National Natural Science Foundation Of China Research Articles

Cytoskeletal and inter-cellular junction remodelling in endometrial organoids under oxygen-glucose deprivation: a new potential pathological mechanism for thin endometria.

What is the pathological mechanism involved in a thin endometrium, particularly under ischaemic conditions? Endometrial dysfunction in patients with thin endometrium primarily results from remodelling in cytoskeletons and cellular junctions of endometrial epithelial cells under ischemic conditions. A healthy endometrium is essential for successful embryo implantation and subsequent pregnancy; ischemic conditions in a thin endometrium compromise fertility outcomes. We recruited 10 patients with thin endometrium and 15 patients with healthy endometrium. Doppler ultrasound and immunohistochemical results confirmed the presence of insufficient endometrial blood perfusion in patients with thin endometrium. Organoids were constructed using healthy endometrial tissue and cultured under oxygen-glucose deprivation (OGD) conditions for 24 h. The morphological, transcriptomic, protein expression, and signaling pathway changes in the OGD organoids were observed. These findings were validated in both thin endometrial tissue and healthy endometrial tissue samples. Endometrial thickness and blood flow were measured during the late follicular phase using transvaginal Doppler ultrasound. Endometrial tissue was obtained via hysteroscopy. Fresh endometrial tissues were used for the generation and culture of human endometrial organoids. Organoids were cultured in an appropriate medium and subjected to OGD to simulate ischemic conditions. Apoptosis and cell death were assessed using Annexin-V/propidium iodide staining. Immunofluorescence analysis, RNA sequencing, western blotting, simple westerns, immunohistochemistry, and electron microscopy were conducted to evaluate cellular and molecular changes. Patients with thin endometrium showed significantly reduced endometrial thickness and altered blood flow patterns compared to those with healthy endometrium. Immunohistochemical staining revealed fewer CD34-positive blood vessels and glands in the thin endometrium group. Organoids cultured under OGD conditions exhibited significant morphological changes, increased apoptosis, and cell death. RNA-seq identified differentially expressed genes related to cytoskeletal remodeling and stress responses. OGD induced a strong cytoskeletal reorganization, mediated by the RhoA/ROCK signaling pathway. Additionally, electron microscopy indicated compromised epithelial integrity and abnormal cell junctions in thin endometrial tissues. Upregulation of hypoxia markers (HIF-1α and HIF-2α) and activation of the RhoA/ROCK pathway were also observed in thin endometrial tissues, suggesting ischemia and hypoxia as underlying mechanisms. none. The study was conducted in an in vitro model, which may not fully replicate the complexity of in vivo conditions. This research provides a new three-dimensional in vitro model of thin endometrium, as well as novel insights into the pathophysiological mechanisms of endometrial ischaemia in thin endometrium, offering potential avenues for identifying therapeutic targets for treating fertility issues related to thin endometrium. This study was supported by the National Natural Science Foundation of China (81925013); National Key Research and Development Project of China (2022YFC2702500, 2021YFC2700303, 2021YFC2700601); the Capital Health Research and Development Project (SF2022-1-4092); the National Natural Science Foundation of China (82288102, 81925013, 82225019, 82192873); Special Project on Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application (Z211100002921054); the Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation(TFJC2023010001). The authors declare that no competing interests exist.

Enhancer demethylation-regulated gene score identified molecular subtypes, inspiring immunotherapy or CDK4/6 inhibitor therapy in oesophageal squamous cell carcinoma

The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. Utilising pre-treatment multi-omics data from an ESCC dataset (n=310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by invitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n=60) and bulk-seq (n=310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n=42), kidney renal clear cell carcinoma (KIRC, n=181), and bladder urothelial carcinoma (BLCA, n=348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n=26), melanoma (n=18), prostate cancer (n=15) cells, and PDX models derived from patients with pancreatic cancer (n=30). Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).

