Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Prognostic value of CD8+T cells related genes and exhaustion regulation of Notch signaling pathway in hepatocellular carcinoma.

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion-a potential target for future immunotherapeutic interventions.

Is a low dose of dexamethasone sufficient to prevent paclitaxel-related hypersensitivity reactions? A retrospective study in patients with gynecologic malignancy.

BACKGROUND: Paclitaxel hypersensitivity reactions (HSRs) are prevalent, especially in females. The common paclitaxel pretreatment, dexamethasone, may inhibit chemotherapy efficacy and accelerate tumor progression. We aimed to balance paclitaxel HSRs and the lowest dexamethasone dose for gynecologic malignancies. METHODS: We retrospectively examined 1,074 cycles of 3-weekly paclitaxel-containing treatment for 231 gynecologic malignancies at Xiangya Hospital. HSR incidence with different dexamethasone regimens was the primary outcome. Risk factors were examined in all cycles using univariate and multivariate models with generalized estimating equations. A subgroup analysis of initial exposure to paclitaxel was also conducted. RESULTS: HSR occurred in 33 patients (14.29%) and 49 cycles (4.56%), including 69.39% in cycles 1-2. There were no severe HSRs (grade ≥3). Different premedication regimens, including dexamethasone dosage and route, ranitidine presence or absence, didn't affect HSR incidence in univariate and multivariate analyzes (p > 0.05). Premenopausal women exerted fewer HSRs (ORadj 0.22, 95%CI 0.08-0.58; p = 0.002). At the first exposure to paclitaxel, more than 10 mg of dexamethasone didn't diminish HSRs (OR 0.83, 95%CI 0.27-2.59; p = 0.753). CONCLUSIONS: In gynecologic malignancies, 10 mg dexamethasone along with 20 mg diphenhydramine may be adequate to prevent paclitaxel HSRs without ranitidine. It is necessary to reevaluate paclitaxel premedication regimens.

Comparing OLIF Combined with Lateral Screw Fixation Versus Minimally Invasive TLIF for Treating Single-Level Degenerative Lumbar Spondylolisthesis: A Retrospective Cohort Study.

BACKGROUND: The present study aimed to compare the clinical and radiological outcomes of oblique lumbar interbody fusion (OLIF) combined with lateral screw fixation and minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) for the treatment of single-level degenerative lumbar spondylolisthesis (DLS). METHODS: Data regarding clinical and radiological outcomes for single-level DLS treated using OLIF combined with lateral screw fixation or Mis-TLIF between November 2017 and June 2020 were retrospectively analyzed. RESULTS: Seventy-five patients with single-level DLS (≥ 2 years' follow-up) were included and divided into 2 groups according to surgical method: OLIF (n=33); and Mis-TLIF (n=42). Operative time, intraoperative blood loss, and length of hospital stay were significantly lower in the OLIF group than that in the Mis-TLIF group. There were no significant differences in preoperative low back pain (LBP), leg pain (LP) visual analog scale (VAS) scores, and Oswestry Disability Index (ODI) between the two groups, although the OLIF group had significantly lower LBP VAS scores at 1, 3, and 6 months postoperatively. Additionally, the LP VAS score was significantly lower in the Mis-TLIF group than that in the OLIF group at 1 month postoperatively, and the ODI of the OLIF group at 3 months postoperatively was significantly lower than that of the Mis-TLIF group. There was no significant difference in the preoperative and postoperative lumbar lordosis angles between the two groups, whereas the postoperative surgical segmental lordosis angle and disc height (1, 6, 12, and 24 months) in the OLIF group were significantly higher than those in the Mis-TLIF group. Additionally, there was no significant difference in complication rates between the two groups (OLIF, 18.2% versus Mis-TLIF, 11.9%; p=0.520). Conclusion OLIF combined with lateral screw fixation yielded better clinical and radiological outcomes than Mis-TLIF in patients with single-level DLS.

Successful surgical treatment of impending paradoxical embolism with pulmonary embolism and myocardial infarction.

BACKGROUND: Paradoxical embolism is a rare cause of acute arterial occlusion. This phenomenon arises when embolic material travels from the venous system crosses an abnormal shunt such as patent foramen ovale, atrial septal defects, ventricular septal defects, or pulmonary arteriovenous malformations, into the arterial system. Impending paradoxical embolism refers to the presence of an entrapped thrombus in the patent foramen ovale. CASE PRESENTATION: We report a case of a 68-year-old female patient who presented with an impending paradoxical embolism, alongside both concomitant pulmonary embolism and myocardial infarction with ST-segment elevation. Swiftly addressed through emergency cardiac surgery and systemic anticoagulation, the patient's condition was effectively treated. CONCLUSIONS: While the ideal treatment strategy for impending paradoxical embolism remains a topic of debate due to limited and inconclusive evidence, emergent open surgery should be contemplated in patients as it signifies a critical clinical emergency.

