bluuebunny/crossref_metadata_2025 huggingface dataset:
ZNF384: A Potential Therapeutic Target for Psoriasis and Alzheimer’s Disease Through Inflammation and Metabolism
Authors: Liu Shougang , Yuan Xiuqing , Su Hang , Liu Fanghua , Zhuang Zhe , Chen Yongfeng
Published: May 2022

Background

Psoriasis is an immune-related skin disease notable for its chronic inflammation of the entire system. Alzheimer’s disease (AD) is more prevalent in psoriasis than in the general population. Immune-mediated pathophysiologic processes may link these two diseases, but the mechanism is still unclear. This article aimed to explore potential molecular mechanisms in psoriasis and AD.

Methods

Gene expression profiling data of psoriasis and AD were acquired in the Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were first applied in two datasets. Differentially expressed genes (DEGs) of two diseases were identified, and common DEGs were selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to explore common biological pathways. Signature transcription factors (STFs) were identified and their diagnostic values was calculated by receiver operating characteristic (ROC) curve analysis in the exploration cohort and verified in the validation cohort. The expression levels of STFs were further investigated in the validation cohort and the GTEx Portal Database. Additionally, four kinds of interaction analysis were performed: correlation analysis among STFs, gene-gene, chemical-protein, and protein-ligand interaction analyses. In the end, we predicted the transcription factor that potentially regulates STFs.

Results

Biosynthesis and metabolic pathways were enriched in GSEA analysis. In ssGSEA analysis, most immunoreaction gene lists exhibited differential enrichment in psoriasis cases, whereas three receptor-related gene lists did in AD. The KEGG analysis of common DEGs redetermined inflammatory and metabolic pathways essential in both diseases. 5 STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) were screened from common DEGs. The ROC analysis indicated that all STFs have diagnostic values in two diseases, especially ZFPM2. The correlation analysis, gene-gene, chemical-protein, and protein-ligand interaction analyses suggested that STFs interplay and involve inflammation and aberrant metabolism. Eventually, ZNF384 was the predicted transcription factor regulating PPARG, ZNF415, HLX, and ANHX.

Conclusions

The STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) may increase the morbidity rate of AD in psoriasis by initiating a positive feedback loop of excessive inflammation and metabolic disorders. ZNF384 is a potential therapeutic target for psoriasis and AD by regulating PPARG, ZNF415, HLX, and ANHX.
Single-Cell Transcriptomics Revealed Subtype-Specific Tumor Immune Microenvironments in Human Glioblastomas
Authors: Xiao Yong , Wang Zhen , Zhao Mengjie , Deng Yanxiang , Yang Mingyu , Su Graham , Yang Kun , Qian Chunfa , Hu Xinhua , Liu Yong , Geng Liangyuan , Xiao Yang , Zou Yuanjie , Tang Xianglong , Liu Hongyi , Xiao Hong , Fan Rong
Published: May 2022

Human glioblastoma (GBM), the most aggressive brain tumor, comprises six major subtypes of malignant cells, giving rise to both inter-patient and intra-tumor heterogeneity. The interaction between different tumor subtypes and non-malignant cells to collectively shape a tumor microenvironment has not been systematically characterized. Herein, we sampled the cellular milieu of surgically resected primary tumors from 7 GBM patients using single-cell transcriptome sequencing. A lineage relationship analysis revealed that a neural-progenitor-2-like (NPC2-like) state with high metabolic activity was associated with the tumor cells of origin. Mesenchymal-1-like (MES1-like) and mesenchymal-2-like (MES2-like) tumor cells correlated strongly with immune infiltration and chronic hypoxia niche responses. We identified four subsets of tumor-associated macrophages/microglia (TAMs), among which TAM-1 co-opted both acute and chronic hypoxia-response signatures, implicated in tumor angiogenesis, invasion, and poor prognosis. MES-like GBM cells expressed the highest number of M2-promoting ligands compared to other cellular states while all six states were associated with TAM M2-type polarization and immunosuppression via a set of 10 ligand–receptor signaling pathways. Our results provide new insights into the differential roles of GBM cell subtypes in the tumor immune microenvironment that may be deployed for patient stratification and personalized treatment.
Environmental Quality and Ecological Risk Assessment of Heavy Metals in the Zhuhai Coast, China
Authors: Wu Jin , Rong Shaowei , Wang Miaowei , Lu Rong , Liu Jingchao
Published: May 2022

