bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of bacterial community composition and co-occurrence network to straw and straw biochar incorporation
Authors: Du Mingcheng , Zhang Jianyun , Wang Guoqing , Liu Cuishan , Wang Zhenlong
Published: September 2022

Microbial decomposition plays a crucial role in the incorporation of straw and straw biochar (SSB) into soil. Lime concretion black soil (LCBS) is a typical low-medium crop yield soil, and it is also one of the main soil types for grain production in China. However, the link between SSB additions and soil bacterial communities in LCBS remains unclear. This study explored the effects of SSB incorporation on bacterial community composition, structure and co-occurrence network patterns at different soil depths and maize growth stages. The results showed that soil PH, soil organic matter and total nitrogen significantly affected the seasonality and stratification of the soil bacterial community. The composition and diversity of bacterial communities were significantly affected by growth period and treatment rather than soil depth. Specifically, the bacterial community diversity increased significantly with crop growth at 0–20 cm, decreased the relative abundance of Actinobacteria, and increased the relative abundance of Proteobacteria and Acidobacteria. SF (straw with fertilizer) and BF (straw biochar with fertilizer) treatments decreased bacterial community diversity. Co-occurrence networks are more complex in BF, S (straw), and SF treatments, and the number of edge network patterns is increased by 92.5, 40, and 60% at the maturity stage compared with F (fertilizer) treatment, respectively. Moreover, the positive effect of straw biochar on the bacterial network pattern increased with time, while the effect of straw weakened. Notably, we found that rare species inside keystone taxa (Gemmatimonadetes and Nitrospirae) play an indispensable role in maintaining bacterial network construction in LCBS. This study offers a comprehensive understanding of the response of soil bacterial communities to SSB addition in LCBS areas, and provides a reference for further improvement of LCBS productivity.
Prediction of protein-protein interaction sites in intrinsically disordered proteins
Authors: Chen Ranran , Li Xinlu , Yang Yaqing , Song Xixi , Wang Cheng , Qiao Dongdong
Published: September 2022

Intrinsically disordered proteins (IDPs) participate in many biological processes by interacting with other proteins, including the regulation of transcription, translation, and the cell cycle. With the increasing amount of disorder sequence data available, it is thus crucial to identify the IDP binding sites for functional annotation of these proteins. Over the decades, many computational approaches have been developed to predict protein-protein binding sites of IDP (IDP-PPIS) based on protein sequence information. Moreover, there are new IDP-PPIS predictors developed every year with the rapid development of artificial intelligence. It is thus necessary to provide an up-to-date overview of these methods in this field. In this paper, we collected 30 representative predictors published recently and summarized the databases, features and algorithms. We described the procedure how the features were generated based on public data and used for the prediction of IDP-PPIS, along with the methods to generate the feature representations. All the predictors were divided into three categories: scoring functions, machine learning-based prediction, and consensus approaches. For each category, we described the details of algorithms and their performances. Hopefully, our manuscript will not only provide a full picture of the status quo of IDP binding prediction, but also a guide for selecting different methods. More importantly, it will shed light on the inspirations for future development trends and principles.
Evaluation of cannabinoid type 2 receptor expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer’s disease
Authors: Kecheliev Vasil , Spinelli Francesco , Herde Adrienne , Haider Achi , Mu Linjing , Klohs Jan , Ametamey Simon M. , Ni Ruiqing
Published: September 2022

Neuroinflammation plays an important role in the pathophysiology of Alzheimer’s disease. The cannabinoid type 2 receptor (CB2R) is an emerging target for neuroinflammation and therapeutics of Alzheimer’s disease. Here, we aim to assess the alterations in brain CB2R levels and evaluate novel CB2R imaging tracers in the arcAß mouse model of Alzheimer’s disease amyloidosis. Immunohistochemical staining for amyloid-ß deposits (6E10), microgliosis (anti-Iba1 and anti-CD68 antibodies), astrocytes (GFAP) and the anti-CB2R antibody was performed on brain slices from 17-month-old arcAß mice. Autoradiography using the CB2R imaging probes [18F]RoSMA-18-d6, [11C]RSR-056, and [11C]RS-028 and mRNA analysis were performed in brain tissue from arcAß and non-transgenic littermate (NTL) mice at 6, 17, and 24 months of age. Specific increased CB2R immunofluorescence intensities on the increased number of GFAP-positive astrocytes and Iba1-positive microglia were detected in the hippocampus and cortex of 17-month-old arcAß mice compared to NTL mice. CB2R immunofluorescence was higher in glial cells inside 6E10-positive amyloid-ß deposits than peri-plaque glial cells, which showed low background immunofluorescence in the hippocampus and cortex of 17-month-old arcAß mice. Ex vivo autoradiography showed that the specific binding of [18F]RoSMA-18-d6 and [11C]RSR-056 was comparable in arcAß and NTL mice at 6, 17, and 24 months of age. The level of Cnr2 mRNA expression in the brain was not significantly different between arcAß and NTL mice at 6, 17, or 24 months of age. In conclusion, we demonstrated pronounced specific increases in microglial and astroglial CB2R expression levels in a mouse model of AD-related cerebral amyloidosis, emphasizing CB2R as a suitable target for imaging neuroinflammation.
Anatomically curated segmentation of human subcortical structures in high resolution magnetic resonance imaging: An open science approach
Authors: Rushmore R. Jarrett , Sunderland Kyle , Carrington Holly , Chen Justine , Halle Michael , Lasso Andras , Papadimitriou G. , Prunier N. , Rizzoni Elizabeth , Vessey Brynn , Wilson-Braun Peter , Rathi Yogesh , Kubicki Marek , Bouix Sylvain , Yeterian Edward , Makris Nikos
Published: September 2022

