Identification of key risk factors for venous thromboembolism in urological inpatients based on the Caprini scale and interpretable machine learning methods.

PURPOSE: To identify the key risk factors for venous thromboembolism (VTE) in urological inpatients based on the Caprini scale using an interpretable machine learning method. METHODS: VTE risk data of urological inpatients were obtained based on the Caprini scale in the case hospital. Based on the data, the Boruta method was used to further select the key variables from the 37 variables in the Caprini scale. Furthermore, decision rules corresponding to each risk level were generated using the rough set (RS) method. Finally, random forest (RF), support vector machine (SVM), and backpropagation artificial neural network (BPANN) were used to verify the data accuracy and were compared with the RS method. RESULTS: Following the screening, the key risk factors for VTE in urology were "(C1) Age," "(C2) Minor Surgery planned," "(C3) Obesity (BMI > 25)," "(C8) Varicose veins," "(C9) Sepsis (< 1 month)," (C10) "Serious lung disease incl. pneumonia (< 1month) " (C11) COPD," "(C16) Other risk," "(C18) Major surgery (> 45 min)," "(C19) Laparoscopic surgery (> 45 min)," "(C20) Patient confined to bed (> 72 h)," "(C18) Malignancy (present or previous)," "(C23) Central venous access," "(C31) History of DVT/PE," "(C32) Other congenital or acquired thrombophilia," and "(C34) Stroke (< 1 month." According to the decision rules of different risk levels obtained using the RS method, "(C1) Age," "(C18) Major surgery (> 45 minutes)," and "(C21) Malignancy (present or previous)" were the main factors influencing mid- and high-risk levels, and some suggestions on VTE prevention were indicated based on these three factors. The average accuracies of the RS, RF, SVM, and BPANN models were 79.5%, 87.9%, 92.6%, and 97.2%, respectively. In addition, BPANN had the highest accuracy, recall, F1-score, and precision. CONCLUSIONS: The RS model achieved poorer accuracy than the other three common machine learning models. However, the RS model provides strong interpretability and allows for the identification of high-risk factors and decision rules influencing high-risk assessments of VTE in urology. This transparency is very important for clinicians in the risk assessment process.

Cell volume regulation modulates macrophage-related inflammatory responses via JAK/STAT signaling pathways.

Cell volume as a characteristic of changes in response to external environmental cues has been shown to control the fate of stem cells. However, its influence on macrophage behavior and macrophage-mediated inflammatory responses have rarely been explored. Herein, through mediating the volume of macrophages by adding polyethylene glycol (PEG), we demonstrated the feasibility of fine-tuning cell volume to regulate macrophage polarization towards anti-inflammatory phenotypes, thereby enabling to reverse macrophage-mediated inflammation response. Specifically, lower the volume of primary macrophages can induce both resting macrophages (M0) and stimulated pro-inflammatory macrophages (M1) to up-regulate the expression of anti-inflammatory factors and down-regulate pro-inflammatory factors. Further mechanistic investigation revealed that macrophage polarization resulting from changing cell volume might be mediated by JAK/STAT signaling pathway evidenced by the transcription sequencing analysis. We further propose to apply this strategy for the treatment of arthritis via direct introduction of PEG into the joint cavity to modulate synovial macrophage-related inflammation. Our preliminary results verified the credibility and effectiveness of this treatment evidenced by the significant inhibition of cartilage destruction and synovitis at early stage. In general, our results suggest that cell volume can be a biophysical regulatory factor to control macrophage polarization and potentially medicate inflammatory response, thereby providing a potential facile and effective therapy for modulating macrophage mediated inflammatory responses. STATEMENT OF SIGNIFICANCE: Cell volume has recently been recognized as a significantly important biophysical signal in regulating cellular functionalities and even steering cell fate. Herein, through mediating the volume of macrophages by adding polyethylene glycol (PEG), we demonstrated the feasibility of fine-tuning cell volume to induce M1 pro-inflammatory macrophages to polarize towards anti-inflammatory M2 phenotype, and this immunomodulatory effect may be mediated by the JAK/STAT signaling pathway. We also proposed the feasible applications of this PEG-induced volume regulation approach towards the treatment of osteoarthritis (OA), wherein our preliminary results implied an effective alleviation of early synovitis. Our study on macrophage polarization mediated by cell volume may open up new pathways for immune regulation through microenvironmental biophysical clues.

