The Chinese version of patient experience with treatment and self-management (PETS vs. 2.0): translation and validation in patients with multimorbidity in primary care in Hong Kong.

BACKGROUND: Validated and comprehensive tools to measure treatment burden are needed for healthcare professionals to understand the treatment burden of patients in China. The study aimed to translate and validate the Chinese version of Patient Experience with Treatment and Self-management (PETS vs. 2.0) in patients with multimorbidity in primary care. METHODOLOGY: The translation process of the 60-item PETS vs. 2.0 followed the Functional Assessment of Chronic Illness Therapy (FACIT) Translation, Formatting, and Testing Guidelines. Computer-assisted assessments were conducted in adult primary care patients with multimorbidity from three general out-patient clinics in Hong Kong. A sample of 502 patients completed the assessments from July to December 2023. Internal reliability was examined using Cronbach's alphas for each domain of the PETS vs. 2.0. Concurrent validity was assessed through the correlations between different domains of PETS vs. 2.0 with established measures including quality of life, frailty, and depression. Confirmatory Factor Analysis (CFA) with maximum likelihood method was carried out to assess the construct validity. RESULTS: The mean age of participants was 64.9 years old and 56.2% were female. Internal consistency reliability was acceptable (alpha ≥ 0.70) for most domains. Higher scores of PETS domains were significantly correlated with worse quality of life, higher level of frailty, and more depressive symptoms (p < 0.05). In CFA, after setting the covariances on the error variances, the adjusted model revealed an acceptable model fit (χ2/df = 1.741; root mean square error of approximation (RMSEA) = 0.038; standardized root mean square residual (SRMR) = 0.058; comparative fit index (CFI) = 0.911; Tucker-Lewis Index (TLI) = 0.903). All standardized factor loadings were 0.30 or above. Significant positive correlations between the latent factors were found for all factor pairs (correlation coefficient < 0.8). CONCLUSIONS: The Chinese version of PETS vs. 2.0 is a reliable and valid tool for assessing the perceived treatment burden in patients with multimorbidity in primary care. All domains and items in the original questionnaires were retained.

Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

STUDY OBJECTIVES: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA. METHODS: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics. RESULTS: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations. CONCLUSIONS: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

The association between telomere length and diabetes mellitus: accumulated evidence from observational studies.

OBJECTIVE: In order to assess the associations between telomere length (TL) and diabetes mellitus (DM), especially type 2 diabetes (T2DM), we performed this systematic review and meta-analysis. METHODS: PubMed, Embase, and Web of Science were thoroughly searched up to July 11, 2023. The pooled standardized mean difference (SMD) and the 95% confidence interval (CI) were evaluated using the random-effects model. Age, sex, study design, duration of diabetes, region, sample size, and body mass index (BMI) were used to stratify subgroup analyses. RESULTS: A total of 37 observational studies involving 18,181 participants from 14 countries were included in the quantitative meta-analysis. In this study, patients with diabetes had shorter TL than the non-diabetic, whether those patients had T1DM (-2.70; 95% CI: -4.47, -0.93; P<0.001), T2DM (-3.70; 95% CI: -4.20, -3.20; P<0.001), or other types of diabetes (-0.71; 95% CI: -1.10, -0.31; P<0.001). Additionally, subgroup analysis of T2DM showed that TL was significantly correlated with age, sex, study design, diabetes duration, sample size, detection method, region, and BMI. CONCLUSION: A negative correlation was observed between TL and DM. To validate this association in the interim, more extensive, superior prospective investigations and clinical trials are required.

Investigating the Potential of CO2 Nanobubble Systems for Enhanced Oil Recovery in Extra-Low-Permeability Reservoirs.

