bluuebunny/crossref_metadata_2025 huggingface dataset:
Nematicidal Activity of Burkholderia arboris J211 Against Meloidogyne incognita on Tobacco
Authors: Zhang Renjun , Ouyang Jin , Xu Xingyang , Li Jie , Rehman Muzammal , Deng Gang , Shu Jie , Zhao Dake , Chen Suiyun , Sayyed R. Z. , Fahad Shah , Chen Yaqiong
Published: June 2022

Root-knot nematode (Meloidogyne incognita) is the most widespread nematode affecting Solanaceae crops. Due to the lack of effective measures to control this nematode, its management can be achieved, using biocontrol agents. This study investigated in vitro efficacy of the antagonistic bacterial strain J211 isolated from tobacco rhizosphere soil against M. incognita, and further assessed its role in controlling nematodes, both in pot and field trials. Phylogenetic analysis of the 16S rRNA gene sequence of strain J211 assigned to Burkholderia arboris. Culture filtrates B. arboris J211 exhibited anematicidal activity against the second-stage juveniles (J2s) of M. incognita, with a 96.6% mortality after 24 h exposure. Inoculation of J211 in tobacco roots significantly reduced the root galling caused by M. incognita, both in pot and field trials. Meanwhile, plant growth-promoting (PGP) traits results showed that J211 had outstanding IAA-producing activity, and the IAA production reached 66.60 mg L−1. In the field study, B. arboris J211 also promoted tobacco growth and increase flue-cured tobacco yield by 8.7–24.3%. Overall, B. arboris J211 as a high-yielding IAA nematicidal strain effectively controlled M. incognita and improved tobacco yield making it a promising alternative bionematocide.
Hepatocyte-Specific Knock-Out of Nfib Aggravates Hepatocellular Tumorigenesis via Enhancing Urea Cycle
Authors: Zhou Li , Wang Qing-Liang , Mao Lin-Hong , Chen Si-Yuan , Yang Zi-Han , Liu Xue , Gao Yu-Hua , Li Xiao-Qin , Zhou Zhi-Hang , He Song
Published: June 2022

Nuclear Factor I B (NFIB) has been reported to promote tumor growth, metastasis, and liver regeneration, but its mechanism in liver cancer is not fully elucidated. The present study aims to reveal the role of NFIB in hepatocellular carcinogenesis. In our study, we constructed hepatocyte-specific NFIB gene knockout mice with CRISPR/Cas9 technology (Nfib−/−; Alb-cre), and induced liver cancer mouse model by intraperitoneal injection of DEN/CCl4. First, we found that Nfib−/− mice developed more tumor nodules and had heavier livers than wild-type mice. H&E staining indicated that the liver histological severity of Nfib−/− group was more serious than that of WT group. Then we found that the differentially expressed genes in the tumor tissue between Nfib−/− mice and wild type mice were enriched in urea cycle. Furthermore, ASS1 and CPS1, the core enzymes of the urea cycle, were significantly upregulated in Nfib−/− tumors. Subsequently, we validated that the expression of ASS1 and CPS1 increased after knockdown of NFIB by lentivirus in normal hepatocytes and also promoted cell proliferation in vitro. In addition, ChIP assay confirmed that NFIB can bind with promoter region of both ASS1 and CPS1 gene. Our study reveals for the first time that hepatocyte-specific knock-out of Nfib aggravates hepatocellular tumor development by enhancing the urea cycle.
Alteration of Visuospatial System as an Early Marker of Cognitive Decline: A Double-Center Neuroimaging Study
Authors: Berente Dalida Borbala , Zsuffa Janos , Werber Tom , Kiss Mate , Drotos Anita , Kamondi Anita , Csukly Gabor , Horvath Andras Attila
Published: June 2022

Amnestic-type mild cognitive impairment (a-MCI) represents the prodromal phase of Alzheimer's disease associated with a high conversion rate to dementia and serves as a potential golden period for interventions. In our study, we analyzed the role of visuospatial (VS) functions and networks in the recognition of a-MCI. We examined 78 participants (32 patients and 46 controls) in a double-center arrangement using neuropsychology, structural, and resting-state functional MRI. We found that imaging of the lateral temporal areas showed strong discriminating power since in patients only the temporal pole (F = 5.26, p = 0.034) and superior temporal gyrus (F = 8.04, p < 0.001) showed reduced cortical thickness. We demonstrated significant differences between controls and patients in various neuropsychological results; however, analysis of cognitive subdomains revealed that the largest difference was presented in VS skills (F = 8.32, p < 0.001). Functional connectivity analysis of VS network showed that patients had weaker connectivity between the left and right frontotemporal areas, while stronger local connectivity was presented between the left frontotemporal structures (FWE corrected p < 0.05). Our results highlight the remarkable potential of examining the VS system in the early detection of cognitive decline. Since resting-state setting of functional MRI simplifies the possible automatization of data analysis, detection of VS system alterations might provide a non-invasive biomarker of a-MCI.
Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Taniguchi Akira , Shindo Akihiro , Tabei Ken-ichi , Onodera Osamu , Ando Yukio , Urabe Takao , Kimura Kazumi , Kitagawa Kazuo , Miyamoto Yoshihiro , Takegami Misa , Ihara Masafumi , Mizuta Ikuko , Mizuno Toshiki , Tomimoto Hidekazu
Published: June 2022

Objectives

Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL.

