The accuracy and interpretability of artificial intelligence (AI) are crucial for the advancement of optical coherence tomography (OCT) image detection, as it can greatly reduce the manual labor ...required by clinicians. By prioritizing these aspects during development and application, we can make significant progress towards streamlining the clinical workflow. In this paper, we propose an explainable ensemble approach that utilizes transfer learning to detect fundus lesion diseases through OCT imaging. Our study utilized a publicly available OCT dataset consisting of normal subjects, patients with dry age-related macular degeneration (AMD), and patients with diabetic macular edema (DME), each with 15 samples. The impact of pre-trained weights on the performance of individual networks was first compared, and then these networks were ensemble using majority soft polling. Finally, the features learned by the networks were visualized using Grad-CAM and CAM. The use of pre-trained ImageNet weights improved the performance from 68.17% to 92.89%. The ensemble model consisting of the three CNN models with pre-trained parameters loaded performed best, correctly distinguishing between AMD patients, DME patients and normal subjects 100% of the time. Visualization results showed that Grad-CAM could display the lesion area more accurately. It is demonstrated that the proposed approach could have good performance of both accuracy and interpretability in retinal OCT image detection.
Solving Mathematics Word Problem (MWP) is a basic ability of humanity, which can be mastered by most students at a young age. The existing artificial intelligence system is not good enough in ...numerical questions, like MWPs. The hard part of this problem is translating natural language sentences in MWP into mathematical expressions or equations. In recent researches, the Transformer network, which proved a great success in machine translation, is applied to automatic mathematic word problem-solving. While previous works have only shown the ability of Transformer model in MWP, how multiple factors such as encoding, decoding, and pre-training affect the performance of Transformer model has not received enough attention. The study is the first to examine the role of these factors experimentally. This paper proposes several methods to improve Transformer network performance in MWPs under the basis of previous studies, achieves higher accuracy compared to the previous state of the art. Pre-training on target tasks dataset improves the translation quality of the Transformer model greatly. Different token encoding and search algorithms also benefit prediction accuracy at the expense of more training and testing time.
Cyclins are primary regulators of the activity of cyclin-dependent kinases, which are known to play critical roles in controlling eukaryotic cell cycle progression. While there has been extensive ...research on cell cycle mechanisms and cyclin function in animals and yeasts, only a small number of plant cyclins have been characterized functionally. In this paper, we describe an exhaustive search for cyclin genes in the Arabidopsis genome and among available sequences from other vascular plants. Based on phylogenetic analysis, we define 10 classes of plant cyclins, four of which are plant-specific, and a fifth is shared between plants and protists but not animals. Microarray and reverse transcriptase-polymerase chain reaction analyses further provide expression profiles of cyclin genes in different tissues of wild-type Arabidopsis plants. Comparative phylogenetic studies of 174 plant cyclins were also performed. The phylogenetic results imply that the cyclin gene family in plants has experienced more gene duplication events than in animals. Expression patterns and phylogenetic analyses of Arabidopsis cyclin genes suggest potential gene redundancy among members belonging to the same group. We discuss possible divergence and conservation of some plant cyclins. Our study provides an opportunity to rapidly assess the position of plant cyclin genes in terms of evolution and classification, serving as a guide for further functional study of plant cyclins.
IMPORTANCE: The EMERGE and ENGAGE phase 3 randomized clinical trials of aducanumab provide a robust data set to characterize amyloid-related imaging abnormalities (ARIA) that occur with treatment ...with aducanumab, an amyloid-β (Aβ)–targeting monoclonal antibody, in patients with mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia. OBJECTIVE: To describe the radiographic and clinical characteristics of ARIA that occurred in EMERGE and ENGAGE. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of data from the EMERGE and ENGAGE trials, which were 2 double-blind, placebo-controlled, parallel-group, phase 3 randomized clinical trials that compared low-dose and high-dose aducanumab treatment with placebo among participants at 348 sites across 20 countries. Enrollment occurred from August 2015 to July 2018, and the trials were terminated early (March 21, 2019) based on a futility analysis. The combined studies consisted of a total of 3285 participants with Alzheimer disease who received 1 or more doses of placebo (n = 1087) or aducanumab (n = 2198; 2752 total person-years of exposure) during the placebo-controlled period. Primary data analyses were performed from November 2019 to July 2020, with additional analyses performed through July 2021. INTERVENTIONS: Participants were randomly assigned 1:1:1 to high-dose or low-dose intravenous aducanumab or placebo once every 4 weeks. Dose titration was used as a risk-minimization strategy. MAIN OUTCOMES AND MEASURES: Brain magnetic resonance imaging