Psychological resilience factors in intensive care nursing: a hybrid multi-criteria decision-making model.

PURPOSE: To analyze the key factors influencing the psychological resilience of intensive care unit (ICU) nurses during the COVID-19 pandemic and put forward suggestions promoting resilience based on key improvement factors and clinical experience. METHODS: Data were collected from 35 ICU nurses in a hospital in Zhejiang Province, China, through a questionnaire survey conducted between January and February 2023. The Decision-Making Trial and Evaluation Laboratory (DEMATEL) method was then used to construct and visualize the relationship structure between the factors. The DEMATEL-based Analytical Network Process (DANP) was applied to determine the influential weights of all factors. Finally, the key improvement factors were identified using importance-performance analysis (IPA). RESULTS: Based on the cause-effect impact network diagram (CEIND), it was concluded that (C 11), (C 22), and (C 32) are the key factors that promote the improvement of psychological resilience among ICU nurses. Additionally, these factors were the key factors that influence psychological resilience. The confidence levels of these results and the gap were 99.6% and 0.4%, respectively, which exceed the threshold value of 95%, indicating good stability. Finally, for the case hospitals, (C 13) was identified as the key improvement factor. CONCLUSIONS: Hospital administrators should support ICU nurses in enhancing their psychological resilience during major epidemics by: (i) Providing training on comprehensive protective measures and nursing skills; (ii) Effectively managing the human resources of nurses in the hospital to reduce their workload; (iii) Increasing social and organizational support for nurses to alleviate anxiety caused by large-scale public health events and improve their psychological resilience.

Static and dynamic interactions within the triple-network model in stroke patients with multidomain cognitive impairments.

BACKGROUND: Internal capsule strokes often result in multidomain cognitive impairments across memory, attention, and executive function, typically due to disruptions in brain network connectivity. Our study examines these impairments by analyzing interactions within the triple-network model, focusing on both static and dynamic aspects. METHODS: We collected resting-state fMRI data from 62 left (CI_L) and 56 right (CI_R) internal capsule stroke patients, along with 57 healthy controls (HC). Using independent component analysis to extract the default mode (DMN), executive control (ECN), and salience networks (SAN), we conducted static and dynamic functional network connectivity analyses (DFNC) to identify differences between stroke patients and controls. For DFNC, we used k-means clustering to focus on temporal properties and multilayer network analysis to examine integration and modularity Q, where integration represents dynamic interactions between networks, and modularity Q measures how well the network is divided into distinct modules. We then calculated the correlations between SFNC/DFNC properties with significant inter-group differences and cognitive scales. RESULTS: Compared to HC, both CI_L and CI_R patients showed increased static FCs between SAN and DMN and decreased dynamic interactions between ECN and other networks. CI_R patients also had heightened static FCs between SAN and ECN and maintained a state with strongly positive FNCs across all networks in the triple-network model. Additionally, CI_R patients displayed decreased modularity Q. CONCLUSION: These findings highlight that stroke can result in the disruption of static and dynamic interactions in the triple network model, aiding our understanding of the neuropathological basis for multidomain cognitive deficits after internal capsule stroke.

Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity.

