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Free-space strong-field terahertz (THz) electromagnetic pulses have emerged as a potent tool for non-equilibrium quantum state control. However, these applications predominantly rely on electric field components, with limited utilization of magnetic field components. A traditional electro-optical sampling technique may encounter constraints due to the field strength saturation effect when detecting strong-field THz pulses. Here we have identified intense THz-induced Zeeman torque signals in CoFe and successfully detected the THz magnetic field components. Through variations in the type of ferromagnetic materials and the thickness of ferromagnetic films, we further refined the detection of THz magnetic field components. Our research revealed that a 15-nm CoFe thin film is more responsive in measuring magnetic field components.
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In the majority of existing multi-view clustering methods, the prerequisite is that the data have the correct cross-view correspondence. However, this strong assumption may not always hold in real-world applications, giving rise to the so-called View-shuffled Problem (VsP). To address this challenge, we propose a novel multi-view clustering method, namely View-shuffled Clustering via the Modified Hungarian Algorithm (VsC-mH). Specifically, we first establish the cross-view correspondence of the shuffled data utilizing strategies of the global alignment and modified Hungarian algorithm (mH) based intra-category alignment. Subsequently, we generate the partition of the aligned data employing matrix factorization. The fusion of these two processes facilitates the interaction of information, resulting in improved quality of both data alignment and partition. VsC-mH is capable of handling the data with alignment ratios ranging from 0 to 100%. Both experimental and theoretical evidence guarantees the convergence of the proposed optimization algorithm. Extensive experimental results obtained on six practical datasets demonstrate the effectiveness and merits of the proposed method.
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The electron extraction from perovskite/C60 interface plays a crucial role in influencing the photovoltaic performance of inverted perovskite solar cells (PSCs). Here, we develop a one-stone-for-three-birds strategy via employing a novel fullerene derivative bearing triple methyl acrylate groups (denoted as C60-TMA) as a multifunctional interfacial layer to optimize electron extraction at the perovskite/C60 interface. It is found that the C60-TMA not only passivates surface defects of perovskite via coordination interactions between C=O groups and Pb2+ cations but also bridge electron transfer between perovskite and C60. Moreover, it effectively induces the secondary grain growth of the perovskite film through strong bonding effect, and this phenomenon has never been observed in prior art reports on fullerene related studies. The combination of the above three upgrades enables improved perovskite film quality with increased grain size and enhanced crystallinity. With these advantages, C60-TMA treated PSC devices exhibit a much higher power conversion efficiency (PCE) of 24.89% than the control devices (23.66%). Besides, C60-TMA benefits improved thermal stability of PSC devices, retaining over 90% of its initial efficiency after aging at 85 °C for 1200 h, primarily due to the reinforced interfacial interactions and improved perovskite film quality.
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Deep learning-based 3D/2D surgical navigation registration techniques achieved excellent results. However, these methods are limited by the occlusion of surgical equipment resulting in poor accuracy. We designed a contrastive learning method that treats occluded and unoccluded X-rays as positive samples, maximizing the similarity between the positive samples and reducing interference from occlusion. The designed registration model has Transformer's residual connection (ResTrans), which enhances the long-sequence mapping capability, combined with the contrast learning strategy, ResTrans can adaptively retrieve the valid features in the global range to ensure the performance in the case of occlusion. Further, a learning-based region of interest (RoI) fine-tuning method is designed to refine the misalignment. We conducted experiments on occluded X-rays that contained different surgical devices. The experiment results show that the mean target registration error (mTRE) of ResTrans is 3.25 mm and the running time is 1.59 s. Compared with the state-of-the-art (SOTA) 3D/2D registration methods, our method offers better performance on occluded 3D/2D registration tasks.
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Altermagnets exhibit momentum-dependent spin-splitting in a collinear antiferromagnetic order due to their peculiar crystallographic and magnetic symmetry, resulting in the creation of spin currents with light elements. Here, we report two two-dimensional (2D) metal-organic framework (MOF) semiconductors, M(pyz)2 (M = Ca and Sr, pyz = pyrazine), which exhibit both altermagnetism and topological nodal point and line by using first-principles calculations and group theory. The altermagnetic 2D MOFs exhibit unconventional spin-splitting and macroscopic zero magnetization caused by 4-fold rotation in crystalline real space and 2-fold rotation in spin space, leading to the generation and control of anisotropic spin currents when an in-plane electric field ( E ) is applied. In particular, pure spin current with the spin Hall effect occurs when E is applied along the angular bisector of the two spin arrangements. Our work indicates the existence of altermagnetic MOF systems and a universal approach to generate electric-field-controlled spin currents for potential applications in antiferromagnetic spintronics.