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

PURPOSE: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. METHODS: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. RESULTS: In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. CONCLUSION: DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Effectiveness of adjuvant traditional Chinese medicine on macrovascular invasion in patients with hepatocellular carcinoma: a real-world propensity score-matched study.

The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387-0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.

Predicting brain age using partition modeling strategy and atlas-based attentional enhancement in the Chinese population.

As a biomarker of human brain health during development, brain age is estimated based on subtle differences in brain structure from those under typical developmental. Magnetic resonance imaging (MRI) is a routine diagnostic method in neuroimaging. Brain age prediction based on MRI has been widely studied. However, few studies based on Chinese population have been reported. This study aimed to construct a brain age predictive model for the Chinese population across its lifespan. We developed a partition prediction method based on transfer learning and atlas attention enhancement. The participants were separated into four age groups, and a deep learning model was trained for each group to identify the brain regions most critical for brain age prediction. The Atlas attention-enhancement method was also used to help the models focus only on critical brain regions. The proposed method was validated using 354 participants from domestic datasets. For prediction performance in the testing sets, the mean absolute error was 2.218 ± 1.801 years, and the Pearson correlation coefficient (r) was 0.969, exceeding previous results for wide-range brain age prediction. In conclusion, the proposed method could provide brain age estimation to assist in assessing the status of brain health.

[New perspective of anticoagulation in intensive care unit: basic and clinical advances in coagulation factor XII and XI inhibitors].

Anticoagulation therapy stands as a key treatment for thrombotic diseases. The consequential bleeding risk tied to existing anticoagulation methods significantly impacts patient prognosis. In the intensive care unit (ICU), patients often necessitate organ support, leading to the inevitable placement of artificial devices in blood vessels, thereby requiring anticoagulation treatment to avert clot formation that might impede organ support. Nevertheless, these patients commonly encounter a heightened risk of bleeding. Hemophilia B, identified in 1953, manifests as a deficiency in coagulation factor XI (FXI), which focused people's perspective on the endogenous coagulation pathway, that is, the contact pathway. Upon interaction between the surface of artificial devices and FXII, FXII activates, subsequently triggering FXI and initiating the "coagulation cascade" within the contact pathway. Inhibitors targeting the contact pathway encompass two primary categories: FXII inhibitors and FXI inhibitors, capable of impeding this process. This article reviews the role of FXII and FXI in activating the contact pathway, seeking to illuminate their contributions to thrombus formation. By listing the relatively mature drugs and their indications, clinicians are familiar with this new anticoagulant.

Looking through the imaging perspective: the importance of imaging necrosis in glioma diagnosis and prognostic prediction - single centre experience.

BACKGROUND: The aim of the study was to investigate the diagnostic value of imaging necrosis (Imnecrosis) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI). PATIENTS AND METHODS: We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Panecrosis) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Imnecrosis was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded. RESULTS: There was a strong degree of inter-observer agreement in defining Imnecrosis (Kappa = 0.668, p < 0.001) and a strong degree of agreement between Imnecrosis and Panecrosis (Kappa = 0.767, p < 0.001). Compared to low-grade gliomas, high-grade gliomas had more Imnecrosis (85.37%, p < 0.001), and Imnecrosis significantly increased with the grade of gliomas increasing. And Imnecrosis was significantly more identified in IDH-wildtype, 1p19q-non-codeletion, and CDKN2A/B-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Imnecrosis was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (ve) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Panecrosis and Imnecrosis with high specificity (83.3% and 91.9%, respectively). CONCLUSIONS: Imnecrosis can provide supplementary evidence beyond Panecrosis in grading, predicting the genotype and prognosis of gliomas, and ve in tumor parenchyma can help to predict tumor necrosis with high specificity.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Altered neurovascular coupling in the children with attention-deficit/hyperactivity disorder: a comprehensive fMRI analysis.