Background: Impaired sensitivity to thyroid hormones (TH) was associated with metabolic syndrome. The study aimed to explore the association between central TH sensitivity indices and insulin resistance (IR) in euthyroid adults with obesity. Methods: This cross-sectional study enrolled 293 euthyroid outpatients with obesity in Beijing Chao-Yang Hospital. We used the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity. IR was assessed by homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin resistance index (hepatic-IR), the Matsuda index, and the adipose tissue insulin resistance index (Adipo-IR). Participants were categorized according to tertiles of TH sensitivity indices. We used multiple linear regressions to explore the associations. Results: There was a significant stepwise increase in HOMA-IR and Adipo-IR from the lowest to the highest tertiles of TH sensitivity indices (all P<0.05). After adjustment for age, sex, body mass index, hypertension, hyperlipidemia, and diabetes, only Adipo-IR was significantly associated with TH sensitivity indices. On average, each unit increased in TFQI, TSHI, and TT4RI was associated with 1.19 (P=0.053), 1.16 (P=0.04), and 1.01 (P=0.03) units increased in Adipo-IR, respectively. There was no significant association between TH sensitivity indices and HOMA-IR, hepatic-IR, and the Matsuda index after adjustment for other risk factors. Conclusions: Reduced central TH sensitivity was associated with increased adipose tissue insulin resistance in euthyroid adults with obesity. The results further confirmed the importance of TH sensitivity on metabolic diseases.

Se vacancies and interface engineering modulated bifunctionality prussian blue analogue derivatives for overall water splitting.

It is a challenging task to design and synthesize stable, and high-performance non-precious metals bifunctional catalysts for water-splitting. Herein, the coupling between Se vacancy and interface engineering is highlighted to synthesize a unique CoFeSe hollow nanocubes structure on MXene-modified nickel foam (NF) by in-situ phase transition from bifunctionality prussian blue analogue (PBA) derivatives (VSe-CoFeSe@MXene/NF). DFT theory reveals that the Se vacancy and interface engineering modulate the surface electronic structure and optimize the surface adsorption energy of the intermediates. Experimental data also confirm that the as-prepared CoFeSe@MF catalyst exhibits advanced electrocatalytic properties, 283 mV (OER) and 67 mV (HER) are required to drive the current density of 10 mA cm-2. Notably, it is assembled into a two-electrode system for integral water decomposition, which only requires a low cell potential of 1.57 V at current of 10 mA cm-2, together with excellent durability for 48 h. The strategy is expected to provide a new direction for the design and construction of highly efficient collaborative integrated water decomposition electrocatalysts.

Altered cerebellar-cerebral dynamic functional connectivity in patients with pontine stroke: a resting-state fMRI study.

Potential changes in patterns of dynamic functional network connections at the cerebellar-cerebral level in pontine infarction (PI) patients remain unclear. The study aimed to investigate the abnormal patterns of dynamic functional connectivity (dFC) between the cerebellar subregions within networks and regions of the cerebral cortex in patients with PI. Forty-six chronic left pontine infarction (LPI), 32 chronic right pontine infarction (RPI), and 50 healthy controls (HCs) were recruited to undergo resting-state fMRI scans. Cerebellar-cerebral dFC was characterized using the sliding window method and seed-based connectivity analyses. Correlations between altered dFC values and clinical variables (The Rey Auditory Verbal Learning Test and Flanker task) in PI patients and healthy controls were investigated. Compared with HCs, the PI groups showed significantly aberrant cerebellar-cerebral dFC between cerebellar subregions within networks and supratentorial cerebral cortex, including executive, default-mode, and motor networks. Furthermore, Correlation analysis showed a decoupling between abnormal dFC and cognitive functions in PI patients. These findings indicate that PI patients are accompanied by damage to cerebellar subregions within networks and cerebellar-cerebral pathways, which may provide a potential target for treatment or an indication of therapeutic efficacy.

Reducing anxiety and enhancing satisfaction in thyroid patients with DietLens application during radioactive iodine therapy: A quasi-experimental study.

