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This article examines the optimal choice strategy of online-to-offline (O2O) food delivery mode for a merchant. In practice, there are four modes that are widely adopted by merchants: 1) The self-built platform and self-delivery (Mode SS); 2) the self-built platform and third-party delivery (Mode ST); 3) the third-party platform and self-delivery (Mode TS); and 4) the third-party platform and third-party delivery (Mode TT). First, we establish the merchant's profit model under each mode. Then, by comparing the merchant's profits under different modes, we analyze the optimal choice strategy of food delivery mode for the merchant. The results show that when third party service providers provide delivery services (TPSPs), if the advertising effect generated by the self-delivery is large and the consumer benefit brought by the third-party platform's promotion is small, the merchant should choose SS; if the advertising effect and the consumer benefit are both small (large), the merchant should choose ST (TS); if the advertising effect is small and the consumer benefit is large, the merchant should choose TT. Furthermore, from the perspective of the O2O food delivery system, TS (TT) is the best mode if the advertising effect is large (small).

Human diseases are traditionally studied as singular, independent entities, limiting researchers’ capacity to view human illnesses as dependent states in a complex, homeostatic system. Here, using time-stamped clinical records of over 151 million unique Americans, we construct a disease representation as points in a continuous, high-dimensional space, where diseases with similar etiology and manifestations lie near one another. We use the UK Biobank cohort, with half a million participants, to perform a genome-wide association study of newly defined human quantitative traits reflecting individuals’ health states, corresponding to patient positions in our disease space. We discover 116 genetic associations involving 108 genetic loci and then use ten disease constellations resulting from clustering analysis of diseases in the embedding space, as well as 30 common diseases, to demonstrate that these genetic associations can be used to robustly predict various morbidities.

Using Sentinel-1A data in 2021, the displacement of Tomur Glacier in the radar line of sight is obtained by repeated orbit differential interferometry. By introducing ice flow factor and combining glacier slope, the vertical deformation is extracted as the surface elevation change. The results of the study found that the overall average annual elevation change of Tomur Glacier decreased by -14.03m, with an average decrease of -0.26 . The reliability of the model was verified, and the results of the comparative study revealed that the glacier thinning rate has been increasing in recent years, and the trend of glacier retreat is becoming more severe.

Spontaneous low-frequency oscillations (LFO) have been widely studied in cerebrovascular disease, but little is known about their role in Moyamoya disease (MMD). The objective of this study was to assess the value of spontaneous LFO in MMD based on wavelet analysis of near-infrared spectroscopy (NIRS) signals.Sixty-four consecutive idiopathic adult patients were prospectively enrolled. The regional tissue oxygenation index (TOI) obtained from continuous NIRS signals. Five frequency intervals of spontaneous LFO (I, 0.0095-0.02 Hz; II, 0.02-0.06 Hz; III, 0.06-0.15 Hz; IV, 0.15-0.40 Hz; and V, 0.40-2.00 Hz) were extracted based on wavelet analysis. The data were compared between the patients and healthy control groups. Clinical features, cognitive function, and disease progression of MMD were analyzed using TOI and frequency interval data.Compared with the healthy control group, patients with MMD had a higher cerebral TOI in both hemispheres. Based on wavelet analysis, the spontaneous LFO of TOI was found to be significantly lower for patients with MMD in frequency intervals II to IV than that for the controls. The spontaneous LFO of TOI is also related to the Suzuki stages in intervals II to IV, stroke in interval III, and cognitive impairment in intervals III to Ⅳ.There were significant differences in spontaneous LFO between patients with MMD and healthy controls. The change in spontaneous LFO in MMD is related to Suzuki stage, cerebral infarction, and cognitive impairment. This might be an effective method for evaluating the severity and monitoring the progression of MMD.

