Resting-State fMRI Study of Vigilance Under Circadian and Homeostatic Modulation Based on Fractional Amplitude of Low-Frequency Fluctuation and Regional Homogeneity in Humans Under Normal Entrained Conditions.

BACKGROUND: How brain neural activity changes at multiple time points throughout the day and the neural mechanisms underlying time-dependent modulation of vigilance are less clear. PURPOSE: To explore the effect of circadian rhythms and homeostasis on brain neural activity and the potential neural basis of time-dependent modulation of vigilance. STUDY TYPE: Prospective. SUBJECTS: A total of 30 healthy participants (22-27 years old). FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted imaging, echo-planar functional MRI (fMRI). ASSESSMENT: Six resting-state fMRI (rs-fMRI) scanning sessions were performed at fixed times (9:00 h, 13:00 h, 17:00 h, 21:00 h, 1:00 h, and 5:00 h) to investigate fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) diurnal variation. The fALFF/ReHo and the result of the psychomotor vigilance task were used to assess local neural activity and vigilance. STATISTICAL TESTS: One-way repeated measures analysis of variance (ANOVA) was used to assess changes in vigilance (P < 0.05) and neural activity in the whole brain (P < 0.001 at the voxel level and P < 0.01 at the cluster level, Gaussian random field [GRF] corrected). Correlation analysis was used to examine the relationship between neural activity and vigilance at all-time points of the day. RESULTS: The fALFF/ReHo in the thalamus and some perceptual cortices tended to increase from 9:00 h to 13:00 h and from 21:00 h to 5:00 h, whereas the key nodes of the default mode network (DMN) tended to decrease from 21:00 h to 5:00 h. The vigilance tended to decrease from 21:00 h to 5:00 h. The fALFF/ReHo in the thalamus and some perceptual cortices was negatively correlated with vigilance at all-time points of the day, whereas the fALFF/ReHo in the key nodes of the DMN was positively correlated with vigilance. DATA CONCLUSION: Neural activities in the thalamus and some perceptual cortices show similar trends throughout the day, whereas the key nodes of the DMN show roughly opposite trends. Notably, diurnal variation of the neural activity in these brain regions may be an adaptive or compensatory response to changes in vigilance. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 1.

Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

Radiomics analysis of lesion-specific pericoronary adipose tissue to predict major adverse cardiovascular events in coronary artery disease.

OBJECTIVE: To investigate the prognostic performance of radiomics analysis of lesion-specific pericoronary adipose tissue (PCAT) for major adverse cardiovascular events (MACE) with the guidance of CT derived fractional flow reserve (CT-FFR) in coronary artery disease (CAD). MATERIALS AND METHODS: The study retrospectively analyzed 608 CAD patients who underwent coronary CT angiography. Lesion-specific PCAT was determined by the lowest CT-FFR value and 1691 radiomic features were extracted. MACE included cardiovascular death, nonfatal myocardial infarction, unplanned revascularization and hospitalization for unstable angina. Four models were generated, incorporating traditional risk factors (clinical model), radiomics score (Rad-score, radiomics model), traditional risk factors and Rad-score (clinical radiomics model) and all together (combined model). The model performances were evaluated and compared with Harrell concordance index (C-index), area under curve (AUC) of the receiver operator characteristic. RESULTS: Lesion-specific Rad-score was associated with MACE (adjusted HR = 1.330, p = 0.009). The combined model yielded the highest C-index of 0.718, which was higher than clinical model (C-index = 0.639), radiomics model (C-index = 0.653) and clinical radiomics model (C-index = 0.698) (all p < 0.05). The clinical radiomics model had significant higher C-index than clinical model (p = 0.030). There were no significant differences in C-index between clinical or clinical radiomics model and radiomics model (p values were 0.796 and 0.147 respectively). The AUC increased from 0.674 for clinical model to 0.721 for radiomics model, 0.759 for clinical radiomics model and 0.773 for combined model. CONCLUSION: Radiomics analysis of lesion-specific PCAT is useful in predicting MACE. Combination of lesion-specific Rad-score and CT-FFR shows incremental value over traditional risk factors.

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

Risk prediction of intraoperative pain in percutaneous microwave ablation of lung tumors under CT guidance.

