Fundamental Research Funds Research Articles

Replicating and Digesting Anomalies in the Chinese A-Share Market

We replicate 469 anomaly variables similar to those studied by Hou et al. (2020) using Chinese A-share data and a reliable testing procedure with mainboard breakpoints and value-weighted returns. We find that 83.37% of the anomaly variables do not generate significant high-minus-low quintile raw return spreads. Further adjusting risk increases the failure rate slightly to 84.22% based on CAPM alphas and 86.99% based on Fama–French three-factor alphas. We show that the conventional procedure using all A-share breakpoints with equal-weighted returns for the anomaly test is indeed problematic as it assigns too much weight to microcaps and has a very limited investment capacity. The CH3-factor, CH4-factor, and q-factor models show the best performance over the whole sample period. The q-factor model is the best performer in the post-2007 subsample period after significant improvements occurred in China’s financial market environment, such as the completion of the split-share structure reform and the implementation of new accounting standards conforming to the International Financial Reporting Standards. The non–state-owned enterprise subsample in the post-2007 period is a cleaner sample in which the CH4-factor and q-factor models are the best performers. This paper was accepted by Lukas Schmid, finance. Funding: Z. Li acknowledges financial support from the National Natural Science Foundation of China [Grant 72103043] and the Fundamental Research Funds for the Central Universities in UIBE [Grants 19QN01 and 22PY053-72103043]. L. X. Liu acknowledges financial support from the National Natural Science Foundation of China [Grants 71872006 and 72273006]. L. X. Liu and X. Liu acknowledge financial support from the Guanghua Thought Leadership Platform of Peking University. K. C. J. Wei acknowledges partial financial support from the Research Grants Council of the Hong Kong Special Administrative Region, China [Grant 15507320]. The authors acknowledge financial support from the Guanghua School of Management, Peking University; the School of Banking and Finance, University of International Business and Economics; and the Non-PAIR Research Centre “Research Centre for Quantitative Finance” at Hong Kong Polytechnic University. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4904 .

Quantifying the Impact of Impact Investing

We propose a quantitative framework for assessing the financial impact of any form of impact investing, including socially responsible investing; environmental, social, and governance (ESG) objectives; and other nonfinancial investment criteria. We derive conditions under which impact investing detracts from, improves on, or is neutral to the performance of traditional mean-variance optimal portfolios, which depends on whether the correlations between the impact factor and unobserved excess returns are negative, positive, or zero, respectively. Using Treynor–Black portfolios to maximize the risk-adjusted returns of impact portfolios, we derive an explicit and easily computable measure of the financial reward or cost of impact investing as compared with passive index benchmarks. We illustrate our approach with applications to biotech venture philanthropy, a semiconductor research and development consortium, divesting from “sin” stocks, ESG investments, and “meme” stock rallies such as GameStop in 2021. This paper was accepted by Agostino Capponi, finance. Funding: Research funding from the National Key Research and Development Program of China [Grant 2022YFA1007900], the National Natural Science Foundation of China [Grant 12271013], Peking University’s Fundamental Research Funds for the Central Universities, and the Massachusetts Institute of Technology Laboratory for Financial Engineering is acknowledged. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01168 .

Durability and cross-reactive immune memory to SARS-CoV-2 in individuals 2 years after recovery from COVID-19: a longitudinal cohort study

