bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter to the Editor: Facial paralysis following messenger RNA COVID-19 Vaccines: The report of two Cases
Authors: SALBAŞ Ender , ÖCEK Özge , ÖCEK Levent , KARAHAN Ali Yavuz
Published: August 2021

The Covid-19 pandemic is a big challenge for all of us and has brought us suffering, death, and fear. This issue is an unprecedented situation and requires an unprecedented response. Fortunately, COVID-19 vaccines have been developed rapidly and in a short period, they were demonstrated to be safe and effective. Also, World Health Organization is working to promote fair access to safe and effective COVID-19 vaccines and coordinates key steps in this process. Nowadays, thankfully more than ten different vaccines have been administered. The vaccination programs started in early December 2020 and more than 20% of the world population has received at least one dose of a COVID-19 vaccine by the end of June 2021 (1,2).

Some of the COVID-19 vaccines have been the first to be produced using the messenger RNA (mRNA) platform. While high effectivity is an expectation of these vaccines also, they are “reactogenic,” meaning that they’re likely to cause a noticeable immune response. So, according to reports, about side effects following vaccination with the Pfizer and Moderna mRNA vaccines the side effects of the COVID-19 vaccine vary with the type of the vaccine (3,4). While the soreness of the site of injection is the most common side effect, other side effects such as headache, fatigue, muscle aches, joint pain, chills, and fever usually last 24 to 48 hours (3,4). Maybe not as a side effect but, an imbalance was reported in the incidence of facial paralysis following the vaccination. Facial paralysis (FP) was reported during the phase 3 clinical trials of mRNA COVID-19 vaccines (3,4). Seven cases were observed in vaccine groups among the 35611 participants (3,4). Also, facial nerve-related disorders such as facial paresis, facial spasms, and nerve disorders were reported as a drug reaction with mRNA COVID-19 vaccines (5). According to reports, we see symptoms of nerve pathology can vary from one to another and range in severity from mild weakness to total paralysis (5). According to World Health Organization Pharmacovigilance Database, almost half of the patients with FP were reported from the United States of America (USA) and the United Kingdom (UK) (5). According to our current knowledge, there is no case reported from Turkey.
In June 2021, we had the opportunity to treat two patients with FP who developed nerve damage following the Pfizer COVID-19 vaccine. The purpose of this letter is to describe the individual situation of two FP patients in detail and to help health professionals make a decision about how to do things in similar features.
НАРОДНОЕ ИСКУССТВО – ЭТО ДУХОВНАЯ КУЛЬТУРА! ПРОБЛЕМА КЛЮЧЕВЫХ ПОНЯТИЙ В ГОСУДАРСТВЕННОЙ СТРАТЕГИИ РАЗВИТИЯ НАРОДНЫХ ХУДОЖЕСТВЕННЫХ ПРОМЫСЛОВ
Authors: Некрасова Мария Александровна
Published: August 2021

Аннотация. Проблемная статья затрагивает крайне важную и болезненную тему – судьбу народных промыслов в современной России; сохраниться ли им в связи с традицией, народными корнями, в тесном контакте с профильными научными центрами или уйти в сферу бизнеса и торговли, подчинившись задачам рынка и произволу потребительского вкуса. Автор обращает внимание на приоритеты народной художественной культуры, которые должно защищать государство, в связи с чем насущная задача в специальном законе, защищающем эту сферу культуры, должна быть решена коллегиально и широко, с широким обсуждением и привлечением специалистов из научных учреждений и народных центров для разработки такого закона.
Abstract. The problematic article touches upon an extremely important and painful topic - the fate of folk crafts in modern Russia; whether they will remain in connection with tradition, national roots, in close contact with specialized scientific centers, or go into the sphere of business and trade, submitting to the tasks of the market and the arbitrariness of consumer taste. The author draws attention to the priorities of folk art culture, which should be protected by the state, in connection with which the urgent task in a special law protecting this sphere of culture should be solved collectively and widely, with wide discussion and the involvement of specialists from scientific institutions and folk centers to develop such a law.
ПИСЬМА ПРОТОИЕРЕЯ МИХАИЛА ЕЖОВА К ВАЛЕНТИНЕ АНДРЕЕВНЕ ЗВОНКОВОЙ (ЧАСТЬ 1)
Authors: Звонкова Валентина Андреевна
Published: August 2021

