bluuebunny/crossref_metadata_2025 huggingface dataset:
A computational model of learning flexible navigation in a maze by layout-conforming replay of place cells
Authors: Gao Yuanxiang
Published: February 2023

Recent experimental observations have shown that the reactivation of hippocampal place cells (PC) during sleep or wakeful immobility depicts trajectories that can go around barriers and can flexibly adapt to a changing maze layout. However, existing computational models of replay fall short of generating such layout-conforming replay, restricting their usage to simple environments, like linear tracks or open fields. In this paper, we propose a computational model that generates layout-conforming replay and explains how such replay drives the learning of flexible navigation in a maze. First, we propose a Hebbian-like rule to learn the inter-PC synaptic strength during exploration. Then we use a continuous attractor network (CAN) with feedback inhibition to model the interaction among place cells and hippocampal interneurons. The activity bump of place cells drifts along paths in the maze, which models layout-conforming replay. During replay in sleep, the synaptic strengths from place cells to striatal medium spiny neurons (MSN) are learned by a novel dopamine-modulated three-factor rule to store place-reward associations. During goal-directed navigation, the CAN periodically generates replay trajectories from the animal's location for path planning, and the trajectory leading to a maximal MSN activity is followed by the animal. We have implemented our model into a high-fidelity virtual rat in the MuJoCo physics simulator. Extensive experiments have demonstrated that its superior flexibility during navigation in a maze is due to a continuous re-learning of inter-PC and PC-MSN synaptic strength.
Toward neural health measurements for cochlear implantation: The relationship among electrode positioning, the electrically evoked action potential, impedances and behavioral stimulation levels
Authors: Lambriks Lars , van Hoof Marc , Debruyne Joke , Janssen Miranda , Hof Janny , Hellingman Katja , Devocht Elke , George Erwin
Published: February 2023

Introduction

Estimating differences in neural health across different sites within the individual cochlea potentially enables clinical applications for subjects with a cochlear implant. The electrically evoked compound action potential (ECAP) is a measure of neural excitability that possibly provides an indication of a neural condition. There are many factors, however, that affect this measure and increase the uncertainty of its interpretation. To better characterize the ECAP response, its relationship with electrode positioning, impedances, and behavioral stimulation levels was explored.

Methods

A total of 14 adult subjects implanted with an Advanced Bionics cochlear electrode array were prospectively followed up from surgery to 6 months postoperative. Insertion depth, distance to the modiolus, and distance to the medial wall were assessed for each electrode by postoperative CT analysis. ECAPs were measured intraoperatively and at three visits postoperatively on all 16 electrodes using the NRI feature of clinical programming software and characterized using multiple parameters. Impedances and behavioral stimulation levels were measured at every fitting session.

Results

Patterns in ECAPs and impedances were consistent over time, but high variability existed among subjects and between different positions in the cochlea. Electrodes located closer to the apex of the cochlea and closer to the modiolus generally showed higher neural excitation and higher impedances. Maximum loudness comfort levels were correlated strongly with the level of current needed to elicit a response of 100 μV ECAP.

Conclusion

Multiple factors contribute to the ECAP response in subjects with a cochlear implant. Further research might address whether the ECAP parameters used in this study will benefit clinical electrode fitting or the assessment of auditory neuron integrity.
A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol
Authors: Zhao Jia-ling , Ai Chi-bo , Wang Li , Yang Shao-jie , Wang Jian , Yang Wei , Tang Jie , Zhang Ling , Li Yan , Yan Ting-qi , Gou Shu , Xie Gui-gui , Xiang Yang
Published: February 2023

Background

Low serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs.

Aim

The Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs.

Methods and design

This is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China.

Outcomes

CHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up.

Discussion

The primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice.

Clinical trial registration

Clinicaltrials.gov, identifier: NCT05589454.
Research progress in extracorporeal shock wave therapy for upper limb spasticity after stroke
Authors: Duan Haoyang , Lian Yawen , Jing Yuling , Xing Jingsong , Li Zhenlan
Published: February 2023

Spasticity is one of the most common complications after stroke. With the gradual intensification of spasticity, stroke patients will have a series of problems such as joint ankylosis and movement restriction, which affect the daily activities and increase the burden on patients' families, medical staff and society. There are many ways to treat post-stroke spasticity before, including physical therapy and exercise therapy, drug therapy, surgery and so on, but not satisfied because of a few shortcomings. In recent years, many researchers have applied extracorporeal shock wave therapy (ESWT) for the treatment of post-stroke spasm and achieved good clinical effect, because it is non-invasive, safe, easy to operate, low cost and other advantages compared with other treatment methods. This article reviews the research progress and existing problems of ESWT in the treatment of post-stroke spasticity.
Case report: Compound heterozygous NUP85 variants cause autosomal recessive primary microcephaly
Authors: Ravindran Ethiraj , Lesca Gaetan , Januel Louis , Goldgruber Linus , Dickmanns Achim , Margot Henri , Kaindl Angela M.
Published: February 2023

