to monitor visitor activities and movements within national parks and other outdoor recreation areas, especially remote and unmonitored locations.

A combined predicting model for benign esophageal stenosis after simultaneous integrated boost in esophageal squamous cell carcinoma patients (GASTO1072).

Purpose: We aimed to develop a combined predicting model for benign esophageal stenosis (BES) after simultaneous integrated boost (SIB) with concurrent chemotherapy in patients with esophageal squamous cell carcinoma (ESCC). Methods: This study included 65 patients with EC who underwent SIB with chemotherapy. Esophageal stenosis was evaluated using esophagograms and the severity of eating disorders. Risk factors were investigated using univariate and multivariate analyses. Radiomics features were extracted based on contrast-enhanced CT (CE-CT) before treatment. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature selection and radiomics signature construction. The model's performance was evaluated using Harrell's concordance index and receiver operating characteristic curves. Results: The patients were stratified into low- and high-risk groups according to BES after SIB. The area under the curves of the clinical model, Rad-score, and the combined model were 0.751, 0.820 and 0.864, respectively. In the validation cohort, the AUCs of these three models were 0.854, 0.883 and 0.917, respectively. The Hosmer-Lemeshow test showed that there was no deviation from model fitting for the training cohort (p=0.451) and validation cohort (p=0.481). The C-indexes of the nomogram were 0.864 and 0.958 for the training and validation cohort, respectively. The model combined with Rad-score and clinical factors achieved favorable prediction ability. Conclusion: Definitive chemoradiotherapy could alleviate tumor-inducing esophageal stenosis but result in benign stenosis. We constructed and tested a combined predicting model for benign esophageal stenosis after SIB. The nomogram incorporating both radiomics signature and clinical prognostic factors showed favorable predictive accuracy for BES in ESCC patients who received SIB with chemotherapy. Trial registration number and date of registration: Registered in www.Clinicaltrial.gov, ID: NCT01670409, August 12, 2012.

Late Toxicities, Failure Patterns, Local Tumor Control, and Survival of Esophageal Squamous Cell Carcinoma Patients After Chemoradiotherapy With a Simultaneous Integrated Boost: A 5-Year Phase II Study.

PURPOSE: We aimed to evaluate the long-term outcomes of concurrent chemoradiotherapy (CCRT) with a simultaneous integrated boost (SIB) of radiotherapy for esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Eighty-seven patients with primary ESCC enrolled in this phase II trial. The majority (92.0%) had locoregionally advanced disease. They underwent definitive chemoradiotherapy. The radiotherapy doses were 66 Gy for the gross tumor and 54 Gy for the subclinical disease. Doses were simultaneously administered in 30 fractions over 6 weeks. The patients also underwent concurrent and adjuvant chemotherapy, which comprised cisplatin and fluorouracil. The study end points were acute and late toxicities, first site of failure, locoregional tumor control, and overall survival rates. RESULTS: The median follow-up time was 65.7 (range, 2.2-97.5) months for all patients and 81.5 (range, 19.4-97.5) months for those alive. There were 17 cases (19.5%) of severe late toxicities, including four cases (4.6%) of grade 5 and seven (8.0%) of grade 3 esophageal ulceration, four (4.6%) of grade 3 esophageal stricture, and two (2.3%) of grade 3 radiation-induced pneumonia. Twenty-three (26.4%) patients had locoregional disease progression. Most (86.7%) locally progressive lesions were within the dose-escalation region in the initial radiation plan, while majority of the recurrent lymph nodes were found out-of-field (83.3%) and in the supraclavicular region (75.0%). The 1-, 2-, 3-, and 5-year locoregional tumor control and overall survival rates were 79.2%, 72.4%, 72.4%, 70.8%, and 82.8%, 66.6%, 61.9%, 58.4%, respectively. Incomplete tumor response, which was assessed immediately after CCRT was an independent risk predictor of disease progression and death in ESCC patients. CONCLUSIONS: CCRT with SIB was well tolerated in ESCC patients during treatment and long-term follow-up. Moreover, patients who underwent CCRT with SIB exhibited improved local tumor control and had better survival outcomes compared to historical data of those who had standard-dose radiotherapy.

Distribution of Peripheral Blood Cells in Esophageal Cancer Patients During Concurrent Chemoradiotherapy Predicts Long-Term Locoregional Progression Hazard After Treatment (GASTO1072).

PURPOSE: Predicting the response to chemoradiotherapy is critical for the optimal management of esophageal cancer; however, it remains an unmet clinical need. This study aimed to evaluate the predictive potential of peri-treatment peripheral blood cells (PBC) in disease progression hazard in esophageal cancer following chemoradiotherapy. PATIENTS AND METHODS: A total of 87 patients with primary esophageal squamous cell carcinoma were subjected to definitive concurrent chemoradiotherapy in a Phase II trial. PBC parameters (hemoglobin, neutrophils, platelets, lymphocytes, and monocytes) were collected at seven time points throughout the course of radiotherapy. The potential of peri-treatment PBC parameters to predict the 3-year cumulative hazard of tumor progression was evaluated. RESULTS: Patients with disease progression displayed distinct distribution patterns of peri-treatment PBC compared to that in patients without disease progression. Greater prediction capabilities for risk of locoregional disease progression were found in PBC collected after the start of radiotherapy compared to those in their pretreatment counterparts, and in individual parameters rather than cell-to-cell ratios. The most predictive PBC parameters were integrated by summation and designated as a PBC score (PBCS), which further augmented their predictive power. Patients classified according to their PBCS (high vs medium v. low) had significantly different 3-year cumulative hazards of locoregional progression (58% vs 29% vs 7%, P = 0.0017). Multivariate analysis confirmed that high PBCS (HR, 12.2; 95% CI, 2.0-76.3; P = 0.007) and medium (HR, 5.8; 95% CI 1.2-27.7; P = 0.028) were independent indicators of locoregional progression. CONCLUSION: Systematic analysis of PBC distribution in esophageal cancer patients undergoing definitive chemoradiotherapy could help predict long-term locoregional progression hazard after treatment.

