Baseline neurological deficit and argatroban plus alteplase in acute ischemic stroke: A post hoc analysis of ARAIS trial.

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

Measurement invariance of the Coparenting Relationship Scale (CRS) across 10 countries.

The purpose of this study was to assess the factor structure and the measurement invariance of the Coparenting Relationship Scale (CRS) across 10 countries based on the seven-factor coparenting model (i.e., Coparenting Agreement, Coparenting Closeness, Exposure to Conflict, Coparenting Support, Endorsement of Partner's Parenting; Division of Labor) proposed by Feinberg (2003). The results of research on coparenting from numerous countries have documented its foundational importance for parent mental health, family relationship quality, child development, and psychopathology. Yet, a cross-country perspective is still lacking. Such a perspective can provide insight into which dimensions of coparenting are universally recognized and which are especially prone to variation. A unique multinational data set, comprised of 15 individual studies collected across 10 countries (Belgium, Brazil, China, Israel, Italy, Japan, Portugal, Switzerland, Turkey, USA) in nine languages was established (N = 9,292; 51.1% mothers). Measurement invariance analyses were conducted. A six-factor structure (original seven factors minus Division of Labor) of the measure was consistent across the different contexts and measurement invariance was achieved at the configural level. There was no support for metric or scalar invariance. These findings provide a basis for the CRS to be used across countries and should inspire future quantitative and qualitative research in cross-country coparenting research to understand what aspects are universal and what aspects of coparenting are linked to specific material, relational, or ideational conditions that underlie high-quality coparenting. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A nomogram for predicting 28-day mortality in elderly patients with acute kidney injury receiving continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

Nomograms for Predicting Risk and Survival of Esophageal Cancer Lung Metastases: a SEER Analysis.

Background: The overall survival rate is notably low for esophageal cancer patients with lung metastases (LM), presenting significant challenges in their treatment. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) program, individuals diagnosed with esophageal cancer between 2010 and 2015 were enrolled. Based on whether esophageal cancer metastasized to the lungs, we used propensity score matching (PSM) to balance correlated variables. Propensity score matching was a critical step in our study that helped to minimize the impact of possible confounders on the study results. We balanced variables related to lung metastases using the PSM method to ensure more accurate comparisons between the study and control groups. Specifically, we performed PSM in the following steps. First, we performed a univariate logistic regression analysis to screen for variables associated with lung metastasis. For each patient, we calculated their propensity scores using a logistic regression model, taking into account several factors, including gender, T-stage, N-stage, surgical history, radiotherapy history, chemotherapy history, and bone/brain/liver metastases. We used a 1:1 matching ratio based on the propensity score to ensure more balanced baseline characteristics between the study and control groups after matching. After matching, we validated the balance of baseline characteristics to ensure that the effect of confounders was minimized. We used logistic regression to identify risk variables for LM, while Cox regression was used to find independent prognostic factors. We then created nomograms and assessed their accuracy using the calibration curve, receiver operating curves (ROC), and C index. Results: In the post-PSM cohort, individuals diagnosed with LM experienced a median overall survival (OS) of 5.0 months (95% confidence interval [CI] 4.3-5.7), which was significantly lower than those without LM (P<0.001). LM has been associated to sex, T stage, N stage, surgery, radiation, chemotherapy, and bone/brain/liver metastases. LM survival was affected by radiation, chemotherapy, and bone/liver metastases. The nomograms' predictive power was proved using the ROC curve, C-index, and validation curve. Conclusion: Patients with LM have a worse chance of surviving esophageal cancer. The nomograms can effectively predict the risk and prognosis of lung metastases from esophageal cancer.

Exploring Schizophrenia Classification Through Multimodal MRI and Deep Graph Neural Networks: Unveiling Brain Region-Specific Weight Discrepancies and Their Association With Cell-Type Specific Transcriptomic Features.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification. STUDY DESIGN: Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions. STUDY RESULTS: Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research. CONCLUSIONS: Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.

Hierarchically porous ZnO derived from zeolitic imidazolate frameworks for high-sensitive MEMS NO2 sensor.

Three-dimensional (3D) porous metal oxide nanomaterials with controllable morphology and well-defined pore size have attracted extensive attention in the field of gas sensing. Herein, hierarchically porous ZnO-450 was obtained simply by annealing Zeolitic Imidazolate Frameworks (ZIF-90) microcrystals at an optimal temperature of 450 °C, and the effect of annealing temperature on the formation of porous nanostructure was discussed. Then the as-obtained ZnO-450 was employed as sensing materials to construct a Micro-Electro-Mechanical System (MEMS) gas sensor for detecting NO2. The MEMS sensor based on ZnO-450 displays the excellent gas-sensing performances at a lower working temperature (190 °C), such as high response value (242.18% @ 10 ppm), fast response/recovery time (9/26 s) and ultralow limit of detection (35 ppb). The ZnO-450 sensor shows better sensing performance for NO2 detection than ZnO-based composites materials or commercial ZnO nanoparticles (NPs), which are attributed to its unique hierarchically structures with high porosity and larger surface area. This ZIFs driven strategy can be expected to pave a new pathway for the design of high-performance NO2 sensors.

