National Natural Science Foundation Of China Research Articles

Use of waste plastic oil as a fuel in reactivity-controlled compression ignition engines: a bibliometric investigation from 2017–23

Abstract Waste plastic oil, generated through the pyrolysis of plastic without oxygen, known as plastic-to-fuel conversion, stands as a promising alternative fuel. This research employs bibliometric analysis, a quantitative method, to comprehensively assess publications in the domain of waste plastic oil integration within reactivity-controlled compression ignition engines. Utilizing Scopus as the primary repository post-2017, the study categorizes information into pivotal aspects, including influential journals, countries, authors, affiliations, document types, thematic areas, sponsors and keywords. The analysis reveals significant contributions from diverse nations, prominently India, China, Turkey and Malaysia. Noteworthy is the prevalence of Energy, Engineering and Chemical Engineering as thematic focal points, with the journal Fuel leading the count followed by the journal Energy emerging as a prominent conduit. Institutional contributions are prolific, led by Gandhi Institute of Technology and Management University and Vellore Institute of Technology. Renowned authors ‘Gugulothu S.K’ and ‘He Z’ play a pivotal role in shaping the discourse. The National Natural Science Foundation of China stands out as a primary patron. This bibliometric analysis provides a structured understanding of waste plastic oil integration in reactivity-controlled compression ignition engines, laying the groundwork for future research avenues. The study identifies potential research platforms beyond Scopus, including Web of Science, CrossRef, Science Direct and Google Scholar, as valuable repositories for further exploration. Moreover, after careful observation of the research articles published by the top 10 authors as found in the study, it was found that the authors share a few common characteristics that helped them in advancing the understanding and application of waste plastic oil in reactivity-controlled compression ignition engines. These are also summarized in the present study with supporting data.

Robust Drone Delivery with Weather Information

Problem definition: Drone delivery has recently garnered significant attention due to its potential for faster delivery at a lower cost than other delivery options. When scheduling drones from a depot for delivery to various destinations, the dispatcher must take into account the uncertain wind conditions, which affect the delivery times of drones to their destinations, leading to late deliveries. Methodology/results: To mitigate the risk of delivery delays caused by wind uncertainty, we propose a two-period drone scheduling model to robustly optimize the delivery schedule. In this framework, the scheduling decisions are made in the morning, with the provision for different delivery schedules in the afternoon that adapt to updated weather information available by midday. Our approach minimizes the essential riskiness index, which can simultaneously account for the probability of tardy delivery and the magnitude of lateness. Using wind observation data, we characterize the uncertain flight times via a cluster-wise ambiguity set, which has the benefit of tractability while avoiding overfitting the empirical distribution. A branch-and-cut (B&C) algorithm is developed for this adaptive distributionally framework to improve its scalability. Our adaptive distributionally robust model can effectively reduce lateness in out-of-sample tests compared with other classical models. The proposed B&C algorithm can solve instances to optimality within a shorter time frame than a general modeling toolbox. Managerial implications: Decision makers can use the adaptive robust model together with the cluster-wise ambiguity set to effectively reduce service lateness at customers for drone delivery systems. Funding: This work was supported by the National Natural Science Foundation of China [Grants 72101049 and 72232001], the Natural Science Foundation of Liaoning Province [Grant 2023-BS-091], the Fundamental Research Funds for the Central Universities [Grant DUT23RC(3)045], and the Major Project of the National Social Science Foundation [Grant 22&ZD151]. Supplemental Material: The online appendices are available at https://doi.org/10.1287/msom.2022.0339 .

