bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolvin E1 Regulates Th17 Function and T Cell Activation
Authors: Oner Fatma , Alvarez Carla , Yaghmoor Wael , Stephens Danielle , Hasturk Hatice , Firatli Erhan , Kantarci Alpdogan
Published: March 2021

Resolvin E1 (RvE1) is a specialized pro-resolving lipid mediator derived from eicosapentaenoic acid and plays a critical role in resolving inflammation and tissue homeostasis. Th17 cells are a distinct group of T helper (Th) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases via the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the Th17-induced progression of inflammation and tissue destruction. In this study, we hypothesized that the RvE1 would restore homeostatic balance and inflammation by targeting the Th17 function. We designed three experiments to investigate the impact of RvE1 on different phases of Th17 response and the potential role of DCs: First CD4+ T cells were induced by IL-6/TGFβ to measure the effect of RvE1 on Th17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated Th17 differentiation in a co-culture model. Third, we measured the effect of RvE1 on DC maturation. RvE1 blocked the CD25, CCR6 and IL-17 expression; IL-17, IL-21, IL-10, and IL-2 production, suggesting inhibition of T cell activation, Th17 stimulation and chemoattraction. RvE1 also suppressed the activation of DCs by limiting their pro-inflammatory cytokine production. Our findings collectively demonstrated that the RvE1 targeted the Th17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.
The Role of Immunological and Clinical Biomarkers to Predict Clinical COVID-19 Severity and Response to Therapy—A Prospective Longitudinal Study
Authors: Copaescu Ana , James Fiona , Mouhtouris Effie , Vogrin Sara , Smibert Olivia C. , Gordon Claire L. , Drewett George , Holmes Natasha E. , Trubiano Jason A.
Published: March 2021

Background

The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined.

Methods

A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited – blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC).

Results

IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06, 35.77) in patients with NIC; and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was amplified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity.

Conclusions

Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.
M2 Macrophages Serve as Critical Executor of Innate Immunity in Chronic Allograft Rejection
Authors: Zhang Hanwen , Li Zhuonan , Li Wei
Published: March 2021

Allograft functional failure due to acute or chronic rejection has long been a major concern in the area of solid organ transplantation for decades. As critical component of innate immune system, the macrophages are unlikely to be exclusive for driving acute or chronic sterile inflammation against allografts. Traditionally, macrophages are classified into two types, M1 and M2 like macrophages, based on their functions. M1 macrophages are involved in acute rejection for triggering sterile inflammation thus lead to tissue damage and poor allograft survival, while M2 macrophages represent contradictory features, playing pivotal roles in both anti-inflammation and development of graft fibrosis and resulting in chronic rejection. Macrophages also contribute to allograft vasculopathy, but the phenotypes remain to be identified. Moreover, increasing evidences are challenging traditional identification and classification of macrophage in various diseases. Better understanding the role of macrophage in chronic rejection is fundamental to developing innovative strategies for preventing late graft loss. In this review, we will update the recent progress in our understanding of diversity of macrophage-dominated innate immune response, and reveal the roles of M2 macrophages in chronic allograft rejection as well.
Transcriptomic Responses of Four Pelagophytes to Nutrient (N, P) and Light Stress
Authors: Kang Yoonja , Harke Matthew J. , Berry Dianna L. , Collier Jackie L. , Wilhelm Steven W. , Dyhrman Sonya T. , Gobler Christopher J.
Published: March 2021

Pelagophytes are abundant picophytoplankton within open ocean ecosystems and the causative algae of harmful brown tide blooms in estuaries. The physiological capabilities facilitating the ecological success of pelagophytes in these diverse ecosystems remains poorly understood. Here, we investigated the transcriptional response of two coastal pelagophytes (Aureococcus anophagefferens and Aureoumbra lagunensis) and two open ocean pelagophytes (Pelagococcus subviridis and Pelagomonas calceolata) to conditions commonly found within the marine ecosystems where they thrive: low concentrations of nitrogen (N), phosphorus (P), or light. OrthoMCL was used to generate a total of 62,653 orthologous groups (OGs) with only a small fraction of these OGs (2,776 or 4.4%) being shared among all four pelagophytes. Of the commonly shared OGs, 8% were significantly differentially abundant under low N, P, or light with the majority associated with energy and lipid metabolism. Distinct responses among pelagophytes included increased abundance of transcripts encoding phosphate transporters (Aureococcus) and transcripts encoding a pyrophosphatase (Aureococcus and Pelagomonas) under low P, the expression of a suite of organic nitrogen-degrading enzymes under low N (Aureoumbra and Pelagomonas), increased abundance of transcripts encoding flavodoxins relative to ferredoxins (Pelagomonas) and transcripts encoding lysophospholipase (Pelagococcus) under low light, and both increases and decreases in abundance of transcripts encoding selenoproteins in all pelagophytes except Pelagococcus. Collectively, this study provides new information on the expressed gene compliment of these poorly characterized taxa and demonstrates that these pelagophytes possess a combination of shared and unique physiological features that likely facilitate their adaptation to distinct environmental conditions.
Exploring Metamaterials’ Structures Through the Relaxed Micromorphic Model: Switching an Acoustic Screen Into an Acoustic Absorber
Authors: Rizzi Gianluca , Collet Manuel , Demore Félix , Eidel Bernhard , Neff Patrizio , Madeo Angela
Published: March 2021