Lanosterol synthase deficiency promotes tumor progression by orchestrating PDL1-dependent tumor immunosuppressive microenvironment.

Lipid metabolic reprogramming is closely related to tumor progression with the mechanism not fully elucidated. Here, we report the immune-regulated role of lanosterol synthase (LSS), an essential enzyme in cholesterol synthesis. Database analysis and clinical sample experiments suggest that LSS was lowly expressed in colon and breast cancer tissues, which indicates poor prognosis. The biological activity of tumor cell lines and tumor progression in NOD scid gamma (NSG) mice were not affected after LSS knockdown, whereas LSS deficiency obviously aggravated tumor burden in fully immunized mice. Flow cytometry analysis showed that LSS knockdown significantly promoted the formation of tumor immunosuppressive microenvironment, characterized by the increase in M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as the decrease in anti-tumoral T lymphocytes. With the inhibition of myeloid infiltration or loss function of T lymphocytes, the propulsive effect of LSS knockdown on tumor progression disappeared. Mechanistically, LSS knockdown increased programmed death ligand 1 (PDL1) protein stability by 2,3-oxidosqualene (OS) binding to PDL1 protein. Anti-PDL1 therapy abolished LSS deficiency-induced immunosuppressive microenvironment and cancer progression. In conclusion, our results show that LSS deficiency promotes tumor progression by establishing an OS-PDL1 axis-dependent immunosuppressive microenvironment, indicative of LSS or OS as a potential hallmark of response to immune checkpoint blockade.

Sustainable efficiency in cities in China-An interaction model among water, energy, and industry.

With the inclusion of "Building Inclusive, safe, Resilient and Sustainable Cities and human Settlements" (SDG11) in the United Nations Sustainable Development Goals (SDGS), the movement to promote sustainable development from an urban perspective is growing globally. Many studies examine urban sustainability efficiency from multiple dimensions, but scant attention targets the interaction among various dimensions. This research combines the water-energy-industry subsystem to evaluate the sustainable development performance of 29 provinces in China from 2018 to 2020. The results show that 1) a water system plays an important role in promoting a city's overall sustainable performance. 2) Urban sustainable efficiency has the characteristics of low value aggregation and high value dispersion in space. 3) Regional and sub-system sustainability efficiencies exhibit clear heterogeneity. 4) Rainfall improves the sustainable efficiency of cities, mainly through water systems. 5) The coupling between water and industrial subsystems is better than that between energy and industrial subsystems, and the coupling between the central region subsystem is the best. This paper offers a new perspective for understanding the current state of sustainability in China's provinces and provides more specific suggestions for improving regional sustainability efficiency in the future.

Macaque Brainnetome Atlas: A multifaceted brain map with parcellation, connection, and histology.

The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data. The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections. The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images. As a demonstrative application, the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure. The resulting resource includes: (1) the thoroughly delineated Macaque Brainnetome Atlas (MacBNA), (2) regional connectivity profiles, (3) the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset (Brainnetome-8), and (4) multi-contrast MRI, neuronal-tracing, and histological images collected from a single macaque. MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function. Therefore, it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.

Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis. OBJECTIVES: Tanshinone IIA (Tan IIA) inhibits BC progression, however, the underlying mechanism remains largely undefined. METHODS: The cytotoxicity of Tan IIA was assessed by CCK-8 and LDH assays. Ferroptosis was monitored by the level of MDA, Fe2+, lipid ROS and GSH. IHC and western blot were employed to detect the localization and expression of SLC7A11, PIAS4, KDM1A and other key molecules. The SUMOylation of SLC7A11 was detected by Ni-beads pull-down assay and Co-IP. Luciferase and ChIP assays were employed to detect the direct association between KDM1A and PIAS4 promoter. The proliferative and metastatic properties of BC cells were assessed by colony formation, CCK-8 and Transwell assays, respectively. The in vitro findings were verified in xenograft and lung metastasis models. RESULTS: Tan IIA promoted ferroptosis by suppressing SLC7A11 in BC cells. Silencing of PIAS4 or KDM1A inhibited cell growth and metastasis in BC. Mechanistically, PIAS4 facilitated the SUMOylation of SLC7A11 via direct binding to SLC7A11, and KDM1A acted as a transcriptional activator of PIAS4. Functional studies further revealed that Tan IIA decreased KDM1A expression, thus suppressing PIAS4 expression transcriptionally. The inhibition of PIAS4-dependent SUMOylation of SLC7A11 further induced ferroptosis, thereby inhibiting proliferation and metastasis in BC. CONCLUSION: Tan IIA promoted ferroptosis and inhibited tumor growth and metastasis via suppressing KDM1A/PIAS4/SLC7A11 axis.