Аннотация. Письма, адресованные В. А. Звонковой, мы печатаем вслед за ее воспоминаниями, чтобы еще более выпукло представить ту ситуацию в церковно-приходской жизни 1950–1970-х гг., которую описывает их автор. Священник, являвшийся духовником юной девушки, раскрывает перед читателем внутренний мир церковного человека в его молодые годы, полные испытаний. Также здесь публикуются письма того же священника Михаила Ежова к двум другим адресатам, сохранившиеся в архиве Звонковой. Это эпистолярное наследие содержит в себе ценные материалы о духовной жизни в советские годы, позволяющие нам говорить о высокой культуре духовничества среди белого духовенства.
Abstract. We are publishing the Letters addressed to V. A. Zvonkova following her memoirs in order to present even more vividly the situation in the parish life of the 1950s–1970s, which their author describes. The priest, who was the confessor of a young girl, reveals to the reader the inner world of a church person in his young years, full of trials. It also publishes letters from the same priest Mikhail Yezhov to two other addressees, preserved in Zvonkova’s archive. This epistolary legacy contains valuable materials about spiritual life in the Soviet years, allowing us to talk about the high culture of clergy among the white clergy.
Facile Assembly of Thermosensitive Liposomes for Active Targeting Imaging and Synergetic Chemo-/Magnetic Hyperthermia Therapy
Authors: An Yanli , Yang Rui , Wang Xihui , Han Yong , Jia Gang , Hu Chunmei , Zhang Zhiyuan , Liu Dongfang , Tang Qiusha
Published: August 2021

Cancer stem cells (CSCs) are thought to be responsible for the recurrence of liver cancer, highlighting the urgent need for the development of effective treatment regimens. In this study, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and thermosensitive magnetoliposomes (TMs) conjugated to anti-CD90 (CD90@17-AAG/TMs) were developed for temperature-responsive CD90-targeted synergetic chemo-/magnetic hyperthermia therapy and simultaneous imaging in vivo. The targeting ability of CD90@DiR/TMs was studied with near-infrared (NIR) resonance imaging and magnetic resonance imaging (MRI), and the antitumor effect of CD90@17-AAG/TM-mediated magnetic thermotherapy was evaluated in vivo. After treatment, the tumors were analyzed with Western blotting, hematoxylin and eosin staining, and immunohistochemical (IHC) staining. The relative intensity of fluorescence was approximately twofold higher in the targeted group than in the non-targeted group, while the T2 relaxation time was significantly lower in the targeted group than in the non-targeted group. The combined treatment of chemotherapy, thermotherapy, and targeting therapy exhibited the most significant antitumor effect as compared to any of the treatments alone. The anti-CD90 monoclonal antibody (mAb)-targeted delivery system, CD90@17-AAG/TMs, exhibited powerful targeting and antitumor efficacies against CD90+ liver cancer stem cells in vivo.
Disruption of Glutamate Release and Uptake-Related Protein Expression After Noise-Induced Synaptopathy in the Cochlea
Authors: Ma Kefeng , Zhang Anran , She Xiaojun , Yang Honglian , Wang Kun , Zhu Yingwen , Gao Xiujie , Cui Bo
Published: August 2021

High-intensity noise can cause permanent hearing loss; however, short-duration medium-intensity noise only induces a temporary threshold shift (TTS) and damages synapses formed by inner hair cells (IHCs) and spiral ganglion nerves. Synaptopathy is generally thought to be caused by glutamate excitotoxicity. In this study, we investigated the expression levels of vesicle transporter protein 3 (Vglut3), responsible for the release of glutamate; glutamate/aspartate transporter protein (GLAST), responsible for the uptake of glutamate; and Na+/K+-ATPase α1 coupled with GLAST, in the process of synaptopathy in the cochlea. The results of the auditory brainstem response (ABR) and CtBP2 immunofluorescence revealed that synaptopathy was induced on day 30 after 100 dB SPL noise exposure in C57BL/6J mice. We found that GLAST and Na+/K+-ATPase α1 were co-localized in the cochlea, mainly in the stria vascularis, spiral ligament, and spiral ganglion cells. Furthermore, Vglut3, GLAST, and Na+/K+-ATPase α1 expression were disrupted after noise exposure. These results indicate that disruption of glutamate release and uptake-related protein expression may exacerbate the occurrence of synaptopathy.
Magnetic Molecularly Imprinted Polymers: Synthesis and Applications in the Selective Extraction of Antibiotics
Authors: Li Junyu , Wang Yiran , Yu Xiuxia
Published: August 2021

