bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory mediators profile in patients hospitalized with COVID-19: A comparative study
Authors: Tufa Abdisa , Gebremariam Tewodros Haile , Manyazewal Tsegahun , Getinet Tewodros , Webb Dominic-Luc , Hellström Per M. , Genet Solomon
Published: July 2022

Abnormal inflammatory mediator concentrations during SARS-CoV-2 infection may represent disease severity. We aimed to assess plasma inflammatory mediator concentrations in patients with SARS-CoV-2 in Addis Ababa, Ethiopia. In this study, 260 adults: 126 hospitalized patients with confirmed COVID-19 sorted into severity groups: severe (n=68) and mild or moderate (n=58), and 134 healthy controls were enrolled. We quantified 39 plasma inflammatory mediators using multiplex ELISA. Spearman rank correlation and Mann-Whitney U test were used to identify mechanistically coupled inflammatory mediators and compare disease severity. Compared to healthy controls, patients with COVID-19 had significantly higher levels of interleukins 1α, 2, 6, 7, 8, 10 and 15, C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), IFN-γ-inducible protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1 alpha (MIP-1α, CCL3), eotaxin-3 (CCL26), interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and fms-like tyrosine kinase 1 (Flt-1). Patients with severe COVID-19 had higher IL-10 and lower macrophage-derived chemokine (MDC, CCL22) compared to the mild or moderate group (P<0.05). In the receiver operating characteristic curve, SAA, IL-6 and CRP showed strong sensitivity and specificity in predicting the severity and prognosis of COVID-19. Greater age and higher CRP had a significant association with disease severity (P<0.05). Our findings reveal that CRP, SAA, VCAM-1, CXCL10, CCL22 and IL-10 levels are promising biomarkers for COVID-19 disease severity, suggesting that plasma inflammatory mediators could be used as warning indicators of COVID-19 severity, aid in COVID-19 prognosis and treatment.
Emergent interactive effects of climate change and contaminants in coastal and ocean ecosystems
Authors: Hatje Vanessa , Sarin Manmohan , Sander Sylvia G. , Omanović Dario , Ramachandran Purvaja , Völker Christoph , Barra Ricardo O. , Tagliabue Alessandro
Published: July 2022

The effects of climate change (CC) on contaminants and their potential consequences to marine ecosystem services and human wellbeing are of paramount importance, as they pose overlapping risks. Here, we discuss how the interaction between CC and contaminants leads to poorly constrained impacts that affects the sensitivity of organisms to contamination leading to impaired ecosystem function, services and risk assessment evaluations. Climate drivers, such as ocean warming, ocean deoxygenation, changes in circulation, ocean acidification, and extreme events interact with trace metals, organic pollutants, excess nutrients, and radionuclides in a complex manner. Overall, the holistic consideration of the pollutants-climate change nexus has significant knowledge gaps, but will be important in understanding the fate, transport, speciation, bioavailability, toxicity, and inventories of contaminants. Greater focus on these uncertainties would facilitate improved predictions of future changes in the global biogeochemical cycling of contaminants and both human health and marine ecosystems.
High-performance dual-band frequency-selective rasorber based on cascaded metasurface
Authors: Li Qiushi , Li Xiaotong , Chen Yanrui , Ding Fan , Chen Cong , Liu Huanhuan , Xiao Shiyi
Published: July 2022

Frequency-selective rasorbers (FSRs), which have absorptive and transmissive properties at different frequencies, are crucial in a wide range of applications in communication and radar engineering. However, the FSRs currently available usually exhibit a single high-performance transmission band, which cannot meet the rising demands for modern multiband communication/radar systems. In this article, we propose a dual-band frequency-selective rasorber that utilizes a cascaded metasurface and is designed with an equivalent circuit model and parameter optimization. In addition, a prototype dual-band frequency-selective rasorber is fabricated and characterized. Microwave measurements present two highly transparent peaks located near 11.5 and 17.5 GHz with an insertion loss of around 0.5 dB. Also, there are two absorption bands with absorptivities higher than 80% at 3.9–10.2 GHz and 13–15 GHz. Such low insertion loss for both transparent bands is achieved by optimizing the position of resistors through mode analysis. Our approach facilitates the manufacture of high-performance multi-band frequency-selective rasorbers for use in multi-band communication systems.
Microwaves, a potential treatment for bacteria: A review
Authors: Zhang Zhen , Wang Jiahao , Hu Yihe , Wang Long
Published: July 2022

Bacteria have brought great harm to the public, especially after the emergence of multidrug-resistant bacteria. This has rendered traditional antibiotic therapy ineffective. In recent years, hyperthermia has offered new treatments to remove bacteria. Microwaves (MW) are a component of the electromagnetic spectrum and can rapidly heat materials. Taking advantage of this characteristic of MW, related studies have shown that both thermal and non-thermal effects of MW can inactivate various bacteria. Even though the understanding of MW in the field of bacteria is not sufficient for widespread use at present, MW has performed well in dealing with microorganisms and controlling infection. This review will focus on the application of MW in bacteria and discuss the advantages, prospects and challenges of using MW in the bacterial field.
Soil pH Determines the Spatial Distribution, Assembly Processes, and Co-existence Networks of Microeukaryotic Community in Wheat Fields of the North China Plain
Authors: Shi Yu , Xu Mengwei , Zhao Yige , Cheng Liang , Chu Haiyan
Published: July 2022