Intratreatment Tumor Volume Change During Definitive Chemoradiotherapy is Predictive for Treatment Outcome of Patients with Esophageal Carcinoma.

BACKGROUND: This study aimed to assess the predictive value of tumor volume changes of esophagus evaluated by serial computed tomography (CT) scans before, during, and after radical chemoradiotherapy (CRT) for treatment outcomes in patients with esophageal cancer (EC). METHODS: Fifty-three patients with histologically confirmed EC were included for analysis. Gross tumor volume of esophagus (GTVe) was manually contoured on the CT images before treatment, at a twentieth fraction of radiotherapy, at completion of CRT and three months after treatment. GTVe reduction ratio (RR) was calculated to reveal changes of tumor volume by time. The Kaplan-Meier method was used to estimate survival and for univariate analysis. The Cox regression model was performed for multivariate analysis. RESULTS: Predominant reduction of GTVe was observed during the first 20 fractions of radiotherapy. Age, pretreatment GTVe, GTVe three months after treatment and GTVe RR at twentieth fraction of radiotherapy were all significantly associated with overall survival (OS) in a univariate analysis. Gender was correlated with locoregional recurrence-free survival (LRRFS) in univariate analysis. Multivariate analysis showed that GTVe ≤20 cc, GTVe RR at twentieth fraction of radiotherapy ≥35% were positive predictive factors of OS and pretreatment GTVe ≤20 cc was prognostic for a favorable LRRFS. CONCLUSION: Pretreatment tumor volume and intratreatment volume reduction ratio are reliable prognostic factors for esophageal cancer treated with definitive CRT.

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer.

OBJECTIVE: To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation. METHODS: Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed. RESULTS: Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups. CONCLUSION: Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy.

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESOwhole); ESOwhole within the treatment field (ESOinfield); ESOinfield, excluding the tumor (ESOinfield-tumor) and ESOwhole, excluding the tumor (ESOwhole-tumor). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESOwhole, ESOinfield, ESOinfield-tumor and ESOwhole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10-2% and 1.5 × 10-3%. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.

Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study.

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.

Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

[Detection of rearrangements of mixed lineage leukemia gene and its clinical significance].

To study the incidence, the types of fusion genes and the clinical significance of rearrangements of mixed lineage leukemia (MLL) gene in acute leukemia (AL), the rearrangements of MLL gene of 60 patients with AL were detected by fluorescence in situ hybridization (FISH) and 6 types of common fusion genes resulting from the rearrangements of MLL gene were detected by nested RT-PCR. The results showed that 7 out of 60 AL patients were found the rearrangements of MLL gene, the incidence of which was 11.67%. 2 out of 7 patients were diagnosed as AML-M(5), 5 patients were diagnosed as B-ALL. The fusion genes of the 2 AML-M(5) patients who had the rearrangements of MLL gene were MLL/AF(9). Among 5 B-ALL patients, 2 patients were confirmed to express MLL/ENL, 1 patient was confirmed to express MLL/AF(4), the other 2 patients did not express the fusion genes. It is concluded that FISH is a fast, specific and sensitive method to detect the rearrangements of MLL gene in AL patients and nested RT-PCR is a convenient and feasible method to detect the types of fusion genes resulting from the rearrangements of MLL gene. The detection of MLL gene rearrangement is of great importance in predicting prognosis and guiding therapy in AL.

[Heat stress characteristics of photosystem II in eggplant].

With lower-and higher heat-resistant varieties of eggplant (Solanum melongena L.) Heibei I and Heibei II as test materials, and by using Plant Efficiency Analyzer (PEA) from Hansatech, this paper measured the fast chlorophyll a fluorescence transient and its parameters. The results showed that PS II construction became more sensitive to heat stress when ambient temperature was higher than 40 degrees C. The F0 went up slowly, and Fv/Fm and deltaF/Fm' came down dramatically. Heibei II had a longer semi-attenuation temperature of Fv/Fm (T50) and deltaF/Fm' (t50) than Heibei I. Under strong heat stress (5 min at 48 degrees C or 20-30 min at 44 degrees C), the K-step in relation to the inactivation of oxygen-evolving complex appeared in fluorescence rise at about 700 micros, and the regular O-J-I-P transient was transformed to O-K-J-I-P one. The K-phase of Heibei I and Heibei II appeared when the treatment time was up to 20 and 30 minutes at 44 degrees C, respectively. In comparing with 35 degrees C heat treatment, the DI0/RC in the parameters of Strasser's specific energy fluxes model was increased by a great extent under 48 degrees C or more heat stress, reflecting a strong safeguard of energy dissipation to PS II. When the temperature of heat stress increased from 35 degrees C to 52 degrees C, the Fvi/Fv of PS II silent reaction centers of Heibei I and Heibei II increased remarkably.