Methods

Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated.

Results

Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia (p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723–0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719–0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551–0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity.

Conclusion

The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML.
Aging-Related Dissociation of Spatial and Temporal N400 in Sentence-Level Semantic Processing: Evidence From Source Analyses
Authors: An Sora , Oh Se Jin , Jun Sang Beom , Sung Jee Eun
Published: June 2022

Age-related differences in sentence-level lexical-semantic processes have been extensively studied, based on the N400 component of event-related potential (ERP). However, there is still a lack of understanding in this regard at the brain-region level. This study explores aging effects on sentence-level semantic processing by comparing the characteristics of the N400 ERP component and brain engagement patterns within individual N400 time windows for two age groups (16 younger adults aged 24.38 ± 3.88 years and 15 older adults aged 67.00 ± 5.04 years) during sentence processing with different plausibility conditions. Our results demonstrated that the N400 effect according to the plausibility condition occurred in different temporal windows in the two age groups, with a delay in the older group. Moreover, it was identified that there was a distinct difference between the groups in terms of the source location of the condition-dependent N400 effect even though no significant difference was derived in its magnitude itself at the sensor-level. Interestingly, the source analysis results indicated that the two groups involved different functional networks to resolve the same semantic violations: the younger group activated the regions corresponding to the typical lexical-semantic network more, whereas the older group recruited the regions belonging to the multiple-demand network more. The findings of this study could be used as a basis for understanding the aging brain in a linguistic context.
The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases
Authors: Blevins Hallie M. , Xu Yiming , Biby Savannah , Zhang Shijun
Published: June 2022

The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs and DAMPs, NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-18. NLRP3 is the most extensively studied inflammasome to date due to its array of activators and aberrant activation in several inflammatory diseases. Studies using small molecules and biologics targeting the NLRP3 inflammasome pathway have shown positive outcomes in treating various disease pathologies by blocking chronic inflammation. In this review, we discuss the recent advances in understanding the NLRP3 mechanism, its role in disease pathology, and provide a broad review of therapeutics discovered to target the NLRP3 pathway and their challenges.
The Role of Genetic Data in Selecting Device-Aided Therapies in Patients With Advanced Parkinson’s Disease: A Mini-Review
Authors: Chan Germaine Hiu-Fai
Published: June 2022

Parkinson’s disease (PD) is a common neurodegenerative disease. At present, 5–10% of PD patients are found to have monogenic form of the disease. Each genetic mutation has its own unique clinical features and disease trajectory. It is unclear if the genetic background can affect the outcome of device-aided therapies in these patients. In general, monogenic PD patients have satisfactory motor outcome after receiving invasive therapies. However, their long-term outcome can vary with their genetic mutations. It appears that patients with leucine-rich repeat kinase-2 (LRRK2) and PRKN mutations tended to have good outcome following deep brain stimulation (DBS) surgery. However, those with Glucocerebrosidase (GBA) mutation were found to have poorer cognitive performance, especially after undergoing subthalamic nucleus DBS surgery. In this review, we will provide an overview of the outcomes of device-aided therapies in PD patients with different genetic mutations.
Associations Between Sleep Duration and Sensory Impairments Among Older Adults in China
Authors: Rong Hongguo , Wang Xiao , Lai Xiaozhen , Yu Weijie , Fei Yutong
Published: June 2022

Objective

Studies of sleep duration in relation to the risk of sensory impairments other than dementia are scarce. Little is known about the associations between sleep duration and sensory impairments in China. This study aims to explore the associations between sleep duration and single or dual sensory impairments (visual and/or hearing).

Methods

This cross-sectional study used the data from 17,668 respondents were drawn from the 2018 survey of the China Health and Retirement Longitudinal Study (CHARLS), an ongoing national longitudinal study of Chinese adults aged 45 years and above. The duration of sleep per night was obtained from face-to-face interviews. The presence of sensory impairments was measured by self-reported visual and hearing functions. Multivariable generalized linear models (GLM) with binomial family and log link to assess the associations between sleep duration and sensory impairments.

Results

Of the 17,668 respondents, 8,396 (47.5%) were men. The mean (SD) age was 62.5 (10.0) years old. Respondents with short (≤ 4, 5 h per night) sleep duration had a significantly higher risk of visual, hearing and dual sensory impairments than those who slept for 7 h per night after adjusting for covariates (P < 0.05). Meanwhile, respondents who slept for 6 h per night had a higher risk of hearing impairment (P = 0.005). Further analysis suggested a U-shaped association between sleep duration and sensory impairments. When sleep duration fell below 8 h, increased sleep duration was associated with a significantly lower risk of visual (OR, 0.93; 95%CI, 0.88–0.98; P = 0.006), hearing (OR, 0.89; 95% CI, 0.86–0.93; P < 0.001), and dual (OR, 0.90; 95% CI, 0.87–0.94; P < 0.001) impairments. When sleep duration exceeded 8 h, the risk of visual (OR, 1.09; 95% CI, 1.00–1.19; P = 0.048), hearing (OR, 1.04; 95% CI, 0.97–1.11; P = 0.269), and dual (OR, 1.07; 95% CI, 1.00–1.14; P = 0.044) impairments would increase facing prolonged sleep duration. Women and the elderly aged over 60 years old were more sensitive to short sleep duration and experienced a higher risk of sensory impairments.