Abstract PO2-27-06: ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer

Abstract Metastasis to distant organs stands as the primary contributor to mortality in cases of breast cancer. While localized breast cancer boasts a 5-year survival rate of roughly 99%, this figure drastically declines to approximately 26% for patients afflicted with distant metastasis. Regrettably, the current therapeutic landscape lacks efficacious and targeted interventions for the treatment of metastatic breast cancer. Our investigation has revealed a significant upregulation of S100A4 in metastatic breast cancer tissues, with notably high expression observed in the malignant pleural effusion of patients in advanced stages of the disease. Upon acceptance of the effective treatment, the expression of S100A4 in malignant pleural effusion decreased, along with a decrease in several cytokines, including IL-6, IL-8, CCL2, and CCL5. The breast cancer cellular models demonstrated that ANXA9 has the ability to regulate the excretion of S100A4 from cells into the surrounding medium. Similarly, the mice model of pleural metastasis indicated that the downregulation of ANXA9 (sh-ANXA9) resulted in decreased levels of S100A4 and cytokines IL-6, IL-8, CCL2, and CCL5 in the mice's hydrothorax. Additionally, our findings suggest that ANXA9 regulates the excretion of S100A4 through phosphorylation of ANXA9. The cellular membrane harbored phosphorylated ANXA9, which exhibited two phosphorylation sites. Upon mutation of these sites, the level of ANXA9 phosphorylation decreased, leading to a reduction in the exocrine release of ANXA9 from cells into the medium. Our research further revealed the significant involvement of ANXA9 in facilitating the progression of breast cancer, thereby suggesting that therapeutic interventions targeting ANXA9 could prove efficacious in treating metastatic breast cancer. This work was supported by Shanghai Sailing Program to Dengfeng Li (No. 20YF1437800), grant from the National Natural Science Foundation of China to Dengfeng li (No. 82103454) and grant from the National Natural Science Foundation of China to Lin Fang (No. 82073204). Citation Format: Xiqian Zhou, Dengfeng Li, Lin Fang, Junyong Zhao. ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-06.

Chemically engineered mTOR-nanoparticle blockers enhance antitumour efficacy

Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression. Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers. Cell-based experiments were carried out to evaluate the effects of the nanoblocker against hepatocellular carcinoma (HCC) cells. The orthotopic and subcutaneous HCC mouse models were established to examine its antitumour activity. Among several fatty acids as promoieties, linoleic acid-conjugated self-assembling nanoblocker exhibited optimal size distribution and superior physiochemical properties. Compared with free agents, PEGylated AZD8055 nanoblocker (termed AZD NB) was pharmacokinetically optimized after intravenous administration. Invivo investigations confirmed that AZD NB significantly suppressed tumour outgrowth in subcutaneous HCCLM3 xenograft, Hepatoma-22, and orthotopic Hepa1-6 liver tumour models. Strikingly, treatment with AZD NB, but not free agent, increased intratumour infiltration of IFN-γ+CD8+ T cells and CD8+ memory T cells, suggesting a potential role of the mTOR nanoblocker to remodel the tumour microenvironment. Overall, a single conjugation with fatty acid transformed a hydrophobic mTOR blocker into a systemically injectable nanomedicine, representing a facile and generalizable strategy for improving the therapeutic index of mTOR inhibition-based cancer therapy. The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents. This work was supported by the National Natural Science Foundation of China (32171368,81721091), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c and JNL-2022010B), State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202310), and Natural Science Foundation of Shandong Province (ZR2023ZD59).

Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma

The widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, B cell heterogeneity in PDAC remains unexplored. Studying TIL-Bs in PDAC aims to identify new treatment strategies. We performed single-cell RNA sequencing to study the heterogeneity of B cells in PDAC. The prognostic and immunologic value of the identified CD38+ B cells was explored in FUSCC (n=147) and TCGA (n=176) cohorts. Flow cytometry was conducted to characterize the relationship between CD38+ B cells and other immune cells, as well as their phenotypic features. Invitro and in vivo experiments were performed to assess the putative effect of CD38+ B cells on antitumor immunity. The presence of CD38+ B cells in PDAC was associated with unfavorable clinicopathological features and poorer overall survival (p<0.001). Increased infiltration of CD38+ B cells was accompanied by reduced natural killer (NK) cells (p=0.021) and increased regulatory T cells (p=0.016). Molecular profiling revealed high expression of IL-10, IL-35, TGF-β, GZMB, TIM-1, CD5 and CD21, confirming their putative regulatory B cell-like features. Co-culture experiments demonstrated suppression of NK cell cytotoxicity by CD38+ B cell-derived IL-10 (p<0.001). Finally, invivo experiments suggested adoptive transfer of CD38+ B cells reduced antitumor immunity and administration of a CD38 inhibitor hampered tumor growth (p<0.001). We discovered regulatory B cell-like CD38+ B cell infiltration as an independent prognostic factor in PDAC. The use of CD38 inhibitor may provide new possibilities for PDAC immunotherapy. This study was supported by the National Natural Science Foundation of China (U21A20374), Shanghai Municipal Science and Technology Major Project (21JC1401500), Scientific Innovation Project of Shanghai Education Committee (2019-01-07-00-07-E00057), Special Project for Clinical Research in the Health Industry of the Shanghai Health Commission (No. 20204Y0265) and Natural Science Foundation of Shanghai (23ZR1479300).