Nucleoporin (NUP) 85 is a member of the Y-complex of nuclear pore complex (NPC) that is key for nucleocytoplasmic transport function, regulation of mitosis, transcription, and chromatin organization. Mutations in various nucleoporin genes have been linked to several human diseases. Among them, NUP85 was linked to childhood-onset steroid-resistant nephrotic syndrome (SRNS) in four affected individuals with intellectual disability but no microcephaly. Recently, we broaden the phenotype spectrum of NUP85-associated disease by reporting NUP85 variants in two unrelated individuals with primary autosomal recessive microcephaly (MCPH) and Seckel syndrome (SCKS) spectrum disorders (MCPH-SCKS) without SRNS. In this study, we report compound heterozygous NUP85 variants in an index patient with only MCPH phenotype, but neither Seckel syndrome nor SRNS was reported. We showed that the identified missense variants cause reduced cell viability of patient-derived fibroblasts. Structural simulation analysis of double variants is predicted to alter the structure of NUP85 and its interactions with neighboring NUPs. Our study thereby further expands the phenotypic spectrum of NUP85-associated human disorder and emphasizes the crucial role of NUP85 in the brain development and function.
Cognitive and motor cortex activation during robot-assisted multi-sensory interactive motor rehabilitation training: An fNIRS based pilot study
Authors: Zheng Jinyu , Ma Qiqi , He Wanying , Huang Yanping , Shi Ping , Li Sujiao , Yu Hongliu
Published: February 2023

Objective

This study aimed to evaluate the effects of multiple virtual reality (VR) interaction modalities based on force-haptic feedback combined with visual or auditory feedback in different ways on cerebral cortical activation by functional near-infrared spectroscopy (fNIRS). Methods: A modular multi-sensory VR interaction system based on a planar upper-limb rehabilitation robot was developed. Twenty healthy participants completed active elbow flexion and extension training in four VR interaction patterns, including haptic (H), haptic + auditory (HA), haptic + visual (HV), and haptic + visual + auditory (HVA). Cortical activation changes in the sensorimotor cortex (SMC), premotor cortex (PMC), and prefrontal cortex (PFC) were measured.

Results

Four interaction patterns all had significant activation effects on the motor and cognitive regions of the cerebral cortex (p < 0.05). Among them, in the HVA interaction mode, the cortical activation of each ROI was the strongest, followed by HV, HA, and H. The connectivity between channels of SMC and bilateral PFC, as well as the connectivity between channels in PMC, was the strongest under HVA and HV conditions. Besides, the two-way ANOVA of visual and auditory feedback showed that it was difficult for auditory feedback to have a strong impact on activation without visual feedback. In addition, under the condition of visual feedback, the effect of fusion auditory feedback on the activation degree was significantly higher than that of no auditory feedback.

Conclusions

The interaction mode of visual, auditory, and haptic multi-sensory integration is conducive to stronger cortical activation and cognitive control. Besides, there is an interaction effect between visual and auditory feedback, thus improving the cortical activation level. This research enriches the research on activation and connectivity of cognitive and motor cortex in the process of modular multi-sensory interaction training of rehabilitation robots. These conclusions provide a theoretical basis for the optimal design of the interaction mode of the rehabilitation robot and the possible scheme of clinical VR rehabilitation.
Effects of whole-body vibration training on cognitive function: A systematic review
Authors: Wen Jiayi , Leng Lu , Hu Min , Hou Xiaohui , Huang Junhao
Published: February 2023

Background

Whole-body vibration (WBV) training is a novel training method that stimulates the human neuromuscular system by the use of vibration, the frequency and amplitude of which are controlled, thereby inducing adaptive changes in the body. WBV training is widely used as a clinical prevention and rehabilitation tool in physical medicine and neuro-rehabilitation as a clinical prevention and rehabilitation tool.

Objectives

The aim of the present study was to review the effects of WBV on cognitive function, provide an evidence-based foundation for future research on WBV training, and promote additional popularization and use of the methodology in clinical practice.

Methods

A systematic review of articles extracted from the following six databases was conducted: PubMed, Web of Science, China National Knowledge Infrastructure, Embase, Cochrane, and Scopus. A literature search was performed on articles in which the effects of WBV on cognitive function were evaluated.

Results

Initially, a total of 340 studies were initially identified, among which 18 articles that satisfied the inclusion criteria were selected for inclusion in the systematic review. Participants were allocated into two groups: patients with cognitive impairment and healthy individuals. The results demonstrated that WBV was both positive and ineffective in its influence on cognitive function.