Soil microeukaryotes play a pivotal role in soil nutrient cycling and crop growth in agroecosystems. However, knowledge of microeukaryotic community distribution patterns, assembly processes, and co-existence networks is greatly limited. Here, microbial eukaryotes in bulk and rhizosphere soils of the North China Plain were investigated. The results showed that soil pH was the driving factor for the microeukaryotic community composition in the bulk and rhizosphere soils. The soil microeukaryotic community could significantly differ between alkaline and acidic soils. The results indicated that the soil pH had a stronger effect than niche differences on community composition. Partial Mantel tests showed that soil pH and spatial distance had similar effects on the microeukaryotic community composition in the bulk soil. However, in the rhizosphere soil, spatial distance had a stronger effect than soil pH. Infer Community Assembly Mechanisms by Phylogenetic bin-based null model (iCAMP) analysis revealed that drift was the most important process driving microeukaryotic community assembly, with an average relative importance of 37.4–71.1%. Dispersal limitation displayed slightly greater importance in alkaline rhizosphere than in alkaline bulk soils. Meanwhile, the opposite trend was observed in acidic soils. In addition, the contribution of each assembly process to each iCAMP lineage “bin” varied according to the acidic or alkaline conditions of the soil and the niche environment. High proportions of positive links were found within the four ecological networks. Alkaline soil networks, especially the alkaline bulk soil network, showed greater complexity than the acidic soil networks. Natural connectivity analysis revealed that the rhizosphere community had a greater stability than the bulk soil community in alkaline soil. This study provides a foundation for understanding the potential roles of microbial eukaryotes in agricultural soil ecosystem functioning.
MycoWiki: Functional annotation of the minimal model organism Mycoplasma pneumoniae
Authors: Elfmann Christoph , Zhu Bingyao , Pedreira Tiago , Hoßbach Ben , Lluch-Senar Maria , Serrano Luis , Stülke Jörg
Published: July 2022

The human pathogen Mycoplasma pneumoniae is viable independently from host cells or organisms, despite its strongly reduced genome with only about 700 protein-coding genes. The investigation of M. pneumoniae can therefore help to obtain general insights concerning the basic requirements for cellular life. Accordingly, M. pneumoniae has become a model organism for systems biology in the past decade. To support the investigation of the components of this minimal bacterium, we have generated the database MycoWiki. (http://mycowiki.uni-goettingen.de) MycoWiki organizes data under a relational database and provides access to curated and state-of-the-art information on the genes and proteins of M. pneumoniae. Interestingly, M. pneumoniae has undergone an evolution that resulted in the limited similarity of many proteins to proteins of model organisms. To facilitate the analysis of the functions of M. pneumoniae proteins, we have integrated structure predictions from the AlphaFold Protein Structure Database for most proteins, structural information resulting from in vivo cross-linking, and protein-protein interactions based on a global in vivo study. MycoWiki is an important tool for the systems and synthetic biology community that will support the comprehensive understanding of a minimal organism and the functional annotation of so far uncharacterized proteins.
Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
Authors: Garcia-Moreno Marina , Jordan Paul M. , Günther Kerstin , Dau Therese , Fritzsch Christian , Vermes Monika , Schoppa Astrid , Ignatius Anita , Wildemann Britt , Werz Oliver , Löffler Bettina , Tuchscherr Lorena
Published: July 2022

Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small colony variants. Recently, osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here, we investigated the interaction between S. aureus and osteoblasts or osteocytes during infection. While osteoblasts are able to induce a strong antimicrobial response and eliminate intracellular S. aureus, osteocytes trigger signals to recruit immune cells and enhance inflammation but fail an efficient antimicrobial activity to clear the bacterial infection. Moreover, we found that extracellular signals from osteocytes enhance intracellular bacterial clearance by osteoblasts. Even though both cell types express Toll-like receptor (TLR) 2, the main TLR responsible for S. aureus detection, only osteoblasts were able to increase TLR2 expression after infection. Additionally, proteomic analysis indicates that reduced intracellular bacterial killing activity in osteocytes is related to low antimicrobial peptide expression. Nevertheless, high levels of lipid mediators and cytokines were secreted by osteocytes, suggesting that they can contribute to inflammation. Taken together, our results demonstrate that osteocytes contribute to severe inflammation observed in osteomyelitis and represent the main niche for S. aureus persistence due to their poor capacity for intracellular antimicrobial response.
Nanopore sequencing technology and its application in plant virus diagnostics
Authors: Sun Kai , Liu Yi , Zhou Xin , Yin Chuanlin , Zhang Pengjun , Yang Qianqian , Mao Lingfeng , Shentu Xuping , Yu Xiaoping
Published: July 2022