Magnetic resonance imaging (MRI)-based brain segmentation has recently been revolutionized by deep learning methods. These methods use large numbers of annotated segmentations to train algorithms that have the potential to perform brain segmentations reliably and quickly. However, training data for these algorithms are frequently obtained from automated brain segmentation systems, which may contain inaccurate neuroanatomy. Thus, the neuroimaging community would benefit from an open source database of high quality, neuroanatomically curated and manually edited MRI brain images, as well as the publicly available tools and detailed procedures for generating these curated data. Manual segmentation approaches are regarded as the gold standard for brain segmentation and parcellation. These approaches underpin the construction of neuroanatomically accurate human brain atlases. In addition, neuroanatomically precise definitions of MRI-based regions of interest (ROIs) derived from manual brain segmentation are essential for accuracy in structural connectivity studies and in surgical planning for procedures such as deep brain stimulation. However, manual segmentation procedures are time and labor intensive, and not practical in studies utilizing very large datasets, large cohorts, or multimodal imaging. Automated segmentation methods were developed to overcome these issues, and provide high data throughput, increased reliability, and multimodal imaging capability. These methods utilize manually labeled brain atlases to automatically parcellate the brain into different ROIs, but do not have the anatomical accuracy of skilled manual segmentation approaches. In the present study, we developed a custom software module for manual editing of brain structures in the freely available 3D Slicer software platform that employs principles and tools based on pioneering work from the Center for Morphometric Analysis (CMA) at Massachusetts General Hospital. We used these novel 3D Slicer segmentation tools and techniques in conjunction with well-established neuroanatomical definitions of subcortical brain structures to manually segment 50 high resolution T1w MRI brains from the Human Connectome Project (HCP) Young Adult database. The structural definitions used herein are associated with specific neuroanatomical ontologies to systematically interrelate histological and MRI-based morphometric definitions. The resulting brain datasets are publicly available and will provide the basis for a larger database of anatomically curated brains as an open science resource.
Effects of reinforcement during the intertrial interval on temporal discrimination: Location version with rats
Authors: Pérez-Calzada Mario , Zamora-Arevalo Oscar
Published: September 2022

Different studies on temporal control of behavior have focused on making modifications to experimental tasks by introducing disruptors to know how these manipulations modify temporal control. The aim of this study was to produce changes in temporal discrimination in a temporal bisection task by using a disruptor associated with motivation, which consisted in delivering reinforcement during the intertrial interval (RITI). Four Wistar rats and a pair of duration 2s−8s were used. There were two types of sessions: baseline generalization, where the disruptor was not applied, and RITI generalization, where the disruptive manipulation was applied. The analysis of results consisted of comparing psychophysical parameters, Signal Detection Theory indices, and latencies to start trials of baseline sessions and disruption sessions. The results showed a change in the point of subjective equality, a change in the psychophysical function, an increasing trend in the latencies to start trials on RITI disruption, and no change in the Signal Detection Theory indices. The results highlight the importance of incorporating motivational explanations to theories of temporal control in non-human organisms.
Training spiking neuronal networks to perform motor control using reinforcement and evolutionary learning
Authors: Haşegan Daniel , Deible Matt , Earl Christopher , D’Onofrio David , Hazan Hananel , Anwar Haroon , Neymotin Samuel A.
Published: September 2022

Artificial neural networks (ANNs) have been successfully trained to perform a wide range of sensory-motor behaviors. In contrast, the performance of spiking neuronal network (SNN) models trained to perform similar behaviors remains relatively suboptimal. In this work, we aimed to push the field of SNNs forward by exploring the potential of different learning mechanisms to achieve optimal performance. We trained SNNs to solve the CartPole reinforcement learning (RL) control problem using two learning mechanisms operating at different timescales: (1) spike-timing-dependent reinforcement learning (STDP-RL) and (2) evolutionary strategy (EVOL). Though the role of STDP-RL in biological systems is well established, several other mechanisms, though not fully understood, work in concert during learning in vivo. Recreating accurate models that capture the interaction of STDP-RL with these diverse learning mechanisms is extremely difficult. EVOL is an alternative method and has been successfully used in many studies to fit model neural responsiveness to electrophysiological recordings and, in some cases, for classification problems. One advantage of EVOL is that it may not need to capture all interacting components of synaptic plasticity and thus provides a better alternative to STDP-RL. Here, we compared the performance of each algorithm after training, which revealed EVOL as a powerful method for training SNNs to perform sensory-motor behaviors. Our modeling opens up new capabilities for SNNs in RL and could serve as a testbed for neurobiologists aiming to understand multi-timescale learning mechanisms and dynamics in neuronal circuits.
Value and limitations of sonography in kidney transplant recipients with special attention to the resistive index – An update
Authors: Stigler Julia , Tiefenthaler Martin
Published: September 2022

