bluuebunny/crossref_metadata_2025 huggingface dataset:
Exopolysaccharide Produced by Probiotic Bacillus albus DM-15 Isolated From Ayurvedic Fermented Dasamoolarishta: Characterization, Antioxidant, and Anticancer Activities
Authors: Vinothkanna Annadurai , Sathiyanarayanan Ganesan , Rai Amit Kumar , Mathivanan Krishnamurthy , Saravanan Kandasamy , Sudharsan Kumaresan , Kalimuthu Palanisamy , Ma Yongkun , Sekar Soundarapandian
Published: March 2022

An exopolysaccharide (EPS) was purified from the probiotic bacterium Bacillus albus DM-15, isolated from the Indian Ayurvedic traditional medicine Dasamoolarishta. Gas chromatography-mass spectrophotometry and nuclear magnetic resonance (NMR) analyses revealed the heteropolymeric nature of the purified EPS with monosaccharide units of glucose, galactose, xylose, and rhamnose. Size-exclusion chromatography had shown the molecular weight of the purified EPS as around 240 kDa. X-ray powder diffraction analysis confirmed the non-crystalline amorphous nature of the EPS. Furthermore, the purified EPS showed the maximum flocculation activity (72.80%) with kaolin clay and emulsification activity (67.04%) with xylene. In addition, the EPS exhibits significant antioxidant activities on DPPH (58.17 ± 0.054%), ABTS (70.47 ± 0.854%) and nitric oxide (58.92 ± 0.744%) radicals in a concentration-dependent way. Moreover, the EPS showed promising cytotoxic activity (20 ± 0.97 μg mL–1) against the lung carcinoma cells (A549), and subsequent cellular staining revealed apoptotic necrotic characters in damaged A549 cells. The EPS purified from the probiotic strain B. albus DM-15 can be further studied and exploited as a potential carbohydrate polymer in food, cosmetic, pharmaceutical, and biomedical applications.
Enolase of Staphylococcus lugdunensis Is a Surface-Exposed Moonlighting Protein That Binds to Extracellular Matrix and the Plasminogen/Plasmin System
Authors: Hussain Muzaffar , Kohler Christian , Becker Karsten
Published: March 2022

The coagulase-negative staphylococcal (CoNS) speciesStaphylococcus lugdunensisis unique in causing serious infections in humans that resemble those ofStaphylococcus aureusrather than those of other CoNS species. The colonization and invasion of host tissue presupposes the presence of adherence factors, but only a few proteins mediating adhesion ofS. lugdunensisto biotic surfaces are known yet. Here, we report on the functionality of theS. lugdunensisenolase (SlEno), which performs two distinct roles, first, as the metabolic enzyme of the glycolysis, and second, as an adherence factor to the extracellular matrix (ECM) of cells. Phylogenetic analyses of the SlEno confirmed their high conservation to enolases of other species and revealed a closer relationship toStaphylococcus epidermidisthan toS. aureus. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry and Western blot experiments, we identified SlEno to be located in the cytoplasm as well as on the cell surface ofS. lugdunensis. Recombinantly generated and surface-associated SlEno showed the usual enolase activity by catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate but, in addition, also displayed strong binding to immobilized laminin, fibronectin, fibrinogen, and collagen type IV in a dose-dependent manner. We also showed a strong binding of SlEno to plasminogen (Plg) and observed a tissue plasminogen activator (tPA)-dependent conversion of Plg to plasmin (Pln) whereby the Plg activation significantly increased in the presence of SlEno. This interaction might be dependent on lysines of the SlEno protein as binding to Plg was inhibited by ε-aminocaproic acid. Furthermore, the enhanced activation of the Plg/Pln system by SlEno enabledS. lugdunensisto migrate through a fibrin matrix. This migration was about 10-fold higher than without exogenously added SlEno. Finally, we observed a significantly higher clearance ofS. lugdunensisby freshly prepared granulocytes and in the presence of anti-SlEno antibodies. In conclusion, these data demonstrate for the first time a moonlighting function of theS. lugdunensisenolase, which is an underrated virulence factor for colonization and invasion of tissues. Hence, SlEno might be a potential vaccine candidate to prevent severe infections caused by this pathogen.
Structure and Function Insight of the α-Glucosidase QsGH13 From Qipengyuania seohaensis sp. SW-135
Authors: Zhai Xingyu , Wu Kaijuan , Ji Rui , Zhao Yiming , Lu Jianhong , Yu Zheng , Xu Xuewei , Huang Jing
Published: March 2022

