The impact of discharge readiness on post-traumatic growth in patients after thyroid cancer surgery: the mediating role of sickness-related stigma.

Objective: To investigate the relationship between post-traumatic growth, morbidity stigma and readiness for discharge in post-operative thyroid cancer patients. Methods: 422 post-operative thyroid cancer patients from three tertiary care hospitals in Hunan and Tianjin were surveyed using the General Information Questionnaire, the Post-traumatic Growth Scale, the Readiness for Discharge Scale, and the Social Influence Scale. Results: Discharge readiness positively predicted the level of post-traumatic growth in thyroid cancer patients (P < 0.01), and morbidity stigma negatively predicted post-traumatic growth (P < 0.01), with morbidity stigma playing a mediated role between discharge readiness and post-traumatic growth. Conclusions: Readiness for discharge can positively predict post-traumatic growth, and morbidity stigma plays a mediating role between readiness for discharge and post-traumatic growth. It is suggested that clinical and nursing staff should strengthen patients' discharge readiness guidance and education, help patients and their families establish an effective feedback mechanism for disease condition and psychological cognitive condition, focus on reducing patients' sense of shame, and improve patients' physical and mental health.

Difference between arterial and venous peak optical density after thrombectomy is associated with functional outcomes.

Background: The density of contrast medium in digital subtraction angiography (DSA) have been used to evaluate the cerebral circulation function. Our aim was to study the effect of difference in arteriovenous peak optical density (POD) after thrombectomy on functional outcomes. Methods: Consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent thrombectomy were reviewed. We processed DSA images with ImageJ software to measure the POD of internal carotid artery (ICA) and cortical veins. The average POD of cortical veins (PODVA) and the POD difference between ICA and cortical veins (PODICA-CV) were calculated. Primary outcome was good functional outcome (modified Rankin scale score of 0-2 at 90 days). Results: One hundred sixty-six patients were finally included in the study. Patients with good functional outcome had lower ipsilateral PODVA (median [interquartile range (IQR)], 257.198 [216.623-296.631] vs. 290.944 [248.647-338.819], p < 0.001) and lower ipsilateral PODICA-CV (median [IQR], 128.463 [110.233-153.624] vs. 182.01 [146.621-211.331], p < 0.001). Multivariable logistic regression analyses showed that ipsilateral PODVA (odds ratio [OR] 0.991, 95% confidence interval [CI] 0.984-0.999, p = 0.019) and ipsilateral PODICA-CV (OR 0.975, 95% CI 0.963-0.986, p < 0.001) were associated with good functional outcome. The predictive ability was significantly enhanced in the model including ipsilateral PODICA-CV (0.893 vs. 0.842, p = 0.027). No correlation was found between ipsilateral PODICA-CV and expanded Thrombolysis in Cerebral Infarction grades (r = -0.133, p = 0.099). Conclusion: Ipsilateral PODICA-CV is an additional indicator of cerebral reperfusion status and predicts functional outcomes after thrombectomy.

Impact of Concurrent Ischaemic Stroke on Unfavourable Outcomes in Men and Women with Dilated Cardiomyopathy.

Background: Growing evidence suggests that concurrent ischaemic stroke (IS) exacerbates the prognosis of patients with dilated cardiomyopathy (DCM) and that this effect may be further influenced by sex. However, the exact effect of sex remains unclear. This study aimed to explore the effects of the relevant risk factors on the prognosis of patients with DCM and concurrent IS. Considering the sex differences in DCM, this study further investigated the impact of concurrent IS on the prognosis of men and women with DCM. Methods: A total of 632 patients with DCM enrolled between 2016 and 2021 were included in this study. Clinical data were obtained from medical records, and all participants were followed up in the outpatient clinic or by telephone for at least 1 year. A Cox proportional hazards model and Kaplan-Meier curves were used to evaluate the effects of concurrent IS on the prognosis of patients with DCM. Results: Patients with DCM complicated with IS (DCM-IS) had significantly lower cumulative survival rates than patients with DCM without IS (non-IS) (74.6% vs. 84.2%, χ 2 = 6.85, p = 0.009). Additionally, IS was associated with greater risks of death and heart transplantation (HTx) in men (75.8% vs. 85.1%, χ 2 = 5.02, p = 0.025), but not in women (71.0% vs. 81.5%, χ 2 = 1.91, p = 0.167). Conclusions: This large-scale multicentre prospective cohort study demonstrated a poorer prognosis in patients with concurrent DCM and IS, particularly among men. Patients with DCM should not be overlooked in IS screening, emphasis should be placed on the occurrence of IS in patients with DCM. Early and proactive secondary prevention of cerebrovascular diseases might improve the prognosis of DCM patients. More intervention studies focusing on men with DCM complicated with IS should be prioritised.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

CD4+CD25+ regulatory T cells ex vivo generated from autologous naïve CD4+ T cells suppress EAE progression.

