bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Self-Care in Older Adults With Type 1 Diabetes Mellitus: How Does Cognition Influence Self-Management
Authors: Taboada Gjorup Ana Lúcia , Snoek Frank J. , van Duinkerken Eelco
Published: September 2021

With increasing knowledge and improvements in options for glycemic control, the life-expectancy of patients with type 1 diabetes mellitus (T1DM) has increased considerably over the past decades. Whereas this is undeniably positive for patients, aging is related to natural decline in cognitive functions. As patients with T1DM across the life-span are susceptible to cognitive deterioration, an interaction with aging may be expected and the risk of development of dementia might be increased. As achieving glycemic control depends on a set of diabetes self-management behaviors, it is imperative to understand how cognitive functions are involved in the upkeep of these behaviors and how cognitive impairment may affect them. In this narrative review, we set out to understand the relationship between cognition and T1DM self-care by first reviewing the glycemic targets in older adults, what treatment options are available, and what cognitive functions they draw upon. We will then review the cognitive literature in older adults that is available and then link both together. Lastly, we finish with clinical recommendations and suggestions for future research.
Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma
Authors: Cong Peilin , Wu Tingmei , Huang Xinwei , Liang Huazheng , Gao Xiaofei , Tian Li , Li Wanrong , Chen Aiwen , Wan Hanxi , He Mengfan , Dai Danqing , Li Zhen , Xiong Lize
Published: September 2021

m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan–Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development.
Using Dictyostelium to Advance Our Understanding of the Role of Medium Chain Fatty Acids in Health and Disease
Authors: Pain Erwann , Shinhmar Sonia , Williams Robin S. B.
Published: September 2021

Ketogenic diets have been utilized for many years to improve health, and as a dietary approach for the treatment of a range of diseases, where the mechanism of these low carbohydrate and high fat diets is widely considered to be through the production of metabolic products of fat breakdown, called ketones. One of these diets, the medium chain triglyceride ketogenic diet, involves high fat dietary intake in the form of medium chain fatty acids (MCFAs), decanoic and octanoic acid, and is commonly used in endurance and high intensity exercises but has also demonstrated beneficial effects in the treatment of numerous pathologies including drug resistant epilepsy, cancer, and diabetes. Recent advances, using Dictyostelium discoideum as a model, have controversially proposed several direct molecular mechanisms for decanoic acid in this diet, independent of ketone generation. Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). These discoveries could potentially impact the treatment of a range of disorders including epilepsy, cancer and bipolar disorder. In this review, we summarize the newly proposed mechanisms for decanoic acid, identified using D. discoideum, and highlight potential roles in health and disease treatment.
Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence
Authors: Shankar Chaitra , Basu Soumya , Lal Binesh , Shanmugam Sathiya , Vasudevan Karthick , Mathur Purva , Ramaiah Sudha , Anbarasu Anand , Veeraraghavan Balaji
Published: September 2021

Background

The incidence of hypervirulent (hv) carbapenem-resistant (CR)Klebsiella pneumoniae(Kp) is increasing globally among various clones and is also responsible for nosocomial infections. The CR-hvKp is formed by the uptake of a virulence plasmid by endemic high-risk clones or by the uptake of plasmids carrying antimicrobial resistance genes by the virulent clones. Here, we describe CR-hvKp from India belonging to high-risk clones that have acquired a virulence plasmid and are phenotypically unidentified due to lack of hypermucoviscosity.

Methods

Twenty-seven CRKp isolates were identified to possessrmpA2by whole-genome sequencing; and resistance and virulence determinants were characterized. Byin silicoprotein modeling (and validation), protein backbone stability analysis, and coarse dynamics study, the fitness of RmpA, RmpA2, and aerobactin-associated proteins-IucA and IutA, were determined to establish a reliable marker for clinical identification of CR-hvKp.

Results

The CR-hvKp belonged to multidrug-resistant (MDR) high-risk clones such as CG11, CG43, ST15, and ST231 and carried OXA-232 as the predominant carbapenemase followed by NDM. The virulence plasmid belonged to IncHI1B replicon type and carried frameshifted and truncatedrmpAandrmpA2. This resulted in a lack of hypermucoviscous phenotype. However, functional aerobactin was expressed in all high-risk clones.In silicoanalysis portrayed that IucA and IutA were more stable than classical RmpA. Furthermore, IucA and IutA had lower conformational fluctuations in the functional domains than the non-functional RmpA2, which increases the fitness cost of the latter for its maintenance and expression among CR-hvKp. Hence, RmpA and RmpA2 are likely to be lost among CR-hvKp owing to the increased fitness cost while coding for essential antimicrobial resistance and virulence factors.