The α-glucosidases play indispensable roles in the metabolic mechanism of organism, prevention, and treatment of the disease, and sugar hydrolysis, and are widely used in chemical synthesis, clinical diagnosis, and other fields. However, improving their catalytic efficiency and production to meet commercial demand remains a huge challenge. Here we detected a novel GH13 family α-glucosidase, QsGH13, from the deep-sea bacterium Qipengyuania seohaensis sp. SW-135. QsGH13 is highly substrate specific and only hydrolyzes sugars containing alpha-1,4 glucoside bonds. For example, its enzymatic activity for p-nitrophenyl-α-D-glucopyranoside was 25.41 U/mg, and the Km value was 0.2952 ± 0.0322 mM. The biochemical results showed that the optimum temperature of QsGH13 is 45°C, the optimum pH is 10.0, and it has excellent biological characteristics such as alkali resistance and salt resistance. The crystal structure of QsGH13 was resolved with a resolution of 2.2 Å, where QsGH13 is composed of a typical TIM barrel catalytic domain A, a loop-rich domain B, and a conserved domain C. QsGH13 crystal belonged to the monoclinic space group P212121, with unit-cell parameters a = 58.816 Å, b = 129.920 Å, c = 161.307 Å, α = γ = β = 90°, which contains two monomers per asymmetric unit. The β → α loop 4 of QsGH13 was located above catalytic pocket. Typical catalytic triad residues Glu202, Asp266, and Glu329 were found in QsGH13. The biochemical properties and structural analysis of QsGH13 have greatly improved our understanding of the catalytic mechanism of GH13 family. This study provides new ideas to broaden the application of α-glucosidase in alcohol fermentation, glycolysis, and other industries.
Low Subicular Volume as an Indicator of Dementia-Risk Susceptibility in Old Age
Authors: Kagerer Sonja M. , Schroeder Clemens , van Bergen Jiri M. G. , Schreiner Simon J. , Meyer Rafael , Steininger Stefanie C. , Vionnet Laetitia , Gietl Anton F. , Treyer Valerie , Buck Alfred , Pruessmann Klaas P. , Hock Christoph , Unschuld Paul G.
Published: March 2022

Introduction

Hippocampal atrophy is an established Alzheimer’s Disease (AD) biomarker. Volume loss in specific subregions as measurable with ultra-high field magnetic resonance imaging (MRI) may reflect earliest pathological alterations.

Methods

Data from positron emission tomography (PET) for estimation of cortical amyloid β (Aβ) and high-resolution 7 Tesla T1 MRI for assessment of hippocampal subfield volumes were analyzed in 61 non-demented elderly individuals who were divided into risk-categories as defined by high levels of cortical Aβ and low performance in standardized episodic memory tasks.

Results

High cortical Aβ and low episodic memory interactively predicted subicular volume [F(3,57) = 5.90,p= 0.018]. The combination of high cortical Aβ and low episodic memory was associated with significantly lower subicular volumes, when compared to participants with high episodic memory (p= 0.004).

Discussion

Our results suggest that low subicular volume is linked to established indicators of AD risk, such as increased cortical Aβ and low episodic memory. Our data support subicular volume as a marker of dementia-risk susceptibility in old-aged non-demented persons.
Multimodal Magnetic Resonance Imaging Reveals Aberrant Brain Age Trajectory During Youth in Schizophrenia Patients
Authors: Huang Jiayuan , Ke Pengfei , Chen Xiaoyi , Li Shijia , Zhou Jing , Xiong Dongsheng , Huang Yuanyuan , Li Hehua , Ning Yuping , Duan Xujun , Li Xiaobo , Zhang Wensheng , Wu Fengchun , Wu Kai
Published: March 2022

Accelerated brain aging had been widely reported in patients with schizophrenia (SZ). However, brain aging trajectories in SZ patients have not been well-documented using three-modal magnetic resonance imaging (MRI) data. In this study, 138 schizophrenia patients and 205 normal controls aged 20–60 were included and multimodal MRI data were acquired for each individual, including structural MRI, resting state-functional MRI and diffusion tensor imaging. The brain age of each participant was estimated by features extracted from multimodal MRI data using linear multiple regression. The correlation between the brain age gap and chronological age in SZ patients was best fitted by a positive quadratic curve with a peak chronological age of 47.33 years. We used the peak to divide the subjects into a youth group and a middle age group. In the normal controls, brain age matched chronological age well for both the youth and middle age groups, but this was not the case for schizophrenia patients. More importantly, schizophrenia patients exhibited increased brain age in the youth group but not in the middle age group. In this study, we aimed to investigate brain aging trajectories in SZ patients using multimodal MRI data and revealed an aberrant brain age trajectory in young schizophrenia patients, providing new insights into the pathophysiological mechanisms of schizophrenia.
Combined Effect of Co-administration of Stromal Cell-Derived Factor-1 and Granulocyte-Colony Stimulating Factor on Rat Model of Alzheimer’s Disease
Authors: Komaki Alireza , Shahidi Siamak , Hashemi-Firouzi Nasrin , Rafat Zahra , Keymoradzadeh Arman , Golipoor Zoleikha
Published: March 2022

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by amyloid plaque deposits, neuronal cell loss, and memory impairment. Granulocyte-colony stimulating factor (G-CSF) is a growth factor associated with AD improvement. Stromal cell-derived factor-1 (SDF-1) mediates therapeutic effects of G-CSF. This study investigated the effect of combination treatment of G-CSF and SDF-1 on amyloid plaque deposits, apoptosis, and behavior of AD rats.