In satellite-terrestrial integrated networks, it is a common practice to schedule real-time tasks from low Earth orbit (LEO) satellites to ground stations (GSs) for data processing. However, the joint task scheduling and resource allocation under unknown environment dynamics (e.g., transmission latency) remains to be a challenging problem. First, the tradeoff between task latencies and energy consumption should be carefully considered when making decisions to minimize task latencies under time-averaged energy consumption constraints. Second, to learn the environment uncertainties and minimize the system performance loss (i.e., regret) in terms of task latencies, both online feedback and offline history should be leveraged efficiently, and the accompanying exploration-exploitation tradeoff should be dealt with in a proper way. In this paper, we formulate the joint task scheduling and resource allocation problem as a constrained combinatorial multi-armed bandit (CMAB) problem. To solve the problem, by integrating online learning, online control, and offline historical information, we propose a Task scheduling and Resource allocation scheme with Data-driven Bandit Learning called TRDBL. Our theoretical and numerical results show that TRDBL achieves a sublinear time-averaged regret while satisfying the time-averaged energy consumption constraints.

Current follicle-stimulating hormone (FSH) drugs meet safety criteria but have suboptimal efficacy, poor patient compliance, and high cost. Alternative FSH-like drugs would help to meet the high market demand. Here, we evaluated X002, an FSH–Fc fusion protein, for bioactivity and half-life in vitro and in vivo. In all cases, the effects of X002 were compared with those of a commercially available short-acting FSH recombinant hormone. First, female Kunming mice (age, 21 to 24 d) were stimulated with pregnant mare serum gonadotropin (PMSG) for 46 h, after which naked oocytes were harvested, treated with X002 or the comparison agent at 37 °C for 4 h, and then evaluated for germinal vesicle breakdown. Second, cumulus–oocyte complexes (COC) were collected from PMSG-stimulated mice and cocultured with X002 or the comparison agent for 14 h; the COC diameters were then measured, and the expression of genes involved in COC expansion were evaluated using quantitative RT-PCR analysis. Third, to assess the pharmacokinetics of X002, female Sprague–Dawley rats (age, 6 to 8 wk) were injected subcutaneously with X002 or the comparison agent; serum samples then were collected at various times and assessed via ELISA. Fourth, to evaluate X002 pharmacodynamics, 26-d-old female Sprague–Dawley rats were treated with X002 or the comparison agent; 84 h later, the rats were stimulated with human chorionic gonadotropin (hCG). At 12 h after hCG injection, euthanasia was performed. Ovaries were removed and weighed, and serum levels of estradiol and progesterone were measured. Finally, to assess superovulation, the oocytes in the fallopian tubes were counted at 108 h after in vivo treatment of rats with X002 or the comparison agent. The data show that X002, a long-acting agent, promoted germinal vesicle breakdown and COC expansion in vitro and in vivo ovarian weight gain and superovulation to a degree similar to the short-acting comparison agent.

Alternative polyadenylation (APA) enables a gene to generate multiple transcripts with different 3′ ends, which is dynamic across different cell types or conditions. Many computational methods have been developed to characterize sample-specific APA using the corresponding RNA-seq data, but suffered from high error rate on both polyadenylation site (PAS) identification and quantification of PAS usage (PAU), and bias toward 3′ untranslated regions. Here we developed a tool for APA identification and quantification (APAIQ) from RNA-seq data, which can accurately identify PAS and quantify PAU in a transcriptome-wide manner. Using 3′ end-seq data as the benchmark, we showed that APAIQ outperforms current methods on PAS identification and PAU quantification, including DaPars2, Aptardi, mountainClimber, SANPolyA, and QAPA. Finally, applying APAIQ on 421 RNA-seq samples from liver cancer patients, we identified >540 tumor-associated APA events and experimentally validated two intronic polyadenylation candidates, demonstrating its capacity to unveil cancer-related APA with a large-scale RNA-seq data set.

Phage contamination is one of the significant problems in the food fermentation industry, which eventually causes economic losses to the industry. Here, we investigated the viability of Lactobacillus plantarum phage P1 and P2 using various biocides treatments (ethanol, isopropanol, sodium hypochlorite and peracetic acid). Results indicated that phage P1 and P2 could be completely inactivated by treatment with 75% ethanol for 5 min, followed by 400 ppm of sodium hypochlorite treatment for 5 min. Phage P2 could be completely inactivated in the reverse sequence, while 800 ppm of sodium hypochlorite was required to achieve a similar effect for phage P1. Moreover, 100% isopropanol could increase the inactivating effect of 75% ethanol. This study may provide basic information on using multiple antimicrobials for phage control in laboratories and food plants.