Plant viruses threaten crop yield and quality; thus, efficient and accurate pathogen diagnostics are critical for crop disease management and control. Recent advances in sequencing technology have revolutionized plant virus research. Metagenomics sequencing technology, represented by next-generation sequencing (NGS), has greatly enhanced the development of virus diagnostics research because of its high sensitivity, high throughput and non-sequence dependence. However, NGS-based virus identification protocols are limited by their high cost, labor intensiveness, and bulky equipment. In recent years, Oxford Nanopore Technologies and advances in third-generation sequencing technology have enabled direct, real-time sequencing of long DNA or RNA reads. Oxford Nanopore Technologies exhibit versatility in plant virus detection through their portable sequencers and flexible data analyses, thus are wildly used in plant virus surveillance, identification of new viruses, viral genome assembly, and evolution research. In this review, we discuss the applications of nanopore sequencing in plant virus diagnostics, as well as their limitations.
Rare bacterial biosphere is more environmental controlled and deterministically governed than abundant one in sediment of thermokarst lakes across the Qinghai-Tibet Plateau
Authors: Ren Ze , Luo Wei , Zhang Cheng
Published: July 2022

Thermokarst lakes are widely distributed in cold regions as a result of ice-rich permafrost thaw. Disentangling the biogeography of abundant and rare microbes is essential to understanding the environmental influences, assembly mechanisms, and responses to climate change of bacterial communities in thermokarst lakes. In light of this, we assessed the abundant and rare bacterial subcommunities in sediments from thermokarst lakes across the Qinghai-Tibet Plateau (QTP). The operational taxonomic unit (OTU) richness was more strongly associated with location and climate factors for abundant subcommunities, while more strongly associated with physicochemical variables for rare subcommunities. The relative abundance of abundant and rare taxa showed opposite patterns with abundant taxa having greater relative abundance at higher latitude and pH, but at lower mean annual precipitation and nutrients. Both the abundant and rare subcommunities had a clear distribution pattern along the gradient of latitude and mean annual precipitation. Abundant subcommunities were dominantly shaped by dispersal limitation processes (80.9%), while rare subcommunities were shaped almost equally by deterministic (47.3%) and stochastic (52.7%) processes. The balance between stochastic and deterministic processes was strongly environmentally adjusted for rare subcommunities, while not associated with environmental changes for abundant subcommunities. The results shed light on biogeography patterns and structuring mechanisms of bacterial communities in thermokarst lakes, improving our ability to predict the influences of future climate change on these lakes.
Successive walnut plantations alter soil carbon quantity and quality by modifying microbial communities and enzyme activities
Authors: Luan Haoan , Liu Yingru , Huang Shaohui , Qiao Wenyan , Chen Jie , Guo Tengfei , Zhang Xiaojia , Guo Suping , Zhang Xuemei , Qi Guohui
Published: July 2022

Knowledge of the spatial–temporal variations of soil organic carbon (SOC) quantity and quality and its microbial regulation mechanisms is essential for long-term SOC sequestration in agroecosystems; nevertheless, this information is lacking in the process of walnut plantations. Here, we used the modified Walkley-Black method, phospholipid fatty acid analysis, and micro-plate enzyme technique to analyze the evolution of SOC stocks and quality/lability as well as microbial communities and enzyme activities at different soil depths in walnut plantations with a chronosequence of 0-, 7-, 14-, and 21-years in the Eastern Taihang Mountains, China. The results indicated that long-term walnut plantations (14-and 21-years) enhanced SOC stocks, improved SOC quality/lability (as indicated by the lability index), and promoted microbial growth and activities (i.e., hydrolase and oxidase activities) in the 0–40 cm soil layers. Besides, these above-mentioned SOC-and microbial-related indices (except for oxidase activities) decreased with increasing soil depths, while oxidase activities were higher in deeper soils (40–60 cm) than in other soils (0–40 cm). The partial least squares path model also revealed that walnut plantation ages and soil depths had positive and negative effects on microbial attributes (e.g., enzyme activities, fungal and bacterial communities), respectively. Meanwhile, the SOC stocks were closely related to the fungal community; meanwhile, the bacterial community affected SOC quality/liability by regulating enzyme activities. Comprehensively, long-term walnut plantations were conducive to increasing SOC stocks and quality through altering microbial communities and activities in the East Taihang Mountains in Hebei, China.
The potential interplay between G-quadruplex and p53: their roles in regulation of ferroptosis in cancer
Authors: Zhang Lulu , Lu Yi , Ma Xiaoli , Xing Yuanxin , Sun Jinbo , Jia Yanfei
Published: July 2022