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Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.
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BACKGROUND: Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target. METHOD: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia. RESULTS: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples. CONCLUSION: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.
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AIMS: A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan. METHODS AND RESULTS: We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department. CONCLUSIONS: Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department.
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COVID-19 , Hospitalização , Infecções Respiratórias , Humanos , China/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Pessoa de Meia-Idade , Criança , Masculino , Adulto , Feminino , Pré-Escolar , Adolescente , Idoso , Lactente , COVID-19/epidemiologia , Fungos/isolamento & purificação , Fungos/genética , Fungos/classificação , Adulto Jovem , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/genética , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Mycoplasma pneumoniae/isolamento & purificação , Mycoplasma pneumoniae/genética , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologiaRESUMO
Exploring and developing new rechargeable halide-ion batteries plays an important role in the advancement and growth of the ion battery family. Here, we systematically explored the feasibility of single-layer MXenes and their hydrogenated derivatives as electrode materials for halide-ion batteries via first-principles theory. The calculated results indicate that halide ions (T ions) can be stably and efficiently adsorbed on the surfaces of M2X and M2XH2, with theoretical specific capacities ranging from 227 to 497 mAh g-1. The diffusion barriers of the T ion on MXenes are from 0.55 to 0.10 eV, comparable to those of the Li ion in graphite and LiCoO2. The electronegativity of halide anions displays significant impacts on their discharge voltage plateaus on M2X, with the highest voltage up to 5.60 V for the F ion. As a comparison, the hydrogenation of M2XH2 with less surface activity raises a 2-3 V voltage reduction. All MXene-based full cells of TxTi2C|TyTi2CH2 (where x = 0-2 and y = 2-0) and TxTi2N|TyTi2NH2 (where x = 0-2 and y = 2-0) demonstrated high full battery specific energies for F-, Cl-, and Br-ion batteries, up to 462 Wh kg-1. These results demonstrate the potential of new halide-ion battery designs, paving the way for future research and innovation in battery technology.
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The continuous release of antibiotics into agroecosystems has raised concerns about the potential negative effects of antibiotic residues on crops. In this study, the toxicological effects of enrofloxacin (ENR) on wheat seedlings were analyzed using a combination of morpho-physiological, transcriptomic, proteomic, and metabolomic approaches. ENR inhibited the growth of wheat (Triticum aestivum L.) roots and induced oxidative stress. In particular, ENR downregulated the oxidative phosphorylation pathway, while it enhanced glycolysis and the tricarboxylic acid cycle, thereby regulating the balance of intracellular energy metabolism. In addition, sustained exposure to excessive reactive oxygen species (ROS) resulted in an increase in reduced glutathione (GSH), a slight decrease in ascorbic acid (AsA), and a significant decrease in the ratio of GSH to oxidized glutathione (GSSG), which imbalanced the AsA-GSH cycle. In addition, the resulting increase in abnormal proteins triggered ubiquitin-independent proteasomal degradation pathways. Further, an increase in abscisic acid (ABA) and a decrease in jasmonic acid (JA) and its derivatives alleviated the inhibitory effect of ENR on the growth of wheat roots. In conclusion, direct damage and signaling by ROS, hormonal regulation, a decrease in the GSH to GSSG ratio, and insufficient energy supply were identified as key factors for the significant inhibition of wheat root growth under ENR stress.