SARS-CoV-2-specific adaptive immunity more than 1 year after initial infection has not been well characterised. The aim of this study was to investigate the durability and cross-reactivity of immunological memory acquired from natural infection against SARS-CoV-2 in individuals recovered from COVID-19 2 years after infection. In this longitudinal cohort study, we recruited patients who had recovered from laboratory-confirmed COVID-19 and were discharged from Jinyintan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We carried out three successive follow-ups between June 16 and Sept 3, 2020 (6 months), Dec 16, 2020, and Feb 7, 2021 (1 year), and Nov 16, 2021, and Jan 10, 2022 (2 years), in which blood samples were taken. We included participants who did not have re-infection or receive a SARS-CoV-2 vaccination (infected-unvaccinated), and participants who received one to three doses of inactivated vaccine 1-2 years after infection (infected-vaccinated). We evaluated the presence of IgG antibodies, neutralising antibodies, and memory B-cell and memory T-cell responses against the prototype strain and delta and omicron variants. In infected-unvaccinated participants, neutralising antibody titres continually declined from 6-month to 2-year follow-up visits, with a half-life of about 141·2 days. Neutralising antibody responses to omicron sublineages (BA.1, BA.1.1, BA.2, BA.4/5, BF.7, BQ.1, and XBB) were poor. Memory B-cell responses to the prototype strain were retained at 2 years and presented cross-reactivity to the delta and omicron BA.1 variants. The magnitude of interferon γ and T-cell responses to SARS-CoV-2 were not significantly different between 1 year and 2 years after infection. Multifunctional T-cell responses against SARS-CoV-2 spike protein and nucleoprotein were detected in most participants. Recognition of the BA.1 variant by memory T cells was not affected in most individuals. The antibody titres and the frequencies of memory B cells, but not memory T cells, increased in infected-vaccinated participants after they received the inactivated vaccine. This study improves the understanding of the duration of SARS-CoV-2-specific immunity without boosting, which has implications for the design of vaccination regimens and programmes. Our data suggest that memory T-cell responses primed by initial viral infection remain highly cross-reactive after 2 years. With the increasing emergence of variants, effective vaccines should be introduced to boost neutralising antibody and overall T-cell responses to newly emerged SARS-CoV-2 variants. Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities for Peking Union Medical College, Beijing Natural Science Foundation, UK Medical Research Council.

Associations of socioeconomic status and healthy lifestyle with incident early-onset and late-onset dementia: a prospective cohort study

Modifiable risk factor estimates are sparse for early-onset dementia incidence. This study aimed to estimate and compare the risk factor profiles of early-onset dementia and late-onset dementia, and to explore the complex relationships between socioeconomic status, lifestyles, and early-onset dementia risk. In this prospective cohort study, we used data from the UK Biobank for analysis of early-onset dementia and late-onset dementia. For early-onset dementia analyses, data were collected on those aged younger than 60 years without prevalent dementia at baseline. For late-onset dementia analyses, data were collected on those aged 65 years or older at the end of follow-up. Participants with missing information on socioeconomic factors were excluded. Two models were used to test associations between early-onset dementia incidence and socioeconomic status. The first model tested associations between socioeconomic status and early-onset and late-onset dementia incidence, adjusting for covariates. Participant socioeconomic status was defined using education level, income, and employment status via latent class analysis. The second model additionally included a healthy lifestyle score, which was constructed using data on smoking, alcohol consumption, physical activity, and the Healthy Diet Index. Incident early-onset dementia was defined as a dementia case diagnosed before 65 years of age. Multivariable-adjusted Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for risk of dementia. We used multivariable-adjusted Cox proportional-hazard regression models to estimate the HR for risk of both early-onset dementia and late-onset dementia. Between 2007 and 2010, 257 345 individuals were included in the analysis of early-onset dementia, and 294 133 older individuals were included in the analysis of late-onset dementia. During a mean follow-up of 11·9-12·5 years, 502 early-onset dementia cases and 5768 late-onset dementia cases were documented. Risk factor profiles were typically dissimilar between early-onset dementia and late-onset dementia. For instance, the age and sex adjusted HR for low socioeconomic status (vs high) was 4·40 (95% CI 3·43-5·65) for early-onset dementia and 1·90 (1·74-2·07) for late-onset dementia, yielding a ratio of HRs of 2·32 (1·78-3·02). After adjusting for various risk factors, participants with low socioeconomic status (vs high) had increased risk for early-onset dementia (3·38, 2·61-4·37), and overall lifestyle mediated 3·2% (1·8-5·7) of the association. Individuals with both low socioeconomic status and unhealthy lifestyles had a higher risk of early-onset dementia (5·40, 3·66-7·97). No significant interaction was observed between lifestyle and socioeconomic status. The association between socioeconomic status and early-onset dementia seemed to be more pronounced in individuals with type 2 diabetes (HR 11·21, 95% CI 2·70-46·57). Early-onset dementia and late-onset dementia might have different risk factor profiles; although risk factors were similar, the magnitude of associations between risk factors and dementia incidence was greater for early-onset dementia. Only a small proportion of the socioeconomic inequity in dementia risk was mediated by healthy lifestyles, which indicates that measures other than healthy lifestyle promotion to improve social determinants of health are warranted. The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Hubei Province Science Fund for Distinguished Young Scholars, and the Fundamental Research Funds for the Central Universities.