Conclusion

Increasing incidence of convergence of AMR and virulence is observed amongK. pneumoniaeglobally, which warrants the need for reliable markers for identifying CR-hvKp. The presence of non-functional RmpA2 among high-risk clones highlights the significance of molecular identification of CR-hvKp. The negative string test due to non-functional RmpA2 among CR-hvKp isolates challenges phenotypic screening and faster identification of this pathotype. This can potentially be counteracted by projecting aerobactin as a stable, constitutively expressed, and functional marker for rapidly evolving CR-hvKp.
Applications of Aptamers in the Diagnosis and Treatment of Ovarian Cancer: Progress From 2016 to 2020
Authors: Ruan Luoshan , Li Xin
Published: September 2021

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides selected from a random single-stranded nucleic acid library using systematic evolution of ligands by exponential enrichment technology. To allow them to bind to molecular targets with the same specificity and precision as that of antibodies, aptamers are folded into secondary or tertiary structures. However, compared to antibodies, aptamers are not immunogenic and are easier to synthesize. Furthermore, they are chemically modified, which protects them from degradation by nucleases. Hence, due to their stability and favorable targeting ability, aptamers are promising for the diagnosis and treatment of diseases. Ovarian cancer has the worst prognosis among all gynecological diseases and is usually diagnosed at the medium and advanced stages due to its nonspecific symptoms. Relapse is common, even if patients receive a standard therapeutic regimen including surgery and chemotherapy; simultaneously, drug resistance and adverse effects are reported in a several patients. Therefore, the safer and more efficient diagnostic and treatment method for ovarian cancer is imperative. Scientists have been trying to utilize aptamer technology for the early diagnosis and accurate treatment of ovarian cancer and some progress has been made in this field. This review discusses the screening of nucleic acid aptamers by targeting ovarian cancer cells and the application of aptamers in the diagnosis and treatment of ovarian cancer.
Disseminated Coccidioidomycosis Following COVID-19 Mimicking Metastatic Thoracic Relapse of Well-Differentiated Liposarcoma: A Case Report
Authors: Nassif Elise F. , Maloney Nolan , Conley Anthony P. , Keung Emily Z.
Published: September 2021

Introduction: COVID-19 is associated with immune dysregulation which may increase susceptibility to atypical infectious diseases, particularly in the vulnerable cancer patient population. Coccidioidomycosis is an endemic fungal infection which presents with mild-to-moderate pneumonia in most cases.

Case Presentation: The presented case is a 67-year-old woman living in the southwestern United States who is under close observation for well-differentiated liposarcoma of the abdominal wall. She presented with persistent cough and fatigue following COVID-19 infection. Imaging revealed new pulmonary nodules, a chest wall mass and bone lesions. The imaging appearance of these lesions was consistent with metastatic disease, although distant metastasis is not typical in well-differentiated liposarcoma. Biopsy of the chest wall mass revealed granulomatous fungal infection and serology was positive for coccidioidomycosis. At the time of diagnosis, the patient was lymphopenic, possibly a sequela of recent COVID-19 infection and which may have contributed to the development of her atypical disseminated form of coccidioidomycosis. Patient was treated with fluconazole for the coccidioidomycosis and continued observation for mild progression of the liposarcoma. On follow-up imaging, the chest wall mass and lung nodules have decreased in size and the patient remains on antifungal treatment. There has been no further increase in the liposarcoma mass.

Conclusion: COVID-19 may be associated with increased risk of atypical forms of infectious diseases in cancer patients, which physicians should be aware of before giving systemic treatments for cancer. In endemic regions, co-infection by coccidioidomycosis should be suspected in cases of persistent symptoms after COVID-19 infection.
Glaucoma Clinical Research: Trends in Treatment Strategies and Drug Development
Authors: Storgaard Line , Tran Thuy Linh , Freiberg Josefine Clement , Hauser Alexander S. , Kolko Miriam
Published: September 2021

Purpose: To investigate the trends and progresses in glaucoma research by searching two major clinical trial registries; clinicaltrials.gov, and Australianclinicaltrials.gov.au.

Methods: All clinical trials with glaucoma covered by Clinicaltrials.gov, and Australianclinicaltrials.gov.au starting the study before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non-treatment trials and divided into three major categories: “laser treatment,” “surgical treatment,” and “medical treatment.” In the category of “medical treatment,” new compounds and their individual targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)-lowering, neuroprotective or vascular. The phase transition success rates were calculated.