Recently, magnetic molecularly imprinted polymers (MMIPs) have integrated molecular imprinting technology (MIT) and magnetic separation technology and become a novel material with specific recognition and effective separation of target molecules. Based on their special function, they can be widely used to detect contaminants such as antibiotics. The antibiotic residues in the environment not only cause harm to the balance of the ecosystem but also induce bacterial resistance to specific antibiotics. Given the above consideration, it is especially important to develop sensitive and selective methods for measuring antibiotics in the complex matrix. The combination of MMIPs and conventional analytical methods provides a rapid approach to separate and determine antibiotics residues. This article gives a systematic overview of synthetic approaches of the novel MMIPs materials, briefly introduces their use in sample pretreatment prior to antibiotic detection, and provides a perspective for future research.
The Role of Non-Typeable Haemophilus influenzae Biofilms in Chronic Obstructive Pulmonary Disease
Authors: Weeks Jake R. , Staples Karl J. , Spalluto C. Mirella , Watson Alastair , Wilkinson Tom M. A.
Published: August 2021

Non-typeable Haemophilus influenzae (NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD). COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation. Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD. NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts. However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa as the cause. NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility. There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD. NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes. These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix. These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including S. pneumoniae and M. catarrhalis. Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or in-vitro bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied. This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung. Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets.
Exercise Prior to Lower Extremity Peripheral Artery Disease Improves Endurance Capacity and Hindlimb Blood Flow by Inhibiting Muscle Inflammation
Authors: Pellegrin Maxime , Bouzourène Karima , Mazzolai Lucia
Published: August 2021

Lower extremity peripheral artery disease (PAD) is associated with functional decline. Physical exercise has been proven to be an effective therapeutic strategy for PAD; however the effect of exercise initiated before PAD remains unknown. Here, we investigated the preventive effects of exercise on endurance capacity, hindlimb perfusion, and on polarization profile of circulating monocytes and limb muscle macrophages. ApoE−/− mice were subjected to 5-week running wheel exercise or remained sedentary before induction of hindlimb ischemia. The two groups were thereafter kept sedentary. Exercised mice prior to PAD showed higher exhaustive treadmill running distance and time than sedentary mice. Preventive exercise also increased perfusion, arteriole density, and muscle regeneration in the ischemic hindlimb. Moreover, preventive exercise prevented ischemia-induced increased gene expression of pro-inflammatory M1 macrophages markers and cytokines in the ischemic muscle, while no changes were observed for anti-inflammatory M2 macrophage markers. Flow cytometry analysis showed that the proportion of circulating pro-inflammatory monocyte subtype decreased whereas that of anti-inflammatory monocytes increased with preventive exercise. Overall, we show that exercise initiated before PAD improves endurance performance and hindlimb perfusion in mice probably via inhibition of M1 macrophage polarization and inflammation in the ischemic muscle. Our study provides experimental evidence for a role of regular exercise in primary prevention of PAD.
Development of Personas to Communicate Narrative-Based Information About the HPV Vaccine on Twitter
Authors: Massey Philip M. , Chiang Shawn C. , Rose Meredith , Murray Regan M. , Rockett Madeline , Togo Elikem , Klassen Ann C. , Manganello Jennifer A. , Leader Amy E.
Published: August 2021

Introduction: Personas are based on real-life typologies of people that can be used to create characters and messages to communicate important health information through relatable narrative storylines. Persona development is data-driven and can involve multiple phases of formative research and evaluation; however, personas are largely underutilized in digital health research. The purpose of this study was to create and document persona development to deliver narrative-focused health education for parents on Twitter with the goal of increasing uptake of HPV vaccination among adolescents.

Methods: Leveraging data from a mixed-method study conducted in the U.S. with a diverse population of parents with adolescents ages 9–14, we used both qualitative and quantitative data (e.g., the National Immunization Survey—Teen, focus groups, and social media) to create personas. These data sources were used to identify and develop key characteristics for personas to reflect a range of parents and their diverse understandings and experiences related to HPV vaccination. A parent advisory board provided insight and helped refine persona development.

Results: Four personas emerged and were characterized as the (1) Informed Altruist, (2) Real Talker, (3) Information Gatherer, and (4) Supporter. Characteristics differed across personas and provided insights into targeted narrative strategies. Described attributes included demographics, psychographics, communication style, vaccine goals and aspirations, vaccine challenges and frustrations, and vaccine hesitancy.

Discussion: This work demonstrates how multiple data sources can be used to create personas to deliver social media messages that can address the diverse preferences and needs of parents for HPV vaccine information. With increasing usage of social media for health information among parents, it is important for researchers to consider marketing and design thinking to create health communication messages that resonate with audiences.
(E-)Learning to Understand and Love Yourself: An Attempt to Teach Healthy Lifestyle in the Midst of Social Unrest
Authors: Lee Wai Sum Amy
Published: August 2021