Conclusion

In this study, short sleep duration was associated with a higher risk of visual and hearing impairments. Future studies are needed to examine the mechanisms of the associations between sleep duration and sensory impairments.
Traditional Chinese Exercises on Pain and Disability in Middle-Aged and Elderly Patients With Neck Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kong Lingjun , Ren Jun , Fang Sitong , He Tianxiang , Zhou Xin , Fang Min
Published: June 2022

Background

With the change of life and work style, more middle-aged and elderly individuals are suffering from neck pain. In China, traditional Chinese exercises (TCEs) are widely used in the management of neck pain, such as Tai Chi, Qigong, Yijinjing, Baduanjin, Liuzijue, and Five-animal exercises. However, the evidence of TCEs for neck pain maintains controversial. Therefore, the current systematic review was conducted to evaluate the effects of TCEs on pain and disability of middle-aged and elderly patients with neck pain.

Methods

A comprehensive literature search was performed in six electronic databases from their inception to January 2022 for randomized controlled trials of TCEs for neck pain. The methodological quality of the included studies was assessed by PEDro scale. The subgroup analysis was conducted based on different TCEs. The I2 statistic was applied to assess the heterogeneity.

Results

Twenty-one studies were included in our review, which were conducted in China, United States, and Germany between 2003 and 2021. Most (86%) of them exceeded the cut off score 6. TCEs included Baduanjin, Yijinjing, Tai Chi, Qigong, and Five-animal exercises. The aggregated results indicated that TCEs showed positive complementary effects in relieving pain (SMD, 1.12; 95% CI, 0.78–1.45; p < 0.00001), especially Baduanjin exercises. Baduanjin exercises also showed beneficial complementary effects in improving flexion (SMD, 0.65; 95% CI, 0.28–1.03; p = 0.0006) and extension (SMD, 0.66; 95% CI, 0.12–1.19; p = 0.02) of the neck. In addition, the aggregated results indicated that TCEs alone showed beneficial effects in improving disability (SMD, 0.74; 95% CI, 0.40–1.08; p < 0.0001) and relieving pain (SMD, 0.81; 95% CI, 0.50–1.13; p < 0.00001) compared with waiting list. The follow-up effects of TCEs were still insufficient.

Conclusion

There was the positive evidence to support the clinical use of TCEs, as a complementary therapy, for middle-aged and elderly patients with neck pain, especially Baduanjin exercises. However, the evidence supporting the effects of TCEs alone for the middle-aged and elderly patients with neck pain was limited due to the small sample size.

Systematic Review Registration

https://inplasy.com/inplasy-2022-4-0083/, identifier INPLASY202240083.
Effect of Different Vitamin D Levels on Cognitive Function in Aged Mice After Sevoflurane Anesthesia
Authors: Zhang Jialei , Zhang Xiaoling , Yang Yongyan , Zhao Jun , Hu Wenqing , Yu Yonghao
Published: June 2022

Although the biological relationship between vitamin D (VD) deficiency and cognitive function has been recognized by many scholars, the theoretical mechanisms involved are still not well-understood. In this study, we demonstrated the role of VD in alleviating the cognitive dysfunction in aged mice caused by sevoflurane anesthesia. Forty female C57BL/6 mice aged 12 months were selected for the experiment. VD (-) and VD (+) mouse models and sevoflurane anesthesia models were established. Mice were randomly divided into normal elderly group (NC group), normal aged mice + sevoflurane anesthesia treatment group (NS group), aged VD (-) mice + sevoflurane anesthesia treatment group [VD (-) group], and aged VD (+) + sevoflurane anesthesia treatment group [VD (+) group]. To compare the emergence time after sevoflurane anesthesia in aged mice with different levels of VD and to test the cognitive function of four groups through the water maze. Inflammatory factor expression and cholinergic activity in hippocampus tissue of all mice were measured at the end of behavioral tests. These data show that, low levels of VD aggravated the delayed emergence and cognitive dysfunction in aged mice caused by sevoflurane anesthesia, while higher levels of VD mitigated this impairment by enhancing cholinergic activity and reducing inflammatory factor expression in the hippocampus.
Development of Atypical Reading at Ages 5 to 9 Years and Processing of Speech Envelope Modulations in the Brain
Authors: Granados Barbero Raúl , Ghesquière Pol , Wouters Jan
Published: June 2022