Hyperthyroidism and thyroid cancer significantly impact health, and often require Radioactive Iodine (RAI) therapy. Anxiety is common in patients undergoing RAI, particularly related to dietary compliance. This study aimed to assess the effectiveness of the mobile health application, DietLens in reducing anxiety and increasing satisfaction in patients preparing for RAI therapy, focusing on low-iodine diet (LID). A quasi-experimental study was conducted in a Singapore tertiary hospital outpatient department from March 13, 2019 to March 27, 2020, involving patients scheduled for their first RAI treatment. Participants were divided into a control group receiving standard care and an intervention group using DietLens alongside standard care. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and satisfaction levels were measured through self-reported questionnaires. In the study, 56 participants were initially divided into control (n = 28) and intervention (n = 28) groups. After accounting for dropouts, 50 participants finished the study, with each group comprising 25 individuals. Anxiety levels were similar between groups pre-intervention. Post-intervention, the intervention group displayed a significant decrease in anxiety levels compared to the control group (independent t-test: t (48) = 2.50, p = 0.02). The multivariate linear regression analysis indicated that being in the intervention group was significantly associated with a decrease in post-intervention anxiety score (ß = -4.03, 95 % CI: -7.33 to -0.72, p = 0.02). Fisher's Exact Test revealed a borderline significant difference in satisfaction with educational materials and the overall treatment process, with 100 % of the intervention group expressing satisfaction compared to 80 % in the control group, resulting in a p-value of 0.052 in both instances. DietLens was effective in reducing anxiety and enhancing satisfaction related to RAI therapy preparation, particularly in managing a LID, highlighting a beneficial role for digital interventions in healthcare settings.

Associations between body weight trajectories and neurodevelopment outcomes at 24 months corrected age in very-low-birth-weight preterm infants: a group-based trajectory modelling study.

Introduction: This study aimed to explore the relationship between the trajectories of body weight (BW) z-scores at birth, discharge, and 6 months corrected age (CA) and neurodevelopmental outcomes at 24 months CA. Methods: Conducted as a population-based retrospective cohort study across 21 hospitals in Taiwan, we recruited 3,334 very-low-birth-weight (VLBW) infants born between 2012 and 2017 at 23-32 weeks of gestation. Neurodevelopmental outcomes were assessed at 24 months CA. Instances of neurodevelopmental impairment (NDI) were defined by the presence of at least one of the following criteria: cerebral palsy, severe hearing loss, profound vision impairment, or cognitive impairment. Group-based trajectory modeling was employed to identify distinct BW z-score trajectory groups. Multivariable logistic regression was used to assess the associations between these trajectories, postnatal comorbidity, and neurodevelopmental impairments. Results: The analysis identified three distinct trajectory groups: high-climbing, mid-declining, and low-declining. Significant associations were found between neurodevelopmental impairments and both cystic periventricular leukomalacia (cPVL) [with an adjusted odds ratio (aOR) of 3.59; p < 0.001] and belonging to the low-declining group (aOR: 2.59; p < 0.001). Discussion: The study demonstrated that a low-declining pattern in body weight trajectory from birth to 6 months CA, along with cPVL, was associated with neurodevelopmental impairments at 24 months CA. These findings highlight the importance of early weight trajectory and specific health conditions in predicting later neurodevelopmental outcomes in VLBW infants.

Efficacy and Safety of Thermal Ablation for Solitary Low-Risk T2N0M0 Papillary Thyroid Carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. RESULTS: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). CONCLUSION: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.

[Prognostic Value of DTA Mutations in Patients with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To investigate the prognostic significance of DTA (DNMT3A, TET2, ASXL1 ) gene mutations in patients with non-M3 acute myeloid leukemia (AML). METHODS: The clinical data of 180 newly diagnosed AML patients hospitalized in the First People's Hospital of Changzhou from January 2018 to April 2022 were retrospectively analyzed. Next-generation sequencing technology was used to detect 150 gene mutations in the patients, and log-rank tests and Cox regression models were used to analyze the prognostic factors. RESULTS: DTA gene mutations were detected in 83 (46.1%) of 180 AML patients. Compared to patients without DTA mutations, patients with DTA mutations were significantly older (P < 0.001). The median overall survival (OS) time and disease-free survival (DFS) time in the DTA mutation group were significantly shorter than those in the group without DTA mutation (both P < 0.05). Multivariate analysis showed that age ≥ 60 years (P < 0.001), with DTA mutation (P =0.018), and intermediate-risk (relative to favorable-risk) (P =0.005) were independent risk factors for OS in AML patients. CONCLUSION: AML patients with DTA mutations are relatively older, with shorter median OS time and DFS time, and poor prognosis.