In the 2012 curriculum reform, an extra year was added to the typical university degree programme in Hong Kong, and this became a good opportunity to provide more structured General Education to students in all major disciplines. Although the mode, units allocation, and actual course content of these GE courses in local universities differ, what they share is a comprehensive coverage across knowledge areas: the arts, the social and natural sciences, and skill sets that students can apply in personal and professional life. The author of this article taught in a Hong Kong university that offers a General Education programme with courses designed and delivered by individual academic departments and supported by relevant administrative units. This article is a reflection on teaching a General Education course in the category of Healthy Lifestyle, open to full-time students of all disciplines, during the fall semester of academic year 2019-2020. During most of the semester, daily life in Hong Kong had been disrupted to different extents, and the emotional landscape across different population groups had been rugged. University students were also affected physically and emotionally during this time, the teaching and learning environment was challenging, and teachers had to create an appropriate teaching and learning experience in view of the external environment and the students’ internal emotional needs. This article shares some useful practices in employing e-learning during a time of unrest, to facilitate the teaching of healthy lifestyle to students. The learning outcomes achieved, as seen in some student work, encourage us to seek further ways to employ e-learning for more effective learning experience for new generations of students, especially in the area of affective learning.
Parathyroid Adenoma With Respiratory-Like Epithelium: Case Report of a Potential Mimic With Unknown Etiology
Authors: Juhlin C. Christofer , Zedenius Jan
Published: August 2021

Parathyroid adenoma is a tumor composed of increased parenchymal tissue, often built-up by chief cells, transitional cells or oncocytic cells arranged in acinar or solid formations. Occasionally, rare histological patterns are reported, including cystic or trabecular arrangements. We present a 47 year-old male patient with primary hyperparathyroidism who underwent focused parathyroidectomy for a right inferior adenoma. Surgery was uneventful, but histologically, normal parathyroid tissue adjacent to a tumorous structure displaying a cystic growth pattern was detected. The cells lining the cyst walls appeared cylindrical and pseudo-stratified, vaguely reminiscent of a respiratory type of epithelium usually associated to branchial cleft cysts or thyroglossal cyst remnants, albeit with a tumorous appearance. The respiratory-like epithelium stained positive for parathyroid markers PTH and GATA3, thereby confirming them as parathyroid-derived. The patient was cured from surgery as he displayed normal calcium and PTH levels postoperatively, and is currently alive and well without signs of relapse 4 years after surgery. This is to our knowledge the first report of a parathyroid tumor displaying a respiratory-like epithelium. Experimentally, canine parathyroid glands can develop ciliated respiratory epithelium in response to inhalation of ozone. Our patient is a construction worker with a hypothetically increased risk of continuous ozone exposure. Although this association remains purely speculative, future investigations of this tumor phenotype could perhaps yield novel insights regarding the frequency of this histological variant, potential clinical associations, and clues regarding influencing factors.
Production Performance Analysis of Class II Hydrate-Bearing Layers Based on an Analytic Aquifer Model
Authors: Yu Jing , Zhuo Lubin , Chen Yang , Sun Wenchao , Liu Yongge
Published: August 2021

In the current numerical simulation studies, bottom water in Class II hydrate-bearing layers is represented by grids with high water saturation that significantly extends the calculation time if the volume of the bottom water is large or grid size is small. Moreover, the influence of the bottom water volume on the depressurization performance of Class II hydrate-bearing layers has not been fully investigated. In this study, the Fetkovich analytic aquifer model was coupled with a simulation model of a hydrate reservoir to accelerate the simulation of Class II hydrate-bearing layers. Then the simulation results and calculation time were compared between the coupled model and the model in which the bottom water layer is only represented by grids. Finally, the influence of the bottom water volume on the productivity of gas and water in the depressurization method was investigated and the variation of pressure, temperature, and hydrate saturation during the production process was analyzed. The results show that the coupled model can significantly reduce the simulation time of Class II hydrate-bearing layer while ensuring calculation accuracy. When the pore volume of the aquifer increases to 20 times that of the bottom water layer, the computation time of a single model in which the bottom water layer is represented by grids is 18.7 times that of the coupled model. Bottom water invasion slows down the depressurization, and therefore, the larger the aquifer, the lower the peak value of gas production, and the later it appears. However, the invading bottom water can provide heat for hydrate dissociation; therefore, the gas production rate of the hydrate-bearing layer with bottom water is higher than that of the hydrate-bearing layer without bottom water in the late development stage. Generally, the presence of bottom water reduces the cumulative gas production and increases the cumulative water production; therefore, the larger the aquifer, the more unfavorable the depressurization development of the hydrate-bearing layer.
Phytomanagement of Metal(loid)-Contaminated Soils: Options, Efficiency and Value
Authors: Moreira Helena , Pereira Sofia I. A. , Mench Michel , Garbisu Carlos , Kidd Petra , Castro Paula M. L.
Published: August 2021