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Enrofloxacina , Raízes de Plantas , Espécies Reativas de Oxigênio , Plântula , Triticum , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Enrofloxacina/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Glutationa/metabolismo , Antibacterianos/toxicidade , Proteômica , Proteínas de Plantas/metabolismo , Metabolômica , MultiômicaRESUMO
As the rising renewable energy demands and lithium scarcity, developing high-capacity anode materials to improve the energy density of potassium-based batteries (PBBs) is increasingly crucial. In this work, a unique orderly multilayered growth (OMLG) mechanism on a 2D-Ca2Si monolayer is theoretically demonstrated for potassium storage by first-principles calculations. The global-energy-minimum Ca2Si monolayer is a semiconductor with isotropic mechanical properties and remarkable electrochemical properties, such as a low potassium ion migration energy barrier of 0.07 eV and a low open circuit voltage ranging from 0.224 to 0.003 V. Most notably, 2D-Ca2Si demonstrates an ultrahigh theoretical specific capacity of 5459 mAh g-1 and a total specific capacity of 610 mAh g-1, reaching up to 89% of the capacity of a potassium metal anode. Remarkably, the OMLG mechanism facilitates stable, dendrite-free deposition of hcp-K metal layers on the 2D-Ca2Si surface, where the ultrahigh and gradually converging lattice match as the layers increase is the key to achieving theoretically near-infinite growth. The study theoretically demonstrates the Ca2Si monolayer a highly promising anode material, and offers a novel potassium storage strategy for designing 2D anode materials with high specific capacity, rapid potassium-ion migration, and good safety.
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Although the safety and short-term outcomes of robotic surgery for sigmoid colon and rectal cancer patients are well-documented, there is limited research on the long-term survival outcomes of robotic colorectal surgery. This is a retrospective study that includes 502 patients who underwent either laparoscopic or robotic anterior resection and abdominoperineal resection for rectal or sigmoid colon cancer between August 2016 and September 2021. All patients were diagnosed with rectal or sigmoid colon adenocarcinoma. Propensity score matching (PSM) was implemented to minimize selection bias. Perioperative outcomes, complication rates, and pathological data were evaluated and compared. The 5-year overall survival rate and disease-free survival rate were calculated and compared. Before matching, patients in the robotic group had earlier pathological T and N stages and were more likely to have received neoadjuvant chemoradiotherapy compared to the laparoscopic group. After matching, most clinicopathological outcomes were similar between the two groups, but the robotic group had longer operative times and a lower conversion rate to open surgery compared with laparoscopic group. After matching for clinical factors, the 5-year DFS rates were 88.19% for the robotic group and 82.46% for the laparoscopic group (P = 0.122), and the OS rates were 90.5% and 79.5% (P = 0.342), showing no significant differences. In the stratified analysis, patients in the robotic surgery group had significantly higher 5-year DFS rates in the following subgroups: age < 65 years, TNM stage I-II, received neoadjuvant therapy, and primary tumor located in the rectum. The safety and efficacy of robotic surgery for sigmoid colon and rectal cancer were validated compared to laparoscopic surgery, with both groups of patients exhibiting comparable long-term prognoses.
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Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Neoplasias do Colo Sigmoide , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias do Colo Sigmoide/cirurgia , Neoplasias do Colo Sigmoide/patologia , Idoso , Resultado do Tratamento , Duração da Cirurgia , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Taxa de Sobrevida , Pontuação de Propensão , Terapia Neoadjuvante , Colo Sigmoide/cirurgia , Intervalo Livre de Doença , AdultoRESUMO
Electrocatalysis is generally confined to dynamic liquid-solid and gas-solid interfaces and is rarely applicable in solid-state reactions. Here, we report a paradigm shift strategy to exploit electrocatalysis to accelerate solid-state reactions in the context of lithium-ion batteries (LIBs). We employ heteroatom doping, specifically boron for silicon and sulfur for phosphorus, to catalyze electrochemical Li-alloying reactions in solid-state electrode materials. The preferential cleavage of polar dopant-host chemical bonds upon lithiation triggers chemical bond breaking of the host material. This solid-state catalysis, distinct from liquid and gas phases, requires a critical doping concentration for optimal performance. Beyond a critical concentration of â¼1 atom %, boron and sulfur doping drastically reduces activation energies and accelerates redox kinetics during lithiation/delithiation processes, leading to markedly enhanced rate performance in boron-doped silicon and sulfur-doped black/red phosphorus anode. Notably, a sulfur-doped black phosphorus anode coupled with a lithium cobalt oxide cathode achieves an ultrafast-charging battery, recharging 80% energy of a battery in 302 Wh kg-1 in 9 min, surpassing the thus far reported LIBs.