Conclusion

The majority of studies suggested that WBV may be a useful strategy for the management of cognitive impairment and should be considered for inclusion in rehabilitation programs. However, the impact of WBV on cognition requires additional, larger, and adequately powered studies.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=376821, identifier CRD42022376821.
Investigating brain cortical activity in patients with post-COVID-19 brain fog
Authors: Wojcik Grzegorz M. , Shriki Oren , Kwasniewicz Lukasz , Kawiak Andrzej , Ben-Horin Yarden , Furman Sagi , Wróbel Krzysztof , Bartosik Bernadetta , Panas Ewelina
Published: February 2023

Brain fog is a kind of mental problem, similar to chronic fatigue syndrome, and appears about 3 months after the infection with COVID-19 and lasts up to 9 months. The maximum magnitude of the third wave of COVID-19 in Poland was in April 2021. The research referred here aimed at carrying out the investigation comprising the electrophysiological analysis of the patients who suffered from COVID-19 and had symptoms of brain fog (sub-cohort A), suffered from COVID-19 and did not have symptoms of brain fog (sub-cohort B), and the control group that had no COVID-19 and no symptoms (sub-cohort C). The aim of this article was to examine whether there are differences in the brain cortical activity of these three sub-cohorts and, if possible differentiate and classify them using the machine-learning tools. he dense array electroencephalographic amplifier with 256 electrodes was used for recordings. The event-related potentials were chosen as we expected to find the differences in the patients' responses to three different mental tasks arranged in the experiments commonly known in experimental psychology: face recognition, digit span, and task switching. These potentials were plotted for all three patients' sub-cohorts and all three experiments. The cross-correlation method was used to find differences, and, in fact, such differences manifested themselves in the shape of event-related potentials on the cognitive electrodes. The discussion of such differences will be presented; however, an explanation of such differences would require the recruitment of a much larger cohort. In the classification problem, the avalanche analysis for feature extractions from the resting state signal and linear discriminant analysis for classification were used. The differences between sub-cohorts in such signals were expected to be found. Machine-learning tools were used, as finding the differences with eyes seemed impossible. Indeed, the A&B vs. C, B&C vs. A, A vs. B, A vs. C, and B vs. C classification tasks were performed, and the efficiency of around 60–70% was achieved. In future, probably there will be pandemics again due to the imbalance in the natural environment, resulting in the decreasing number of species, temperature increase, and climate change-generated migrations. The research can help to predict brain fog after the COVID-19 recovery and prepare the patients for better convalescence. Shortening the time of brain fog recovery will be beneficial not only for the patients but also for social conditions.
Effects of primary angle-closure glaucoma on interhemispheric functional connectivity
Authors: Shu Yongqiang , Huang Yuying , Chen Jingting , Chen Liting , Cai Guoqian , Guo Yu , Li Shenghong , Gao Junwei , Zeng Xianjun
Published: February 2023

Background

Previous studies on primary angle-closure glaucoma (PACG) primarily focused on local brain regions or global abnormal brain activity; however, the alteration of interhemispheric functional homotopy and its possible cause of brain-wide functional connectivity abnormalities have not been well-studied. Little is known about whether brain functional alteration could be used to differentiate from healthy controls (HCs) and its correlation with neurocognitive impairment.

Methods

Forty patients with PACG and 40 age- and sex-matched healthy controls were recruited for this study; resting-state functional magnetic resonance imaging (rs-fMRI), and clinical data were collected. We used the voxel-mirrored homotopic connectivity (VMHC) method to explore between-group differences and selected brain regions with statistically significant differences as regions of interest for whole-brain functional connectivity analysis. Partial correlation was used to evaluate the association between abnormal VMHC values in significantly different regions and clinical parameters, with with age and sex as covariates. Finally, the support vector machine (SVM) model was performed in classification prediction of PACG.

Results

Compared with healthy controls, patients with PACG exhibited significantly decreased VMHC values in the lingual gyrus, insula, cuneus, and pre- and post-central gyri; no regions exhibited increased VMHC values. Subsequent functional connectivity analysis revealed extensive functional changes in functional networks, particularly the default mode, salience, visual, and sensorimotor networks. The SVM model showed good performance in classification prediction of PACG, with an area under curve (AUC) of 0.85.

Conclusion

Altered functional homotopy of the visual cortex, sensorimotor network, and insula may lead to impairment of visual function in PACG, suggesting that patients with PACG may have visual information interaction and integration dysfunction.
Evaluation of preoperative visual pathway impairment in patients with non-functioning pituitary adenoma using diffusion tensor imaging coupled with optical coherence tomography
Authors: Pang Yanhua , Tan Zhi , Chen Xinxin , Liao Zhihui , Yang Xin , Zhong Qin , Huang Baqi , Zhong Qianshuo , Zhong Jingxiang , Mo Wei
Published: February 2023

Objective

Optic chiasma compression and associated visual impairment induced by a non-functioning pituitary adenoma (NFPA) is commonly assessed by the optic disk and retina but is inadequate to understand the entire visual pathway impairment. We aim to evaluate the use of optical coherence tomography (OCT) coupled with diffusion tensor imaging (DTI) for the preoperative evaluation of visual pathway impairment.

Methods

Fifty-three patients with NFPA (categorized into mild and heavy compression subgroups) were subjected to OCT to calculate the thickness of the circumpapillary retinal nerve fiber layer (CP-RNFL), macular ganglion cell complex (GCC), macular ganglion cell layer (GCL), and macular inner plexus layer (IPL), as well as to DTI to calculate the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values.

Results

Compared to mild compression, heavy compression caused decreased FA value, increased ADC value of several segments of the visual pathway, thin temporal CP-RNFL, and quadrant macular GCC, IPL, and GCL. Average CP-RNFL thickness, inferior-macular inner-ring IPL and GCC thicknesses, inferior CP-RNFL thickness, and superior CP-RNFL thickness were the best indicators of the impairment of the optic nerve, optic chiasma, optic tract, and optic radiation, respectively.

