Unveiling the structural transformation and activity origin of heteroatom-doped carbons for hydrogen evolution.

Heteroatom-doped carbon materials have been widely used in many electrocatalytic reduction reactions. Their structure-activity relationships are mainly explored based on the assumption that the doped carbon materials remain stable during electrocatalysis. However, the structural evolution of heteroatom-doped carbon materials is often ignored, and their active origins are still unclear. Herein, taking N-doped graphite flake (N-GP) as the research model, we present the hydrogenation of both N and C atoms and the consequent reconstruction of the carbon skeleton during the hydrogen evolution reaction (HER), accompanied by a remarkable promotion of the HER activity. The N dopants are gradually hydrogenated and almost completely dissolved in the form of ammonia. Theoretical simulations demonstrate that the hydrogenation of the N species leads to the reconstruction of the carbon skeleton from hexagonal to 5,7-topological rings (G5-7) with thermoneutral hydrogen adsorption and easy water dissociation. P-, S-, and Se-doped graphites also show similar removal of doped heteroatoms and the formation of G5-7 rings. Our work unveils the activity origin of heteroatom-doped carbon toward the HER and opens a door to rethinking the structure-performance relationships of carbon-based materials for other electrocatalytic reduction reactions.

NAc-DBS corrects depression-like behaviors in CUMS mouse model via disinhibition of DA neurons in the VTA.

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system-dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles. Deep brain stimulation (DBS) applied to the NAc alleviates the depressive symptoms of MDD. However, the mechanism underlying the effects of this DBS has remained elusive. In this study, using the chronic unpredictable mild stress (CUMS) mouse model, we investigated the behavioral and neurobiological effects of NAc-DBS on the multidimensional depression-like phenotypes induced by CUMS by integrating behavioral, in vivo microdialysis coupled with high-performance liquid chromatography-electrochemical detector (HPLC-ECD), calcium imaging, pharmacological, and genetic manipulation methods in freely moving mice. We found that long-term and repeated, but not single, NAc-DBS induced robust antidepressant responses in CUMS mice. Moreover, even a single trial NAc-DBS led to the elevation of the γ-aminobutyric acid (GABA) neurotransmitter, accompanied by the increase in dopamine (DA) neuron activity in the VTA. Both the inhibition of the GABAA receptor activity and knockdown of the GABAA-α1 gene in VTA-GABA neurons blocked the antidepressant effect of NAc-DBS in CUMS mice. Our results showed that NAc-DBS could disinhibit VTA-DA neurons by regulating the level of GABA and the activity of VTA-GABA in the VTA and could finally correct the depression-like behaviors in the CUMS mouse model.

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report.

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study.

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.

Relationship between ODI and sleep structure of obstructive sleep apnea and cardiac remodeling.

PURPOSE: The purpose of the study was to evaluate the quantitative relationship between Oxygen Desaturation Index (ODI) and sleep structure of obstructive sleep apnea (OSA) and cardiac remodeling. METHODS: In this study, patients were enrolled from January 2015 to October 2022, and were divided into 3 groups according to AHI: patients with AHI < 15, patients with 15 ≤ AHI < 30, and 260 patients with AHI ≥ 30. Stratified linear regression was used to analyze independent risk factors for cardiac remodeling in OSA. RESULTS: A total of 479 patients were enrolled. We found that compared with AHI < 15 group (n = 120), the group with AHI > 30 (n = 260) had increased left atrial anteroposterior diameter, left ventricular end-diastolic internal diameter, left ventricular posterior wall thickness, right ventricular anteroposterior diameter, and interventricular septal thickness (P < 0.05). The group with 15 ≤ AHI ≤ 30 (n = 99) had increased left atrial anteroposterior diameter (P < 0.05). Multivariate linear regression revealed that N2 sleep was an independent risk factor for left ventricular posterior wall thickness, with positive correlation (p < 0.05). N3 sleep was an independent risk factor for transverse right atrial diameter and right ventricular anteroposterior diameter, with negative correlation (P < 0.05). ODI was an independent risk factor for interventricular septal thickness, with positive correlation (P < 0.05). The arousal index was an independent risk factor for increased left atrial anteroposterior diameter, with positive correlation (P < 0.05). CONCLUSIONS: Increased ODI is an independent risk factor for interventricular septal thickness, while decreased slow wave sleep is an independent risk factor for right heart remodeling in OSA.

The value of circadian heart rate variability for the estimation of obstructive sleep apnea severity in adult males.