OBJECTIVES: To evaluate the effect of intraoperative pain in microwave ablation of lung tumors (MWALT) on local efficacy and establish the pain risk prediction model. METHODS: It was a retrospectively study. Consecutive patients with MWALT from September 2017 to December 2020 were divided into mild and severe pain groups. Local efficacy was evaluated by comparing technical success, technical effectiveness, and local progression-free survival (LPFS) in two groups. All cases were randomly allocated into training and validation cohorts at a ratio of 7:3. A nomogram model was established using predictors identified by logistics regression in training dataset. The calibration curves, C-statistic, and decision curve analysis (DCA) were used to evaluate the accuracy, ability, and clinical value of the nomogram. RESULTS: A total of 263 patients (mild pain group: n = 126; severe pain group: n = 137) were included in the study. Technical success rate and technical effectiveness rate were 100% and 99.2% in the mild pain group and 98.5% and 97.8% in the severe pain group. LPFS rates at 12 and 24 months were 97.6% and 87.6% in the mild pain group and 91.9% and 79.3% in the severe pain group (p = 0.034; HR: 1.90). The nomogram was established based on three predictors: depth of nodule, puncture depth, and multi-antenna. The prediction ability and accuracy were verified by C-statistic and calibration curve. DCA curve suggested the proposed prediction model was clinically useful. CONCLUSIONS: Severe intraoperative pain in MWALT reduced the local efficacy. An established prediction model could accurately predict severe pain and assist physicians in choosing a suitable anesthesia type. CLINICAL RELEVANCE STATEMENT: This study firstly provides a prediction model for the risk of severe intraoperative pain in MWALT. Physicians can choose a suitable anesthesia type based on pain risk, in order to improve patients' tolerance as well as local efficacy of MWALT. KEY POINTS: • The severe intraoperative pain in MWALT reduced the local efficacy. • Predictors of severe intraoperative pain in MWALT were the depth of nodule, puncture depth, and multi-antenna. • The prediction model established in this study can accurately predict the risk of severe pain in MWALT and assist physicians in choosing a suitable anesthesia type.

Altered static and dynamic indices of intrinsic brain activity in patients with subcortical ischemic vascular disease: a resting-state functional magnetic resonance imaging analysis.

PURPOSE: To explore the static and dynamic characteristics of intrinsic brain activity (IBA) in subcortical ischemic vascular disease (SIVD) patients with or without cognitive impairment. METHODS: In total, 90 participants were recruited, including 32 SIVD patients with cognitive impairment (SIVD-CI, N = 32), 26 SIVD patients with no cognitive impairment (SIVD-NCI, N = 26), and 32 healthy controls (HC, N = 32) matched for age, gender, and education. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and neuropsychological tests. Amplitude of low-frequency fluctuation (ALFF) was calculated to reflect static alterations of regional IBA. Sliding window analysis was conducted in order to explore the dynamic characteristics. RESULTS: Both SIVD-CI and SIVD-NCI group showed significantly decreased ALFF in left angular gyrus (ANG), whereas SIVD-CI group showed increased ALFF in right superior frontal gyrus (SFG), compared with HCs. Furthermore, SIVD-CI group showed significantly decreased ALFF dynamics (dALFF) in right precuneus (PreCu) and left dorsal anterior cingulate cortex (dACC), compared with HC and SIVD-NCI groups (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). No dynamic changes were detected between SIVD-NCI group and HC group. The mean ALFF value in left ANG of SIVD-CI group was correlated with the score of delayed memory scale. CONCLUSION: ANG may be a vulnerable brain region in SIVD patients. Temporal dynamic analysis could serve as a sensitive and promising method to investigate IBA alterations in SIVD patients.

The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a genetic neurodegenerative disorder characterized by cerebellar ataxia, tremor, and cognitive dysfunction. We examined the impact of dual-task (DT) cognitive-motor interference and fast-paced (FP) gait on gait and turning in FXTAS. Thirty participants with FXTAS and 35 age-matched controls underwent gait analysis using an inertial sensor-based 2-min walk test under three conditions: (1) self-selected pace (ST), (2) FP, and (3) DT with a concurrent verbal fluency task. Linear regression analyses were performed to assess the association between FXTAS diagnosis and gait and turn outcomes. Correlations between gait variables and fall frequency were also calculated. FXTAS participants had reduced stride length and velocity, swing time, and peak turn velocity and greater double limb support time and number of steps to turn compared to controls under all three conditions. There was greater dual task cost of the verbal fluency task on peak turn velocity in men with FXTAS compared to controls. Additionally, stride length variability was increased and cadence was reduced in FXTAS participants in the FP condition. Stride velocity variability under FP gait was significantly associated with the number of self-reported falls in the last year. Greater motor control requirements for turning likely made men with FXTAS more susceptible to the negative effects of DT cognitive interference. FP gait exacerbated gait deficits in the domains of rhythm and variability, and increased gait variability with FP was associated with increased falls. These data may inform the design of rehabilitation strategies in FXTAS.

