Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1-nitropyrene (1-NP), a key component of motor vehicle exhaust, on autism-like behaviors in a mouse model. Three-chamber test finds that prenatal 1-NP exposure causes autism-like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1-NP-exposed weaning pups. Immunofluorescence finds that prenatal 1-NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1-NP exposure retards tangential migration of GAD67-positive interneurons and downregulates interneuron migration-related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1-NP exposure reduces hydroxymethylation of interneuron migration-related genes through inhibiting ten-eleven translocation (TET) activity in fetal forebrain. Supplement with alpha-ketoglutarate (α-KG), a cofactor of TET enzyme, reverses 1-NP-induced hypohydroxymethylation at specific sites of interneuron migration-related genes. Moreover, α-KG supplement alleviates 1-NP-induced migration retardation of interneurons in fetal forebrain. Finally, maternal α-KG supplement improves 1-NP-induced autism-like behaviors in weaning offspring. In conclusion, prenatal 1-NP exposure causes autism-like behavior partially by altering DNA hydroxymethylation of interneuron migration-related genes in developing brain.

Dramatically Enhanced Mechanical Properties of Nano-TiN-Dispersed n-Type Bismuth Telluride by Multi-Effect Modulation.

Bismuth telluride (Bi2Te3)-based alloys have been extensively employed in energy harvesting and refrigeration applications for decades. However, commercially produced Bi2Te3-based alloys using the zone-melting (ZM) technique often encounter challenges such as insufficient mechanical properties and susceptibility to cracking, particularly in n-type Bi2Te3-based alloys, which severely limit the application scenarios for bismuth telluride devices. In this work, we seek to enhance the mechanical properties of n-type Bi2Te2.7Se0.3 alloys while preserving their thermoelectrical performance by a mixed mechanism of grain refinement and the TiN composite phase-introduced pinning effect. These nanoscale processes, coupled with the addition of TiN, result in a reduction in grain size. The pinning effects of nano-TiN contribute to increased resistance to crack propagation. Finally, the TiN-dispersed Bi2Te2.7Se0.3 samples demonstrate increased hardness, bending strength and compressive strength, reaching 0.98 GPa, 36.3 MPa and 74 MPa. When compared to the ZM ingots, those represent increments of 181%, 60% and 67%, respectively. Moreover, the thermoelectric performance of the TiN-dispersed Bi2Te2.7Se0.3 samples is identical to the ZM ingots. The samples exhibit a peak dimensionless figure of merit (ZT) value of 0.957 at 375 K, with an average ZT value of 0.89 within the 325-450 K temperature range. This work has significantly enhanced mechanical properties, increasing the adaptability and reliability of bismuth telluride devices for various applications, and the multi-effect modulation of mechanical properties demonstrated in this study can be applied to other thermoelectric material systems.

Combined diffusion tensor imaging and quantitative susceptibility mapping to characterize normal-appearing white matter in self-limited epilepsy with centrotemporal spikes.

PURPOSE: In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. METHODS: 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. RESULTS: Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. CONCLUSION: Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features.

Hydrogel: a new material for intravesical drug delivery after bladder cancer surgery.

The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT). However, this procedure may miss small lesions or incompletely remove them, resulting in cancer recurrence or progression. As a result, intravesical instillation of chemotherapy or immunotherapy drugs is often used as an adjunctive treatment after TURBT to prevent cancer recurrence. In the traditional method, drugs are instilled into the patient's bladder through a urinary catheter under sterile conditions. However, this treatment exposes the bladder mucosa to the drug directly, leading to potential side effects like chemical cystitis. Furthermore, this treatment has several limitations, including a short drug retention period, susceptibility to urine dilution, low drug permeability, lack of targeted effect, and limited long-term clinical efficacy. Hydrogel, a polymer material with a high-water content, possesses solid elasticity and liquid fluidity, making it compatible with tissues and environmentally friendly. It exhibits great potential in various applications. One emerging use of hydrogels is in intravesical instillation. By employing hydrogels, drug dilution is minimized, and drug absorption, retention, and persistence in the bladder are enhanced due to the mucus-adhesive and flotation properties of hydrogel materials. Furthermore, hydrogels can improve drug permeability and offer targeting capabilities. This article critically examines the current applications and future prospects of hydrogels in the treatment of bladder cancer.

Ultra-small, low-cost, and simple-to-control PSP projector based on SLCD technology.