Methods

Intracerebroventricular amyloid-beta [Aβ(1-42)] peptide was used to induce AD in Aβ rats. There were six groups including naive control, sham-operated, Aβ, Aβ + G-CSF, Aβ + SDF-1, and Aβ + G-CSF + SDF-1. SDF-1 intra-cerebroventricular (ICV), G-CSF Subcutaneous (SC), or a combination of them were administered to Aβ rats weekly for 2 months. The cognition and memory were assessed using the novel object recognition, passive avoidance, and Morris water maze tests. Next, rat brains were removed and the amyloid plaque and apoptosis were detected in the brain and hippocampus using immunohistochemistry and TUNEL assay, respectively.

Results

The amyloid-beta and apoptotic cell levels dropped in groups receiving SDF-1 and G-CSF combination compared to the Aβ group. Also, number of microglial cells increased significantly in the combination group compared to other treatment groups. Moreover, learning and memory were significantly improved in the combination group compared to the Aβ groups (P < 0.05).

Conclusion

SDF-1 and G-CSF combination therapy can offer a promising strategy for AD.
Attention-Guided Multi-Scale Feature Fusion Network for Low-Light Image Enhancement
Authors: Cui HengShuai , Li Jinjiang , Hua Zhen , Fan Linwei
Published: March 2022

Low-light image enhancement has been an important research branch in the field of computer vision. Low-light images are characterized by poor visibility, high noise and low contrast. To improve low-light images generated in low-light environments and night conditions, we propose an Attention-Guided Multi-scale feature fusion network (MSFFNet) for low-light image enhancement for enhancing the contrast and brightness of low-light images. First, to avoid the high cost computation arising from the stacking of multiple sub-networks, our network uses a single encoder and decoder for multi-scale input and output images. Multi-scale input images can make up for the lack of pixel information and loss of feature map information caused by a single input image. The multi-scale output image can effectively monitor the error loss in the image reconstruction process. Second, the Convolutional Block Attention Module (CBAM) is introduced in the encoder part to effectively suppress the noise and color difference generated during feature extraction and further guide the network to refine the color features. Feature calibration module (FCM) is introduced in the decoder section to enhance the mapping expression between channels. Attention fusion module (AFM) is also added to capture contextual information, which is more conducive to recovering image detail information. Last, the cascade fusion module (CFM) is introduced to effectively combine the feature map information under different perceptual fields. Sufficient qualitative and quantitative experiments have been conducted on a variety of publicly available datasets, and the proposed MSFFNet outperforms other low-light enhancement methods in terms of visual effects and metric scores.
Disrupted Cerebellar-Default Mode Network Functional Connectivity in Major Depressive Disorder With Gastrointestinal Symptoms
Authors: Ding Yudan , Ou Yangpan , Yan Haohao , Fu Xiaoya , Yan Meiqi , Li Huabing , Liu Feng , Guo Wenbin
Published: March 2022

Gastrointestinal (GI) symptoms are one of the common somatic symptoms presented in patients with major depressive disorder (MDD). Higher frequency of GI symptoms and higher GI symptom burden were linked to greater depression severity and increased risk of suicide ideation. However, few studies have explored the underlying mechanisms of GI symptoms in MDD. Based on previous studies, the cerebellar-DMN circuits may play a potentially critical role in GI symptoms comorbid with depression. Fifty-two first-episode drug-naive patients with MDD (35 with GI symptoms and 17 without GI symptoms) and 28 matched healthy controls were recruited in the current study and underwent resting-state functional magnetic resonance imaging scan. Cerebellar seed-based functional connectivity maps were established. Relative to depressed patients without GI symptoms, significantly increased cerebellar-anterior default mode network (DMN) connectivities were found in those with GI symptoms. Both increased and decreased functional connectivities were found between cerebellum and posterior DMN in patients with GI symptoms compared with those without GI symptoms and healthy controls. Moreover, the right Crus I - right superior temporal gyrus connectivity value was related to severity of GI symptoms and depression in all patients with MDD. The support vector machine analysis demonstrated a satisfactory classification accuracy (89%) of the disrupted cerebellar-DMN connectivities for correctly identifying MDD patients with GI symptoms. These results revealed the possible neural mechanisms for the involvement of cerebellar-DMN circuits in GI symptoms co-occurred with MDD.
Explosive Synchronization-Based Brain Modulation Reduces Hypersensitivity in the Brain Network: A Computational Model Study
Authors: Kim MinKyung , Harris Richard E. , DaSilva Alexandre F. , Lee UnCheol
Published: March 2022