Different studies have suggested that during speech processing readers with dyslexia present atypical levels of neural entrainment as well as atypical functional hemispherical asymmetries in comparison with typical readers. In this study, we evaluated these differences in children and the variation with age before and after starting with formal reading instruction. Synchronized neural auditory processing activity was quantified based on auditory steady-state responses (ASSRs) from EEG recordings. The stimulation was modulated at syllabic and phonemic fluctuation rates present in speech. We measured the brain activation patterns and the hemispherical asymmetries in children at three age points (5, 7, and 9 years old). Despite the well-known heterogeneity during developmental stages, especially in children and in dyslexia, we could extract meaningful common oscillatory patterns. The analyses included (1) the estimations of source localization, (2) hemispherical preferences using a laterality index, measures of neural entrainment, (3) signal-to-noise ratios (SNRs), and (4) connectivity using phase coherence measures. In this longitudinal study, we confirmed that the existence of atypical levels of neural entrainment and connectivity already exists at pre-reading stages. Overall, these measures reflected a lower ability of the dyslectic brain to synchronize with syllabic rate stimulation. In addition, our findings reinforced the hypothesis of a later maturation of the processing of beta rhythms in dyslexia. This investigation emphasizes the importance of longitudinal studies in dyslexia, especially in children, where neural oscillatory patterns as well as differences between typical and atypical developing children can vary in the span of a year.
Association Between Dopaminergic Medications and the Evolution of REM Sleep Behavior Disorder in Parkinson's Disease
Authors: Cao Ruihua , Ma Ruolin , Wang Kai , Hu Panpan
Published: June 2022

REM sleep behavior disorder (RBD) is closely associated with Parkinson's disease (PD), however, the influence of dopaminergic replacement therapy (DRT) on the clinical course of RBD in PD remains less understood. The objective of our study is to investigate how DRTs modify the evolution of RBD in a longitudinal cohort study of initially de novo PD patients. Four hundred and five drug-naive patients with early-stage PD were included. RBD symptoms were assessed using the 10-item RBD Screening Questionnaire (RBDSQ) at baseline and during the 5-year follow-up. A generalized estimating equation was used to examine predictors of the evolution of RBD symptoms. For patients without baseline pRBD, patients on levodopa treatment showed a greater increase in RBDSQ scores than those not on levodopa treatment, and the increase in RBDSQ scores was significantly correlated with the levodopa-LEDD. Moreover, the changes in RBDSQ scores at a given post-baseline visit were significantly associated with the use of levodopa (OR = 1.875, p = 0.008) and the combined use of levodopa and DA (OR = 2.188, p = 0.012), as well as the levodopa-LEDD (OR = 1.001, p = 0.005) at that visit. The use of DA alone or the DA-LEDD was not a significant predictor of changes in RBDSQ scores. Similarly, a conversion from pRBD negative to pRBD positive was significantly associated with levodopa-LEDD (OR = 1.001, p = 0.014) but not DA-LEDD. Together, these finding implicated that the use of levodopa may act as a contributing factor to the increasing prevalence of RBD after the onset of PD, suggesting different mechanisms underlying prodromal RBD and late-onset RBD.
Machine Learning-Based Model for Prediction of Hemorrhage Transformation in Acute Ischemic Stroke After Alteplase
Authors: Xu Yanan , Li Xiaoli , Wu Di , Zhang Zhengsheng , Jiang Aizhong
Published: June 2022

Hemorrhage transformation (HT) is the most dreaded complication of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). The prediction of HT after IVT is important in the treatment decision-making for AIS. We designed and compared different machine learning methods, capable of predicting HT in AIS after IVT. A total of 345 AIS patients who received intravenous alteplase between January 2016 and June 2021 were enrolled in this retrospective study. The demographic characteristics, clinical condition, biochemical data, and neuroimaging variables were included for analysis. HT was confirmed by head computed tomography (CT) or magnetic resonance imaging (MRI) within 48 h after IVT. Based on the neuroimaging results, all of the patients were divided into the non-HT group and the HT group. Then, the variables were applied in logistic regression (LR) and random forest (RF) algorithms to establish HT prediction models. To evaluate the accuracy of the machine learning models, the models were compared to several of the common scales used in clinics, including the multicenter stroke survey (MSS) score, safe implementation of treatments in stroke (SITS) score, and SEDAN score. The performance of these prediction models was evaluated using the receiver operating characteristic (ROC) curve (AUC). Forty-five patients had HT (13.0%) within 48 h after IVT. The ROC curve results showed that the AUCs of HT that were predicted by the RF model, LR model, MSS, SITS, and SEDAN scales after IVT were 0.795 (95% CI, 0.647–0.944), 0.703 (95% CI, 0.515–0.892), 0.657 (95% CI, 0.574–0.741), 0.660 (95% CI, 0.580–0.740) and 0.655 (95% CI, 0.571–0.739), respectively. The RF model performed better than the other models and scales. The top four most influential factors in the RF importance matrix plot were triglyceride, Lpa, the baseline NIHSS, and hemoglobin. The SHapley Additive exPlanation values made the RF prediction model clinically interpretable. In this study, an RF machine learning method was successfully established to predict HT in AIS patients after intravenous alteplase, which the sensitivity was 66.7%, and the specificity was 80.7%.
Temporal Grading Index of Functional Network Topology Predicts Pain Perception of Patients With Chronic Back Pain
Authors: Li Zhonghua , Zhao Leilei , Ji Jing , Ma Ben , Zhao Zhiyong , Wu Miao , Zheng Weihao , Zhang Zhe
Published: June 2022

