bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and Drug Resistance of Neonatal Bloodstream Infection Pathogens in East China Children’s Medical Center From 2016 to 2020
Authors: Zhang Xin , Li Yang , Tao Yunzhen , Ding Yu , Shao Xuejun , Li Wei
Published: March 2022

Introduction

To analyze the pathogen distribution and drug resistance of newborns with bloodstream infection (BSI) to help clinicians choose the appropriate empirical antibiotic therapy for clinical infection control.

Methods

A total of 707 neonatal BSI cases were retrospectively analyzed. The bacteria in blood culture-positive samples were cultured, identified, and analyzed for drug sensitivity by routine methods. Statistical software was used to compare and analyze the basic data, pathogenic information, and drug resistance of the main bacteria.

Results

The 5-year average positive rate of neonatal blood culture was 2.50%. The number of specimens submitted for inspection in 2020 significantly decreased. The top five infectious pathogens with the highest proportion were coagulase-negativeStaphylococcus(67.35%), of whichStaphylococcus epidermidishad the highest proportion (31.26%), followed byEscherichia coli(12.87%),Klebsiella pneumoniae(9.05%),Streptococcus agalactiae(8.63%), andStaphylococcus aureus(3.25%). Gram-positive (G+) bacteria were dominant, accounting for 69.45%. The main G+bacteria had a higher rate of resistance to erythromycin and penicillin G. The main Gram-negative (G–) bacteria had a high resistance rate to a variety of antibacterial drugs, especially cephalosporin antibiotics. The overall resistance ofK. pneumoniaewas higher than that ofE. coli. The top two fungi detected wereCandida parapsilosisandCandida albicans. C. parapsilosisdid not appear to be resistant to antibiotics, whileC. albicanswas resistant to multiple antibiotics. The type of microbial infection had a statistically significant difference in the positive rate among the age at delivery and wards (p< 0.05). There were significant differences in the detection of fungi among these groups (p< 0.05). The positive rate of G+bacteria in the term newborns was significantly higher than that in the preterm newborns (p< 0.05). Preterm newborns are more susceptible to pneumonia.

Conclusion

G+bacteria are the main pathogens of neonatal BSI. Preterm newborns are more likely to be infected with G–bacteria.E. coliandK. pneumoniaeare the most common G–bacteria, and both have a high resistance rate to a variety of antibacterial drugs. According to the distribution characteristics and drug resistance, it is very important to select antibiotics reasonably.
Analysis of the Gut Bacterial Community of Wild Larvae of Anastrepha fraterculus sp. 1: Effect of Host Fruit, Environment, and Prominent Stable Associations of the Genera Wolbachia, Tatumella, and Enterobacter
Authors: Salgueiro Julieta , Nussenbaum A. Laura , Milla Fabián H. , Asimakis Elias , Goane Lucía , Ruiz M. Josefina , Bachmann Guillermo E. , Vera María T. , Stathopoulou Panagiota , Bourtzis Kostas , Deutscher Ania T. , Lanzavecchia Silvia B. , Tsiamis George , Segura Diego F.
Published: March 2022

The genusAnastrepha(Diptera Tephritidae) includes some of the most important fruit fly pests in the Americas. Here, we studied the gut bacterial community of 3rd instar larvae ofAnastrepha fraterculussp. 1 through Next Generation Sequencing (lllumina) of the V3-V4 hypervariable region within the 16S rRNA gene. Gut bacterial communities were compared between host species (guava and peach), and geographical origins (Concordia and Horco Molle in Argentina) representing distinct ecological scenarios. In addition, we explored the effect of spatial scale by comparing the samples collected from different trees within each geographic origin and host species. We also addressed the effect of fruit size on bacterial diversity. The gut bacterial community was affected both by host species and geographic origin. At smaller spatial scales, the gut bacterial profile differed among trees of the same species and location at least in one host-location combination. There was no effect of fruit size on the larval gut bacteriome. Operational Taxonomic Units (OTUs) assigned toWolbachia,TatumellaandEnterobacterwere identified in all samples examined, which suggest potential, non-transient symbioses. Better knowledge on the larval gut bacteriome contributes valuable information to develop sustainable control strategies againstA. fraterculustargeting key symbionts as the Achilles’ heel to control this important fruit fly pest.
Pseudotargeted Metabolomic Fingerprinting and Deep Learning for Identification and Visualization of Common Pathogens
Authors: Feng Ying , Chen Moutong , Wei Xianhu , Zhu Honghui , Zhang Jumei , Zhang Youxiong , Xue Liang , Huang Lanyan , Chen Guoyang , Chen Minling , Ding Yu , Wu Qingping
Published: March 2022