Fibromyalgia (FM) is a chronic pain condition that is characterized by hypersensitivity to multimodal sensory stimuli, widespread pain, and fatigue. We have previously proposed explosive synchronization (ES), a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition, as a potential mechanism of the hypersensitive FM brain. Therefore, we hypothesized that converting a brain network from ES to general synchronization (GS) may reduce the hypersensitivity of FM brain. To find an effective brain network modulation to convert ES into GS, we constructed a large-scale brain network model near criticality (i.e., an optimally balanced state between order and disorders), which reflects brain dynamics in conscious wakefulness, and adjusted two parameters: local structural connectivity and signal randomness of target brain regions. The network sensitivity to global stimuli was compared between the brain networks before and after the modulation. We found that only increasing the local connectivity of hubs (nodes with intense connections) changes ES to GS, reducing the sensitivity, whereas other types of modulation such as decreasing local connectivity, increasing and decreasing signal randomness are not effective. This study would help to develop a network mechanism-based brain modulation method to reduce the hypersensitivity in FM.
Nitrate Metabolism and Ischemic Cerebrovascular Disease: A Narrative Review
Authors: Wang Yicong , Chen Weiqi , Zhou Jian , Wang Yongjun , Wang Hao , Wang Yilong
Published: March 2022

Inorganic and organic nitrates are present in vivo and in vitro. Inorganic nitrate is considered a pool of nitric oxide (NO), but it can be converted into nitrite and NO through various mechanisms. It plays an important role in the regulation of complex physiological and biochemical reactions, such as anti-inflammatory processes and the inhibition of platelet aggregation, which are closely related to the pathology and treatment of cerebrovascular disease. Ischemic cerebrovascular disease is characterized by high incidence, recurrence, and disability rates. Nitrate, nitrite, and NO were recently found to be involved in cerebrovascular disease. In this review, we describe the relationship between cerebrovascular disease and nitrate metabolism to provide a basis for further advances in laboratory and clinical medicine.
Brain Functional Topology Alteration in Right Lateral Occipital Cortex Is Associated With Upper Extremity Motor Recovery
Authors: Huang Qianqian , Lin Dinghong , Huang Shishi , Cao Yungang , Jin Yun , Wu Bo , Fan Linyu , Tu Wenzhan , Huang Lejian , Jiang Songhe
Published: March 2022

Stroke is a chief cause of sudden brain damage that severely disrupts the whole-brain network. However, the potential mechanisms of motor recovery after stroke are uncertain and the prognosis of poststroke upper extremity recovery is still a challenge. This study investigated the global and local topological properties of the brain functional connectome in patients with subacute ischemic stroke and their associations with the clinical measurements. A total of 57 patients, consisting of 29 left-sided and 28 right-sided stroke patients, and 32 age- and gender-matched healthy controls (HCs) were recruited to undergo a resting-state functional magnetic resonance imaging (rs-fMRI) study; patients were also clinically evaluated with the Upper Extremity Fugl-Meyer Assessment (FMA_UE). The assessment was repeated at 15 weeks to assess upper extremity functional recovery for the patient remaining in the study (12 left- 20 right-sided stroke patients). Global graph topological disruption indices of stroke patients were significantly decreased compared with HCs but these indices were not significantly associated with FMA_UE. In addition, local brain network structure of stroke patients was altered, and the altered regions were dependent on the stroke site. Significant associations between local degree and motor performance and its recovery were observed in the right lateral occipital cortex (R LOC) in the right-sided stroke patients. Our findings suggested that brain functional topologies alterations in R LOC are promising as prognostic biomarkers for right-sided subacute stroke. This cortical area might be a potential target to be further validated for non-invasive brain stimulation treatment to improve poststroke upper extremity recovery.
Added Value of Arterial Spin Labeling in Detecting Posterior Reversible Encephalopathy Syndrome as a Stroke Mimic on Baseline Neuroimaging: A Single Center Experience
Authors: Weinstein Joseph D. , Hamam Omar , Urrutia Victor C. , Lu Hanzhang , Luna Licia P. , Tekes-Brady Aylin , Bahouth Mona , Yedavalli Vivek
Published: March 2022

Differentiating stroke from stroke mimics is a diagnostic challenge in every day practice. Posterior Reversible Encephalopathy Syndrome (PRES) is an important stroke mimic with nonspecific symptomatology, making prompt and accurate diagnosis challenging. Baseline neuroimaging plays a pivotal role in detection and differentiation of stroke from many common mimics and is thus critical in guiding appropriate management. In particular, MR perfusion (MRP) imaging modalities provide added value through detection and quantification of multiple physiological parameters. Arterial Spin Labeling (ASL) is a non-contrast, noninvasive MRP technique increasingly used in clinical practice; however, there is limited description of ASL in PRES in the existing literature. In this single center retrospective pilot study, we investigate the added value of ASL in detecting PRES in the largest series to date. We hope this study can serve as the basis for larger scale investigations exploring the utility of ASL in detecting stroke mimics such as PRES for accurate and efficient management of such patients.
Minimally Invasive Surgery for ICH Evacuation Combined With Deferoxamine Treatment Increased Perihematomal Claudin-5 and ZO-1 Expression Levels and Decreased BBB Permeability in Rabbits
Authors: Ren Siying , Han Shanshan , Wang Likun , Huang Yuanxin , Wu Jing , Wu Guofeng
Published: March 2022

Objective

To investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.

Methods

We randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.

Results

Purdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.