Ferroptosis is a novel form of regulated cell death trigged by various biological processes, and p53 is involved in different ferroptosis regulations and functions as a crucial regulator. Both DNA and RNA can fold into G-quadruplex in GC-rich regions and increasing shreds of evidence demonstrate that G-quadruplexes have been associated with some important cellular events. Investigation of G-quadruplexes is thus vital to revealing their biological functions. Specific G-quadruplexes are investigated to discover new effective anticancer drugs. Multiple modulations have been discovered between the secondary structure G-quadruplex and p53, probably further influencing the ferroptosis in cancer. G-quadruplex binds to ferric iron-related structures directly and may affect the p53 pathways as well as ferroptosis in cancer. In addition, G-quadruplex also interacts with p53 indirectly, including iron-sulfur cluster metabolism, telomere homeostasis, lipid peroxidation, and glycolysis. In this review, we summarized the latent interplay between G-quadruplex and p53 which focused mainly on ferroptosis in cancer to provide the potential understanding and encourage future studies.
Investigation of coenzyme Q10 status, serum amyloid-β, and tau protein in patients with dementia
Authors: Chang Po-Sheng , Chou Hsi-Hsien , Lai Te-Jen , Yen Chi-Hua , Pan Ji-Cyun , Lin Ping-Ting
Published: July 2022

Objectives

Dementia is an oxidative stress-related disease. Coenzyme Q10 is a nutrient that occurs naturally in the human body and acts as an antioxidant. The purpose of this study was to investigate the relationships of coenzyme Q10 status, biomarkers for dementia (amyloid β and tau protein), and antioxidant capacity in patients with dementia.

Methods

Eighty dementia patients aged ≥60 years and with a mini mental state examination (MMSE) score ≤ 26 were enrolled. The levels of coenzyme Q10, total antioxidant capacity (TAC), amyloid β, and tau protein were measured.

Results

A total of 73% of patients had a low coenzyme Q10 status. Patients with low coenzyme Q10 status had a significantly higher level of serum amyloid β-42 and amyloid β-42/40 ratio (p < 0.05). Coenzyme Q10 status was significantly correlated with the values of TAC, MMSE score, amyloid β-42, and amyloid β-42/40 ratio (p < 0.05) but not with tau protein. Additionally, a high proportion of moderate dementia patients were found to have low coenzyme Q10 status (p = 0.07).

Conclusion

Patients with dementia suffered from coenzyme Q10 deficiency, and the degree of deficiency was related to the level of amyloid-β and antioxidant capacity. Since adequate level of coenzyme Q10 may delay the progression of dementia, monitoring coenzyme Q10 status in patients with dementia is necessary.
Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis
Authors: Chen Leian , Niu Xiaoqian , Wang Yuye , Lv Shuang , Zhou Xiao , Yang Ziyuan , Peng Dantao
Published: July 2022

Objective

Detecting plasma tau biomarkers used to be impossible due to their low concentrations in blood samples. Currently, new high-sensitivity assays made it a reality. We performed a systematic review and meta-analysis in order to test the accuracy of plasma tau protein in diagnosing Alzheimer's disease (AD) or mild cognitive impairment (MCI).

Methods

We searched PubMed, Cochrane, Embase and Web of Science databases, and conducted correlation subgroup analysis, sensitivity analysis and publication bias analysis using R Programming Language.

Results

A total of 56 studies were included. Blood t-tau and p-tau levels increased from controls to MCI to AD patients, and showed significant changes in pairwise comparisons of AD, MCI and normal cognition. P-tau217 was more sensitive than p-tau181 and p-tau231 in different cognition periods. In addition, ultrasensitive analytical platforms, immunomagnetic reduction (IMR), increased the diagnostic value of tau proteins, especially the diagnostic value of t-tau.

Conclusion

Both t-tau and p-tau are suitable AD blood biomarkers, and p-tau217 is more sensitive than other tau biomarkers to differentiate MCI and AD. Detection techniques also have an impact on biomarkers' results. New ultrasensitive analytical platforms of IMR increase the diagnostic value of both t-tau and p-tau biomarkers.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42021264701.
Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study
Authors: Long Qijia , Lv Zongxia , Zhao Jingyuan , Shi Ke , Li Chunyan , Fan Binglin , Zheng Jinou
Published: July 2022

Background:

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease with typical clinical features. Whether and how cerebral gray matter structural damage inherent to the disorder affects cognitive function in patients is still unclear. Therefore, this study aimed to explore the changes in cerebral gray matter volume and whether these alterations contribute to cognitive impairment and mood disorders.

Methods

Forty patients with anti-NMDAR encephalitis and forty healthy controls (HCs) matched for gender, age, and education were recruited. All participants underwent attention network tests (ANT), neuropsychological tests and magnetic resonance imaging (MRI). Voxel-based morphological analysis (VBM) and correlation analysis was performed on all participants. Finally, according to the course of disease, patients were divided into two groups: NMDARE_SD (short duration; course ≤ 2 years since diagnosis) and NMDARE_LD (long duration; course >2 years since diagnosis), to evaluate gray matter volume changes that differ as a function of disease course.