Conclusion

DTI and OCT parameters can effectively evaluate visual pathway impairment and are beneficial for the objective preoperative evaluation of visual pathway impairment in patients with NFPA.
Adaptive neuroplasticity in the default mode network contributing to absence of central sensitization in primary dysmenorrhea
Authors: Lee Lin-Chien , Chen Ya-Yun , Li Wei-Chi , Yang Ching-Ju , Liu Ching-Hsiung , Low Intan , Chao Hsiang-Tai , Chen Li-Fen , Hsieh Jen-Chuen
Published: February 2023

Introduction

Primary dysmenorrhea (PDM), the most prevalent gynecological problem among women of reproductive age, presents as a regular pattern of cyclic menstrual pain. The presence or absence of central sensitization (i.e., pain hypersensitivity) in cases of PDM is a contentious issue. Among Caucasians, the presence of dysmenorrhea is associated with pain hypersensitivity throughout the menstrual cycle, indicating pain amplification mediated by the central nervous system. We previously reported on the absence of central sensitization to thermal pain among Asian PDM females. In this study, functional magnetic resonance imaging was used to reveal mechanisms underlying pain processing with the aim of explaining the absence of central sensitization in this population.

Methods

Brain responses to noxious heat applied to the left inner forearm of 31 Asian PDM females and 32 controls during their menstrual and periovulatory phases were analyzed.

Results and discussion

Among PDM females experiencing acute menstrual pain, we observed a blunted evoked response and de-coupling of the default mode network from the noxious heat stimulus. The fact that a similar response was not observed in the non-painful periovulatory phase indicates an adaptive mechanism aimed at reducing the impact of menstrual pain on the brain with an inhibitory effect on central sensitization. Here we propose that adaptive pain responses in the default mode network may contribute to the absence of central sensitization among Asian PDM females. Variations in clinical manifestations among different PDM populations can be attributed to differences in central pain processing.
Trait sensitivity to negative feedback in rats is associated with increased expression of serotonin 5-HT2A receptors in the ventral hippocampus
Authors: Surowka Paulina , Noworyta Karolina , Smaga Irena , Filip Malgorzata , Rygula Rafal
Published: February 2023

One of the most important yet still underappreciated mechanisms of depression is distorted cognition, with aberrant sensitivity to negative feedback being one of the best-described examples. As serotonin has been identified as an important modulator of sensitivity to feedback and because the hippocampus has been implicated in the mediation of learning from positive and negative outcomes, the present study aimed to identify differences in the expression of various genes encoding 5-HT receptors in this brain region between the rats displaying trait sensitivity and insensitivity to negative feedback. The results demonstrated that trait sensitivity to negative feedback is associated with increased mRNA expression of the 5-HT2A receptors in the rat ventral hippocampus (vHipp). Further analysis revealed that this increased expression might be modulated epigenetically by miRNAs with a high target score for the Htr2a gene (miR-16-5p and miR-15b-5p). Additionally, although not confirmed at the protein level, trait sensitivity to negative feedback was associated with decreased expression of mRNA encoding the 5-HT7 receptor in the dorsal hippocampus (dHipp). We observed no statistically significant intertrait differences in the expression of the Htr1a, Htr2c, and Htr7 genes in the vHipp and no statistically significant intertrait differences in the expression of the Htr1a, Htr2a, and Htr2c genes in the dHipp of the tested animals. These results suggest that resilience to depression manifested by reduced sensitivity to negative feedback may be mediated via these receptors.
Effect of Frying Process on Nutritional Property, Physicochemical Quality, and in vitro Digestibility of Commercial Instant Noodles
Authors: Wang Jin , Li Ang , Hu Jiaqiang , Zhang Bowei , Liu Jingmin , Zhang Yan , Wang Shuo
Published: February 2023

The effects of frying process on the nutritional property, physicochemical quality, and in vitro digestibility of instant noodle products are investigated in this study. Scanning electron microscope (SEM) and Fourier transform infrared spectrometer (FT-IR) were also used to explore the changes in the microstructure and protein transformation. Noodles, after the frying process, showed a lower proportion of carbohydrate, protein, fiber, and also total starch and digestible starch, but higher content of fat and resistant starch in the proximate analysis. The frying process was also considered to improve the texture, surface color, and sensory properties of instant noodle products, accompanied by better cooking quality, including shorter cooking time and lower cooking loss during the rehydration. The honeycomb-like, porous, and less uniformed structure, and also the higher levels of β-sheets and β-turns, and the lower proportion of α-helixes of protein structure from fried instant noodle was also observed. The in vitro digestibility of starch and protein were downregulated in the fried group (81.96% and 81.31, respectively, on average) compared with the non-fried group (97.58% and 88.78, respectively, on average). Thus, the frying process lowered the glycemic index and regulated protein secondary structure by inhibiting continuous digesting enzyme activity, generating starch-lipid complexes, and changing the levels of protein transformation. In conclusion, our findings will provide an innovative evaluation of the frying process on instant noodles and even other various starch-based prepared food products.
Association between dietary caffeine, coffee, and tea consumption and depressive symptoms in adults: A systematic review and dose-response meta-analysis of observational studies
Authors: Torabynasab Kimia , Shahinfar Hossein , Payandeh Nastaran , Jazayeri Shima
Published: February 2023

Background

Recent studies have reported an association between dietary caffeine intake (coffee and tea) and the presence of depressive symptoms. However, the findings are not conclusive.