Conclusions

MIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.
A Predictive Coding Framework for Understanding Major Depression
Authors: Gilbert Jessica R. , Wusinich Christina , Zarate Carlos A.
Published: March 2022

Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These “priors” serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling. Accumulating evidence also suggests that depression is characterized by impaired local and long-range prediction signaling across multiple sensory domains. This review highlights the electrophysiological and neuroimaging evidence for disrupted predictive processing in depression. The discussion is framed around the manner in which disrupted generative predictions about the sensorium could lead to depressive symptomatology, including anhedonia and negative bias. In particular, the review focuses on studies of sensory deviance detection and reward processing, highlighting research evidence for both disrupted generative predictions and prediction error signaling in depression. The role of the monoaminergic and glutamatergic systems in predictive coding processes is also discussed. This review provides a novel framework for understanding depression using predictive coding principles and establishes a foundational roadmap for potential future research.
Spatio-Temporal Brain Dynamic Differences in Fluid Intelligence
Authors: Tschentscher Nadja , Sauseng Paul
Published: March 2022

Human fluid intelligence is closely linked to the sequential solving of complex problems. It has been associated with a distributed cognitive control or multiple-demand (MD) network, comprising regions of lateral frontal, insular, dorsomedial frontal, and parietal cortex. Previous neuroimaging research suggests that the MD network may orchestrate the allocation of attentional resources to individual parts of a complex task: in a complex target detection task with multiple independent rules, applied one at a time, reduced response to rule-critical events across the MD network in lower fluid intelligence was observed. This was in particular the case with increasing task complexity (i.e., larger sets of rules), and was accompanied by impairment in performance. Here, we examined the early spatiotemporal neural dynamics of this process in electroencephalography (EEG) source analyses using a similar task paradigm. Levels of fluid intelligence specifically predicted early neural responses in a left inferiorparietal MD region around 200–300 ms post stimulus onset. Evoked source amplitudes in left parietal cortex within this early time window also correlated with behavioural performance measures. Like in previous research, we observed impaired performance in lower fluid intelligence with increasing number of task rules. This links fluid intelligence to a process of attentional focus on those parts of a task that are most critical for the current behaviour. Within the MD system, our time re-resolved measures suggest that the left parietal cortex specifically impacts on early processes of attentional focus on task critical features. This is novel evidence on the neurocognitive correlates of fluid intelligence suggesting that individual differences are critically linked to an early process of attentional focus on task-relevant information, which is supported by left parietal MD regions.
Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication
Authors: Tokariev Anton , Oberlander Victoria C. , Videman Mari , Vanhatalo Sampsa
Published: March 2022

Up to five percent of human infants are exposed to maternal antidepressant medication by serotonin reuptake inhibitors (SRI) during pregnancy, yet the SRI effects on infants’ early neurodevelopment are not fully understood. Here, we studied how maternal SRI medication affects cortical frequency-specific and cross-frequency interactions estimated, respectively, by phase-phase correlations (PPC) and phase-amplitude coupling (PAC) in electroencephalographic (EEG) recordings. We examined the cortical activity in infants after fetal exposure to SRIs relative to a control group of infants without medical history of any kind. Our findings show that the sleep-related dynamics of PPC networks are selectively affected by in utero SRI exposure, however, those alterations do not correlate to later neurocognitive development as tested by neuropsychological evaluation at two years of age. In turn, phase-amplitude coupling was found to be suppressed in SRI infants across multiple distributed cortical regions and these effects were linked to their neurocognitive outcomes. Our results are compatible with the overall notion that in utero drug exposures may cause subtle, yet measurable changes in the brain structure and function. Our present findings are based on the measures of local and inter-areal neuronal interactions in the cortex which can be readily used across species, as well as between different scales of inspection: from the whole animals to in vitro preparations. Therefore, this work opens a framework to explore the cellular and molecular mechanisms underlying neurodevelopmental SRI effects at all translational levels.
Integrated Positron Emission Tomography/Magnetic Resonance Imaging for Resting-State Functional and Metabolic Imaging in Human Brain: What Is Correlated and What Is Impacted
Authors: Shan Yi , Wang Zhe , Song Shuangshuang , Xue Qiaoyi , Ge Qi , Yang Hongwei , Cui Bixiao , Zhang Miao , Zhou Yun , Lu Jie
Published: March 2022

Integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) could simultaneously obtain both functional MRI (fMRI) and 18F-fluorodeoxyglucose (FDG) PET and thus provide multiparametric information for the analysis of brain metabolism. In this study, we aimed to, for the first time, investigate the interplay of simultaneous fMRI and FDG PET scan using a randomized self-control protocol. In total, 24 healthy volunteers underwent PET/MRI scan for 30–40 min after the injection of FDG. A 22-min brain scan was separated into MRI-off mode (without fMRI pulsing) and MRI-on mode (with fMRI pulsing), with each one lasting for 11 min. We calculated the voxel-wise fMRI metrics (regional homogeneity, amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, and degree centrality), resting networks, relative standardized uptake value ratios (SUVr), SUVr slope, and regional cerebral metabolic rate of glucose (rCMRGlu) maps. Paired two-sample t-tests were applied to assess the statistical differences between SUVr, SUVr slope, correlation coefficients of fMRI metrics, and rCMRGlu between MRI-off and MRI-on modes, respectively. The voxel-wise whole-brain SUVr revealed no statistical difference (P > 0.05), while the SUVr slope was significantly elevated in sensorimotor, dorsal attention, ventral attention, control, default, and auditory networks (P < 0.05) during fMRI scan. The task-based group independent-component analysis revealed that the most active network components derived from the combined MRI-off and MRI-on static PET images were frontal pole, superior frontal gyrus, middle temporal gyrus, and occipital pole. High correlation coefficients were found among fMRI metrics with rCMRGlu in both MRI-off and MRI-on mode (P < 0.05). Our results systematically evaluated the impact of simultaneous fMRI scan on the quantification of human brain metabolism from an integrated PET/MRI system.
How Does the Central Nervous System for Posture and Locomotion Cope With Damage-Induced Neural Asymmetry?
Authors: Le Ray Didier , Guayasamin Mathias
Published: March 2022

In most vertebrates, posture and locomotion are achieved by a biomechanical apparatus whose effectors are symmetrically positioned around the main body axis. Logically, motor commands to these effectors are intrinsically adapted to such anatomical symmetry, and the underlying sensory-motor neural networks are correspondingly arranged during central nervous system (CNS) development. However, many developmental and/or life accidents may alter such neural organization and acutely generate asymmetries in motor operation that are often at least partially compensated for over time. First, we briefly present the basic sensory-motor organization of posturo-locomotor networks in vertebrates. Next, we review some aspects of neural plasticity that is implemented in response to unilateral central injury or asymmetrical sensory deprivation in order to substantially restore symmetry in the control of posturo-locomotor functions. Data are finally discussed in the context of CNS structure-function relationship.
Determination of Tropomyosin in Shrimp and Crab by Liquid Chromatography–Tandem Mass Spectrometry Based on Immunoaffinity Purification
Authors: Fan Sufang , Ma Junmei , Li Chunsheng , Wang Yanbo , Zeng Wen , Li Qiang , Zhou Jinru , Wang Liming , Wang Yi , Zhang Yan
Published: March 2022

A UPLC-MS/MS method was developed for the detection of tropomyosin (TM) in shrimp and crab. After simple extraction, the samples were purified by immunoaffinity column and then digested by trypsin. The obtained sample was separated by Easy-nLC 1000-Q Exactive. The obtained spectrums were analyzed by Thermo Proteome Discoverer 1.4 software and then ANIQLVEK with high sensitivity was selected as the quantitative signature peptide. Isotope-labeled internal standard was used in the quantitative analysis. The method showed good linearity in the range of 5–5,000 μg/L with a limit of quantification (LOQ) of 0.1 mg/kg. The average recoveries were 77.22–95.66% with RSDs ≤ 9.97%, and the matrix effects were between 88.53 and 112.60%. This method could be used for rapid screening and quantitative analysis of TM in shrimp and crab. Thus, it could provide technical support for self-testing of TM by food manufacturers and promote further improvement of allergen labeling in China.
Potential Role of APEX1 During Ferroptosis
Authors: Guo Nan , Chen Yan , Zhang Yuhong , Deng Yonghao , Zeng Fancai , Li Xiang
Published: March 2022

Ferroptosis is a recently discovered category of programmed cell death. It is much different from other types of cell death such as apoptosis, necrosis and autophagy. The main pathological feature of ferroptosis is the accumulation of iron-dependent lipid peroxidation. The typical changes in the morphological features of ferroptosis include cell volume shrinkage and increased mitochondrial membrane area. The mechanisms of ferroptosis may be mainly related to lipid peroxidation accumulation, imbalance in amino acid antioxidant system, and disturbance of iron metabolism. Besides, hypoxia-inducible factor (HIF), nuclear factor-E2-related factor 2 (Nrf2), and p53 pathway have been demonstrated to be involved in ferroptosis. At present, the molecular mechanisms of ferroptosis pathway are still unmapped. In this review, an outlook has been put forward about the crucial role of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) in the regulation of ferroptosis. APEX1 plays an important role in the regulation of intracellular redox balance and can be used as a potential inhibitor of ferroptotic cell death. Bioinformatics analysis indicated that the mRNA level of APEX1 is decreased in cases of ferroptosis triggered by erastin. Besides, it was found that there was a significant correlation between APEX1 and genes in the ferroptosis pathway. We have discussed the possibility to employ APEX1 inducers or inhibitors in the regulation of ferroptosis as a new strategy for the treatment of various human diseases.
The Development of AXL Inhibitors in Lung Cancer: Recent Progress and Challenges
Authors: Sang Yun Beom , Kim Joo-Hang , Kim Chang-Gon , Hong Min Hee , Kim Hye Ryun , Cho Byoung Chul , Lim Sun Min
Published: March 2022

