SLHSD: hybrid scaffolding method based on short and long reads.

In genome assembly, scaffolding can obtain more complete and continuous scaffolds. Current scaffolding methods usually adopt one type of read to construct a scaffold graph and then orient and order contigs. However, scaffolding with the strengths of two or more types of reads seems to be a better solution to some tricky problems. Combining the advantages of different types of data is significant for scaffolding. Here, a hybrid scaffolding method (SLHSD) is present that simultaneously leverages the precision of short reads and the length advantage of long reads. Building an optimal scaffold graph is an important foundation for getting scaffolds. SLHSD uses a new algorithm that combines long and short read alignment information to determine whether to add an edge and how to calculate the edge weight in a scaffold graph. In addition, SLHSD develops a strategy to ensure that edges with high confidence can be added to the graph with priority. Then, a linear programming model is used to detect and remove remaining false edges in the graph. We compared SLHSD with other scaffolding methods on five datasets. Experimental results show that SLHSD outperforms other methods. The open-source code of SLHSD is available at https://github.com/luojunwei/SLHSD.

Drug resistance prediction and resistance genes identification in Mycobacterium tuberculosis based on a hierarchical attentive neural network utilizing genome-wide variants.

Prediction of antimicrobial resistance based on whole-genome sequencing data has attracted greater attention due to its rapidity and convenience. Numerous machine learning-based studies have used genetic variants to predict drug resistance in Mycobacterium tuberculosis (MTB), assuming that variants are homogeneous, and most of these studies, however, have ignored the essential correlation between variants and corresponding genes when encoding variants, and used a limited number of variants as prediction input. In this study, taking advantage of genome-wide variants for drug-resistance prediction and inspired by natural language processing, we summarize drug resistance prediction into document classification, in which variants are considered as words, mutated genes in an isolate as sentences, and an isolate as a document. We propose a novel hierarchical attentive neural network model (HANN) that helps discover drug resistance-related genes and variants and acquire more interpretable biological results. It captures the interaction among variants in a mutated gene as well as among mutated genes in an isolate. Our results show that for the four first-line drugs of isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA), the HANN achieves the optimal area under the ROC curve of 97.90, 99.05, 96.44 and 95.14% and the optimal sensitivity of 94.63, 96.31, 92.56 and 87.05%, respectively. In addition, without any domain knowledge, the model identifies drug resistance-related genes and variants consistent with those confirmed by previous studies, and more importantly, it discovers one more potential drug-resistance-related gene.

The prognostic value of machine learning techniques versus cox regression model for head and neck cancer.

BACKGROUND: Accurate prognostic prediction for head and neck cancer (HNC) is important for the improvement of clinical management. We aimed to compare the prognostic value of various machine learning techniques (MLTs) and statistical Cox regression model for different types of HNC. METHODS: Clinical data of HNC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1974 to 2016. The prediction performance of five ML models, including random forest (RF), gradient boosting decision tree (GBDT), support vector machine (SVM), neural network (NN) and deep learning (DL), were compared with the statistical Cox regression model by estimating the concordance index (C-index), integrated Brier score (IBS), time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Our results showed that the RF model outperformed all other models in prognostic prediction for all tumor sites of HNC, particularly for major salivary gland cancer (MSGC, C-index: 88.730 ± 0.8700, IBS: 7.680 ± 0.4800), oral cavity cancer (OCC, C-index: 84.250 ± 0.6700, IBS: 11.480 ± 0.3300) and oropharyngeal cancer (OPC, C-index: 82.510 ± 0.5400, IBS: 10.120 ± 0.1400). Meanwhile, we analyzed the importance of each clinical variable in the RF model, in which age and tumor size presented the strongest positive prognostic effects. Additionally, similar results can be observed in the internal (6th edition of the AJCC TNM staging system cohort) and external validations (the TCGA HNC cohort). CONCLUSIONS: The RF model is a promising prognostic prediction tool for HNC patients, regardless of the anatomic subsites.