The coupling between resting-state cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signals reflects the mechanism of neurovascular coupling (NVC), which have not been illustrated in attention-deficit/hyperactivity disorder (ADHD). Fifty ADHD and 42 age- and gender-matched typically developing controls (TDs) were enrolled. The NVC imaging metrics were investigated by exploring the Pearson correlation coefficients between CBF and BOLD-derived quantitative maps (ALFF, fALFF, DCP maps). Three types of NVC metrics (CBF-ALFF, CBF-fALFF, CBF-DCP coupling) were compared between ADHD and TDs group, and the inner association between altered NVC metrics and clinical variables in ADHD group was further analyzed. Compared to TDs, ADHD showed significantly reduced whole-brain CBF-ALFF coupling (P < 0.001). Among regional level (all PFDR < 0.05), ADHD showed significantly lower CBF-ALFF coupling in bilateral thalamus, default-mode network (DMN) involving left anterior cingulate (ACG.L) and right parahippocampal gyrus (PHG.R), execution control network (ECN) involving right middle orbital frontal gyrus (ORBmid.R) and right inferior frontal triangular gyrus (IFGtriang.R), and increased CBF-ALFF coupling in attention network (AN)-related left superior temporal gyrus (STG.L) and somatosensory network (SSN))-related left rolandic operculum (ROL.L). Furthermore, increased CBF-fALFF coupling was found in the visual network (VN)-related left cuneus and negatively correlated with the concentration index of ADHD (R = - 0.299, PFDR = 0.035). Abnormal regional NVC metrics were at widespread neural networks in ADHD, mainly involved in DMN, ECN, SSN, AN, VN and bilateral thalamus. Notably, this study reinforced the insights into the neural basis and pathophysiological mechanism underlying ADHD.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Tumor Multiregional Mean Apparent Propagator (MAP) Features in Evaluating Gliomas-A Comparative Study With Diffusion Kurtosis Imaging (DKI).

BACKGROUND: Glioma classification affects treatment and prognosis. Reliable imaging methods for preoperatively evaluating gliomas are essential. PURPOSE: To evaluate tumor multiregional mean apparent propagator (MAP) features in glioma diagnosis and to compare those with diffusion-kurtosis imaging (DKI). STUDY TYPE: Retrospective study. SUBJECTS: 70 untreated glioma patients (31 LGGs (low-grade gliomas), 34 women; mean age, 47 ± 12 years, training (60%, n = 42) and testing cohorts (40%, n = 28)). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-MRI using q-space Cartesian grid sampling with 11 different b-values. ASSESSMENT: Tumor multiregional MAP (mean squared displacement (MSD); q-space inverse variance (QIV); non-Gaussianity (NG); axial/radial non-Gaussianity (NGAx, NGRad); return-to-origin/axis/plane probability (RTOP, RTAP, and RTPP)); and DKI metrics (axial/mean/radial kurtosis (AK, MK, and RK)) on tumor parenchyma (TP) and peritumoral areas (PT) in histopathologically gliomas grading and genotyping were assessed. STATISTICAL TESTS: Mann-Whitney U; Kruskal-Wallis; Benjamini-Hochberg; Bonferroni-correction; receiver operating curve (ROC) and area under curve (AUC); DeLong's test; Random Forest (RF). P value<0.05 was considered statistically significant after multiple comparisons correction. RESULTS: Compared with LGGs, MSD, and QIV were significantly lower in TP, whereas NG, NGAx, NGRad, RTOP, RTAP, RTPP, and DKI metrics were significantly higher in HGGs (high-grade gliomas) (P ≤ 0.007), as well as in isocitrate-dehydrogenase (IDH)-mutated than IDH-wildtype gliomas (P ≤ 0.039). These trends were reversed for PT (tumor grades, P ≤ 0.011; IDH-mutation status, P ≤ 0.012). ROC analysis showed that, in TP, DKI metrics performed best in TP (AUC 0.83), whereas in PT, RTPP performed best (AUC 0.77) in glioma grading. AK performed best in TP (AUC 0.77), whereas MSD and RTPP performed best in PT (AUC 0.73) in IDH genotyping. Further RF analysis with DKI and MAP demonstrated good performance in grading (AUC 0.91, Accuracy 82%) and IDH genotyping (AUC 0.87, Accuracy 79%). DATA CONCLUSION: Tumor multiregional MAP features could effectively evaluate gliomas. The performance of MAP may be similar to DKI in TP, while in PT, MAP may outperform DKI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Thyroid dysfunction associated with iodine-contrast media: A real-world pharmacovigilance study based on the FDA adverse event reporting system.

Objective: To comprehensively analyze characteristics of thyroid dysfunction associated with iodine contrast media (ICM) based on data from the FDA adverse event reporting system (FAERS). Methods: Disproportionate analysis was employed to identify signals of thyroid dysfunction caused by ICM, and descriptive analysis was performed to examine the clinical characteristics of reported cases involving ICM-related thyroid dysfunctions. Results: A total of 83 adverse event reports were identified, documenting thyroid dysfunctions associated with ICM agents. Treatment with ICM was significantly associated with higher reporting of hypothyroidism ([ROR] = 2.21, 95 % CI: 1.59-3.08; IC025 = 0.58) and hyperthyroidism (ROR = 3.49, 95 % CI: 2.37-5.13; IC025 = 1.14). Among the six ICM agents investigated, iodixanol demonstrated the highest signal strength in both hypothyroidism (ROR = 9.47) and hyperthyroidism (ROR = 5.44). Hypothyroidism and hyperthyroidism almost occurred in the first 30 days after ICM administration (76.9 % and 70 % of patients, respectively). Furthermore, the proportion of severe outcomes in hyperthyroidism was significantly higher than that in hypothyroidism (12/26 vs. 2/35, P = 0.009). Conclusion: The present study highlights the varying risks of thyroid dysfunction associated with different ICM agents, with iodixanol exhibiting the highest signal intensity. Hypothyroidism and hyperthyroidism associated with ICM generally manifest within the first month following administration. Consequently, monitoring of thyroid function during this period is strongly recommended for ICM agents presenting higher risk profiles.