Status and Prospect of Two-Dimensional Materials in Electrolytes for All-Solid-State Lithium Batteries.

Replacing liquid electrolytes and separators in conventional lithium-ion batteries with solid-state electrolytes (SSEs) is an important strategy to ensure both high energy density and high safety. Searching for fast ionic conductors with high electrochemical and chemical stability has been the core of SSE research and applications over the past decades. Based on the atomic-level thickness and infinitely expandable planar structure, numerous two-dimensional materials (2DMs) have been exploited and applied to address the most critical issues of low ionic conductivity of SSEs and lithium dendrite growth in all-solid-state lithium batteries. This review introduces the research process of 2DMs in SSEs, then summarizes the mechanisms and strategies of inert and active 2DMs toward Li+ transport to improve the ionic conductivity and enhance the electrode/SSE interfacial compatibility. More importantly, the main challenges and future directions for the application of 2DMs in SSEs are considered, including the importance of exploring the relationship between the anisotropic structure of 2DMs and Li+ diffusion behavior, the exploitation of more 2DMs, and the significance of in situ characterizations in elucidating the mechanisms of Li+ transport and interfacial reactions. This review aims to provide a comprehensive understanding to facilitate the application of 2DMs in SSEs.

Integration of Kupffer cells into human iPSC-derived liver organoids for modeling liver dysfunction in sepsis.

Maximizing the potential of human liver organoids (LOs) for modeling human septic liver requires the integration of innate immune cells, particularly resident macrophage Kupffer cells. In this study, we present a strategy to generate LOs containing Kupffer cells (KuLOs) by recapitulating fetal liver hematopoiesis using human induced pluripotent stem cell (hiPSC)-derived erythro-myeloid progenitors (EMPs), the origin of tissue-resident macrophages, and hiPSC-derived LOs. Remarkably, LOs actively promote EMP hematopoiesis toward myeloid and erythroid lineages. Moreover, supplementing with macrophage colony-stimulating factor (M-CSF) proves crucial in sustaining the hematopoietic population during the establishment of KuLOs. Exposing KuLOs to sepsis-like endotoxins leads to significant organoid dysfunction that closely resembles the pathological characteristics of the human septic liver. Furthermore, we observe a notable functional recovery in KuLOs upon endotoxin elimination, which is accelerated by using Toll-like receptor-4-directed endotoxin antagonist. Our study represents a comprehensive framework for integrating hematopoietic cells into organoids, facilitating in-depth investigations into inflammation-mediated liver pathologies.

A cross-sectional investigation of factors influencing mpox vaccine hesitancy for students in Southwest China.

From July to September 2023, China reported over 1, 400 confirmed cases of mpox transmitted mainly through sexual contact between males. Meanwhile, the percentage of men who have sex with men at universities in southwestern China is increasing every year, which is likely to lead to a potential spread of mpox on campuses. Vaccination is an effective preventive measure against infectious diseases, this study examined the willingness of university students in Southwest China to receive the mpox vaccine and analyzed the factors influencing their decision. A cross-sectional survey was conducted among 7311 university students from 10 universities in Southwest China between August 13 and September 1, 2023. The survey revealed a hesitancy rate of 56.13% toward the mpox vaccine, with the most common reason being concerns about vaccine safety (1407/4104, 34.29%). Univariate analysis identified 13 variables that significantly differed between the vaccine acceptance and vaccine hesitancy groups. Multivariate logistic regression analyses indicated protective factors for vaccine hesitancy, such as sexually transmitted diseases, previous knowledge about mpox, frequent information about mpox, people can get reinfection of mpox, and worries about mpox endemic in China. Additionally, the confidence and convenience dimensions in the 3Cs model were identified as risk factors for mpox vaccine hesitancy. This study found a high rate of vaccine hesitancy among university students in Southwest China regarding the mpox vaccine. Collaboration between university and healthcare departments is recommended to address mpox vaccine hesitancy among college students, thereby promoting their willingness to receive the mpox vaccine.

Piperlongumine, a Piper longum-derived amide alkaloid, protects mice from ovariectomy-induced osteoporosis by inhibiting osteoclastogenesis via suppression of p38 and JNK signaling.