A phase 2 trial of mini-hyper-CVD, blinatumomab, and ponatinib in Philadelphia positive acute lymphoblastic leukemia.

Twenty adults with newly diagnosed (ND) or relapsed/refractory (RR) Ph-positive acute lymphoblastic leukemia (ALL), or chronic myeloid leukemia in lymphoid blast phase (CML-LBP), were treated with mini-hyperCVD, ponatinib, and blinatumomab. Complete molecular response was achieved in 78% of ND patients, while CR/CRi was achieved in 100% of RR and CML-LBP. The 3-year overall survival rate was 76% (95% CI, 47%-90%).

Oocyte-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early-growing follicles by mitochondrial fission defect-reactive oxygen species-DNA damage.

BACKGROUND: Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. METHODS AND RESULTS: We generated eukaryotic translation initiation factor 5 (Eif5) conditional knockout mice aiming to investigate the function of eIF5 during oocyte growth and follicle development. Here, we demonstrated that Eif5 deletion in mouse primordial and growing oocytes both resulted in the apoptosis of oocytes within the early-growing follicles. Further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission-related proteins (p-DRP1, FIS1, MFF and MTFR) and upregulated the levels of the integrated stress response-related proteins (AARS1, SHMT2 and SLC7A1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased adenosine triphosphate content and mtDNA copy numbers, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNA damage response proteins (γH2AX, p-CHK2 and p-p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti-apoptotic protein BCL-xL. CONCLUSION: These findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early-growing follicles via mitochondrial fission defects, excessive ROS accumulation and DNA damage. This study provides new insights into pathogenesis, genetic diagnosis and potential therapeutic targets for POI. KEY POINTS: Eif5 deletion in oocytes leads to arrest in oocyte growth and follicle development. Eif5 deletion in oocytes impairs the translation of mitochondrial fission-related proteins, followed by mitochondrial dysfunction. Depletion of Eif5 causes oocyte apoptosis via ROS accumulation and DNA damage response pathway.

Toxicological mechanism of cannabidiol (CBD) exposure on zebrafish embryonic development.

Cannabidiol (CBD) is the main component of plant Cannabis (Cannabis sativa), which exhibits strong antioxidant and anti-inflammatory activities. With the legalization of CBD in the United States, it is an inevitable tendency for its global legalization in the future. Therefore, it has become an urgent task to conduct the toxicological evaluation of CBD before clinical application. In this study, the developmental toxicities of CBD on zebrafish embryos were systematically evaluated, and the mechanisms were revealed. The results showed that the phenotype of liver degeneration was observed in 96 hpf zebrafish embryos after 0.1-5 µmol/L CBD exposure, further RT-qPCR experiments indicated that the above result may attributed by the the alterations of FABP10A, GCLC, and GSR. Besides, 1 and 5 µmol/L CBD contributed to the developmental toxicities of heart and eye in zebrafish embryos, characterizing by the decrease in heart rate, the phenotype of pericardial edema, and the reduce of eye area. Compared to other organs, the liver of zebrafish displayed the most sensitive characteristic to CBD exposure, as 0.1 µmol/L CBD already led to the phenotype of liver degeneration. In summary, this paper provided theoretical supports for CBD toxicology research, and laid the foundation for its future clinical application.

Synergistic mechanism of botanical pesticide camptothecin encapsulated in a nanocarrier against fall armyworm: Enhanced stability and amplified growth suppression.

