Tracking the extensive three-dimensional motion of single ions by an engineered point-spread function.

Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Citrus-derived flavanones as neuraminidase inhibitors: In vitro and in silico study.

Neuraminidase (NA) has been well-studied as a therapeutic target for Influenza. However, resistance to the influenza virus has been observed recently. Out of special interest in the utilization of dietary antivirals from citrus, in vitro inhibition activity against NA and in silico studies including molecular docking, molecular dynamic simulation, and a predictive ADMET study, were performed on five citrus-derived flavanones. Encouragingly, citrus-derived flavanones displayed comparable or even more potent in vitro inhibitory activity than oseltamivir carboxylate against NA. Orange peel extract exhibited higher activity than hesperidin. Among the tested compounds, neohesperidin, forming strong hydrogen-bonding interactions with key arginine residues, exhibited the most effective inhibitory activity against NAs from C. perfringens, consistent with the results of molecular dynamics simulations. Although the molecular docking results were inconsistent with the in vitro activity, the binding energy was identical against the wild-type and mutant, suggesting a lower likelihood of developing drug resistance. Moreover, predictive ADMET studies showed favorable pharmacokinetic properties for the tested compounds. Overall, citrus fruit peel emerges as a promising dietary supplement for prevention and treatment of influenza. These findings elucidate the impact of flavanones on NA activity, and the analysis of their binding modes provides valuable insights into the mechanism of NA inhibition.

Integrative Analyses Reveal the Correlation Between the Airway Microbiome and Host Metabolism in Severe Community-acquired Pneumonia.

Community-acquired pneumonia (CAP) is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe CAP remains unclear. To address this knowledge gap, we conducted a comprehensive analysis utilizing 16S sequencing and LC-MS/MS metabolomics data to characterize the microbial profile in sputum and metabolic profile in serum in patients with severe community-acquired pneumonia (sCAP). Our analysis identified 13 genera through LEfSe analysis and 15 metabolites meeting specific criteria (P < 0.05, VIP ≥ 2, and |Log2(FC)| ≥ 2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in sCAP patients have important implications for optimizing early diagnosis and developing individualized therapeutic strategies.

Screening for carotid atherosclerosis: development and validation of a high-precision risk scoring tool.

Objective: This study aimed to investigate the prevalence of carotid atherosclerosis (CAS), especially among seniors, and develop a precise risk assessment tool to facilitate screening and early intervention for high-risk individuals. Methods: A comprehensive approach was employed, integrating traditional epidemiological methods with advanced machine learning techniques, including support vector machines, XGBoost, decision trees, random forests, and logistic regression. Results: Among 1,515 participants, CAS prevalence reached 57.4%, concentrated within older individuals. Positive correlations were identified with age, systolic blood pressure, a history of hypertension, male gender, and total cholesterol. High-density lipoprotein (HDL) emerged as a protective factor against CAS, with total cholesterol and HDL levels proving significant predictors. Conclusions: This research illuminates the risk factors linked to CAS and introduces a validated risk scoring tool, highlighted by the logistic classifier's consistent performance during training and testing. This tool shows potential for pinpointing high-risk individuals in community health programs, streamlining screening and intervention by clinical physicians. By stressing the significance of managing cholesterol levels, especially HDL, our findings provide actionable insights for CAS prevention. Nonetheless, rigorous validation is paramount to guarantee its practicality and efficacy in real-world scenarios.

The effects of different lung parts, age, and batches on the lung microbiota of healthy rats.

BACKGROUND: Rat models are valuable tools to study the lung microbiota in diseases. Yet the impacts of different lung parts, young and mature adult stages, and the different batches of the same conditions on the healthy rat lung microbiome have not been investigated. METHODS: The rat lung microbiome was analyzed to clarify the lung part-dependent and age-dependent differences and to evaluate the effects of several 'batch environmental factors' on normal rats, after eliminating potential contamination. RESULTS: The results showed that the contamination could be identified and excluded. The lung microbiome from left and right lung parts was very similar so one representative part could be used in the microbiome study. There were significantly different lung microbial communities between the young and mature adult groups, and also between the different feeding batches groups of the same repetitive feeding conditions, but a common lung microbiota characterized by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria as the most dominant phyla were present in all adult rats. It indicated that the experiment under the same condition of the same rats batch was needed to compare the difference in the lung microbiota and repeated experiments were necessary to confirm the results. CONCLUSION: These data represented that the lung bacterial communities were dynamic and rapidly susceptible to environmental influence, clustered strongly by age or different feeding batches but similar in the different lung tissue parts. This study improved the basic understanding of the potential effects on the lung microbiome of healthy rats.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

FACT mediates the depletion of macroH2A1.2 to expedite gene transcription.