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.

Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

BACKGROUND: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. AIMS: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). METHODS: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. RESULTS: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. DATA ACCESS STATEMENT: Data from this study are available and can be accessed upon request.

A Pilot Study on Tocilizumab in Very-Late-Onset Myasthenia Gravis.

Objective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG). Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months. Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period. Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.

Prognosis and Prediction of Asymptomatic Intracranial Hemorrhage After Endovascular Thrombectomy: A Multi-Center Study.

PURPOSE: The impact of asymptomatic intracranial hemorrhage (aICH) on functional outcomes after endovascular thrombectomy (EVT) remains unclear, and tools for forecasting this complication are lacking. We aim to evaluate the clinical relevance of aICH and establish a prediction model. METHODS: Data of patients who received EVT for acute anterior-circulation large vessel occlusion in 3 comprehensive hospitals were retrospectively analyzed. Asymptomatic intracranial hemorrhage was defined as any hemorrhage detected after EVT that did not fulfill the definition of symptomatic intracranial hemorrhage in the European Cooperative Acute Stroke Study. Logistic regression models were performed to assess the impact of aICH on 90-day functional outcomes and identify the predictors of aICH, which were then used to establish a prediction model. The discrimination, calibration, and clinical utility of the model were evaluated. RESULTS: This study included 460 patients, among whom 152 (33.0%) developed aICH after EVT. Asymptomatic intracranial hemorrhage was negatively associated with 90-day excellent outcomes (adjusted odds ratio [OR]: 0.414, 95% confidence interval [CI]: 0.230-0.745, p=0.003) and good outcome (adjusted OR: 0.603, 95% CI: 0.374-0.971, p=0.037), but not with mortality (adjusted OR: 1.110, 95% CI: 0.611-2.017, p=0.732) after adjusted for other predictors of functional outcome. Pre-stroke anticoagulant therapy (OR: 2.233, 95% CI: 1.073-4.647, p=0.032), Alberta stroke program early CT score (OR: 0.842, 95% CI: 0.754-0.939, p=0.002), site of occlusion (internal carotid artery occlusion as the reference; M1 segment of middle cerebral artery occlusion, OR: 2.827, 95% CI: 1.409-5.674, p=0.003; tandem occlusion, OR: 3.928, 95% CI: 1.752-8.806, p=0.001), intravenous thrombolysis (OR: 2.091, 95% CI: 1.362-3.209, p=0.001), and successful recanalization (OR: 0.383, 95% CI: 0.213-0.689, p=0.001) were identified as the predictors of aICH, which were incorporated into a nomogram model. The area under the receiver operating characteristic curve of the model was 0.707 (95% CI: 0.657-0.757), and the calibration plot demonstrated good consistency between actual observed and predicted probability of aICH. Decision curve analysis showed that patients might benefit from the model. CONCLUSION: Asymptomatic intracranial hemorrhage was negatively associated with favorable functional outcome after EVT. We established a nomogram model for predicting aICH, which requires external clinical validation. CLINICAL IMPACT: The impact of asymptomatic intracranial hemorrhage after endovascular thrombectomy on mid-term functional outcome has been controversial. We found that asymptomatic intracranial hemorrhage may also decreased the likelihood of 90-day favourable functional outcome after endovascular thrombectomy, supporting the notion that asymptomatic intracranial hemorrhage at the acute stage may not be benign. Moreover, we established a prediction model for this complication, which may improve clinical evaluation and management of patients who would receive endovascular thrombectomy for large vessel occlusion.

Expression profiles of human somatic mesenchymal stem cells derived from fresh endometrium, ectopic-endometrium and umbilical cord.