The rapid urbanization and industrialization in the coastal Zhuhai have resulted in severe heavy metal contamination. Heavy metals are extensively used as indicators of coastal contamination, but the comparability among different geographic environments needs to be further explored and scrutinized. In this study, heavy metals (i.e., As, Zn, Cd, Cr, Hg, Cu, and Pb) in surface seawater (20 sites), sediments (10 sites), and organisms (13 sites, shellfish, algae, fish, and crustaceans) were analyzed to assess the distribution, enrichment, and ecological risk in the coastal regions of Zhuhai (2017 and 2018). The results showed that Cu, Zn, and Pb exceeded the standards of seawater, indicating the presence of anthropogenic pollution. Meanwhile, the ecological risk results showed that Cd and Cu indicated moderately high environmental risks. The quantity and quality of heavy metals in organisms showed different trends in the sea, which affected marine organisms in the northeastern area. The main factors contributing to the ecological risk of these two heavy metals are the emissions from chemical companies. Therefore, preserving the high biological diversity in this area is important to ensure the health and productivity of the seawater ecosystem in the coastal area. These results may play a key role in promoting decision makers to manage the sustainability of the Zhuhai coast.
Experimental Study on the Optimization of Polymer-Modified Cement-Based Composite Sealing Materials and Mechanical Properties and Permeability of Cemented Coal Bodies
Authors: Zhang Baoyong , Yu Yue , Gao Xia , Wu Qiang , Zhang Qiang , Liu Chuanhai
Published: May 2022

As a critical technical issue, gas extraction borehole sealing significantly restricts the effects of gas extraction. Polymer-modified cement-based composite (PMCC) sealing materials were developed to improve the sealing effect of gas extraction drilling. In this study, a self-built mechanical property and permeability test platform for grouting-based cemented coal bodies was used to test the viscosity, gelation time, and mechanical properties of PMCC sealing materials and the permeability of cemented coal bodies. Through the obtained relevant results, it was demonstrated that the material viscosity of PMCC sealing materials and the permeability and compressive strength of cemented bodies are under the influence of additive ratios. Moreover, the viscosity of sealing materials was found to be linearly related to the gelation time. In particular, the higher the viscosity, the shorter the gelation time. Additionally, on one hand, it was found that the viscosity of such sealing materials is positively correlated to the compressive strength of cemented coal bodies. On the other hand, it forms a negative correlation with their permeability. Based on relevant analysis outcomes, it was deemed that the sufficient hydration reaction and the interspace reticulate microstructure formed by the polymer of PMCC sealing materials allow the cemented coal body to achieve high compressive strength and low permeability.
Composites Made of Carbon Nanotubes and Silver Nanoparticles for Conductive Aerosol-Jet Deposition Ink: The Double-Edged Sword of Functionalization
Authors: Schulman Omri , Samira Raz , Lachman Noa
Published: May 2022

Optimizing conductive ink for Direct-Write Additive Manufacturing, this work explores the effect of carboxylic functionalization of multi-walled carbon nanotubes on their affinity to silver nanoparticles deposited on them. We show a correlation between functionalization and the size of the resulted NPs: the diameter of the silver NPs deposited on pristine CNTs (∼5 nm diameter) is third of that of NPs deposited on functionalized CNTs (∼15 nm). Electrical characterization of the silver-decorated CNT-based ink shows a more significant improvement in conductivity of the functionalized CNTs-decorated with silver compared to the pristine one (maximal ∼40 and ∼20% increase in conductivity over their undecorated counterpart, respectively). However, CNT functionalization severely damages the conductivity of the CNTs themselves, resulting in a much lower conductivity. This “double-edged sword” effect of functionalization results in the highest absolute specific conductivity (3.79 × 103 S/m) achieved by decorating pristine CNTs with 25 wt% of silver. Nevertheless, the observed enhanced conductivity and the ability to control the composite’s morphology by functionalization allow fine-tuning of morphology-based properties, such as surface enhanced Raman scattering and optimization of the ink for sensing applications.
Macular Retinal Microvasculature of Hyperopia, Emmetropia, and Myopia in Children
Authors: Lv Liang , Li Mu , Chang Xuejiao , Zhu Mengxia , Liu Ying , Wang Ping , Xiang Yan
Published: May 2022

Purpose

To compare macular retinal microcirculation in myopia, emmetropia, and hyperopia groups and investigate the relationship between macular retinal microcirculation and axial length (AL) in children.

Methods

Forty myopic, 29 emmetropic, and 34 hyperopic eyes were included. All the recruited eyes underwent optical coherence tomography angiography (OCTA) examinations. After adjusting the image size by the Littmann method and Bennett formula, the vessel density (VD) of the deep capillary plexus (DCP) and superficial vascular plexus (SVP) were assessed.

Results

The VD of the DCP was significantly lower in the myopia group than in the hyperopia group, whereas no significant differences in the VD of the SVP were observed among the myopia, emmetropia, and hyperopia groups. The VD of the DCP was significantly associated with AL, spherical equivalent (SE), and foveal retinal thickness (FRT), whereas the VD of the SVP was only significantly associated with FRT but not with AL or SE.