Purpose

This study aimed to examine the correlation between the consumption of dietary caffeine (coffee and tea) and the presence of depressive symptoms in adults.

Methods

PubMed and Scopus databases were searched until December 2021. Two investigators analyzed data from identified studies and rated the quality of the evidence using the GRADE approach. Using the random-effects models, we estimated the relative risks (RRs) and 95% confidence intervals (CIs). We also modeled the dose-response associations through a one-stage, weighted mixed-effects meta-analysis.

Results

A total of 29 eligible studies included a total of 422,586 participants. On comparing the highest with the lowest category in cohort studies, we identified an inverse association between the intake of coffee and depressive symptoms (RR: 0.89, 95%CI: 0.82–0.95; I2 = 63.7%, GRADE = low). There was a 4% reduction in the risk of depression associated with an increase in coffee intake of 240 ml/day (RR: 0.96, 95%CI: 0.95, 0.98; I2 = 22.7%). By comparing the highest category with the lowest category in cohort studies, we discovered that caffeine intake was inversely associated with depressive symptoms (RR: 0.86, 95%CI: 0.79, 0.93; I2 = 0.0%, GRADE = moderate). Based on our data analysis, no correlation exists between tea consumption and depressive symptoms.

Conclusion

According to our findings, coffee and dietary caffeine may have a protective effect against the development of depression. However, no evidence suggesting a link between tea consumption and reduced depressive symptoms has been found. Therefore, further longitudinal studies are needed to substantiate the causal relationship between coffee, tea, and caffeine and the risk of depression.
Prediction of active marker of seabuckthorn polysaccharides for prevention and treatment of cervical cancer and mechanism study
Authors: Feng Xuehua , Song Zurong , Tao Ali , Gong Panpan , Pei Wenqing , Zong Rumin
Published: February 2023

Objective

To predict the target of Seabuckthorn polysaccharides in the prevention and treatment of cervical cancer, and to explore its multi-target and multi-pathway mechanism.

Methods

Using the Swisstarget database, a total of 61 potential targets of polysaccharide active components were obtained. Cervical cancer related targets were obtained from the GeneCards database. The correlation score was greater than 5 targets for 2727; 15 intersection targets of active ingredients and disease were obtained by Venn diagram. Cytoscape3.6.0 software was used to construct the Polysaccharide composition-Target-Disease Network and Protein-Protein Interaction Networks (PPI). Cytoscape3.6.0 software was used for visualization and network topology analysis to obtain core targets. Kyoto encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were analyzed using Metascape database. SailVina and PyMOL software were used for molecular docking to verify binding strength.

Results

A total of 15 core targets were obtained for cervical cancer. These targets are significantly enriched in HIF-1 signaling pathway, Galactose metabolism, EGFR tyrosine kinase inhibitor resistance, growth factor receptor binding, carbohydrate binding, protein homodimerization activity and other GO and KEGG entries; Molecular docking showed that ADA and GLB1 were well bound to Glucose, D-Mannose, and Galactose.

Conclusion

The effect of seabuckthorn polysaccharides on the prevention and treatment of cervical cancer is characterized by multi-component, multi-target and multi-pathway, which provides scientific basis for further research on the activity of seabuckthorn polysaccharides.
The prognostic value and response to immunotherapy of immunogenic cell death-associated genes in breast cancer
Authors: Zhao Rongling , Wang Wenkang , Pan Limin , Lv Xuefeng , He Yi , Lian Wenping , Ma Yajie , Zhang Xinyu , Yu Ruijing , Zhao Shuai , Guo Xiaona , Huang Tao , Peng Mengle
Published: February 2023

Breast cancer (BRCA) remains the most prevalent cancer worldwide and the tumor microenvironment (TME) has been discovered to exert a wide influence on the overall survival and therapeutic response. Numerous lines of evidence reported that the effects of immunotherapy of BRCA were manipulated by TME. Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is capable of fueling adaptive immune responses and aberrant expression of ICD-related genes (ICDRGs) can govern the TME system by emitting danger signals or damage-associated molecular patterns (DAMPs). In the current study, we obtained 34 key ICDRGs in BRCA. Subsequently, using the transcriptome data of BRCA from the TCGA database, we constructed a risk signature based on 6 vital ICDRGs, which had a good performance in predicting the overall survival of BRCA patients. We also examined the efficacy of our risk signature in the validation dataset (GSE20711) in the GEO database and it performed excellently. According to the risk model, patients with BRCA were divided into high-risk and low-risk groups. Also, the unique immune characteristics and TME between the two subgroups and 10 promising small molecule drugs targeting BRCA patients with different ICDRGs risk have been investigated. The low-risk group had good immunity indicated by T cell infiltration and high immune checkpoint expression. Moreover, the BRCA samples could be divided into three immune subtypes according to immune response severity (ISA, ISB, and ISC). ISA and ISB predominated in the low-risk group and patients in the low-risk group exhibited a more vigorous immune response. In conclusion, we developed an ICDRGs-based risk signature that can predict the prognosis of BRCA patients and offer a novel therapeutic strategy for immunotherapy, which would be of great significance in the BRCA clinical setting.
Discovery of protein biomarkers for venous thromboembolism in non-small cell lung cancer patients through data-independent acquisition mass spectrometry
Authors: Liu Yanhong , Gao Lan , Fan Yanru , Ma Rufei , An Yunxia , Chen Guanghui , Xie Yan
Published: February 2023