While the design of always new metamaterials with exotic static and dynamic properties is attracting deep attention in the last decades, little effort is made to explore their interactions with other materials. This prevents the conception of (meta-)structures that can enhance metamaterials’ unusual behaviors and that can be employed in real engineering applications. In this paper, we give a first answer to this challenging problem by showing that the relaxed micromorphic model with zero static characteristic length can be usefully applied to describe the refractive properties of simple meta-structures for extended frequency ranges and for any direction of propagation of the incident wave. Thanks to the simplified model’s structure, we are able to efficiently explore different configurations and to show that a given meta-structure can drastically change its overall refractive behavior when varying the elastic properties of specific meta-structural elements. In some cases, changing the stiffness of a homogeneous material which is in contact with a metamaterial’s slab, reverses the structure’s refractive behavior by switching it from an acoustic screen (total reflection) into an acoustic absorber (total transmission). The present paper clearly indicates that, while the study and enhancement of the intrinsic metamaterials’ properties is certainly of great importance, it is even more challenging to enable the conception of meta-structures that can eventually boost the use of metamaterials in real-case applications.
Phytic Acid: Properties and Potential Applications in Dentistry
Authors: Nassar Mohannad , Nassar Rania , Maki Husain , Al-Yagoob Abdullah , Hachim Mahmood , Senok Abiola , Williams David , Hiraishi Noriko
Published: March 2021

Inositol hexaphosphate (IP6) is the most abundant inositol phosphate in nature and an essential molecule for different biological functions. IP6 has a unique structure granting it distinctive properties; a high negative charge density provides IP6 with an immense chelating ability and valuable antioxidant properties. IP6 is also simple and cost-effective to produce. These features have attracted researchers and entrepreneurs to further study IP6 for a wide variety of applications in areas such as pharmaceutical, food and chemical industries, medicine, pharmacy, nutrition, and dentistry. The interest in IP6 in the dental field unfolded many decades ago following identification of a cariostatic ability and a positive impact on reducing enamel dissolution. Subsequently, IP6’s anti-plaque, anti-calculus and cement-forming properties have been investigated. Despite encouraging findings, there was a phase of decreased attention to IP6 which slowed down research progress. However, the potential use of IP6 has recently been revisited through several publications that provided deeper understanding into its mechanisms of action in the aforementioned applications. Studies have also explored new applications in endodontics, adhesive, preventive and regenerative dentistry, and IP6’s role in improving the characteristics and performance of dental materials. Evidence of the merits of IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights of future use of IP6 in the fields of orthodontics, implant and pediatric dentistry.
Identification of Novel Sensitive and Reliable Serovar-Specific Targets for PCR Detection of Salmonella Serovars Hadar and Albany by Pan-Genome Analysis
Authors: Ye Qinghua , Shang Yuting , Chen Moutong , Pang Rui , Li Fan , Xiang Xinran , Wang Chufang , Zhou Baoqing , Zhang Shuhong , Zhang Jumei , Yang Xiaojuan , Xue Liang , Ding Yu , Wu Qingping
Published: March 2021

The accurate and rapid classification of Salmonella serovars is an essential focus for the identification of isolates involved in disease in humans and animals. The purpose of current research was to identify novel sensitive and reliable serovar-specific targets and to develop PCR method for Salmonella C2 serogroups (O:8 epitopes) in food samples to facilitate timely treatment. A total of 575 genomic sequences of 16 target serovars belonging to serogroup C2 and 150 genomic sequences of non-target serovars were analysed by pan-genome analysis. As a result, four and three specific genes were found for serovars Albany and Hadar, respectively. Primer sets for PCR targeting these serovar-specific genes were designed and evaluated based on their specificity; the results showed high specificity (100%). The sensitivity of the specific PCR was 2.8 × 101–103 CFU/mL and 2.3 × 103–104 CFU/mL for serovars Albany and Hadar, respectively, and the detection limits were 1.04 × 103–104 CFU/g and 1.16 × 104–105 CFU/g in artificially contaminated raw pork samples. Furthermore, the potential functions of these serovar-specific genes were analysed; all of the genes were functionally unknown, except for one specific serovar Albany gene known to be a encoded secreted protein and one specific gene for serovars Hadar and Albany that is a encoded membrane protein. Thus, these findings demonstrate that pan-genome analysis is a precious method for mining new high-quality serovar-targets for PCR assays or other molecular methods that are highly sensitive and can be used for rapid detection of Salmonella serovars.
Genomic Feature Analysis of Betacoronavirus Provides Insights Into SARS and COVID-19 Pandemics
Authors: Li Xin , Chang Jia , Chen Shunmei , Wang Liangge , Yau Tung On , Zhao Qiang , Hong Zhangyong , Ruan Jishou , Duan Guangyou , Gao Shan
Published: March 2021