Conclusions

The myopic VD of the DCP was significantly lower than the hyperopic one, and the VD of the DCP was significantly associated with AL, indicating that myopia has a lower VD of the DCP, and AL could have a negative effect on the VD of the DCP. Thus, early myopic axial stretching might decrease retinal blood perfusion of the DCP in children.
2,5-Diketopiperazines From a Sponge-Derived Fungus Aspergillus sclerotiorum
Authors: Wang Chao-Yi , Liu Xiao-Han , Zheng Yao-Yao , Ning Xing-Yan , Zhang Ya-Hui , Fu Xiu-Mei , Li Xin , Shao Chang-Lun , Wang Chang-Yun
Published: May 2022

Three new 2,5-diketopiperazines, speramide C (1), 3,21-epi-taichunamide F (2), and 2-epi-amoenamide C (3), along with four known analogs (4–7), were obtained from the sponge-derived fungus Aspergillus sclerotiorum GDST-2013-0501 collected from the South China Sea. The chemical structures of new compounds were elucidated by analyzing NMR and MS spectroscopy data, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compound 1 represents the first prenylated indole alkaloid with an ethylene oxide ring at the isopentenyl side chain. Compound 4 displayed DNA topoisomerase I inhibitory activity and antibacterial activity against Staphylococcus epidermidis. The low cytotoxic or non-cytotoxic compound 4 displayed DNA topoisomerase I inhibitory activity, which could provide a starting point for the development of antitumor agents.
Atypical Carboxysome Loci: JEEPs or Junk?
Authors:   USF Genomics Class 2020,   USF Genomics Class 2021, Sutter Markus , Kerfeld Cheryl A. , Scott Kathleen M.
Published: May 2022

Carboxysomes, responsible for a substantial fraction of CO2 fixation on Earth, are proteinaceous microcompartments found in many autotrophic members of domain Bacteria, primarily from the phyla Proteobacteria and Cyanobacteria. Carboxysomes facilitate CO2 fixation by the Calvin-Benson-Bassham (CBB) cycle, particularly under conditions where the CO2 concentration is variable or low, or O2 is abundant. These microcompartments are composed of an icosahedral shell containing the enzymes ribulose 1,5-carboxylase/oxygenase (RubisCO) and carbonic anhydrase. They function as part of a CO2 concentrating mechanism, in which cells accumulate HCO3− in the cytoplasm via active transport, HCO3− enters the carboxysomes through pores in the carboxysomal shell proteins, and carboxysomal carbonic anhydrase facilitates the conversion of HCO3− to CO2, which RubisCO fixes. Two forms of carboxysomes have been described: α-carboxysomes and β-carboxysomes, which arose independently from ancestral microcompartments. The α-carboxysomes present in Proteobacteria and some Cyanobacteria have shells comprised of four types of proteins [CsoS1 hexamers, CsoS4 pentamers, CsoS2 assembly proteins, and α-carboxysomal carbonic anhydrase (CsoSCA)], and contain form IA RubisCO (CbbL and CbbS). In the majority of cases, these components are encoded in the genome near each other in a gene locus, and transcribed together as an operon. Interestingly, genome sequencing has revealed some α-carboxysome loci that are missing genes encoding one or more of these components. Some loci lack the genes encoding RubisCO, others lack a gene encoding carbonic anhydrase, some loci are missing shell protein genes, and in some organisms, genes homologous to those encoding the carboxysome-associated carbonic anhydrase are the only carboxysome-related genes present in the genome. Given that RubisCO, assembly factors, carbonic anhydrase, and shell proteins are all essential for carboxysome function, these absences are quite intriguing. In this review, we provide an overview of the most recent studies of the structural components of carboxysomes, describe the genomic context and taxonomic distribution of atypical carboxysome loci, and propose functions for these variants. We suggest that these atypical loci are JEEPs, which have modified functions based on the presence of Just Enough Essential Parts.
Seasonality and Meteorological Factors Associated With Different Hand, Foot, and Mouth Disease: Serotype-Specific Analysis From 2010 to 2018 in Zhejiang Province, China
Authors: Chen Yijuan , Sun Wanwan , Ling Feng , Sun Jimin , Cao Yanli , Chen Zhiping , Miao Ziping
Published: May 2022

Background

Hand-foot-mouth disease (HFMD) is caused by a group of enteroviruses (EVs) and has a high incidence in children; some subtypes had high mortalities in children. The subtypes of HFMD had a different incidence across seasons. Thereby, we suspect that the infection of HFMD is varied by meteorological factors. However, studies examining serotype-specific associations between meteorological factors and HFMD incidence were rare.

Methods

We obtained all HFMD cases that occurred from 1 January 2010 to 31 December 2018 in Zhejiang province from the China Information System for Disease Control and Prevention (CISDCP). Daily meteorological data for Zhejiang province were provided by the China Methodological Data Sharing Service System and linked to HFMD cases based on residential addresses and dates of onset. The associations between meteorological factors and HFMDs were examined using distributed lag non-linear models (DLNMs) for each serotype.

Results

Overall, the incidences of all HFMD cases were increasing in study years, while the number of severe and fatality cases were decreasing. The dominant serotypes varied by study year. The association between temperature and incidence of both CVA16 and EV71 serotypes showed an inverted U shape. The risk ratio for CVA16 was increasing when temperature is 11–25°C, reaching the maximum RR at 18°C and humidity above 77% can promote the occurrence with CVA16, and temperature between 11 and 32°C with the maximum RR at 21°C and relative humidity above 77% are risk conditions of the occurrence of HFMD associated with EV71. For other enteroviruses causing HFMD, temperature above 11°C and humidity above 76% have a risk effect. CVA16, EV71, and all enteroviruses of HFMD have a maximum effect on lag day 0, and temperature is 35, 34, and 33°C respectively, while the enteroviruses of HFMD other than EV71 and CVA16 has a maximum effect when the temperature is 33°C and the lag time is 7 days.

