bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional homogeneity alterations in multifrequency bands in patients with basal ganglia stroke: A resting-state functional magnetic resonance imaging study
Authors: Li Qianqian , Hu Su , Mo Yingmin , Chen Hao , Meng Chaoguo , Zhan Linlin , Li Mengting , Quan Xuemei , Gao Yanyan , Cheng Lulu , Hao Zeqi , Jia Xize , Liang Zhijian
Published: August 2022

Objective

The aim of this study was to investigate the spontaneous regional neural activity abnormalities in patients with acute basal ganglia ischemic stroke (BGIS) using a multifrequency bands regional homogeneity (ReHo) method and to explore whether the alteration of ReHo values was associated with clinical characteristics.

Methods

In this study, 34 patients with acute BGIS and 44 healthy controls (HCs) were recruited. All participants were examined by resting-state functional magnetic resonance imaging (rs-fMRI). The ReHo method was used to detect the alterations of spontaneous neural activities in patients with acute BGIS. A two-samplet-test comparison was performed to compare the ReHo value between the two groups, and a Pearson correlation analysis was conducted to assess the relationship between the regional neural activity abnormalities and clinical characteristics.

Results

Compared with the HCs, the patients with acute BGIS showed increased ReHo in the left caudate and subregions such as the right caudate and left putamen in conventional frequency bands. In the slow-5 frequency band, patients with BGIS showed decreased ReHo in the left medial cingulum of BGIS compared to the HCs and other subregions such as bilateral caudate and left putamen. No brain regions with ReHo alterations were found in the slow-4 frequency band. Moreover, we found that the ReHo value of left caudate was positively correlated with the NIHSS score.

Conclusion

Our findings revealed the alterations of ReHo in patients with acute BGIS in a specific frequency band and provided a new insight into the pathogenesis mechanism of BGIS. This study demonstrated the frequency-specific characteristics of ReHo in patients with acute BGIS, which may have a positive effect on the future neuroimaging studies.
Identification of a cytokine profile in serum and cerebrospinal fluid of pediatric and adult spinal muscular atrophy patients and its modulation upon nusinersen treatment
Authors: Bonanno Silvia , Cavalcante Paola , Salvi Erika , Giagnorio Eleonora , Malacarne Claudia , Cattaneo Marco , Andreetta Francesca , Venerando Anna , Pensato Viviana , Gellera Cinzia , Zanin Riccardo , Arnoldi Maria Teresa , Dosi Claudia , Mantegazza Renato , Masson Riccardo , Maggi Lorenzo , Marcuzzo Stefania
Published: August 2022

Background and objectives

Multisystem involvement in spinal muscular atrophy (SMA) is gaining prominence since different therapeutic options are emerging, making the way for new SMA phenotypes and consequent challenges in clinical care. Defective immune organs have been found in preclinical models of SMA, suggesting an involvement of the immune system in the disease. However, the immune state in SMA patients has not been investigated so far. Here, we aimed to evaluate the innate and adaptive immunity pattern in SMA type 1 to type 3 patients, before and after nusinersen treatment.

Methods

Twenty one pediatric SMA type 1, 2, and 3 patients and 12 adult SMA type 2 and 3 patients were included in this single-center retrospective study. A Bio-Plex Pro-Human Cytokine 13-plex Immunoassay was used to measure cytokines in serum and cerebrospinal fluid (CSF) of the study cohort before and after 6 months of therapy with nusinersen.

Results

We detected a significant increase in IL-1β, IL-4, IL-6, IL-10, IFN-γ, IL-17A, IL-22, IL-23, IL-31, and IL-33, in serum of pediatric and adult SMA patients at baseline, compared to pediatric reference ranges and to adult healthy controls. Pediatric patients showed also a significant increase in TNF-α and IL-17F levels at baseline. IL-4, IFN-γ, Il-22, IL-23, and IL-33 decreased in serum of pediatric SMA patients after 6 months of therapy when compared to baseline. A significant decrease in IL-4, IL-6, INF-γ, and IL-17A was detected in serum of adult SMA patients after treatment. CSF of both pediatric and adult SMA patients displayed detectable levels of all cytokines with no significant differences after 6 months of treatment with nusinersen. Notably, a higher baseline expression of IL-23 in serum correlated with a worse motor function outcome after treatment in pediatric patients. Moreover, after 6 months of treatment, patients presenting a higher IL-10 concentration in serum showed a better Hammersmith Functional Motor Scale Expanded (HFMSE) score.

Discussion

Pediatric and adult SMA patients show an inflammatory signature in serum that is reduced upon SMN2 modulating treatment, and the presence of inflammatory mediators in CSF. Our findings enhance SMA knowledge with potential clinical and therapeutic implications.
Chromobox 7/8 serve as independent indicators for glioblastoma via promoting proliferation and invasion of glioma cells
Authors: Zheng Zong-Qing , Yuan Gui-Qiang , Kang Na-Ling , Nie Qian-Qian , Zhang Guo-Guo , Wang Zhong
Published: August 2022

Background

The chromobox family, a critical component of epigenetic regulators, participates in the tumorigenesis and progression of many malignancies. However, the roles of the CBX family members (CBXs) in glioblastoma (GBM) remain unclear.