OBJECTIVES: The study investigated the stem cell expression profiles and differentiation capacities of mesenchymal stem cells (MSCs) from different tissues, specifically human eutopic endometrium MSCs (eut-MSCs), ectopic endometrium MSCs (ect-MSCs), and umbilical cord MSCs (UC-MSCs). Our aim was to identify any similarities in subpopulations among these MSCs and lay a foundation for MSCs repair. MATERIAL AND METHODS: MSCs were isolated from endometrial tissue (n = 5), endometriosis tissue (n = 6), and umbilical cords (n = 7). Flow cytometry was used to examine cell phenotype, and three lineage tests were conducted to evaluate the differentiation capacity of the MSCs. RESULTS: Eut-MSCs expressed CD44 (98.00 ± 0.96%), CD73 (99.54 ± 0.02%), CD140b (99.16 ± 0.50%), CD146 (93.87 ± 2.27%), SUSD2 (50.76 ± 8.15%), and CD271 (2.1 ± 1.22%). Ect-MSCs expressed CD44 (98.23 ± 1.60%), CD73 (99.63 ± 0.04%), CD140b (98.13 ± 0.53%), CD146 (93.88 ± 3.19%), SUSD2 (49.33 ± 6.36%), and CD271 (2.85 ± 1.17%). UC-MSCs expressed CD44 (99.11 ± ± 0.42%), CD73 (99.65 ± 0.12%), CD140b (99.84 ± 0.42%), CD146 (88.09 ± 4.20%), SUSD2 (72.87 ± 7.13%), and CD271 (6.19 ± 2.08%). The expression of SUSD2 and CD271 in UC-MSCs was slightly but not significantly higher than that in ect-MSCs and eut-MSCs. However, CD44, CD73, CD140b, and CD146 showed similar expression levels in UC-MSCs, ect-MSCs, and eut-MSCs. All three types of MSCs demonstrated the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. CONCLUSIONS: Our findings indicate that ect-MSCs, eut-MSCs, and UC-MSCs have similar stem cell phenotypes and the ability to differentiate into three lineages.

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer's disease.

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aß analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aß1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1ß and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1ß, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aß1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

Expression, Purification, and Crystallization of the Vγ9Vδ2 T-cell Receptor Recognizing Protein/Peptide Antigens.

γδ T cells, especially Vγ9Vδ2 T cells, play an important role in mycobacterial infection. We have identified some Vγ9Vδ2 T cells that recognize protein/peptide antigens derived from mycobacteria, which may induce protective immune responses to mycobacterial infection. To clarify the structural basis of the molecular recognition mechanism, we tried many methods to express the Vγ9Vδ2 T-cell receptor (TCR). The Vγ9Vδ2 TCR was not expressed well in a prokaryotic expression system or a baculovirus expression system, even after extensive optimization. In a mammalian cell expression system, the Vγ9Vδ2 TCR was expressed in the form of a soluble heterodimer, which was suitable for crystal screening. Reduced-temperature cultivation (cold shock) increased the yield of the recombinant TCR. The recombinant purified TCR was used for crystal trials, and crystals that could be used for X-ray diffraction were obtained. Although we have not yet determined the crystal structure of the Vγ9Vδ2 TCR, we have established a procedure for Vγ9Vδ2 TCR expression and purification, which is useful for basic research and potentially for clinical application.

Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.

Background: Increasing evidence indicates the importance of CD8+ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8+ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity. Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8+ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS. Results: We found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM. Conclusion: The dysregulation of antigen-specific CD8+ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.

Risk factors assessment and a Bayesian network model for predicting ischemic stroke in patients with cardiac myxoma.

Objective: This study aims to identify relevant risk factors, assess the interactions between variables, and establish a predictive model for ischemic stroke (IS) in patients with cardiac myxoma (CM) using the Bayesian network (BN) approach. Methods: Data of patients with CM were collected from three tertiary comprehensive hospitals in Beijing from January 2002 to January 2022. Age, sex, medical history, and information related to CM were extracted from the electronic medical record system. The BN model was constructed using the tabu search algorithm, and the conditional probability of each node was calculated using the maximum likelihood estimation method. The probability of each node of the network and the interrelationship between IS and its related factors were qualitatively and quantitatively analyzed. A receiver operating characteristic (ROC) curve was also plotted. Sensitivity, specificity, and area under the curve (AUC) values were calculated and compared between the BN and logistic regression models to evaluate the efficiency of the predictive model. Results: A total of 416 patients with CM were enrolled in this study, including 61 with and 355 without IS. The BN model found that cardiac symptoms, systemic embolic symptoms, platelet counts, and tumor with high mobility were directly associated with the occurrence of IS in patients with CM. The BN model for predicting CM-IS achieved higher scores on AUC {0.706 [95% confidence interval (CI), 0.639-0.773]} vs. [0.697 (95% CI, 0.629-0.766)] and sensitivity (99.44% vs. 98.87%), but lower scores on accuracies (85.82% vs. 86.06%) and specificity (6.56% vs. 11.48%) than the logistic regression model. Conclusion: Cardiac symptoms, systemic embolic symptoms, platelet counts, and tumor with high mobility are candidate predictors of IS in patients with CM. The BN model was superior or at least non-inferior to the traditional logistic regression model, and hence is potentially useful for early IS detection, diagnosis, and prevention in clinical practice.