Carbon Capture, Utilization, and Storage (CCUS) stands as one of the effective means to reduce carbon emissions and serves as a crucial technical pillar for achieving experimental carbon neutrality. CO2-enhanced oil recovery (CO2-EOR) represents the foremost method for CO2 utilization. CO2-EOR represents a favorable technical means of efficiently developing extra-low-permeability reservoirs. Nevertheless, the process known as the direct injection of CO2 is highly susceptible to gas scrambling, which reduces the exposure time and contact area between CO2 and the extra-low-permeability oil matrix, making it challenging to utilize CO2 molecular diffusion effectively. In this paper, a comprehensive study involving the application of a CO2 nanobubble system in extra-low-permeability reservoirs is presented. A modified nano-SiO2 particle with pro-CO2 properties was designed using the Pickering emulsion template method and employed as a CO2 nanobubble stabilizer. The suitability of the CO2 nanobubbles for use in extra-low-permeability reservoirs was evaluated in terms of their temperature resistance, oil resistance, dimensional stability, interfacial properties, and wetting-reversal properties. The enhanced oil recovery (EOR) effect of the CO2 nanobubble system was evaluated through core experiments. The results indicate that the CO2 nanobubble system can suppress the phenomena of channeling and gravity overlap in the formation. Additionally, the system can alter the wettability, thereby improving interfacial activity. Furthermore, the system can reduce the interfacial tension, thus expanding the wave efficiency of the repellent phase fluids. The system can also improve the ability of CO2 to displace the crude oil or water in the pore space. The CO2 nanobubble system can take advantage of its size and high mass transfer efficiency, among other advantages. Injection of the gas into the extra-low-permeability reservoir can be used to block high-gas-capacity channels. The injected gas is forced to enter the low-permeability layer or matrix, with the results of core simulation experiments indicating a recovery rate of 66.28%. Nanobubble technology, the subject of this paper, has significant practical implications for enhancing the efficiency of CO2-EOR and geologic sequestration, as well as providing an environmentally friendly method as part of larger CCUS-EOR.

Cumulative effects of experimental nitrogen deposition on soil chemistry in a desert steppe: A 12-year field study.

Although the effects of human-enhanced atmospheric nitrogen (N) deposition are well documented, the response of dryland soils to N deposition remains unclear owing to the divergence in hydrological outputs and soil heterogeneity. We selected a typical desert steppe in western China to simulate the effects of long-term N deposition by applying 0 (CK), 3.5, 7, and 14 g N m-2 yr-1 for 12 consecutive years. We found that, compared with the CK plots, the total N content of the upper (0-10 cm) and lower (10-20 cm) soil layers in fertilized plots increased by 8.3-14.6 % and 2.4-8.2 %, respectively. Correspondingly, the available, NH4+-, and NO3--N contents in the upper soil significantly increased by 25.5-68.3 %. However, in the lower soil, available and NO3--N contents were significantly lower than those in the CK plots, and their variation trend was opposite to that of NH4+-N, implying N turnover and leaching. As a result, the upper and lower soil pH in fertilized plots significantly decreased by 0.36-0.53 and 0.31-0.37 units; however, their CaCO3 content significantly increased by 9.8-22.8 % and 7.2-30.3 %, respectively. The total phosphorus (P) content in the upper and lower soil layers in fertilized plots significantly increased and decreased by 3.6-51.3 % and 16.7-62.5 %, respectively, however, both significantly decreased along the N fertilization gradient. Furthermore, the upper and lower soil organic carbon (SOC) content in the fertilized plots significantly increased by 57.7-78.1 % and 19.2-27.4 %, respectively. Pearson's correlation analysis revealed that available soil P was significantly negatively correlated with plant shoot Mn content (a proxy for rhizosphere carboxylates), whereas dissolved OC, SOC, and CaCO3 were significantly positively correlated, suggesting that Ca cycling is involved in P cycling and SOC sequestration. Our study suggests that long-term N input exacerbates P limitation in desert steppes, however, enhances SOC sequestration.

Gemcitabine, capecitabine, and tislelizumab in recurrent/metastatic nasopharyngeal carcinoma following prior anti-PD-1 therapy failure: A retrospective study.