Evidence of positive selection of genetic variants associated with PCOS.

Was polycystic ovary syndrome (PCOS), which impairs fertility and adheres to the evolutionary paradox, subject to evolutionary selection during ancestral times and did rapidly diminish in prevalence? This study strengthened the hypothesis that positive selection of genetic variants occurred and may account for the high prevalence of PCOS observed today. PCOS is a complex endocrine disorder characterized by both reproductive and metabolic disturbances. As a heritable disease that impairs fertility, PCOS should diminish rapidly in prevalence; however, it is the most common cause of female subfertility globally. Few scientific genetic studies have attempted to provide evidence for the positive selection of gene variants underlying PCOS. We performed an evolutionary analysis of 2,504 individuals from 14 populations of the 1000 Genomes Project. We tested the signature of positive selection for 37 single-nucleotide polymorphisms (SNPs) associated with PCOS in previous genome-wide association studies using six parameters of positive selection. Analyzing the evolutionary indices together, there was obvious positive selection at the PCOS-related SNPs loci, especially within the original evolution window of humans, demonstrated by significant Tajima's D values. Compared to the genome background, six of the 37 SNPs in or close to five genes (DENN domain-containing protein 1A: DENND1A, chromosome 9 open reading frame 3: AOPEP, aminopeptidase O: THADA, diacylglycerol kinase iota: DGKI, and netrin receptor UNC5C: UNC5C) showed significant evidence of positive selection, among which DENND1A, AOPEP, and THADA represent the set of most established susceptibility genes for PCOS. First, only well-documented SNPs were selected from well-designed experiments. Second, it is difficult to determine which hypothesis of PCOS evolution is at play. After considering the most significant functions of these genes, we found that they had a wide variety of functions with no obvious association between them. Our findings provide additional evidence for the positive evolution of PCOS. Our analyses require confirmation in a larger study with more evolutionary indicators and larger data range. Further research to identify the roles of the DENND1A, AOPEP, THADA, DGKI, and UNC5C genes is also necessary. This study was supported by the National Key Research and Development Program of China (2021YFC2700400 and 2021YFC2700701), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (82192874, 31871509, and 82071606), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors have no conflicts of interest to disclose. N/A.

Deciphering the DNA methylome in women with PCOS diagnosed using the new international evidence-based guidelines.

Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based guidelines? A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls. PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based guidelines. This cross-sectional case-control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls. A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites. We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952). The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required. This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based guideline, and it provided new molecular insight into the application of the new guidelines. This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest. N/A.

Translanguaging in a French-medium CLIL course: An action research on a novice teacher’s course preparation

While translanguaging has been regarded as an appropriate approach to addressing the challenges that teachers and learners experience in content and language integrated learning (CLIL) classrooms, few studies have discussed translanguaging practices in the preparation of content for third language integrated learning courses. This study aims to explore teachers’ translanguaging practices when preparing CLIL courses through the medium of languages other than English (LOTEs) in a Chinese tertiary education institution. To address the research objective, we collected data including one novice CLIL teacher’s course planning and design documents, teaching materials and other reference materials, along with reflective reports written by the teacher. Through a frequency analysis and a thematic analysis of the data, this research not only documented the dynamic flow of translanguaging practices during CLIL course preparation, but also identified multiple functions served by different languages in the CLIL context. These findings have the potential to inform LOTE teachers involved in CLIL classrooms about different translanguaging pedagogies, and enrich the theoretical framework of translanguaging. FUNDING INFORMATION. This paper was supported by Program for Innovative Research Team of Shanghai University of Finance and Economics (IRTSHUFE) under Grant [2020110925] and by [the Fundamental Research Funds for the Central Universities, SUFE] under Grant [2020110892].