A Nomogram Prognostic Model for Advanced Hepatocellular Carcinoma Based on the Interaction Between CD8+T Cell Counts and Age.

Objective: CD8+T cells are essential components of the adaptive immune system and are crucial in the body's immune system. This study aimed to investigate how the prognosis of patients with advanced hepatocellular carcinoma (HCC) was affected by their CD8+ T cell counts and age and established an effective nomogram model to predict the overall survival (OS). Methods: A total of 427 patients with advanced HCC from Beijing Ditan Hospital, Capital Medical University, were enrolled in this study and randomly divided into training and validation groups, with 300 and 127 individuals in each group, respectively. Cox regression analysis was used to screen for independent risk factors for advanced HCC, and the interactive relationship between CD8+T cells and patient age was examined to establish a nomogram prediction model. Results: Cox multivariate regression and interaction analyses indicated that tumor number, tumor size, aspartate aminotransferase (AST), C-reactive protein (CRP), relationship of CD8+T cell counts and age were independent predictors of 6-month OS in patients with advanced HCC, and the nomogram model was established based on these factors. The area under the receiver operating characteristic curve (AUC) of the nomogram model for predicting the 3-month, 6-month, and 12-month OS rates were 0.821, 0.802, and 0.756, respectively. Moreover, in clinical practice, patients with true-positive survival benefit more than true-positive death, therefore, we selected 25% as the clinical decision threshold probability based on probability density functions (PDFs) and clinical utility curves (CUCs), which can distinguish approximately 92% of patients who died and 37% of patients who survived. Conclusion: The nomogram model based on CD8+T cell counts and age accurately assessed the prognosis of patients with advanced HCC and suggested that high CD8+T cell levels are beneficial to the survival of patients with advanced HCC.

Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI.

Evaluation of myelin content is crucial for attention-deficit/hyperactivity disorder (ADHD). To estimate myelin content in ADHD based on synthetic MRI-based method and compare it with established diffusion tensor imaging (DTI) method. Fifth-nine ADHD and fifty typically developing (TD) children were recruited. Global and regional myelin content (myelin volume fraction [MVF] and myelin volume [MYV]) were assessed using SyMRI and compared with DTI metrics (fractional anisotropy and mean/radial/axial diffusivity). The relationship between significant MRI parameters and clinical variables were assessed in ADHD. No between-group differences of whole-brain myelin content were found. Compared to TDs, ADHD showed higher mean MVF in bilateral internal capsule, external capsule, corona radiata, and corpus callosum, as well as in left tapetum, left superior fronto-occipital fascicular, and right cingulum (all PFDR-corrected < 0.05). Increased MYV were found in similar regions. Abnormalities of DTI metrics were mainly in bilateral corticospinal tract. Besides, MVF in right retro lenticular part of internal capsule was negatively correlated with cancellation test scores (r = - 0.41, P = 0.002), and MYV in right posterior limb of internal capsule (r = 0.377, P = 0.040) and left superior corona radiata (r = 0.375, P = 0.041) were positively correlated with cancellation test scores in ADHD. Increased myelin content underscored the important pathway of frontostriatal tract, posterior thalamic radiation, and corpus callosum underlying ADHD, which reinforced the insights into myelin quantification and its potential role in pathophysiological mechanism and disease diagnosis. Prospectively registered trials number: ChiCTR2100048109; date: 2021-07.

Modification of histidine repeat proteins by inorganic polyphosphate.

Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate that is present in nearly all organisms studied to date. A remarkable function of polyP involves its attachment to lysine residues via non-enzymatic post-translational modification (PTM), which is presumed to be covalent. Here, we show that proteins containing tracts of consecutive histidine residues exhibit a similar modification by polyP, which confers an electrophoretic mobility shift on NuPAGE gels. Our screen uncovers 30 human and yeast histidine repeat proteins that undergo histidine polyphosphate modification (HPM). This polyP modification is histidine dependent and non-covalent in nature, although remarkably it withstands harsh denaturing conditions-a hallmark of covalent PTMs. Importantly, we show that HPM disrupts phase separation and the phosphorylation activity of the human protein kinase DYRK1A, and inhibits the activity of the transcription factor MafB, highlighting HPM as a potential protein regulatory mechanism.