Methods

The mRNA expression of CBXs was analyzed in tissues and cell lines by Oncomine and Cancer Cell Line Encyclopedia (CCLE). The differential expression of CBXs at the mRNA level was explored in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases with the “beeswarm” R package. The protein expression of CBXs in GBM was further examined on Human Protein Atlas (HPA). The correlations between CBXs and IDH mutation and between CBXs and GBM subtypes were investigated in the TCGA portal and CGGA database with the “survminer” R package. The alteration of CBXs and their prognostic value were further determined via the cBioPortal and CGGA database with the “survival” R package. The univariate and multivariate analyses were performed to screen out the independent prognostic roles of CBXs in the CGGA database. Cytoscape was used to visualize the functions and related pathways of CBXs in GBM. U251 and U87 glioma cells with gene intervention were used to validate the role of CBX7/8 in tumor proliferation and invasion. Proliferation/invasion-related markers were conducted by Western blot and immunostaining.

Results

CBXs presented significantly differential expressions in pan-cancers. CBX2/3/5/8 were upregulated, whereas CBX6/7 were downregulated at mRNA level in GBM of TCGA and CGGA databases. Similarly, high expression of CBX2/3/5 and low expression of CBX6/8 were further confirmed at the protein level in the HPA. CBX2/6/7 were positively correlated with IDH mutation and CBX1/2/4/5/8 were closely related to GBM subtypes. CBX7 and CBX8 presented the independent prognostic factors for GBM patient survival. GO and KEGG analyses indicated that CBXs were closely related to the histone H3-K36, PcG protein complex, ATPase, and Wnt pathway. The overexpression of CBX7 and underexpression of CBX8 significantly inhibited the proliferation and invasion of glioma cells in vivo and in vitro.

Conclusion

Our results suggested that CBX7 and CBX8 served as independent prognostic indicators that promoted the proliferation and invasion of glioma cells, providing a promising strategy for diagnosing and treating GBM.
Analysis of risk factors for the development of cognitive dysfunction in patients with cerebral small vessel disease and the construction of a predictive model
Authors: Zhang Le , Gao Fulin , Zhang Yamin , Hu Pengjuan , Yao Yuping , Zhang Qingzhen , He Yan , Shang Qianlan , Zhang Yi
Published: August 2022

Background

Cognitive dysfunction in cerebral small vessel disease (CSVD) is a common cause of vascular dementia. The purpose of this study was to find independent risk factors for the development of cognitive dysfunction in patients with CSVD and establish a risk prediction model, in order to provide a reference for clinical diagnosis and treatment of such patients.

Methods

In this study, clinical data of patients with CSVD admitted to the Department of Neurology in Gansu Provincial Hospital from December 2019 to December 2021 were collected, and 159 patients were finally included after strict screening according to the inclusion and exclusion criteria. There were 43 patients with normal function and 116 patients with cerebral small vessel disease cognitive impairment (CSVDCI). The logistic multivariable regression model was used to screen out the independent risk factors of cognitive dysfunction in patients with CSVD, and the nomogram of cognitive dysfunction in patients with CSVD was constructed based on the results of the logistic multivariable regression analysis. Finally, the accuracy of the prediction model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).

Results

The results of multivariable logistic regression analysis showed that hypertension (OR = 2.683, 95% CI 1.119–6.432, P = 0.027), homocysteine (Hcy) (OR = 1.083, 95% CI 1.026–1.143, P = 0.004), total CSVD MRI Score (OR = 1.593, 95% CI 1.025–2.475, P = 0.039) and years of schooling (OR = 0.883, 95% CI 0.798–0.978, P = 0.017) were independent risk factors for the development of cognitive dysfunction in patients with CSVD. The C-index of this prediction model was 0.806 (95% CI 0.735–0.877), and the calibration curve, ROC curve, and DCA curve all showed good predictive power in the nomogram.

Conclusions

The nomogram constructed in this study has high accuracy and clinical utility in predicting the occurrence of cognitive dysfunction in patients with CSVD. For patients with CSVD with the above risk factors, active clinical intervention and prevention are required during clinical consultation and disease management to avoid cognitive impairment as much as possible.
Relationship between circadian syndrome and stroke: A cross-sectional study of the national health and nutrition examination survey
Authors: Wang Yuling , Yang Ling , Zhang Yan , Liu Junyan
Published: August 2022

Aim

The aim of this study was to assess the relationship of circadian syndrome and stroke.

Methods

We performed a cross-sectional analysis of 11,855 participants from the National Health and Nutrition Examination Survey (NHANES) database between 2005 and 2018, and collected the baseline characteristics. Multivariate logistic regression models were developed to explore the association between circadian syndrome and stroke. Simultaneously, subgroup analyses based on the difference of gender, race, and components associated with circadian syndrome also were performed. The odds ratio (OR) and 95% CI were calculated in this study.