In December 2019, the world awoke to a new betacoronavirus strain named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Betacoronavirus consists of A, B, C and D subgroups. Both SARS-CoV and SARS-CoV-2 belong to betacoronavirus subgroup B. In the present study, we divided betacoronavirus subgroup B into the SARS1 and SARS2 classes by six key insertions and deletions (InDels) in betacoronavirus genomes, and identified a recently detected betacoronavirus strains RmYN02 as a recombinant strain across the SARS1 and SARS2 classes, which has potential to generate a new strain with similar risk as SARS-CoV and SARS-CoV-2. By analyzing genomic features of betacoronavirus, we concluded: (1) the jumping transcription and recombination of CoVs share the same molecular mechanism, which inevitably causes CoV outbreaks; (2) recombination, receptor binding abilities, junction furin cleavage sites (FCSs), first hairpins and ORF8s are main factors contributing to extraordinary transmission, virulence and host adaptability of betacoronavirus; and (3) the strong recombination ability of CoVs integrated other main factors to generate multiple recombinant strains, two of which evolved into SARS-CoV and SARS-CoV-2, resulting in the SARS and COVID-19 pandemics. As the most important genomic features of SARS-CoV and SARS-CoV-2, an enhanced ORF8 and a novel junction FCS, respectively, are indispensable clues for future studies of their origin and evolution. The WIV1 strain without the enhanced ORF8 and the RaTG13 strain without the junction FCS “RRAR” may contribute to, but are not the immediate ancestors of SARS-CoV and SARS-CoV-2, respectively.
Metagenomic Insight Into Patterns and Mechanism of Nitrogen Cycle During Biocrust Succession
Authors: Wang Qiong , Han Yingchun , Lan Shubin , Hu Chunxiang
Published: March 2021

The successional ecology of nitrogen cycling in biocrusts and the linkages to ecosystem processes remains unclear. To explore this, four successional stages of natural biocrust with five batches of repeated sampling and three developmental stages of simulated biocrust were studied using relative and absolute quantified multi-omics methods. A consistent pattern across all biocrust was found where ammonium assimilation, mineralization, dissimilatory nitrite to ammonium (DNiRA), and assimilatory nitrate to ammonium were abundant, while denitrification medium, N-fixation, and ammonia oxidation were low. Mathematic analysis showed that the nitrogen cycle in natural biocrust was driven by dissolved organic N and NO3–. pH and SO42– were the strongest variables affecting denitrification, while C:(N:P) was the strongest variable affecting N-fixation, DNiRA, nitrite oxidation, and dissimilatory nitrate to nitrite. Furthermore, N-fixation and DNiRA were closely related to elemental stoichiometry and redox balance, while assimilatory nitrite to ammonium (ANiRA) and mineralization were related to hydrological cycles. Together with the absolute quantification and network models, our results suggest that responsive ANiRA and mineralization decreased during biocrust succession; whereas central respiratory DNiRA, the final step of denitrification, and the complexity and interaction of the whole nitrogen cycle network increased. Therefore, our study stresses the changing environmental functions in the biocrust N-cycle, which are succession-dependent.
Combining Multicolor FISH with Fluorescence Lifetime Imaging for Chromosomal Identification and Chromosomal Sub Structure Investigation
Authors: Bhartiya Archana , Robinson Ian , Yusuf Mohammed , Botchway Stanley W.
Published: March 2021