Texture analysis of MR images to identify the differentiated degree in hepatocellular carcinoma: a retrospective study.

BACKGROUND: To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) to identify the differentiated degree of hepatocellular carcinoma (HCC). METHOD: One hundred four participants were enrolled in this retrospective study. Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture features were analyzed by MaZda, and B11 program was used for data analysis and classification. The diagnosis efficiencies of texture features and conventional imaging features in identifying the differentiated degree of HCC were assessed by receiver operating characteristic analysis. The relationship between texture features and differentiated degree of HCC was evaluated by Spearman's correlation coefficient. RESULTS: The grey-level co-occurrence matrix -based texture features were most frequently extracted and the nonlinear discriminant analysis was excellent with the misclassification rate ranging from 3.33 to 14.93%. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively, while the AUC of tumor size was 0.649, 0.660 and 0.517 respectively. The tumor size was significantly different between poorly- and moderately-HCC (p = 0.014). The COMBINE AUC values were not increased with tumor size combined. CONCLUSIONS: Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI was valuable and might be a promising method in identifying the differentiated degree of HCC. The poorly-differentiated HCC was more heterogeneous than well- and moderately-differentiated HCC.

Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.

BACKGROUND: Premutation size (55-199 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome, but it is unclear whether smaller "gray" zone expansions of 41-54 repeats are also associated with movement disorders. The objectives of this study were to determine the association between the FMR1 gene gray zone expansions, AGG interspersions, and the presence of parkinsonism and motor and cognitive function in an elderly community-based population. METHODS: Automated FMR1 polymerase chain reaction was performed on existing samples from 2 longitudinal aging studies whose subjects agreed to brain donation. A detailed clinical evaluation including a modified Unified Parkinson's Disease Rating Scale score, a composite score of global motor function, 17 cognitive tests summarized as a global measure of cognition, and neuropathological examination were obtained for genotyped participants. RESULTS: The average age of the population (n = 2362) was 85.9 ± 7.3 years, and average age at death was 88.6 ± 6.4 years (n = 1326), with 72% women. The prevalence of FMR1 gray zone alleles was 5.2% (122 of 2362). There was no difference between participants with gray zone expansions or those lacking AGG interspersions compared with normal participants in global cognition, global motor function, clinical diagnosis, or pathological changes. Gray zone alleles were associated with signs of parkinsonism in men (P = 0.01), and gray zone carrier men were more likely to die (hazard ratio, 2.34; 95% confidence interval, 1.31-4.16). CONCLUSIONS: This is the largest study to investigate gray zone alleles in a community population. The key findings are that in men, the gray zone allele is associated with signs of parkinsonism and higher risk of death, but not with intranuclear neuronal inclusions. © 2020 International Parkinson and Movement Disorder Society.

Thymoquinone: An Effective Natural Compound for Kidney Protection.

Kidney disease is a common health problem worldwide. Acute or chronic injuries may interfere with kidney functions, eventually resulting in irreversible kidney damage. A number of recent studies have shown that the plant-derived natural products have an extensive potential for renal protection. Thymoquinone (TQ) is an essential compound derived from Nigella Sativa (NS), which is widely applied in the Middle East as a folk medicine. Previous experiments have demonstrated that TQ has a variety of potential pharmacological effects, including anti-oxidant, antibacterial, antitumor, immunomodulatory, and neuroprotective activities. In particular, the prominent renal protective efficacy of TQ has been demonstrated in both in vivo and in vitro experiments. TQ can prevent acute kidney injuries from various xenobiotics through anti-oxidation, anti-inflammatory, and anti-apoptosis effects. In addition, TQ exhibited significant pharmacological effects on renal cell carcinoma, renal fibrosis, and urinary calculi. The essential mechanisms involve scavenging ROS and increasing anti-oxidant activity, decreasing inflammatory mediators, inducing apoptosis, and inhibiting migration and invasion. The purpose of this review is to conclude the pharmacological effects and the potential mechanisms of TQ in renal protection, shedding new light on the exploration of medicinal phyto-protective agents targeting kidneys.