Results

All the participants were divided into the non-stroke group and the stroke group. There were approximately 3.48% patients exclusively with stroke and 19.03% patients exclusively with circadian syndrome in our study. The results suggested that the risk of stroke in patients with circadian syndrome was higher than that in patients without circadian syndrome (OR = 1.322, 95 CI%: 1.020–1.713). Similar associations were found in women with circadian syndrome (OR = 1.515, 95 CI%: 1.086–2.114), non-Hispanic whites with circadian syndrome (OR = 1.544, 95 CI%: 1.124–2.122), participants with circadian syndrome who had elevated waist circumference (OR = 1.395, 95 CI%: 1.070–1.819) or short sleep (OR = 1.763, 95 CI%: 1.033–3.009).

Conclusion

Circadian syndrome was associated with the risk of stroke. Particularly, we should pay more close attention to the risk of stroke in those populations who were female, non-Hispanic whites, had the symptoms of elevated waist circumference or short sleep.
Hyper and hypo attention networks activations affect social development in children with autism spectrum disorder
Authors: Sabag Maya , Geva Ronny
Published: August 2022

Children with autism spectrum disorder (ASD) experience a range of social and non-social attention deficits. To date, most studies assessed the neurological framework or discrete behavioral traits related to one attention network, leaving a gap in the understanding of the developmental cascade affecting the inter-relations among attention networks in ASD in a pervasive manner. We propose a theoretical framework that integrates the behavioral deficits and neurological manifestations through a cohesive developmental prism of attention networks’ activations while assessing their impact on social deficits in children with ASD. Insights arising from the model suggest hyper-and-hypoactivation of posterior attention networks leads to an altered prefrontal anterior attention network weight in ways that conjointly impact social performance in ASD. This perspective on how attention networks develop and interact in ASD may inform future research directions regarding ASD and attention development.
Prediction model for suicide based on back propagation neural network and multilayer perceptron
Authors: Lyu Juncheng , Shi Hong , Zhang Jie , Norvilitis Jill
Published: August 2022

Introduction

The aim was to explore the neural network prediction model for suicide based on back propagation (BP) and multilayer perceptron, in order to establish the popular, non-invasive, brief and more precise prediction model of suicide.

Materials and method

Data were collected by psychological autopsy (PA) in 16 rural counties from three provinces in China. The questionnaire was designed to investigate factors for suicide. Univariate statistical methods were used to preliminary filter factors, and BP neural network and multilayer perceptron were employed to establish the prediction model of suicide.

Results

The overall percentage correct of samples was 80.9% in logistic regression model. The total coincidence rate for all samples was 82.9% and the area under ROC curve was about 82.0% in the Back Propagation Neural Network (BPNN) prediction model. The AUC of the optimal multilayer perceptron prediction model was above 90% in multilayer perceptron model. The discrimination efficiency of the multilayer perceptron model was superior to BPNN model.

Conclusions

The neural network prediction models have greater accuracy than traditional methods. The multilayer perceptron is the best prediction model of suicide. The neural network prediction model has significance for clinical diagnosis and developing an artificial intelligence (AI) auxiliary clinical system.
Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study
Authors: Chen Chen , Lou Min-Min , Sun Yi-Min , Luo Fang , Liu Feng-Tao , Luo Su-Shan , Wang Wen-Yuan , Wang Jian
Published: August 2022

Introduction

Phospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson’s disease (namely, PARK14). Compared to idiopathic Parkinson’s disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14.

Design

This case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson’s disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation.

Methods

The diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson’s disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants’ serum using UHPLC-QTOF/MS analysis, a well-established technology.

Results

We quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients’ serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models.

Conclusion

The significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation.
Behavioral state-dependent oscillatory activity in prefrontal cortex induced by chronic social defeat stress
Authors: Liu Tiaotiao , Qi Chengxi , Bai Wenwen , Tian Xin , Zheng Xuyuan
Published: August 2022

Chronic stress contributes to the onset and exacerbation of major depressive disorder (MDD) through the oscillatory activity in the prefrontal cortex (PFC). However, the oscillations on which chronic social stress converges to yield the behavioral state of social avoidance are largely unknown. Here, we use a chronic social defeat stress model and in vivo electrophysiological recordings to uncover a novel neurophysiological measure that predicts the social behavioral state in stressed animals. First, in this study, we find that chronic social defeat stress model induces depression-like behaviors (anhedonia and social avoidance). Second, we find statistically significant differences in PFC oscillatory activity across different frequency ranges in social behavioral state, and the oscillatory activity correlates with stress-induced behavioral state. Finally, we show that the social behavioral states are accurately decoded from the oscillatory activity based on machine learning. Together, these results demonstrate that naturally occurring differences in PFC oscillation underlie the social behavioral state that accompanies the emergence of stress-induced behavioral dysfunction.
CT perfusion-based delta-radiomics models to identify collateral vessel formation after revascularization in patients with moyamoya disease
Authors: Li Jizhen , Zhang Yan , Yin Di , Shang Hui , Li Kejian , Jiao Tianyu , Fang Caiyun , Cui Yi , Liu Ming , Pan Jun , Zeng Qingshi
Published: August 2022

Purpose

To build CT perfusion (CTP)-based delta-radiomics models to identify collateral vessel formation after revascularization in patients with moyamoya disease (MMD).