Results: One-thousand five hundred and thirty-seven trials were identified. Sixty-three percent (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). The majority of medical trials evaluated IOP-lowering compounds, while trials with neuroprotective or vascular compounds accounted for only 5 and 3%, respectively. Eighty-eight new compounds were identified. Phase I, II, and III transition success rates were 63, 26, and 47%, respectively.

Conclusion: The number of clinical trials in glaucoma research has increased significantly over the last 30 years. Among the most recently evaluated compounds, all three main treatment strategies were represented, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are assessed for a potential anti-glaucomatous effect. Phase II and III success rates were below previously reported success rates for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmological research and gain a better understanding of responders and non-responders.
Ultrasound-Guided Triamcinolone Acetonide Hydrodissection for Carpal Tunnel Syndrome: A Randomized Controlled Trial
Authors: Wang Jia-Chi , Hsu Po-Cheng , Wang Kevin A. , Chang Ke-Vin
Published: September 2021

Background: Despite the wide use of corticosteroid hydrodissection for carpal tunnel syndrome (CTS), there is insufficient evidence to confirm its efficacy. This study aimed to compare the effectiveness of corticosteroid hydrodissection vs. corticosteroid perineural injection alone on clinical and electrophysiological parameters in patients with CTS.

Method: This prospective randomized controlled trial (RCT) was conducted in a tertiary care center with a follow-up period of 12 weeks. Subjects were randomly assigned to either ultrasound-guided hydrodissection with a mixture of 1 mL of triamcinolone acetonide (10 mg/mL), 1 mL of 2% lidocaine, and 8 mL normal saline or ultrasound-guided perineural injection with 1 mL of triamcinolone acetonide (40 mg/mL) and 1 mL of 2% lidocaine. The primary outcome measure was the symptom severity subscale (SSS) of Boston Carpal Tunnel Questionnaire (BCTQ) scores at baseline and at 6 and 12 weeks' post-treatment. The secondary outcomes included the functional status subscale (FSS) of BCTQ and the distal motor latency and sensory nerve conduction velocity of the median nerve. The effect of interventions on the designated outcome was analyzed using a 3 × 2 repeated measures analysis of variance. The within-subject and among-subject factors were differences in time (before the intervention, and 6 and 12 weeks after injection) and intervention types (with or without hydrodissection), respectively.

Results: Sixty-four patients diagnosed with CTS were enrolled. Both groups experienced improvement in the SSS and FSS of BCTQ and median nerve distal motor latency and sensory nerve conduction velocity. However, group-by-time interactions were not significant in any outcome measurements. No serious adverse events were reported in either group, except for two patients in the hydrodissection group who reported minor post-injection pain on the first day after the intervention, which resolved spontaneously without the need for additional treatments.

Conclusion: Hydrodissection did not provide an additional benefit compared to corticosteroid perineural injection alone. More prospective studies are needed to investigate the long-term effectiveness of corticosteroid hydrodissection, as well as its influence on median nerve mobility.
Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci
Authors: Gostev Vladimir , Leyn Semen , Kruglov Alexander , Likholetova Daria , Kalinogorskaya Olga , Baykina Marina , Dmitrieva Natalia , Grigorievskaya Zlata , Priputnevich Tatiana , Lyubasovskaya Lyudmila , Gordeev Alexey , Sidorenko Sergey
Published: September 2021

Coagulase-negative staphylococci (CoNS) for a long time were considered avirulent constituents of the human and warm-blooded animal microbiota. However, at present,S. epidermidis,S. haemolyticus, andS. hominisare recognized as opportunistic pathogens. Although linezolid is not registered for the treatment of CoNS infections, it is widely used off-label, promoting emergence of resistance. Bioinformatic analysis based on maximum-likelihood phylogeny and Bayesian clustering of the CoNS genomes obtained in the current study and downloaded from public databases revealed the existence of international linezolid-resistant lineages, each of which probably had a common predecessor. Linezolid-resistantS. epidermidissequence-type (ST) 2 from Russia, France, and Germany formed a compact group of closely related genomes with a median pairwise single nucleotide polymorphism (SNP) difference of fewer than 53 SNPs, and a common ancestor of this lineage appeared in 1998 (1986–2006) before introduction of linezolid in practice. Another compact group of linezolid-resistantS. epidermidiswas represented by ST22 isolates from France and Russia with a median pairwise SNP difference of 40; a common ancestor of this lineage appeared in 2011 (2008–2013). Linezolid-resistantS. hominisST2 from Russia, Germany, and Brazil also formed a group with a high-level genome identity with median 25.5 core-SNP differences; the appearance of the common progenitor dates to 2003 (1996–2012). Linezolid-resistantS. hominisisolates from Russia demonstrated associated resistance to teicoplanin. Analysis of a midpoint-rooted phylogenetic tree of the group confirmed the genetic proximity of Russian and German isolates; Brazilian isolates were phylogenetically distant.repUS5-like plasmids harboringcfrwere detected inS. hominisandS. haemolyticus.
Key Amino Acids for Pepper Vein Yellows Virus P0 Protein Pathogenicity, Gene Silencing, and Subcellular Localization
Authors: Wang Lishuang , Tian Peijie , Yang Xiuling , Zhou Xueping , Zhang Songbai , Li Chun , Yang Xuehui , Liu Yong
Published: September 2021