Matrix-assisted laser desorption/ionization time-of-flight mass (MALDI-TOF) spectrometry fingerprinting has reduced turnaround times, costs, and labor as conventional procedures in various laboratories. However, some species strains with high genetic correlation have not been directly distinguished using conventional standard procedures. Metabolomes can identify these strains by amplifying the minor differences because they are directly related to the phenotype. The pseudotargeted metabolomics method has the advantages of both non-targeted and targeted metabolomics. It can provide a new semi-quantitative fingerprinting with high coverage. We combined this pseudotargeted metabolomic fingerprinting with deep learning technology for the identification and visualization of the pathogen. A variational autoencoder framework was performed to identify and classify pathogenic bacteria and achieve their visualization, with prediction accuracy exceeding 99%. Therefore, this technology will be a powerful tool for rapidly and accurately identifying pathogens.
Selenite Reduction by Proteus sp. YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles
Authors: Wang Yuting , Ye Qing , Sun Yujun , Jiang Yulu , Meng Bo , Du Jun , Chen Jingjing , Tugarova Anna V. , Kamnev Alexander A. , Huang Shengwei
Published: March 2022

Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). However, the current knowledge of the molecular mechanism of selenite reduction remains limited. In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. YS02. Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. It is revealed that 197 genes were significantly upregulated, and 276 genes were significantly downregulated under selenite treatment. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs.
Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells
Authors: Yang Caiqin , Guo Xin , Li Jianjie , Han Jingwan , Jia Lei , Wen Hong-Ling , Sun Chengxi , Wang Xiaolin , Zhang Bohan , Li Jingyun , Chi Yujia , An Tongtong , Wang Yuyan , Wang Ziping , Li Hanping , Li Lin
Published: March 2022

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT–qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.
The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells
Authors: de Paula Jéssica I. , Lopes-Torres Eduardo J. , Jacobs-Lorena Marcelo , Paes Marcia Cristina , Cha Sung-Jae
Published: March 2022

Background

Chagas is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. On the order of seven million people are infected worldwide and current therapies are limited, highlighting the urgent need for new interventions. T. cruzi trypomastigotes can infect a variety of mammalian cells, recognition and adhesion to the host cell being critical for parasite entry. This study focuses on trypomastigote surface ligands involved in cell invasion.

Methods

Three selection rounds of a phage peptide display library for isolation of phages that bind to trypomastigotes, resulted in the identification of the N3 dodecapeptide. N3 peptide binding to T. cruzi developmental forms (trypomastigotes, amastigotes and epimastigotes) was evaluated by flow cytometry and immunofluorescence assays. Parasite invasion of Vero cells was assessed by flow cytometry and immunofluorescence assays.

Results

Phage display screening identified the N3 peptide that binds preferentially to the surface of the trypomastigote and amastigote infective forms as opposed to non-infective epimastigotes. Importantly, the N3 peptide, but not a control scrambled peptide, inhibits trypomastigote invasion of Vero cells by 50%.

Conclusion

The N3 peptide specifically binds to T. cruzi, and by doing so, inhibits Vero cell infection. Follow-up studies will identify the molecule on the parasite surface to which the N3 peptide binds. This putative T. cruzi ligand may advance chemotherapy design and vaccine development.
High-Frequency Hearing Loss Is Associated With Anxiety and Brain Structural Plasticity in Older Adults
Authors: Ma Wen , Zhang Yue , Li Xiao , Liu Siqi , Gao Yuting , Yang Jing , Xu Longji , Liang Hudie , Ren Fuxin , Gao Fei , Wang Yao
Published: March 2022

Age-related hearing loss (ARHL) is a kind of symmetrical and slow sensorineural hearing loss, which is a common condition in older adults. The characteristic of ARHL is hearing loss beginning in the high-frequency region and spreading toward low-frequency with age. Previous studies have linked it to anxiety, suggesting that brain structure may be involved in compensatory plasticity after partial hearing deprivation. However, the neural mechanisms of underlying ARHL-related anxiety remain unclear. The purpose of this cross-sectional study was to explore the interactions among high-frequency hearing loss and anxiety as well as brain structure in older adults. Sixty-seven ARHL patients and 68 normal hearing (NH) controls participated in this study, and the inclusion criterion of ARHL group was four-frequency (0.5, 1, 2, and 4 kHz) pure tone average (PTA) > 25 decibels hearing level of the better hearing ear. All participants performed three-dimensional T1-weighted magnetic resonance imaging (MRI), pure tone audiometry tests, anxiety and depression scales. Our results found gray matter volume (GMV) decreased in 20 brain regions in the ARHL group compared with the NH group, and a positive correlation existed between high-frequency pure tone audiometry (H-PT) and anxiety scores in the ARHL group. Among 20 brain regions, we also found the GMVs of the middle cingulate cortex (MCC), and the hippocampal/parahippocampal (H-P) regions were associated with H-PT and anxiety scores in all participants separately. However, the depressive symptoms indicated no relationship with hearing assessment or GMVs. Our findings revealed that the crucial role of MCC and H-P in a link of anxiety and hearing loss in older adults.
The Effects of Electroencephalogram Feature-Based Transcranial Alternating Current Stimulation on Working Memory and Electrophysiology
Authors: Zeng Lanting , Guo Mingrou , Wu Ruoling , Luo Yu , Wei Pengfei
Published: March 2022