Satisficing Approach to On-Demand Ride Matching

Online ride-hailing platforms have developed into an integral part of the transportation infrastructure in many countries. The primary task of a ride-hailing platform is to match trip requests to drivers in real time. Although both passengers and drivers prefer a prompt pickup to initiate the trips, it is often difficult to find a nearby driver for every passenger. If the driver is far from the pickup point, the passenger may cancel the trip while the driver is heading toward the pickup point. For the platform to be profitable, the trip cancellation rate must be maintained at a low level. We propose a computationally efficient data-driven approach to ride matching, in which a pickup time target is imposed on each trip request and an optimization problem is formulated to maximize the joint probability of all the pickup times meeting the targets. By adjusting pickup time targets individually, this approach may assign more high-value trip requests to nearby drivers, thus boosting the platform’s revenue while maintaining a low cancellation rate. In numerical experiments, the proposed approach outperforms several ride-matching policies used in practice. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms—Discrete. Funding: This work of D. Rong and X. Sun was supported in part by the National Natural Science Foundation of China [Grant 71971165], the National Key Research and Development Program of China [Grant 2021YFB3301801], the MOE Project of Humanities and Social Science of China [Grant 19YJE630002], and the Soft Science Research Program of Shannxi [Grant 2018KRZ005]. The work of S. He was supported in part by the Singapore Ministry of Education Social Science Research Council [Grant MOE2022-SSRTG-029]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2021.0210 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2021.0210 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .

Ground states and first radial excitations of vector tetraquark states with explicit P-waves via QCD sum rules* *Supported by the National Natural Science Foundation of China (12175068)

In this study, we chose the diquark-antidiquark type four-quark currents with an explicit P-wave between the diquark and antidiquark pairs to study the ground states and first radial excitations of the hidden-charm tetraquark states with quantum numbers . We also obtained the lowest vector tetraquark masses and made possible assignments of the existing states. There indeed exists a hidden-charm tetraquark state with at an energy of approximately 4.75 GeV as the first radial excitation that accounts for the BESIII data.

Optimal use of β-lactams in neonates: machine learning-based clinical decision support system

BackgroundAccurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. MethodsFive β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. FindingsFor a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT>MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was > 80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. InterpretationAn ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses. FundingThis work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

Cross section measurement for the 232Th(n, f ) reaction in the 4.50−5.40 MeV region using a time projection chamber* *This study was financially Supported by the National Natural Science Foundation of China (12075008), the Key Laboratory of Nuclear Data foundation (6142A08200103), the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515120027), and the State Key Laboratory of Nuclear

Accurate cross sections of neutron induced fission reactions are required in the design of advanced nuclear systems and the development of fission theory. Time projection chambers (TPCs), with their track reconstruction and particle identification capabilities, are considered the best detectors for high-precision fission cross section measurements. The TPC developed by the back-streaming white neutron source (Back-n) team of the China Spallation Neutron Source (CSNS) was used as the fission fragment detector in measurements. In this study, the cross sections of the 232Th(n, f) reaction at five neutron energies in the 4.50−5.40 MeV region were measured. The fission fragments and α particles were well identified using our TPC, which led to a higher detection efficiency of the fission fragments and smaller uncertainty of the measured cross sections. Ours is the first measurement of the 232Th(n, f) reaction using a TPC for the detection of fission fragments. With uncertainties less than 5%, our cross sections are consistent with the data in different evaluation libraries, including JENDL-4.0, ROSFOND-2010, CENDL-3.2, ENDF/B-VIII.0, and BROND-3.1, whose uncertainties can be reduced after future improvement of the measurement.

Simulation and Modelling as Catalysts for Renewable Energy: A Bibliometric Analysis of Global Research Trends

This study investigates the application of advanced simulation and modeling technologies to optimize the performance and reliability of renewable energy systems. Given the urgent need to combat climate change and reduce greenhouse gas emissions, integrating renewable energy sources into existing infrastructure is essential. Using bibliometric methods, our research spans from 1979 to 2023, identifying key publications, institutions, and trends. The analysis revealed a significant annual growth rate of 16.78% in interest in simulation and modeling, with a notable surge in published articles, reaching 921 in 2023. This indicates heightened research activity and interest. Our findings highlight that optimization, policy frameworks, and energy management are central themes. Leading journals like Energies, Energy, and Applied Energy play significant roles in disseminating research. Key findings also emphasize the importance of international collaboration, with countries like China, the USA, and European nations playing significant roles. The three-field plot analysis demonstrated interconnections between keywords, revealing that terms like “renewable energy sources”, “optimization”, and “simulation” are central to the research discourse. Core funding agencies, such as the National Natural Science Foundation of China (NSFC) and the European Union, heavily support this research. This study underscores the importance of policies and sustainability indicators in promoting renewable energy technologies. These insights emphasize the need for ongoing innovation and interdisciplinary collaboration to achieve a sustainable energy future.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study

Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25mg days 1-21 plus dexamethasone 40mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p<0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n=9) and 70% (n=16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n=7) complete remission, 57% (n=13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p=0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p=0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n=12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n=2, 9%), glucose intolerance (n=2, 9%), edema (n=2, 9%), insomnia (n=1, 4%), and tremor (n=1, 4%). Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial

Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0-2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adults

Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score(derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.

Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study

The combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients. This open-label, single-center, single-arm phase I study utilizing a "3+3" design enrolled children with relapsed/refractory (R/R) solid tumors. Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50mg/m2) in combination with cyclophosphamide (1500mg/m2), mesna (1500mg/m2), and vincristine (1.5mg/m2, maximum 2mg) once every 3 weeks. The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612. Between January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30mg/m2. The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of TP53 mutation may be an adverse prognostic factor. The VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30mg/m2 once every 3 weeks. CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].

Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase

The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking. We extracted adverse event reports of hematological malignancies (HMs) patients with clearly definable SPMs from the FAERS and VigiBase databases (2017-2023). Disproportionality analysis using reporting odds ratio (ROR) and adjusted ROR was performed to assess associations between SPMs and CAR-T therapy. Time-to-onset analysis explored factors affecting SPM manifestation. SPMs post CAR T-cell therapy include HMs and solid tumors. T-cell lymphoma and myelodysplastic syndromes were consistently identified as positive signals across the overall and subgroup analyses. Hematological SPMs showed earlier onset with increasing annual incidence post CAR-T therapy, whereas solid tumors exhibit delayed manifestation. SPMs in CAR-T recipients had significantly earlier onset than non-recipients. Furthermore, age-specific characteristics reveal earlier SPM manifestations in pediatric, adolescent, and young adult populations compared to older populations post CAR-T therapy. The current SPM profile highlights the necessity of long-term safety monitoring for all CAR-T recipients given the observed yearly increase of SPMs. Customizing long-term SPM screening across different age groups may enhance early detection and intervention strategies, ultimately improving patient outcomes in the follow-up of CAR-T recipients. This work was supported by grants from the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020), the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750, 82172811, and 82260546), the Guangdong Basic and Applied Basic Research Foundation (Guangdong-Guangzhou Joint Funds) (2022A1515111212), and the Science and Technology Program of Guangzhou (2023A04J1257).

Searching for 76Ge neutrinoless double beta decay with the CDEX-1B experiment* *Supported by the National Key Research and Development Program of China (2017YFA0402201, 2022YFA1604701, 2022YFA1605000) and the National Natural Science Foundation of China (12322511, 12175112, 12005111, 11725522)

We operated a p-type point contact high purity germanium (PPCGe) detector (CDEX-1B, 1.008 kg) in the China Jinping Underground Laboratory (CJPL) for 500.3 days to search for neutrinoless double beta ( ) decay of 76Ge. A total of 504.3 kg day effective exposure data was accumulated. The anti-coincidence and the multi/single-site event (MSE/SSE) discrimination methods were used to suppress the background in the energy region of interest (ROI, 1989–2089 keV for this work) with a factor of 23. A background level of 0.33 counts/ (keV kg yr) was realized. The lower limit on the half life of 76Ge decay was constrained as , corresponding to the upper limits on the effective Majorana neutrino mass: 3.2–7.5 .

Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcoma

Current surveillance modalities of osteosarcoma relapse exhibit limited sensitivity and specificity. Although circulating tumor DNA (ctDNA) has been established as a biomarker of minimal residual disease (MRD) in many solid tumors, a sensitive ctDNA detection technique has not been thoroughly explored for longitudinal MRD detection in osteosarcoma. From August 2019 to June 2023, 59 patients diagnosed with osteosarcoma at the First Affiliated Hospital of Sun Yat-sen University were evaluated in this study. Tumor-informed MRD panels were developed through whole exome sequencing (WES) of tumor tissues. Longitudinal blood samples were collected during treatment and subjected to multiplex PCR-based next-generation sequencing (NGS). Kaplan-Meier curves and Log-rank tests were used to compare outcomes, and Cox regression analysis was performed to identify prognostic factors. WES analysis of 83 patients revealed substantial mutational heterogeneity, with non-recurrent mutated genes accounting for 58.1%. Tumor-informed MRD panels were successfully obtained for 85.5% of patients (71/83). Among 59 patients with successful MRD panel customization and available blood samples, 13 patients exhibited positive ctDNA detection after surgery. Patients with negative post-operative ctDNA had better event-free survival (EFS) compared to those with positive ctDNA, at 1-6 months after surgery, after adjuvant chemotherapy, and more than 6 months after surgery (p<0.05). In both univariate and multivariate Cox regression analysis, ctDNA results emerged as a significant predictor of EFS (p<0.05). ctDNA detection preceded positive imaging in 5 patients, with an average lead time of 92.6 days. Thirty-nine patients remained disease-free, with ctDNA results consistently negative or turning negative during follow-up. Our study underscores the applicability of tumor-informed deep sequencing of ctDNA in osteosarcoma MRD surveillance and, to our knowledge, represents the largest cohort to date. ctDNA detection is a significant prognostic factor, enabling the early identification of tumor relapse and progression compared to standard imaging, thus offering valuable insights in guiding osteosarcoma patient management. The Grants of National Natural Science Foundation of China (No. 82072964, 82072965, 82203798, 82203026), the Natural Science Foundation of Guangdong (No. 2023A1515012659, 2023A1515010302), and the Regional Combination Project of Basic and Applied Basic Research Foundation of Guangdong (No. 2020A1515110010).