Socioeconomic inequalities in physical, psychological, and cognitive multimorbidity in middle-aged and older adults in 33 countries: a cross-sectional study

Many physical, psychological, and cognitive disorders are highly clustered among populations with low socioeconomic status. However, the extent to which socioeconomic status is associated with different combinations of these disorders is unclear, particularly outside high-income countries. We aimed to evaluate these associations in 33 countries including high-income countries, upper-middle-income countries, and one lower-middle-income country. This cross-sectional multi-region study pooled individual-level data from seven studies on ageing between 2017 and 2020. Education and total household wealth were used to measure socioeconomic status. Physical disorder was defined as having one or more of the self-reported chronic conditions. Psychological and cognitive disorders were measured by study-specific instruments. The outcome included eight categories: no disorders, physical disorder, psychological disorder, cognitive disorder, and their four combinations. Multivariable-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for the associations of socioeconomic status with these outcomes separately for high-income countries, upper-middle-income countries, and the lower-middle-income country. Among 167 376 individuals aged 45 years and older, the prevalence of multimorbidity was 24·5% in high-income countries, 33·9% in upper-middle-income countries, and 8·1% in the lower-middle-income country (India). Lower levels of education, household wealth, and a combined socioeconomic status score were strongly associated with physical, psychological, and cognitive multimorbidity in high-income countries and upper-middle-income countries, with ORs (low vs high socioeconomic status) for physical-psychological-cognitive multimorbidity of 12·36 (95% CI 10·29-14·85; p<0·0001) in high-income countries and of 23·84 (18·85-30·14; p<0·0001) in upper-middle-income countries. The associations in the lower-middle-income country were mixed. Participants with both a low level of education and low household wealth had the highest odds of multimorbidity (eg, OR for physical-psychological-cognitive multimorbidity 21·21 [15·95-28·19; p<0·0001] in high-income countries, 37·07 [25·66-53·56; p<0·0001] in upper-middle-income countries, and 54·96 [7·66-394·38; p<0·0001] in the lower-middle-income country). In study populations from high-income countries, upper-middle-income countries, and the lower-middle-income country, the odds of multimorbidity, which included physical, psychological, and cognitive disorders, were more than ten times greater in individuals with low socioeconomic status. Equity-oriented policies and programmes that reduce social inequalities in multimorbidity are urgently needed to achieve Sustainable Development Goals. Zhejiang University, Fundamental Research Funds for the Central Universities, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Wellcome Trust, Medical Research Council, National Institute on Aging, and Academy of Finland. For the Chinese translation of the abstract see Supplementary Materials section.

Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma.

The overactivation of NF-κB signaling is a key hallmark for the pathogenesis of extranodal natural killer/T cell lymphoma (ENKTL), a very aggressive subtype of non-Hodgkin's lymphoma yet with rather limited control strategies. Previously, we found that the dysregulated exportin-1 (also known as CRM1) is mainly responsible for tumor cells to evade apoptosis and promote tumor-associated pathways such as NF-κB signaling. Herein we reported the discovery and biological evaluation of a potent small molecule CRM1 inhibitor, LFS-1107. We validated that CRM1 is a major cellular target of LFS-1107 by biolayer interferometry assay (BLI) and the knockdown of CRM1 conferred tumor cells with resistance to LFS-1107. We found that LFS-1107 can strongly suppresses the growth of ENKTL cells at low-range nanomolar concentration yet with minimal effects on human platelets and healthy peripheral blood mononuclear cells. Treatment of ENKTL cells with LFS-1107 resulted in the nuclear retention of IkBα and consequent strong suppression of NF-κB transcriptional activities, NF-κB target genes downregulation and attenuated tumor cell growth and proliferation. Furthermore, LFS-1107 exhibited potent activities when administered to immunodeficient mice engrafted with human ENKTL cells. Therefore, LFS-1107 holds great promise for the treatment of ENKTL and may warrant translation for use in clinical trials. Yang's laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301), the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (Personal Target Discovery for Metabolic Diseases).