Kidney transplantation has become the standard treatment for end-stage renal disease. Even though the success rates are high, early and late post-transplant complications remain a major clinical problem due to the risk of graft failure. Therefore, it is of highest interest to early diagnose post-transplant complications. Ultrasound with color coded Duplex analysis plays a crucial role in imaging mechanical and vascular complications. In this article, we give an update of the visualizable complications in kidney transplant recipients and discuss the value of resistive index (RI) measurement with its limitations in allograft rejection.
VEGF to CITED2 ratio predicts the collateral circulation of acute ischemic stroke
Authors: Lu Minyi , Liu Yuben , Xian Zhiqiang , Yu Xiaoyao , Chen Jian , Tan Sheng , Zhang Peidong , Guo Yang
Published: September 2022

Objective

The research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells (PBMCs) in the collateral circulation of acute ischemic stroke (AIS).

Methods

In an observational study of patients with AIS, the western blot was applied to test the protein expression of VEGF and CITED2. Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.

Results

A total of 67 patients with AIS were included in the study. Binary logistic regression analysis indicated the VEGF/CITED2 (OR 165.79, 95%CI 7.25–3,791.54, P = 0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve of the VEGF/CITED2 was 0.861 (95%CI 0.761–0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.

Conclusion

In patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT05345366.
Head shaking does not alter vestibulo ocular reflex gain in vestibular migraine
Authors: Patel Priyani , Castro Patricia , Koohi Nehzat , Arshad Qadeer , Gargallo Lucia , Carmona Sergio , Kaski Diego
Published: September 2022

Vestibular Migraine (VM) is the most common cause of non-positional episodic vestibular symptoms. Patients with VM commonly report increased motion sensitivity, suggesting that vestibular responses to head movement may identify changes specific to VM patients. Here we explore whether the vestibulo-ocular reflex (VOR) gain alters in response to a clinical “headshake” maneuver in patients with VM. Thirty patients with VM in the inter-ictal phase, 16 patients with Benign Positional Paroxysmal Vertigo (BPPV) and 15 healthy controls were recruited. Patients responded to the question “Do you feel sick reading in the passenger seat of a car?” and completed a validated motion sickness questionnaire as a measure of motion sensitivity. Lateral canal vHIT testing was performed before and after headshaking; the change in VOR gain was calculated as the primary outcome. Baseline VOR gain was within normal limits across all participants. There was no significant change in VOR gain after headshaking in any group (p = 0.264). Patients were 4.3 times more likely to be in the VM group than in the BPPV group if they reported nausea when reading in the passenger seat of a car. We postulate that a headshake stimulus may be insufficient to disrupt cortical interactions and induce a change in VOR gain. Alternatively, changes in VOR gain may only be apparent in the acute phase of VM. Reading in the passenger seat of a car was considered uncomfortable in all VM patients suggesting that this specific question may be useful for the diagnosis of VM.
The functional connectivity of the basal ganglia subregions changed in mid-aged and young males with chronic prostatitis/chronic pelvic pain syndrome
Authors: Lan Xi , Niu Xuan , Bai Wei-Xian , Li Hai-Ning , Zhu Xin-Yi , Ma Wen-Jun , Li Jian-Long , Dun Wang-Huan , Zhang Ming , He Juan
Published: September 2022

Background

The Basal ganglia (BG) played a crucial role in the brain-level mechanisms of chronic pain disorders. However, the functional changes of BG in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still poorly understood. This study investigated the BG subregions’ resting-state functional connectivity (rs-FC) in CP/CPPS patients compared with healthy controls.

Methods

Twenty eight patients with CP/CPPS and 28 age- and education-matched healthy males underwent clinical measurements and 3T brain MR imaging, including T1-weighted structural images and resting-state functional imaging. The data were analyzed by the seeded-based rs-FC analysis. Then, a machine learning method was applied to assess the feasibility of detecting CP/CPPS patients through the changed rs-FC.

Results

Compared with healthy males, patients presented decreased rs-FC between the BG subregions and right middle cingulate cortex, and correlated with pain (r = 0.51, p-uncorrected = 0.005) and urinary symptoms (r = –0.4, p-uncorrected = 0.034). The left superior temporal gyrus and right supramarginal gyrus showed decreased rs-FC with the BG subregions as well. The area under the receiver operating characteristic curve of 0.943 (accuracy = 80%, F1-score = 80.6%) was achieved for the classification of CP/CPPS patients and healthy males with support vector machine (SVM) based on the changed rs-FC.