Conclusion

This study shows that meteorological factors have an effect on the occurrence of different HFMD serotypes. Local control strategies for public health should be taken in time to prevent and reduce the risk of HFMD while the weather is getting warmer and wetter.
Characterization and Identification of a New Daidzein Reductase Involved in (S)-Equol Biosynthesis in Clostridium sp. ZJ6
Authors: Hu Yunfei , Yang Chunfang , Song Can , Zhong Weixuan , Li Baiyuan , Cao Linyan , Chen Huahai , Zhao Changhui , Yin Yeshi
Published: May 2022

(S)-equol (EQ) is an isoflavone with high estrogen-like activity in the human body, and is only produced by some gut bacteria in vivo. It plays an important role in maintaining individual health, however, the dearth of resources associated with (S)-EQ-producing bacteria has seriously restricted the production and application of (S)-EQ. We report here a new functional gene KEC48-07020 (K-07020) that was identified from a chick (S)-EQ-producing bacterium (Clostridium sp. ZJ6, ZJ6). We found that recombinant protein of K-07020 possessed similar function to daidzein reductase (DZNR), which can convert daidzein (DZN) into R/S-dihydrodaidzein (R/S-DHD). Interestingly, K-07020 can reversely convert (R/S)-DHD (DHD oxidase) into DZN even without cofactors under aerobic conditions. Additionally, high concentrations of (S)-EQ can directly promote DHD oxidase but inhibit DZNR activity. Molecular docking and site-directed mutagenesis revealed that the amino acid > Arg75 was the active site of DHD oxidase. Subsequently, an engineered E. coli strain based on K-07020 was constructed and showed higher yield of (S)-EQ than the engineered bacteria from our previous work. Metagenomics analysis and PCR detection surprisingly revealed that K-07020 and related bacteria may be prevalent in the gut of humans and animals. Overall, a new DZNR from ZJ6 was found and identified in this study, and its bidirectional enzyme activities and wide distribution in the gut of humans and animals provide alternative strategies for revealing the individual regulatory mechanisms of (S)-EQ-producing bacteria.
Disrupted Topological Organization of Resting-State Functional Brain Networks in Age-Related Hearing Loss
Authors: Yong Wei , Song Jiajie , Xing Chunhua , Xu Jin-Jing , Xue Yuan , Yin Xindao , Wu Yuanqing , Chen Yu-Chen
Published: May 2022

Purpose

Age-related hearing loss (ARHL), associated with the function of speech perception decreases characterized by bilateral sensorineural hearing loss at high frequencies, has become an increasingly critical public health problem. This study aimed to investigate the topological features of the brain functional network and structural dysfunction of the central nervous system in ARHL using graph theory.

Methods

Forty-six patients with ARHL and forty-five age, sex, and education-matched healthy controls were recruited to undergo a resting-state functional magnetic resonance imaging (fMRI) scan in this study. Graph theory was applied to analyze the topological properties of the functional connectomes by studying the local and global organization of neural networks.

Results

Compared with healthy controls, the patient group showed increased local efficiency (Eloc) and clustering coefficient (Cp) of the small-world network. Besides, the degree centrality (Dc) and nodal efficiency (Ne) values of the left inferior occipital gyrus (IOG) in the patient group showed a decrease in contrast with the healthy control group. In addition, the intra-modular interaction of the occipital lobe module and the inter-modular interaction of the parietal occipital module decreased in the patient group, which was positively correlated with Dc and Ne. The intra-modular interaction of the occipital lobe module decreased in the patient group, which was negatively correlated with the Eloc.

Conclusion

Based on fMRI and graph theory, we indicate the aberrant small-world network topology in ARHL and dysfunctional interaction of the occipital lobe and parietal lobe, emphasizing the importance of dysfunctional left IOG. These results suggest that early diagnosis and treatment of patients with ARHL is necessary, which can avoid the transformation of brain topology and decreased brain function.
The Role and Modulation of Spinal Perineuronal Nets in the Healthy and Injured Spinal Cord
Authors: Sánchez-Ventura Judith , Lane Michael A. , Udina Esther
Published: May 2022

Rather than being a stable scaffold, perineuronal nets (PNNs) are a dynamic and specialized extracellular matrix involved in plasticity modulation. They have been extensively studied in the brain and associated with neuroprotection, ionic buffering, and neural maturation. However, their biological function in the spinal cord and the effects of disrupting spinal PNNs remain elusive. The goal of this review is to summarize the current knowledge of spinal PNNs and their potential in pathological conditions such as traumatic spinal cord injury (SCI). We also highlighted interventions that have been used to modulate the extracellular matrix after SCI, targeting the glial scar and spinal PNNs, in an effort to promote regeneration and stabilization of the spinal circuits, respectively. These concepts are discussed in the framework of developmental and neuroplastic changes in PNNs, drawing similarities between immature and denervated neurons after an SCI, which may provide a useful context for future SCI research.
Anatomy and Function of Ventral Tegmental Area Glutamate Neurons
Authors: Cai Jing , Tong Qingchun
Published: May 2022