Shadows and weak gravitational lensing for black holes within Einstein-Maxwell-scalar theory* *Supported by the National Natural Science Foundation of China (11675143), and the National Key Research and Development Program of China (2020YFC2201503). M.A and B.A wish to acknowledge the support from Research Grant F-FA-2021-432 of the Ministry of Higher Education, Science and Innovations of the Republic of Uzbekistan.

In this study, we investigated the optical properties of charged black holes within the Einstein-Maxwell-scalar (EMS) theory. We evaluated the shadow cast by these black holes and obtained analytical solutions for both the radius of the photon sphere and that of the shadow. We observed that black hole parameters γ and β both influence the shadow of black holes. We also found that the photon sphere and shadow radius increase as a consequence of the presence of the parameter γ. Interestingly, the shadow radius decreases first and then remains unchanged owing to the impact of the parameter β. Finally, we analyzed the weak gravitational lensing and total magnification of lensed images around black holes. We found that the charge of the black holes and the parameter β both have a significant impact, reducing the deflection angle. Similarly, the same behavior for the total magnification was observed, also as a result of the effect of the charge of the black holes and the parameter β.

Signaling Targeting Cost Through List Price

Data analytics enable firms to offer personalized prices to targeted consumers but at a cost. We study a competitive personalized pricing game where the entrant is uncertain about the incumbent’s targeting cost. We demonstrate that implementing personalized pricing through a “list price-discount” scheme allows the incumbent to signal its targeting cost via the list price. This signaling mechanism is effective because the list price serves as a price ceiling, which limits the incumbent’s ability to extract consumer surplus through personalized discounts. The high-cost incumbent can strategically set its list price below the full-information level to separate itself from the low-cost incumbent. Interestingly, the high-cost incumbent prefers separating over pooling only when there is a moderate variation in the incumbents’ targeting costs. Personalized pricing can affect firms differently, benefiting the incumbent but hurting the entrant. Asymmetric information about targeting costs weakens the high-cost incumbent’s incentive to offer personalized discounts, resulting in lower total targeting costs and potentially increasing social surplus. These findings shed light on government regulations and transparency policies regarding personalized pricing. This paper was accepted by Dmitri Kuksov, marketing. Funding: P. Yu was supported by the National Natural Science Foundation of China [Grants 72371038 and 72033003]. J. Zhang was supported by the National Natural Science Foundation of China [Grants 72371061 and 72232001]. Supplemental Material: The online appendices are available at https://doi.org/10.1287/mnsc.2023.02031 .

Prospects for weighing neutrinos in interacting dark energy models using joint observations of gravitational waves and γ-ray bursts* *Supported by the National Natural Science Foundation of China (12305069, 11947022, 11975072, 11875102, 11835009), the National SKA Program of China (2022SKA0110200, 2022SKA0110203), the National 111 Project (B16009), and the Program of the Education Department of Liaoning Province, China (JYTMS20231695)

Cosmological observations can be used to weigh neutrinos, but this method is model-dependent, with results relying on the cosmological model considered. If we consider interactions between dark energy and dark matter, the neutrino mass constraints differ from those derived under the standard model. On the contrary, gravitational wave (GW) standard siren observations can measure absolute cosmological distances, helping to break parameter degeneracies inherent in traditional cosmological observations, thereby improving constraints on neutrino mass. This paper examines the constraints on neutrino mass within interacting dark energy (IDE) models and explores how future GW standard siren observations could enhance these results. For multi-messenger GW observations, we consider the joint observations of binary neutron star mergers by third-generation ground-based GW detectors and short γ-ray burst observations by missions similar to the THESEUS satellite project. Using current cosmological observations (CMB+BAO+SN), we obtain an upper limit on the neutrino mass in the IDE models of 0.15 (or 0.16) eV. With the inclusion of GW data, the upper limit on the neutrino mass improves to 0.14 eV. This indicates that in the context of IDE models, the improvement in neutrino mass constraints from GW observations is relatively limited. However, GW observations significantly enhance the constraints on other cosmological parameters, such as matter density parameter, the Hubble constant, and coupling strength between dark energy and dark matter.