Improvements in the health-related quality-of-life benefit of cancer drugs approved in China, 2005–2020: an observational study

BackgroundHealth-related quality of life (HRQoL), along with overall survival (OS), is a critical study endpoint for measuring the clinical benefits of cancer drugs. Previous studies have examined the OS benefit of new cancer drugs approved in China. However, their HRQoL benefits have not been systematically evaluated. We aimed to characterise the measurement and improvement of HRQoL associated with cancer drugs approved in China. MethodsThis mixed-methods study comprises of a literature review and a cross-sectional study, including all antineoplastic agents approved in China between January 1, 2005 and December 31, 2020. A systematic search was conducted on December 31, 2023 to extract HRQoL information of identified drugs. We extracted information on the characteristics of HRQoL assessment and statistically significant HRQoL gains compared with the control treatment. FindingsA total of 64 novel cancer drugs, corresponding to 115 cancer indications, supported by randomised clinical trials were approved in China between 2005 and 2020. Among the indications, 78 (67·8%) used HRQoL as an endpoint in the pivotal trial. By December 31, 2023, after a median follow-up of 5·3 (range, 3·0-18·8) years from approval, HRQoL information was available for more than half of the indications (75, 65·2%). Thirty-three indications (28·7%) reported statistically significant improvement in HRQoL, with 22 (19·1%) also having documented OS benefit. Approximately one-third of the indications (39, 33·9%) showed no difference in HRQoL, with 21 (18·3%) having documented OS gains. Three indications (2·6%) reported worsening HRQoL. The most commonly used HRQoL measurements were individual disease-specific instruments (62 of 75, 82·7%) while the most frequently employed analysis metric was the mean change scores from baseline (56 of 75, 74·7%). InterpretationFewer than one-third of cancer indications approved in China had shown HRQoL improvements. There was considerable heterogeneity in the analysis and reporting of HRQoL benefits associated with new cancer drugs approved in China. These findings emphasise the important role of HRQoL evaluation and analysis in clinical research and the necessity of improving the standardization of HRQoL assessment. FundingNational Natural Science Foundation of China (72274004)

VHL mutation drives human clear cell renal cell carcinoma progression through PI3K/AKT-dependent cholesteryl ester accumulation

Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness invitro and invivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China

Cardiovascular disease (CVD) has been found to be particularly vulnerable to climate change and temperature variability. This study aimed to assess the extent to which human-induced climate change contributes to future heat-related CVD burdens. Daily data on CVD mortality and temperature were collected in 161 Chinese communities from 2007 to 2013. The association between heat and CVD mortality was established using a two-stage time-series design. Under the natural forcing, human-induced, and combined scenarios, we then separately projected excess cause-/age-/region-/education-specific mortality from future high temperature in 2010-2100, assuming no adaptation and population changes. Under shared socioeconomic pathway with natural forcing scenario (SSP2-4.5-nat), heat-related attributable fraction of CVD deaths decreased slightly from 3.3% [95% empirical confidence interval (eCI): 0.3, 5.8] in the 2010s to 2.8% (95% eCI: 0.1, 5.2) in the 2090s, with relative change of-0.4% (95% eCI:-0.8, 0.0). However, for combined natural and human-induced forcings, this estimate would surge to 8.9% (95% eCI: 1.5, 15.7), 14.4% (95% eCI: 1.5, 25.3), 21.3% (95% eCI:-0.6, 39.4), and 28.7% (95% eCI:-3.3, 48.0) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. When excluding the natural forcing, the number of human-induced heat-related CVD deaths would increase from approximately eight thousand (accounting for 31% of total heat-related CVD deaths) in the 2010s to 33,052 (68%), 63,283 (80%), 101,091 (87%), and 141,948 (90%) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. Individuals with stroke, females, the elderly, people living in rural areas, and those with lower education level would exhibit heightened susceptibility to future high temperature. In addition, Southern and Eastern regions of China were expected to experience a faster increase in heat-related attributable fraction of CVD deaths. Human activities would significantly amplify the future burden of heat-related CVD. Our study findings suggested that active adaptation and mitigation measures towards future warming could yield substantial health benefits for the patients with CVD. National Natural Science Foundation of China.