Results

Compared to HCs, patients with anti-NMDAR encephalitis showed decreased executive control ability and lower MoCA score, while increased anxiety and depression as reflected by HAMA and HAMD24 scores (all P < 0.05). In VBM analysis, patients showed decreased gray matter volume in bilateral thalamus, left medial prefrontal cortex (mPFC_L), left superior temporal gyrus (STG_L), and left rectus gyrus. In the analysis stratified by disease course, the NMDARE_LD group exhibited decreased gray matter volume in the left precuneus and right posterior cerebellar lobe compared to the NMDARE_SD group.

Conclusions

Patients with anti-NMDAR encephalitis have cognitive, executive, and emotional dysfunction, and the sites of gray matter atrophy are concentrated in the thalamus, frontal lobe, and temporal lobe. These abnormalities may be involved in the process of cognitive and affective dysfunction.Patients with different courses of anti-NMDAR encephalitis have different brain atrophy sites. These results may help to clarify the contradiction between clinical and imaging manifestations of anti NMDAR encephalitis, which is worthy of further longitudinal studies.
“Rogue” [DEspR+CD11b+] neutrophil subset correlates with severity in spontaneous intracerebral hemorrhage
Authors: Herrera Victoria L. M. , Takahashi Courtney E. , Nguyen Mai Q. , Mosaddeghi Julie Z. , Denis Ridiane , Greer David M. , Ruiz-Opazo Nelson
Published: July 2022

Objective

Cumulative clinical, cellular, and molecular evidence reinforces the role of neutrophils in secondary brain injury in spontaneous intracerebral hemorrhage (sICH). However, since generalized neutrophil inhibition is detrimental, identification of targetable “rogue” neutrophil subsets associated with sICH severity is key.

Methods

In a pilot prospective observational study of consented patients with sICH, we immunotyped whole blood to assess circulating neutrophil markers (~day 3 after ICH symptoms onset): (a) DEspR±CD11b± neutrophils by flow cytometry, (b) DEspR±CD11b± neutrophil extracellular trap (NET)-forming neutrophils by immunofluorescence cytology, and (c) neutrophil-lymphocyte ratio (NLR). Using Spearman rank correlation (r) with Bonferroni correction, we assessed the association of neutrophil markers with same-day clinical and neuroimaging parameters of sICH severity, index ICH score, 90-day modified Rankin Scale (mRS) score, and potential interrelationships. As comparators, we assessed same-day plasma biomarkers elevated in sICH: interleukin-6/IL-6, myeloperoxidase/MPO, soluble-terminal complement complex/sC5b-9, endothelin-1/ET-1, and mitochondrial/nuclear DNA ratio (mt/nDNA ratio).

Results

We detected strong correlations [r(n = 13) > 0.71, power > 0.8, Bonferroni corrected pB < 0.05] for all three neutrophil markers with 90-day mRS score, differentially for DEspR+CD11b+ neutrophil counts, and NLR with perihematomal edema (PHE) volume and for DEspR+CD11b+ NET-forming neutrophil counts with intraparenchymal hemorrhage (IPH)-volume. Only DEspR+CD11b+ neutrophil counts show a strong correlation with index ICH score, same-day Glasgow Coma Scale (GCS) score, and NLR and NET-forming neutrophil counts. The sum of the ICH score and three neutrophil markers exhibited the highest correlation: [r(n = 13) 0.94, pB = 10−5]. In contrast, plasma biomarkers tested were elevated except for MPO but exhibited no correlations in this pilot study.

Conclusion

Strong correlation with multiple sICH severity measures, NET formation, and NLR identifies DEspR+CD11b+ neutrophils as a putative “rogue” neutrophil subset in sICH. The even stronger correlation of the sum of three neutrophil markers and the index ICH score with 90-day mRS outcome reinforces early neutrophil-mediated secondary brain injury as a key determinant of outcome in patients with sICH. Altogether, data provide a basis for the formal study of the DEspR+CD11b+ neutrophil subset as a potential actionable biomarker for neutrophil-driven secondary brain injury in sICH. Data also show ex vivo analysis of patients with sICH neutrophils as a translational milestone to refine hypotheses between preclinical and clinical studies.
A preliminary trial of botulinum toxin type A in patients with vestibular migraine: A longitudinal fMRI study
Authors: Oh Sun-Young , Kang Jin-Ju , Kim Sohui , Lee Jong-Min , Kim Ji-Soo , Dieterich Marianne
Published: July 2022

Objective

This study aims to investigate the efficacy of botulinum toxin type A (BTX-A) in the prophylactic management of vestibular migraine (VM) and to determine whether this treatment modulates intrinsic functional brain network.

Methods

Vestibular migraine patients (n = 20, mean age 45.4 years) who were resistant to conventional prophylactic therapies had BTX-A injection and rs-fMRI before and 2 months after the injection. We also measured the changes in the frequency of vertigo and migraine attacks, symptomatic functional disability scores, and neuropsychiatric inventories.