Understanding the structure of chromatin in chromosomes during normal and diseased state of cells is still one of the key challenges in structural biology. Using DAPI staining alone together with Fluorescence lifetime imaging (FLIM), the environment of chromatin in chromosomes can be explored. Fluorescence lifetime can be used to probe the environment of a fluorophore such as energy transfer, pH and viscosity. Multicolor FISH (M-FISH) is a technique that allows individual chromosome identification, classification as well as assessment of the entire genome. Here we describe a combined approach using DAPI as a DNA environment sensor together with FLIM and M-FISH to understand the nanometer structure of all 46 chromosomes in the nucleus covering the entire human genome at the single cell level. Upon DAPI binding to DNA minor groove followed by fluorescence lifetime measurement and imaging by multiphoton excitation, structural differences in the chromosomes can be studied and observed. This manuscript provides a blow by blow account of the protocol required to perform M-FISH-FLIM of whole chromosomes.
α-Synuclein Up-regulates Monoamine Oxidase A Expression and Activity via Trans-Acting Transcription Factor 1
Authors: Jia Congcong , Cheng Cheng , Li Tianbai , Chen Xi , Yang Yuting , Liu Xinyao , Li Song , Le Weidong
Published: March 2021

Abnormal α-Synuclein (α-SYN) aggregates are the pathological hallmarks of Parkinson’s disease (PD), which may affect dopamine (DA) neuron function and DA metabolism. Monoamine oxidase A (MAOA) is an enzyme located on the outer mitochondrial membrane that catalyzes the oxidative deamination of DA. Both α-SYN and MAOA are associated with PD pathogenesis, suggesting possible crosstalk between these two molecules. In the present study, we aimed to investigate the potential impacts of α-SYN on MAOA function and further explore the underlying mechanisms. Our study showed that overexpression of α-SYN [both wild-type (WT) and A53T] increased MAOA function via upregulating its expression without impacting MAOA stability. Overexpression of α-SYNWT or α-SYNA53T enhanced the transcription activity of the MAOA promoter region containing the binding sites of cell division cycle associated 7 like (R1, a transcriptional repressor of MAOA) and trans-acting transcription factor 1 (Sp1, a transcription factor of MAOA). Interestingly, α-SYN selectively increased Sp1 expression, thereby enhancing the binding capacity of Sp1 with MAOA promoter to increase MAOA expression. Taken together, our findings demonstrate that α-SYN can upregulate MAOA expression via modulation of Sp1 and may shed light on future studies of α-SYN associated PD pathogenesis.
Deletion of the Thrombin Proteolytic Site in Neurofascin 155 Causes Disruption of Nodal and Paranodal Organization
Authors: Dutta Dipankar J. , Fields R. Douglas
Published: March 2021

In the central nervous system, myelin is attached to the axon in the paranodal region by a trimolecular complex of Neurofascin155 (NF155) in the myelin membrane, interacting with Caspr1 and Contactin1 on the axolemma. Alternative splicing of a single Neurofascin transcript generates several different Neurofascins expressed by several cell types, but NF155, which is expressed by oligodendrocytes, contains a domain in the third fibronectinIII-like region of the molecule that is unique. The immunoglobulin 5–6 domain of NF155 is essential for binding to Contactin1, but less is known about the functions of the NF155-unique third fibronectinIII-like domain. Mutations and autoantibodies to this region are associated with several neurodevelopmental and demyelinating nervous system disorders. Here we used Crispr-Cas9 gene editing to delete a 9 bp sequence of NF155 in this unique domain, which has recently been identified as a thrombin binding site and implicated in plasticity of the myelin sheath. This small deletion results in dysmyelination, eversion of paranodal loops of myelin, substantial enlargement of the nodal gap, a complete loss of paranodal septate junctions, and mislocalization of Caspr1 and nodal sodium channels. The animals exhibit tremor and ataxia, and biochemical and mass spectrometric analysis indicates that while NF155 is transcribed and spliced normally, the NF155 protein is subsequently degraded, resulting in loss of the full length 155 kDa native protein. These findings reveal that this 9 bp region of NF155 in its unique third fibronectinIII-like domain is essential for stability of the protein.
Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial
Authors: Lv Shuyu , Zhao Wenbo , Rajah Gary B. , Dandu Chaitu , Cai Lipeng , Cheng Zhe , Duan Honglian , Dai Qingqing , Geng Xiaokun , Ding Yuchuan
Published: March 2021

Background: Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated.

Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio (n = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume.

Discussions: This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS.

Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR2000038727.
Case Report: Migraine-Like Headache With Visual Aura Initiated by Endovascular Coiling Treatment for a Posterior Cerebral Artery Aneurysm
Authors: Chen Xin , Zhang Juan , Li Han-Li , Deng Zi-Ru , Wang Long , Cao Li , Xie Cheng-Juan , Wang Yu
Published: March 2021

Cervical, anterior, and middle cerebral artery aneurysm is a causative factor for migraine, and endovascular treatment usually improves migraine headache. Posterior cerebral artery (PCA) aneurysm is a rare condition, and its association with migraine is very rarely reported. In addition, endovascular coiling treatment causing migraine-like headache has never been reported. Here, we describe a newly developed migraine-like headache with visual aura after endovascular coiling treatment for PCA aneurysm in a 31-year-old female patient. One month after the endovascular therapy, the patient stopped using the antiplatelet agents clopidogrel and aspirin and presented with an episodic headache attack twice a month with typical migraine features, including visual aura, right-sided temporal throbbing pain accompanied with nausea, vomiting, and photophobia. The recurrence of migraine-like headache with visual aura was terminated by clopidogrel administration. The generation of the migraine-like headache with visual aura is probably associated with microemboli due to endovascular coiling. This case supports the hypothesis that migraine with aura can be associated with microemboli of variant origins.
Case Report: Anti-NMDA Receptor Encephalitis With Bilateral Hearing Loss as the Initial Symptom
Authors: Cheng Hongjiang , Yang Fengbing , Zhang Jing , Xu Lina , Jia Longbin , Zhao Doudou , Liu Wei , Li Huimin
Published: March 2021

Introduction: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease associated with the NMDA receptor. This paper describes a patient who presented with bilateral hearing loss as the initial symptom of anti-NMDAR encephalitis.

Case Report: We describe a 31-year-old young female with anti-NMDAR encephalitis who presented with bilateral severe hearing loss after brief loss of consciousness and then accompanied by other symptoms, such as generalized tonic–clonic seizures, manic episodes, excessive salivation, severe cognitive impairment, and complex non-convulsive status epilepticus. Great improvement was achieved by a combined treatment of steroid, IVIG, and plasmapheresis, especially after surgical removal of the ovarian teratoma. When she was discharged on hospital day 43, her hearing loss obtained a significant improvement.

Conclusion: This case study and literature review investigated the impairment of hearing loss and its subsequent treatment in patients with anti-NMDAR encephalitis.
Robust Cortical Thickness Morphometry of Neonatal Brain and Systematic Evaluation Using Multi-Site MRI Datasets
Authors: Liu Mengting , Lepage Claude , Kim Sharon Y. , Jeon Seun , Kim Sun Hyung , Simon Julia Pia , Tanaka Nina , Yuan Shiyu , Islam Tasfiya , Peng Bailin , Arutyunyan Knarik , Surento Wesley , Kim Justin , Jahanshad Neda , Styner Martin A. , Toga Arthur W. , Barkovich Anthony James , Xu Duan , Evans Alan C. , Kim Hosung
Published: March 2021

The human brain grows the most dramatically during the perinatal and early post-natal periods, during which pre-term birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal magnetic resonance imaging (MRI) pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the cerebrospinal fluid (CSF)/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 pre-term and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532 ± 0.035 mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with post-menstrual age (PMA) at scan (p < 0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3 mm at 28 weeks of PMA to 1.8 mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.
Spinal Epidural Cavernous Hemangiomas: A Clinical Series of 9 Cases and Literature Review
Authors: Zhao Liyan , Jiang Yining , Wang Yubo , Bai Yang , Sun Ying , Li Yunqian
Published: March 2021

Objective

Spinal epidural cavernous hemangiomas are very rare vascular lesions and are, therefore, seldom reported and easily misdiagnosed. Herein, we present a series of 9 cases with spinal epidural cavernous hemangiomas and discuss their pathogenesis, clinical characteristics, radiological findings, differential diagnosis, surgical interventions, pathological characteristics, and prognosis.

Methods

We retrospectively retrieved and analyzed the data of patients with pure epidural cavernous hemangiomas, who underwent spinal magnetic resonance imaging, and surgical intervention at the First Hospital of Jilin University, China, between January 2005 and December 2019. The data on patients’ clinical manifestations, imaging characteristics, surgical intervention, histopathological findings, and postoperative follow-up were also recorded and analyzed.

Results

In all, 5 men and 4 women with the mean age of 61 years (range, 41–78 years) were recruited. All patients experienced a gradual onset of symptoms and a slowly progressive clinical course, and no patient presented an acute onset of symptoms. The clinical manifestations include myelopathic signs in 8 patients (88.9%) and radicular symptoms in 3 patients (33.3%). On T1-weighted imaging, 6 lesions appeared isointense (55.6%), and 4 lesions exhibited hypointense (44.4%) signals. On T2-weighted imaging, 8 lesions appeared hyperintense (88.9%), and 1 lesion was heterogeneously intense (11.1%). Following gadolinium administration, 5 lesions appeared homogeneous with significant enhancement (55.6%), 1 lesion was homogeneous and mild enhancement (11.1%), and 3 lesions were heterogeneous with mild enhancement (33.3%). All patients received early microsurgery assisted by intraoperative electrophysiologic monitoring and neuronavigation in the lateral position via the posterior midline approach. Five patients underwent total laminectomy (55.6%), and 4 underwent hemilaminectomy (44.4%). Total excision was achieved in all cases. The average follow-up period was 55.1 months (ranging 10–123 months). All patients exhibited significant clinical improvement of their neurological deficits and achieved a favorable outcome with no recorded recurrence at last follow-up.