The histone variant macroH2A is generally linked to transcriptionally inactive chromatin, but how macroH2A regulates chromatin structure and functions in the transcriptional process remains elusive. This study reveals that while the integration of human macroH2A1.2 into nucleosomes does not affect their stability or folding dynamics, it notably hinders the maintenance of facilitates chromatin transcription's (FACT's) function. We show that FACT effectively diminishes the stability of macroH2A1.2-nucleosomes and expedites their depletion subsequent to the initial unfolding process. Furthermore, we identify the residue S139 in macroH2A1.2 as a critical switch to modulate FACT's function in nucleosome maintenance. Genome-wide analyses demonstrate that FACT-mediated depletion of macroH2A-nucleosomes allows the correct localization of macroH2A, while the S139 mutation reshapes macroH2A distribution and influences stimulation-induced transcription and cellular response in macrophages. Our findings provide mechanistic insights into the intricate interplay between macroH2A and FACT at the nucleosome level and elucidate their collective role in transcriptional regulation and immune response of macrophages.

Ischemic core volume is associated with hemorrhagic transformation post endovascular thrombectomy.

INTRODUCTION: Symtomatic hemorrhagic transformation(sHT) was defined as any intracerebral hemorrhage that combined with clinical deterioration. While recent studies showed low rates of sHT in large core ischemic strokes treated with endovascular thrombectomy (EVT), the specific impact of core size on overall hemorrhagic transformation (HT) remains unclear. We aim to investigate the relationship between ischemic core size and development of HT post thrombectomy. METHODS: This prospective study enrolled acute ischemic stroke (AIS) patients with anterior large vessel occlusion undergoing EVT who had baseline MRI from 2017-2019. Pre-EVT Arterial Spin Labeling (ASL) and Diffusion-Weighted Imaging (DWI) scans were performed for volume calculations. Primary outcome was HT assessed within 72 hours post EVT. Multivariable logistic regression was used to analyze the associations between baseline DWI and ASL volumes and HT occurrence. Discriminative ability for HT was compared using receiver operating curve analysis (c-statistic). RESULTS: We included 101 patients (median age: 64 [IQR 56-74] years, baseline NIHSS 13 [IQR 9-16]). Median DWI and ASL volume were 21.0 ml [IQR 8.3-47.2] and 105ml [59.5-172.9], respectively. 36.8% recieved intravenous thrombolysis before EVT. HT occurred in 36.6% of patients, including 16.8% with sHT. Baseline DWI volume was independently associated with HT (OR=1.030, 95% CI 1.008 to 1.053, P=0.009), while ASL volume wasn't statistically significant(P=0.330). The DWI model was superior to ASL model in predicting HT within 72 hours (c-statistic, 0.787).Neither DWI (P=0.149) nor ASL volume (P=0.834) effectively indicated sHT. CONCLUSIONS: DWI-based ischemic core volume correlates significantly with HT within 72 hours post successful thrombectomy. This highlights the potential clinical utility of DWI in guiding treatment decisions for this population.

Glycerol metabolism contributes to competition by oral streptococci through production of hydrogen peroxide.

As a biological byproduct from both humans and microbes, glycerol's contribution to microbial homeostasis in the oral cavity remains understudied. In this study, we examined glycerol metabolism by Streptococcus sanguinis, a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II (manL), glycerol metabolism (glp and dha pathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H2O2), transcription, and competition with Streptococcus mutans. Biochemical assays identified the glp pathway as a novel source for H2O2 production by S. sanguinis that is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that the glp pathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of either manL or ccpA increased the expression of spxB and a second, H2O2-non-producing glycerol metabolic pathway (dha), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness of S. sanguinis against S. mutans. The glp pathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate source for growth, benefit from the catabolism of glycerol through production of both ATP and H2O2. IMPORTANCE: Glycerol is an abundant carbohydrate in the oral cavity. However, little is understood regarding the metabolism of glycerol by commensal streptococci, some of the most abundant oral bacteria. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. In this study, we show that Streptococcus sanguinis, a commensal associated with dental health, can degrade glycerol for persistence and competition through two pathways, one of which generates hydrogen peroxide at levels capable of inhibiting Streptococcus mutans. Preliminary studies suggest that several additional commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis, which warrants further exploration.

Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of ß-cell function.

OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.

Combating coal-burning-borne endemic arsenism in Shaanxi Province, Northwest China: The impact of high-arsenic coal ban, improved cook-stoves, and health education.