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire through a complex intra-VTA and long-range neuronal network. In this review, we summarize the features of VTA glutamate neurons from three perspectives, namely, cellular properties, neural connections, and behavioral functions. Delineation of VTA glutamatergic pathways and their interactions with VTA DA neurons in regulating behaviors may reveal previously unappreciated functions of the VTA in other physiological processes.
Research Hotspots and Trends of Peripheral Nerve Injuries Based on Web of Science From 2017 to 2021: A Bibliometric Analysis
Authors: Zhang Shiwen , Huang Meiling , Zhi Jincao , Wu Shanhong , Wang Yan , Pei Fei
Published: May 2022

Background

Peripheral nerve injury (PNI) is very common in clinical practice, which often reduces the quality of life of patients and imposes a serious medical burden on society. However, to date, there have been no bibliometric analyses of the PNI field from 2017 to 2021. This study aimed to provide a comprehensive overview of the current state of research and frontier trends in the field of PNI research from a bibliometric perspective.

Methods

Articles and reviews on PNI from 2017 to 2021 were extracted from the Web of Science database. An online bibliometric platform, CiteSpace, and VOSviewer software were used to generate viewable views and perform co-occurrence analysis, co-citation analysis, and burst analysis. The quantitative indicators such as the number of publications, citation frequency, h-index, and impact factor of journals were analyzed by using the functions of “Create Citation Report” and “Journal Citation Reports” in Web of Science Database and Excel software.

Results

A total of 4,993 papers was identified. The number of annual publications in the field remained high, with an average of more than 998 publications per year. The number of citations increased year by year, with a high number of 22,272 citations in 2021. The United States and China had significant influence in the field. Johns Hopkins University, USA had a leading position in this field. JESSEN KR and JOURNAL OF NEUROSCIENCE were the most influential authors and journals in the field, respectively. Meanwhile, we found that hot topics in the field of PNI focused on dorsal root ganglion (DRG) and satellite glial cells (SGCs) for neuropathic pain relief and on combining tissue engineering techniques and controlling the repair Schwann cell phenotype to promote nerve regeneration, which are not only the focus of research now but is also forecast to be of continued focus in the future.

Conclusion

This is the first study to conduct a comprehensive bibliometric analysis of publications related to PNI from 2017 to 2021, whose bibliometric results can provide a reliable source for researchers to quickly understand key information in this field and identify potential research frontiers and hot directions.
Management of Cerebral Herniation Secondary to Lead Encephalopathy: A Case Report
Authors: Das Somnath , Hataway Felicia , Boudreau Hunter S. , Alam Yasaman , George Jordan A. , Rushton William , Atti Sukhshant , Kaur Manmeet , Holland Marshall T.
Published: May 2022

Background

Adult lead encephalopathy is a rare but critical condition to recognize in modern healthcare settings. Few reports have described the medical and neurosurgical management of severe adult lead encephalopathy.

Case Presentation

A 22 year old woman presented with severe headache, anemia, vomiting, 40-lb weight loss, and constipation. At the time of presentation, she had extensive colonic radiopaque material and a serum lead concentration of 87 mcg/dl (normal <10). She rapidly developed anisocoria requiring emergent ventriculostomy insertion. Following CSF diversion, ICP mitigation, and lead chelation, she considerably improved in <2 weeks.

Conclusion

We report one of the few instances of successful surgical and medical management of adult lead encephalopathy. Dedicated neurocritical care and neurosurgical teams are necessary in conjunction with toxicology in order to manage the advanced sequalae of severe lead poisoning.
Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache
Authors: Yalinay Dikmen Pinar , Ari Cagla , Sahin Erdi , Ertas Mustafa , Mayda Domac Fusun , Ilgaz Aydinlar Elif , Sahin Aysenur , Ozge Aynur , Ozguner Hilal , Karadas Omer , Shafiyev Javid , Vuralli Doga , Aktan Cile , Oguz-Akarsu Emel , Karli Necdet , Zarifoglu Mehmet , Bolay Hayrunisa , Ekizoglu Esme , Kocasoy Orhan Elif , Tasdelen Bahar , Baykan Betul
Published: May 2022

Objective

To investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis.

Methods

A total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences.

Results

Cluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smoking (76.0 vs. 33.0%; p=0.002), higher rates of smoking at diagnosis (78.0 vs. 32.0%; p=0.006), higher rates of parental smoking/tobacco exposure during childhood (72.0 vs. 33.0%; p = 0.010), longer duration of attacks with (44.21 (34.44) min. vs. 34.51 (24.97) min; p=0.005) and without (97.50 (63.58) min. vs. (83.95 (49.07) min; p = 0.035) treatment and higher rates of emergency department visits in the last year (81.0 vs. 26.0%; p< 0.001).