Objectives: Real-world data (RWD) from the clinical care of patients captured through Electronic Health Records (EHRs) is a valuable resource for research. Understanding the relationship between characteristics and outcomes of patients treated in the real world and in oncology clinical trials by producing evaluable trial-like populations from RWD can advance clinical and regulatory knowledge. Methods: RWD from the Flatiron Health EHR-derived, de-identified, longitudinal database were compared with pooled patient-level data from the three randomized controlled trials (RCTs) supporting regular approval of CDK4/6 inhibitors for patients with previously untreated hormone receptor-positive, HER- metastatic breast cancer (mBC). The RCT group included patients who received aromatase inhibitor (AI) monotherapy (RCT-control), and an experimental group (RCT-experimental) that received a cyclin dependent kinase 4/6 (CDK4/6) inhibitor + AI. The real-world control group (rwCG) of patients initiating AI monotherapy was selected using the key eligibility criteria across the RCTs. Patients from the rwCG were matched to the RCT-control and the RCT-experimental patients, respectively. Matching (1:1) was performed through the propensity score (PS) method adjusting for baseline covariates of age, race, site of disease, ECOG PS, and metastatic disease (recurrent, De novo). Multiple imputation (MI) was adopted to impute missing ECOG PS in the rwCG due to the high percentage of missingness. Progression-free survival (PFS) and overall survival (OS) were analyzed for the following groups: A) rwCG and RCT- control B) rwCG and RCT-experimental and C) RCT-control and RCT-experimental. To assess the feasibility of RCT control arm replication, we assessed whether the trial replication hazard ratio (HR) estimates from analysis B were within the published trial estimates’ 95% confidence intervals (CIs). HR and their 95% CIs were estimated using Cox proportional hazard model. Results: A total of 1292 patients were selected from the EHR-derived database to comprise the rwCG and 1827 patients were pooled across the RCTs (1106 for RCT-experimental and 721 patients for RCT-control). With MI, 520 rwCG patients were matched to the RCT-control for analysis A, and 658 rwCG patients were matched to the RCT-experimental for analysis B. The results are summarized in Table 1. The point estimate of the PFS HR comparing the rwCG to the RCT-experimental was within the 95% CIs for three RCTs. For OS, the point estimate of the HR was within the 95% CI for MONALESSA-2 but not for PALOMA-2. Conclusion: PFS and OS appeared longer in the RCT-control than in the rwCG, and the difference was more pronounced in OS. While it appears that there is greater similarity for PFS than for OS based on the results of the matched analysis of RCT- experimental vs. rwCG, evaluation of PFS results are limited by substantial differences in assessment and outcome definitions for progression between RCT-control (RECIST) and rwCG. Despite PS matching, there are apparent differences between patients treated in RCTs and routine practice, highlighting the importance of clinical setting, trial selection, study design, and use of randomization. There are still outstanding feasibility questions on the evaluation of OS and further research is required to understand factors potentially impacting the outcomes between RCTs and RWD. Table 1: Estimated Treatment Effects in PFS and OS, rwCG vs RCT-control vs RCT-experimental Citation Format: Christy Osgood, Jiaxin Fan, Xin Gao, Catherine Keane, Jonathan Bryan, James P. Roose, Erik Bloomquist, Aracelis Torres, Shrujal Baxi, Nathan Nussbaum, Fatima Rizvi, Shenghui Tang, Irene Nunes, Julia Beaver, Donna R. Rivera, Lynn Howie, Prashni Paliwal, Laleh Amiri-Kordestani. Feasibility of generating an external control comparator using RWD by matching with previously conducted RCTs: CDK4/6 Inhibitors for the treatment of Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-03.