Conclusion

These findings provide evidence of altered BG subregions’ rs-FC in CP/CPPS, which may contribute to our understanding of the BG’s role in CP/CPPS.
The comparison of largemouth bass (Micropterus salmoides) fed trash fish and formula feeds: Growth, flesh quality and metabolomics
Authors: Xu Xiaoying , Yang Hang , Xu Zhen , Li Xiaoqin , Leng Xiangjun
Published: September 2022

This study compared the growth, flesh quality and metabolomics of largemouth bass (Micropterus salmoides) fed trash fish and formula feeds. Trash fish (TF), self-made feed (SF) and commercial feed (CF) were prepared with crude protein levels of 172.2 g/kg, 503.5 g/kg and 504.1 g/kg (666.2 g/kg, 547.3 g/kg and 535.1 g/kg based on dry matter), respectively. Then, the three diets were fed to largemouth bass with an initial body weight of 75.0 ± 0.1 g for 12 weeks. SF and CF groups presented significantly lower feed intake (FI), feed conversion ratio (FCR) and higher protein efficiency ratio (PER) than TF group based on dry matter basis without affecting the weight gain (P < 0.05). The yellowness (b*) in dorsal muscle, flesh heat-insoluble collagen and free flavor amino acids contents in SF group were significantly higher (P < 0.05), while drip loss were significantly lower (P < 0.05) than those of TF group. Compared to TF group, SF and CF groups showed significantly higher flesh polyunsaturated fatty acids (PUFAs), n-3 PUFAs and n-6 PUFAs contents, flesh hardness, shear force and muscle fiber density (P < 0.05), and lower flesh total free amino acids, essential amino acids, muscle fiber diameter, intestine villus height and muscular thickness (P < 0.05). The serum total protein, triglyceride and cholesterol levels in SF group were significantly lower than those in TF and CF groups (P < 0.05). In the muscle metabolomics, 177 differential metabolites were detected between SF and TF groups, which mainly enriched in pathways as biosynthesis of amino acid, histidine metabolism, glycine, serine and threonine metabolism, etc. Conclusively, feeding largemouth bass with formula feeds improved flesh fatty acid profile and flesh texture without negative effects on the growth, but the flesh free amino acids contents were lower than the fish fed trash fish.
Inverse association of serum carotenoid levels with prevalence of hypertension in the general adult population
Authors: Zhu Xu , Shi Mengshaw , Pang Hui , Cheang Iokfai , Zhu Qingqing , Guo Qixin , Gao Rongrong , Liao Shengen , Zhou Yanli , Zhang Haifeng , Li Xinli , Yao Wenming
Published: September 2022

Carotenoid levels are inversely associated with blood pressure (BP). This study focused on the effects of individual and combined serum carotenoids on BP and hypertension, which have not been established to date. Data from National Health and Nutrition Examination Survey (NHANES) 2001–2006 were analyzed in this cross-sectional study. Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were applied to explore the associations of six serum carotenoids (α-carotene, β-cryptoxanthin, lutein/zeaxanthin, trans-lycopene, trans-β-carotene, and cis-β-carotene), individually and in combination, with BP/hypertension. The linearity of correlations was further assessed using restricted cubic spline (RCS) regression. A total of 11,336 adults were included for analysis. Data from multivariate models showed that all six carotenoids were independently and negatively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP; all p < 0.05). Compared to the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.64 [0.52–0.77]), β-cryptoxanthin (OR = 0.74 [0.60–0.90]), trans-β-carotene (OR = 0.50 [0.40–0.61]), and cis-β-carotene (OR = 0.47 [0.35–0.64]) were significantly and inversely related to hypertension (all p < 0.05). Moreover, WQS analysis revealed that the combination of all six serum carotenoids was negatively associated with BP and hypertension (all P<0.001), among which trans-β-carotene was the most significant contributor to the protective effect against hypertension (weight, 59.50%). Dose-response analyses demonstrated a linear inverse association of all carotenoids with hypertension (p for non-linearity > 0.05). Our collective findings indicate that higher levels of all six mixed serum carotenoids are correlated with decreased prevalence of hypertension, among which β-carotene exerts the most significant effect, which may provide a basis and direction for further studies.
Global leaders malnutrition initiative-defined malnutrition affects long-term survival of different subgroups of patients with gastric cancer: A propensity score-matched analysis
Authors: Cai Wentao , Yang Hui , Zheng Jingwei , Huang Jianqiang , Ji Weiping , Lu Yangbin , Yang Xinxin , Zhang Weiteng , Shen Xian , Chen Xiaodong
Published: September 2022

