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Background: Efgartigimod is an approved biologic for generalized myasthenia gravis (gMG), which is an autoimmune disease and can potentially be life-threatening. However, the therapeutic response to efgartigimod among the acetylcholine receptor gMG (AChR-gMG) subtypes remains inconclusive. Objective: To explore the patterns and predictors for the therapeutic response to efgartigimod among AChR-gMG subtypes. Design: This prospective, observational study included AChR-gMG patients treated with efgartigimod at 15 centers in China with a follow-up for at least 20 weeks. Methods: The primary outcome was the proportion of minimal symptom expression (MSE) responders, denoted by a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 0 or 1 within 4 weeks and maintained for ⩾4 weeks. AChR antibody-positive MG (AChR-MG) subtypes were classified into early onset myasthenia gravis (EOMG), late-onset myasthenia gravis (LOMG), and thymoma-associated myasthenia gravis (TAMG). The predictive factors for MSE responders were identified by univariate and multivariate logistic regression analysis. Results: One hundred sixteen patients were included with a median follow-up duration of 238 days (172.5–306.3). There were 50 (43.1%) patients with EOMG, 28 (24.1%) with LOMG and 38 (32.8%) with TAMG. After efgartigimod initiation, 35 (30.2%) patients were MSE responders, and the proportion of MSE responders was highest in the LOMG group (42.9%). The MG-ADL score reduction in the LOMG group was more significant than in the EOMG group by weeks 16 and 20 (both p = 0.022). Response patterns to efgartigimod among the AChR-MG subtypes differed as measured by the proportion of improved patients and MSE. LOMG presented sustained symptom control, while EOMG and TAMG showed more fluctuations. Eight TAMG patients (21.1%) switched to another biologic (p = 0.005). Baseline MG-ADL was an independent predictor for therapeutic response to efgartigimod (p < 0.001). Conclusion: Our findings revealed patterns of treatment responses among AChR-gMG subtypes, with LOMG patients potentially presenting a more sustained response. These findings likely provide preliminary data for precision therapy in MG in the era of biologics. Trial registration: NCT04535843. Plain language summary: Patterns and predictors of therapeutic response to efgartigimod in AChR generalized myasthenia gravis Myasthenia Gravis (MG) is an autoimmune disorder that can lead to potentially life-threatening complications. Efgartigimod is an approved biologic for generalized myasthenia gravis (gMG). However, the patterns and predictors of therapeutic response to efgartigimod among the acetylcholine receptor-generalized MG (AChR-gMG) subtypes remain inconclusive. Our findings revealed patterns of treatment responses among AChR-gMG subtypes, with LOMG patients potentially presenting a more sustained response. [ABSTRACT FROM AUTHOR]

The agronomic knowledge graph can provide accurate and reliable service support for agricultural production management. Agronomic knowledge often comes from unstructured text data, and efficient annotation of agricultural text data and construction of knowledge extraction models suitable for the characteristics of agronomic knowledge are two key points to create an agronomic knowledge graph. The proportion of attributes in agronomic knowledge is relatively high, but currently, the attribute annotation function of existing annotation tools is incomplete, and the annotation function and process are unclear. A scalable natural language annotation framework was proposed, which was able to flexibly configure the annotation process and annotation objects as needed, and the named entity was annotated in the corresponding mode. The current knowledge extraction models are mostly based on input text sequences, which has the problem of low feature utilization. However, the entities and attributes in agronomic knowledge have high similarity, and the position and type of entities and attributes can be directly calculated through their common features. An entity and attribute recognition model based on target localization, EntityDetectModel, was proposed. Firstly, Bert was used to extract text features with contextual information. Then, convolutional neural networks were used to extract features at different depths, and inter layer feature fusion was used to improve feature expression ability. Finally, the corresponding positions and types of named entities with different sizes were calculated based on the features at different depths. EntityDetectModel was compared with the other entity and relationship extraction models published in recent years and the results showed that the precision, recall, and F1 of EntityDetectModel were 91.0%, 83.4%, and 87.0%, respectively, which were superior to other comparison models. Using EntityDetectModel, a wheat agronomic knowledge graph was constructed. [ABSTRACT FROM AUTHOR]

Background: China has a large number of myasthenia gravis (MG) patients, creating an urgent need for rapid and tolerable treatment options. As the first-approved Fc receptor antagonist, efgartigimod has bright prospects for treating MG. However, real-world evidence on its application within the Chinese MG population are limited. Objective: This study aims to evaluate the rapid efficacy and safety of efgartigimod in Chinese MG population. Design: This single-center prospective study enrolled Chinese MG patients aged 18 and older who were treated with efgartigimod, classified as Myasthenia Gravis Foundation of America I–IV, with a baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 4. Methods: Patients received efgartigimod at a dose of 10 mg/kg infused once weekly for 4 weeks. During the treatment, the corticosteroids dosage could be adjusted as appropriate or the non-steroidal immunosuppressive therapies (NSISTs) added. Prior to each infusion, patients' MG-ADL scores, IgG levels, and routine laboratory tests were evaluated, while also recording the prednisone tapering and any adverse events occurring during the treatment. Results: Twenty five Chinese MG patients were enrolled between November 2023 and June 2024, including 3 with ocular MG (OMG) and 22 with generalized MG (GMG). During the 8-week follow-up, in GMG patients, whether positive for acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies, the overall efficacy was significant. Within one treatment cycle, 18 (82%) patients showed a reduction of at least 2 points in MG-ADL scores and sustained for at least 4 weeks, and 6 (27%) attained minimal symptom expression (MSE) and sustained for at least 4 weeks. Only 1 patient experienced exacerbation. Among OMG patients, 1 achieved MSE within the treatment cycle, while 2 showed minor improvements. Patients who added tacrolimus concurrently with efgartigimod did not achieve better improvement in MG-ADL scores compared to others. The average reduction in prednisone dosage was 27.4%. Only one patient experienced transient vomiting and diarrhea, with no serious adverse reactions reported. Conclusion: This study confirmed the short-term efficacy and safety of efgartigimod in Chinese MG patients. However, in clinical practice, careful consideration is needed regarding its application in OMG and whether to add NSISTs regimen during the treatment. Efgartigimod could potentially serve as an alternative to long-term corticosteroids therapy. [ABSTRACT FROM AUTHOR]

Objects in farmlands often have characteristic of small volume and high density with variable light and complex background, and the available object detection models could not get satisfactory recognition results. Taking bees as research objects, a method that could overcome the influence from the complex backgrounds, the difficulty in small object feature extraction was proposed, and a detection algorithm was created for small objects irrelevant to image size. Firstly, the original image was split into some smaller sub-images to increase the object scale, and the marked objects were assigned to the sub-images to produce a new dataset. Then, the model was trained again using transfer learning to get a new object detection model. A certain overlap rate was set between two adjacent sub-images in order to restore the objects. The objects from each sub-image was collected and then non-maximum suppression (NMS) was performed to delete the redundant detection boxes caused by the network, an improved NMS named intersection over small NMS (IOS-NMS) was then proposed to delete the redundant boxes caused by the overlap between adjacent sub-images. Validation tests were performed when sub-image size was set was 300×300, 500×500 and 700×700, the overlap rate was set as 0.2 and 0.05 respectively, and the results showed that when using single shot multibox detector (SSD) as the object detection model, the recall rate and precision was generally higher than that of SSD with the maximum difference 3.8% and 2.6%, respectively. In order to further verify the algorithm in small target recognition with complex background, three bee images with different scales and different scenarios were obtained from internet and test experiments were conducted using the new proposed algorithm and SSD. The results showed that the proposed algorithm could improve the performance of target detection and had strong scale adaptability and generalization. Besides, the new algorithm required multiple forward reasoning for a single image, so it was not time-efficient and was not suitable for edge calculation.

Objective: Efgartigimod, a neonatal Fc receptor antagonist, facilitates antibody degradation including pathogenic IgGs. The ADAPT study demonstrated the tolerability and efficacy of efgartigimod in the treatment of generalized myasthenia gravis (gMG). However, very limited evidence is available for the Chinese population, and it remains inconclusive about which kind of patients are selected to preferentially receive efgartigimod in real‐world settings. Methods: This multicenter cohort study included gMG patients treated at 14 neuromuscular reference centers in China. The Myasthenia Gravis Activities of Daily Living (MG‐ADL) score, immunosuppressants, and the incidence of treatment‐emergent adverse events (TEAEs) were prospectively collected. Results: Of the 1640 gMG admitted between September and December 2023, 61 (3.7%) received efgartigimod for at least one treatment cycle. Among them, 56 cases (92%) were anti‐AChR antibody‐positive, 4 were anti‐MuSK antibody‐positive, and 1 was seronegative. Thymoma‐associated myasthenia gravis accounted for most cases (44%, 27 out of 61). The principal causes of efgartigimod initiation included MG acute exacerbation (MGAE) (48%, 29 out of 61) and myasthenic crisis (MC) (15%, 9 out of 61). Clinically meaningful improvement was rapidly achieved in 97% (58 out of 61) of patients at 1.3 ± 0.7 weeks. By week 12, the MG‐ADL score reduced to 3.8 ± 4.1 (baseline:10.5 ± 5.2) for all participants, while it reduced to 4.0 ± 4.7 for MGAE and 3.8 ± 4.2 for MC, respectively. All but one TMG patient required no additional rescue therapies after efgartigimod initiation. 11.5% (7 out of 61) reported ≥1 TEAEs. Interpretation: This multicenter cohort study demonstrated the efficacy of efgartigimod in rapid control of gMG. Patients with MGAE or MC would benefit from efgartigimod treatment. [ABSTRACT FROM AUTHOR]

The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Wireless sensor network (WSN) nodes exchange information via wireless signals, whose power can attenuate at different levels according to the propagation environment. The branches and leaves of young apple trees are much sparser than that of adult apple trees. Propagation rules such as propagation distance and attenuation rate are the parameters necessary to know before applying a WSN to a young apple orchard. Field tests were performed, and propagation distance and packet loss rate (PLR) were computed and compared under the two cases: a young apple orchard in fruit period and an open space to find the effect of the apple trees on radio propagation. A model of antenna height and propagation distance was created to forecast the extra path loss caused by the young trees. Validation experiments were performed in a different young apple orchard, and the validation results showed that 70% of R2 were higher than 0.7, while the smallest being 0.65; 80% RMSE were smaller than 5. The new model was also compared with some classical models such as Cost 235, FITU, ITU-R, and Weissberger model, and the new model was proved to be the best. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epigenetic regulation of neprilysin (NEP) gene in mouse neuroblastoma Neuro-2a (N2a) cells and further determine the interaction between DNA methylation and histone acetylation., Methods: N2a cells were treated with DNA methylation inhibitor, 5-aza-deoxycytidine (5-Aza-dc) at 3 and 5 μmol/L for 48 hours and histone deacetylase inhibitor, trichostatin A (TSA) at 300, 500 and 700 nmol/L for 24 hours. The expression of NEP after the treatment was evaluated by reverse transcription PCR(RT-PCR) and Western blotting. Bisulfite sequencing PCR (BSP) assay was utilized to detect the methylation status of NEP gene promoter regions. The level of acetylated histone H3 on NEP promoter was measured by chromatin immunoprecipitation (ChIP) assay., Results: 5-Aza-dc induced the demethylation of NEP gene and significantly increased NEP expression in a dose-dependent manner (P<0.01). TSA treatment significantly enhanced NEP expression by elevating the acetylation of histone H3 on NEP promoter (P<0.01, P<0.05). However, methylation status of NEP promoter was not altered by TSA treatment (P>0.05)., Conclusion: The expression of NEP gene is regulated by DNA methylation and histone acetylation in N2a cells. Histone acetylation has no effect on DNA methylation.