Chronic back pain (CBP) is a maladaptive health problem affecting the brain function and behavior of the patient. Accumulating evidence has shown that CBP may alter the organization of functional brain networks; however, whether the severity of CBP is associated with changes in dynamics of functional network topology remains unclear. Here, we generated dynamic functional networks based on resting-state functional magnetic resonance imaging (rs-fMRI) of 34 patients with CBP and 34 age-matched healthy controls (HC) in the OpenPain database via a sliding window approach, and extracted nodal degree, clustering coefficient (CC), and participation coefficient (PC) of all windows as features to characterize changes of network topology at temporal scale. A novel feature, named temporal grading index (TGI), was proposed to quantify the temporal deviation of each network property of a patient with CBP to the normal oscillation of the HCs. The TGI of the three features achieved outstanding performance in predicting pain intensity on three commonly used regression models (i.e., SVR, Lasso, and elastic net) through a 5-fold cross-validation strategy, with the minimum mean square error of 0.25 ± 0.05; and the TGI was not related to depression symptoms of the patients. Furthermore, compared to the HCs, brain regions that contributed most to prediction showed significantly higher CC and lower PC across time windows in the CBP cohort. These results highlighted spatiotemporal changes in functional network topology in patients with CBP, which might serve as a valuable biomarker for assessing the sensation of pain in the brain and may facilitate the development of CBP management/therapy approaches.
Flow Diversion vs. Stent-Assisted Coiling in the Treatment of Intradural Large Vertebrobasilar Artery Aneurysms
Authors: Wu Qiaowei , Li Chunxu , Xu Shancai , Wang Chunlei , Ji Zhiyong , Qi Jingtao , Li Yuchen , Sun Bowen , Shi Huaizhang , Wu Pei
Published: June 2022

Objective

To compare the safety, angiographic, and long-term clinical outcomes of intradural large vertebrobasilar artery (VBA) aneurysms following flow diversion (FD) or conventional stent-assisted coiling (SAC).

Methods

We performed a retrospective study of 66 consecutive patients with intradural large VBA aneurysms between 2014 and 2021 who underwent FD or SAC. Patients' characteristics, postprocedural complications, and clinical and angiographic outcome details were reviewed.

Results

A total of 66 intradural large VBA aneurysms were included, including 42 (63.6%), which were treated with SAC (SAC group) and 24 (36.4%), which were treated with FD (FD group). Clinical follow-up was obtained at the median of 24.0 [interquartile range (IQR) 12.0–45.0] months, with 34 (81.0%) patients achieved the modified Rankin Scale (mRS) ≤ 2 in the SAC group and 21 (87.5%) patients in the FD group. Thirteen (19.7%) patients experienced neurological complications, of which 9 (13.6%) patients first occurred during the periprocedural phase and 4 (6.1%) patients first occurred during follow-up. The overall complication rate and periprocedural complication rate were both higher in the SAC group, but did not reach statistical significance (23.8 vs. 12.5%, P = 0.430; 16.7 vs. 8.3%, P = 0.564). The mortality rates were similar between the groups (11.9 vs. 12.5%). Angiographic follow-up was available for 46 patients at the median of 7 (IQR 6–14) months, with a numerically higher complete occlusion rate in the SAC group (82.1 vs. 55.6%, P = 0.051) and similar adequate aneurysm occlusion rates between the groups (85.7 vs. 83.3%, P = 1.000). In the multivariate analysis, ischemic onset (P = 0.019), unilateral vertebral artery sacrifice (P = 0.008), and older age (≥60 years) (P = 0.031) were significantly associated with complications.

Conclusion

There was a trend toward lower complication rate and lower complete occlusion rate for intradural large VBA aneurysms following FD as compared to SAC. FD and SAC have comparable mortality rates and favorable outcomes. Ischemic onset, unilateral vertebral artery sacrifice, and older age could increase the risk of complications.
Correlation Between Ictal Signs and Anatomical Subgroups in Temporal Lobe Seizures: A Stereoelectroencephalography Study
Authors: Zhang Bo , Wang Jing , Wang Mengyang , Wang Xiongfei , Guan Yuguang , Liu Zhao , Zhang Yao , Liu Changqing , Zhao Meng , Xie Pandeng , Zhu Mingwang , Li Tianfu , Luan Guoming , Zhou Jian
Published: June 2022

Objective

Ictal semiology is a fundamental part of the presurgical evaluation of patients with temporal lobe epilepsy. We aimed to identify different anatomical and semiologic subgroups in temporal lobe seizures, and investigate the correlation between them.

Methods

We enrolled 93 patients for whom stereoelectroencephalography exploration indicated that the seizure-onset zone was within the temporal lobe. Ictal signs and concomitant stereoelectroencephalography changes were carefully reviewed and quantified, and then cluster analysis and the Kendall correlation test were used to associate ictal signs with the temporal structures of patients.

Results

Clustering analysis identified two main groups of temporal structures. Group 1 consisted of the medial temporal lobe structures and the temporal pole, which were divided into two subgroups. Group 1A included the hippocampal head, hippocampal body, and amygdala, and this subgroup correlated significantly with oroalimentary automatisms, feeling of fear, and epigastric auras. Group 1B included the hippocampal tail, temporal pole, and parahippocampal gyrus, and this subgroup correlated significantly with manual and oroalimentary automatisms. Group 2 consisted of the cortical structures of the temporal lobe and was also divided into two subgroups. Group 2A included the superior and middle temporal gyrus, correlated significantly with bilateral rictus/facial contraction, generalized tonic–clonic seizure, and manual automatisms. Group 2B included Heschl's gyrus, the inferior temporal gyrus, and the fusiform gyrus, and this subgroup correlated significantly with auditory auras, focal hypokinetics, unilateral upper and lower limbs tonic posture/clonic signs, head/eye deviation, unilateral versive signs, and generalized tonic–clonic seizure.