Objective

Non-small cell lung cancer (NSCLC) patients present a high incidence of venous thromboembolism (VTE) with poor prognosis. It is crucial to identify and diagnose VTE early. The study aimed to identify potential protein biomarkers and mechanism of VTE in NSCLC patients via proteomics research.

Methods

Proteomic analysis of the human plasma was performed through data-independent acquisition mass spectrometry for 20 NSCLC patients with VTE, and 15 NSCLC patients without VTE. Significantly differentially expressed proteins were analyzed by multiple bioinformatics method for further biomarker analysis.

Results

A total of 280 differentially expressed proteins were identified in VTE and non-VTE patients, where 42 were upregulated and 238 were downregulated. These proteins were involved in acute-phase response, cytokine production, neutrophil migration and other biological processes related to VTE and inflammation. Five proteins including SAA1, S100A8, LBP, HP and LDHB had significant change between VTE and non-VTE patients, with the area under the curve (AUC) were 0.8067, 0.8308, 0.7767, 0.8021, 0.8533, respectively.

Conclusions

SAA1, S100A8, LBP, HP and LDHB may serve as potential plasma biomarkers for diagnosis VTE in NSCLC patients.
Preservation of the integrity of facial nerve in vestibular schwannoma microsurgery: A consecutive study of 127 clinical cases focusing on nervus intermedius
Authors: Li Yue , Peng Hao , Zhang Sen , Long Wenyong , Pan Yimin , Li Yang , Wu Changwu , Xiao Kai , Wang Xiangyu , Su Jun , Qin Chaoying , Liu Qing
Published: February 2023

Background

Nervus intermedius (NI) injuries are not given enough attention by neurosurgeons during vestibular schwannoma (VS) surgery. Preservation of NI function is essential for the integrity and continuity of the facial nerve, although this can be challenging. We identified the risk factors for NI injury and proposed our experience for optimizing NI preservation based on our cases.

Methods

We retrospectively analyzed clinical data from a consecutive series of 127 patients with VS who underwent microsurgery via the retrosigmoid approach from 2017 to 2021 at our institution. The baseline characteristics of the patients were collected from the medical records, and the incidence of NI dysfunction symptoms was obtained by outpatient and online video follow-up 6 months after surgery. The surgical procedures and techniques used were described in detail. The data were analyzed in relation to sex, age, tumor location (left or right), Koos grading scale, internal acoustic canal (IAC) invasion (TFIAC Classification), brainstem adhesion, tumor characteristics (cystic or solid), tumor necrosis, and preoperative House–Brackmann (HB) grading by univariate and multivariate analyses.

Results

Gross tumor removal was achieved in 126 (99.21%) patients. Subtotal removal was performed on one patient (0.79%). Twenty-three of our cases exhibited facial nerve palsy preoperatively; 21 patients had HB grade II facial palsy, and two had HB grade III. Two months after surgery, 97 (76.38%) patients had normal function of the motor portion of the facial nerve; 25 (19.69%) patients had HB Grade II facial palsy, five had Grade III (3.94%), and zero (0%) had Grade IV. Postoperatively, 15 patients experienced newly gained dry eyes (11.81%), whereas 21 cases of lacrimal disturbances (16.54%), nine of taste disturbances (7.09%), seven of xerostomia (5.51%), five of nasal hypersecretions (3.94%), and seven of hypersalivation (5.51%) were identified in our cases. Univariate and multivariate analyses revealed that the Koos grading scale and tumor characteristics (solid or cystic) were correlated with NI injury (p <0.01).

Conclusion

The data in this study demonstrate that although the motor function of the facial nerve is well preserved, NI disturbance is still common after VS surgery. Maintaining the integrity and continuity of the facial nerve is key to NI function. Performing bidirectional and subperineurium dissection based on even and adequate debulking is beneficial for NI preservation in VS surgery. Higher Koos grading and cystic characteristics of VS are associated with postoperative NI injuries. These two parameters can be used to guide the delineation of surgical strategy and predict the prognosis of NI function preservation.
A survival nomogram model constructed with common clinical characteristics to assist clinical decisions for diffuse low-grade gliomas: A population analysis based on SEER database
Authors: Ao Lei , Shi Dongjie , Liu Dan , Yu Hua , Xu Li , Xia Yongzhi , Hao Shilei , Yang Yaying , Zhong Wenjie , Zhou Junjie , Xia Haijian
Published: February 2023

Background

The prognosis of diffuse low-grade gliomas (DLGGs, WHO grade 2) is highly variable, making it difficult to evaluate individual patient outcomes. In this study, we used common clinical characteristics to construct a predictive model with multiple indicators.