The growing loss of soil functionality due to contamination by metal(loid)s, alone or in combination with organic pollutants, is a global environmental issue that entails major risks to ecosystems and human health. Consequently, the management and restructuring of large metal(loid)-polluted areas through sustainable nature-based solutions is currently a priority in research programs and legislation worldwide. Over the last few years, phytomanagement has emerged as a promising phytotechnology, focused on the use of plants and associated microorganisms, together withad hocsite management practices, for an economically viable and ecologically sustainable recovery of contaminated sites. It promotes simultaneously the recovery of soil ecological functions and the decrease of pollutant linkages, while providing economic revenues,e.g.by producing non-food crops for biomass-processing technologies (biofuel and bioenergy sector, ecomaterials, biosourced-chemistry, etc.), thus contributing to the international demand for sustainable and renewable sources of energy and raw materials for the bioeconomy. Potential environmental benefits also include the provision of valuable ecosystem services such as water drainage management, soil erosion deterrence, C sequestration, regulation of nutrient cycles, xenobiotic biodegradation, and metal(loid) stabilization. Phytomanagement relies on the proper selection of (i) plants and (ii) microbial inoculants with the capacity to behave as powerful plant allies,e.g., PGPB: plant growth-promoting bacteria and AMF: arbuscular mycorrhizal fungi. This review gives an up-to-date overview of the main annual, perennial, and woody crops, as well as the most adequate cropping systems, presently used to phytomanage metal(loid)-contaminated soils, and the relevant products and ecosystems services provided by the various phytomanagement options. Suitable bioaugmentation practices with PGPB and AMF are also discussed. Furthermore, we identify the potential interest of phytomanagement for stakeholders and end-users and highlight future opportunities boosted by an effective engagement between environmental protection and economic development. We conclude by presenting the legal and regulatory framework of soil remediation and by discussing prospects for phytotechnologies applications in the future.
Hierarchical, Memory-Based Movement Models for Translocated Elk (Cervus canadensis)
Authors: Falcón-Cortés Andrea , Boyer Denis , Merrill Evelyn , Frair Jacqueline L. , Morales Juan Manuel
Published: August 2021

The use of spatial memory is well-documented in many animal species and has been shown to be critical for the emergence of spatial learning. Adaptive behaviors based on learning can emerge thanks to an interdependence between the acquisition of information over time and movement decisions. The study of how spatio-ecological knowledge is constructed throughout the life of an individual has not been carried out in a quantitative and comprehensive way, hindered by the lack of knowledge of the information an animal already has of its environment at the time monitoring begins. Identifying how animals use memory to make beneficial decisions is fundamental to developing a general theory of animal movement and space use. Here we propose several mobility models based on memory and perform hierarchical Bayesian inference on 11-month trajectories of 21 elk after they were released in a completely new environment. Almost all the observed animals exhibited preferential returns to previously visited patches, such that memory and random exploration phases occurred. Memory decay was mild or negligible over the study period. The fact that individual elk rapidly become used to a relatively small number of patches was consistent with the hypothesis that they seek places with predictable resources and reduced mortality risks such as predation.
Association Between Human Leukocyte Antigen Class I and II Diversity and Non-virus-associated Solid Tumors
Authors: Liu Zhiwei , Hildesheim Allan
Published: August 2021

Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (Ptrend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors.
The Impact of Single Nucleotide Polymorphism in the Long Non-coding MEG3 Gene on MicroRNA-182 and MicroRNA-29 Expression Levels in the Development of Breast Cancer in Egyptian Women
Authors: Shaker Olfat , Ayeldeen Ghada , Abdelhamid Amr
Published: August 2021

Early-stage detection of BC is a critical factor for effective treatment of the disease and can increase the survival rate of BC patients. Long non-coding RNAs can act as miRNA decoys by sequestering miRNAs, thus acting as competing endogenous RNAs and leading to re-expression of miRNA target genes. Maternally expressed 3 (MEG3) is LncRNA and it was reported to be tumor suppressor in breast cancer. The study aims to investigate the effect of MEG3 SNP (rs7158663 G/A) and its association with breast cancer risk in the Egyptian population. In addition, demonstrate the consequence of the MEG3 polymorphism on the expression levels of MEG3, miR-182, and miRNA-29. MEG3 rs7158663 G/A was genotyped and serum MEG3, miRNA-182, and miRNA-29 were measured in 180 breast cancer, 120 FA, and 150 controls by the qPCR. Frequencies of MEG3 rs7158663 GA/AA genotype and A allele were significantly higher in BC patients compared to the controls results showed that serum MEG3 levels were significantly lower, according to the presence of the A allele in different study groups while the expression of miR-182 and miRNA 29 were significantly elevated. MEG3, miR-182, and miRNA-29 are key genes involved in the development of BC, are considered as a novel potential non-invasive diagnostic biomarker for BC.
Bioinformatics Analysis of circRNA Expression and Construction of “circRNA-miRNA-mRNA” Competing Endogenous RNAs Networks in Bipolar Disorder Patients
Authors: Fu Yonghui , He Wenfeng , Zhou Chaoxiong , Fu Xia , Wan Qigen , He Ling , Wei Bo
Published: August 2021