Botanical pesticides are one of the most promising alternatives to synthetic insecticides for green pest management. However, their efficacies must be further improved to meet real needs. Here we designed a nanoscale camptothecin (CPT) encapsulated in a star polycation (SPc) and determined its bioactivity against a devastating agricultural pest, Spodoptera frugiperda. The self-assembly of CPT/SPc complex was mainly driven by hydrogen bonding and Van der Waals forces to decrease the particle size from 789 to 298 nm. With the help of SPc, the contact angle of CPT decreased from 116° to 92° on maize leaves, and its retention was increased from 5.53 to 11.97 mg/cm2. The stability of SPc-loaded CPT was also improved in an alkaline environment, which is beneficial for its acting in lepidopteran insect guts. The CPT/SPc complex had stronger larvicidal activity and ovicidal activity against S. frugiperda than CPT alone, led to more complex transcriptomic changes in larvae, and had obvious adverse impacts on the activities of two digestive enzymes. Our findings demonstrated that the encapsulation of CPT by SPc-based nanodelivery system enabled better insecticidal activities against S. frugiperda, which holds great promise for the development of more efficient and sustainable pest control strategies to meet the demands of modern crop protection.

[Different levels and clinical significance of growth differentiation factor-15 in patients with atrial fibrillation].

OBJECTIVE: To measure the concentration of growth differentiation factor-15 (GDF-15) in the serum of patients with atrial fibrillation (AF), to study the correlations between the levels of GDF-15 and different factors including basic clinical information, biochemical examinations, and atrial structure, and further to explore the association between GDF-15 and AF types and structural remodeling. METHODS: AF patients who were admitted to the ward of the Department of Cardiology at Peking University Third Hospital between October 2017 and October 2019 were prospectively enrolled. Patients admitted to the ward at the same time with sinus rhythm and no prior AF history were enrolled in the control group. Clinical information and blood samples of the patients were collected. Enzyme-linked immunosorbent assay was used to measure the concentration of GDF-15. SPSS 23.0 was used for statistical analysis. RESULTS: In the study, 156 AF patients (64 persistent AF and 92 paroxysmal AF) and 38 patients of the control group were included. Serum GDF-15 levels in the AF group were significantly higher than in the control group [1 112 (723, 1 525) ng/L vs. 697 (499, 825) ng/L, P < 0.001]. Serum GDF-15 levels in the persistent AF group were significantly higher than in the paroxysmal AF group [1 140 (858, 1 708) ng/L vs. 1 090 (662, 1 374) ng/L, P=0.047]. The area under the curve (AUC) of serum GDF-15 levels for prediction of AF was 0.736 (95%CI: 0.651-0.822, P < 0.001). The cut-off value was 843.2 ng/L with a sensitivity of 68.2% and a specificity of 78.9%. The AUC of serum GDF-15 levels for prediction of persistent AF was 0.594 (95%CI: 0.504-0.684, P=0.047). The cut-off va-lue was 771.5 ng/L with a sensitivity of 82.8% and a specificity of 35.9%. Spearman rank correlation analysis showed that the serum GDF-15 levels were positively correlated with age (r=0.480, P < 0.001), left atrial pressure (LAP, r=0.300, P < 0.001), and also negatively correlated with left atrial appendage flow velocity (LAAV, r=-0.252, P=0.002). Multiple linear regression analysis showed that age and LAP affected the GDF-15 levels significantly (P < 0.05). Logistic regression analysis suggested GDF-15 (OR=1.002, 95%CI: 1.001-1.003, P=0.004) and left atrial diameter (LAD, OR=1.400, 95%CI: 1.214-1.616, P < 0.001) were independent predictors of AF. CONCLUSIONS: Serum GDF-15 levels are higher in AF patients. Meanwhile, serum GDF-15 levels are higher in persistent AF patients than paroxysmal AF patients. GDF-15 is associated with AF and atrial structural remodeling.

Fe7S8 coupled with VS4 heterogeneous interface engineering driven by FeV bimetallic MOFs: An efficient all-pH and durable hydrogen evolution.