OBJECTIVES: Heart rate variability (HRV) is becoming more prevalent as a measurable parameter in wearable sleep-monitoring devices, which are simple and effective instruments for illness evaluation. Currently, most studies on investigating OSA severity and HRV have measured heart rates during wakefulness or sleep. Therefore, the objective of this study was to investigate the circadian rhythm of HRV in male patients with OSA and its value for the estimation of OSA severity using group-based trajectory modeling. METHODS: Patients with complaints of snoring were enrolled from the Sleep Center of Shandong Qianfoshan Hospital. Patients were divided into 3 groups according to apnea hypopnea index (AHI in events/h), as follows: (<15, 15≤AHI<30, and ≥30). HRV parameters were calculated using 24 h Holter monitoring, which included time-domain and frequency-domain indices. Circadian differences in the standard deviation of normal to normal (SDNN) were evaluated for OSA severity using analysis of variance, trajectory analysis, and multinomial logistic regression. RESULTS: A total of 228 patients were enrolled, 47 with mild OSA, 48 moderate, and 133 severe. Patients with severe OSA exhibited reduced triangular index and higher very low frequency than those in the other groups. Circadian HRV showed that nocturnal SDNN was considerably higher than daytime SDNN in patients with severe OSA. The difference among the OSA groups was significant at 23, 24, 2, and 3 o'clock sharp between the severe and moderate OSA groups (all P<0.05). The heterogeneity of circadian HRV trajectories in OSA was strongly associated with OSA severity, including sleep structure and hypoxia-related parameters. Among the low-to-low, low-to-high, high-to-low, and high-to-high groups, OSA severity in the low-to-high group was the most severe, especially compared with the low-to-low and high-to-low SDNN groups, respectively. CONCLUSIONS: Circadian HRV in patients with OSA emerged as low daytime and high nocturnal in SDNN, particularly in men with severe OSA. The heterogeneity of circadian HRV revealed that trajectories with low daytime and significantly high nighttime were more strongly associated with severe OSA. Thus, circadian HRV trajectories may be useful to identify the severity of OSA.

Structural Degradation of M-N-C (M=Co, Ni and Fe) Single-Atom Electrocatalysts at Industrial-Grade Current Density for Long-Term Reduction.

M-N-C single-atom catalysts (SACs) are promising electrode materials for many electro-reduction reactions. However, their stability is far from practical applications, and their deactivation mechanism has been rarely investigated. Herein, we demonstrate the structural degradation of M-N-C (M=Co, Ni, and Fe) at industrial-grade current density for long-term electro-reduction. Both M-N and N-C bonds are broken, resulting in the gradual hydrogenation and dissolution of N in the form of ammonia. The residual M is finally converted to M-containing core-shell nanoparticles after sequential dissolution, redeposition, and electro-reduction. The destruction of the M-N-C structure and the formation of nanoparticles greatly affect the electrocatalytic performance. Our work highlights the structural degradation and deactivation mechanism of M-N-C-type SACs under strong reductive conditions and provides useful information for inspiring researchers to develop new strategies to improve the electrocatalytic stability of similar types of materials.

Numerical fitting of Extrapolated semisolid Magnetization transfer Reference (NEMR) signals: Improved detection of ischemic stroke.

PURPOSE: To propose a novel Numerical fitting method of the Extrapolated semisolid Magnetization transfer Reference (NEMR) signal for quantifying the CEST effect. THEORY AND METHODS: Modified two-pool Bloch-McConnell equations were used to numerically fit the magnetization transfer (MT) and direct water saturation (DS) signals at far off-resonance frequencies, which was subsequently extrapolated into the frequency range of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) pools. Then the subtraction of the fitted two-pool z-spectrum and the experimentally acquired z-spectrum yielded APT# and NOE# signals mostly free of MT and DS contamination. Several strategies were used to accelerate the NEMR fitting. Furthermore, the proposed NEMR method was compared with the conventional extrapolated semisolid magnetization transfer reference (EMR) and magnetization transfer ratio asymmetry (MTRasym ) methods in simulations and stroke patients. RESULTS: The combination of RF downsampling, MT lineshape look-up table, and conversion of MATLAB code to C code accelerated the NEMR fitting by over 2700-fold. Monte-Carlo simulations showed that NEMR had higher accuracy than EMR and eliminated the requirement of the steady-state condition. In ischemic stroke patients, the NEMR maps at 1 µT removed hypointense artifacts seen on EMR and MTRasym images, and better depicted stroke lesions than EMR. For NEMR, NOE# yielded significantly (p < 0.05) stronger signal contrast between stroke and normal tissues than APT# at 1 µT. CONCLUSION: The proposed NEMR method is suitable for arbitrary saturation settings and can remove MT and DS contamination from the CEST signal for improved detection of ischemic stroke.