Conclusions

Cluster one and cluster two patients had different phenotypic features, possibly indicating different underlying genetic mechanisms. The cluster 1 phenotype may suggest a genetic or biology-based etiology, whereas the cluster two phenotype may be related to epigenetic mechanisms. Toxic exposure to cigarettes, either personally or secondarily, seems to be an important factor in the cluster two subgroup, inducing drug resistance and longer attacks. We need more studies to elaborate the causal relationship and the missing links of neurobiological pathways of cigarette smoking regarding the identified distinct phenotypic classes of patients with CH.
Testing for Antibodies Against Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in the Diagnosis of Patients With Suspected Autoimmune Myelopathy
Authors: Alkabie Samir , Budhram Adrian
Published: May 2022

Autoimmune myelopathies are immune-mediated disorders of the spinal cord that can cause significant neurologic disability. Discoveries of antibodies targeting aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) have facilitated the diagnosis of autoimmune myelopathies that were previously considered to be atypical presentations of multiple sclerosis (MS) or idiopathic, and represent major advancements in the field of autoimmune neurology. The detection of these antibodies can substantially impact patient diagnosis and management, and increasing awareness of this has led to a dramatic increase in testing for these antibodies among patients with suspected autoimmune myelopathy. In this review we discuss test methodologies used to detect these antibodies, the role of serum vs. cerebrospinal fluid testing, and the value of antibody titers when interpreting results, with the aim of helping laboratorians and clinicians navigate this testing when ordered as part of the diagnostic evaluation for suspected autoimmune myelopathy.
Embodiment Comfort Levels During Motor Imagery Training Combined With Immersive Virtual Reality in a Spinal Cord Injury Patient
Authors: Pais-Vieira Carla , Gaspar Pedro , Matos Demétrio , Alves Leonor Palminha , da Cruz Bárbara Moreira , Azevedo Maria João , Gago Miguel , Poleri Tânia , Perrotta André , Pais-Vieira Miguel
Published: May 2022

Brain–machine interfaces combining visual, auditory, and tactile feedback have been previously used to generate embodiment experiences during spinal cord injury (SCI) rehabilitation. It is not known if adding temperature to these modalities can result in discomfort with embodiment experiences. Here, comfort levels with the embodiment experiences were investigated in an intervention that required a chronic pain SCI patient to generate lower limb motor imagery commands in an immersive environment combining visual (virtual reality -VR), auditory, tactile, and thermal feedback. Assessments were made pre-/ post-, throughout the intervention (Weeks 0–5), and at 7 weeks follow up. Overall, high levels of embodiment in the adapted three-domain scale of embodiment were found throughout the sessions. No significant adverse effects of VR were reported. Although sessions induced only a modest reduction in pain levels, an overall reduction occurred in all pain scales (Faces, Intensity, and Verbal) at follow up. A high degree of comfort in the comfort scale for the thermal-tactile sleeve, in both the thermal and tactile feedback components of the sleeve was reported. This study supports the feasibility of combining multimodal stimulation involving visual (VR), auditory, tactile, and thermal feedback to generate embodiment experiences in neurorehabilitation programs.
Decreased Exercise-Induced Changes in Prefrontal Cortex Hemodynamics Are Associated With Depressive Symptoms
Authors: Crum James , Ronca Flaminia , Herbert George , Funk Sabina , Carmona Estela , Hakim Uzair , Jones Isla , Hamer Mark , Hirsch Joy , Hamilton Antonia , Tachtsidis Ilias , Burgess Paul W.
Published: May 2022

People with a depressed mood tend to perform poorly on executive function tasks, which require much of the prefrontal cortex (PFC), an area of the brain which has also been shown to be hypo-active in this population. Recent research has suggested that these aspects of cognition might be improved through physical activity and cognitive training. However, whether the acute effects of exercise on PFC activation during executive function tasks vary with depressive symptoms remains unclear. To investigate these effects, 106 participants were given a cardiopulmonary exercise test (CPET) and were administered a set of executive function tests directly before and after the CPET assessment. The composite effects of exercise on the PFC (all experimental blocks) showed bilateral activation changes in dorsolateral (BA46/9) and ventrolateral (BA44/45) PFC, with the greatest changes occurring in rostral PFC (BA10). The effects observed in right ventrolateral PFC varied depending on level of depressive symptoms (13% variance explained); the changes in activation were less for higher levels. There was also a positive relationship between CPET scores (VO2peak) and right rostral PFC, in that greater activation changes in right BA10 were predictive of higher levels of aerobic fitness (9% variance explained). Since acute exercise ipsilaterally affected this PFC subregion and the inferior frontal gyrus during executive function tasks, this suggests physical activity might benefit the executive functions these subregions support. And because physical fitness and depressive symptoms explained some degree of cerebral upregulation to these subregions, physical activity might more specifically facilitate the engagement of executive functions that are typically associated with hypoactivation in depressed populations. Future research might investigate this possibility in clinical populations, particularly the neural effects of physical activity used in combination with mental health interventions.
Photolysis for the Removal and Transformation of Pesticide Residues During Food Processing: A State-of-the-Art Minireview
Authors: Xiao Qian , Xuan Xiaoxu , Boczkaj Grzegorz , Yoon Joon Yong , Sun Xun
Published: May 2022