Rational design and preparation of a multiphase electrocatalyst for hydrogen evolution reaction (HER) has become a hot research topic, while applicable and pH versatility of vanadium tetrasulfide (VS4) and heptairon octasulfide (Fe7S8) composites have rarely been reported. Here, the facile topological sulfide self-template sacrifice method using FeV bimetallic MOFs is designed to obtain Fe7S8 coupled with VS4 heterostructures, enhancing the electron precipitation in the catalysts and attracts electrons to migrate. According to DFT simulations, the electronic coupling at the atomic orbital level and the modulation of interfacial electrons among various interfaces play a crucial role in enhancing the intermediate state process of the hydrogen evolution reaction (HER) across the entire pH range, promoting the optimal d-band centroid value (εd). Reassuringly, the prepared 3D Fe7S8/VS4 electrodes possessed excellent performances of η10 = 53 mV, η10 = 135 mV and η10 = 38 mV in a conventional three-electrode configuration in a 1 M KOH, 1 M Na2SO4, and 0.5 M H2SO4, and the stabilized currents can all be maintained for 48 h. This innovative design of in situ heterostructured materials constructed from dual transition metal sulfides provides inspiring ideas for the preparation of all-pH catalysts.

Double C-H Amination of Naphthylamine Derivatives by the Cross-Dehydrogenation Coupling Reaction.

A high-efficiency tandem process has been developed for the formation of two C-N bonds through a cross-dehydrogenative coupling (CDC) amination of spiro[acridine-9,9'-fluorene]s (SAFs) with amines. This method offers a strategically innovative and atom-economical approach to obtaining diamine-substituted SAFs. Notably, the approach eliminates the need for metal catalysts and other additives, relying solely on O2 as the oxidant. A self-activation mechanism has been proposed to elucidate the effective double amination in the CDC process.

Hepatic insulin resistance affects the efficacy of metformin in patients with newly diagnosed type 2 diabetes: A Sub-Analysis of the MARCH trial.

AIM: Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients. METHODS: We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment. RESULTS: Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of ß cell function (HOMA-ß), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI. CONCLUSIONS: Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-ß, IR, and lower Matsuda index were indicators of better hepatic IR improvement.

Hierarchical multi-level dynamic hyperparameter deformable image registration with convolutional neural network.

Objective. To enable the registration network to be trained only once, achieving fast regularization hyperparameter selection during the inference phase, and to improve registration accuracy and deformation field regularity.Approach. Hyperparameter tuning is an essential process for deep learning deformable image registration (DLDIR). Most DLDIR methods usually perform a large number of independent experiments to select the appropriate regularization hyperparameters, which are time-consuming and resource-consuming. To address this issue, we propose a novel dynamic hyperparameter block, which comprises a distributed mapping network, dynamic convolution, attention feature extraction layer, and instance normalization layer. The dynamic hyperparameter block encodes the input feature vectors and regularization hyperparameters into learnable feature variables and dynamic convolution parameters which changes the feature statistics of the high-dimensional features layer feature variables, respectively. In addition, the proposed method replaced the single-level structure residual blocks in LapIRN with a hierarchical multi-level architecture for the dynamic hyperparameter block in order to improve registration performance.Main results. On the OASIS dataset, the proposed method reduced the percentage of|Jϕ|⩽0by 28.01%, 9.78%and improved Dice similarity coefficient by 1.17%, 1.17%, compared with LapIRN and CIR, respectively. On the DIR-Lab dataset, the proposed method reduced the percentage of|Jϕ|⩽0by 10.00%, 5.70%and reduced target registration error by 10.84%, 10.05%, compared with LapIRN and CIR, respectively.Significance. The proposed method can fast achieve the corresponding registration deformation field for arbitrary hyperparameter value during the inference phase. Extensive experiments demonstrate that the proposed method reduces training time compared to DLDIR with fixed regularization hyperparameters while outperforming the state-of-the-art registration methods concerning registration accuracy and deformation smoothness on brain dataset OASIS and lung dataset DIR-Lab.