was used to monitor patients for ARIA; associated symptoms were reported as adverse events. RESULTS: Of 3285 included participants, the mean (SD) age was 70.4 (7.45) years; 1706 participants (52%) were female, 2661 (81%) had mild cognitive impairment due to Alzheimer disease, and 1777 (54%) used symptomatic medications for Alzheimer disease. A total of 764 participants from EMERGE and 709 participants from ENGAGE were categorized as withdrawn before study completion, most often owing to early termination of the study by the sponsor. Unless otherwise specified, all results represent analyses from the 10-mg/kg group. During the placebo-controlled period, 425 of 1029 patients (41.3%) experienced ARIA, with serious cases occurring in 14 patients (1.4%). ARIA-edema (ARIA-E) was the most common adverse event (362 of 1029 35.2%), and 263 initial events (72.7%) occurred within the first 8 doses of aducanumab; 94 participants (26.0%) with an event exhibited symptoms. Common associated symptoms among 103 patients with symptomatic ARIA-E or ARIA-H were headache (48 46.6%), confusion (15 14.6%), dizziness (11 10.7%), and nausea (8 7.8%). Incidence of ARIA-E was highest in aducanumab-treated participants who were apolipoprotein E ε4 allele carriers. Most events (479 of 488 98.2%) among those with ARIA-E resolved radiographically; 404 of 488 (82.8%) resolved within 16 weeks. In the placebo group, 29 of 1076 participants (2.7%) had ARIA-E (apolipoprotein E ε4 carriers: 16 of 742 2.2%; noncarriers, 13 of 334 3.9%). ARIA-microhemorrhage and ARIA–superficial siderosis occurred in 197 participants (19.1%) and 151 participants (14.7%), respectively. CONCLUSIONS AND RELEVANCE: In this integrated safety data set from EMERGE and ENGAGE, the most common adverse event in the 10-mg/kg group was ARIA-E, which occurred in 362 of the 1029 patients (35.2%) in the 10-mg/kg group with at least 1 postbaseline MRI scan, with 94 patients (26.0%) experiencing associated symptoms. The most common associated symptom was headache. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifiers: NCT02484547, NCT02477800
Abstract
TianQin is a planned space-based gravitational wave (GW) observatory consisting of three Earth-orbiting satellites with an orbital radius of about $10^5 \, {\rm km}$. The satellites will ...form an equilateral triangle constellation the plane of which is nearly perpendicular to the ecliptic plane. TianQin aims to detect GWs between $10^{-4} \, {\rm Hz}$ and $1 \, {\rm Hz}$ that can be generated by a wide variety of important astrophysical and cosmological sources, including the inspiral of Galactic ultra-compact binaries, the inspiral of stellar-mass black hole binaries, extreme mass ratio inspirals, the merger of massive black hole binaries, and possibly the energetic processes in the very early universe and exotic sources such as cosmic strings. In order to start science operations around 2035, a roadmap called the 0123 plan is being used to bring the key technologies of TianQin to maturity, supported by the construction of a series of research facilities on the ground. Two major projects of the 0123 plan are being carried out. In this process, the team has created a new-generation $17 \, {\rm cm}$ single-body hollow corner-cube retro-reflector which was launched with the QueQiao satellite on 21 May 2018; a new laser-ranging station equipped with a $1.2 \, {\rm m}$ telescope has been constructed and the station has successfully ranged to all five retro-reflectors on the Moon; and the TianQin-1 experimental satellite was launched on 20 December 2019—the first-round result shows that the satellite has exceeded all of its mission requirements.
Imbalanced classes and dimensional disasters are critical challenges in medical image classification. As a classical machine learning model, the n-gram model has shown excellent performance in ...addressing this issue in text classification. In this study, we proposed an algorithm to classify medical images by extracting their n-gram semantic features. This algorithm first converts an image classification problem to a text classification problem by building an n-gram corpus for an image. After that, the algorithm was based on the n-gram model to classify images. The algorithm was evaluated by two independent public datasets. The first experiment is to diagnose benign and malignant thyroid nodules. The best area under the curve (AUC) is 0.989. The second experiment is to diagnose the type of fundus lesion. The best result is that it correctly identified 86.667% of patients with dry age-related macular degeneration (AMD), 93.333% of patients with diabetic macular edema (DME), and 93.333% of normal individuals.
Capacitive transducers are the core of electrostatic space accelerometers and have been applied in several space science missions. However, the noise of the front-end circuit in a capacitive ...transducer is a major limitation to capacitance resolution. The current theoretical models cannot accurately and comprehensively describe the performance of the front-end circuit in an ultra-high precision capacitive transducer. In this study, we modified the sensitivity and noise models of the front-end circuit and verified them by precision experiments. Under the guidance of the corrected models, we optimized the total stray capacitance by thickening the insulating layer between the shield and signal from 123 pF to 38 pF, thereby reducing the noise to 0.08 aF/Hz<inline-formula> <tex-math notation="LaTeX">^{\text {1/2}} </tex-math></inline-formula>. We believe that this work will support the development of an ultrasensitive electrostatic accelerometer for application in space science missions.