As defined by the Global Leaders Malnutrition Initiative (GLIM), malnutrition is strongly associated with a lower quality of life and poor prognosis in gastric cancer patients. However, few studies have precisely explored the predictors of malnutrition, as defined by the GLIM, for overall survival (OS) after gastric cancer surgery in subgroups of patients stratified according to population characteristics. Our research aimed to analyze whether the predictors of malnutrition defined by the GLIM for postoperative OS in gastric cancer patients differ across subgroups. Patients who underwent radical gastric cancer surgery at our center between July 2014 and February 2019 were included in the study. Propensity score matching (PSM) was used to minimize bias. The study population was divided into malnourished and normal groups based on whether they were malnourished as defined by the GLIM. Univariate and multivariate analyses were performed to identify the risk factors affecting OS. The Kaplan–Meier curve and log-rank test were performed to determine the survival rate difference between subgroups. Overall, 1,007 patients were enrolled in the research. Multivariate analysis showed that malnutrition among the patients was 33.47%. Additionally, GLIM-defined malnutrition was an independent risk factor [hazard ratio (HR): 1.429, P = 0.001] for a shorter OS in gastric cancer patients. Furthermore, subgroup analysis showed that the GLIM was more appropriate for predicting OS in older aged patients (≥65 years), females, those with comorbidities (Charlson comorbidity index ≥ 2), and those with advanced gastric cancer (TNM stage = 3). GLIM-defined malnutrition affects the long-term survival of gastric cancer patients, especially older patients, females, patients with comorbidities, and patients with advanced gastric cancer.
Global landscape of 2-hydroxyisobutyrylation in human pancreatic cancer
Authors: Lu Yun , Li Xiangyu , Zhao Kai , Qiu Peng , Deng Zhengdong , Yao Wei , Wang Jianming
Published: September 2022

As a new type of post-translational modification (PTM), lysine 2-hydroxyisobutyrylation (Khib) was firstly identified in histones and functioned as a regulator of transactivation in mammals. However, the role of Khib proteins remains to be investigated. Here, we firstly identified 10,367 Khib sites on 2,325 modified proteins in seven patients with pancreatic cancer by applying liquid chromatography with tandem mass spectrometry (LC-MS/MS) qualitative proteomics techniques. Among them, 27 Khib-modified sites were identified in histones. Bioinformatics analysis revealed that the Khib-modified proteins were mainly distributed in the cytoplasm and enhanced in metabolic pathways, including glycolysis/gluconeogenesis, the tricarboxylic acid cycle (TCA cycle), and fatty acid degradation. In an overlapping comparison of lysine 2-hydroxyisobutyrylation, succinylation, and acetylation in humans, 105 proteins with 80 sites were modified by all three PTMs, suggesting there may be a complex network among the different modified proteins and sites. Furthermore, MG149, which was identified as a Tip60 inhibitor, significantly decreased the total Khib modification level in pancreatic cancer (PC) and strongly suppressed PC’s proliferation, migration, and invasion ability. Overall, our study is the first profiling of lysine 2-hydroxyisobutyrylome and provides a new database for better investigating Khib in PC.
Utility of dual-layer spectral-detector CT imaging for predicting pathological tumor stages and histologic grades of colorectal adenocarcinoma
Authors: Chen Weicui , Ye Yongsong , Zhang Daochun , Mao Liting , Guo Lei , Zhang Hanliang , Du Xiaohua , Deng Weiwei , Liu Bo , Liu Xian
Published: September 2022

Objectives

To assess the utility of Dual-layer spectral-detector CT (DLCT) in predicting the pT stage and histologic grade for colorectal adenocarcinoma (CRAC).

Methods

A total of 131 patients (mean 62.7 ± 12.9 years; 72 female, 59 male) with pathologically confirmed CRAC (35 pT1-2, 61 pT3, and 35 pT4; 32 high grade and 99 low grade), who received dual-phase DLCT were enrolled in this retrospective study. Normalized iodine concentration (NIC), slope of the spectral HU curve (λHU), and effective atomic number (Eff-Z) were measured for each lesion by two radiologists independently. Intraobserver reliability and interobserver agreement were assessed. The above values were compared between three pT-stage and two histologic-grade groups. The correlation between the pT stages and above values were assessed. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic efficacy.

Results

Intra-class correlation coefficients were ranged from 0.856 to 0.983 for all measurements. Eff-Z [7.21(0.09) vs 7.31 (0.10) vs 7.35 (0.19)], NICAP [0.11 (0.05) vs 0.15 (0.08) vs 0.15 (0.08)], NICVP [0.27 (0.06) vs 0.34 (0.11) vs 0.35 (0.12)], λHUAP [1.20 (0.45) vs 1.93 (1.18) vs 2.37 (0.91)], and λHUVP [2.07 (0.68) vs 2.35 (0.62) vs 3.09 (1.07)] were significantly different among pT stage groups (all P<0.001) and exhibited a positive correlation with pT stages (r= 0.503, 0.455, 0.394, 0.512, 0.376, respectively, all P<0.001). Eff-Z [7.37 (0.10) vs 7.28 (0.08)], NICAP[0.20 (0.10) vs 0.13 (0.08)], NICVP[0.35 (0.07) vs 0.31 (0.11)], and λHUAP [2.59 (1.11) vs 1.63 (0.75)] in the high-grade group were markedly higher than those in the low-grade group (all P<0.05). For discriminating the advanced- from early-stage CARC, the AUCs of Eff-Z, NICAP, NICVP, λHUAP, and λHUVP were 0.83, 0.80, 0.79, 0.86, and 0.68, respectively (all P<0.001). For discriminating the high- from low-grade CARC, the AUCs of Eff-Z, NICAP, NICVP, and λHUAP were 0.81, 0.81, 0.64, and 0.81, respectively (all P<0.05).