Results

After BTX-A injection, the mean monthly frequencies of migraine and vertigo episodes decreased significantly compared with the baseline (p < 0.01, paired t-test). The Headache Impact Test-6 score and the Migraine Disability Assessment, and the vertigo parameters, measured by the Dizziness Handicap Inventory and the Vertigo Symptom Scale, showed an improvement, as did the anxiety and depression scores 2 months after BTX-A treatment. The low-frequency fluctuation analysis of the rs-fMRI data found significant changes in the functional connectivity of the right superior temporal gyrus. Adoption of this cluster as the seed region increased the functional connectivity with the left post-central gyrus, right supramarginal gyrus, and right middle temporal gyrus after BTX-A treatment.

Conclusion

This prospective study suggests that BTX-A treatment is effective at ameliorating migraine and vertigo symptoms in VM patients who were resistant to conventional therapies. Along with symptomatic improvements, changes in the functional connectivity within the multisensory vestibular and pain networks suggest a dysmodulation of multimodal sensory integration and abnormal cortical processing of the vestibular and pain signals in VM patients.
Cold Cognition as Predictor of Treatment Response to rTMS; A Retrospective Study on Patients With Unipolar and Bipolar Depression
Authors: Rostami Reza , Kazemi Reza , Nasiri Zahra , Ataei Somayeh , Hadipour Abed L. , Jaafari Nematollah
Published: July 2022

Background

Cognitive impairments are prevalent in patients with unipolar and bipolar depressive disorder (UDD and BDD, respectively). Considering the fact assessing cognitive functions is increasingly feasible for clinicians and researchers, targeting these problems in treatment and using them at baseline as predictors of response to treatment can be very informative.

Method

In a naturalistic, retrospective study, data from 120 patients (Mean age: 33.58) with UDD (n = 56) and BDD (n = 64) were analyzed. Patients received 20 sessions of bilateral rTMS (10 Hz over LDLPFC and 1 HZ over RDLPFC) and were assessed regarding their depressive symptoms, sustained attention, working memory, and executive functions, using the Beck Depression Inventory (BDI-II) and Neuropsychological Test Automated Battery Cambridge, at baseline and after the end of rTMS treatment course. Generalized estimating equations (GEE) and logistic regression were used as the main statistical methods to test the hypotheses.

Results

Fifty-three percentage of all patients (n = 64) responded to treatment. In particular, 53.1% of UDD patients (n = 34) and 46.9% of BDD patients (n = 30) responded to treatment. Bilateral rTMS improved all cognitive functions (attention, working memory, and executive function) except for visual memory and resulted in more modulations in the working memory of UDD compared to BDD patients. More improvements in working memory were observed in responded patients and visual memory, age, and sex were determined as treatment response predictors. Working memory, visual memory, and age were identified as treatment response predictors in BDD and UDD patients, respectively.

Conclusion

Bilateral rTMS improved cold cognition and depressive symptoms in UDD and BDD patients, possibly by altering cognitive control mechanisms (top-down), and processing negative emotional bias.
Effect of fermented oyster (Crassostrea gigas) extracts and regular walking on muscle strength and mass in older adults with relatively low muscle mass: A randomized controlled trial
Authors: Lee Ye Li , Lee Sang Yeoup
Published: July 2022

Introduction

Oysters possess an excellent nutritional profile containing γ-aminobutyric acid (GABA). Previous data suggest that GABA is a potent bioactive compound for improving muscle health. Lactic acid fermentation is thought to increase GABA content. However, the effect of oral supplementation of fermented oyster extracts (FO) on human muscle strength and mass is unclear. Therefore, we tested the effects and safety of consumption of FO combined with regular walking for 12 weeks on muscle strength and mass in older adults with relatively low muscle mass.

Materials and methods

A randomized controlled trial was conducted on 54 adults between 50 and 78 years of age. Participants were randomized to receive either placebo or 1,200 mg FO daily for 12 weeks. By fermentation with Lactobacillus brevis BJ20, FO was prepared from Crassostrea gigas. At baseline and at 12 weeks after treatment, the following parameters of the participants were examined: knee strengths, handgrip strengths, body composition, blood tests, and 24-h dietary recall. All participants were required to walk for 30–60 min/day for >3 days/week during the trial period. Physical activity was assessed using an exercise log during the study.

Results

Of the 54 participants, 49 completed the trial without reporting adverse effects. FO supplementation over 12 weeks did not cause any increase in knee or grip strength compared to the control group. Also, no differences were observed in the muscle mass, growth hormone, muscle biomarkers, anti-inflammatory markers, and antioxidative markers between the two groups. None of the participants experienced adverse events. Application of FO was well tolerated, and no notable adverse effect was reported in both groups.

Discussion

FO supplementation with regular walking did not improve remarkably muscle function compared to regular walking alone in adults with relatively low muscle mass.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT04109911].
Anemia and Bone Marrow Suppression After Intra-Arterial Chemotherapy in Children With Retinoblastoma: A Retrospective Analysis
Authors: Zeng Changjuan , Han Minglei , Fan Jiayan , He Xiaoyu , Jia Renbing , Li Li , Wen Xuyang , Song Xuefei , Hou Lili
Published: July 2022

Background

Retinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC.