Demand for ultra-small, inexpensive, and high-accurate 3D shape measurement devices is growing rapidly, especially in the industrial and consumer electronics sectors. Phase shifting profilometry (PSP) is a powerful candidate due to its advantages of high accuracy, great resolution, and insensitivity to ambient light. As a key component in PSP, the projector used to generate the phase-shifting sinusoidal fringes must be ultra-small (several millimeters), low-cost, and simple to control. However, existing projection methods make it difficult to meet these requirements simultaneously. In this paper, we present a modern technique that can be used to fabricate the desired projector. A specifically designed device based on segmented liquid crystal display (SLCD) technology is used to display the projected patterns, and a cylindrical lens is used as the projection lens. The SLCD device can display four sets of specific filled binary patterns, each yielding a sinusoidal fringe, and all four sinusoidal fringes satisfy the four-step phase shift relation. 3D shape measurement experiments verify the performance of the projector. Considering that the size of SLCD devices can be reduced to a few millimeters, the proposed technique can be easily used to manufacture ultra-small, low-cost, and simple-to-control PSP projectors.

Biventricular intraventricular mechanical and electrical dyssynchrony in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. Methods: Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results: 77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer-specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan-Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. Conclusions: The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.

A bimetallic nanozyme coordinated with quercetin for efficient radical scavenging and treatment of acute kidney injury.

Acute kidney injury (AKI), characterized by tissue inflammation and oxidative damage, is a common and potentially life-threatening complication in patients. Quercetin, a natural antioxidant, possesses diverse pharmacological properties. However, limited stability and bioavailability hinder its clinical utilization. Moreover, the application of nanotechnology in antioxidant strategies for AKI treatment faces significant knowledge gaps. These gaps stem from limited understanding of the therapeutic mechanisms and renal clearance pathways. To tackle these issues, this study aims to develop an anti-oxidation nanozyme through the coordination of quercetin (Que) with a ruthenium (Ru) doped platinum (Pt) nanozyme (RuPt nanozyme). Compared to using Que or the RuPt nanozyme alone, the combined use of Que and the nanozyme led to enhanced antioxidant activities, especially in ABTS and DPPH free radical scavenging activities. Moreover, the modified nanozyme showed remarkable efficacy in scavenging reactive oxygen species and inhibiting apoptosis in a H2O2-induced cellular model. Additionally, the in vivo study showed that the coordination-modified nanozyme effectively alleviated glycerol- and cisplatin-induced AKI by inhibiting oxidative stress. Furthermore, this nanozyme exhibited superior therapeutic efficacy when compared to free quercetin and the RuPt nanozyme. In conclusion, the findings of our study suggest that the quercetin modified RuPt nanozyme (QCN) exhibits remarkable biocompatibility and holds significant promise for the therapeutic management of AKI.

Imaging characteristics and prognostic factors of Behcet's disease with arterial involvement: A long-term follow-up study.

PURPOSE: To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement. METHODS: In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors. RESULTS: Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1-15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality. CONCLUSIONS: Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement.

Inspired in Adversity: How Inspiration Mediates the Effects of Emotions on Coping Strategies.

Purpose: Inspiration is a psychological construct that has been relatively understudied in times of difficulty. This study aims to investigate the mediating effect of inspiration on the relationship between emotions and coping strategies in the context of adversity and to testify the effect in Chinese as well as the International societies. Participants and Methods: Using the snowball sampling method, two survey studies were conducted among 523 Chinese and 503 international participants during and soon after the local Covid-19 outbreak to testify how positive and negative emotions contributed to various coping strategies and whether the experience of inspiration mediated these relations. Structural equation modeling (SEM) was used to analyze the data. Results: Positive emotions had a higher impact on problem-solving and seeking social support coping strategies, whereas negative emotions had a higher impact on avoidance coping strategy. Both positive and negative emotions had positive relationships with inspiration, but positive emotions had a higher impact than negative ones. The indirect effects of emotions on problem-solving and social support coping strategies through inspiration were significantly positive, while the avoidance coping strategy was not influenced by the experience of inspiration. Conclusion: The results suggest that being inspired in both positive and negative emotions is positively related to approach coping strategies in adverse situations such as COVID-19, with the effect patterns slightly differing between Chinese participants and their Western counterparts. This study highlights the importance of inspiration experience as a motivational state that can help individuals bring newly acquired ideas into fruition, especially during times of difficulty. By understanding the role of inspiration in the context of adversity, public health systems can better assist individuals in different societies to cope with the challenges they face.