Methods

Fifty-three MMD patients who underwent CTP and digital subtraction angiography (DSA) examination were retrospectively enrolled. Patients were divided into good and poor groups based on postoperative DSA. CTP parameters, such as mean transit time (MTT), time to drain (TTD), time to maximal plasma concentration (Tmax), and flow extraction product (FE), were obtained. CTP efficacy in evaluating surgical treatment were compared between the good and poor groups. The changes in the relative CTP parameters (ΔrMTT, ΔrTTD, ΔrTmax, and ΔrFE) were calculated to evaluate the differences between pre- and postoperative CTP values. CTP parameters were selected to build delta-radiomics models for identifying collateral vessel formation. The identification performance of machine learning classifiers was assessed using area under the receiver operating characteristic curve (AUC).

Results

Of the 53 patients, 36 (67.9%) and 17 (32.1%) were divided into the good and poor groups, respectively. The postoperative changes of ΔrMTT, ΔrTTD, ΔrTmax, and ΔrFE in the good group were significantly better than the poor group (p < 0.05). Among all CTP parameters in the perfusion improvement evaluation, the ΔrTTD had the largest AUC (0.873). Eleven features were selected from the TTD parameter to build the delta-radiomics model. The classifiers of the support vector machine and k-nearest neighbors showed good diagnostic performance with AUC values of 0.933 and 0.867, respectively.

Conclusion

The TTD-based delta-radiomics model has the potential to identify collateral vessel formation after the operation.
Alterations in local activity and functional connectivity in patients with postherpetic neuralgia after short-term spinal cord stimulation
Authors: Fan Xiaochong , Ren Huan , Bu Chunxiao , Lu Zhongyuan , Wei Yarui , Xu Fuxing , Fu Lijun , Ma Letian , Kong Cunlong , Wang Tao , Zhang Yong , Liu Qingying , Huang Wenqi , Bu Huilian , Yuan Jingjing
Published: August 2022

Introduction

The efficacy of short-term spinal cord stimulation (stSCS) as a treatment for neuropathic pain in patients with postherpetic neuralgia (PHN) has already been validated. However, the potential alterations in brain functionality that are induced by such treatment have yet to be completely elucidated.

Methods

This study use resting-state functional magnetic resonance imaging (rs-fMRI) to detect the changes in regional homogeneity (ReHo) and degree centrality (DC) related to stimulator-induced pain relief in patients with PHN. A total of 10 patients with PHN underwent an MRI protocol at baseline and after stSCS. Alterations in ReHo and DC were then compared between baseline and after stSCS. We investigated the relationship between clinical parameters and functional changes in the brain.

Results

Clinical parameters on pain, emotion, and sleep quality were correlated with ReHo and DC. ReHo and DC were significantly altered in the middle temporal gyrus, precuneus, superior frontal gyrus, supramarginal gyrus, inferior parietal lobule, rolandic operculum, middle occipital gyrus, superior parietal gyrus, and the precentral gyrus after stSCS. A significant correlation was detected between ReHo changes in the middle occipital gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. A significant negative correlation was detected between DC changes in the middle temporal gyrus, rolandic operculum, supramarginal gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality.

Conclusion

This study found that stSCS is able to induce ReHo and DC changes in patients with PHN, thus suggesting that stSCS can change brain function to alleviate pain, sleep, and emotional disorder.
Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice
Authors: Cheng Hao , Wang Ning , Ma Xingyu , Wang Pengfei , Dong Wenwen , Chen Ziyuan , Wu Mingzhe , Wang Ziwei , Wang Linlin , Guan Dawei , Zhao Rui
Published: August 2022

Excessive iron released by hemoglobin and necrotic tissues is the predominant factor that aggravates the outcome of traumatic brain injury (TBI). Regulating the levels of iron and its metabolism is a feasible way to alleviate damage due to TBI. However, the spatial-temporal iron metabolism and iron deposition in neurons and glial cells after TBI remains unclear. In our study, male C57BL/6 mice (8–12 weeks old, weighing 20–26 g) were conducted using controlled cortical impact (CCI) models, combined with treatment of iron chelator deferoxamine (DFO), followed by systematical evaluation on iron deposition, cell-specific expression of iron metabolic proteins and ferroptosis in ipsilateral cortex. Herein, ferroptosis manifest by iron overload and lipid peroxidation was noticed in ipsilateral cortex. Furthermore, iron deposition and cell-specific expression of iron metabolic proteins were observed in the ipsilateral cortical neurons at 1–3 days post-injury. However, iron overload was absent in astrocytes, even though they had intense TBI-induced oxidative stress. In addition, iron accumulation in oligodendrocytes was only observed at 7–14 days post-injury, which was in accordance with the corresponding interval of cellular repair. Microglia play significant roles in iron engulfment and metabolism after TBI, and excessive affects the transformation of M1 and M2 subtypes and activation of microglial cells. Our study revealed that TBI led to ferroptosis in ipsilateral cortex, iron deposition and metabolism exhibited cell-type-specific spatial-temporal changes in neurons and glial cells after TBI. The different effects and dynamic changes in iron deposition and iron metabolism in neurons and glial cells are conducive to providing new insights into the iron-metabolic mechanism and strategies for improving the treatment of TBI.
Snack timing affects tissue clock and metabolic responses in male mice
Authors: Begemann Kimberly , Oster Henrik
Published: August 2022