Dynamic changes in gene expression during follicle development and the efficacy of four timed AI protocols in non-suckling female yaks (Bos grunniens).

The objectives of the study were to investigate changes in the mRNA expression levels of five genes during antral follicle development and to assess the efficacy of four timed-artificial insemination (TAI) protocols in female yaks (Bos grunniens). RT-qPCR analysis revealed that expression levels were greater for follicle-stimulating hormone receptor and bone morphogenic protein 15 in the small follicle, luteinizing hormone receptor, and kit ligand in the large follicle, and growth differentiation factor 9 in the medium follicle (p < 0.05). Non-suckling yaks were treated as a 7-d CIDR, and PGF2α + eCG at CIDR withdrawal and TAI with frozen yak semen at 56-58 h after PGF2α (PPe-7d); either a 7-d CIDR (PPG-7d) or a 5-d CIDR (PPG-5d), and PGF2α at CIDR withdrawal and TAI + GnRH at 70-72 h after PGF2α; and GnRH treatment on Day 0, followed by PGF2α on Day 7 and TAI + GnRH on Day 9 (GPG-7d). The results showed that the pregnancy rate (P/AI) was greater in PPG-5d than in GPG-7d (p < 0.05), but the P/AI was not different among the other TAI protocols. In conclusion, the expression levels of these genes in follicles are dynamically changed during antral follicle development in yaks. The PPG-5d protocol achieved a greater P/AI.

Load quantification and effect evaluation of urban non-point source pollution in the Licun River based on SWAT model.

With the gradual control of point source pollution, the impact of urban nonpoint source pollution on river water quality is becoming more prominent. Regarding the current problem that nonpoint source pollution loads in urban basins are difficult to quantify and the impact on water quality is difficult to analyze, the Licun River basin in Qingdao was selected as the research object. Through the field survey and surface accumulation sampling analysis of the basin, the evaluation model of urban nonpoint source pollution was constructed by revising the land type data of the basin and the urban database of the SWAT model. The results showed that concentration of nitrate in precipitation was most sensitive to the simulation of nitrogen loading; organic P in baseflow was most sensitive to the simulation of phosphorus loading. The Nash-Sutcliffe efficiency coefficient (ENS) and the coefficients of determination (R2) of the SWAT model for runoff, total phosphorus (TP), and total nitrogen (TN) in the simulation validation period meet the model requirements,indicating a good model fit. In addition, the spatial and temporal distribution characteristics of urban nonpoint source pollution of TN and TP in 2021 were analyzed. In July, rainfall-runoff from the Licun River basin was the most polluted.

[Application of Precision Nursing Based on Multidisciplinary Collaboration Model in Older Patients Undergoing Thoracoscopic Surgery for Lung Cancer].

Objective: To examine the application effect of precision nursing strategies based on multidisciplinary collaboration model in older patients undergoing thoracoscopic surgery for lung cancer. Methods: A total of 100 patients who were admitted to our hospital for thoracoscopic surgery for lung cancer between July 2022 and March 2023 were prospectively enrolled for the study. They were assigned, with a random number table, to two groups, a control group receiving routine nursing care and an experimental group receiving nursing care based on multidisciplinary collaborative precision nursing strategies. Their lung function, anxiety and depression scores, and quality of life were assessed at three points of time, including upon admission, one week after surgery, and one month after surgery, and comparison was made between the two groups. Results: There were significant differences in forced expiratory volume in one second (FEV1) at the three time points ( F=156.787, P<0.001) and the ratio of FEV1 to forced vital capacity (FVC) (FEV1/FVC%) at the three time points ( F=25.587, P<0.001) between two groups. There were significant difference between the findings for FEV1, FEV1/FVC%, FVC, and maximum voluntary ventilation (MVV) indexes at 1 week and those at 1 month after surgery in the experimental group ( P<0.05). After the surgery, the pulmonary function of the experimental group was better than that of the control group. The anxiety and depression scores of the experimental group were lower than those of the control group, with the difference being statistically significant ( P<0.05), which suggested that the experimental group showed improvement in anxiety and depression in comparison with the control group. Regarding the quality of life, there were significant differences between the two groups in the scores for the functional dimension ( F=109.798, P<0.001), the symptom dimension ( F=106.936, P<0.001), other items ( F=78.798, P<0.001), and overall health dimensions ( F=174.307, P<0.001). At 1 week and 1 month after surgery, the experimental group had higher scores for the functional dimension and lower scores for the symptom dimension than the control group did, with the differences being statistically significant ( P<0.05). The overall health status of the experimental group was better than that of the control group. Conclusion: Precision nursing strategies based on multidisciplinary collaboration model can effectively help improve the lung function, the mood, and the quality of life of patients in the short term, showing considerable promise for wide clinical application.