Pesticide residues are of great significant issue that exerted adverse effects on humans. There is a need for effective and non-toxic decontamination of pesticide residues during food processing. In this minireview, the recent advances in the degradation of pesticide residues by photolysis have been firstly described during food processing. The mechanisms of pesticide residues destruction by photolysis were discussed accordingly. Finally, applications of photolysis in the degradation of pesticide residues from beverages, fresh produce, and food rinse waste were also summarized.
Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity
Authors: Wang Ruiguan , Li Jiangbo , Zhang Changjian , Guan Xin , Qin Boyu , Jin Rui , Qin Lingmei , Xu Shanrong , Zhang Xiaona , Liu Rong , Ye Qinong , Cheng Long
Published: May 2022

Telomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming is a hallmark of cancer and accompanied with increased expression of key metabolic enzymes. Whether these enzymes influence telomerase activity and cell immortalization remains unclear. In the current study, we screened metabolic enzymes using telomerase activity assay and identified lactate dehydrogenase B (LDHB) as a regulator of telomerase activity. Sodium lactate and sodium pyruvate did not influence telomerase activity, indicating LDHB regulates telomerase activity independent of its metabolism regulating function. Further studies revealed that LDHB directly interacted with TERT and regulated the interaction between TERT and TERC. Additionally, long-term knockdown of LDHB inhibited cancer cell growth and induced cell senescence in vitro and in vivo. Higher LDHB expression was detected in pancreatic cancer tissues compared with that in adjacent normal tissues and expression of LDHB correlated negatively with prognosis. Thus, we identified LDHB as the first glucose metabolic enzyme contributing to telomerase activity and pancreatic cancer cell immortalization.
Prevention and Treatment of Side Effects of Immunotherapy for Bladder Cancer
Authors: Lou Kecheng , Feng Shangzhi , Zhang Guoxi , Zou Junrong , Zou Xiaofeng
Published: May 2022

Bladder cancer (BC) is one of the most important tumors of the genitourinary system, associated with high morbidity and mortality rates. Over the years, various antitumor treatments have been developed, and immunotherapy is one of the most effective methods. Immunotherapy aims to activate the body’s immune system to kill cancer cells. It has been established that immunotherapy drugs can be classified into “non-targeted” and “targeted” drugs depending on their site of action. Immunotherapy is reportedly effective for BC. Even though it can attack cancer cells, it can also cause the immune system to attack healthy cells, which can occur at any time during treatment and sometimes even after immunotherapy is stopped. Importantly, different types of immunotherapies can cause different side effects. Side effects may manifest themselves as signs or as symptoms. The prevention and treatment of side effects caused by immunotherapy is an important part of cancer patient management.
SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases
Authors: Omar Abdelsattar M. , Khayat Maan T. , Ahmed Farid , Muhammad Yosra A. , Malebari Azizah M. , Ibrahim Sara M. , Khan Mohammad I. , Shah Dhaval K. , Childers Wayne E. , El-Araby Moustafa E.
Published: May 2022

Tirbanibulin (KX2-391, KX-01), a dual non-ATP (substrate site) Src kinase and tubulin-polymerization inhibitor, demonstrated a universal anti-cancer activity for variety of cancer types. The notion that KX2-391 is a highly selective Src kinase inhibitor have been challenged by recent reports on the activities of this drug against FLT3-ITD mutations in some leukemic cell lines. Therefore, we hypothesized that analogues of KX2-391 may inhibit oncogenic kinases other than Src. A set of 4-aroylaminophenyl-N-benzylacetamides were synthesized and found to be more active against leukemia cell lines compared to solid tumor cell lines. N-(4-(2-(benzylamino)-2-oxoethyl)phenyl)-4-chlorobenzamide (4e) exhibited activities at IC50 0.96 µM, 1.62 µM, 1.90 µM and 4.23 µM against NB4, HL60, MV4-11 and K562 leukemia cell lines, respectively. We found that underlying mechanisms of 4e did not include tubulin polymerization or Src inhibition. Such results interestingly suggested that scaffold-hopping of KX2-391 may change the two main underlying cytotoxic mechanisms (Src and tubulin). Kinase profiling using two methods revealed that 4e significantly reduces the activities of some other potent oncogenic kinases like the MAPK member ERK1/2 (>99%) and it also greatly upregulates the pro-apoptotic c-Jun kinase (84%). This research also underscores the importance of thorough investigation of total kinase activities as part of the structure-activity relationship studies.
Transcriptome Profiles Reveal a 12-Signature Metabolic Prediction Model and a Novel Role of Myo-Inositol Oxygenase in the Progression of Prostate Cancer
Authors: Liu Wangrui , Xiang Jianfeng , Wu Xinrui , Wei Shiyin , Huang Haineng , Xiao Yu , Zhai Bo , Wang Tao
Published: May 2022