Significance

The temporal structures can be categorized according to the level at which each structure participates in seizures, and different anatomical subgroups can be correlated with different ictal signs. Identifying specific semiologic features can help us localize the epileptogenic zone and thus develop stereoelectroencephalography electrode implantation and surgical resection protocols for patients with temporal lobe epilepsy.
Written Language Acquisition Is Both Shaped by and Has an Impact on Brain Functioning and Cognition
Authors: Pegado Felipe
Published: June 2022

Spoken language is a distinctive trace of our species and it is naturally acquired during infancy. Written language, in contrast, is artificial, and the correspondences between arbitrary visual symbols and the spoken language for reading and writing should be explicitly learned with external help. In this paper, I present several examples of how written language acquisition is both shaped by and has an impact on brain function and cognition. They show in one hand how our phylogenetic legacy influences education and on the other hand how ontogenetic needs for education can rapidly subdue deeply rooted neurocognitive mechanisms. The understanding of this bidirectional influences provides a more dynamic view of how plasticity interfaces phylogeny and ontogeny in human learning, with implications for both neurosciences and education.
Magnetic Resonance Imaging and Its Clinical Correlation in Spinocerebellar Ataxia Type 3: A Systematic Review
Authors: Yap Kah Hui , Abdul Manan Hanani , Yahya Noorazrul , Azmin Shahrul , Mohamed Mukari Shahizon Azura , Mohamed Ibrahim Norlinah
Published: June 2022

Background

Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The heterogeneous clinical presentation of SCA3 necessitates correlations between magnetic resonance imaging (MRI) and clinical findings in reflecting progressive disease changes. At present, an attempt to systematically examine the brain-behavior relationship in SCA3, specifically, the correlation between MRI and clinical findings, is lacking.

Objective

We investigated the association strength between MRI abnormality and each clinical symptom to understand the brain-behavior relationship in SCA3.

Methods

We conducted a systematic review on Medline and Scopus to review studies evaluating the brain MRI profile of SCA3 using structural MRI (volumetric, voxel-based morphometry, surface analysis), magnetic resonance spectroscopy, and diffusion tensor imaging, including their correlations with clinical outcomes.

Results

Of 1,767 articles identified, 29 articles met the eligibility criteria. According to the National Institutes of Health quality assessment tool for case-control studies, all articles were of excellent quality. This systematic review found that SCA3 neuropathology contributes to widespread brain degeneration, affecting the cerebellum and brainstem. The disease gradually impedes the cerebral cortex and basal ganglia in the late stages of SCA3. Most findings reported moderate correlations (r = 0.30–0.49) between MRI features in several regions and clinical findings. Regardless of the MRI techniques, most studies focused on the brainstem and cerebellum.

Conclusions

Clinical findings suggest that rather than individual brain regions, the connectivity between different brain regions in distributed networks (i.e., cerebellar-cerebral network) may be responsible for motor and neurocognitive function in SCA3. This review highlights the importance of evaluating the progressive changes of the cerebellar-cerebral networks in SCA3 patients, specifically the functional connectivity. Given the relative lack of knowledge about functional connectivity on SCA3, future studies should investigate possible functional connectivity abnormalities in SCA3 using fMRI.
Strong Selectional Forces Fine-Tune CpG Content in Genes Involved in Neurological Disorders as Revealed by Codon Usage Patterns
Authors: Khandia Rekha , Sharma Anushri , Alqahtani Taha , Alqahtani Ali M. , Asiri Yahya I. , Alqahtani Saud , Alharbi Ahmed M. , Kamal Mohammad Amjad
Published: June 2022

Neurodegenerative disorders cause irreversible damage to the neurons and adversely affect the quality of life. Protein misfolding and their aggregation in specific parts of the brain, mitochondrial dysfunction, calcium load, proteolytic stress, and oxidative stress are among the causes of neurodegenerative disorders. In addition, altered metabolism has been associated with neurodegeneration as evidenced by reductions in glutamine and alanine in transient global amnesia patients, higher homocysteine-cysteine disulfide, and lower methionine decline in serum urea have been observed in Alzheimer’s disease patients. Neurodegeneration thus appears to be a culmination of altered metabolism. The study’s objective is to analyze various attributes like composition, physical properties of the protein, and factors like selectional and mutational forces, influencing codon usage preferences in a panel of genes involved directly or indirectly in metabolism and contributing to neurodegeneration. Various parameters, including gene composition, dinucleotide analysis, Relative synonymous codon usage (RSCU), Codon adaptation index (CAI), neutrality and parity plots, and different protein indices, were computed and analyzed to determine the codon usage pattern and factors affecting it. The correlation of intrinsic protein properties such as the grand average of hydropathicity index (GRAVY), isoelectric point, hydrophobicity, and acidic, basic, and neutral amino acid content has been found to influence codon usage. In genes up to 800 amino acids long, the GC3 content was highly variable, while GC12 content was relatively constant. An optimum CpG content is present in genes to maintain a high expression level as required for genes involved in metabolism. Also observed was a low codon usage bias with a higher protein expression level. Compositional parameters and nucleotides at the second position of codons played essential roles in explaining the extent of bias. Overall analysis indicated that the dominance of selection pressure and compositional constraints and mutational forces shape codon usage.
Natural Products of Plants and Animal Origin Improve Albumen Quality of Chicken Eggs
Authors: Obianwuna Uchechukwu Edna , Oleforuh-Okoleh Vivian U. , Wang Jing , Zhang Hai-Jun , Qi Guang-Hai , Qiu Kai , Wu Shu-Geng
Published: June 2022

Albumen quality is recognized as one of the major yardsticks in measuring egg quality. The elasticity of thick albumen, a strong bond in the ovomucin-lysozyme complex, and excellent biological properties are indicators of high-quality albumen. The albumen quality prior to egg storage contribute to enhance egg’s shelf life and economic value. Evidence suggests that albumen quality can deteriorate due to changes in albumen structure, such as the degradation of β-ovomucin subunit and O-glyosidic bonds, the collapse of the ovomucin-lysozyme complex, and a decrease in albumen protein-protein interaction. Using organic minerals, natural plants and animal products with antioxidant and antimicrobial properties, high biological value, no residue effect and toxicity risk could improve albumen quality. These natural products (e.g., tea polyphenols, marigold extract, magnolol, essential oils, Upro (small peptide), yeast cell wall, Bacillus species, a purified amino acid from animal blood, and pumpkin seed meal) are bio-fortified into eggs, thus enhancing the biological and technological function of the albumen. Multiple strategies to meeting laying hens’ metabolic requirements and improvement in albumen quality are described in this review, including the use of amino acids, vitamins, minerals, essential oils, prebiotics, probiotics, organic trace elements, and phytogenic as feed additives. From this analysis, natural products can improve animal health and consequently albumen quality. Future research should focus on effects of these natural products in extending shelf life of the albumen during storage and at different storage conditions. Research in that direction may provide insight into albumen quality and its biological value in fresh and stored eggs.
Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Perioperative and Survival Outcomes
Authors: Ma Xiao , Zhao Weixin , Li Bin , Yu Yongfu , Ma Yuan , Thomas Mathew , Zhang Yawei , Xiang Jiaqing , Zhang Yiliang
Published: June 2022

Background

Immune checkpoint inhibitors (ICI) improve survival in patients with late-stage esophageal squamous cell carcinoma (ESCC) but have not been fully evaluated in locally advanced ESCC.

Method

We retrospectively assessed outcomes of consecutive, treatment-naïve locally advanced ESCC (stage III or IVA) adults treated with neoadjuvant ICI plus chemotherapy followed by surgery, who refused or lacked access to radiotherapy, with regards to surgery feasibility, pathological response, and relapse-free survival (RFS).

Results

We uneventfully treated 34 patients with the combined regimen in 2020. None reported grade III or higher toxic effects. All underwent surgery as planned: 32 received complete (R0) resections and 2 had microscopically positive margins (R1). Tumor downstaging occurred in 33 (97.1%) patients and 11 (32.4%) had pathologically complete response of the primary lesion. Median postoperative length of stay was 12 days (interquartile range: 11 to 17). All patients resumed a semi-liquid diet on discharge. The 90-day postoperative morbidity rate was 20.6% (7/34) with no mortalities. The 1-year RFS was 77.8% [95% CI, 64.2-94.2].

Conclusion

Neoadjuvant ICI plus chemotherapy was safe and resulted in significant downstaging, rendering inoperable tumors operable, relieving symptoms of dysphagia and prolonging survival for locally advanced ESCC patients who refused or lacked access to radiotherapy.
Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma
Authors: Barco Sebastiano , Lavarello Chiara , Cangelosi Davide , Morini Martina , Eva Alessandra , Oneto Luca , Uva Paolo , Tripodi Gino , Garaventa Alberto , Conte Massimo , Petretto Andrea , Cangemi Giuliana
Published: June 2022

Neuroblastoma (NB) is the most common extracranial malignant tumor in children. Although the survival rate of NB has improved over the years, the outcome of NB still remains poor for over 30% of cases. A more accurate risk stratification remains a key point in the study of NB and the availability of novel prognostic biomarkers of “high-risk” at diagnosis could help improving patient stratification and predicting outcome.