Development and refinement of diagnostic and therapeutic strategies for managing patients with cardiogenic stroke: An arduous journey.

Cardioembolic stroke, referred to as cardiogenic stroke, is a clinical syndrome in which emboli from the heart pass through the circulatory system and cause cerebral artery embolism and corresponding brain dysfunction. Compared to other subtypes of ischemic stroke, cardiogenic stroke presents with more etiologies, greater severity, worse prognosis, and a higher recurrence rate. In this minireview, we provide new insights into the etiological classification, diagnostic methods, and interventions of cardiogenic stroke.

Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells.

Unveiling the principles governing embryonic stem cell (ESC) differentiation into specific lineages is critical for understanding embryonic development and for stem cell applications in regenerative medicine. Here, we establish an intersection between LIF-Stat3 signaling that is essential for maintaining murine (m) ESCs pluripotency, and the glycolytic enzyme, the platelet isoform of phosphofructokinase (Pfkp). In the pluripotent state, Stat3 transcriptionally suppresses Pfkp in mESCs while manipulating the cells to lift this repression results in differentiation towards the ectodermal lineage. Pfkp exhibits substrate specificity changes to act as a protein kinase, catalyzing serine phosphorylation of the developmental regulator Lin41. Such phosphorylation stabilizes Lin41 by impeding its autoubiquitination and proteasomal degradation, permitting Lin41-mediated binding and destabilization of mRNAs encoding ectodermal specification markers to favor the expression of endodermal specification genes. This provides new insights into the wiring of pluripotency-differentiation circuitry where Pfkp plays a role in germ layer specification during mESC differentiation.

Clinical features, risk factors and survival in cardiac myxoma-related ischemic stroke: A multicenter case-control study.

BACKGROUND: Cardiac myxoma (CM) is an important etiology of stroke in young adults, but studies on CM-related ischemic stroke (CM-IS) are limited and conflicting. Hence, we investigated clinical characterizations, risk factors of CM-IS, and short-term survival after surgical resection. METHODS: We performed a retrospective analysis of data from all CM patients at three referral management centers and conducted follow-up examination. RESULTS: Among 414 CM patients, 402 were recruited for further analysis, including 54 patients with CM-IS and 348 patients with CM without stroke (Non-stroke). In the acute phase, patients presented with NIHSS 3 (interquartile range: 0-10) and clinical presentation comprising neurological, cardiac and constitutional symptoms. Multivariate analysis showed that the factors associated with an increased risk of CM-IS were tumor width < 30 mm [OR = 2.652, 95% CI: 1.061-6.627, P = 0.037], tumors with high-mobility (OR = 2.700, 95% CI: 1.357-5.371, P = 0.005), thrombus on the tumor surface (OR = 1.856, 95% CI: 1.003-3.434, P = 0.049), and lower B-type natriuretic peptide (BNP) levels (OR = 0.995, 95% CI: 0.989-0.999, P = 0.047). The overall three-year survival rate was 95.7% (95% CI: 94.9-96.5) in CM-IS patients who underwent surgery. CONCLUSIONS: CM-IS patients had mild or moderate neurologic deficits with various presentations at disease onset. Narrower tumor width, tumors with high-mobility, thrombus on the tumor surface, and lower BNP levels are potential predictors of CM-IS development. Surgical removal of CM is safe and efficacious in patients with CM-IS.

A Bayesian network-based approach for identifying risk factors and predicting ischemic stroke in infective endocarditis patients.