Transcriptomic study of yak mammary gland tissue during lactation.

Yak milk, a high-quality milk, is one of the best raw materials for dairy products and economically important to pastoral herdsmen. To make a further understanding of the molecular differences in mammary tissues of the yaks with different milk production during lactation, in this study, we took the use of RNA-seq to perform high-throughput sequencing and analysis of the mammary gland transcriptomes of both high-yielding yak and low-yielding yaks during lactation. By the comparison and analysis of the transcriptome data for the mammary gland tissue of high-yielding yak and low-yield yak, 144 differential genes were screened out, of which 49 were upregulated and 95 were downregulated. Further functional analysis indicated that these differential genes involved in multiple classes based on Gene Ontology (GO) and multiple Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The GO analysis showed that the functions of the differential genes are closely related to the carbohydrate metabolism and other biological processes. KEGG pathway analysis revealed that these genes are mostly enriched in the pathway of antigen processing and presentation, phagosome pathway and type I diabetes pathway and enriched followed by extracellular matrix receptor interaction pathway. Moreover, several other pathways related to amino acid metabolism also showed significant enrichment. Here, the mammary gland transcriptomes of high-yielding yak and low-yielding yaks during lactation have for the first time been compared, and the related differential genes have been screened out and analyzed. Our study paves a way for the further elucidation of the basic molecular mechanism of yak mammary gland tissue, and at the same time provides new ideas for improving the milk production of yaks.

Genomic characterization of a nebovirus strain with a novel RdRp genotype in yaks.

Neboviruses (NeVs) are important causative agents of calf diarrhea that belong to the family Caliciviridae. In this study, we investigated the genomic characteristics of a NeV strain from yaks that has a novel RdRp genotype. The complete genome of this strain (YAK/NRG-A9/19/CH) is 7454 nt in length and shares 68.3%-79.7% nt sequence identity with those of other NeVs. The RNA-dependent RNA polymerase (RdRp) gene of this strain shares 66.5%-78.5% nt sequence identity (74.0%-89.3% aa sequence identity) with the eight available complete NeV RdRp sequences, and a phylogenetic analysis based on these sequences showed that the new strain formed an independent branch, indicating that the RdRp of strain YAK/NRG-A9/19/CH may represent a novel RdRp genotype of NeV. These results contribute to a further understanding of the molecular characteristics and genetic evolution of NeVs.

A C2H2-Type Zinc-Finger Protein from Millettia pinnata, MpZFP1, Enhances Salt Tolerance in Transgenic Arabidopsis.

C2H2 zinc finger proteins (ZFPs) play important roles in plant development and response to abiotic stresses, and have been studied extensively. However, there are few studies on ZFPs in mangroves and mangrove associates, which represent a unique plant community with robust stress tolerance. MpZFP1, which is highly induced by salt stress in the mangrove associate Millettia pinnata, was cloned and functionally characterized in this study. MpZFP1 protein contains two zinc finger domains with conserved QALGGH motifs and targets to the nucleus. The heterologous expression of MpZFP1 in Arabidopsis increased the seeds' germination rate, seedling survival rate, and biomass accumulation under salt stress. The transgenic plants also increased the expression of stress-responsive genes, including RD22 and RD29A, and reduced the accumulation of reactive oxygen species (ROS). These results indicate that MpZFP1 is a positive regulator of plant responses to salt stress due to its activation of gene expression and efficient scavenging of ROS.