Methods

Children with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression.

Results

Data of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p <0.0001, chi-square test) and bone marrow suppression (p = 0.001, chi-square test). Moreover, the number of children with Rb who had an increased cross-level change in the severity of anemia and degree of bone marrow suppression was 80 (41.24%) and 64 (32.49%), respectively. The univariate regression analysis showed that numerous factors (such as pre-IAC intravenous chemotherapy, results of pre-IAC routine blood tests, and some serological indicators for liver and kidney function) affected the anemia severity and degree of bone marrow suppression in children with Rb after IAC. Additionally, the predictive model of the multivariate regression could predict anemia and bone marrow suppression.

Conclusion

Children with Rb may have an increased risk of anemia and bone marrow suppression after IAC, but this is temporary and can be influenced by several factors. Therefore, IAC should be maintained as the standard of care. We generated predictive equations for predicting anemia severity and degree of bone marrow suppression, which can guide the prediction and timely control of anemia and bone marrow suppression after IAC.
A distinct lipid metabolism signature of acute myeloid leukemia with prognostic value
Authors: Li Ding , Liang Jiaming , Yang Wei , Guo Wenbin , Song Wenping , Zhang Wenzhou , Wu Xuan , He Baoxia
Published: July 2022

Background

Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy characterized by extensive genetic abnormalities that might affect the prognosis and provide potential drug targets for treatment. Reprogramming of lipid metabolism plays important roles in tumorigenesis and progression and has been newly recognized a new hallmark of malignancy, and some related molecules in the signal pathways could be prognostic biomarkers and potential therapeutic targets for cancer treatment. However, the clinical value of lipid metabolism reprogramming in AML has not been systematically explored. In this study, we aim to explore the clinical value of lipid metabolism reprogramming and develop a prognostic risk signature for AML.

Methods

We implemented univariate Cox regression analysis to identify the prognosis-related lipid metabolism genes, and then performed LASSO analysis to develop the risk signature with six lipid metabolism-related genes (LDLRAP1, PNPLA6, DGKA, PLA2G4A, CBR1, and EBP). The risk scores of samples were calculated and divided into low- and high-risk groups by the median risk score.

Results

Survival analysis showed the high-risk group hold the significantly poorer outcomes than the low-risk group. The signature was validated in the GEO datasets and displayed a robust prognostic value in the stratification analysis. Multivariate analysis revealed the signature was an independent prognostic factor for AML patients and could serve as a potential prognostic biomarker in clinical evaluation. Furthermore, the risk signature was also found to be closely related to immune landscape and immunotherapy response in AML.

Conclusions

Overall, we conducted a comprehensive analysis of lipid metabolism in AML and constructed a risk signature with six genes related to lipid metabolism for the malignancy, prognosis, and immune landscape of AML, and our study might contribute to better understanding in the use of metabolites and metabolic pathways as the potential prognostic biomarkers and therapeutic targets for AML.
Prognostic Role of Combined EGFR and Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma
Authors: Wongpattaraworakul Wattawan , Gibson-Corley Katherine N. , Choi Allen , Buchakjian Marisa R. , Lanzel Emily A. , Rajan KD Anand , Simons Andrean L.
Published: July 2022

Background

Epidermal growth factor receptor (EGFR) is well known as a general prognostic biomarker for head and neck tumors, however the specific prognostic value of EGFR in oral squamous cell carcinoma (OSCC) is controversial. Recently, the presence of tumor-infiltrating T cells has been associated with significant survival advantages in a variety of disease sites. The present study will determine if the inclusion of T cell specific markers (CD3, CD4 and CD8) would enhance the prognostic value of EGFR in OSCCs.

Methods

Tissue microarrays containing 146 OSCC cases were analyzed for EGFR, CD3, CD4 and CD8 expression using immunohistochemical staining. EGFR and T cell expression scores were correlated with clinicopathological parameters and survival outcomes.

Results

Results showed that EGFR expression had no impact on overall survival (OS), but EGFR-positive (EGFR+) OSCC patients demonstrated significantly worse progression free survival (PFS) compared to EGFR-negative (EGFR-) patients. Patients with CD3, CD4 and CD8-positive tumors had significantly better OS compared to CD3, CD4 and CD8-negative patients respectively, but no impact on PFS. Combined EGFR+/CD3+ expression was associated with cases with no nodal involvement and significantly more favorable OS compared to EGFR+/CD3- expression. CD3 expression had no impact on OS or PFS in EGFR- patients. Combinations of EGFR/CD8 and EGFR/CD4 expression showed no significant differences in OS or PFS among the expression groups.