Prostate adenocarcinoma (PRAD) is an extremely common type of cancer in the urinary system. Here, we aimed to establish a metabolic signature to identify novel targets in a predictive model of PRAD patients. A total of 133 metabolic differentially expressed genes (MDEGs) were identified with significant prognostic value. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a 12-mRNA signature model, a metabolic prediction model (MPM), in 491 PRAD patients. The risk score of the MPM significantly predicted the progression of PRAD patients (p < 0.001, area under the curve (AUC) = 0.745). Furthermore, myo-inositol oxygenase (MIOX), the most prominently upregulated metabolic enzyme and hub gene in the protein–protein interaction network of the MPM, showed significant prognostic implications. Next, MIOX expression in normal prostate tissues was lower than in PRAD tissues, and high MIOX expression was significantly associated with disease progression (p = 0.005, HR = 2.274) in 81 PRAD patients undergoing first-line androgen receptor signaling inhibitor treatment from the Renji cohort. Additionally, MIOX was significantly involved in the abnormal immune infiltration of the tumor microenvironment and associated with the DNA damage repair process of PRAD. In conclusion, this study provides the first opportunity to comprehensively elucidate the landscape of prognostic MDEGs, establish novel prognostic modeling of MPM using large-scale PRAD transcriptomic data, and identify MIOX as a potential prognostic target in PRAD patients from multiple cohorts. These findings help manage risk assessment and provide valuable insights into treatment strategies for PRAD.
Regulatory Emotional Self-Efficacy Buffers the Effect of Heart Rate Variability on Functional Capacity in Older Adults With Chronic Low Back Pain
Authors: Morais Calia A. , DeMonte Lucas C. , Bartley Emily J.
Published: May 2022

Introduction

Chronic low back pain is one of the leading causes of disability globally among older adults. Prevailing research suggests that autonomic dysregulation places individuals at increased risk for chronic pain. This study examines the moderating role of emotional self-efficacy (ESE) on the relationship between heart rate variability (HRV) and pain related-outcomes, including movement-evoked pain (MEP) and physical functioning.

Methods

In a secondary analysis of the Adaptability and Resilience in Aging Adults (ARIAA) study, a total of 58 adults (aged 60 and older) with chronic low back pain (cLBP) completed the PROMIS self-efficacy for managing emotions questionnaire and the 6-minute walk test (6 MWT) to assess functional capacity and MEP. Heart rate variability, indexed by the frequency domain, was assessed for 5 min during rest.

Results

For pain-related outcomes, having a lower body mass index (p = 0.03) was associated with better functional capacity on the 6MWT, while higher education level (p = 0.01) and less pain duration (p = 0.00) were correlated with lower MEP. After controlling for sex, age, and body mass index, an increase in low-frequency HRV (LF-HRV) was associated with poorer physical functioning among individuals low in ESE (b = −0.12 p = 0.03). No significant moderation effects were observed for MEP.

Conclusion

Our results bring attention to the degree to which ESE influences the relationship between LF-HRV and physical functioning. Interventions that enhance adaptive psychological processes such as ESE may dampen ANS dysregulation and mitigate risk for adverse pain outcomes among older adults with cLBP.
Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome—Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial
Authors: Welzel Tatjana , Schöbi Nina , André Maya C. , Bailey Douggl G. N. , Blanchard-Rohner Geraldine , Buettcher Michael , Grazioli Serge , Koehler Henrik , Perez Marie-Helene , Trück Johannes , Vanoni Federica , Zimmermann Petra , Atkinson Andrew , Sanchez Carlos , Whittaker Elizabeth , Faust Saul N. , Bielicki Julia A. , Schlapbach Luregn J. ,   the Swissped Recovery Trial
Published: May 2022

Introduction

In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG.

Methods and Analysis

Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned.

Significance

Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments.

Ethics and Dissemination

The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362).

Registration Details

The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT 04826588).
Case Report: Jejunoileal Atresia With Persistent Poor Bowel Function Can Occur After Surgical Correction for Hirschsprung Disease
Authors: AlBassam Bassam N. , Al-Shammari Ahmad A. , AlQahtani Saleh A. , Hassan Elham
Published: May 2022

Jejunoileal atresia (JIA) is one of the common etiologies of intestinal obtrusion in neonates. However, cases of concomitant ileal atresia and Hirschsprung disease (HD) rarely occur. We report the case of a male infant who had JIA concomitantly with HD that was re-anastomosed. The patient underwent an exploratory laparotomy to resect the dilated terminal ileum. Subsequently, owing to a significantly dilated proximal bowel, he underwent a second exploratory laparotomy. However, he continued to have feeding intolerance postoperatively. He had colonic aganglionosis and was diagnosed with HD. A third laparotomy was then performed. Additionally, he had recurrent episodes of gram-negative bacteremia, especially candida parapsilosis fungemia, despite receiving antibiotics and antifungal, and there were no identifiable underlying genetic or immunological causes. Finally, the patient had recurrent episodes of hypoglycemia, central hypothyroidism, and multiple organ failure and died at the age of 7 months. The concomitant ileal atresia and HD was thought to be due to a common intrauterine vascular accident, together with loss of bowel, thereby acting as a barrier for the caudal migration of neuromeric cells and leading to colonic aganglionosis. In this case, ileal atresia was associated with colonic aganglionosis, central hypothyroidism, and persistent bacteremia, which is a unique finding. In cases of JIA, persistent poor bowel function after surgical correction of concomitant HD should be considered.