Transcranial alternating current stimulation (tACS) can influence cognitive functions by modulating brain oscillations. However, results regarding the effectiveness of tACS in regulating cognitive performance have been inconsistent. In the present study, we aimed to find electroencephalogram (EEG) characteristics associated with the improvements in working memory performance, to select tACS stimulus targets and frequency based on this feature, and to explore effects of selected stimulus on verbal working memory. To achieve this goal, we first investigated the EEG characteristics associated with improvements in working memory performance with the aid of EEG analyses and machine learning techniques. These analyses suggested that 8 Hz activity in the prefrontal region was related to accuracy in the verbal working memory task. The tACS stimulus target and pattern were then selected based on the EEG feature. Finally, the selected tACS frequency (8 Hz tACS in the prefrontal region) was applied to modulate working memory. Such modulation resulted significantly greater improvements, compared with 40 Hz and sham modulations (especially for participants with weak verbal working memory). In conclusion, using EEG features related to positive behavioral changes to select brain regions and stimulation patterns for tACS is an effective intervention for improving working memory. Our results contribute to the groundwork for future tACS closed-loop interventions for cognitive deterioration.
Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study
Authors: Li Lian , Ding Guangliang , Zhang Li , Davoodi-Bojd Esmaeil , Chopp Michael , Li Qingjiang , Zhang Zheng Gang , Jiang Quan
Published: March 2022

Objective

Impaired glymphatic waste clearance function during brain aging leads to the accumulation of metabolic waste and neurotoxic proteins (e.g., amyloid-β, tau) which contribute to neurological disorders. However, how the age-related glymphatic dysfunction exerts its effects on different cerebral regions and affects brain waste clearance remain unclear.

Methods

We investigated alterations of glymphatic transport in the aged rat brain using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and advanced kinetic modeling. Healthy young (3–4 months) and aged (18–20 months) male rats (n = 12/group) underwent the identical MRI protocol, including T2-weighted imaging and 3D T1-weighted imaging with intracisternal administration of contrast agent (Gd-DTPA). Model-derived parameters of infusion rate and clearance rate, characterizing the kinetics of cerebrospinal fluid (CSF) tracer transport via the glymphatic system, were evaluated in multiple representative brain regions. Changes in the CSF-filled cerebral ventricles were measured using contrast-induced time signal curves (TSCs) in conjunction with structural imaging.

Results

Compared to the young brain, an overall impairment of glymphatic transport function was detected in the aged brain, evidenced by the decrease in both infusion and clearance rates throughout the brain. Enlarged ventricles in parallel with reduced efficiency in CSF transport through the ventricular regions were present in the aged brain. While the age-related glymphatic dysfunction was widespread, our kinetic quantification demonstrated that its impact differed considerably among cerebral regions with the most severe effect found in olfactory bulb, indicating the heterogeneous and regional preferential alterations of glymphatic function.

Conclusion

The robust suppression of glymphatic activity in the olfactory bulb, which serves as one of major efflux routes for brain waste clearance, may underlie, in part, age-related neurodegenerative diseases associated with neurotoxic substance accumulation. Our data provide new insight into the cerebral regional vulnerability to brain functional change with aging.
Alterations in Cortical-Subcortical Metabolism in Temporal Lobe Epilepsy With Impaired Awareness Seizures
Authors: Hou Jiale , Zhu Haoyue , Xiao Ling , Zhao Charlie Weige , Liao Guang , Tang Yongxiang , Feng Li
Published: March 2022

Objective

The features of cerebral metabolism associated with loss of consciousness in patients with temporal lobe epilepsy (TLE) have not been fully elucidated. We aim to investigate the alterations in cortical-subcortical metabolism in temporal lobe epilepsy with impaired awareness seizures (IAS).

Methods

Regional cerebral metabolism was measured using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with TLE-IAS and healthy controls. All patients had a comprehensive evaluation to confirm their seizure origin and lateralization. Videos of all seizures were viewed and rated by at least two epileptologists to identify the state of consciousness when a seizure occurred. By synthesizing the seizure history, semeiology, and video EEG of all patients, as long as the patients had one seizure with impaired awareness, she/he will be included. 76 patients with TLE-IAS and 60 age-matched healthy controls were enrolled in this study. Regional cerebral metabolic patterns were analyzed for TLE-IAS and healthy control groups using statistical parametric mapping. Besides, we compared the MRI-negative patients and MRI-positive patients with healthy controls, respectively.