A neuroimaging biomarker for Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN): a cross-sectional study

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a worldwide public health challenge. A neuroimaging biomarker would significantly improve early diagnosis and intervention, ultimately enhancing the quality of life for affected individuals and reducing the burden on healthcare systems. Cross-sectional and longitudinal data (10,099 participants with 13,380 scans) from 12 independent datasets were used in the present study (this study was performed between September 1, 2021 and February 15, 2023). The Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN) score was developed via integrated regional- and network-based measures under an ensemble machine learning model based on structural MRI data. We systematically assessed whether IBRAIN could be a neuroimaging biomarker for AD. IBRAIN accurately differentiated individuals with AD from NCs (AUC=0.92) and other neurodegenerative diseases, including Frontotemporal dementia (FTD), Parkinson's disease (PD), Vascular dementia (VaD) and Amyotrophic Lateral Sclerosis (ALS) (AUC=0.92). IBRAIN was significantly correlated to clinical measures and gene expression, enriched in immune process and protein metabolism. The IBRAIN score exhibited a significant ability to reveal the distinct progression of prodromal AD (i.e., Mild cognitive impairment, MCI) (Hazard Ratio (HR)=6.52 [95% CI: 4.42∼9.62], p<1×10-16), which offers similar powerful performance with Cerebrospinal Fluid (CSF) Aβ (HR=3.78 [95% CI: 2.63∼5.43], p=2.13×10-14) and CSF Tau (HR=3.77 [95% CI: 2.64∼5.39], p=9.53×10-15) based on the COX and Log-rank test. Notably, the IBRAIN shows comparable sensitivity (beta=-0.70, p<1×10-16) in capturing longitudinal changes in individuals with conversion to AD than CSF Aβ (beta=-0.26, p=4.40×10-9) and CSF Tau (beta=0.12, p=1.02×10-5). Our findings suggested that IBRAIN is a biologically relevant, specific, and sensitive neuroimaging biomarker that can serve as a clinical measure to uncover prodromal AD progression. It has strong potential for application in future clinical practice and treatment trials. Science and Technology Innovation 2030 Major Projects, the National Natural Science Foundation of China, Beijing Natural Science Funds, the Fundamental Research Funds for the CentralUniversity, and the Startup Funds for Talents at Beijing Normal University.

Holographic Schwinger effect in spinning black hole backgrounds* *Supported by the National Natural Science Foundation of China (NSFC) (12375140) and the Fundamental Research Funds for the Central Universities, China University of Geosciences (Wuhan) (G1323523064)

We perform a potential analysis for the holographic Schwinger effect in spinning Myers-Perry black holes. We compute the potential between the produced pair by evaluating the classical action of a string attached on a probe D3-brane at an intermediate position in the AdS bulk. We find that increasing the angular momentum reduces the potential barrier, thus enhancing the Schwinger effect, consistent with previous findings obtained via the local Lorentz transformation. In particular, these effects are more visible for the particle pair lying in the transversal plane compared with that along the longitudinal orientation. In addition, we discuss how the Schwinger effect changes with the shear viscosity to entropy density ratio at strong coupling under the influence of angular momentum.

Intelligent prognosis evaluation system for stage I-III resected non-small-cell lung cancer patients on CT images: a multi-center study

Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744-0.846), internal validation set (0.783; 95% CI: 0.744-0.825) and external validation set (0.817; 95% CI: 0.786-0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p<0.05 for all). The IPES provided a non-invasive way to obtain prognosis-related information from patients. The identification of IPES for resected NSCLC patients with low and high prognostic risk in the same TNM stage or with the same EGFR genotype suggests that IPES have potential to offer more personalized treatment and surveillance suggestion for NSCLC patients. This study was funded by the National Natural Science Foundation of China (grant 62272055, 92259303, 92059203), New Cornerstone Science Foundation through the XPLORER PRIZE, Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (K.C.), Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), BUPT Excellent Ph.D. Students Foundation (CX2022104).