Alterations in the gut mycobiome with coronary artery disease severity

BackgroundCoronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. MethodsIn this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FindingsBased on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. InterpretationIn conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FundingThis work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, 2024 Reform and Development Program of Beijing Institute of Respiratory Medicine, the Beijing Natural Science Foundation (No. 7222068); the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202308); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study

The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P=0.023; 0.879 [0.767-0.950], P=0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P>0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P=0.041) to the level of senior pathologists (both P>0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P<0.0001;-34%, P<0.0001;-29%, P<0.0001; and-27%, P=0.00031). ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Politically Affiliated Analysts

Government ownership of financial intermediaries is pervasive around the world. In this study, we examine the impact of common government ownership between the brokerage and listed firms on the information production role of brokerage firms. We show that affiliated analysts tend to issue more optimistic recommendations for stocks of firms controlled by the same government entity that controls their brokerage firms. This optimistic bias is particularly pronounced during periods of economic shocks. Our study demonstrates this by utilizing additional tariff impositions and tariff exemptions during the U.S.–China trade war as exogenous negative and positive shocks, respectively. Additionally, our study indicates that stocks recommended by politically affiliated analysts tend to underperform those recommended by independent analysts, implying that the optimism stems from conflicts of interest rather than superior information. Furthermore, our research highlights that sophisticated investors perceive the potential bias and incorporate it into their trading. Consistent with an exchange of favors story, politically affiliated brokerage firms receive a larger allocation during the issuance of local government debt, whereas governments subscribe for more shares during seasoned equity offerings by these affiliated brokerage firms. This paper was accepted by Kay Giesecke, finance. Funding: The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China [Grants 71972088, 72132002, and 71991473], the National Social Science Foundation of China [Grants 21ZDA010 and 22VRC145], and the Innovation and Talent Base for Digital Technology and Finance [Grant B21038]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.00579 .

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study.

Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study

Background:Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.Methods:Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).Results:Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p&lt;0.001; Beta = –0.98 in women, p&lt;0.001).Conclusions:Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.Funding:This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Global, regional, and national burden of premenstrual syndrome, 1990-2019: an analysis based on the Global Burden of Disease Study 2019.