AXL, along with MER and TYRO3, is a receptor tyrosine kinase from the TAM family. Although AXL itself is not thought to be a potent oncogenic driver, overexpression of AXL is known to trigger tumor cell growth, survival, invasion, metastasis, angiogenesis, epithelial to mesenchymal transition, and immune suppression. Overexpression of AXL is associated with therapy resistance and poor prognosis. Therefore, it is being studied as a marker of prognosis in cancer treatment or as a target in various cancer types. Recently, many preclinical and clinical studies on agents with various mechanisms targeting AXL have been actively conducted. They include small molecule inhibitors, monoclonal antibodies, and antibody-drug conjugates. This article reviewed the fundamental role of AXL in solid tumors, and the development in research of AXL inhibitors in recent years. Emphasis was placed on the function of AXL in acquired therapy resistance in patients with non-small cell lung cancer (NSCLC). Since clinical needs increase in NSCLC patients with acquired resistance after initial therapy, recent research efforts have focused on a combination treatment with AXL inhibitors and tyrosine kinase inhibitors or immunotherapy to overcome resistance. Lastly, we deal with challenges and limitations encountered in the development of AXL inhibitors.
Integration of MRI-Based Radiomics Features, Clinicopathological Characteristics, and Blood Parameters: A Nomogram Model for Predicting Clinical Outcome in Nasopharyngeal Carcinoma
Authors: Fang Zeng-Yi , Li Ke-Zhen , Yang Man , Che Yu-Rou , Luo Li-Ping , Wu Zi-Fei , Gao Ming-Quan , Wu Chuan , Luo Cheng , Lai Xin , Zhang Yi-Yao , Wang Mei , Xu Zhu , Li Si-Ming , Liu Jie-Ke , Zhou Peng , Wang Wei-Dong
Published: March 2022

Purpose

This study aimed to develop a nomogram model based on multiparametric magnetic resonance imaging (MRI) radiomics features, clinicopathological characteristics, and blood parameters to predict the progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC).

Methods

A total of 462 patients with pathologically confirmed nonkeratinizing NPC treated at Sichuan Cancer Hospital were recruited from 2015 to 2019 and divided into training and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used for radiomics feature dimension reduction and screening in the training cohort. Rad-score, age, sex, smoking and drinking habits, Ki-67, monocytes, monocyte ratio, and mean corpuscular volume were incorporated into a multivariate Cox proportional risk regression model to build a multifactorial nomogram. The concordance index (C-index) and decision curve analysis (DCA) were applied to estimate its efficacy.

Results

Nine significant features associated with PFS were selected by LASSO and used to calculate the rad-score of each patient. The rad-score was verified as an independent prognostic factor for PFS in NPC. The survival analysis showed that those with lower rad-scores had longer PFS in both cohorts (p < 0.05). Compared with the tumor–node–metastasis staging system, the multifactorial nomogram had higher C-indexes (training cohorts: 0.819 vs. 0.610; validation cohorts: 0.820 vs. 0.602). Moreover, the DCA curve showed that this model could better predict progression within 50% threshold probability.

Conclusion

A nomogram that combined MRI-based radiomics with clinicopathological characteristics and blood parameters improved the ability to predict progression in patients with NPC.
Please Place Your Seat in the Full Upright Position: A Technical Framework for Landing Upright Radiation Therapy in the 21st Century
Authors: Hegarty Sarah , Hardcastle Nicholas , Korte James , Kron Tomas , Everitt Sarah , Rahim Sulman , Hegi-Johnson Fiona , Franich Rick
Published: March 2022

Delivering radiotherapy to patients in an upright position can allow for increased patient comfort, reduction in normal tissue irradiation, or reduction of machine size and complexity. This paper gives an overview of the requirements for the delivery of contemporary arc and modulated radiation therapy to upright patients. We explore i) patient positioning and immobilization, ii) simulation imaging, iii) treatment planning and iv) online setup and image guidance. Treatment chairs have been designed to reproducibly position seated patients for treatment and can be augmented by several existing immobilisation systems or promising emerging technologies such as soft robotics. There are few solutions for acquiring CT images for upright patients, however, cone beam computed tomography (CBCT) scans of upright patients can be produced using the imaging capabilities of standard Linacs combined with an additional patient rotation device. While these images will require corrections to make them appropriate for treatment planning, several methods indicate the viability of this approach. Treatment planning is largely unchanged apart from translating gantry rotation to patient rotation, allowing for a fixed beam with a patient rotating relative to it. Rotation can be provided by a turntable during treatment delivery. Imaging the patient with the same machinery as used in treatment could be advantageous for online plan adaption. While the current focus is using clinical linacs in existing facilities, developments in this area could also extend to lower-cost and mobile linacs and heavy ion therapy.
Deep Learning Model for Intracranial Hemangiopericytoma and Meningioma Classification
Authors: Chen Ziyan , Ye Ningrong , Jiang Nian , Yang Qi , Wanggou Siyi , Li Xuejun
Published: March 2022

Background

Intracranial hemangiopericytoma/solitary fibrous tumor (SFT/HPC) is a rare type of neoplasm containing malignancies of infiltration, peritumoral edema, bleeding, or bone destruction. However, SFT/HPC has similar radiological characteristics as meningioma, which had different clinical managements and outcomes. This study aims to discriminate SFT/HPC and meningioma via deep learning approaches based on routine preoperative MRI.