Uncertainties of critical temperatures based on higher-order fluctuations of the largest fragment charge* *Supported by the National Natural Science Foundation of China (11875328, 12075327), the Key Laboratory of Nuclear Data foundation (JCKY2022201C157), and the Fundamental Research Funds for the Central Universities, Sun Yat-sen University (22lgqb39)

The new signature of liquid-gas phase transition has been well indicated by the higher-order fluctuations of the largest fragment charge, but the uncertainties of critical temperatures based on this signature have not been revealed. This study extracts the critical temperatures of liquid-gas phase transition in nuclear reactions and investigates their uncertainties. Utilizing the isospin-dependent quantum molecular dynamics model in conjunction with the statistical model GEMINI enables us to describe the dynamical path from the initial to the final state. An isotope thermometer and a quantum fluctuation thermometer are employed to extract the nuclear temperature. The higher-order fluctuations of the largest fragment charge and critical temperatures are studied in 124Sn + 120Sn collisions ranging from 400 to 1000 MeV/nucleon and 124Sn + AZ collisions at 600 MeV/nucleon. Observations revealed that the pseudo-critical point is robustly indicated by the higher-order fluctuations of the largest fragment charge. The critical temperatures extracted by the isotope thermometer are relatively consistent, with an uncertainty of 15%, while those obtained by the quantum fluctuation thermometer are heavily influenced by the incident energy and mass number of target nuclei. The excitation energy and bound charge are used for event-sorting. These two ensembles represent the statistical properties of the initial and final states of the system, respectively. The initial-final correlations of statistical properties might lead to two phenomena. First, the size distribution of the largest fragment at the pseudo-critical point based on the ensemble is wide, while that based on ensemble exhibits bimodality, which is a typical characteristic in the liquid-gas coexistence of a finite system. Second, the temperature at the pseudo-critical point based on the ensemble is higher than that based on the ensemble. Furthermore, the projectile-like system exhibits a significant dynamical effect in its evolution path from the initial to final state, closely associated with the fluctuation of critical temperature.

Gauss-Bonnet solution with a cloud of strings in de Sitter and anti-de Sitter space* *Supported by the National Natural Science Foundation of China (12275087) and the Fundamental Research Funds for the Central Universities.

In this study, we investigate exact spherically symmetric Gauss-Bonnet black hole solutions surrounded by a cloud of string fluid with the cosmological constant in dimensions. Both charged and uncharged cases are considered. We focus on the de Sitter solutions in the main text and provide the anti-de Sitter solutions in the appendix. We analyze the features of event horizons and thermodynamic properties of the black hole solutions. The mass, Hawking temperature, thermal stability, and phase transitions are discussed. Moreover, the equation of state and critical phenomena associated with these solutions are explored.

Chronic diseases and multimorbidity patterns, their recent onset, and risk of new-onset Parkinson's disease and related functional degeneration in older adults: a prospective cohort study

Certain chronic diseases contribute to increased risks of Parkinson's disease (PD), but the association between time-varying multimorbidity patterns and new-onset PD remains underexplored. Data were from the Survey of Health, Ageing and Retirement in Europe (SHARE) waves 5-8 conducted between January 2013 and March 2020. Eleven chronic diseases were included, with ≥2 denoting multimorbidity. Three multimorbidity patterns were further defined: somatic multimorbidity (SMM), neuropsychiatric multimorbidity (NPM), and cardiometabolic multimorbidity (CMM). PD-related function degeneration included functional limitations, mobility limitations, depressive symptoms, and cognitive decline. Time-dependent analyses, competing-risk analyses, and mixed-effect models were utilised. In this prospective cohort study, 557 developed new-onset PD during follow-ups among 64,273 participants included at baseline, as defined by participants' self-reported physician diagnoses. Participants with (vs. without) multimorbidity, SMM, NPM, and CMM were at 1.40-2.70 times higher PD risk after considering the competing role of all-cause death, which remained significant in all sensitivity analyses and were more pronounced in lower-income participants (P for interaction <0.05). Similarly, they tended to develop functional degeneration faster than those without these multimorbidity patterns (P<0.05). Participants with recent-onset (newly diagnosed in 2015) multimorbidity patterns were at 1.45-3.72 times higher risk of PD than those never diagnosed. Interestingly, they were at comparable or even higher (though P values for >0.05) PD risk compared to participants with multimorbidity patterns diagnosed in 2013 or before. Furthermore, recent-onset (vs. prior diagnosed) NPM exhibited faster functional deterioration and cognitive decline (P for difference <0.05). Our findings suggest that promoting early prevention of multimorbidity, especially recent-onset multimorbidity and NPM, could prevent some subsequent cases of PD and related functional degeneration among older adults. However, further studies are needed to confirm this association. The National Key Research and Development Program, Ministry of Science and Technology, China; Zhongnanshan Medical Foundation of Guangdong Province; Major Project of the National Social Science Fund of China; Fundamental Research Funds for the Central Universities.