Clinical features and long-term survival in idiopathic pulmonary arterial hypertension with thyroid dysfunction: insights from a national multicentre prospective study.

Background: Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction. Methods: A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2-5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex. Results: In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment. Conclusion: IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.

A WRKY transcription factor, PyWRKY71, increased the activities of antioxidant enzymes and promoted the accumulation of cadmium in poplar.

Cadmium (Cd) pollution poses significant threats to the ecological environment and human health. Currently, phytoremediation is recognized as an environmentally friendly approach for mitigating Cd pollution, with increasing attention on the utilization of transgenic plants in Cd-contaminated soil remediation. In this study, we isolated and cloned PyWRKY71 from Populus yunnanensis and conducted a pot experiment to validate its enhanced functionality in conferring Cd tolerance to woody plants (poplar). During the experiment, the increase in plant height of the OE-87 line (overexpression poplar) was 1.46 times than that of the wild type (WT). Moreover, PyWRKY71 significantly promoted the accumulation of Cd in poplar, especially in the roots, where the Cd content in the OE-45 and OE-87 lines was 1.42 times than that in the WT. The chlorophyll content of transgenic poplar leaves was higher than that of the WT, reflecting a protective mechanism of PyWRKY71. Additionally, the activities of other antioxidants, including POD, SOD, CAT, and MDA, were elevated in transgenic poplars, bolstering their tolerance to Cd stress. In summary, PyWRKY71 exhibits substantial potential in regulating plant tolerance to Cd stress. This study not only provides a solid scientific foundation but also introduces a novel modified poplar variety for the remediation of Cd pollution.

Right heart thrombus in acute pulmonary embolism: A single center experience in China.

Right heart thrombus (RHT) is a rare but life-threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT-APE in Chinese patients. In this study, 17 RHT-APE and 329 non-RHT-APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow-up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT-APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non-RHT-APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate-high risk stratification, decreased right ventricular (RV) motion, NT-proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan-Meier analysis showed non-RHT had better prognosis than RHT patients (30-day survival: log-rank: p < 0.001; 90-day survival: log-rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30-day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30- and 90-day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT-proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT.

Changed cortical thickness and sulcal depth in pediatric acute lymphoblastic leukemia survivors treated with chemotherapy only.

The purpose of this study is to observe the changes of cortical morphological characteristics and their potential contribution to cognitive function in ALL survivors by using surface-based morphometry (SBM). Using SBM analysis, we calculated and compared group differences in cortical thickness, sulcal depth, gyrification, and fractal dimension of the cerebral cortex between 18 pediatric ALL survivors treated on chemotherapy-only protocols and off treatment within 2 years, and 18 healthy controls (HCs) with two-sample t-tests [P < 0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical characteristic values and cognitive function parameters were investigated with partial correlation analysis, taking age as a covariate. We found decreased cortical thickness mainly located in the prefrontal and temporal region, and increased sulcal depth in left rostral middle frontal cortex and left pars orbitalis in the ALL survivors compared to HCs. There were no statistically significant differences in the gyrification and fractal dimension between the two groups. In ALL survivors, cortical thickness and sulcal depth of above areas values revealed no significant correlation with the cognitive function parameters. In conclusion, pediatric ALL survivors show decreased cortical thickness in prefrontal and temporal regions, and increased sulcal depth in prefrontal region. These results suggest that SBM-based approach can be used to assess changes of cortical morphological characteristics in pediatric ALL survivors.

Quantitative susceptibility mapping shows lower brain iron content in children with childhood epilepsy with centrotemporal spikes.

PURPOSE: The dysregulation of brain iron homeostasis is closely relevant to a multitude of chronic neurological disorders. This study employed quantitative susceptibility mapping (QSM) to detect and compare whole-brain iron content between childhood epilepsy with centrotemporal spikes (CECTS) children and typically developing children. MATERIALS AND METHODS: 32 children with CECTS and 25 age- and gender-matched healthy children were enrolled. All participants were imaged with 3.0-T MRI to acquire the structural and susceptibility-weighted data. The susceptibility-weighted data were processed using STISuite toolbox to obtain QSM. The magnetic susceptibility difference between the two groups was compared using voxel-wise and region of interest methods. Multivariable linear regression, controlling for age, were employed to investigate the associations between the brain magnetic susceptibility and age at onset. RESULTS: Lower magnetic susceptibility was mainly observed in sensory- and motor-related brain regions in children with CECTS, including bilateral middle frontal gyrus, supplementary motor area, midcingulate cortex, paracentral lobule and precentral gyrus, the magnetic susceptibility of right paracentral lobule, right precuneus and left supplementary motor area were found to have positive correlation with the age at onset. CONCLUSIONS: This study suggests that the potential iron deficiency in certain brain regions is associated with CECTS, which might be helpful for further illumination of potential pathogenesis mechanism of CECTS.

Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.

Background: Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer. Methods: The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis. Results: After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust. Conclusions: PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.

Molecular risk factors for locoregional recurrence in resected non-small cell lung cancer.

BACKGROUND: Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non-small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. METHODS: A total of 118 patients who underwent tumor resection with mutation-detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. RESULTS: Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3-year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR-free survival as compared to patients with wild-type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. CONCLUSIONS: Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Cerebellar Metastasis Manifesting as a Cyst with Mural Nodule(s): Differentiating It From Hemangioblastoma on MRI.

BACKGROUND: A cyst with mural nodule(s) (CMN) is a rare imaging finding of cerebellar metastasis (CMET). It is a great challenge to differentiate it from cerebellar hemangioblastoma (CHB). In the present study, we explore the differences in the magnetic resonance imaging (MRI) characteristics of the 2 tumors. METHODS: Patients with pathologically confirmed CMET or CHB at our hospital from July 2009 to September 2021 were enrolled in the present study. All the patients underwent conventional head MRI (before and after contrast administration) before surgery and had ≥1 lesion in the cerebellum that presented as CMN on MRI. The clinical and MRI features were compared between the 2 groups. RESULTS: A total of 33 patients (10 with CMET and 23 with CHB) met the study criteria. The CMET patients were significantly older than were the CHB patients (median age, 59.5 years vs. 37 years; P = 0.002). Compared with the CHB group, the CMET group showed significantly higher occurrence rates of multiple mural nodules (72.7% vs. 8.7%), lack of vascular flow voids (100% vs. 65.2%), isointense or hypointense mural nodules on fluid-attenuated inversion recovery imaging (100.0% vs. 22.7%), restricted diffusion of mural nodules (22.2% vs. 0.0%), mildly enhanced mural nodules (90.9% vs. 4.3%), and a ring-enhanced pattern of the cyst wall (100% vs. 8.7%; P < 0.05 for all). CONCLUSIONS: When CMN is detected in the cerebellum on MRI, older age, multiple mural nodules, absence of vascular flow voids, isointense or hypointense mural nodule on fluid-attenuated inversion recovery sequence, restricted diffusion of the mural nodule, mildly enhanced mural nodules, and a ring-enhanced pattern of the cyst wall are the clinical and imaging features that strongly indicate the likelihood of metastasis, rather than CHB.

Tumor-Naïve Circulating Tumor DNA as an Early Response Biomarker for Patients Treated With Immunotherapy in Early Phase Clinical Trials.

PURPOSE: To evaluate early circulating tumor DNA (ctDNA) kinetics using a tumor-naïve assay and correlate it with clinical outcomes in early phase immunotherapy (IO) trials. METHODS: Plasma samples were analyzed using a 425-gene next-generation sequencing panel at baseline and before cycle 2 (3-4 weeks) in patients with advanced solid tumors treated with investigational IO agents. Variant allele frequency (VAF) for mutations in each gene, mean VAF (mVAF) from all mutations, and change in mVAF between both time points were calculated. Hyperprogression (HyperPD) was measured using Matos and Caramella criteria. RESULTS: A total of 162 plasma samples were collected from 81 patients with 27 different tumor types. Patients were treated in 37 different IO phase I/II trials, 72% of which involved a PD-1/PD-L1 inhibitor. ctDNA was detected in 122 plasma samples (75.3%). A decrease in mVAF from baseline to precycle 2 was observed in 24 patients (37.5%) and was associated with longer progression-free survival (hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.77; P < .01) and overall survival (HR, 0.54; 95% CI, 0.3 to 0.96; P = .03) compared with an increase. These differences were more marked if there was a >50% decrease in mVAF for both progression-free survival (HR, 0.29; 95% CI, 0.13 to 0.62; P < .001) and overall survival (HR, 0.23; 95% CI, 0.09 to 0.6; P = .001). No differences in mVAF changes were observed between the HyperPD and progressive disease patients. CONCLUSION: A decrease in ctDNA within 4 weeks of treatment was associated with treatment outcomes in patients in early phase IO trials. Tumor-naïve ctDNA assays may be useful for identifying early treatment benefits in phase I/II IO trials.