The Value of Radiomics Features Based on HRCT in Predicting whether the Lung Sub-Centimeter Pure Ground Glass Nodule is Benign or Malignant.

OBJECTIVE: In this study, a radiomics model was created based on High-Resolution Computed Tomography (HRCT) images to noninvasively predict whether the sub-centimeter pure Ground Glass Nodule (pGGN) is benign or malignant. METHODS: A total of 235 patients (251 sub-centimeter pGGNs) who underwent preoperative HRCT scans and had postoperative pathology results were retrospectively evaluated. The nodules were randomized in a 7:3 ratio to the training (n=175) and the validation cohort (n=76). The volume of interest was delineated in the thin-slice lung window, from which 1316 radiomics features were extracted. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to select the radiomics features. Univariate and multivariable logistic regression were used to evaluate the independent risk variables. The performance was assessed by obtaining Receiver Operating Characteristic (ROC) curves for the clinical, radiomics, and combined models, and then the Decision Curve Analysis (DCA) assessed the clinical applicability of each model. RESULTS: Sex, volume, shape, and intensity mean were chosen by univariate analysis to establish the clinical model. Two radiomics features were retained by LASSO regression to build the radiomics model. In the training cohort, the Area Under the Curve (AUC) of the radiomics (AUC=0.844) and combined model (AUC=0.871) was higher than the clinical model (AUC=0.773). In evaluating whether or not the sub-centimeter pGGN is benign, the DCA demonstrated that the radiomics and combined model had a greater overall net benefit than the clinical model. CONCLUSION: The radiomics model may be useful in predicting the benign and malignant sub-centimeter pGGN before surgery.

A nomogram based on MRI radiomics features of mesorectal fat for diagnosing T2- and T3-stage rectal cancer.

PURPOSE: To develop and validate a nomogram for the preoperative diagnosis of T2 and T3 stage rectal cancer using MRI radiomics features of mesorectal fat. METHODS: The data of 288 patients with T2 and T3 stage rectal cancer were retrospectively collected. Radiomics features were extracted from the lesion region of interest (ROI) in the MRI high-resolution T2WI, apparent diffusion coefficient (ADC), and diffusion-weighted imaging (DWI) sequences. After using ICC inter-group consistency analysis and Pearson correlation analysis to reduce dimensions, LASSO regression analysis was performed to select features and calculate Rad-score for each sequence. Then, Combined_Radscore and nomogram were constructed based on the LASSO-selected features and clinical data for each sequence. Receiver operating characteristic curve (ROC) area under the curve (AUC) was used to evaluate the performance of the Rad-score model and nomogram. Decision curve analysis (DCA) was performed to evaluate the clinical usability of the radiomics nomogram, which were combined with calibration curves to evaluate the prediction accuracy. RESULTS: The nomogram based on MRI-report T status and Combined_Radscore achieved AUCs of 0.921 and 0.889 in the training and validation cohorts, respectively. CONCLUSION: The nomogram can be stated that the radiomics nomogram based on multi-sequence MRI imaging of the mesorectal fat has excellent diagnosing performance for preoperative differentiation of T2 and T3 stage rectal cancer.

The Effects of PICALM rs3851179 and Age on Brain Atrophy and Cognition Along the Alzheimer's Disease Continuum.

Rs3851179, a variant of PICALM gene, and age are the risk factors of Alzheimer's disease (AD). AD is divided into early-onset AD (EOAD, < 65 years) and late-onset AD (LOAD, ≥ 65 years) by age. The purpose was to investigate the impact of different genotypes of PICALM rs3851179 on brain atrophy and cognitive decline across the AD continuum in different age groups. Four hundred seven cognitive normal (CN) controls, 362 mild cognitive impairment (MCI) patients, and 94 AD patients were enrolled to assess the interaction between AD continuum, age status, and PICALM on gray matter volume (GMV), global cognition, memory function, and executive function using full factorial ANCOVA (3 × 2 × 2). The interaction between AD continuum and PICALM significantly affected the GMV of the left putamen (PUT.L). rs3851179 A-allele carriers did not show a significant decrease in PUT.L GMV from CN to MCI to AD, while GG-allele carriers did. The interaction between AD continuum and age status was significant on GMV of the left angular gyrus (ANG.L) and right superior occipital gyrus (SOG.R). LOAD had higher GMV of ANG.L and SOG.R than EOAD. The interactive effects among AD continuum, age status, and PICALM were not significant on GMV but were significant on global cognition and executive function. The A-allele was found to have a protective effect on global cognition and executive function in EOAD, but not significantly so in LOAD. PICALM rs3851179 A-allele might alleviate the atrophy of PUT.L across the AD continuum than GG-allele. Age status did not affect the interaction between AD continuum and PICALM on brain atrophy. The ANG.L and SOG.R atrophied more severely in EOAD than in LOAD. Rs3851179 A-allele was protective for global cognition and executive function in EOAD.