Self-Powered Temperature Sensor with Seebeck Effect Transduction for Photothermal-Thermoelectric Coupled Immunoassay.

A self-powered temperature sensor based on Seebeck effect transduction was designed for photothermal-thermoelectric coupled immunoassay of α-fetoprotein (AFP). In this system, glucose oxidase (GOx)-conjugated detection antibody was first captured onto the microplate by target-induced sandwich-type immunoreaction. Thereafter, the as-generated hydrogen peroxide via the GOx-glucose system oxidized 3,3',5,5'-tetrametylbenzidine (TMB) into photothermal product oxidized TMB (ox-TMB). Under near-infrared (NIR) laser irradiation, the temperature change of ox-TMB was read out in an electrical signal by the flexible thermoelectric module in a 3D-printed integrated detection device. Under optimal conditions, the photothermal-thermoelectric coupled immunoassay exhibited a limit of detection of 0.39 ng mL-1 AFP over a dynamic linear range from 0.5 to 60 ng mL-1. Impressively, such a strategy presented herein offers tremendous potentials for applying many other high-efficiency thermoelectric materials in ultrasensitive biosensors.

A polypyrrole-polydimethylsiloxane sponge-based compressible capacitance sensor with molecular recognition for point-of-care immunoassay.

A highly compressible and all-solid-state polydimethylsiloxane (PDMS) sponge-based flexible capacitance sensor modified with polypyrrole (PPy) was designed as the signal readout for the sensitive immunoassay of prostate-specific antigen (PSA). This system mainly consisted of a compressible capacitance sensor, immunoreaction protocol and gas delivery channel. The capacitance sensor was connected to a single microplate by a syringe, whereas the immunoreaction was carried out in the microplate. The conjugated catalase with the detection antibody via biotin-streptavidin interaction could trigger gas generation to cause a pressure change, thus resulting in the increase in the capacitance of the PPy-PDMS sponge observed with an LCR-6100 digital bridge capacitance meter. By coupling with the capacitance sensor, the capacitance change could be monitored in real time to achieve portable detection of PSA. Under the optimal conditions, the compressible supercapacitor PPy-PDMS sponge showed great electrochemical performance and remained stable under compressive strains. The capacitance increased with increasing target PSA concentration within a dynamic working range of 0.1-50 ng mL-1 at a detection limit of 57 pg mL-1. Moreover, acceptable reproducibility, precision and high specificity were obtained from PSA analysis, and were in good accordance with the commercial PSA ELISA kit.

Reduction of non-uniformity for a 16 × 16 arrayed waveguide grating router based on silica waveguides.

Here, a newly designed 16×16 cyclic arrayed waveguide grating router, capable of achieving loss uniformity across the whole free spectral range (FSR), is fabricated and experimentally demonstrated. This device is based on commonly used silica waveguides, which are compatible with basic planar lightwave circuit technology. The design, simulation, and experimental verification of the proposed method are presented, with the experimental results showing that the loss non-uniformity of FSR reduced from 2.70 to 1.05 dB using this new design. This design brings in only tiny changes of mask and real estate.

Utilizing soft constraints to enhance medical relation extraction from the history of present illness in electronic medical records.

Relation extraction between medical concepts from electronic medical records has pervasive applications as well as significance. However, previous researches utilizing machine learning algorithms judge the semantic types of medical concept pair mentions independently. In fact, different concept pair mentions in the same context are of dependencies which can provide beneficial evidences for identifying their relation types. To the best of our knowledge, only one study has considered such dependencies in discharge summaries. However, its hard constraints are not applied effectively to the History of Present Illness (HPI) in electronic Medical Records. According to the writing characteristics of HPI records, we generalize two regularities of dependencies among concept pairs mentioned in an HPI record to enhance the performance of relation extraction. We incorporate the two soft constraints corresponding to the regularities and the posterior probabilities returned by a local classifier into a joint inference process which applies Integer Quadratic Programming method to carry out collective classification for all concept pair mentions in an HPI record. We implement four local classification models including support vector machine, logistics regression, random forest and piecewise convolutional neural networks to examine the performance of our approach. A series of experimental results demonstrate that our collective classification method has made a principal improvement and outperforms the other state-of-the-art methods.