Conclusions

The quantitative parameters derived from DLCT may provide new markers for assessing pT stages and histologic differentiation in patients with CRAC.
Development and validation of a prognostic nomogram for bone metastasis from lung cancer: A large population-based study
Authors: Li Weihua , Guo Zixiang , Zou Zehui , Alswadeh Momen , Wang Heng , Liu Xuqiang , Li Xiaofeng
Published: September 2022

Background

Bone is one of the most common metastatic sites of advanced lung cancer, and the median survival time is significantly shorter than that of patients without metastasis. This study aimed to identify prognostic factors associated with survival and construct a practical nomogram to predict overall survival (OS) in lung cancer patients with bone metastasis (BM).

Methods

We extracted the patients with BM from lung cancer between 2011 and 2015 from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regressions were performed to identify independent prognostic factors for OS. The variables screened by multivariate Cox regression analysis were used to construct the prognostic nomogram. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability.

Results

A total of 7861 patients were included in this study and were randomly divided into training (n=5505) and validation (n=2356) cohorts using R software in a ratio of 7:3. Cox regression analysis showed that age, sex, race, grade, tumor size, histological type, T stage, N stage, surgery, brain metastasis, liver metastasis, chemotherapy and radiotherapy were independent prognostic factors for OS. The C-index was 0.723 (95% CI: 0.697-0.749) in the training cohorts and 0.738 (95% CI: 0.698-0.778) in the validation cohorts. The AUC of both the training cohorts and the validation cohorts at 3-month (0.842 vs 0.859), 6-month (0.793 vs 0.814), and 1-year (0.776 vs 0.788) showed good predictive performance, and the calibration curves also demonstrated the reliability and stability of the model.

Conclusions

The nomogram associated with the prognosis of BM from lung cancer was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.
The impact of merkel cell polyomavirus positivity on prognosis of merkel cell carcinoma: A systematic review and meta-analysis
Authors: Yang Aimin , Wijaya Wilson Adrian , Yang Lei , He Yinhai , Cen Ying , Chen Junjie
Published: September 2022

Introduction

There are numerous findings over the past decade have indicated that Merkel cell carcinoma (MCC) may have two pathways of pathogenesis: one related to ultraviolet irradiation and the other to the Merkel cell polyomavirus (MCPyV). However, the predictive and clinicopathological value of MCPyV positivity in MCC patients is still debatable. This article aims to examine the most recent data regarding this issue.

Methods

The thorough literature searches were conducted in the Medline Ovid, PubMed, Web of Science, the Cochrane CENTRAL Databases, and Embase Databases until December 31, 2021. The associations between overall survival (OS), Merkel cell carcinoma-specific survival (MSS), recurrence-free survival (RFS), progression-free survival (PFS), clinicopathologic features, and MCPyV positivity were examined in our meta-analysis.

Results

This meta-analysis included a total of 14 studies involving 1595 patients. Our findings demonstrated a significant correlation between MCPyV positivity and improved OS (HR=0.61, 95%CI:0.39-0.94, P=0.026) and improved PFS (HR=0.61, 95% CI: 0.45-0.83, P=0.002). MCPyV positivity did not, however, appear to be associated with either MSS (HR=0.61, 95%CI: 0.28-1.32, P=0.209) or RFS (HR= 0.93, 95%CI: 0.37-2.34, P=0.873). Pooled results revealed a correlation between MCPyV positivity with gender (male vs. female, OR=0.606, 95%CI: 0.449-0.817, P=0.001), histopathological stage (AJCC I-II vs. III-IV, OR=1.636, 95%CI: 1.126-2.378, P=0.010) and primary site (head and neck vs. other sites, OR=0.409, 95%CI: 0.221-0.757, P=0.004).