Results

There were no significant differences in the age and sex of TLE-IAS patients and healthy control. TLE-IAS patients showed extensive bilateral hypermetabolism in the frontoparietal regions, cingulate gyrus, corpus callosum, occipital lobes, basal ganglia, thalamus, brainstem, and cerebellum. The region of metabolic change was more extensive in right TLE-IAS than that of the left, including extensive hypometabolism in the ipsilateral temporal, frontal, parietal, and insular lobes. And contralateral temporal lobe, bilateral frontoparietal regions, occipital lobes, the anterior and posterior regions of the cingulate gyrus, bilateral thalamus, bilateral basal ganglia, brainstem, and bilateral cerebellum showed hypermetabolism. The TLE patients with impaired awareness seizure showed hypermetabolism in the cortical-subcortical network including the arousal system. Additionally, 48 MRI-positive and 28 MRI-negative TLE-IAS patients were included in our study. TLE-IAS patients with MRI-negative and MRI-positive were both showed hypermetabolism in the cingulate gyrus. Hypometabolism in the bilateral temporal lobe was showed in the TLE-IAS with MRI-positive.

Conclusion

These findings suggested that the repetitive consciousness impairing ictal events may have an accumulative effect on brain metabolism, resulting in abnormal interictal cortical-subcortical metabolic disturbance in TLE patients with impaired awareness seizure. Understanding these metabolic mechanisms may guide future clinical treatments to prevent seizure-related awareness deficits and improve quality of life in people with TLE.
Low-Light Image Enhancement Network Based on Recursive Network
Authors: Liu Fangjin , Hua Zhen , Li Jinjiang , Fan Linwei
Published: March 2022

In low-light environments, image acquisition devices do not obtain sufficient light sources, resulting in low brightness and contrast of images, which poses a great obstacle for other computer vision tasks to be performed. To enable other vision tasks to be performed smoothly, it is essential to enhance the research on low-light image enhancement algorithms. In this article, a multi-scale feature fusion image enhancement network based on recursive structure is proposed. The network uses a dual attention module-Convolutional Block Attention Module. It was abbreviated as CBAM, which includes two attention mechanisms: channel attention and spatial attention. To extract and fuse multi-scale features, we extend the U-Net model using the inception model to form the Multi-scale inception U-Net Module or MIU module for short. The learning of the whole network is divided into T recursive stages, and the input of each stage is the original low-light image and the inter-mediate estimation result of the output of the previous recursion. In thet-th recursion, CBAM is first used to extract channel feature information and spatial feature information to make the network focus more on the low-light region of the image. Next, the MIU module fuses features from three different scales to obtain inter-mediate enhanced image results. Finally, the inter-mediate enhanced image is stitched with the original input image and fed into thet+ 1th recursive iteration. The inter-mediate enhancement result provides higher-order feature information, and the original input image provides lower-order feature information. The entire network outputs the enhanced image after several recursive cycles. We conduct experiments on several public datasets and analyze the experimental results subjectively and objectively. The experimental results show that although the structure of the network in this article is simple, the method in this article can recover the details and increase the brightness of the image better and reduce the image degradation compared with other methods.
Functional MRI Studies in Friedreich's Ataxia: A Systematic Review
Authors: Vavla Marinela , Arrigoni Filippo , Peruzzo Denis , Montanaro Domenico , Frijia Francesca , Pizzighello Silvia , De Luca Alberto , Della Libera Emma , Tessarotto Federica , Guerra Paola , Harding Ian H. , Martinuzzi Andrea
Published: March 2022

Friedreich's ataxia (FRDA) is an inherited neurodegenerative movement disorder with early onset, widespread cerebral and cerebellar pathology, and no cure still available. Functional MRI (fMRI) studies, although currently limited in number, have provided a better understanding of brain changes in people with FRDA. This systematic review aimed to provide a critical overview of the findings and methodologies of all fMRI studies conducted in genetically confirmed FRDA so far, and to offer recommendations for future study designs. About 12 cross-sectional and longitudinal fMRI studies, included 198 FRDA children and young adult patients and, 205 healthy controls (HCs), according to the inclusion criteria. Details regarding GAA triplet expansion and demographic and clinical severity measures were widely reported. fMRI designs included motor and cognitive task paradigms, and resting-state studies, with widespread changes in functionally activated areas and extensive variability in study methodologies. These studies highlight a mixed picture of both hypoactivation and hyperactivation in different cerebral and cerebellar brain regions depending on fMRI design and cohort characteristics. Functional changes often correlate with clinical variables. In aggregate, the findings provide support for cerebro-cerebellar loop damage and the compensatory mechanism hypothesis. Current literature indicates that fMRI is a valuable tool for gaining in vivo insights into FRDA pathology, but addressing that its limitations would be a key to improving the design, interpretation, and generalizability of studies in the future.
Critical Angiographic and Sonographic Analysis of Intra Aneurysmal and Downstream Hemodynamic Changes After Flow Diversion
Authors: Raychev Radoslav , Sirakov Stanimir , Sirakov Alexander , Saber Hamidreza , Vinuela Fernando , Jahan Reza , Nour May , Szeder Viktor , Colby Geoffrey , Duckwiler Gary , Tateshima Satoshi
Published: March 2022