Methods

We enrolled 236 patients with histopathological diagnosis of SFT/HPC (n = 144) and meningioma (n = 122) from 2010 to 2020 in Xiangya Hospital. Radiological features were extracted manually, and a radiological diagnostic model was applied for classification. And a deep learning pretrained model ResNet-50 was adapted to train T1-contrast images for predicting tumor class. Deep learning model attention mechanism was visualized by class activation maps.

Results

Our study reports that SFT/HPC was found to have more invasion to venous sinus (p = 0.001), more cystic components (p < 0.001), and more heterogeneous enhancement patterns (p < 0.001). Deep learning model achieved a high classification accuracy of 0.889 with receiver-operating characteristic curve area under the curve (AUC) of 0.91 in the validation set. Feature maps showed distinct clustering of SFT/HPC and meningioma in the training and test cohorts, respectively. And the attention of the deep learning model mainly focused on the tumor bulks that represented the solid texture features of both tumors for discrimination.
Treatment-Free Remission in Chronic Myeloid Leukemia Patients Treated With Low-Dose TKIs: A Feasible Option Also in the Real-Life. A Campus CML Study
Authors: Iurlo Alessandra , Cattaneo Daniele , Artuso Silvia , Consonni Dario , Abruzzese Elisabetta , Binotto Gianni , Bocchia Monica , Bonifacio Massimiliano , Castagnetti Fausto , Galimberti Sara , Gozzini Antonella , Iezza Miriam , Latagliata Roberto , Luciano Luigiana , Maggi Alessandro , Miggiano Maria Cristina , Pregno Patrizia , Rege-Cambrin Giovanna , Russo Sabina , Scortechini Anna Rita , Tafuri Agostino , Tiribelli Mario , Fava Carmen , Rosti Gianantonio , Foa Robin , Breccia Massimo , Saglio Giuseppe
Published: March 2022

Treatment-free remission (TFR) has become a primary therapeutic goal in CML and is also considered feasible by international guidelines. TKIs dose reduction is often used in real-life practice to reduce adverse events, although its impact on TFR is still a matter of debate. This study aimed to explore the attitude of Italian hematologists towards prescribing TKIs at reduced doses and its impact on TFR. In September 2020, a questionnaire was sent to 54 hematology centers in Italy participating to the Campus CML network. For each patient, data on the main disease characteristics were collected. Most of the hematologists involved (64.4%) believed that low-dose TKIs should not influence TFR. Indeed, this approach was offered to 194 patients. At the time of TFR, all but 3 patients had already achieved a DMR, with a median duration of 61.0 months. After a median follow-up of 29.2 months, 138 (71.1%) patients were still in TFR. Interestingly, TFR outcome was not impaired by any of the variables examined, including sex, risk scores, BCR-ABL1 transcript types, previous interferon, type and number of TKIs used before treatment cessation, degree of DMR or median duration of TKIs therapy. On the contrary, TFR was significantly better after dose reduction due to AEs; furthermore, patients with a longer DMR duration showed a trend towards prolonged TFR. This survey indicates that low-dose TKI treatment is an important reality. While one third of Italian hematologists still had some uncertainties on TFR feasibility after using reduced doses of TKIs outside of clinical trials, TFR has often been considered a safe option even in patients treated with low-dose TKIs in the real-life setting. It should be noted that only 28.9% of our cases had a molecular recurrence, less than reported during standard dose treatment. Consequently, TFR is not impaired using low-dose TKIs.
The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin
Authors: Vogeley Christian , Rolfes Katharina M. , Krutmann Jean , Haarmann-Stemmann Thomas
Published: March 2022

Cutaneous squamous cell carcinoma (SCC) is one of the most frequent malignancies in humans and academia as well as public authorities expect a further increase of its incidence in the next years. The major risk factor for the development of SCC of the general population is the repeated and unprotected exposure to ultraviolet (UV) radiation. Another important risk factor, in particular with regards to occupational settings, is the chronic exposure to polycyclic aromatic hydrocarbons (PAH) which are formed during incomplete combustion of organic material and thus can be found in coal tar, creosote, bitumen and related working materials. Importantly, both exposomal factors unleash their carcinogenic potential, at least to some extent, by activating the aryl hydrocarbon receptor (AHR). The AHR is a ligand-dependent transcription factor and key regulator in xenobiotic metabolism and immunity. The AHR is expressed in all cutaneous cell-types investigated so far and maintains skin integrity. We and others have reported that in response to a chronic exposure to environmental stressors, in particular UV radiation and PAHs, an activation of AHR and downstream signaling pathways critically contributes to the development of SCC. Here, we summarize the current knowledge about AHR’s role in skin carcinogenesis and focus on its impact on defense mechanisms, such as DNA repair, apoptosis and anti-tumor immune responses. In addition, we discuss the possible consequences of a simultaneous exposure to different AHR-stimulating environmental factors for the development of cutaneous SCC.