Bipolar disorder (BD) is a severe mood disorder disease in China, and its underlying pathogenesis remains unknown. Circular RNAs (circRNAs) have been reported to play a key role in mental disorders and can be used as competitive endogenous RNAs (ceRNAs). However, little is known about the correlation of circRNAs with BD. In this study, Deep RNA sequencing was used to identify differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs) between BD patients and a control group. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed RNAs (DE-RNAs). In all 9,593 circRNAs and 20,030 mRNAs were found in the two groups of specimens, among which 50 DE-circRNAs and 244 DE-mRNAs were significantly upregulated, and 44 DE-circRNAs and 294 DE-mRNAs were significantly downregulated. Based on the regulatory mechanism of ceRNAs, circRNAs can directly bind microRNAs (miRNAs) to affect mRNA expression, and the expression trends of circRNAs and mRNAs are consistent. According to this mechanism, we constructed two ceRNA networks by using the RNA sequencing data. The function of these DE-circRNAs was further elucidated by enrichment analysis. In summary, the present study showed that the circRNA expression profile of BD patients is altered, and a ceRNA regulatory network was constructed, which provided a hypothesis about the pathogenesis of BD.
Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study
Authors: Cossu Davide , Yokoyama Kazumasa , Sechi Leonardo Antonio , Hattori Nobutaka
Published: August 2021

Background

Mitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS).

Objective

To determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders.

Methods

Protein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched controls.

Results

CSF and serum concentrations of PINK1 were higher in patients with MS than in patients with NMOSD (p = 0.004 and p < 0.001, respectively), MOGAD (p = 0.008 and p = 0.011, respectively), and controls (p = 0.021 and p = 0.002, respectively). CSF and concentrations of PARKIN were elevated in patients with MS in comparison with those in controls (p = 0.016 and p = 0.05, respectively).

Conclusions

Our study highlighted the importance of mitophagy in MS and suggested the potential application of PINK1 and PARKIN as biomarkers to predict disease activity.
Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study
Authors: Wang Jingqi , Cui Chunping , Lu Yaxin , Chang Yanyu , Wang Yuge , Li Rui , Shan Yilong , Sun Xiaobo , Long Youming , Wang Honghao , Wang Zhanhang , Lee Michael , He Shane , Lu Zhengqi , Qiu Wei , Tan Sha
Published: August 2021

Objective

To explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity.

Method

Patients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage.

Results

One hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with apheresis (8%), IVMP combined with intravenous immunoglobulin (18%) and other therapies (3%). EDSS scores decreased significantly from a medium of 4 (interquartile range 3.0–5.5) at attack to 3.5 (3.0–4.5) at discharge, 3.5 (2.0–4.0) at the 1-month visit and 3.0 (2.0–4.0) at the 3-month visit (p<0.01 in all comparisons). The remission rate was 38.0% at discharge and 63.3% at the 1-month visit. Notably, relapse occurred in 12.2% of 74 patients by the 6-month follow-up. Higher levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-10, IL-13, and IL-1 receptor antagonist, predicted remission at the 1-month visit (OR=9.33, p=0.04). Serum NfL levels correlated positively with onset EDSS scores in acute-phase NMOSD (p<0.001, R2 = 0.487).

Conclusions

Outcomes of NMOSD attacks were generally moderate. A high level of serum Th2-related cytokines predicted remission at the 1-month visit, and serum NfL may serve as a biomarker of disease severity at attack.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04101058, identifier NCT04101058.
Seasonal Variability in the Zooplankton Community Structure in a Sub-Arctic Fjord as Revealed by Morphological and Molecular Approaches
Authors: Coguiec Estelle , Ershova Elizaveta A. , Daase Malin , Vonnahme Tobias R. , Wangensteen Owen S. , Gradinger Rolf , Præbel Kim , Berge Jørgen
Published: August 2021