Methods

We identified 2459 patients diagnosed with astrocytoma and oligodendroglioma from 2000 to 2018 in the SEER database. After removing invalid information, we randomly divided the cleaned patient data into training and validation groups. We performed univariate and multivariate Cox regression analyses and constructed a nomogram. Receiver operating characteristic (ROC) curve, c-index, calibration curve, and subgroup analyses were used to assess the accuracy of the nomogram by internal and external validation.

Results

After univariate and multivariate Cox regression analyses, we identified seven independent prognostic factors, namely, age (P<0.001), sex (P<0.05), histological type (P<0.001), surgery (P<0.01), radiotherapy (P<0.001), chemotherapy (P<0.05) and tumor size (P<0.001). The ROC curve, c-index, calibration curve, and subgroup analyses of the training group and the validation group showed that the model had good predictive value. The nomogram for DLGGs predicted patients’ 3-, 5- and 10-year survival rates based on these seven variables.

Conclusions

The nomogram constructed with common clinical characteristics has good prognostic value for patients with DLGGs and can help physicians make clinical decisions.
STAT3 gain-of-function syndrome
Authors: Vogel Tiphanie P. , Leiding Jennifer W. , Cooper Megan A. , Forbes Satter Lisa R.
Published: February 2023

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation and decreased T regulatory cells may contribute to autoimmunity. While T cell exhaustion and apoptosis defects likely contribute to the lymphoproliferative phenotype, no conclusive correlations are yet established. Here we review the known mechanistic and clinical characteristics of this heterogenous PIRD.
Case report: Catecholamine cardiomyopathy in children with neuroblastoma
Authors: Xu Xiaoyan , Liu Meiqi , Zhang Yanmin , Wang Jie , Lei Xi , Wang Juanli , Zhou Yafei , Wang Tao
Published: February 2023

Introduction

Many endocrine diseases, such as neuroblastoma (NB), can be linked with acquired cardiomyopathy and heart failure. Neuroblastoma’s cardiovascular manifestations are typically hypertension, electrocardiogram (ECG) changes, and conduction disturbances.

Case Presentation

A 5-year-old 8-month-old girl was admitted to the hospital with ventricular hypertrophy and hypertension (HT) and heart failure. She had no previous history of HT. On color doppler echocardiography, the left atrium and left ventricle were enlarged. The left ventricular ejection fraction (EF) was as low as 40%, and the ventricular septum and left ventricular free wall were thickened. The internal diameters of both coronary arteries were widened. Abdominal computed tomography scan (CT) demonstrated an 8.7 cm × 7.1 cm × 9.5 cm tumor behind the left peritoneum. In urine catecholamines analysis, free-norepinephrine (f-NE), free-dopamine (f-DA), free-normetanephrine (f-NMN), free-3-methoxytyramine (f-3MT), vanillylmandelic acid (VMA), and homovanillic acid (HVA) levels were all greater than the normal range for 24 h except free-metanephrine (f-MN) and free-epinephrine (f-E). Based on these findings, we diagnosed her as NB complicated by catecholamine cardiomyopathy manifested by hypertrophic cardiomyopathy (HCM). Oral metoprolol, spironolactone, captopril and amlodipine furosemide, and intravenously injected sodium nitroprusside and phentolamine were employed for treating HT. After the tumor resection, the blood pressure (BP) and urinary catecholamine levels were all restored. After a follow-up of 7 months, echocardiography indicated normalization of ventricular hypertrophy and function.

Conclusion

This is a rare report showing catecholamine cardiomyopathy in NB children. Tumor resection leads to a return to normal of the catecholamine cardiomyopathy manifested as HCM.
Numerical investigation of non-linear inverse Compton scattering in double-layer targets
Authors: Galbiati Marta , Formenti Arianna , Grech Mickael , Passoni Matteo
Published: February 2023

Non-linear inverse Compton scattering (NICS) is of significance in laser-plasma physics and for application-relevant laser-driven photon sources. Given this interest, we investigated this synchrotron-like photon emission in a promising configuration achieved when an ultra-intense laser pulse interacts with a double-layer target (DLT). Numerical simulations with two-dimensional particle-in-cell codes and analytical estimates are used for this purpose. The properties of NICS are shown to be governed by the processes characterizing laser interaction with the near-critical and solid layers composing the DLT. In particular, electron acceleration, laser focusing in the low-density layer, and pulse reflection on the solid layer determine the radiated power, the emitted spectrum, and the angular properties of emitted photons. Analytical estimates, supported by simulations, show that quantum effects are relevant at laser intensities as small as ∼1021 W/cm2 Target and laser parameters affect the NICS competition with bremsstrahlung and the conversion efficiency and average energy of emitted photons. Therefore, DLT properties could be exploited to tune and enhance photon emission in experiments and future applications.
Molecular cloning and functional characterization of the promoter of a novel Aspergillus flavus inducible gene (AhOMT1) from peanut
Authors: Zhuang Yuhui , Sharif Yasir , Zeng Xiaohong , Chen Suzheng , Chen Hua , Zhuang Chunhong , Deng Ye , Ruan Miaohong , Chen Shuanglong , Weijian Zhuang
Published: February 2023