Introduction

Successful treatment of intracranial aneurysms after flow diversion (FD) is dependent on the flow modulating effect of the device. We aimed to investigate the intra-aneurysmal and parent vessel hemodynamic changes, as well as the incidence of silent emboli following treatment with various FD devices.

Methods

We evaluated the appearance of the eclipse sign in nine distinct phases of cerebral angiography before and immediately after FD placement in correlation with aneurysm occlusion. Angiographic and clinical data of consecutive procedures were analyzed retrospectively. Patients who had successful FD procedure without adjunctive coiling, visible eclipse sign on post embolization angiography, and reliable follow-up angiographic data were included in the analysis. Detailed analysis of hemodynamic data from transcranial doppler after FD was performed in selected patients, such as monitoring for silent emboli.

Results

Among all patients (N = 65) who met inclusion criteria, complete aneurysm occlusion at 12 months was achieved in 89% (58/65). Eclipse sign prior to FD was observed in 42% (27/65) with unchanged appearance in 4.6% (3/65) of the treated patients. None of these three patients achieved complete aneurysm occlusion. Among all analyzed variables, such as aneurysm size, device type used, age, and appearance of the eclipse sign pre- and post-FD, the most reliable predictor of permanent aneurysm occlusion at 12 months was earlier, prolonged, and sustained eclipse sign visibility in more than three angiographic phases in comparison to the baseline (p < 0.001). Elevation in flow velocities within the ipsilateral vascular territory was noted in 70% (9/13), and bilaterally in 54% (7/13) of the treated patients. None of the patients had silent emboli.

Conclusions

Intra-aneurysmal and parent vessel hemodynamic changes after FD can be reliably assessed by the cerebral angiography and transcranial doppler with important implications for the prediction of successful treatment.
The Whiplash Disease Reconsidered
Authors: Astrup Jens , Gyntelberg Finn
Published: March 2022

The natural course of the whiplash disease is reconsidered in relation to the predominant view of its cause. It is assumed that a whiplash-type trauma is causing an acute tissue injury such as a distortion or sprain in the neck followed by neck pain and headache, which then tends to become a chronic pain condition. We conclude that the whiplash disease typically evolves following a minor trauma without any signs of a tissue injury. It presents with central neuromotor dysfunction, such as electromyography (EMG) hyperactivity and abnormal activation patterns associated with dyscoordination of the involved and adjacent muscle groups. This indicates a central neurological rather than a peripheral traumatic pathology. This view places the cause of the whiplash disease within the central nervous system, and, in concordance with the EMG abnormalities and motor dyscoordination, we suggest the term cervical spinal dyssynergia for this pathology. It provides a new paradigm for further investigations of this disease as well as a window for possible specific neuropharmacological therapy directed towards dysfunctional neuromotor control.
Ferroptosis-Related Gene Contributes to Immunity, Stemness and Predicts Prognosis in Glioblastoma Multiforme
Authors: Dong Jiawei , Zhao Hongtao , Wang Fang , Jin Jiaqi , Ji Hang , Yan Xiuwei , Wang Nan , Zhang Jiheng , Hu Shaoshan
Published: March 2022

Ferroptosis, a recently discovered regulated programmed cell death, is associated with tumorigenesis and progression in glioblastoma. Based on widely recognized ferroptosis-related genes (FRGs), the regulation of ferroptosis patterns and corresponding characteristics of immune infiltration of 516 GBM samples with GSE13041, TCGA-GBM, and CGGA-325 were comprehensively analyzed. Here, we revealed the expression, mutations, and CNV of FRGs in GBM. We identified three distinct regulation patterns of ferroptosis and found the hub genes of immunity and stemness among DEGs in three patterns. A prognostic model was constructed based on five FRGs and verified at the mRNA and protein level. The risk score can not only predict the prognosis but also the degree of immune infiltration and ICB responsiveness by functional annotation. The overall assessment of FRGs in GBM patients will guide the direction of improved research and develop new prognostic prediction tools.
Disrupted Brain Functional Network Topology in Essential Tremor Patients With Poor Sleep Quality
Authors: Peng Jiaxin , Yang Jing , Li Junying , Lei Du , Li Nannan , Suo Xueling , Duan Liren , Chen Chaolan , Zeng Yan , Xi Jing , Jiang Yi , Gong Qiyong , Peng Rong
Published: March 2022