Pepper vein yellows virus (PeVYV) is a newly recognized Polerovirus extracted from Chinese pepper. The symptoms of PeVYV-infested pepper plants comprise intervein yellow staining, leaf curl formation and other malformations, and leaf internodal shrinkage, but the roles of the viral proteins remain undetermined. The P0 protein of the genus Polerovirus has established post-transcriptional gene silencing (PTGS) activity. This investigation focused on the PeVYV-encoded P0 protein and assessed its potential virulence capacity, PTGS activity, and tendencies to localize in the nucleus. This study revealed that P0 influenced the pathogenic properties of a specific heterologous potato virus X. In addition, P0 proteins impaired local gene silencing, although they did not regulate generalized gene silencing within Nicotiana benthamiana 16c plants. Furthermore, P0 proteins localized mainly in the nucleus, particularly in the nucleolus. P0 deletion mutagenesis demonstrated that the F-box motif (56–72 amino acids, AAs) of P0 was essential for symptom determination, inhibition of PTGS, and subcellular localization. Mutation analysis of the F-box motif of P0 protein indicated that AA 57 of the P0 protein was a pivotal site in symptom development and that AA 56 of the P0 protein was indispensable for inhibiting PTGS and subcellular localization. The outcomes obtained here suggest that further studies should be conducted on the molecular mechanisms of amino acids of the F-box domain of P0 protein in the interaction of PeVYV with plants.
Exploration of the Diversity of Clustered Regularly Interspaced Short Palindromic Repeats-Cas Systems in Clostridium novyi sensu lato
Authors: Le Gratiet Thibault , Le Marechal Caroline , Devaere Marie , Chemaly Marianne , Woudstra Cédric
Published: September 2021

Classified as the genospecies Clostridium novyi sensu lato and distributed into four lineages (I–IV), Clostridium botulinum (group III), Clostridium novyi, and Clostridium haemolyticum are clostridial pathogens that cause animal diseases. Clostridium novyi sensu lato contains a large mobilome consisting of plasmids and circular bacteriophages. Here, we explored clustered regularly interspaced short palindromic repeats (CRISPR) arrays and their associated proteins (Cas) to shed light on the link between evolution of CRISPR-Cas systems and the plasmid and phage composition in a study of 58 Clostridium novyi sensu lato genomes. In 55 of these genomes, types I-B (complete or partial), I-D, II-C, III-B, III-D, or V-U CRISPR-Cas systems were detected in chromosomes as well as in mobile genetic elements (MGEs). Type I-B predominated (67.2%) and was the only CRISPR type detected in the Ia, III, and IV genomic lineages. Putative type V-U CRISPR Cas14a genes were detected in two different cases: next to partial type-IB CRISPR loci on the phage encoding the botulinum neurotoxin (BoNT) in lineage Ia and in 12 lineage II genomes, as part of a putative integrative element related to a phage-inducible chromosomal island (PICI). In the putative PICI, Cas14a was associated with CRISPR arrays and restriction modification (RM) systems as part of an accessory locus. This is the first time a PICI containing such locus has been detected in C. botulinum. Mobilome composition and dynamics were also investigated based on the contents of the CRISPR arrays and the study of spacers. A large proportion of identified protospacers (20.2%) originated from Clostridium novyi sensu lato (p1_Cst, p4_BKT015925, p6_Cst, CWou-2020a, p1_BKT015925, and p2_BKT015925), confirming active exchanges within this genospecies and the key importance of specific MGEs in Clostridium novyi sensu lato.
Rhizosphere Soil Bacterial Communities of Continuous Cropping-Tolerant and Sensitive Soybean Genotypes Respond Differently to Long-Term Continuous Cropping in Mollisols
Authors: Yuan Ming , Yu Taobing , Shi Qihan , Han Dongwei , