Background: Nipocalimab (a fully human, effectorless anti-neonatal Fc receptor (FcRn) monoclonal antibody) may ameliorate gMG disease manifestations by selectively targeting FcRn IgG recycling and lowering IgG, including pathogenic autoantibodies in generalized myasthenia gravis (gMG). The objective was to evaluate the effectiveness and safety of intravenous nipocalimab added to background standard-of-care therapy in adolescents with gMG. Methods: Seropositive patients (12-<18 years) with gMG (MGFA Class II-IV) on stable therapy but inadequately controlled, were enrolled in a 24-week open label study. Nipocalimab was administered as a 30 mg/kg IV loading dose followed by 15 mg/kg IV every 2 Weeks. Results: Seven adolescents were enrolled; 5 completed 24-weeks of dosing. The mean(SD) age was 14.1(1.86) years; seven were anti-AChR+, six were female. Mean(SD) baseline MG-ADL/QMG scores were 4.29(2.430)/12.50(3.708). Nipocalimab showed a significant reduction in total serum IgG at week-24; the mean(SD) change from baseline to week-24 for total serum IgG was -68.98%(7.561). The mean(SD) change in MG-ADL/QMG scores at week-24 was -2.40(0.418)/-3.80(2.683); 4 of 5 patients achieved minimum symptom expression (MG-ADL score 0-1) by week-24. Nipocalimab was well-tolerated; there were no serious adverse events. There were no clinically meaningful laboratory changes. Conclusions: Nipocalimab demonstrated efficacy and safety in this 6-month trial in seropositive adolescents with gMG.

Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.

Echocardiographic Z-score models play a crucial role in defining cardiac pathology in paediatric patients. There are multiple models that practitioners utilize in the United States without guiding principles to standardize their use. Discrepant interpretations can occur depending on the model chosen, even if standardized Z-score cutoffs are applied. In this study, a survey was developed to assess pediatric cardiologists’ use of Z-score systems when evaluating and treating patients with isolated bicuspid aortic valve. The majority of respondents reported using Z-score cutoffs to evaluate the degree of aortic root and ascending aorta dilation. For the aortic root, mild, moderate, and severe dilation averaged at 2.13 (SD = 0.32), 3.59 (SD = 0.49), and 5.11 (SD = 0.84), respectively. Similar cutoffs were reported for determining ascending aorta dilation. A large proportion of respondents primarily used the Boston system (36%, 18/50) or Boston and Pediatric Heart Network systems together (36%, 18/50). There were also differences in management decisions, such as implementing competitive sports restrictions, based on Z-scores and the 2015 Task Force 7 Bethesda exercise guidelines. These survey results demonstrate variability that exists among paediatric cardiologists in their use of Z-scores for describing aortic root and ascending aorta dilation in patients with isolated bicuspid aortic valve and suggests the need for implementation of national guidelines for Z-score usage.

Marine litter poses a complex challenge in Indonesia, necessitating a well-informed and coordinated strategy for effective mitigation. This study investigates the seasonality of plastic concentrations around Sulawesi Island in central Indonesia during monsoon-driven wet and dry seasons. By using open data and methodologies including the HYCOM and Parcels models, we simulated the dispersal of plastic waste over 3 months during both the southwest and northeast monsoons. Our research extended beyond data analysis, as we actively engaged with local communities, researchers and policymakers through a range of outreach initiatives, including the development of a web application to visualize model results. Our findings underscore the substantial influence of monsoon-driven currents on surface plastic concentrations, highlighting the seasonal variation in the risk to different regional seas. This study adds to the evidence provided by coarser resolution regional ocean modelling studies, emphasizing that seasonality is a key driver of plastic pollution within the Indonesian archipelago. Inclusive international collaboration and a community-oriented approach were integral to our project, and we recommend that future initiatives similarly engage researchers, local communities and decision-makers in marine litter modelling results. This study aims to support the application of model results in solutions to the marine litter problem.

Ultrafast optical probing is a widely used method of underdense plasma diagnostic. In relativistic plasma, the motion blur limits spatial resolution in the direction of motion. For many high-power lasers the initial pulse duration of 30–50 fs results in a 10–15 μm motion blur, which can be reduced by probe pulse post-compression. Here we used the compression after compressor approach [Phys.-Usp. 62, 1096 (2019); JINST 17 P07035 (2022)], where spectral broadening is performed in thin optical plates and is followed by reflections from negative-dispersion mirrors. Our initially low-intensity probe beam was down-collimated for a more efficient spectral broadening and higher probe-to-self-emission intensity ratio. The setup is compact, fits in a vacuum chamber and can be implemented within a short experimental time slot. We proved that the compressed pulse retained the high quality necessary for plasma probing.

Echinococcosis poses a significant threat to public health. The Chinese government has implemented prevention and control measures to mitigate the impact of the disease. By analyzing data from the Chinese Center for Disease Control and Prevention and the State Council of the People’s Republic of China, we found that implementation of these measures has reduced the infection rate by nearly 50% between 2004 to 2022 (from 0.3975 to 0.1944 per 100,000 person-years). Nonetheless, some regions still bear a significant disease burden, and lack of detailed information limites further evaluation of the effects on both alveolar and cystic echinococcosis. Our analysis supports the continuing implementation of these measures and suggests that enhanced wildlife management, case-based strategies, and surveillance systems will facilitate disease control.