What is the burden of premenstrual syndrome (PMS) at the global, regional, and national levels across 21 regions and 204 countries and territories? Over the past few decades, the global prevalent cases of PMS have grown significantly from 652.5 million in 1990 to 956.0 million in 2019, representing a 46.5% increase. PMS, which affects almost half of reproductive women worldwide, has substantial social, occupational, academic, and psychological effects on women's lives. However, no comprehensive and detailed epidemiological estimates of PMS by age and socio-demographic index (SDI) at global, regional, and national levels have been reported. An age- and SDI-stratified systematic analysis of the prevalence and years lived with disability (YLD) of PMS by age and SDI across 21 regions and 204 countries and territories has been performed. The prevalence and YLD of PMS from 1990 to 2019 were retrieved directly from the Global Burden of Diseases (GBD) 2019 study. The number, rates per 100000 persons, and average annual percentage changes (AAPCs) of prevalence and YLD were estimated at the global, regional, and national levels. Globally, the prevalent cases of PMS increased by 46.5% from 652.5 million in 1990 to 956.0 million in 2019; in contrast, however, the age-standardized prevalence rate was approximately stable at 24431.15/100000 persons in 1990 and 24406.51/100000 persons in 2019 (AAPC, 0[95% CI: -0.01 to 0.01]). Globally, the YLD was 8.0 million in 2019 and 5.4 million in 1990, with a sizable increase over the past 30 years. The age-standardized YLD rate was stable (AAPC 0.01, P = 0.182), at 203.45/100000 persons in 1990 and 203.76/100000 persons in 2019. The age-standardized burden estimates were the highest in the low-middle SDI regions and the lowest in the high SDI regions. Peaks in burden rate estimates were all observed in the 40-44 years age group. Regional age-standardized burden estimates were the highest in South Asia and the lowest in Western Sub-Saharan Africa. The national age-standardized burden estimates were the highest in Pakistan and the lowest in Niger. The accuracy of the results depended on the quality and quantity of the GBD 2019 data. Fortunately, the GBD study endeavoured to retrieve data globally and applied multiple models to optimize the completeness, accuracy, and reliability of the data. In addition, the GBD study took the country as its basic unit and neglected the influence of race. Further study is warranted to compare differences in PMS burden associated with race. Finally, no data are available on the aetiology and risk information related to PMS, which might help us to better understand the trends and age distribution of PMS and help local governments formulate more detailed policies and comprehensive interventions. Although the age-standardized prevalence/YLD rate has been stable over the past 30 years, the absolute number of prevalent cases and YLD grew significantly worldwide from 1990 to 2019. Public health-related policies should be implemented to reduce the prevalence and alleviate the symptoms of PMS. Lifestyle changes and cognitive-behavioral therapy are critical in helping to reduce the burden of PMS. This study was supported by the National Key Research and Development Program of China (grant number 2022YFC2704100) and the National Natural Science Foundation of China (No. 82001498, No. 82371648). The authors declare no conflict of interest. N/A.

Earnings Management via Not-Wholly-Owned Subsidiaries

We investigate an unexplored mechanism of earnings management: income shifting from not-wholly-owned subsidiaries to help the parent company avoid losses at the expense of subsidiaries. Consolidated net income attributable to the parent company (i.e., net income) increases through this mechanism, as the parent company enjoys the full amount of the shifted earnings rather than sharing them with minority investors. We design an empirical model to directly estimate the amount of income shifted from subsidiaries to parent firms. Employing this measure, we find that firms opportunistically decrease earnings of their not-wholly-owned subsidiaries to manage net income upward to avoid losses. The results are stronger for firms with high noncontrolling ownership, firms with large subsidiaries, firms with strong influence over not-wholly-owned subsidiaries, and firms with a high level of related-party transactions. Our results are robust to alternative research designs, including controls for within-firm variations, alternative earnings thresholds, propensity score matching, and entropy balancing techniques. Our mechanism of earnings management is generalizable to other earnings management scenarios, such as share pledging. This paper was accepted by Brian Bushee, accounting. Funding: X. Zhang thanks the National Natural Science Foundation of China [Grant 72102243] for financial support. M. Luo thank the financial support from National Natural Science Foundation of China [Grant 71840011], and the Research Center for Digital Financial Assets at School of Economics and Management of Tsinghua University. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.03090 .

Color image encryption algorithm based on novel dynamic DNA encoding and chaotic system* *This work was supported by the Open Fund of Advanced Cryptography and System Security Key Laboratory of Sichuan Province (Grant No. SKLACSS–202208), the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant no. KJZD-M202000501), Sponsored by Natural Science Foundation of Chongqing (CSTB2023NSCQ-LZX0139) and National Natural Science Foundation of China (No.61772295).

To enhance the security of image data, prevent unauthorized access, tampering, and leakage, maintain personal privacy, protect intellectual property rights, and ensure the integrity of images during transmission and storage. This study introduces an innovative color image encryption scheme based on dynamic DNA encoding operations and chaotic systems. By simulating a quantum random walk, a random key is generated to enhance the security of the confidential system. In addition, we integrated the enhanced Josephus problem into DNA coding rules to create dynamic DNA coding rules. At the same time, we proposed a dynamic double-loop DNA XOR operation, which fully utilizes the random sequence generated by the generalized Hamiltonian chaos system to precisely control the loop direction, starting point, and number of operations. This enhances the complexity of the encryption algorithm. After sufficient experimental verification and in-depth research and analysis, our innovative design not only enhances the difficulty of cracking while ensuring image quality but also provides reliable protection for the security of image data.