Conclusion

These results imply that MCPyV positivity may present a promising predictive biomarker for human MCC and call for further study.
Predicting IDH subtype of grade 4 astrocytoma and glioblastoma from tumor radiomic patterns extracted from multiparametric magnetic resonance images using a machine learning approach
Authors: Kandalgaonkar Pashmina , Sahu Arpita , Saju Ann Christy , Joshi Akanksha , Mahajan Abhishek , Thakur Meenakshi , Sahay Ayushi , Epari Sridhar , Sinha Shwetabh , Dasgupta Archya , Chatterjee Abhishek , Shetty Prakash , Moiyadi Aliasgar , Agarwal Jaiprakash , Gupta Tejpal , Goda Jayant S.
Published: September 2022

Background and purpose

Semantic imaging features have been used for molecular subclassification of high-grade gliomas. Radiomics-based prediction of molecular subgroups has the potential to strategize and individualize therapy. Using MRI texture features, we propose to distinguish between IDH wild type and IDH mutant type high grade gliomas.

Methods

Between 2013 and 2020, 100 patients were retrospectively analyzed for the radiomics study. Immunohistochemistry of the pathological specimen was used to initially identify patients for the IDH mutant/wild phenotype and was then confirmed by Sanger’s sequencing. Image texture analysis was performed on contrast-enhanced T1 (T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on MR image slices followed by single-slice multiple sampling image augmentation. Both whole tumor multislice segmentation and single-slice multiple sampling approaches were used to arrive at the best model. Radiomic features were extracted, which included first-order features, second-order (GLCM—Grey level co-occurrence matrix), and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression, followed by radiomic classification using Support Vector Machine (SVM) and a 10-fold cross-validation strategy for model development. The area under the Receiver Operator Characteristic (ROC) curve and predictive accuracy were used as diagnostic metrics to evaluate the model to classify IDH mutant and wild-type subgroups.

Results

Multislice analysis resulted in a better model compared to the single-slice multiple-sampling approach. A total of 164 MR-based texture features were extracted, out of which LASSO regression identified 14 distinctive GLCM features for the endpoint, which were used for further model development. The best model was achieved by using combined T1C and T2W MR images using a Quadratic Support Vector Machine Classifier and a 10-fold internal cross-validation approach, which demonstrated a predictive accuracy of 89% with an AUC of 0.89 for each IDH mutant and IDH wild subgroup.

Conclusion

A machine learning classifier of radiomic features extracted from multiparametric MRI images (T1C and T2w) provides important diagnostic information for the non-invasive prediction of the IDH mutant or wild-type phenotype of high-grade gliomas and may have potential use in either escalating or de-escalating adjuvant therapy for gliomas or for using targeted agents in the future.
Proteomics and phosphoproteomics of chordoma biopsies reveal alterations in multiple pathways and aberrant kinases activities
Authors: Hang Jing , Ouyang Hanqiang , Wei Feng , Zhong Qihang , Yuan Wanqiong , Jiang Liang , Liu Zhongjun
Published: September 2022

Background

Chordoma is a slow-growing but malignant subtype of bone sarcoma with relatively high recurrence rates and high resistance to chemotherapy. It is urgent to understand the underlying regulatory networks to determine more effective potential targets. Phosphorylative regulation is currently regarded as playing a significant role in tumorigenesis, and the use of tyrosine kinase inhibitors in clinical practice has yielded new promise for the treatment of a variety of sarcoma types.

Materials and methods

We performed comprehensive proteomic and phosphoproteomic analyses of chordoma using four-dimensional label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. The potential aberrantly expressed kinases and their functions were validated using western blotting and CCK-8 assays.

Results

Compared with paired normal muscle tissues, 1,139 differentially expressed proteins (DEPs) and 776 differentially phosphorylated proteins (DPPs) were identified in chordoma tumor tissues. The developmentally significant Wnt-signaling pathway and oxidative phosphorylation were aberrant in chordoma. Moreover, we predicted three kinases (AURA, CDK9, and MOK) with elevated activity by kinase-pathway network analysis (KiPNA) and verified their increased expression levels. The knockdown of these kinases markedly suppressed chordoma cell growth, and this was also the case for cells treated with the CDK9 inhibitor AZD4573. We additionally examined 208 proteins whose expression and phosphorylation levels were synergetically altered.

Conclusions

We herein depicted the collective protein profiles of chordomas, providing insight into chordomagenesis and the potential development of new therapeutic targets.
Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
Authors: Zhu Zeen , Wang Xueni , Zhang Wunai , Gong Mengyuan , Zhang Simei , Yang Bao , Qu Bolun , Wu Zheng , Ma Qingyong , Wang Zheng , Qian Weikun
Published: September 2022

Purpose

The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis.

Methods

CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits.

Results

The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH–GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin.

Conclusion

Huaier can activate ferroptosis by inducing autophagy in PCs.
Radiation-induced sarcomas: A single referral cancer center experience and literature review
Authors: Laurino Simona , Omer Ludmila Carmen , Albano Francesco , Marino Graziella , Bianculli Antonella , Solazzo Angela Pia , Sgambato Alessandro , Falco Geppino , Russi Sabino , Bochicchio Anna Maria
Published: September 2022

Background and objective

The oncogenic effect of ionizing radiation is widely known. Sarcomas developing after radiation therapy (RT), termed “iatrogenic disease of success”, represent a growing problem, since the advancements in cancer management and screening programs have increased the number of long-term cancer survivors. Although many patients have been treated with radiation therapy, only few data are available on radiation-induced sarcomas (RIS).