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease that results from overproduction and hyperactivation of osteoclasts caused by insufficient estrogen in women after menopause. Current therapeutic strategies are mainly focused on treating PMOP patients who have already developed severe bone loss or even osteoporotic fractures. Obviously, a better strategy is to prevent PMOP from occurring in the first place. However, such reagents are largely lacking. Piperlongumine (PLM), an amide alkaloid extracted from long pepper Piper longum, exhibits the anti-osteoclastogenic effect in normal bone marrow macrophages (BMMs) and the protective effect against osteolysis induced by titanium particles in mice. This study examined the preventive effect of PLM on PMOP and explored the potential mechanism of this effect using both ovariectomized mice and their primary cells. The result showed that PLM (5 and 10 mg kg-1) administered daily for 6 weeks ameliorated ovariectomy-induced bone loss and osteoclast formation in mice. Further cell experiments showed that PLM directly suppressed osteoclast formation, F-actin ring formation, and osteoclastic resorption pit formation in BMMs derived from osteoporotic mice, but did not obviously affect osteogenic differentiation of bone marrow stromal cells (BMSCs) from these mice. Western blot analysis revealed that PLM attenuated maximal activation of p38 and JNK pathways by RANKL stimulation without affecting acute activation of NF-κB, AKT, and ERK signaling. Furthermore, PLM inhibited expression of key osteoclastogenic transcription factors NFATc1/c-Fos and their target genes (Dcstamp, Atp6v0d2, Acp5, and Oscar). Taken together, our findings suggest that PLM inhibits osteoclast formation and function by suppressing RANKL-induced activation of the p38/JNK-cFos/NFATc1 signaling cascade, thereby preventing ovariectomy-induced osteoporosis in mice. Thus, PLM can potentially be used as an anti-resorption drug or dietary supplement for the prevention of PMOP.

Erratum: PFKFB4 promotes angiogenesis via IL-6/STAT5A/P-STAT5 signaling in breast cancer: Erratum.

[This corrects the article DOI: 10.7150/jca.66773.].

Genomics-Microbiome Based Assessment of Bidirectional Causality Between Gut Microbiota and Psoriasis.

Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.

Pyrene and its derivatives increase lung adverse effects by activating aryl hydrocarbon receptor transcription.

Derivatives of polycyclic aromatic hydrocarbons (PAHs) pose significant threat to environment and human health due to their widespread and potential hazards. However, adverse effects and action mechanisms of PAH derivatives on human health have not been attempted yet. Herein, we chose pyrene and its derivatives (1-hydroxypyrene, 1-nitropyrene, and 1-methylpyrene) to investigate adverse effect mechanism to human lungs using in vitro and in vivo methods. Results showed that pyrene derivatives have higher lung health risks than original pyrene. They can activate AhR, subsequently affecting expression of downstream target genes CYP1A1 and CYP1B1. The binding energies of pyrene and its derivatives ranged from -16.07 to -27.25 kcal/mol by molecular dynamics simulations, implying that pyrene and its derivatives acted as agonists of AhR and increased adverse effects on lungs. Specifically, 1-nitropyrene exhibited stabler binding conformation and stronger AhR expression. In addition, sensitivity of pyrene and its derivatives to AhR activation was attributed to type and number of key amino acids in AhR, that is, pyrene (Leu293), 1-nitropyrene (Cys333, Met348, and Val381), 1-hydroxypyrene (Leu293 and Phe287), and 1-methylpyrene (Met348). In summary, we provide a universal approach for understanding action mechanisms of PAH derivatives on human health, and their adverse effects should be taken seriously.

FFCM-MRF: An accurate and generalizable cerebrovascular segmentation pipeline for humans and rhesus monkeys based on TOF-MRA.

PURPOSE: Cerebrovascular segmentation and quantification of vascular morphological features in humans and rhesus monkeys are essential for prevention, diagnosis, and treatment of brain diseases. However, current automated whole-brain vessel segmentation methods are often not generalizable to independent datasets, limiting their usefulness in real-world environments with their heterogeneity in participants, scanners, and species. MATERIALS AND METHODS: In this study, we proposed an automated, accurate and generalizable segmentation method for magnetic resonance angiography images called FFCM-MRF. This method integrated fast fuzzy c-means clustering and Markov random field optimization by vessel shape priors and spatial constraints. We used a total of 123 human and 44 macaque MRA images scanned at 1.5 T, 3 T, and 7 T MRI from 9 datasets to develop and validate the method. RESULTS: FFCM-MRF achieved average Dice similarity coefficients ranging from 69.16 % to 89.63 % across multiple independent datasets, with improvements ranging from 3.24 % to 7.3 % compared to state-of-the-art methods. Quantitative analysis showed that FFCM-MRF can accurately segment major arteries in the Circle of Willis at the base of the brain and small distal pial arteries while effectively reducing noise. Test-retest analysis showed that the model yielded high vascular volume and diameter reliability. CONCLUSIONS: Our results have demonstrated that FFCM-MRF is highly accurate and reliable and largely independent of variations in field strength, scanner platforms, acquisition parameters, and species. The macaque MRA data and user-friendly open-source toolbox are freely available at OpenNeuro and GitHub to facilitate studies of imaging biomarkers for cerebrovascular and neurodegenerative diseases.

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.