Deciphering two decades of cellular reprogramming in cancer: A bibliometric analysis of evolving trends and research frontiers.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002-2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled "Hallmarks of Cancer: The Next Generation". A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to "extracellular vesicles," "cancer therapy," and "cellular plasticity". Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

Intravenous administration of IL-12 encoding self-replicating RNA-lipid nanoparticle complex leads to safe and effective antitumor responses.

Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Therapies that can synergistically modulate innate immunity and stimulate adaptive anti-tumor responses are of great interest for cancer immunotherapy. Here we investigated the lipid nanoparticle-encapsulated self-replicating RNA (srRNA) encoding IL-12 (referred to as JCXH-211) for the treatment of cancers. Both local (intratumoral) and systemic (intravenous) administration of JCXH-211 in tumor-bearing mice induced a high-level expression of IL-12 in tumor tissues, leading to modulation of tumor microenvironment and systemic activation of antitumor immunity. Particularly, JCXH-211 can inhibit the tumor-infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). When combined with anti-PD1 antibody, it was able to enhance the recruitment of T cells and NK cells into tumors. In multiple mouse solid tumor models, intravenous injection of JCXH-211 not only eradicated large preestablished tumors, but also induced protective immune memory that prevented the growth of rechallenged tumors. Finally, intravenous injection of JCXH-211 did not cause noticeable systemic toxicity in tumor-bearing mice and non-human primates. Thus, our study demonstrated the feasibility of intravenous administration of JCXH-211 for the treatment of advanced cancers.

Regulatory mechanism of macrophage polarization based on Hippo pathway.

Macrophages are found to infiltrate and migrate in a large number of Tumor-associated macrophages (TMEs) and other macrophages in the microenvironment of tumors and related diseases, and undergo phenotypic changes in response to a variety of cytokines, mainly including the primary phenotype M2 and the anti-tumor phenotype M1. The Hippo signaling pathway affects the development of cancer and other diseases through various biological processes, such as inhibition of cell growth. In this review, we focus on immune cells within the microenvironment of tumors and other diseases, and the role of the Hippo pathway in tumors on macrophage polarization in the tumor microenvironment (TME) and other diseases.

Preoperative predicting invasiveness of lung adenocarcinoma manifesting as ground-glass nodules based on multimodal images of dual-layer spectral detector CT radiomics models.

OBJECTIVE: To construct and validate conventional and radiomics models based on dual-layer spectral CT radiomics for preoperative prediction of lung ground glass nodules (GGNs) invasiveness. MATERIALS AND METHODS: A retrospective study was conducted on 176 GGNs patients who underwent chest non-contrast enhancement scan on dual-layer spectral detector CT at our hospital within 2 weeks before surgery. Patients were randomized into the training cohort and testing cohort. Clinical features, imaging features and spectral quantitative parameters were collected to establish a conventional model. Radiomics models were established by extracting 1781 radiomics features form regions of interest of each spectral image [120 kVp poly energetic images (PI), 60 keV images and electron density maps], respectively. After selecting the optimal radiomic features and integrating multiple machine learning models, the conventional model, PI model, 60 keV model, electron density (ED) model and combined model based on multimodal spectral images were finally established. The performance of these models was assessed through the evaluation of discrimination, calibration, and clinical application. RESULTS: In the conventional model, age, vacuole sign, 60 keV and ED were independent risk factors of invasiveness. The combined model using logistic regression-least absolute shrinkage and selection operator classifiers was the optimal model with a higher area under the curve of the training (0.961, 95% confidence interval, CI: 0.932-0.991) and testing set (0.944, 0.890-0.999). CONCLUSION: The combined models are helpful to predict the invasiveness of GGNs before surgery and guide the individualized treatment of patients.