To eliminate the epidemic of coal-burning-borne endemic arsenism (CBBA), our study organized and implemented comprehensive measures including high-arsenic coal ban, improved cook-stoves, and health education. We also aimed to promote the application value of these measures in preventing and controlling CBBA to the world. From 2004 to 2005, through a stratified random sampling method, we selected 58,256 individuals to investigate the prevalence of CBBA and the arsenic levels in 1287 environmental and biological specimens. The prevalence of CBBA was 19.26 % and significantly associated with the arsenic levels in coal, pepper, corn and hair, which were at or exceeded national upper limits. To timely prevent and control the disease, the comprehensive measures have been implemented since 2005 to present. Comparison and correlation analyses were utilized to evaluate the effectiveness of these measures in reducing the prevalence of CBBA. According to statistics, 73 high-arsenic coal mines were banned and over 99 % households in endemic areas accepted stove improvements and diversified health education. Monitoring studies during 2010-2019 has confirmed that these measures led to a decrease in urine arsenic levels among endemic residents, and they developed novel dietary practices, such as properly drying, storage, and washing of food. Additionally, the awareness rate of CBBA increased from less than 70 % to over 95 %. Finally, the prevalence of CBBA has decreased to 0.153 % investigated by a census involving 2.076 million endemic residents in 2019. In summary, CBBA in northwest China has been successfully controlled through banning on high-arsenic coal, introducing improved cook-stoves, and providing health education.

The next frontier in immunotherapy: potential and challenges of CAR-macrophages.

Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers a promising approach to target and eradicate tumor cells by utilizing macrophages' phagocytic and antigen-presenting abilities. However, challenges such as the complex tumor microenvironment (TME), variability in antigen expression, and immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of CAR-MΦ action, optimal construct designs, and interactions within the TME. It also delves into the ex vivo manufacturing challenges of CAR-MΦ, discussing autologous and allogeneic sources and the importance of stringent quality control. The potential synergies of integrating CAR-MΦ with existing cancer therapies like checkpoint inhibitors and conventional chemotherapeutics are examined to highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways for CAR-MΦ therapies are scrutinized alongside established protocols for CAR-T cells, identifying unique considerations essential for clinical trials and market approval. Proposed safety monitoring frameworks aim to manage potential adverse events, such as cytokine release syndrome, crucial for patient safety. Consolidating current research and clinical insights, this review seeks to refine CAR-MΦ therapeutic applications, overcome barriers, and suggest future research directions to transition CAR-MΦ therapies from experimental platforms to standard cancer care options.

RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance.

Background: RAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated. Methods: A variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of in vitro cellular experiments. Results: RAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC > 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC. Conclusion: Overexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.

UV-activated calcium peroxide system enables simultaneous organophosphorus degradation, phosphate recovery, and carbon fixation.

Advanced oxidation processes are a desirable technology for treatment of contaminants of emerging concern. Nevertheless, conventional advanced oxidation of organophosphorus compounds releases inorganic phosphate, posing downstream concerns related to eutrophication. For this reason, we evaluated the ultraviolet light-activated calcium peroxide (UV/CaO2) system for effective treatment of organophosphorus compounds and concurrent capture of the mineralization products, phosphate. The degradation mechanisms, reaction kinetics, and mineralizations were assessed to determine the overall efficiency and performance of the UV/CaO2 process. Knowledge gaps related to photocatalysis in the UV/CaO2 system were not only addressed, but also leveraged to identify unique advantages for removal of organophosphorus compounds and their degradation products. Experimental results confirmed that the UV/CaO2 system effectively mineralized organophosphorus compounds and recovered inorganic phosphate; additionally, collaborative carbon fixation performance of the system reveals the potential of carbon utilization. These outcomes were facilitated by the alkaline environment generated by CaO2. The recovered solids contained most of the phosphorus and carbon from the parent compounds. Ultimately, these findings provide transformative, new insights into the development and application of advanced oxidation processes that prevent downstream concerns related to mineralization products, especially inorganic phosphorus and carbon.

Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4-6 weeks.

BACKGROUND: A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus. METHODS: In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement. Relevant information, including SARS-CoV-2 infection, and other potential risk factors were collected. Conditional logistic regression was used to test possible associations between fetal situs inversus and SARS-CoV-2 infection at different gestational weeks as well as individual risk factors. FINDINGS: A total of 52 pregnant women diagnosed with fetal situs inversus between January 1 and October 31, 2023 and 208 matched controls with normal fetuses were enrolled. We found no association between an increased risk of fetal situs inversus with gestational SARS-CoV-2 infection or with other risk factors. However, fetal situs inversus was significantly associated with SARS-CoV-2 infection specifically in gestational weeks 4-6 (adjusted odds ratio [aOR] 6.54 [95% confidence interval 1.76-24.34]), but not with infection at other gestational ages, after adjusting for covariates. CONCLUSIONS: Increased risk of fetal situs inversus is significantly associated with maternal SARS-CoV-2 infection at gestational weeks 4-6, corresponding to the fetal developmental window for visceral lateralization in humans. FUNDING: National Key R&D Program of China, etc.

LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling.

High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

Amniotic fluid proteomic analysis identifies IL1RL1, APOE, and NECTIN4 as new biomarkers for preterm birth.

BACKGROUND: Despite extensive research, the identification of effective biomarkers for early prediction of preterm birth (PTB) continues to be a challenging endeavor. This study aims to identify amniotic fluid (AF) protein biomarkers useful for the early diagnosis of PTB. METHODS: We initially identified the protein expression profiles in the AF of women with PTB (n = 22) and full-term birth (FTB, n = 22), from the First People's Hospital of Yunnan Province who underwent amniocentesis from November 2019 to February 2020, using mass spectrometry employing the data-independent acquisition (DIA) technique, and then analyzed differentially expressed proteins (DEPs). Subsequently, the least absolute shrinkage and selection operator (LASSO) and random forest analysis were employed to further screen the key proteins for PTB biomarker identification. The receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analyses (DCA) were utilized to assess the discrimination and calibration of the key biomarkers. RESULTS: A total of 25 DEPs were identified between the PTB and FTB groups, comprising 13 up-regulated and 12 down-regulated proteins. Three key protein biomarkers for early PTB diagnosis were identified: IL1RL1 (interleukin-1 receptor-like 1), APOE (apolipoprotein E), and NECTIN4 (nectin cell adhesion molecule 4). The results of the ROC analysis showed that the area under the curve (AUC) of the three proteins combined as a biomarker for early diagnosis of PTB was 0.913 (95% CI: 0.823-1.000), with a sensitivity of 0.864 and a specificity of 0.955, both superior to those of the individual biomarkers. Bootstrap internal validation revealed a concordance index (C-index) of 0.878, with a sensitivity of 0.812 and a specificity of 0.773, indicating the robust predictive performance of these biomarkers. CONCLUSIONS: We identified three previously unexplored yet potentially useful protein biomarkers in AF for early PTB diagnosis: IL1RL1, APOE, and NECTIN4.

The acceptability and effectiveness of artificial intelligence-based chatbot for hypertensive patients in community: protocol for a mixed-methods study.

BACKGROUND: Chatbots can provide immediate assistance tailored to patients' needs, making them suitable for sustained accompanying interventions. Nevertheless, there is currently no evidence regarding their acceptability by hypertensive patients and the factors influencing the acceptability in the real-world. Existing evaluation scales often focus solely on the technology itself, overlooking the patients' perspective. Utilizing mixed methods can offer a more comprehensive exploration of influencing factors, laying the groundwork for the future integration of artificial intelligence in chronic disease management practices. METHODS: The mixed methods will provide a holistic view to understand the effectiveness and acceptability of the intervention. Participants will either receive the standard primary health care or obtain a chatbot speaker. The speaker can provide timely reminders, on-demand consultations, personalized data recording, knowledge broadcasts, as well as entertainment features such as telling jokes. The quantitative part will be conducted as a quasi-randomized controlled trial in community in Beijing. And the convergent design will be adopted. When patients use the speaker for 1 month, scales will be used to measure patients' intention to use the speaker. At the same time, semi-structured interviews will be conducted to explore patients' feelings and influencing factors of using speakers. Data on socio-demography, physical examination, blood pressure, acceptability and self-management behavior will be collected at baseline, as well as 1,3,6, and 12 months later. Furthermore, the cloud database will continuously collect patients' interactions with the speaker. The primary outcome is the efficacy of the chatbot on blood pressure control. The secondary outcome includes the acceptability of the chatbot speaker and the changes of self-management behavior. DISCUSSION: Artificial intelligence-based chatbot speaker not only caters to patients' self-management needs at home but also effectively organizes intricate and detailed knowledge system for patients with hypertension through a knowledge graph. Patients can promptly access information that aligns with their specific requirements, promoting proactive self-management and playing a crucial role in disease management. This study will serve as a foundation for the application of artificial intelligence technology in chronic disease management, paving the way for further exploration on enhancing the communicative impact of artificial intelligence technology. TRIAL REGISTRATION: Biomedical Ethics Committee of Peking University: IRB00001052-21106, 2021/10/14; Clinical Trials: ChiCTR2100050578, 2021/08/29.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy.

OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.