Phyto- and zooplankton in Arctic and sub-Arctic seas show very strong seasonal changes in diversity and biomass. Here we document the seasonal variability in the mesozooplankton community structure in a sub-Arctic fjord in Northern Norway based on monthly sampling between November 2018 and February 2020. We combined traditional morphological zooplankton identification with DNA metabarcoding of a 313 base pair fragment of the COI gene. This approach allowed us to provide the most detailed mesozooplankton species list known for this region across an entire year, including both holo- and meroplankton. The zooplankton community was dominated by small copepods throughout the sampling period both in terms of abundance and relative sequence counts. However, meroplankton was the most diverse group, especially within the phylum polychaeta. We identified four distinct periods based on the seasonal analysis of the zooplankton community composition. The pre-spring bloom period (February–March) was characterized by low abundance and biomass of zooplankton. The spring bloom (April) was characterized by the presence of Calanus young stages, cirripedia and krill eggs. The spring-summer period (May–August) was characterized by a succession of meroplankton and a relatively high abundance of copepods of the genus Calanus spp. Finally, the autumn-winter period (September–December) was characterized by a high copepod diversity and a peak in abundance of small copepods (e.g., Oithona similis, Acartia longiremis, Pseudocalanus acuspes, Pseudocalanus elongatus, Pseudocalanus moultoni, Pseudocalanus minutus). During this period, we also observed an influx of boreal warm-water species which were notably absent during the rest of the year. Both the traditional community analysis and metabarcoding were highly complementary and with a few exceptions showed similar trends in the seasonal changes of the zooplankton community structure.
‘Candidatus Liberibacter asiaticus’ Multimeric LotP Mediates Citrus sinensis Defense Response Activation
Authors: Merli Marcelo L. , Padgett-Pagliai Kaylie A. , Cuaycal Alexandra E. , Garcia Lucila , Marano Maria Rosa , Lorca Graciela L. , Gonzalez Claudio F.
Published: August 2021

‘Candidatus Liberibacter asiaticus’ is known as the most pathogenic organism associated with citrus greening disease. Since its publicized emergence in Florida in 2005, ‘Ca. L. asiaticus’ remains unculturable. Currently, a limited number of potential disease effectors have been identified through in silico analysis. Therefore, these potential effectors remain poorly characterized and do not fully explain the complexity of symptoms observed in citrus trees infected with ‘Ca. L. asiaticus.’ LotP has been identified as a potential effector and have been partially characterized. This protein retains structural homology to the substrate binding domain of the Lon protease. LotP interacts with chaperones like GroEL, Hsp40, DnaJ, and ClpX and may exercise its biological role through interactions with different proteins involved in proteostasis networks. Here, we evaluate the interactome of LotP—revealing a new protein–protein interaction target (Lon-serine protease) and its effect on citrus plant tissue integrity. We found that via protein–protein interactions, LotP can enhance Lon protease activity, increasing the degradation rate of its specific targets. Infiltration of purified LotP strained citrus plant tissue causing photoinhibition and chlorosis after several days. Proteomics analysis of LotP tissues recovering after the infiltration revealed a large abundance of plant proteins associated with the stabilization and processing of mRNA transcripts, a subset of important transcription factors; and pathways associated with innate plant defense were highly expressed. Furthermore, interactions and substrate binding module of LotP suggest potential interactions with plant proteins, most likely proteases.
Characterization of an Endophytic Strain Talaromyces assiutensis, CPEF04 With Evaluation of Production Medium for Extracellular Red Pigments Having Antimicrobial and Anticancer Properties
Authors: Mishra Rahul Chandra , Kalra Rishu , Dilawari Rahul , Deshmukh Sunil Kumar , Barrow Colin J. , Goel Mayurika
Published: August 2021

Considering the worldwide demand for colorants of natural origin, the utilization of ascomycete fungi as a prolific pigment producer unfolds a novel way to obtain these pigments for various applications, including food, cosmetic, and medical use. The presence of very few natural red pigment alternatives in the market also attracts research and industry priorities to unearth novel and sustainable red pigment producers. The present work is an attempt to identify a novel source of red color obtained from endophytic fungi isolated from terrestrial and marine habitats. Based upon the fungal capacity for pigment production, seven isolates of endophytic fungi were recognized as prospective pigment producers. Out of all, fungal isolate CPE04 was selected based upon its capacity to produce profuse extracellular red pigment. The isolate was identified as Talaromyces assiutensis, employing morphological features and phylogenetic characterization by internal transcribed spacer (ITS) sequences. To understand the chemical behavior of pigment molecules, an investigation of the chemical profile of fungal culture filtrate dried powder (CFDP) was performed using ultra-high-performance liquid chromatography-diode array detector-mass spectrometry (UPLC–DAD–MS). In total, eight compounds having pigment and pharmaceutical application were tentatively identified using UPLC–DAD–MS. Considering the commercial aspect of the stated work, an effort was also made for standardizing the upscaling of the pigment molecule. Investigations were performed for optimum medium and culturing conditions for maximum pigment production. CFDP was found to have a significant antibacterial activity against the bacterial pathogens Staphylococcus aureus (MTCC737), Vibrio cholerae (N16961), and methicillin-resistant S. aureus (MRSA) (ATCC BAA811). The CFDP showed a minimum inhibitory concentration at 64, 128, and 256 μg/ml against S. aureus, MRSA, and V. cholerae. A concentration-dependent (50–400 μg/ml) anticancer effect on HeLa cancer line was also observed, having a half-maximal inhibitory concentration (IC50) at 300 μg/ml. The antioxidant potential of CFDP has also been proven with the help of an antioxidant assay against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (IC50, 32.01 μg/ml); DNA nicking assay and reactive oxygen species were generated in HeLa cancer line cells. The CFDP was also found to have no cytotoxicity toward HEK 293 T cell line using alamar blue (resazurin), a cell metabolic activity reagent.
Paeonol Attenuates Quorum-Sensing Regulated Virulence and Biofilm Formation in Pseudomonas aeruginosa
Authors: Yang Dan , Hao Suqi , Zhao Ling , Shi Fei , Ye Gang , Zou Yuanfeng , Song Xu , Li Lixia , Yin Zhongqiong , He Xiaoli , Feng Shiling , Chen Helin , Zhang Yu , Gao Yuanze , Li Yinglun , Tang Huaqiao
Published: August 2021

