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Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18–65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA, excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12–16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4–90·6]) than in the standard therapy group (75·7% [69·9–81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. For the Chinese translation of the abstract see Supplementary Materials section.

Background There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors. Methods In this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics. Results From February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n  = 55; Phase Ib, n  = 48). The median follow-up was 10.1 months (range 0.7–28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments. Conclusions IBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs.

In molecules, the nonadiabatic couplings between two adiabatic potentials build the avoided crossing (AC) region. The rovibronic resonances in the AC region of two-coupled potentials are very special, since they are not in the bound state region of the adiabatic potentials, and they usually do not play important roles on the scatterings and are less discussed. Exemplified in particle scattering, resonances in the AC region are comprehensively investigated. The effects of resonances in the AC region on the scattering cross sections strongly depend on the nonadiabatic couplings of the system, it can be very significant as sharp peaks, or inconspicuous buried in the background. More importantly, it shows a simple quantity proposed by Zhu and Nakamura (1992 J. Chem. Phys. 97 8497) to classify the coupling strength of nonadiabatic interactions, can be well applied to quantitatively estimate the importance of resonances in the AC region. Example applications of the quantity for real molecules (MgH, CO and OH) can well explain the evolutions of cross sections in the AC region published in the literatures. This work provides a simple and practical way to determine the candidate molecules when studying the resonances in the AC region.

Introduction Sunflower seeds are prone to producing defective products during planting, production, and preservation due to issues such as foreign matter mixing, heat damage, mildew, and insect infestation. These defects ultimately affect the overall quality of the products. With increasing consumer demand for high-quality sunflower seeds, efficient sorting has become a crucial part of quality assurance. However, traditional hand-sorting methods (usually 0.005kg/s) are inefficient and insufficient to meet current demands. Objective This study aims to address the challenges of sorting cooked sunflower seeds, which differ in color from raw seeds due to skin abrasion and soup water impregnation during preparation. We developed a new algorithm in collaboration with Meiya Company to introduce color-sorting technology specifically designed for ripe seeds, thereby improving consumer satisfaction and product quality. Main Results Compared to manual selection, the new color-sorting technology achieved an average removal rate of defective products of approximately 99.4%, a significant improvement from the previous rate of around 66%. It can also achieve a 100% removal rate for certain foreign elements, such as insects, animal feces, and yellow seeds. The by-product rate of color selection is about 0.02%, comparable to the 0.01% for manual selection. Additionally, the implementation of this technology can save enterprises more than 5 million yuan per year. Conclusion The introduction of the ripe seed color-sorting technology significantly enhances the removal rate of defective products while maintaining a low by-product rate. This technology not only improves the overall quality of sunflower seed products but also provides substantial economic benefits for companies, demonstrating significant practical implications for the industry.

Background Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments. Methods We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration. Results The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys ( p  < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models ( p  < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli ( p  < 0.05), and the number of type II alveolar epithelium in elderly macaques ( p  < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models ( p  < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation ( p  < 0.05). Conclusions BMMSC treatment inhibited age-associated lung tissue degeneration.

Adding three cycles of induction chemotherapy with gemcitabine and cisplatin to concurrent chemoradiotherapy improved 3-year recurrence-free survival (85.3%, vs. 76.5% with concurrent chemoradiotherapy alone) and overall survival (94.6% vs. 90.3%). Patients receiving induction chemotherapy were more likely to have grade 3 or 4 myelosuppression, nausea, and vomiting.

The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67 + proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67 + Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry ( n  = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry ( n  = 249) demonstrated that Ki67 + Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67 + Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial ( n  = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67 + Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Ultraviolet (UV) photodissociation provides valuable insights into fragmentation patterns and photochemical reactions. However, the limited overlap between vibrational bound states and continuum states hinders efficient quantum excitation. We address this challenge by embedding the ground bound potential into the dissociative continuum using a frequency-selected UV pulse. This pulse creates vibrational resonances by coupling the dissociative continuum with unpopulated vibrationally excited levels of the ground state, without initiating photoexcitation itself. Our findings demonstrate that the photodissociation spectra can be significantly manipulated by tuning the embedding pulse frequency to tailor the asymmetric profiles of the vibrational resonances. This is illustrated in our simulations of kinetic energy release spectra for both diatomic and polyatomic molecules. These proof-of-principle examples offer opportunities for manipulating the yield of photofragmentation and the pathways of photochemical reactions in various molecular systems. The quantum excitation of photodissociation is restricted by the overlap between vibrational bound and continuum states. The authors manipulate the dynamics by generating new vibrational Fano resonances and controlling the asymmetric profiles of these resonances using an embedded ultraviolet pulse.

Purpose Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and is particularly prevalent in southern China. Unfortunately, international guidelines, such as NCCN or ESMO, fail to adequately coincide with clinical practice in China, making it difficult to achieve precision personalized therapy in China. The aim of this guideline is to better promote a “Multidisciplinary Team to Holistic Integrative Medicine\" (MDT to HIM) system for the prevention, screening, diagnosis, treatment, and rehabilitation of NPC. Methods The China Anti-Cancer Association (CACA) invited domestic multi-disciplinary experts, involving radiologists, oncologists, surgeons, pathologists, herbalists, physiatrists, and psychologists, to write, discuss, and revise the guidelines. Based on the integration of research evidence, clinical experience, and patient needs, the domestic experts have iteratively developed these guidelines to provide proper and feasible management of NPC. Results and conclusion The CACA Guidelines for Holistic Integrative Management of Nasopharyngeal Carcinoma are more suitable for China's clinical practice, highlight Chinese characteristics, and have important clinical significance.