PURPOSE: To evaluate the effectiveness and safety of low-dose gemcitabine and metronomic capecitabine in combination with tislelizumab for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who have previously received other anti-PD-1 therapies. METHODS: This retrospective, observational study included patients with RM-NPC who had prior treatment with anti-PD-1 therapy and subsequently received tislelizumab along with low-dose gemcitabine and metronomic capecitabine between March 2019 and August 2023. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: Among 25 eligible patients, 8 (20%) achieved a complete response (CR). The objective response rate (ORR) was 68%, and the disease control rate (DCR) was 80%. The 1-year PFS rate was 78%. All patients experienced treatment-related adverse events, which were all grade 1 or 2. CONCLUSION: The combination of tislelizumab with low-dose gemcitabine and metronomic capecitabine demonstrated promising antitumor effectiveness in RM-NPC patients who had failed previous anti-PD-1 therapy, with a manageable safety profile.

Integrated environmental assessment of a diversion-project-type urban water source considering the risks of novel and legacy contaminants.

The water diversion project is an effective engineering approach to overcome water scarcity as a water source for the area. However, the complex environmental conditions of long-distance water diversion bring many uncertainties for water security. In this study, we assessed the pollution condition and risk levels of emerging contaminants and traditional contaminants in the water and soil along a water diversion project in Tianjin. Then, we assessed the influence of eco-economic characteristics on environmental conditions and established a comprehensive assessment framework of water source sustainability by analytic hierarchy process (AHP). The results showed that excessive nutrient elements and heavy metal pollution mainly contributed to environmental problems in the water source area. Contrary to pollution assessment, the soil ecosystem was more subject to environmental pressure due to atmospheric deposition. The health risk assessment indicated that all contaminants had negligible non-carcinogenic risks for adults, with arsenic being considered a priority pollutant. The statistical analysis results indicated land use allocation was the most important factor in the environmental management of the water source area. According to the result of the integrated environmental assessment, the main characteristics of pressure zones were high pollution levels and human activity intensity. It is urgent to control agricultural pollution and allocate land use rationally for water source pressure zones. By considering the risks of traditional and emerging contaminants in water and soil, this study could support urban water source management and the sustainable development of the water diversion project.

Elucidation of hemilabile-coordination-induced tunable regioselectivity in single-site Rh-catalyzed heterogeneous hydroformylation.

Revealing key factors that modulate the regioselectivity in heterogeneous hydroformylation requires identifying and monitoring the dynamic evolution of the truly active center under real reaction conditions. However, unambiguous in situ characterizations are still lacking. Herein, we elaborately construct a series of Rh-POPs catalysts for propylene hydroformylation which exhibited tunable regioselectivity. Multi-technique approaches reveal the unique microenvironment of the diverse HRh(CO)(PPh3-frame)2 sites with distinct P-Rh-P bite angles ranging from 90° to 120° and 158° to 168°, respectively. In situ time-resolved XAFS, FT-IR, and quasi-in situ Solid-state NMR experiments combined with DFT calculations explain the dynamic evolution of the electronic and coordinate state of the distinct active sites induced by hemilabile PPh3-frame ligands and further disclose the regulatory mechanism of regioselectivity. These state-of-the-art techniques and multiscale analysis advance the understanding of how hemilabile coordination influences regioselectivity and will provide a new thought to modulate the regioselectivity in future industrial processes.

Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS.

BACKGROUND: Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression. METHODS: In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 µm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min. RESULTS: The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable. CONCLUSIONS: This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. CONCLUSION: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Water-soluble biodegradable polyesters with pH and ionic responsivity.

The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body.

The clinical and genetic spectrum of mitochondrial diseases in China: A multicenter retrospective cross-sectional study.

Mitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large-scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.0 (18.5) years. The predominant phenotype was mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (45.0%). Mitochondrial DNA (mtDNA) mutations were prevalent (87.4%), with m.3243A>G being the most common locus (48.7%). Meanwhile, POLG mutations in nuclear DNA (nDNA) accounted for 16.5%. Comparative analysis based on age groups (with a cut-off at 14 years) revealed the highest prevalence of MELAS, with Leigh syndrome (LS) and chronic progressive external ophthalmoplegia (CPEO) being the second most common phenotypes in junior and senior groups, respectively. Notably, the most commonly mutated nuclear genes varied across age groups. In conclusion, MELAS predominated in this Chinese MtD cohort, underscored by m.3243A>G and POLG as principal mtDNA mutations and pathogenic nuclear genes. The phenotypic and genotypic disparities observed among different age cohorts highlight the complex nature of MtDs.

Synergistic engineering of heterostructure and oxygen vacancy in cobalt hydroxide/aluminum oxyhydroxide as bifunctional electrocatalysts for urea-assisted hydrogen production.

Designing inexpensive, high-efficiency and durable bifunctional catalysts for urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) is an encouraging tactic to produce hydrogen with reduced energy expenditure. Herein, oxygen vacancy-rich cobalt hydroxide/aluminum oxyhydroxide heterostructure on nickel foam (denoted as Co(OH)2/AlOOH/NF-100) has been fabricated using one step hydrothermal process. Theoretical calculation and experimental results indicate the electrons transfer from Co(OH)2 to highly active AlOOH results in the interfacial charge redistribution and optimization of electronic structure. Abundant oxygen vacancies in the heterostructure could improve the conductivity and simultaneously serve as the active sites for catalytic reaction. Consequently, the optimal Co(OH)2/AlOOH/NF-100 demonstrates excellent electrocatalytic performance for HER (62.9 mV@10 mA cm-2) and UOR (1.36 V@10 mA cm-2) due to the synergy between heterointerface and oxygen vacancies. Additionally, the in situ electrochemical impedance spectrum (EIS) for UOR suggests that the heterostructured catalyst exhibits rapid reaction kinetics, mass transfer and current response. Importantly, the urea-assisted electrolysis composed of the Co(OH)2/AlOOH/NF-100 manifests a low cell voltage (1.48 V @ 10 mA cm-2) in 1 M KOH containing 0.5 M urea. This work presents a promising avenue to the development of HER/UOR bifunctional electrocatalysts.

Hamiltonian diversity: effectively measuring molecular diversity by shortest Hamiltonian circuits.

In recent years, significant advancements have been made in molecular generation algorithms aimed at facilitating drug development, and molecular diversity holds paramount importance within the realm of molecular generation. Nonetheless, the effective quantification of molecular diversity remains an elusive challenge, as extant metrics exemplified by Richness and Internal Diversity fall short in concurrently encapsulating the two main aspects of such diversity: quantity and dissimilarity. To address this quandary, we propose Hamiltonian diversity, a novel molecular diversity metric predicated upon the shortest Hamiltonian circuit. This metric embodies both aspects of molecular diversity in principle, and we implement its calculation with high efficiency and accuracy. Furthermore, through empirical experiments we demonstrate the high consistency of Hamiltonian diversity with real-world chemical diversity, and substantiate its effects in promoting diversity of molecular generation algorithms. Our implementation of Hamiltonian diversity in Python is available at: https://github.com/HXYfighter/HamDiv .Scientific contributionWe propose a more rational molecular diversity metric for the community of cheminformatics and drug development. This metric can be applied to evaluation of existing molecular generation methods and enhancing drug design algorithms.

Spatiotemporal aberrations due to the groove density mismatching of compression gratings in ultra-intense femtosecond lasers.

The groove density mismatching of compression gratings, an often-neglected key issue, can induce significant spatiotemporal aberrations especially for super-intense femtosecond lasers. We mainly investigate the angular chirp and the consequent degradation of the effective focused intensity introduced by the groove density mismatching of compression gratings in ultra-intense femtosecond lasers. The results indicate that the tolerances of grating groove density mismatching will rapidly decrease with the beam aperture or spectral bandwidth increases. For our 100PW laser under construction, the grating groove density mismatching should be as small as 0.001 gr/mm if the drop of effective focused intensity has to be controlled below 15%. More importantly, new angular chirp compensation schemes are proposed for both double-grating and four-grating compressors. This work reveals the importance of groove density matching of compression gratings, and can provide helpful guidelines for the design of ultra-intense femtosecond lasers.