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Excitonic insulators are long-sought-after quantum materials predicted to spontaneously open a gap by the Bose condensation of bound electron-hole pairs, namely, excitons, in their ground state. Since the theoretical conjecture, extensive efforts have been devoted to pursuing excitonic insulator platforms for exploring macroscopic quantum phenomena in real materials. Reliable evidence of excitonic character has been obtained in layered chalcogenides as promising candidates. However, owing to the interference of intrinsic lattice instabilities, it is still debatable whether those features, such as the charge density wave and gap opening, are primarily driven by the excitonic effect or by the lattice transition. Herein, we develop an intercalation chemistry strategy for obtaining a novel charge-transfer excitonic insulator in organic-inorganic superlattice interfaces that serves as an ideal platform to decouple the excitonic effect from the lattice effect. In this system, we observe a narrow excitonic gap, formation of a charge density wave without periodic lattice distortion, and metal-insulator transition, providing visualized evidence of exciton condensation occurring in thermal equilibrium. Our findings identify self-assembly intercalation chemistry as a new strategy for developing novel excitonic insulators.
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Currently, providing patients, particularly those with acute myocardial infarction (AMI), with comprehensive cardiac rehabilitation (CR) has been challenging because of the inadequate availability of medical resources in developing countries. To ensure balance between disease instability and early rehabilitation, strategies for facilitating professional and comprehensive CR opportunities for patients with AMI must be explored.A prospective cohort study was carried out on 1,533 patients with AMI who were admitted to a tertiary hospital between July 2018 and October 2019. Following the principle of voluntarism, 286 patients with AMI participated in home-center-based CR (HCB group), whereas 1,247 patients received usual care (UC group). The primary endpoint of this study was the occurrence of cardiovascular events at 30 months after AMI. Moreover, the study analyzed factors that influence participation rate and effectiveness of the CR model.After analysis, a significant difference in the occurrence of cardiovascular endpoints between the HCB group and the UC group was observed (harzard ratio, 0.68 [95%CI, 0.51-0.91], P = 0.008), with participation in home-center-based CR being an independent influencing factor. Multivariate regression analysis revealed age, gender, smoking history, triglyceride levels, and ejection fraction as independent factors that influence participation rate. Female gender, peak oxygen uptake per kilogram body weight, and ventilation/carbon dioxide production slope were identified as factors that affect the effectiveness of the CR model.In the context of developing countries, this study demonstrates that the home-center-based CR model is efficient and analyzes factors that influence participation rate and effectiveness of the model. These findings provide practical insights for further development of CR programs.
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Reabilitação Cardíaca , Infarto do Miocárdio , Humanos , Masculino , Feminino , Reabilitação Cardíaca/métodos , Infarto do Miocárdio/reabilitação , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Resultado do Tratamento , Serviços de Assistência DomiciliarRESUMO
Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.
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BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP. METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy. RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy. CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.
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Líquido da Lavagem Broncoalveolar , Infecções Comunitárias Adquiridas , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Metagenômica/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , Adulto , Pneumonia/diagnóstico , Pneumonia/microbiologia , Pneumonia/tratamento farmacológico , Escarro/microbiologia , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Adulto JovemRESUMO
BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Terapia Neoadjuvante , Piridinas , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Terapia Neoadjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto Jovem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , AdolescenteRESUMO
Lensless imagers based on diffusers or encoding masks enable high-dimensional imaging from a single-shot measurement and have been applied in various applications. However, to further extract image information such as edge detection, conventional post-processing filtering operations are needed after the reconstruction of the original object images in the diffuser imaging systems. Here, we present the concept of a temporal compressive edge detection method based on a lensless diffuser camera, which can directly recover a time sequence of edge images of a moving object from a single-shot measurement, without further post-processing steps. Our approach provides higher image quality during edge detection, compared with the "conventional post-processing method." We demonstrate the effectiveness of this approach by both numerical simulation and experiments. The proof-of-concept approach can be further developed with other image post-processing operations or versatile computer vision assignments toward task-oriented intelligent lensless imaging systems.
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Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. Objectives: This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan-Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002-1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127-2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.