Sleep disturbances, especially poor quality of sleep (QoS), are common among essential tremor (ET) patients and may have adverse effects on their quality of life, but the etiology driving the poor QoS in these individuals remains inadequately understood. Few data are available on the neuroimaging alterations of ET with poor QoS. Thirty-eight ET patients with poor QoS (SleET), 48 ET patients with normal QoS (NorET), and 80 healthy controls (HCs) participated in this study. All subjects underwent a 3.0-T magnetic resonance imaging (MRI) scan for resting-state functional MRI data collection. Then, the whole-brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions. Graph theory and network-based statistical analyses were performed. We used a non-parametric permutation test for group comparisons of topological metrics. Partial correlation analyses between the topographical features and clinical characteristics were conducted. The SleET and NorET groups exhibited decreased clustering coefficients, global efficiency, and local efficiency and increased the characteristic path length. Both of these groups also showed reduced nodal degree and nodal efficiency in the left superior dorsolateral frontal gyrus, superior frontal medial gyrus (SFGmed), posterior cingulate gyrus (PCG), lingual gyrus, superior occipital gyrus, right middle occipital gyrus, and right fusiform gyrus. The SleET group additionally presented reduced nodal degrees and nodal efficiency in the right SFGmed relative to the NorET and HC groups, and nodal efficiency in the right SFGmed was negatively correlated with the Pittsburgh Sleep Quality Index score. The observed impaired topographical organizations of functional brain networks within the central executive network (CEN), default mode network (DMN), and visual network serve to further our knowledge of the complex interactions between tremor and sleep, adding to our understanding of the underlying neural mechanisms of ET with poor QoS.
Global MicroRNAs Expression Profile Analysis Reveals Possible Regulatory Mechanisms of Brain Injury Induced by Toxoplasma gondii Infection
Authors: Hou Zhaofeng , Wang Lele , Su Dingzeyang , Cai Weimin , Zhu Yu , Liu Dandan , Huang Siyang , Xu Jinjun , Pan Zhiming , Tao Jianping
Published: March 2022

Toxoplasma gondii (T. gondii) is an obligate intracellular parasitic protozoan that can cause toxoplasmosis in humans and other endotherms. T. gondii can manipulate the host gene expression profile by interfering with miRNA expression, which is closely associated with the molecular mechanisms of T. gondii-induced brain injury. However, it is unclear how T. gondii manipulates the gene expression of central nervous system (CNS) cells through modulation of miRNA expression in vivo during acute and chronic infection. Therefore, high-throughput sequencing was used to investigate expression profiles of brain miRNAs at 10, 25, and 50 days post-infection (DPI) in pigs infected with the Chinese I genotype T. gondii strain in this study. Compared with the control group 87, 68, and 135 differentially expressed miRNAs (DEMs) were identified in the infected porcine brains at 10, 25, and 50 DPI, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that a large number significantly enriched GO terms and KEGG pathways were found, and were mostly associated with stimulus or immune response, signal transduction, cell death or apoptosis, metabolic processes, immune system or diseases, and cancers. miRNA–gene network analysis revealed that the crucial connecting nodes, including DEMs and their target genes, might have key roles in the interactions between porcine brain and T. gondii. These results suggest that the regulatory strategies of T. gondii are involved in the modulation of a variety of host cell signaling pathways and cellular processes, containing unfolded protein response (UPR), oxidative stress (OS), autophagy, apoptosis, tumorigenesis, and inflammatory responses, by interfering with the global miRNA expression profile of CNS cells, allowing parasites to persist in the host CNS cells and contribute to pathological damage of porcine brain. To our knowledge, this is the first report on miRNA expression profile in porcine brains during acute and chronic T. gondii infection in vivo. Our results provide new insights into the mechanisms underlying T. gondii-induced brain injury during different infection stages and novel targets for developing therapeutic agents against T. gondii.
Uncovering Cortical Units of Processing From Multi-Layered Connectomes
Authors: Albers Kristoffer Jon , Liptrot Matthew G. , Ambrosen Karen Sandø , Røge Rasmus , Herlau Tue , Andersen Kasper Winther , Siebner Hartwig R. , Hansen Lars Kai , Dyrby Tim B. , Madsen Kristoffer H. , Schmidt Mikkel N. , Mørup Morten
Published: March 2022