Snacking of small quantities of palatable food items throughout the day is common in modern societies and is promoted by 24/7 lifestyles. Long-term mistimed high-caloric food intake disrupts endogenous circadian rhythms and supports the development of obesity and other metabolic disorders. However, less is known about the time-of-day dependent effects of snacking. We hypothesized that already a single snacking episode may affect the circadian regulation of metabolic parameters, in particular when the snack is consumed during the daily rest phase. We performed an acute snack experiment in mice by providing access to chow or chocolate either at day- or nighttime and assessed snack effects on core body temperature, locomotor activity, and gene expression in metabolic tissues. Our results show that daytime chocolate snacking leads to a higher body temperature and locomotor activity increase compared to chow and nighttime intake. This goes along with altered clock and metabolic gene expression in peripheral tissues. Changes in nutrient uptake transporter gene expression in the small intestine suggest increased glucose resorption after daytime snacking. Our results indicate an early mechanism for the adipogenic effect of mistimed high-calorie snacking.
Global adoption of single-shot targeted intraoperative radiotherapy (TARGIT-IORT) for breast cancer—better for patients, better for healthcare systems
Authors: Vaidya Jayant Sharad , Vaidya Uma Jayant , Baum Michael , Bulsara Max Kishor , Joseph David , Tobias Jeffrey S.
Published: August 2022

Micro abstract

Targeted intraoperative radiotherapy (TARGIT-IORT) is delivered immediately after lumpectomy for breast cancer. We estimated its impact. At least 44,752 patients with breast cancer were treated with TARGIT-IORT in 260 centres in 35 countries, saving >20 million miles of travel and preventing ~2,000 non–breast cancer deaths. The TARGIT-IORT website (https://targit.org.uk/travel) provides maps and tools to find the nearest centre offering TARGIT-IORT and travel savings.

Background

Targeted intraoperative radiotherapy (TARGIT-IORT) delivers radiotherapy targeted to the fresh tumour bed exposed immediately after lumpectomy for breast cancer. TARGIT-A trial found TARGIT-IORT to be as effective as whole-breast radiotherapy, with significantly fewer deaths from non–breast cancer causes. This paper documents its worldwide impact and provides interactive tools for clinicians and patients.

Method

Centres using TARGIT-IORT provided the date of the first case and the total number of patients. We plotted these data on a customised Google Map. An interactive web-based tool provided directions to the closest centre. Using the data from the TARGIT-A trial, we estimated the total savings in travel miles, carbon footprint, and the number of non–breast cancer deaths that might be prevented.

Results

Data from 242 (93%) of the 260 centres treating patients from 35 countries were available. From the first patient treated in 1998 to early 2020, at least 44,752 women with breast cancer have been treated with TARGIT-IORT. The TARGIT-IORT website (https://targit.org.uk/travel) displays the Google Map of centres with number of cases and an interactive tool for patients to find the nearest centre offering TARGIT-IORT and their travel savings. Scaling up to the already treated patients, >20 million miles of travel would have been saved and about 2,000 deaths prevented.

Conclusion

One can ascertain the number of patients treated with a novel treatment. These data show how widely TARGIT-IORT has now been adopted and gives an indication of its beneficial worldwide impact on a large number of women with breast cancer.
Real-time fully automated dosimetric computation for CT images in the clinical workflow: A feasibility study
Authors: Porzio Massimiliano , Anam Choirul
Published: August 2022

Background

Currently, the volume computed tomography dose index (CTDIvol), the most-used quantity to express the output dose of a computed tomography (CT) patient’s dose, is not related to the real size and attenuation properties of each patient. The size-specific dose estimates (SSDE), based on the water-equivalent diameter (DW) overcome those issues. The proposed methods found in the literature do not allow real-time computation of DW and SSDE.

Purpose

This study aims to develop a software to compute DW and SSDE in a real-time clinical workflow.

Method

In total, 430 CT studies and scans of a water-filled funnel phantom were used to compute accuracy and evaluate the times required to compute the DW and SSDE. Two one-sided tests (TOST) equivalence test, Bland–Altman analysis, and bootstrap-based confidence interval estimations were used to evaluate the differences between actual diameter and DW computed automatically and between DW computed automatically and manually.

Results

The mean difference between the DW computed automatically and the actual water diameter for each slice is −0.027% with a TOST confidence interval equal to [−0.087%, 0.033%]. Bland–Altman bias is −0.009% [−0.016%, −0.001%] with lower limits of agreement (LoA) equal to −0.0010 [−0.094%, −0.068%] and upper LoA equal to 0.064% [0.051%, 0.077%]. The mean difference between DW computed automatically and manually is −0.014% with a TOST confidence interval equal to [−0.056%, 0.028%] on phantom and 0.41% with a TOST confidence interval equal to [0.358%, 0.462%] on real patients. The mean time to process a single image is 13.99 ms [13.69 ms, 14.30 ms], and the mean time to process an entire study is 11.5 s [10.62 s, 12.63 s].