Conclusions

Spinal epidural cavernous hemangiomas are rare vascular malformations. Early surgical treatment with total resection is an optimum treatment, particularly for patients with an acute exacerbation onset. The prognosis is mostly good and depends predominantly on the severity of the preoperative status.
Evaluation of 18F-FMISO PET and 18F-FDG PET Scans in Assessing the Therapeutic Response of Patients With Metastatic Colorectal Cancer Treated With Anti-Angiogenic Therapy
Authors: Lee Sze Ting , Tebbutt Niall , Gan Hui Kong , Liu Zhanqi , Sachinidis John , Pathmaraj Kunthi , Scott Andrew Mark
Published: March 2021

Introduction

Tumor hypoxia and angiogenesis are implicated in tumor growth and metastases, and anti-angiogenic therapies have an important role in treating patients with metastatic colorectal cancer. However, the prevalence of hypoxia has not been fully evaluated in colorectal liver metastases, and hypoxic response to anti-angiogenic therapy has not been clearly established. The aims of the study were to evaluate the changes seen on 18F-FMISO and 18F-FDG PET scans in patients treated with anti-angiogenic therapy, and to correlate these measures of hypoxia and metabolism with clinical outcomes, and blood biomarkers of angiogenesis.

Methods

Patients with metastatic colorectal carcinoma planned for treatment with bevacizumab and chemotherapy received routine staging investigations prior to any treatment, including a FDG PET scan. A FMISO PET scan was performed within 4 weeks of staging tests, with blood specimens collected at that time for serum VEGF and osteopontin measurement. Follow-up FDG and FMISO scans were performed after 1 cycle of treatment. Results were compared to response (RECIST), progression free survival (PFS), and overall survival (OS).

Results

A total of 15 patients were recruited into this prospective trial, of which 13 patients were evaluable for assessment of treatment follow-up. Baseline FDG uptake was higher than FMISO uptake, and there was a significant decrease in FDG uptake (SUVmax and TGV) but not FMISO uptake (SUVmax and TNR) after treatment. There was a positive correlation between FDG and FMISO SUVmax on both baseline and post-treatment PET scans. Blood biomarkers of serum VEGF and osteopontin were significantly correlated with the FDG and FMISO PET parameters.

Conclusions

This study shows that hypoxia in metastatic colorectal cancer, assessed by FMISO PET, shows minor changes following initial treatment with anti-angiogenic therapy, but is associated with therapeutic response. FDG PET uptake changes (SUVmax, TLG) are also associated with response to anti-angiogenic therapy. These findings demonstrate the interplay between tumor metabolism and hypoxic regulation following anti-angiogenic treatment of metastatic colorectal cancer.
The Significant Role of the Microfilament System in Tumors
Authors: Jiang Xin , Qin Yiming , Kun Liu , Zhou Yanhong
Published: March 2021

Actin is the structural protein of microfilaments, and it usually exists in two forms: monomer and polymer. Among them, monomer actin is a spherical molecule composed of a polypeptide chain, also known as spherical actin. The function of actin polymers is to produce actin filaments, so it is also called fibroactin. The actin cytoskeleton is considered to be an important subcellular filament system. It interacts with numerous relevant proteins and regulatory cells, regulating basic functions, from cell division and muscle contraction to cell movement and ensuring tissue integrity. The dynamic reorganization of the actin cytoskeleton has immense influence on the progression and metastasis of cancer as well. This paper explores the significance of the microfilament network, the dynamic changes of its structure and function in the presence of a tumor, the formation process around the actin system, and the relevant proteins that may be target molecules for anticancer drugs so as to provide support and reference for interlinked cancer treatment research in the future.
Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting the PI3K–AKT Pathway and Activating the AMPK–ROS Pathway
Authors: Wei Xuan , Shi Juanjuan , Lin Qianhan , Ma Xiaoxue , Pang Yingxin , Mao Hongluan , Li Rui , Lu Wei , Wang Yu , Liu Peishu
Published: March 2021

Background: Ovarian cancer is the most lethal female genital malignancy. Although cisplatin is the first-line chemotherapy to treat ovarian cancer patients along with debulking surgeries, its efficacy is limited due to the high incidence of cisplatin resistance. ATP citrate lyase (ACLY) has been shown to be a key metabolic enzyme and is associated with poor prognosis in various cancers, including ovarian cancer. Nevertheless, no studies have probed the mechanistic relationship between ACLY and cisplatin resistance.