Exploring the influencing factors on acne, melasma, and rosacea: A case-control study in China.

BACKGROUND: The severity and treatment response of acne, melasma, and rosacea may be influenced by various currently unclear internal and external factors. This study aimed to provide evidence to the influencing factors for the mentioned conditions through a real-world case-control study. METHODS: An online survey consisting of 60 questions was implemented, collecting information on demographics, socioeconomics, genetic factors, lifestyle habits, environmental exposures, and skin care behaviors. Then we constructed univariate and multivariate logistic regressions. Furthermore, we analyzed the dose-response relationship between exposure and outcome. RESULTS: A total of 399 individuals, including 94 acne patients, 107 melasma patients, and 91 rosacea patients were included. Acne and melasma were positively correlated with screen time (acne: odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.25-4.02; melasma: OR: 1.59, 95% CI: 1.09-2.31), while exercise exerted a protective effect on both acne (OR: 0.31, 95% CI: 0.13-0.77) and melasma (OR: 0.42, 95% CI: 0.22-0.80) in a dose-response relationship. In addition, males were associated with an elevated risk of acne (OR: 6.62, 95% CI: 1.01-43.26). Aging (OR: 1.15, 95% CI: 1.07-1.24) and irregular bowel movements (OR: 2.99, 95% CI: 1.11-8.08) were independent risk factors for melasma. Rosacea was positively associated with BMI (OR: 1.17, 95% CI: 1.01-1.35). CONCLUSION: In our study, we highlighted exercise as an independent protective factor for both acne and melasma in a dose-response trend. Inversely, extended use of electronic equipment was independently associated with higher risks of acne and melasma. Rosacea, however, was more likely to be related with BMI.

ARTEMIS: An independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions.

INTRODUCTION: Breast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis. OBJECTIVES: Using DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models. RESULTS: ARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR=15.43, 95 % CI: 9.57-24.88, P=3.06 × 10-29). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC3-year = 0.844 (95 % CI: 0.805-0.883), AUC5-year = 0.816 (95 % CI: 0.775-0.857), and C-index = 0.803 (95 % CI: 0.776-0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95 % CI: 1.038-1.083) and 1.090 (95 % CI: 1.057-1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (Pt = 0.4: NB3-year = 0.019, NB5-year = 0.062; NR3-year = 69.21 %, NR5-year = 56.01 %). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/. CONCLUSION: ARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.

LIFR regulates cholesterol-driven bidirectional hepatocyte-neutrophil cross-talk to promote liver regeneration.

Liver regeneration is under metabolic and immune regulation. Despite increasing recognition of the involvement of neutrophils in regeneration, it is unclear how the liver signals to the bone marrow to release neutrophils after injury and how reparative neutrophils signal to hepatocytes to reenter the cell cycle. Here we report that loss of the liver tumour suppressor Lifr in mouse hepatocytes impairs, whereas overexpression of leukaemia inhibitory factor receptor (LIFR) promotes liver repair and regeneration after partial hepatectomy or toxic injury. In response to physical or chemical damage to the liver, LIFR from hepatocytes promotes the secretion of cholesterol and CXCL1 in a STAT3-dependent manner, leading to the efflux of bone marrow neutrophils to the circulation and damaged liver. Cholesterol, via its receptor ERRα, stimulates neutrophils to secrete hepatocyte growth factor to accelerate hepatocyte proliferation. Altogether, our findings reveal a LIFR-STAT3-CXCL1-CXCR2 axis and a LIFR-STAT3-cholesterol-ERRα-hepatocyte growth factor axis that form bidirectional hepatocyte-neutrophil cross-talk to repair and regenerate the liver.