High-Risk Factors for Suppurative Mastitis in Lactating Women.

BACKGROUND Acute mastitis is a common disease occurring in postpartum lactating women. This study aimed to identify the high-risk factors for suppurative mastitis (SM) in women who were breastfeeding. MATERIAL AND METHODS A total of 262 non-SM patients and 63 SM patients admitted to the Department of Breast and Thyroid Surgery of Liaocheng People's Hospital were retrospectively enrolled in this study. The high-risk factors for SM during lactation were determined by assessing admission time after acute mastitis, galactostasis, primipara or pluripara, nipple injuries, antibiotic treatment course, and diabetes. RESULTS The incidence of SM in patients with admission time greater than 72 h after occurrence of acute mastitis was significantly higher than that in patients whose admission time was less than 72 h (p<0.0001). Patients with galactostasis were more prone to develop SM compared to patients without galactostasis (p<0.0001), and the incidence of SM in primiparous patients was significantly higher than that in pluriparous patients (p=0.003). The incidence rate of SM was significantly higher in patients with diabetes than in patients without diabetes (p=0.002). Patients with nipple injuries were more prone to suffer from SM relative to the patients without nipple injuries (p<0.0001). However, there was no significant difference in the incidence of SM according to the antibiotic treatment course (p=0.134). CONCLUSIONS SM during lactation was closely associated with admission time after the occurrence of acute mastitis, galactostasis, primipara, diabetes, and nipple injuries.

Supervised methods for symptom name recognition in free-text clinical records of traditional Chinese medicine: an empirical study.

Clinical records of traditional Chinese medicine (TCM) are documented by TCM doctors during their routine diagnostic work. These records contain abundant knowledge and reflect the clinical experience of TCM doctors. In recent years, with the modernization of TCM clinical practice, these clinical records have begun to be digitized. Data mining (DM) and machine learning (ML) methods provide an opportunity for researchers to discover TCM regularities buried in the large volume of clinical records. There has been some work on this problem. Existing methods have been validated on a limited amount of manually well-structured data. However, the contents of most fields in the clinical records are unstructured. As a result, the previous methods verified on the well-structured data will not work effectively on the free-text clinical records (FCRs), and the FCRs are, consequently, required to be structured in advance. Manually structuring the large volume of TCM FCRs is time-consuming and labor-intensive, but the development of automatic methods for the structuring task is at an early stage. Therefore, in this paper, symptom name recognition (SNR) in the chief complaints, which is one of the important tasks to structure the FCRs of TCM, is carefully studied. The SNR task is reasonably treated as a sequence labeling problem, and several fundamental and practical problems in the SNR task are studied, such as how to adapt a general sequence labeling strategy for the SNR task according to the domain-specific characteristics of the chief complaints and which sequence classifier is more appropriate to solve the SNR task. To answer these questions, a series of elaborate experiments were performed, and the results are explained in detail.

Phomopamide A, a cyclic pentadepsipeptide with α-glucosidase inhibition activity from the endophytic fungus Diaporthe sp.

An undescribed cytotoxic cyclopeptide named phomopamide A (1) was isolated from Diaporthe sp., which is an endophytic fungus from Artemisia argyi. Phomopamide A (1) featured an pentadepsipeptide skeleton and composed of two Phe, one Val, one Leu, and one 2-hydroxyoctanoic acid units. The structure of this new compound was fully characterised on the basis of extensive spectroscopic analysis. Moreover, phomopamide A was evaluated for in vitro cyctotoxic and α-glucosidase inhibitory activity. As a result, phomopaminde A exhibited no cytotoxic activity against four tumour cell lines, while it showed a potent α-glucosidase inhibition effect with IC50 value of 62.35 µM.