Modern diffusion and functional magnetic resonance imaging (dMRI/fMRI) provide non-invasive high-resolution images from which multi-layered networks of whole-brain structural and functional connectivity can be derived. Unfortunately, the lack of observed correspondence between the connectivity profiles of the two modalities challenges the understanding of the relationship between the functional and structural connectome. Rather than focusing on correspondence at the level of connections we presently investigate correspondence in terms of modular organization according to shared canonical processing units. We use a stochastic block-model (SBM) as a data-driven approach for clustering high-resolution multi-layer whole-brain connectivity networks and use prediction to quantify the extent to which a given clustering accounts for the connectome within a modality. The employed SBM assumes a single underlying parcellation exists across modalities whilst permitting each modality to possess an independent connectivity structure between parcels thereby imposing concurrent functional and structural units but different structural and functional connectivity profiles. We contrast the joint processing units to their modality specific counterparts and find that even though data-driven structural and functional parcellations exhibit substantial differences, attributed to modality specific biases, the joint model is able to achieve a consensus representation that well accounts for both the functional and structural connectome providing improved representations of functional connectivity compared to using functional data alone. This implies that a representation persists in the consensus model that is shared by the individual modalities. We find additional support for this viewpoint when the anatomical correspondence between modalities is removed from the joint modeling. The resultant drop in predictive performance is in general substantial, confirming that the anatomical correspondence of processing units is indeed present between the two modalities. Our findings illustrate how multi-modal integration admits consensus representations well-characterizing each individual modality despite their biases and points to the importance of multi-layered connectomes as providing supplementary information regarding the brain's canonical processing units.
Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
Authors: Xu Zhibin , Tian Ye , Li A.-Xiang , Tang Jiahang , Jing Xiao-Yuan , Deng Chunshan , Mo Zhizhun , Wang Jiaxuan , Lai Juan , Liu Xuemei , Guo Xuantong , Li Tao , Li Shupeng , Wang Liping , Lu Zhonghua , Chen Zuxin , Liu Xin-an
Published: March 2022

The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.
Transgenic Canola Oil Improved Blood Omega-3 Profiles: A Randomized, Placebo-Controlled Trial in Healthy Adults
Authors: Lin Xinjie Lois , Baisley Joshua , Bier Anthony , Vora Drasty , Holub Bruce
Published: March 2022

Long-chain omega-3 polyunsaturated fatty acids (LC-ω3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play key roles in physiological functions and disease prevention. The nutrient gap in meeting LC-ω3 intake recommendations in the U.S. and globally can be addressed by alternative sources of LC-ω3. This randomized, placebo-controlled, seamless phase I/II study evaluated the pharmacokinetics, safety, and efficacy of a transgenic LC-ω3-rich canola oil in healthy adults. Participants (n = 33/group) were randomized to receive low-, mid-, or high-dose of the LC-ω3-rich oil (providing 285, 570, or 1,140 mg LC-ω3 PUFA, respectively) or placebo (corn oil). After one dose, plasma ω3 (primary outcome) levels were assessed over a 72 h pharmacokinetic period. Whole blood and red blood cells (RBC) ω3 and serum cardiovascular biomarkers were assessed during a 16-week continuation period with daily supplementation. Compared to low-dose and placebo, high-dose group showed greater DHA AUC0−72h and Cmax. A linear response was observed for DHA and EPA AUC0−72h. Compared to placebo, high- and mid-dose groups showed increased whole blood DHA, EPA, α-linolenic acids (ALA) (high-dose only), omega-3 score, and omega-3 index after 4 weeks, and increased DHA and EPA in RBC after 16 weeks (P < 0.05). No changes in cardiovascular biomarkers were seen. Overall, this LC-ω3-rich oil demonstrated good DHA bioavailability and significantly improved short and long-term blood LC-ω3 profiles. Sixteen weeks of daily supplementation of the LC-ω3-rich oil was safe and well-tolerated.
Exploration of a Novel Prognostic Nomogram and Diagnostic Biomarkers Based on the Activity Variations of Hallmark Gene Sets in Hepatocellular Carcinoma
Authors: Zhong Xiongdong , Yu Xianchang , Chang Hao
Published: March 2022

Background

The initiation and progression of tumors were due to variations of gene sets rather than individual genes. This study aimed to identify novel biomarkers based on gene set variation analysis (GSVA) in hepatocellular carcinoma.

Methods

The activities of 50 hallmark pathways were scored in three microarray datasets with paired samples with GSVA, and differential analysis was performed with the limma R package. Unsupervised clustering was conducted to determine subtypes with the ConsensusClusterPlus R package in the TCGA-LIHC (n = 329) and LIRI-JP (n = 232) cohorts. Differentially expressed genes among subtypes were identified as initial variables. Then, we used TCGA-LIHC as the training set and LIRI-JP as the validation set. A six-gene model calculating the risk scores of patients was integrated with the least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses. Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves were performed to assess predictive performances. Multivariate Cox regression analyses were implemented to select independent prognostic factors, and a prognostic nomogram was integrated. Moreover, the diagnostic values of six genes were explored with the ROC curves and immunohistochemistry.