Methods

We examined the medical and radiological records of 186 patients with histologically proven soft tissue and bone sarcomas, which referred to IRCCS CROB Centro di Riferimento Oncologico della Basilicata from January 2009 to May 2022. Among them, seven patients received a histological diagnosis of secondary RIS, according to Cahan’s criteria. Clinicopathological features and treatment follow-up data of RIS patients were retrospectively analyzed.

Results

Among these secondary RIS, five arose in irradiated breast cancer (5/2,570, 0.19%) and two in irradiated head and neck cancer (2/1,986, 0.10%) patients, with a mean onset latency time of 7.3 years. The histology of RIS was one desmoid tumor, two angiosarcomas, one chondrosarcoma, two leiomyosarcomas, and one undifferentiated pleomorphic sarcoma. Out of the seven RIS, one received radiotherapy, one received electrochemotherapy (ECT), one received a second-line chemotherapy, three were subjected to three lines of chemotherapy, and one underwent radiofrequency ablation, chemotherapy, and ECT. Median survival time is 36 months. No significant survival differences were found stratifying patients for age at RT, latency time, and age at RIS diagnosis.

Conclusions

RIS represents a possible complication for long-survivor cancer patients. Therefore, adherence to a strict follow-up after the radiation treatment is recommended to allow early diagnosis and optimal management of RIS patients. After the planned follow-up period, considering the long-term risk to develop a RIS, a specific multispecialty survivorship care plan could be of benefit for patients.
The risk factors and early predictive model of hematotoxicity after CD19 chimeric antigen receptor T cell therapy
Authors: Wang Yang , Song Zhiqiang , Geng Yuke , Gao Lei , Xu Lili , Tang Gusheng , Ni Xiong , Chen Li , Chen Jie , Wang Tao , Fu Weijia , Feng Dongge , Yu Xuejun , Wang Libing , Yang Jianmin
Published: September 2022

Hematotoxicity is the most common long-term adverse event after chimeric antigen receptor T cell (CAR-T) therapy. Here, a total of 71 patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) or large B-cell lymphoma (LBCL) were used to develop an early hematotoxicity predictive model and verify the accuracy of this model. The incidences of early hematotoxicity at 3 month following CAR-T infusion in B-ALL and LBCL were 45.5% and 38.5%, respectively. Multivariate analyses revealed that the severity of cytokine release syndrome (CRS) was an independent risk factor affecting early hematotoxicity. The analysis between the peak cytokine levels and early hematotoxicity suggested that tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were closely associated with early hematotoxicity. Then, an early predictive model of hematotoxicity was constructed based on the peak contents of TNF-α and CRP. This model could diagnose early hematotoxicity with positive predictive values of 87.7% and 85.0% in training and validation cohorts, respectively. Lastly, we constructed the nomogram for clinical practice to predict the risk of early hematotoxicity, which performed well compared with the observed probability. This early predictive model is instrumental in the risk stratification of CAR-T recipients with hematotoxicity and early intervention for high-risk patients.
Visualizing the knowledge domains and research trends of childhood asthma: A scientometric analysis with CiteSpace
Authors: Wu Jinghua , Yu Yi , Yao Xinmeng , Zhang Qinzhun , Zhou Qin , Tang Weihong , Huang Xianglong , Ye Chengyin
Published: September 2022

Background

Asthma is one of the most common chronic diseases in children globally. In recent decades, advances have been made in understanding the mechanism, diagnosis, treatment and management for childhood asthma, but few studies have explored its knowledge structure and future interests comprehensively.

Objective

This scientometric study aims to understand the research status and emerging trends of childhood asthma.

Methods

CiteSpace (version 5.8.R3) was used to demonstrate national and institutional collaborations in childhood asthma, analyze research subjects and journal distribution, review research keywords and their clusters, as well as detect research bursts.

Results

A total of 14,340 publications related to childhood asthma were extracted from Web of Science (core database) during January 2011 to December 2021. The results showed that academic activities of childhood asthma had increased steadily in the last decade. Most of the research was conducted by developed countries while China, as a developing country, was also actively engaged in this field. In addition to subjects of allergy and immunology, both public health aspects and ecological environmental impacts on the disease were emphasized recently in this research field. Keywords clustering analysis indicated that research on asthma management and atopy was constantly updated and became the two major research focuses recently, as a significant shift in research hotspots from etiology and diagnosis to atopic march and asthma management was identified. Subgroup analysis for childhood asthma management and atopy suggested that caregiver- or physician-based education and interventions were emerging directions for asthma management, and that asthma should be carefully studied in the context of atopy, together with other allergic diseases.

Conclusions

This study presented a comprehensive and systematic overview of the research status of childhood asthma, provided clues to future research directions, and highlighted two significant research trends of asthma management and atopy in this field.