Objective: This study aimed to seek the risk factors and develop a predictive model for ischemic stroke (IS) in patients with infective endocarditis (IE) utilizing a Bayesian network (BN) approach. Methods: Data were obtained from the electronic medical records of all adult patients at three hospitals between 1 January 2018, and 31 December 2022. Two predictive models, logistic regression and BN, were used. Patients were randomly assigned to the training and test sets in a 7:3 ratio. We established a BN model with the training dataset and validated it with the testing dataset. The Bayesian network model was built by using the Tabu search algorithm. The areas under the receiver operating characteristic curve (AUCs), calibration curve, and decision curve were used to evaluate the prediction performance between the BN and logistic models. Results: A total of 542 patients [mean (SD) age, 49.6 (15.3) years; 137 (25.3%) female] were enrolled, including 151 (27.9%) with IS and 391 (72.1%) without IS. Hyperlipidemia, hypertension, age, vegetation size (>10 mm), S. aureus infection, and early prosthetic valve IE were closely correlated with IS. The BN models outperformed the logistic regression in training and testing sets, with accuracies of 76.06% and 74.1%, AUC of 0.744 and 0.703, sensitivities of 25.93% and 20.93%, and specificities of 96.27% and 90.24%, respectively. Conclusion: The BN model is more efficient than the logistic regression model. Therefore, BN models may be suitable for the early diagnosis and prevention of IS in IE patients.

Risk factors, clinical features, and outcomes of patients with hypertrophic cardiomyopathy complicated by ischemic stroke: A single-center retrospective study.

Objective: This study aimed to explore risk factors, clinical features, and prognosis of patients with hypertrophic cardiomyopathy (HCM) complicated by ischemic stroke (IS). Methods: We conducted a retrospective analysis of all HCM patient data and a 1-year follow-up study. Results: Totally, 506 patients with HCM, including 71 with IS, were enrolled. Older age (≥63 years) was associated with an increased risk of IS in HCM patients (OR = 1.045, 95% CI: 1.018-1.072, p = 0.001). Among 37 patients complicated by IS, 22 (59.5%, 22/37) manifested as cardioembolism (CE) subtype, and 13 (35.1%, 3/37) small artery occlusion (SAO) subtype, according to TOAST classification. In the acute phase, the IS patients presented with NIHSS 4 (interquartile range: 1, 10). Multi-infarction was more common than single infarction (72.7 vs. 27.3%), while cortical + subcortical infarction (CE group: 50%) or subcortical infarction (SAO group: 53.8%) constituted most IS cases. Additionally, the blood supply areas of anterior circulation (CE group: 45.5%; SAO group: 92.3%) or anterior + posterior circulation (CE group: 50%) were mainly involved. The 1-year survival rate of HCM patients with concomitant IS was 81.8%, and IS was associated with 1-year all-cause death in HCM patients (HR = 5.689, 95% CI: 1.784-18.144, p = 0.003). Conclusion: Older age is a risk factor for IS occurrence in HCM patients. Patients with HCM complicated by IS had mild or moderate neurologic deficits at disease onset. CE and SAO subtypes predominate in patients with concomitant IS, especially the former. Multiple cortical and subcortical infarctions are their neuroimaging characteristics, mainly involving the anterior circulation or anterior + posterior circulation. Is is a risk factor for all-cause death in HCM patients within 1 year.

Risk factors and a Bayesian network model to predict ischemic stroke in patients with dilated cardiomyopathy.

Objective: This study aimed to identify risk factors and create a predictive model for ischemic stroke (IS) in patients with dilated cardiomyopathy (DCM) using the Bayesian network (BN) approach. Materials and methods: We collected clinical data of 634 patients with DCM treated at three referral management centers in Beijing between 2016 and 2021, including 127 with and 507 without IS. The patients were randomly divided into training (441 cases) and test (193 cases) sets at a ratio of 7:3. A BN model was established using the Tabu search algorithm with the training set data and verified with the test set data. The BN and logistic regression models were compared using the area under the receiver operating characteristic curve (AUC). Results: Multivariate logistic regression analysis showed that hypertension, hyperlipidemia, atrial fibrillation/flutter, estimated glomerular filtration rate (eGFR), and intracardiac thrombosis were associated with IS. The BN model found that hyperlipidemia, atrial fibrillation (AF) or atrial flutter, eGFR, and intracardiac thrombosis were closely associated with IS. Compared to the logistic regression model, the BN model for IS performed better or equally well in the training and test sets, with respective accuracies of 83.7 and 85.5%, AUC of 0.763 [95% confidence interval (CI), 0.708-0.818] and 0.822 (95% CI, 0.748-0.896), sensitivities of 20.2 and 44.2%, and specificities of 98.3 and 97.3%. Conclusion: Hypertension, hyperlipidemia, AF or atrial flutter, low eGFR, and intracardiac thrombosis were good predictors of IS in patients with DCM. The BN model was superior to the traditional logistic regression model in predicting IS in patients with DCM and is, therefore, more suitable for early IS detection and diagnosis, and could help prevent the occurrence and recurrence of IS in this patient cohort.