Conclusion

The system shows that it is possible to have highly accurate DW and SSDE in almost real-time without affecting the clinical workflow of CT examinations.
Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
Authors: Chen Ting , Zhang Siwen , Zhou Dongmei , Lu Peipei , Mo Xianglai , Tamrakar Rashi , Yang Xi
Published: August 2022

Background

Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, its carcinogenic mechanism is still unclear, looking for both diseases’ transcriptome levels, the same changes as we are looking for NAFLD may provide a potential mechanism of action of HCC. Thus, our study aimed to discover the coexisting pathogenic genes of NAFLD and HCC.

Methods

We performed a variance analysis with public data for both diseases. At the same time, weighted gene correlation network analysis (WGCNA) was used to find highly correlated gene modules in both diseases. The darkturquoise gene module was found to be highly correlated with both diseases. Based on the diagnosis related module genes and the differential genes of the two diseases, we constructed diagnostic and prognostic models by logistic regression, univariate Cox regression, and LASSO regression. Public datasets verified the results. Meanwhile, we built a competing endogenous RNA (ceRNA) network based on the model genes and explored the related pathways and immune correlation involved in the two diseases by using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Immunohistochemistry was used to verify the different expression of ABCC5 and TUBG1 among the normal liver, NAFLD, and HCC tissues. Sodium palmitate/sodium oleate was used to establish high-fat cell models, and Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify the messenger RNA (mRNA) expression of ABCC5 in lipidization cells.

Results

A total of 26 upregulated genes and 87 downregulated genes were found using limma package identification analysis. According to WGCNA, the darkturquoise gene module was highly correlated with the prognosis of both diseases. The coexisting genes acquired by the two groups were only three central genes, that is, ABCC5, DHODH and TUBG1. The results indicated that the diagnostic and prognostic models constructed by ABCC5 and TUBG1 genes had high accuracy in both diseases. The results of immunohistochemistry showed that ABCC5 and TUBG1 were significantly overexpressed in NAFLD and HCC tissues compared with normal liver tissues. The Oil Red O staining and triglyceride identified the successful construction of HepG2 and LO2 high-fat models using PA/OA. The results of RT-qPCR showed that the lipidization of LO2 and HepG2 increased the mRNA expression of ABCC5.

Conclusions

The gene model constructed by ABCC5 and TUBG1 has high sensibility and veracity in the diagnosis of NAFLD as well as the diagnosis and prognosis of HCC. ABCC5 and TUBG1 may play an important role in the development of NAFLD to HCC. In addition, lipidization could upregulate the mRNA expression of ABCC5 in HCC.
Clinical study of total bone marrow combined with total lymphatic irradiation pretreatment based on tomotherapy in hematopoietic stem cell transplantation of acute leukemia
Authors: Kong Fanyang , Liu Shuaipeng , Liu Lele , Pi Yifei , Pei Yuntong , Xu Dandan , Jia Fei , Han Bin , Guo Yuexin
Published: August 2022

Objective

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treatment of refractory and relapsed acute leukemia, and the preconditioning methods before transplantationis one of the important factors affecting the survival of patients. Radiotherapy combined with chemotherapy is the most commonly used preconditioning method before transplantation. This study evaluated the safety and efficacy of total bone marrow combined with total lymphatic irradiation as a preconditioning method before hematopoietic stem cell transplantation.

Methods

Seventeen patients with acute leukemia who were admitted to our center from 2016 to 2020 were selected. The median age was 17 years (8-35). The target area for TMLI includes the total bone marrow and total lymphatic space, and the organs at risk include the lens, lungs, kidneys, intestine, heart, and liver. The patients received a total bone marrow and lymphatic irradiation preconditioning regimen, the related acute adverse reactions were graded, and the prognosis of the patients after transplantation was observed.

Results

During patient preconditioning, only grade 1-2 toxicity was observed, and grade 3-4 toxicity did not occur. Except for one patient whose platelets were not engrafted, all the other patients were successfully transplanted. The median time of neutrophil implantation was 14 d (9-15 d), and the median time of platelet implantation was 14 d (13-21 d). With a median follow-up of 9 months (2-48), 4 relapses occurred, 3 died, and 10 leukemia patients survived and were disease-free. One-year overall survival was 69.8%, cumulative recurrence was 19.5%, disease-free-survival was 54.2%.

Conclusion

The Allo-HSCT pretreatment regimen of total bone marrow combined with total lymphatic irradiation is safe and effective in the treatment of malignant hematological diseases. Total bone marrow combined with total lymphatic irradiation may completely replace total body irradiation, and the clinically observed incidence of acute toxicity is not high.
Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
Authors: Li Yan , Xu Ziyi , Xie Tongji , Xing Puyuan , Ying Jianming , Li Junling
Published: August 2022

EGFR mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to EGFR-TKIs. However, resistance to EGFR-TKIs is inevitable in the majority of EGFR-mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still under investigation. Owing to the selective pressure, intratumoral heterogeneity may exist after resistance, especially in patients after multiple lines of treatment. For those patients, it is important to choose therapies focused on the trunk/major clone of the tumor in order to achieve optimal clinical benefit. Here, we will report an EGFR-mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including EGFR amplification, large fragment deletion of RB1, and histological transformations after targeted treatments. In our case, EGFR amplification seemed to be the major clone of the resistant mechanism according to the next-generation sequencing (NGS) results of both liquid biopsy monitoring and tissue biopsies. In consideration of the high EGFR amplification level, the patient was administered by combination treatment with EGFR-TKI plus nimotuzumab, an anti-EGFR monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our case sheds light on the treatment of EGFR-mutant patients with EGFR amplification and indicates that a combination of EGFR-TKI with anti-EGFR mAb might be one of the possible treatment options based on genetic tests. Moreover, the decision on therapeutic approaches should focus on the major clone of the tumor and should make timely adjustments according to the dynamic changes of genetic characteristics during treatment.
Non-coding RNA in rhabdomyosarcoma progression and metastasis
Authors: Ramadan Farah , Saab Raya , Hussein Nader , Clézardin Philippe , Cohen Pascale A. , Ghayad Sandra E.
Published: August 2022

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma of skeletal muscle differentiation, with a predominant occurrence in children and adolescents. One of the major challenges facing treatment success is the presence of metastatic disease at the time of diagnosis, commonly associated with the more aggressive fusion-positive subtype. Non-coding RNA (ncRNA) can regulate gene transcription and translation, and their dysregulation has been associated with cancer development and progression. MicroRNA (miRNA) are short non-coding nucleic acid sequences involved in the regulation of gene expression that act by targeting messenger RNA (mRNA), and their aberrant expression has been associated with both RMS initiation and progression. Other ncRNA including long non-coding RNA (lncRNA), circular RNA (circRNA) and ribosomal RNA (rRNA) have also been associated with RMS revealing important mechanistic roles in RMS biology, but these studies are still limited and require further investigation. In this review, we discuss the established roles of ncRNA in RMS differentiation, growth and progression, highlighting their potential use in RMS prognosis, as therapeutic agents or as targets of treatment.
Deep learning-based automatic segmentation for size and volumetric measurement of breast cancer on magnetic resonance imaging
Authors: Yue Wenyi , Zhang Hongtao , Zhou Juan , Li Guang , Tang Zhe , Sun Zeyu , Cai Jianming , Tian Ning , Gao Shen , Dong Jinghui , Liu Yuan , Bai Xu , Sheng Fugeng
Published: August 2022

Purpose

In clinical work, accurately measuring the volume and the size of breast cancer is significant to develop a treatment plan. However, it is time-consuming, and inter- and intra-observer variations among radiologists exist. The purpose of this study was to assess the performance of a Res-UNet convolutional neural network based on automatic segmentation for size and volumetric measurement of mass enhancement breast cancer on magnetic resonance imaging (MRI).

Materials and methods

A total of 1,000 female breast cancer patients who underwent preoperative 1.5-T dynamic contrast-enhanced MRI prior to treatment were selected from January 2015 to October 2021 and randomly divided into a training cohort (n = 800) and a testing cohort (n = 200). Compared with the masks named ground truth delineated manually by radiologists, the model performance on segmentation was evaluated with dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). The performance of tumor (T) stage classification was evaluated with accuracy, sensitivity, and specificity.

Results

In the test cohort, the DSC of automatic segmentation reached 0.89. Excellent concordance (ICC > 0.95) of the maximal and minimal diameter and good concordance (ICC > 0.80) of volumetric measurement were shown between the model and the radiologists. The trained model took approximately 10–15 s to provide automatic segmentation and classified the T stage with an overall accuracy of 0.93, sensitivity of 0.94, 0.94, and 0.75, and specificity of 0.95, 0.92, and 0.99, respectively, in T1, T2, and T3.

Conclusions

Our model demonstrated good performance and reliability for automatic segmentation for size and volumetric measurement of breast cancer, which can be time-saving and effective in clinical decision-making.
S-Ketamine oral thin film—Part 2: Population pharmacodynamics of S-ketamine, S-norketamine and S-hydroxynorketamine
Authors: Simons Pieter , Olofsen Erik , van Velzen Monique , van Lemmen Maarten , van Dasselaar Tom , Mohr Patrick , Hammes Florian , van der Schrier Rutger , Niesters Marieke , Dahan Albert
Published: August 2022