In this paper we show a biomarker discovery approach applied to the plasma of 172 NB patients. Plasma samples from a first cohort of NB patients and age-matched healthy controls were used for untargeted metabolomics analysis based on high-resolution mass spectrometry (HRMS). Differential expression analysis highlighted a number of metabolites annotated with a high degree of identification. Among them, 3-O-methyldopa (3-O-MD) was validated in a second cohort of NB patients using a targeted metabolite profiling approach and its prognostic potential was also analyzed by survival analysis on patients with 3 years follow-up. High expression of 3-O-MD was associated with worse prognosis in the subset of patients with stage M tumor (log-rank p < 0.05) and, among them, it was confirmed as a prognostic factor able to stratify high-risk patients older than 18 months. 3-O-MD might be thus considered as a novel prognostic biomarker of NB eligible to be included at diagnosis among catecholamine metabolite panels in prospective clinical studies. Further studies are warranted to exploit other potential biomarkers highlighted using our approach.
A Novel Prognostic Signature Based on Glioma Essential Ferroptosis-Related Genes Predicts Clinical Outcomes and Indicates Treatment in Glioma
Authors: Yun Debo , Wang Xuya , Wang Wenbo , Ren Xiao , Li Jiabo , Wang Xisen , Liang Jianshen , Liu Jie , Fan Jikang , Ren Xiude , Zhang Hao , Shang Guanjie , Sun Jingzhang , Chen Lei , Li Tao , Zhang Chen , Yu Shengping , Yang Xuejun
Published: June 2022

Background

Ferroptosis is a form of programmed cell death (PCD) that has been implicated in cancer progression, although the specific mechanism is not known. Here, we used the latest DepMap release CRISPR data to identify the essential ferroptosis-related genes (FRGs) in glioma and their role in patient outcomes.

Methods

RNA-seq and clinical information on glioma cases were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). FRGs were obtained from the FerrDb database. CRISPR-screened essential genes (CSEGs) in glioma cell lines were downloaded from the DepMap portal. A series of bioinformatic and machine learning approaches were combined to establish FRG signatures to predict overall survival (OS) in glioma patients. In addition, pathways analysis was used to identify the functional roles of FRGs. Somatic mutation, immune cell infiltration, and immune checkpoint gene expression were analyzed within the risk subgroups. Finally, compounds for reversing high-risk gene signatures were predicted using the GDSC and L1000 datasets.

Results

Seven FRGs (ISCU, NFS1, MTOR, EIF2S1, HSPA5, AURKA, RPL8) were included in the model and the model was found to have good prognostic value (p < 0.001) in both training and validation groups. The risk score was found to be an independent prognostic factor and the model had good efficacy. Subgroup analysis using clinical parameters demonstrated the general applicability of the model. The nomogram indicated that the model could effectively predict 12-, 36-, and 60-months OS and progression-free interval (PFI). The results showed the presence of more aggressive phenotypes (lower numbers of IDH mutations, higher numbers of EGFR and PTEN mutations, greater infiltration of immune suppressive cells, and higher expression of immune checkpoint inhibitors) in the high-risk group. The signaling pathways enriched closely related to the cell cycle and DNA damage repair. Drug predictions showed that patients with higher risk scores may benefit from treatment with RTK pathway inhibitors, including compounds that inhibit RTKs directly or indirectly by targeting downstream PI3K or MAPK pathways.

Conclusion

In summary, the proposed cancer essential FRG signature predicts survival and treatment response in glioma.
Integrated Multi-Omics Analysis Model to Identify Biomarkers Associated With Prognosis of Breast Cancer
Authors: Fan Yeye , Kao Chunyu , Yang Fu , Wang Fei , Yin Gengshen , Wang Yongjiu , He Yong , Ji Jiadong , Liu Liyuan
Published: June 2022

Background

With the rapid development and wide application of high-throughput sequencing technology, biomedical research has entered the era of large-scale omics data. We aim to identify genes associated with breast cancer prognosis by integrating multi-omics data.

Method

Gene-gene interactions were taken into account, and we applied two differential network methods JDINAC and LGCDG to identify differential genes. The patients were divided into case and control groups according to their survival time. The TCGA and METABRIC database were used as the training and validation set respectively.

Result

In the TCGA dataset, C11orf1, OLA1, RPL31, SPDL1 and IL33 were identified to be associated with prognosis of breast cancer. In the METABRIC database, ZNF273, ZBTB37, TRIM52, TSGA10, ZNF727, TRAF2, TSPAN17, USP28 and ZNF519 were identified as hub genes. In addition, RPL31, TMEM163 and ZNF273 were screened out in both datasets. GO enrichment analysis shows that most of these hub genes were involved in zinc ion binding.

Conclusion

In this study, a total of 15 hub genes associated with long-term survival of breast cancer were identified, which can promote understanding of the molecular mechanism of breast cancer and provide new insight into clinical research and treatment.
Beyond Infections: New Warning Signs for Inborn Errors of Immunity in Children
Authors: Costagliola Giorgio , Peroni Diego G. , Consolini Rita
Published: June 2022

Patients with inborn errors of immunity (IEI) are susceptible to developing a severe infection-related clinical phenotype, but the clinical consequences of immune dysregulation, expressed with autoimmunity, atopy, and lymphoproliferation could represent the first sign in a significant percentage of patients. Therefore, during the diagnostic work-up patients with IEI are frequently addressed to different specialists, including endocrinologists, rheumatologists, and allergologists, often resulting in a delayed diagnosis. In this paper, the most relevant non-infectious manifestations of IEI are discussed. Particularly, we will focus on the potential presentation of IEI with autoimmune cytopenia, non-malignant lymphoproliferation, severe eczema or erythroderma, autoimmune endocrinopathy, enteropathy, and rheumatologic manifestations, including vasculitis and systemic lupus erythematosus. This paper aims to identify new warning signs to suspect IEI and help in the identification of patients presenting with atypical/non-infectious manifestations.