Omicron breakthrough infections in wild-type SARS-CoV-2 vaccinees elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V.

Omicron BF.7 became the predominant SARS-CoV-2 variant in Beijing after the abolishment of Zero-COVID policy in December 2022. The ability of antibodies elicited by BF.7 infection to cross-react with SARS-CoV-2-like viruses is unknown. This study aimed to investigate the cross-reactive neutralizing antibodies against SARS-CoV-2-related pangolin coronavirus GX_P2V in sera from vaccinated and/or SARS-CoV-2-infected individuals. All vaccinated individuals who recovered from Omicron BF.7 breakthrough infections exhibited substantially higher levels of neutralizing antibodies against GX_P2V, compared to other subject groups, with a geometric mean titer (GMT) of 362. Uninfected individuals who received four-mixed-dose vaccines also demonstrated higher levels of neutralizing antibodies (GMT = 44) against GX_P2V than those uninfected individuals who received two- or three-dose vaccines and those unvaccinated convalescents of wild-type SARS-CoV-2. This study highlights the significance of prior vaccinations with wild-type SARS-CoV-2 vaccines in generating potent cross-protective immunity against future spillovers of SARS-CoV-2-like viruses.

Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model.

Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related coronavirus GX_P2V and transcription- and replication-competent SARS-CoV-2 virus-like particles in vitro and block viral entry into cells. We confirmed that bovine Lf (bLf) blocked the binding between human angiotensin-converting enzyme 2 and SARS-CoV-2 spike protein by combining receptor-binding domain (RBD). Importantly, bLf inhibited RNA-dependent RNA polymerase (RdRp) activity of both SARS-CoV-2 and SARS-CoV in vitro in the nanomolar range. So far, no biological macromolecules have been reported to inhibit coronavirus RdRp. Our result indicated that bLf plays a major role in inhibiting viral replication. bLf treatment reduced viral load in lungs and tracheae and alleviated pathological damage. Our study provides evidence that bLf prevents SARS-CoV-2 infection by combining SARS-CoV-2 spike protein RBD and inhibiting coronaviruses' RdRp activity, and may be a promising candidate for the treatment of coronavirus disease 2019.

A circuit from lateral septum neurotensin neurons to tuberal nucleus controls hedonic feeding.

Feeding behavior is regulated by both the homeostatic needs of the body and hedonic values of the food. Easy access to palatable energy-dense foods and the consequent obesity epidemic stress the urgent need for a better understanding of neural circuits that regulate hedonic feeding. Here, we report that neurotensin-positive neurons in the lateral septum (LSNts) play a crucial role in regulating hedonic feeding. Silencing LSNts specifically promotes feeding of palatable food, whereas activation of LSNts suppresses overall feeding. LSNts neurons project to the tuberal nucleus (TU) via GABA signaling to regulate hedonic feeding, while the neurotensin signal from LSNts→the supramammillary nucleus (SUM) is sufficient to suppress overall feeding. In vivo calcium imaging and optogenetic manipulation reveal two populations of LSNts neurons that are activated and inhibited during feeding, which contribute to food seeking and consumption, respectively. Chronic activation of LSNts or LSNts→TU is sufficient to reduce high-fat diet-induced obesity. Our findings suggest that LSNts→TU is a key pathway in regulating hedonic feeding.

Predictors of ghost infarct core on baseline computed tomography perfusion in stroke patients with successful recanalization after mechanical thrombectomy.