Multiregional-based magnetic resonance imaging radiomics model for predicting tumor deposits in resectable rectal cancer.

PURPOSE: To establish and validate an integrated model incorporating multiregional magnetic resonance imaging (MRI) radiomics features and clinical factors to predict tumor deposits (TDs) preoperatively in resectable rectal cancer (RC). METHODS: This study retrospectively included 148 resectable RC patients [TDs+ (n = 45); TDs- (n = 103)] from August 2016 to August 2022, who were divided randomly into a testing cohort (n = 45) and a training cohort (n = 103). Radiomics features were extracted from the volume of interest on T2-weighted images (T2WI) and diffusion-weighted images (DWI) from pretreatment MRI. Model construction was performed after feature selection. Finally, five classification models were developed by support vector machine (SVM) algorithm to predict TDs in resectable RC using the selected clinical factor, single-regional radiomics features (extracted from primary tumor), and multiregional radiomics features (extracted from the primary tumor and mesorectal fat). Receiver-operating characteristic (ROC) curve analysis was employed to assess the discrimination performance of the five models. The AUCs of five models were compared by DeLon's test. RESULTS: The training and testing cohorts included 31 (30.1%) and 14 (31.1%) patients with TDs, respectively. The AUCs of multiregional radiomics, single-regional radiomics, and the clinical models for predicting TDs were 0.839, 0.765, and 0.793, respectively. An integrated model incorporating multiregional radiomics features and clinical factors showed good predictive performance for predicting TDs in resectable RC (AUC, 0.931; 95% CI, 0.841-0.988), which demonstrated superiority over clinical model (P = 0.016), the single-regional radiomics model (P = 0.042), and the multiregional radiomics model (P = 0.025). CONCLUSION: An integrated model combining multiregional MRI radiomic features and clinical factors can improve prediction performance for TDs and guide clinicians in implementing treatment plans individually for resectable RC patients.

Effects of race and test preparation resources on standardized test scores, a pilot study.

BACKGROUND: Little research exists on the relationship between pre-examination resources, race, and standardized test outcomes. This study aimed to determine the effect of test preparation resources and race on test scores. METHODS: We surveyed medical students at an allopathic institution on the use of test preparation materials and their test scores. Students were grouped by self-identified race. Underrepresented in Medicine (URiM) students were defined as Black/African American (AA), Hispanic/Latino (HL), Native American (NA) and multiple races. Univariate analysis and linear regression were used for statistical analysis. RESULTS: 192 students completed the survey (response rate = 33%). URiM students reported more MCAT attempts than other students. No differences between scores existed between races. There was no association between scores and the use of test preparation resources. CONCLUSIONS: We found that URiM students took the MCAT more times than their peers; however, we found no racial/ethnic differences in examination preparation resources or scores.

[Hydrochemical Characteristics and Control Factors of Groundwater in Shunping County, Hebei Province].

In order to study the chemical characteristics and ion source of groundwater and further serve the scientific development and management of water resources in Shunping County. A total of 33 groups of karst water and 12 groups of pore water samples were collected systematically in Shunping County, and the hydrochemical types, composition characteristics, and main controlling factors of various types of groundwater were analyzed by using Gibbs diagram, ion ratio relation, and multivariate statistical analysis methods, and the contribution rates of various sources to groundwater solutes were evaluated. The results showed that the pore water and karst water in the study area were weakly alkaline, with TDS ranging from 245.89 to 430.00 mg·L-1 and 223.54 to 1347.80 mg·L-1, respectively. The anion components of groundwater were mainly HCO3- and Ca2+. Groundwater in the study area could be grouped into PW1 and PW2 pore water and KW1, KW2, and KW3 karst water. PW1 and KW1 were HCO3-Ca·Mg type, PW2 was HCO3·Cl-Ca·Mg type, KW2 was HCO3·NO3-Ca·Mg type, and KW3 was SO4-Ca·Mg type with high salinity. The weathering of carbonate rock mainly composed of dolomite and silicate rock mainly composed of albiar and potassium feldspar were the main material sources of groundwater, and their contributions to each water body were 39.69% to 66.13% and 11.87% to 58.38%. Sewage discharge and fertilizer use in human activities had significant effects on KW2 groundwater and PW1, PW2, and KW1 groundwater, respectively. In addition, the contribution rate of atmospheric precipitation to each water body ranged from 1.09% to 7.94% on average.