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Background: SIRPα-Fc-CD40L is a hexameric, bi-functional fusion protein consisting of SIRPα linked to CD40L via an inert Fc linker. This molecule competitively inhibits CD47 to enhance tumor ...cell phagocytosis and activates CD40 to increase antigen processing and cross-presentation by antigen presenting cells (APCs) to CD8 T cells, thus bridging innate and adaptive immunity. Methods: This first-in-human, Phase 1 dose escalation study evaluated SL-172154 in patients (pts) with advanced platinum resistant ovarian, fallopian tube and primary peritoneal cancers (PROC). SL-172154 was administered intravenously across 5 dose levels (0.1, 0.3, 1.0, 3.0, 10mg/kg). Dose escalation followed a modified toxicity probability interval 2 design. Objectives included evaluation of safety, dose-limiting toxicity (DLT), recommended phase 2 dose, pharmacokinetic and pharmacodynamic (PD) parameters, and antitumor activity per RECIST 1.1. Results: As of 3 Jan 2023, 27 pts (median age 66 years range 33-85; median of 4 prior systemic therapies range 2-9) with ovarian (70%), fallopian tube (15%) or primary peritoneal (15%) cancer were dosed. Treatment-emergent AEs (>15%) regardless of grade (G) included infusion related reaction (IRR) (67%), fatigue (44%), nausea (33%), back pain (26%), constipation, diarrhea (both 22%), decreased appetite and pruritus (both 19%). There was one DLT of G3 ALT increased at 10mg/kg requiring dose interruption for resolution. A maximum tolerated dose was not reached. G3/4 treatment-related AEs (>1pt) were AST increased (G3) and lymphopenia (G4), each in 2 pts (7%); all were fully resolved with no dose modifications. There were no fatal AEs, no AEs that led to drug discontinuation and no events of cytokine release syndrome. The frequency of IRR events increased with increasing dose, and slowing the rate of infusion was utilized for mitigation. SL-172154 Cmax and AUC increased with dose with greater than proportional exposure noted at 3 and 10mg/kg potentially due to target saturation. These findings were supported by dose-dependent target engagement of CD47 and CD40 on CD4 T cells and B cells respectively, approaching 100% by 3 mg/kg. Rapid dose-dependent egress of CD40+ B cells was maximal at ≥3mg/kg. SL-172154 induced dose-dependent responses in IL-12, CXCL-8, CXCL-10, IL-10, CCL2, CCL20, and CCL22, which also approached a plateau at ≥3mg/kg. Analysis of peripheral and tumor immunophenotypes and anti-drug antibodies in response to SL-172154 is ongoing and will be presented. Best response was stable disease in 6/27 response evaluable (22%) pts. Conclusions: SL-172154 is well tolerated in heavily pretreated PROC pts. IRRs were readily manageable. Maximal CD47 and CD40 target engagement and CD40-dependent PD effects were observed with ≥3mg/kg SL-172154. 3mg/kg is a safe, tolerable, and pharmacologically active dose for evaluation in combination studies in pts with PROC. Clinical trial information: NCT04406623 .
High-precision, continuously variable weak force testing is required for high-precision drag-free control with micro-thrust of spacecrafts, which is a key technology for space gravitational wave ...detection programs, such as TianQin, LISA, and Taiji. The continuously variable micro-thrust range is 0.1∼100μN, and the noise is below 0.1 μNHz−1/2 from 10−4Hz to 1 Hz. The torsion pendulum is considered as the most classical weak force measurement tool. However, the large response of non-sensitive modes makes it unsuitable for dynamic weak force measurements. In this study, a dynamic test system is developed for continuously varying weak forces using a torsion pendulum. We pre-applied a stress to the torsion pendulum using a double wire structure, which can effectively reduce the interference of other modes, and used feedback control to improve the stability. The evaluation results obtained using the external continuously variable electrostatic force indicate that the measurement range of the system covers 100 μN, the response time is approximately 1.6 s, and the noise is below 0.1 μNHz−1/2 from 0.9×10−4Hz to 1.4 Hz, which can meet the requirements of the micro-thrust test in space gravitational wave detection missions.
•A torsion pendulum with pre-stress enhances the non-sensitive directional stiffness.•Using the system dynamic response function to evaluate the weak force performance.•The results meet the requirements of space-borne gravitational wave detection.
•To obtain the accurate correction coefficient, a new pilot tone correction method based on LSM is also proposed to evaluate experimental results.•After pilot tone correction, the phase fluctuation ...is mostly less than 10 µrad.•The correlation between the signal corrected before and after by LSM method is less than half of that by NPT method.•The noise floor of the phasemeter was about 5 µrad/√Hz, meets the TianQin requirement of 1 pm/√Hz.
As a central payload of TianQin space-borne gravitational wave detector, inter satellite laser interferometer allows to measure distance variance with extremely high precision. The readout system, or phasemeter, is often based on all digital phase locked loop in an FPGA. However, sampling jitter is one of the main inevitable noise sources during digitization. Here we use the pilot tone correction to suppress sampling jitter noise. To obtain accurate correction coefficient rather than preset values by normal pilot tone (NPT) correction, a least squares method (LSM) is presented. The experimental results show that the noise floor after pilot tone correction reaches 5 µrad/Hz1/2, which meets the TianQin project displacement noise requirement of 1 pm/Hz1/2. Besides, the correlation between the signal corrected before and after by LSM method is less than half of that by NPT method.
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