OBJECTIVES: To assess the predictors of ghost infarct core (GIC) in stroke patients achieving successful recanalization after mechanical thrombectomy (MT), based on final infarct volume (FIV) calculated from follow-up diffusion-weighted imaging (DWI). METHODS: A total of 115 consecutive stroke patients who had undergone baseline computed tomography perfusion (CTP) scan, achieved successful recanalization after MT, and finished follow-up DWI evaluation were retrospectively enrolled. Ischemic core volume was automatically generated from baseline CTP, and FIV was determined manually based on follow-up DWI. Stroke-related risk factors and demographic, clinical, imaging, and procedural data were collected and assessed. Univariate and multivariate analyses were applied to identify the predictors of GIC. RESULTS: Of the 115 included patients (31 women and 84 men; median age, 66 years), 18 patients (15.7%) showed a GIC. The GIC group showed significantly shorter time interval from stroke onset to CTP scan and that from stroke onset to recanalization (both p < 0.001), but higher ischemic core volume (p < 0.001), hypoperfused area volume (p < 0.001), mismatch area volume (p = 0.006), and hypoperfusion ratio (p = 0.001) than the no-GIC group. In multivariate analysis, time interval from stroke onset to CTP scan (odds ratio [OR], 0.983; p = 0.005) and ischemic core volume (OR, 1.073; p < 0.001) were independently associated with the occurrence of GIC. CONCLUSIONS: In stroke patients achieving successful recanalization after MT, time interval from stroke onset to CTP and ischemic core volume are associated with the occurrence of GIC. Patients cannot be excluded from MT solely based on baseline CTP-derived ischemic core volume, especially for patients with a shorter onset time. KEY POINTS: • Ghost infarct core (GIC) was found in 15.7% of patients with acute ischemic stroke (AIS) in our study cohort. • GIC was associated with stroke onset time, volumetric parameters derived from CTP, and collateral status indicated by HIR. • Time interval from stroke onset to CTP scan and ischemic core volume were independent predictors of GIC.

ASPECTS-based net water uptake outperforms target mismatch for outcome prediction in patients with acute ischemic stroke and late therapeutic window.

OBJECTIVE: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window. METHODS: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve. RESULTS: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%). CONCLUSION: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection. CLINICAL RELEVANCE STATEMENT: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window. KEY POINTS: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window.

Diffusion-relaxation correlation spectrum imaging for predicting tumor consistency and gross total resection in patients with pituitary adenomas: a preliminary study.

OBJECTIVE: To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs). METHODS: Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis. RESULTS: Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05). CONCLUSION: DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs. CLINICAL RELEVANCE STATEMENT: DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs. KEY POINTS: • DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). • [Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. • The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785).

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis.

PURPOSE: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. MATERIALS AND METHODS: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. RESULTS: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells' (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. CONCLUSIONS: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

Spatial accuracy of computed tomography perfusion to estimate the follow-up infarct on diffusion-weighted imaging after successful mechanical thrombectomy.

BACKGROUND: Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated. METHODS: This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement. RESULTS: In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001). CONCLUSIONS: CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement.

Impact on etiology diagnosis by high-resolution vessel wall imaging in young adults with ischemic stroke or transient ischemic attack.

PURPOSE: The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA). METHODS: A total of 253 young adults (aged 18-45 years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI. RESULTS: The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01). CONCLUSIONS: HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.

A nomogram for predicting thrombus composition in stroke patients with large vessel occlusion: combination of thrombus density and perviousness with clinical features.

PURPOSE: To establish a nomogram incorporating pretreatment imaging parameters and clinical characteristics for predicting the thrombus composition of acute ischemic stroke (AIS) with large vessel occlusion (LVO). METHODS: We retrospectively enrolled patients with occlusion of the Middle Cerebral Artery (MCA) who underwent Mechanical Thrombectomy (MT). Retrieved thrombi were stained with Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB). Thrombi are assigned to the Fibrin-rich or RBC-rich group based on the relative fractions of Red Blood Cells (RBC), fibrin, and platelet. The independent risk factors for Fibrin-rich clots were determined via univariate and multivariate logistic regression analysis and were then integrated to establish a nomogram. RESULTS: In total, 98 patients were included in this study. Patients with fibrin-rich clots had worse functional outcome [modified Rankin scale (mRS) 0-2, 34.7% vs 63.2%, p = 0.005], longer procedure time (76.8 min vs 50.8 min, p = 0.001), and increased maneuvers of MT (1.84 vs 1.46, p = 0.703) than those with RBC-rich clots. The independent risk factors for Fibrin-rich clots were lower perviousness measured by Non-Contrast Computer Tomography (NCCT) and CT Angiography (CTA), lower thrombus relative attenuation on NCCT, elevated Platelet-WBC ratio (PWR) of admission peripheral blood, and previous antithrombotic medication. The nomogram showed good discrimination with an area under the Receiver Operating Characteristic (ROC) curve (AUC) of 0.852 (95% CI: 0.778-0.926). The calibration curve and decision curve analysis also displayed satisfactory accuracy and clinical utility. CONCLUSION: This study has developed and internally validated an easy-to-use nomogram which can help predict clot composition and optimize therapeutic strategies for thrombectomy.