The Bullwhip Effect in Servitized Manufacturers

The shift to a service-oriented economy has driven traditional product-oriented manufacturing firms to integrate various services into their businesses. This study aims to provide empirical evidence on how manufacturers’ service offerings impact demand variability and intrafirm bullwhip effects. Through “bag-of-words” text mining on 10-K filings of U.S.-listed manufacturing firms, we propose a novel measurement to identify annual services offered. We validate the measurement’s statistical and economic significance and verify its consistency with the results obtained using the large language model (i.e., GPT-4). Services are categorized as complementing product sales (e.g., maintenance and repair) or substituting product sales entirely (e.g., machine hours). Utilizing difference-in-difference techniques, we find robust evidence that manufacturers’ service offerings reduce the bullwhip effect in two steps: basic complementing services decrease demand variability, whereas advanced substituting services mitigate intrafirm bullwhip. Moreover, servitization mainly minimizes demand variability through information channels, whereas increased production efficiency decreases intrafirm bullwhip. Our findings contribute to understanding manufacturers’ business model innovations by demonstrating that servitization can smooth demand and mitigate intrafirm bullwhip. This paper was accepted by Karan Girotra, operations management. Funding: This work was supported by the National Natural Science Foundation of China [Grants 71931007, 72091214] and General Research Fund by Hong Kong Research Grants Council [Grant 14505320]. Supplemental Material: The data and the online appendix are available at https://doi.org/10.1287/mnsc.2023.01026 .

Prediction of anaerobic digestion performance by quantum convolutional reconstruction gated recurrent neural network* *This work was supported by the Open Fund of Advanced Cryptography and System Security Key Laboratory of Sichuan Province (Grant No. SKLACSS202208), National Natural Science Foundation of China (No.61772295),and the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant no.KJZD-M202000501).

Methane as a renewable energy source has become a hot topic in recent years. Methane is a bioenergy source produced during the anaerobic digestion of organic waste, and the anaerobic digestion process must be monitored and controlled to produce the required amount of methane in a stable manner. Mathematical modeling is used to simulate digester operation to predict the biogas production from anaerobic digestion, to avoid reactor loading or performance degradation, and to ensure efficient operation of the system. In this paper, a Quantum Convolutional Reconstruction Gated Recurrent Neural Network is proposed. The original data features are extracted by convolutional neural network to reduce the dimensionality and retain the information, the parameterized quantum circuit is integrated in the gating recurrent unit, and the quantum reset gate and quantum update gate are constructed. The information extracted by the Convolution Neural networks is input into the quantum gated recurrent neural network, and the quantum storage unit integrates the information into the hidden layer state, thus processing the hidden layer state information more efficiently. The experimental results show that the prediction accuracy of the A Quantum Convolution Reconstructed Gated Recurrent Neural Network is improved from 81.95 to 88.21%, and the MAE value is reduced from 54.53% to 37.38%.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis

BackgroundPatients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear.MethodsWe tested a novel “all-in-one” strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored.ResultsAfter CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease–negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100).ConclusionsOur findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.)

Optimal Contracts for Time-Inconsistent Consumers with Heterogeneous Beliefs

In many markets (e.g., cell phones, video games), firms offer menus of contracts that include some tariffs charging per-use prices above marginal cost and others below marginal cost. We term this puzzling phenomenon as two-sided deviations from marginal cost pricing and present a potential explanation based on two well-recognized consumer characteristics. The first one is that consumers’ actual consumptions may depart systematically from their initial plans (i.e., time-inconsistent preferences). In addition, consumers can be either sophisticated or naive in their beliefs about their time inconsistency (i.e., heterogenous beliefs). We characterize properties of the optimal contracts for a firm to screen the time-inconsistent consumers with heterogeneous beliefs. We articulate the conditions under which the optimal menu may account for two-sided deviations from marginal cost pricing. We also show that, contrary to intuition, a higher degree of time inconsistency may reduce firm profit and increase social welfare. Meanwhile, reducing consumer naivete may harm the society. Moreover, we confirm that our main results are robust to the presence of time-consistent consumers. This paper was accepted by Dmitri Kuksov, marketing. Funding: This work was supported by the Hunan Provincial Natural Science Foundation of China [Grant 2022JJ40102]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.02653 .