Methods: Survival analysis was mainly carried out online. Bioinformatic analysis was performed in R/R studio. Proliferative activity was measured by MTT and colony formation assays. Cell cycle and apoptosis analysis were performed by flow cytometry. The acquired-cisplatin-resistant cell line A2780/CDDP was generated by exposing A2780 to cisplatin at gradually elevated concentrations. MTT assay was used to calculate IC50 values of cisplatin. A xenograft tumor assay was used test cell proliferation in vivo.

Results: Higher expression of ACLY was found in ovarian cancer tissue and related to poor prognosis. Knockdown of ACLY in A2780, SKOV3, and HEY cells inhibited cell proliferation, caused cell-cycle arrest by modulating the P16–CDK4–CCND1 pathway, and induced apoptosis probably by inhibiting p-AKT activity. Bioinformatic analysis of the GSE15709 dataset revealed upregulation of ACLY and activation of PI3K–AKT pathway in cells with acquired cisplatin resistance, in line with observations on A2780/CDDP cells that we generated. Knockdown of ACLY alleviated cisplatin resistance, and works synergistically with cisplatin treatment to induce apoptosis in A2780/CDDP cells by inhibiting the PI3K–AKT pathway and activating AMPK–ROS pathway. The ACLY-specific inhibitor SB-204990 showed the same effect. In A2780/CDDP cells, AKT overexpression could attenuate cisplatin re-sensitization caused by ACLY knockdown.

Conclusions: Knockdown of ACLY attenuated cisplatin resistance by inhibiting the PI3K–AKT pathway and activating the AMPK–ROS pathway. These findings suggest that a combination of ACLY inhibition and cisplatin might be an effective strategy for overcoming cisplatin resistance in ovarian cancer.
Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update
Authors: Lin Yiping , Li Yuke , Zeng Yuanlian , Tian Bin , Qu Xiaolan , Yuan Qianghua , Song Ying
Published: March 2021

Magnolol (MG) is one of the primary active components of Magnoliae officinalis cortex, which has been widely used in traditional Chinese and Japanese herbal medicine and possesses a wide range of pharmacological activities. In recent years, attention has been drawn to this component due to its potential as an anti-inflammatory and antitumor drug. To summarize the new biological and pharmacological data on MG, we screened the literature from January 2011 to October 2020. In this review, we provide an actualization of already known anti-inflammatory, cardiovascular protection, antiangiogenesis, antidiabetes, hypoglycemic, antioxidation, neuroprotection, gastrointestinal protection, and antibacterial activities of MG. Besides, results from studies on antitumor activity are presented. We also summarized the molecular mechanisms, toxicity, bioavailability, and formulations of MG. Therefore, we provide a valid cognition of MG.
Farey Trees Explain Sequential Effects in Choice Response Time
Authors: Annand Colin T. , Fleming Sheila M. , Holden John G.
Published: March 2021

The latencies of successive two-alternative, forced-choice response times display intricately patterned sequential effects, or dependencies. They vary as a function of particular trial-histories, and in terms of the order and identity of previously presented stimuli and registered responses. This article tests a novel hypothesis that sequential effects are governed by dynamic principles, such as those entailed by a discrete sine-circle map adaptation of the Haken Kelso Bunz (HKB) bimanual coordination model. The model explained the sequential effects expressed in two classic sequential dependency data sets. It explained the rise of a repetition advantage, the acceleration of repeated affirmative responses, in tasks with faster paces. Likewise, the model successfully predicted an alternation advantage, the acceleration of interleaved affirmative and negative responses, when a task’s pace slows and becomes more variable. Detailed analyses of five studies established oscillatory influences on sequential effects in the context of balanced and biased trial presentation rates, variable pacing, progressive and differential cognitive loads, and dyadic performance. Overall, the empirical patterns revealed lawful oscillatory constraints governing sequential effects in the time-course and accuracy of performance across a broad continuum of recognition and decision activities.
Acid-Catalyzed Conversion of Cellulose Into Levulinic Acid With Biphasic Solvent System
Authors: Ma Changyue , Cai Bo , Zhang Le , Feng Junfeng , Pan Hui
Published: March 2021