Results

Patients could be separated into two subtypes with different prognoses in both cohorts based on the identified differential hallmark pathways. Six prognostic genes (ASF1A, CENPA, LDHA, PSMB2, SRPRB, UCK2) were included in the risk score signature, which was demonstrated to be an independent prognostic factor. A nomogram including 540 patients was further integrated and well-calibrated. ROC analyses in the five cohorts and immunohistochemistry experiments in solid tissues indicated that CENPA and UCK2 exhibited high and robust diagnostic values.

Conclusions

Our study explored a promising prognostic nomogram and diagnostic biomarkers in hepatocellular carcinoma.
Comprehensive Risk System Based on Shear Wave Elastography and BI-RADS Categories in Assessing Axillary Lymph Node Metastasis of Invasive Breast Cancer—A Multicenter Study
Authors: Zhang Huiting , Dong Yijie , Jia Xiaohong , Zhang Jingwen , Li Zhiyao , Chuan Zhirui , Xu Yanjun , Hu Bin , Huang Yunxia , Chang Cai , Xu Jinfeng , Dong Fajin , Xia Xiaona , Wu Chengrong , Hu Wenjia , Wu Gang , Li Qiaoying , Chen Qin , Deng Wanyue , Jiang Qiongchao , Mou Yonglin , Yan Huannan , Xu Xiaojing , Yan Hongju , Zhou Ping , Shao Yang , Cui Ligang , He Ping , Qian Linxue , Liu Jinping , Shi Liying , Zhao Yanan , Xu Yongyuan , Song Yanyan , Zhan Weiwei , Zhou Jianqiao
Published: March 2022

Purpose

To develop a risk stratification system that can predict axillary lymph node (LN) metastasis in invasive breast cancer based on the combination of shear wave elastography (SWE) and conventional ultrasound.

Materials and Methods

A total of 619 participants pathologically diagnosed with invasive breast cancer underwent breast ultrasound examinations were recruited from a multicenter of 17 hospitals in China from August 2016 to August 2017. Conventional ultrasound and SWE features were compared between positive and negative LN metastasis groups. The regression equation, the weighting, and the counting methods were used to predict axillary LN metastasis. The sensitivity, specificity, and the areas under the receiver operating characteristic curve (AUC) were calculated.

Results

A significant difference was found in the Breast Imaging Reporting and Data System (BI-RADS) category, the “stiff rim” sign, minimum elastic modulusof the internal tumor and peritumor region of 3 mm between positive and negative LN groups (p < 0.05 for all). There was no significant difference in the diagnostic performance of the regression equation, the weighting, and the counting methods (p > 0.05 for all). Using the counting method, a 0–4 grade risk stratification system based on the four characteristics was established, which yielded an AUC of 0.656 (95% CI, 0.617–0.693, p < 0.001), a sensitivity of 54.60% (95% CI, 46.9%–62.1%), and a specificity of 68.99% (95% CI, 64.5%–73.3%) in predicting axillary LN metastasis.

Conclusion

A 0–4 grade risk stratification system was developed based on SWE characteristics and BI-RADS categories, and this system has the potential to predict axillary LN metastases in invasive breast cancer.
UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
Authors: Luo Yiqiao , Han Shanshan , Yan Bin , Ji Huihui , Zhao Lian , Gladkich Jury , Herr Ingrid
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancreatic cells, TCGA, GEO-derived pancreatic tissues (malignant, n=413; nonmalignant, n=234), a pancreatic tissue array (n=96), and pancreatic tissues from our clinic (malignant, n=20; nonmalignant, n=20) were examined by a gene array, RT-qPCR, Western blotting, MTT, colony formation, wound-healing, siRNA-mediated gene silencing, bioinformatics, xenotransplantation, and immunohistochemistry assays. The cell cycle inhibitor, UHMK1, was identified to have the strongest correlation with H19. UHMK1 expression was enhanced in PDAC, and high UHMK1 expression correlated with tumor stage, and lower overall survival. siRNA-mediated UHMK1 downregulation inhibited progression signaling. siRNA-mediated downregulation of H19 or UHMK1 inhibited tumor proliferation and xenograft growth. Based on the correlation between UHMK1 expression and clinical parameters, we developed a nomogram that reliably predicts patient prognosis and overall survival. Together, we characterized UHMK1 as an H19-induced oncogene and verified it as a novel PDAC prognostic marker for overall survival.