Conclusion

Altogether these results suggest that the expression of CD3+ tumor-infiltrating T cells can enhance the prognostic value of EGFR expression and warrants further investigation as prognostic biomarkers for OSCC.
Metabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer
Authors: Montero-Calle Ana , Gómez de Cedrón Marta , Quijada-Freire Adriana , Solís-Fernández Guillermo , López-Alonso Victoria , Espinosa-Salinas Isabel , Peláez-García Alberto , Fernández-Aceñero María Jesús , Ramírez de Molina Ana , Barderas Rodrigo
Published: July 2022

Approximately 25% of colorectal cancer (CRC) patients experience systemic metastases, with the most frequent target organs being the liver and lung. Metabolic reprogramming has been recognized as one of the hallmarks of cancer. Here, metabolic and functional differences between two CRC cells with different metastatic organotropisms (metastatic KM12SM CRC cells to the liver and KM12L4a to the lung when injected in the spleen and in the tail vein of mice) were analysed in comparison to their parental non-metastatic isogenic KM12C cells, for a subsequent investigation of identified metabolic targets in CRC patients. Meta-analysis from proteomic and transcriptomic data deposited in databases, qPCR, WB, in vitro cell-based assays, and in vivo experiments were used to survey for metabolic alterations contributing to their different organotropism and for the subsequent analysis of identified metabolic markers in CRC patients. Although no changes in cell proliferation were observed between metastatic cells, KM12SM cells were highly dependent on oxidative phosphorylation at mitochondria, whereas KM12L4a cells were characterized by being more energetically efficient with lower basal respiration levels and a better redox management. Lipid metabolism-related targets were found altered in both cell lines, including LDLR, CD36, FABP4, SCD, AGPAT1, and FASN, which were also associated with the prognosis of CRC patients. Moreover, CD36 association with lung metastatic tropism of CRC cells was validated in vivo. Altogether, our results suggest that LDLR, CD36, FABP4, SCD, FASN, LPL, and APOA1 metabolic targets are associated with CRC metastatic tropism to the liver or lung. These features exemplify specific metabolic adaptations for invasive cancer cells which stem at the primary tumour.
Risk of human papillomavirus infection and cervical intraepithelial lesions in Chinese renal transplant recipients
Authors: Chen Ming , Cui Qiulin , Chen Meilian , Xia Meng , Liu Duo , Chen Peisong , Wang Changxi , He Mian
Published: July 2022

Objective

While human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear.

Methods

From 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed.

Results

Our study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P<0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time.

Conclusion

RTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.
Sema3d Restrained Hepatocellular Carcinoma Progression Through Inactivating Pi3k/Akt Signaling via Interaction With FLNA
Authors: Li Yiming , Xu Cong , Sun Bo , Zhong Fangjing , Cao Momo , Yang Lianyue
Published: July 2022

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide due to the high incidence rate of metastasis and recurrence. Semaphorin 3d (Sema3d) has been shown to play a critical role in vascular development during early embryogenesis and several forms of cancer progression via regulating cell migration. However, the function of Sema3d in hepatocellular carcinoma (HCC) remains elusive. This study aimed to explore the function and mechanisms of Sema3d in HCC. In our study, Sema3d expression was significantly downregulated in HCC tissues and cell lines. Downregulated Sema3d was closely correlated with aggressive clinicopathological features and poor clinical outcomes in HCC patients. Moreover, overexpression of Sema3d in HCCLM3 cells was significantly inhibited and knockdown of Sema3d in PLC/PRF/5 cells promoted proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of HCC cells in vitro and tumor growth, EMT, and metastasis in vivo. Furthermore, the RNA sequencing and gene set enrichment analysis (GSEA) indicated that these phenotypic and functional changes in Sema3d-interfered HCC cells were mediated by the Pi3k/Akt signaling pathway, and co-IP–combined mass spectrometry indicated Sema3d might interact with FLNA. Finally, we proved that Sema3d exerted its tumor-restraining effect by interacting with FLNA to inactivate the Pi3k/Akt signaling pathway and remodel the cytoskeleton. Our data showed that Sema3d restrained hepatocellular carcinoma proliferation, invasion, and metastasis through inactivating Pi3k/Akt via interaction with FLNA, which may serve as a novel prognostic predictor and a potential therapeutic target for HCC patients.
RET signaling pathway and RET inhibitors in human cancer
Authors: Regua Angelina T. , Najjar Mariana , Lo Hui-Wen
Published: July 2022

Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or proteomic alterations, most of which confer constitutive activation of RET. Activating RET alterations, such as point mutations or gene fusions, enhance activity of signaling pathways downstream of RET, namely PI3K/AKT, RAS/RAF, MAPK, and PLCγ pathways, to promote cell proliferation, growth, and survival. Given the important role that mutant RET plays in metastatic cancers, significant efforts have been made in developing inhibitors against RET kinase activity. These efforts have led to FDA approval of Selpercatinib and Pralsetinib for NSCLC, as well as, additional selective RET inhibitors in preclinical and clinical testing. This review covers the current biological understanding of RET signaling, the impact of RET hyperactivity on tumor progression in multiple tumor types, and RET inhibitors with promising preclinical and clinical efficacy.