Peanut is an important oil and food legume crop grown in more than one hundred countries, but the yield and quality are often impaired by different pathogens and diseases, especially aflatoxins jeopardizing human health and causing global concerns. For better management of aflatoxin contamination, we report the cloning and characterization of a novel A. flavus inducible promoter of the O-methyltransferase gene (AhOMT1) from peanut. The AhOMT1 gene was identified as the highest inducible gene by A. flavus infection through genome-wide microarray analysis and verified by qRT-PCR analysis. AhOMT1 gene was studied in detail, and its promoter, fussed with the GUS gene, was introduced into Arabidopsis to generate homozygous transgenic lines. Expression of GUS gene was studied in transgenic plants under the infection of A. flavus. The analysis of AhOMT1 gene characterized by in silico assay, RNAseq, and qRT-PCR revealed minute expression in different organs and tissues with trace or no response to low temperature, drought, hormones, Ca2+, and bacterial stresses, but highly induced by A. flavus infection. It contains four exons encoding 297 aa predicted to transfer the methyl group of S-adenosyl-L-methionine (SAM). The promoter contains different cis-elements responsible for its expression characteristics. Functional characterization of AhOMT1P in transgenic Arabidopsis plants demonstrated highly inducible behavior only under A. flavus infection. The transgenic plants did not show GUS expression in any tissue(s) without inoculation of A. flavus spores. However, GUS activity increased significantly after inoculation of A. flavus and maintained a high level of expression after 48 hours of infection. These results provided a novel way for future management of peanut aflatoxins contamination through driving resistance genes in A. flavus inducible manner.
The Bcl-2-associated athanogene gene family in tobacco (Nicotiana tabacum) and the function of NtBAG5 in leaf senescence
Authors: Gu Linxin , Hou Bing , Chen Xiao , Wang Yu , Chang Pingan , He Xiaohong , Gong Daping , Sun Quan
Published: February 2023

Leaf senescence in tobacco is closely related to leaf maturation and secondary metabolites. Bcl-2-associated athanogene (BAG) family members are highly conserved proteins and play key roles in senescence, growth and development, and resistance to biotic and abiotic stresses. Herein, the BAG family of tobacco was identified and characterized. In total, 19 tobacco BAG protein candidate genes were identified and divided into two classes, class I comprising NtBAG1a–e, NtBAG3a–b, and NtBAG4a–c and class II including NtBAG5a–e, NtBAG6a–b, and NtBAG7. Genes in the same subfamily or branch of the phylogenetic tree exhibited similarities in gene structure and the cis-element on promoters. RNA-seq and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that the expression of NtBAG5c–f and NtBAG6a–b was upregulated in senescent leaves, implying that they play a role in regulating leaf senescence. NtBAG5c was localized in the nucleus and cell wall as a homology of leaf senescence related gene AtBAG5. Further, the interaction of NtBAG5c with heat-shock protein 70 (HSP70) and sHSP20 was demonstrated using yeast two-hybrid experiment. Virus-induced gene silencing indicated that NtBAG5c reduced the lignin content and increased superoxide dismutase (SOD) activity and hydrogen peroxide (H2O2) accumulation. In NtBAG5c-silenced plants, the expression of multiple senescence-related genes cysteine proteinase (NtCP1), SENESCENCE 4 (SEN4) and SENESCENCE-ASSOCIATED GENE 12 (SAG12) was downregulated. In conclusion, tobacco BAG protein candidate genes were identified and characterized for the first time.
Struggling the Islamic State in Austral Africa: The SADC military intervention in Cabo Delgado (Mozambique) and its limits
Authors: Bussotti Luca , Coimbra Ermenegildo Júlio
Published: February 2023

This article analyses how SADC (Southern Africa Development Community) faced the threat of Islamic terrorism in one of its member states, Mozambique, since October 2017. This research is focused on the SADC strategy for counter-terrorism, having as its main perspective the military intervention, in a permanent dialogue with the political level of decision. The difficulties in organizing the military intervention in Mozambique by SADC demonstrated a lack of “Sadcnesses” or a common spirit and vision within this organization. In addition, the presence of many other international players on the field runs the risks of turning the conflict into an international clash between the West, led by the United States, and Islamic radicalism, in Mozambique present with Al-Shabaab and ISIS. The results of the SAMIM (SADC Mission in Mozambique) operation have not been satisfactory, and Mozambican people continue to be threatened by the incursions of well-armed and trained terrorist groups. This study used a qualitative approach based on a bibliographical as well as documental analysis of SADC documents and declarations. A comparative perspective with other African cases of a significant presence of terroristic groups helped the authors to better understand the jihadist attacks in Mozambique as well as the merely military approach to fight them.