With the prevalence of multidrug-resistant bacteria and clinical -acquired pathogenic infections, the development of quorum-sensing (QS) interfering agents is one of the most potential strategies to combat bacterial infections and antibiotic resistance. Chinese herbal medicines constitute a valuable bank of resources for the identification of QS inhibitors. Accordingly, in this research, some compounds were tested for QS inhibition using indicator strains. Paeonol is a phenolic compound, which can effectively reduce the production of violacein without affecting its growth in Chromobacterium violaceum ATCC 12472, indicating its excellent anti-QS activity. This study assessed the anti-biofilm activity of paeonol against Gram-negative pathogens and investigated the effect of paeonol on QS-regulated virulence factors in Pseudomonas aeruginosa. A Caenorhabditis elegans infection model was used to explore the anti-infection ability of paeonol in vivo. Paeonol exhibited an effective anti-biofilm activity against Gram-negative bacteria. The ability of paeonol to interfere with the AHL-mediated quorum sensing systems of P. aeruginosa was determined, found that it could attenuate biofilm formation, and synthesis of pyocyanin, protease, elastase, motility, and AHL signaling molecule in a concentration- and time-dependent manner. Moreover, paeonol could significantly downregulate the transcription level of the QS-related genes of P. aeruginosa including lasI/R, rhlI/R, pqs/mvfR, as well as mediated its virulence factors, lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS. In vivo studies revealed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans, showing a moderate protective effect on C. elegans. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of P. aeruginosa and that further research elucidating the anti-QS mechanism of this compound in vivo is warranted.
Assessing the Influence of Environmental Sources on the Gut Mycobiome of Tibetan Macaques
Authors: Sun Binghua , Xia Yingna , Davison Samuel , Gomez Andres , Garber Paul A. , Amato Katherine R. , Xu Xiaojuan , Xia Dong-po , Wang Xi , Li Jin-hua
Published: August 2021

The distribution and availability of microbes in the environment has an important effect on the composition of the gut microbiome of wild vertebrates. However, our current knowledge of gut-environmental interactions is based principally on data from the host bacterial microbiome, rather than on links that establish how and where hosts acquire their gut mycobiome. This complex interaction needs to be clarified. Here, we explored the relationship between the gut fungal communities of Tibetan macaques (Macaca thibetana) and the presence of environmental (plant and soil) fungi at two study sites using the fungal internal transcribed spacer (ITS) and next generation sequencing. Our findings demonstrate that the gut, plant and soil fungal communities in their natural habitat were distinct. We found that at both study sites, the core abundant taxa and ASVs (Amplicon Sequence Variants) of Tibetan macaques’ gut mycobiome were present in environmental samples (plant, soil or both). However, the majority of these fungi were characterized by a relatively low abundance in the environment. This pattern implies that the ecology of the gut may select for diverse but rare environmental fungi. Moreover, our data indicates that the gut mycobiome of Tibetan macaques was more similar to the mycobiome of their plant diet than that present in the soil. For example, we found three abundant ASVs (Didymella rosea, Cercospora, and Cladosporium) that were present in the gut and on plants, but not in the soil. Our results highlight a relationship between the gut mycobiome of wild primates and environmental fungi, with plants diets possibly contributing more to seeding the macaque’s gut mycobiome than soil fungi.
Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke
Authors: Zhou Xiangyue , Li Youwei , Lenahan Cameron , Ou Yibo , Wang Minghuan , He Yue
Published: August 2021

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.