At present, the problem of unbalanced and inadequate development in our country is most prominent in rural areas, mainly manifested in: periodical oversupply and undersupply of agricultural products coexist, the quality of agricultural supply needs to be improved urgently; The overall level of rural development needs to be improved urgently. The implementation of the rural revitalization strategy is an inevitable requirement to solve the contradiction between the people's growing needs for a better life and unbalanced and inadequate development, it is an inevitable requirement to realize the "two centenary" goals, and it is an inevitable requirement to realize the common prosperity of all people. Inevitably required.

Systemic elimination of senescent cells using senolytic drugs presents therapeutic effects on age-related diseases, including senile osteoporosis. However, low bioavailability and potential side effects of senolytics restrict clinical application. Therefore, we developed a bone-targeted delivery system for senolytics to effective treatment of senile osteoporosis. In this study, quercetin was screened out as the ideal senolytics for eliminating senescent BMSCs. Treatment of quercetin efficiently decreased the senescence markers in senescent BMSCs models. After treatment with quercetin in vitro, cell mitosis and calcification staining assay confirmed that the proliferation and osteogenesis of the senescent BMSCs populations were enhanced. To enhance the effectiveness and minimize the side effect of treatment, liposomes decorated with bone affinity peptide (DSS)

In patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC.In this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated.Between 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]).This real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.

Today, timestamped web documents related to a general news query flood the Internet, and timeline summarization targets this concisely by summarizing the evolution trajectory of events along the timeline. Unlike traditional document summarization, timeline summarization needs to model the time series information of the input events and summarize important events in chronological order. To tackle this challenge, in this article we propose our Unified Timeline Summarizer, which can generate abstractive and extractive timeline summaries in time order. Concretely, in the encoder part, we propose a graph-based event encoder that relates multiple events according to their content dependency and learns a global representation of each event. In the decoder part, to ensure the chronological order of the abstractive summary, we propose to extract the feature of event-level attention in its generation process with sequential information retained and use it to simulate the evolutionary attention of the ground truth summary. The event-level attention can also be used to assist in extracting a summary, where the extracted summary also comes in time sequence. We augment the previous Chinese large-scale timeline summarization dataset and collect a new English timeline dataset. Extensive experiments conducted on these datasets and on the out-of-domain Timeline 17 dataset show that our Unified Timeline Summarizer achieves state-of-the-art performance in terms of both automatic and human evaluations. 1

Fucoidans isolated from brown seaweeds are potential ingredients in the cosmetic industry. In our preosvious study, a fucoidan was isolated from the brown seaweed Turbinaria ornata (TO-F10) and the anti-inflammatory effect of TO-F10 was evaluated. In order to further explore the potential of TO-F10 in cosmetics, in the present study, antioxidant and photoprotective effects of TO-F10 were investigated. TO-F10 remarkably protected Vero cells against AAPH-stimulated cell death by reducing apoptosis via scavenging intracellular reactive oxygen species (ROS). In addition, TO-F10 increased the survival rate of AAPH-treated zebrafish by suppressing oxidative stress displayed in reducing the levels of ROS, cell death, and lipid peroxidation. Furthermore, TO-F10 effectively attenuated UVB-induced in vitro and in vivo photodamage. TO-F10 increased the viability of UVB-irradiated human keratinocytes via suppressing apoptosis by reducing the intracellular ROS level. Besides, TO-F10 effectively attenuated in vivo photodamage stimulated by UVB irradiation via inhibiting oxidative stress and inflammatory response in zebrafish. These results demonstrate that TO-F10 possesses in vitro and in vivo antioxidant and photoprotective effects, and suggest TO-F10 is a potential ingredient in the cosmetic industry.

Combining the stochastic surface walking, global neural network potential and molecular dynamics methods, the atomic origins of capacity degradations and safety issues in highly delithiated LixCoO2 are revealed.

In this study, a unique mechanical exfoliation route, liquid-electric effect, is applied to prepare few-layer black phosphorene using black phosphorus powders through liquid pulsed discharge.