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

Infection prevention program leaders report frequent use of criteria to distinguish recently recovered coronavirus disease 2019 (COVID-19) cases from actively infectious cases when incidentally positive asymptomatic patients were identified on routine severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. Guidance on appropriate interpretation of high-sensitivity molecular tests can prevent harm from unnecessary precautions that delay admission and impede medical care.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

Planting patterns have significant effects on rice growth. Nonetheless, little is known about differences in annual crop yield and resource utilization among mechanized rice planting patterns in a rice–wheat cropping system. Field experiments were conducted from 2014 to 2017 using three treatments: pot seedling transplanting for rice and row sowing for wheat (PST-RS), carpet seedling transplanting for rice and row sowing for wheat (CST-RS) and row sowing for both crops (RS-RS). The results showed that, compared with RS-RS, PST-RS and CST-RS prolonged annual crop growth duration by 25–26 and 13–15 days, increased effective accumulated temperature by 399 and 212°C days and increased cumulative solar radiation by 454 and 228 MJ/m2 because of the earlier sowing of rice by 28 and 16 days in PST-RS and CST-RS, respectively. Compared with RS-RS, the annual crop yield of PST-RS and CST-RS increased by 3.1–3.8 and 2.0–2.6 t/ha, respectively, because of the increase in the number of spikelets/kernels per hectare, aboveground biomass, mean leaf area index and grain–leaf ratio. In addition, temperature production efficiency, solar radiation production efficiency and solar radiation use efficiency were higher in PST-RS, followed by CST-RS and RS-RS. These results suggest that mechanized rice planting patterns such as PST-RS increase annual crop production in rice–wheat cropping systems by increasing yield and solar energy utilization.

Unmanned aerial vehicle (UAV) swarm coverage is one of the key technologies for multi-UAV cooperation, which plays an important role in collaborative investigation, detection, rescue and other applications. Aiming at the coverage optimisation problem of UAV in the target area, a collaborative visual coverage control method under positioning uncertainty is presented. First, the visual perception area with imprecise localisation, UAV model and sensor model are created based on the given task environment. Second, a regional division algorithm for the target task area is designed based on the principle of Guaranteed Voronoi (GV) diagram. Then a visual area coverage planning algorithm is designed, in which the task area is allocated to the UAV according to the corresponding weight coefficient of each area, and the input control law is adjusted by the expected state information of the UAV, so that the optimal coverage quality target value and the maximum coverage of the target area can be achieved. Finally, three task scenarios for regional division and coverage planning are simulated respectively, the results show that the proposed area coverage planning algorithm can realise the optimal regional distribution and can obtain more than 90% coverage in different scenarios.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

OBJECTIVES/GOALS: Our overall goal is to identify the processes used by the human visual system to encode visual stimuli into perceptual representations. In this project, our objective is (i) to collect a dataset of human neural activity in response to 1000 naturalistic color images and (ii) to determine how image parameters drive different parts of the human brain. METHODS/STUDY POPULATION: We recorded iEEG data in 4 human subjects who had been implanted for epilepsy monitoring. Each subject was presented 10 sets of 100 naturalistic stimuli, taken from the Natural Scenes Dataset (Allen et al., 2021), on a screen for 1 second each with 1 second rest intervals between stimuli. The subjects were instructed to fixate on a red dot at the center of the screen and were prompted to recall whether they had seen 3 additional test stimuli at the end of each set to encourage attentiveness. We calculated significant neural responses at each electrode by comparing evoked potentials and high frequency power changes during each stimulus vs. rest. Electrodes with significant responses were then mapped to anatomic locations in each subjects brain and then collectively to a standard brain. RESULTS/ANTICIPATED RESULTS: The natural image set elicited significant evoked potentials and high frequency responses at electrodes in each subject. Response latencies, from 80 to 300 ms after stimulus onset, portrayed the evolution of visual processing along the visual pathways, through key sites such as the early visual cortex, ventral temporal cortex, intraparietal sulcus, and frontal eye field. These responses differed significantly from those elicited by simple patterns, which drove early visual cortex but less so in later regions. DISCUSSION/SIGNIFICANCE: These data show that the human brain responds differently to more complex images. Determining the human brains response to naturalistic images is essential for encoding models that describe the processing in the human visual system. These models may further future efforts for electrical neurostimulation therapies such as for restoring vision.

ABSTRACT IMPACT: This study characterizes interactions between human limbic circuitry and ventral temporal cortex using single pulse electrical stimulation, which may inform emerging stimulation therapies for epilepsy. OBJECTIVES/GOALS: The goal of electrical brain stimulation treatment is to modulate brain network function. However, stimulation inputs to different brain sites alter the network in a variety of ways. This study examines that variability by characterizing responses in a target region while stimulating multiple other brain sites. METHODS/STUDY POPULATION: We measured voltages in intracranial EEG in 6 patients who had electrodes implanted for epilepsy monitoring. We stimulated pairs of electrodes at multiple sites in the brain with a single pulse every 5 to 7 s and measured the resulting corticocortical evoked potential (CCEP) responses in the ventral temporal cortex (VTC). Using a novel clustering method, we uncovered sets of distinct canonical response shapes from the 20 to 500 ms post-stimulation period. This allowed us to group stimulation sites that evoked similar responses. We then related each group to high frequency, broadband, changes in spectral power as a reflection of local neuronal activity. RESULTS/ANTICIPATED RESULTS: We found that the VTC receives strong inputs specifically from the amygdala and hippocampus, both in terms of amplitude and broadband spectral power change. However, inputs from the hippocampus produced a different canonical shape than those from the amygdala. We also observed that VTC responses to inputs from the insula clustered in shape with those from the amygdala. These clustering patterns were consistent across subjects, although the actual shapes of the clusters showed variability. We further observed that some shapes were more associated with increases in overall neuronal activity than others, as reflected by broadband spectral power change. DISCUSSION/SIGNIFICANCE OF FINDINGS: Stimulation of connected sites may drive excitability at the target region in ways that are described by sets of full-time-course responses. By capturing their shapes, we can begin to decipher canonical input types at the circuit level. This approach might identify how stimulation inputs can be tailored to therapy while mitigating adverse effects.