Ketamine is a versatile drug used for many indications and is administered via various routes. Here, we report on the pharmacodynamics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S-ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two 50 mg S-ketamine oral thin films in a crossover design, placed for 10 min sublingually (n = 15) or buccally (n = 5). The following measurements were made for 6 h following the film placement: antinociception using three distinct pain assay; electrical, pressure, and heat pain, and drug high on an 11-point visual analog scale. Blood samples were obtained for the measurement of plasma S-ketamine, S-norketamine, and S-hydroxynorketamine concentrations. A population pharmacodynamic analysis was performed in NONMEM to construct a pharmacodynamic model of S-ketamine and its metabolites. P-values < 0.01 were considered significant. The sublingual and buccal 50 and 100 mg S-ketamine oral thin films were antinociceptive and produced drug high with effects lasting 2–6 h, although a clear dose-response relationship for antinociception could not be established. The effects were solely related to the parent compound with no contribution from S-norketamine or S-hydroxynorketamine. S-ketamine potency was lower for antinociception (C50 ranging from 1.2 to 1.7 nmol/mL) than for drug high (C50 0.3 nmol/ml). The onset/offset of effect as defined by the blood-effect-site equilibration half-life did not differ among endpoints and ranged from 0 to 5 min. In conclusion, the 50-mg S-ketamine oral thin film was safe and produced long-term antinociception in all three nociceptive assays with side effects inherent to the use of ketamine. The study was registered at the trial register of the Dutch Cochrane Center (www.trialregister.nl) under identifier NL9267 and the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database under number 2020-005185-33.
Iron status of exclusively breastfed low-birth-weight infants born to anemic mothers and effect of maternal iron supplementation for 3 versus 6 months: A randomized double-blind placebo control trial
Authors: Fatima Tarannum , Faridi Mohammad Moonis Akbar , Srivastava Geetika
Published: August 2022

Background

The effect of maternal iron supplementation during lactation on the iron status of exclusively breastfed low-birth-weight (LBW) infants is not known.

Objective

(1) To find out the number of LBW exclusively breastfed infants having hemoglobin < 10.5 g/dL at 6 months when mothers received iron. (2) To find out the proportion of anemic infants when mothers received iron for 3 and 6 months.

Design

The Clinical Trials Registry, India (CTRI) registered trial (CTRI/2018/08/015516) double-blind randomized control trial participants: A total of 80 anemic mothers and exclusively breastfed LBW infants.

Intervention

A total of 80 anemic mothers and exclusively breastfed infants, birth weight 1,500–2,499 g, randomized into two groups of 40 each. Mothers received daily iron for 3 months and placebo for the next 3 months in group A and iron for 6 months in group B. Iron profile of mothers and infants measured at recruitment and 6 months.

Results

In total, 26.6% infants developed anemia till 6 months of age, and number of anemic infants were similar whether mothers received iron for 3 (n = 9) or 6 months (n = 11). Hemoglobin (12.89 + 0.46 vs. 12.44 + 0.48 g/dL; p < 0.001) and serum ferritin (27.45 + 7.60 vs. 18.94 + 5.36 ng/mL; p < 0.001) were significantly higher in infants at 6 months of age whose mothers received iron for 6 months in comparison to 3 months. Conclusion: totally, 26.6% exclusively breastfed infants developed anemia till 6 months of age when mothers took iron; number of anemic infants were not different if mothers received iron for 3 or 6 months. A significant increase was noted in serum ferritin with slightly higher hemoglobin of infants when mothers received iron for longer duration.

Clinical trial registration

[http://ctri.nic.in/Clinicaltrials/pubview.php], identifier [CTRI/2018/08/015516].
Thromboembolic complications in children with COVID-19 and MIS-C: A narrative review
Authors: Trapani Sandra , Rubino Chiara , Lasagni Donatella , Pegoraro Francesco , Resti Massimo , Simonini Gabriele , Indolfi Giuseppe
Published: August 2022

COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have been associated with a higher incidence of hypercoagulability and thromboembolic events (TEs), even in children, leading to relevant morbidity, and mortality. However, our understanding of such complications in childhood is limited. To better understand the incidence, clinical manifestations, risk factors, and management of COVID-19 and MIS-C-related TEs in children, a review of the current literature and a brief update on pathophysiology are given. Sixty-two studies, describing 138 patients with TEs associated with COVID-19 or MIS-C, were included. The overall number of TEs was 157, as 16 patients developed multiple TEs: venous TEs represented the majority (54%), followed by arterial thrombosis (38%, mainly represented by arterial ischemic stroke-AIS), and intracardiac thrombosis (ICT) (8%). Within the venous TEs group, pulmonary embolism (PE) was the most frequent, followed by deep venous thrombosis, central venous sinus thrombosis, and splanchnic venous thrombosis. Notably, 10 patients had multiple types of venous TEs, and four had both venous and arterial thrombosis including a newborn. Most of them (79 cases,57%) had at least one predisposing condition, being obesity the most frequent (21%), especially in patients with PE, followed by malignancy (9%). In 35% of cases, no data about the outcome were available About one-third of cases recovered, 12% improved at discharge or follow-up, and 6% had persistent neurological sequelae. The mortality rate was 12%, with death due to comorbidities in most cases. Most fatalities occurred in patients with arterial thrombosis. Pediatricians should be aware of this life-threatening possibility facing children with SARS-CoV-2 infection or its multisystemic inflammatory complication, who abruptly develop neurological or respiratory impairment. A prompt intensive care is essential to avoid severe sequelae or even exitus.