Deep learning-based companion robot on senile dementia patients

BackgroundThere are currently at least 50 million dementia patients worldwide, and this number is expected to reach 152 million by 2050, of which about 60-70% will be Alzheimer’s patients. The companion robot based on deep learning is a product of the development of artificial intelligence technology, which is of great significance to the physical and mental health of the elderly, so it is used in the research on the treatment of Alzheimer’s patients.Subjects and Methods100 patients with Alzheimer’s disease in a hospital were selected for the study, and 50 patients were randomly divided into experimental group and control group. In the experiment, 50 patients with Alzheimer in the experimental group used a companion robot based on deep learning for auxiliary treatment while carrying out daily treatment. The control group of 50 patients did not receive any adjuvant therapy in addition to daily treatment. After three months of treatment, the study used the 3D-CAM and the mini–mental state examination (MMSE) to collect the treatment status of all patients, and used the SPSS23.0 statistical software to statistically analyze the collected data.ResultsAfter statistical analysis, the results of the two groups were obtained. The scores of 3D-CAM and MMSE in the experimental group were significantly higher than those in the control group and the difference was statistically significant.ConclusionsCompanion robots based on deep learning are helpful in the treatment of Alzheimer’s patients. They can improve the therapeutic effect and have certain social value.AcknowledgementThe Fundamental Research Funds in Heilongjiang Provincial Universities (No.135309356); Qiqihar University Young Teachers’ Scientific Research Initiation Support Program (No.2012k-M17).

Law education reform in universities on reducing college students’ learning anxiety

BackgroundWith the rapid development of society, the learning anxiety of college students is gradually increasing. Law education emphasizes rational thinking and behavioral norms, enabling college students to establish a correct outlook on life. Therefore, law education should be an important part of psychological health interventions for college students.Subjects and MethodsThe study selected 120 students with learning anxiety and randomly divided them into two groups. One group is a blank group, which only uses traditional legal education. The other group is the experimental group, which adopts an educational approach that combines psychology and law to reform. The experimental period lasted for one semester, and the course arrangements of the two groups were consistent. Before and after the experiment, a questionnaire survey was conducted using the Self Rating Anxiety Scale (SAS). Based on the experimental results, the psychological relief of anxiety in the two groups was analyzed.ResultsThe number of students in the blank group who had mild, moderate, or severe learning anxiety before the experiment began was 64, 53, and 3, respectively. In the experimental group, there were 62, 54, and 4 students who had mild, moderate, and severe cases of learning anxiety, respectively. After the test, there were 71, 47, and 2 students in the control group who had mild, moderate, or severe learning anxiety, respectively. In the experimental group, there were 81, 27, and 0 students who did not have learning anxiety, respectively. The number of students with mild to severe learning anxiety increased.ConclusionsThe integration of psychological reform in law teaching can effectively alleviate the learning anxiety of college students.AcknowledgementThe Fundamental Research Funds for the Central Universities (No.3132022297); National Social Science Fund of China (No.21CFX055).

Consistency of Pantheon+ supernovae with a large-scale isotropic universe* *Supported by the National Natural Science Fund of China (12147102, 12275034) and the Fundamental Research Funds for the Central Universities of China (2023CDJXY-048)

We investigate the possible anisotropy of the universe using data on the most up-to-date type Ia supernovae, i.e., the Pantheon+ compilation. We fit the full Pantheon+ data with the dipole-modulated ΛCDM model and find that the data are well consistent with a null dipole. We further divide the full sample into several subsamples with different high-redshift cutoffs . It is shown that the dipole appears at the confidence level only if , and in this redshift region, the dipole is very stable, almost independent of the specific value of . For , the dipole amplitude is , pointing toward , which is approximately away from the CMB dipole. This implies that the full Pantheon+ sample is consistent with a large-scale isotropic universe, but the low-redshift anisotropy could not be purely explained by the peculiar motion of the local universe.

DNA damage repair profiling of esophageal squamous cell carcinoma uncovers clinically relevant molecular subtypes with distinct prognoses and therapeutic vulnerabilities

DNA damage repair (DDR) is a critical process that maintains genomic integrity and plays essential roles at both the cellular and organismic levels. Here, we aimed to characterize the DDR profiling of esophageal squamous cell carcinoma (ESCC), investigate the prognostic value of DDR-related features, and explore their potential for guiding personalized treatment strategies. We analyzed bulk and single-cell transcriptomics data from 377 ESCC cases from our institution and other publicly available cohorts to identify major DDR subtypes. The heterogeneity in cellular and functional properties, tumor microenvironment (TME) characteristics, and prognostic significance of these DDR subtypes were investigated using immunogenomic analysis and invitro experiments. Additionally, we experimentally validated a combinatorial immunotherapy strategy using syngeneic mouse models of ESCC. DDR alteration profiling enabled us to identify two distinct DDR subtypes, DDRactive and DDRsilent, which exhibited independent prognostic values in locoregional ESCC but not in metastatic ESCC. The DDRsilent subtype was characterized by an inflamed but immune-suppressed microenvironment with relatively high immune cell infiltration, abnormal immune checkpoint expression, T-cell exhaustion, and enrichment of cancer-related pathways. Moreover, DDR subtyping indicates that BRCA1 and HFM1 are robust and independent prognostic factors in locoregional ESCC. Finally, we proposed and verified that the concomitant triggering of GITR or blockade of BTLA with PD-1 blockade or cisplatin chemotherapy represents effective combination strategies for high-risk locoregional ESCC tumors. Our discovery of DDR-based molecular subtypes will enhance our understanding of tumor heterogeneity and have significant clinical implications for the therapeutic and management strategies of locoregional ESCC. This study was supported by the National Key R&D Program of China (2021YFC2501000, 2022YFC3401003), National Natural Science Foundation of China (82172882), the Beijing Natural Science Foundation (7212085), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310027).

Density-dependent relativistic mean field approach and its application to single-Λ hypernuclei in oxygen hyperisotopes* *Supported by the Fundamental Research Funds for the Central Universities, Lanzhou University (lzujbky-2022-sp02, lzujbky-2023-stlt01), the National Natural Science Foundation of China (11875152, 12275111), and the Strategic Priority Research Program of Chinese Academy of Sciences (XDB34000000)

The in-medium feature of nuclear force, which includes both nucleon-nucleon () and hyperon-nucleon () interactions, impacts the description of single-Λ hypernuclei. With the alternated mass number or isospin of hypernuclei, such effects may be unveiled by analyzing the systematic evolution of the bulk and single-particle properties. From a density-dependent meson-nucleon/hyperon coupling perspective, a new effective interaction in the covariant density functional (CDF) theory, namely, DD-LZ1-, is obtained by fitting the experimental data of Λ separation energies for several single-Λ hypernuclei. It is then used to study the structure and transition properties of single-Λ hypernuclei in oxygen hyperisotopes, in comparison with those determined using several selected CDF Lagrangians. A discrepancy is explicitly observed in the isospin evolution of spin-orbit splitting with various effective interactions, which is attributed to the divergence of the meson-hyperon coupling strengths with increasing density. In particular, the density-dependent CDFs introduce an extra contribution to reduce the value but enhance the isospin dependence of the splitting, which originates from the rearrangement terms of Λ self-energies. In addition, the characteristics of hypernuclear radii are studied along the isotopic chain. Owing to the impurity effect of the Λ hyperon, a size shrinkage is observed in the matter radii of hypernuclei compared with the cores of normal nuclei, and its magnitude is further elucidated to correlate with the incompressibility of nuclear matter. Moreover, there is a sizable model-dependent trend in which the Λ hyperon radii evolve with neutron number, which is decided partly by the in-medium interactions and core polarization effects.