An Efficient Scenario Reduction Method for Problems with Higher Moment Coherent Risk Measures

In this paper, we present an efficient scenario reduction method for optimization problems whose objective function is the higher moment coherent risk (HMCR) measures. Compared with existing approaches, our method places greater emphasis on the characteristics of optimization problems. Because the value of HMCR measures only depends on a small subset of scenarios that correspond to high cost or loss, our approach is based mostly on the concept of ineffective scenarios previously proposed in the literature, which entails identifying the scenarios whose removal from the problem results in no change of the optimal value. We test our method on a simple portfolio optimization problem with only nine risky assets and a realistic one with 50 risky assets and cardinality constraints. Results show that our scenario reduction method can yield a more accurate optimal solution and optimal value, along with a smaller reduced-scenario set. Even at the same reduction level, our method continues to outperform the existing scenario reduction methods. Interestingly, the portfolio produced by our method is also more diversified than others. History: Accepted by Pascal Van Hentenryck, Area Editor for Computational Modeling: Methods &amp; Analysis. Funding: This work was supported by the National Natural Science Foundation of China [Grants 71720107002 and U1901223]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0375 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0375 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .

Determination of the number of ψ(3686) events taken at BESIII* *The BESIII Collaboration thanks the staff of BEPCII and the IHEP computing center for their strong support. This work is supported in part by National Key R&D Program of China under Contracts Nos. 2020YFA0406300, 2020YFA0406400; National Natural Science Foundation of China (NSFC) under Contracts Nos. 12150004, 11635010, 11735014, 11835012, 11935015,

The number of ψ(3686) events collected by the BESIII detector during the 2021 run period is determined to be (2259.3±11.1)×106 by counting inclusive ψ(3686) hadronic events. The uncertainty is systematic and the statistical uncertainty is negligible. Meanwhile, the numbers of ψ(3686) events collected during the 2009 and 2012 run periods are updated to be (107.7±0.6)×106 and (345.4±2.6)×106, respectively. Both numbers are consistent with the previous measurements within one standard deviation. The total number of ψ(3686) events in the three data samples is (2712.4±14.3)×106.

Exploring global research trends in Chinese medicine for atherosclerosis: a bibliometric study 2012-2023.

While Traditional Chinese Medicine (TCM) boasts an extensive historical lineage and abundant clinical expertise in addressing atherosclerosis, this field is yet to be penetrated adequately by bibliometric studies. This study is envisaged to evaluate the contemporary scenario of TCM in conjunction with atherosclerosis over the preceding decade while also identifying forthcoming research trends and emerging topics via the lens of bibliometric analysis. Literature pertaining to TCM and atherosclerosis, circulated between January 1, 2012 and November 14, 2023, was garnered for the purpose of this research. The examination embraced annual publications, primary countries/regions, engaged institutions and authors, scholarly journals, references, and keywords, utilizing analytical tools like Bibliometrix, CiteSpace, ScimagoGraphica, and VOSviewer present in the R package. This field boasts a total of 1,623 scholarly articles, the majority of which have been contributed by China in this field, with significant contributions stemming from the China Academy of Traditional Chinese Medicine and the Beijing University of Traditional Chinese Medicine. Moreover, this field has received financial support from both the National Natural Science Foundation of China and the National Key Basic Research Development Program. Wang Yong tops the list in terms of publication count, while Xu Hao's articles take the lead for the total number of citations, positioning them at the core of the authors' collaborative network. The Journal of Ethnopharmacology leads with the most publications and boasts the greatest total number of citations. Principal research foci within the intersection of Chinese Medicine and Atherosclerosis encompass disease characteristics and pathogenic mechanisms, theoretical underpinnings and syndrome-specific treatments in Chinese medicine, potentialities of herbal interventions, and modulation exerted by Chinese medicines on gut microbiota. This analysis offers a sweeping survey of the contemporary condition, principal foci, and progressive trends in worldwide research related to Traditional Chinese Medicine (TCM) and atherosclerosis. It further delves into an in-depth dissection of prominent countries, research institutions, and scholars that have made noteworthy strides in this discipline. Additionally, the report analyzes the most cited articles, research developments, and hotspots in the field, providing a reference for future research directions for clinical researchers and practitioners.