Effect of postoperative exercise training on physical function and quality of life of lung cancer patients with chronic obstructive pulmonary disease: A randomized controlled trial.

BACKGROUND: Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients. However, whether postoperative exercise is beneficial to lung cancer patients comorbid with chronic obstructive pulmonary disease remains unknown. METHODS: Eighty-four patients diagnosed with both lung cancer and chronic obstructive pulmonary disease were randomized into the exercise group and control group. Both groups were given standard postoperative rehabilitation for 1 week. After that, oxygen therapy (if needed) and nebulization were given to the control group, while patients in the exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the control group. The exercise programs consisted of 24 training sessions. RESULTS: In both groups, the functional status and the results of the pulmonary function test decreased from baseline to the endpoint. However, after surgery and the intervention program, both the maximal oxygen consumption in the cardiopulmonary exercise test and walking distance in the 6-minute walk test in the exercise group were significantly better than those in the control group [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = 0.016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = 0.040]. Force vital capacity and forced expiratory volume in the first second in the exercise group were better than those in the control group, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = 0.254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = 0.497]. The decline in the standard score of the QLQ-C30 (V3.0) was smaller in the exercise group, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = 0.318]. CONCLUSION: This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of chronic obstructive pulmonary disease.

R6G on graphene: high Raman detection sensitivity, yet decreased Raman cross-section.

Several recent studies have demonstrated the use of single and few-layer graphene as a substrate for the enhancement of Raman scattering by adsorbed molecules in a method termed graphene-enhanced Raman spectroscopy (GERS). Here we determine the resonance Raman scattering cross-section for the dye molecule rhodamine 6G (R6G) adsorbed on bilayer graphene. For the 1650 cm(-1) R6G mode, we obtain a cross-section of 5.1 × 10(-24) cm(2)·molecule(-1), a greater than 3-fold reduction from the previously reported solution value. We show that the absorption spectrum of adsorbed R6G can be measured using micro-optical contrast spectroscopy, and we find that detuning of the molecular resonance explains the decreased Raman scattering cross-section. We find no evidence for a graphene Raman enhancement process. We also study the graphene thickness dependence of the adsorbed R6G Raman signal and show that a model incorporating electromagnetic interference effects can qualitatively explain the decrease in signal with increasing graphene thickness.

Efficacy and tolerability of docetaxel and cisplatin plus S-1 for advanced gastric cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of docetaxel and cisplatin plus S-1 (DCS) combination chemotherapy in advanced gastric cancer patients. METHODS: Chemo-naive patients with advanced gastric cancer, ECOG performance status of 0 to 1, and adequate organ function were eligible. All patients received docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, plus S-1 orally 40-60 mg bid depending on body surface area on days 1-14, every 21 days. Efficacy and adverse events were evaluated every two cycles. RESULTS: Fifty-nine patients were enrolled from February 2009 to January 2011 and 56 of them were evaluated for efficacy and tolerability. After a median follow up of 17.6 months, the objective response rate (RR) was 75%, the disease control rate (DCR) 83.9%, the median progression free survival (PFS) and overall survival (OS) 6.5 (95% CI, 5.6-7.3) months and 15.5 (95% CI, 13.9-17.0) months, respectively. The median number of chemotherapy cycles was 5. Grade 3 or 4 adverse effects included neutropenia (60.7%), vomiting (14.3%), neurotoxicity (12.5%), thrombocytopenia (10.7%), diarrhea (10.7%), impaired liver function (3.6%), and hand-foot syndrome (1.8%). CONCLUSION: Our study shows that DCS regimen is active against advanced gastric cancer with acceptable toxicities and it may be used as a new choice of first-line chemotherapy for patients with advanced gastric cancer.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).