In this work, acid-catalyzed conversion of cellulose into levulinic acid in a biphasic solvent system was developed. Compared to a series of catalysts investigated in this study, the Amberlyst-15 as a more efficient acid catalyst was used in the hydrolysis of cellulose and further dehydration of derived intermediates into levulinic acid. Besides, the mechanism of biphasic solvent system in the conversion of cellulose was studied in detail, and the results showed biphasic solvent system can promote the conversion of cellulose and suppress the polymerization of the by-products (such as lactic acid).The reaction conditions, such as temperature, time, and catalyst loading were changed to investigate the effect on the yield of levulinic acid. The results indicated that an appealing LA yield of 59.24% was achieved at 200°C and 180 min with a 2:1 ratio of Amberlyst-15 catalyst and cellulose in GVL/H2O under N2 pressure. The influence of different amounts of NaCl addition to this reaction was also investigated. This study provides an economical and environmental-friendly method for the acid-catalyzed conversion of cellulose and high yield of the value-added chemical.
Psychometric Properties of the Bern Illegitimate Tasks Scale – Spanish Version
Authors: Valdivieso Portilla Denisse Lizette , Gonzalez Rosero Angélica , Alvarado-Villa Geovanny , Moncayo-Rizzo Jorge
Published: March 2021

In recent years, a new factor for work stress has been studied along with stress as an offense to self-theory. Illegitimate tasks refer to assignments that are unnecessary or are not related to the employee’s role. Because of this, the Bern Illegitimate Tasks Scale was developed, which measures illegitimate tasks in terms of unreasonable tasks and unnecessary tasks. There are no studies in Latin America on illegitimate tasks, so the purpose of this research is to translate and validate the Bern Illegitimate Tasks Scale. The study was performed with a sample of nursing staff from a hospital in Guayaquil, Ecuador. Written informed consent was obtained from each of the participants. The reliability of the questionnaire was evaluated and its structural validity was verified by exploratory factor analysis and confirmatory factor analysis. The internal consistency of the whole scale, measured by Cronbach’s alpha, was 0.857. Moreover, the unnecessary and unreasonable subscales measure were 0.846 and 0.841, respectively. The exploratory factor analysis supported a two-factor model that explained 73.96% of the variance. Additionally, the confirmatory factor analysis showed good indexes of fit (GFI = 0.915, CFI = 0.955, TLI = 0.933, SRMR = 0.084, and RMSEA = 0.087). The Spanish version of the Bern Illegitimate Tasks Scale presents good psychometric properties and can be applied to nurses in the Ecuadorian population.
Meridian-Specific and Post-Optical Deficits of Spatial Vision in Human Astigmatism: Evidences From Psycho-Physical and EEG Scalings
Authors: Gu Li , Wang Yiyao , Feng Lei , Li Saiqun , Zhang Mengwei , Ye Qingqing , Zhuang Yijing , Lu Zhong-Lin , Li Jinrong , Yuan Jin
Published: March 2021

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia (MA). Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function (CSF) and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism (AST group, 20 eyes) and thirteen participants with (MA group, 19 eyes) were recruited in the current study. CSFs and spatial sweep visual evoked potentials (sVEP) were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF (AULCSF), spatial frequency threshold corresponding to 80% contrast gratings (SF threshold at 80% ctr), and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian (measured with horizontal gratings) was lower than that along strong meridian (measured with vertical gratings) in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions.
Visual Search in 3D: Effects of Monoscopic and Stereoscopic Cues to Depth on the Validity of Feature Integration Theory and Perceptual Load Theory
Authors: Greene Ciara M. , Broughan John , Hanlon Anthony , Keane Seán , Hanrahan Sophia , Kerr Stephen , Rooney Brendan
Published: March 2021

Previous research has successfully used feature integration theory to operationalise the predictions of Perceptual Load Theory, while simultaneously testing the predictions of both models. Building on this work, we test the extent to which these models hold up in a 3D world. In two experiments, participants responded to a target stimulus within an array of shapes whose apparent depth was manipulated using a combination of monoscopic and stereoscopic cues. The search task was designed to test the predictions of (a) feature integration theory, as the target was identified by a single feature or a conjunction of features and embedded in search arrays of varying size, and (b) perceptual load theory, as the task included congruent and incongruent distractors presented alongside search tasks imposing high or low perceptual load. Findings from both experiments upheld the predictions of feature integration theory, regardless of 2D/3D condition. Longer search times in conditions with a combination of monoscopic and stereoscopic depth cues suggests that binding features into three-dimensional objects requires greater attentional effort. This additional effort should have implications for perceptual load theory, yet our findings did not uphold its predictions; the effect of incongruent distractors did not differ between conjunction search trials (conceptualised as high perceptual load) and feature search trials (low perceptual load). Individual differences in susceptibility to the effects of perceptual load were evident and likely explain the absence of load effects. Overall, our findings suggest that feature integration theory may be useful for predicting attentional performance in a 3D world.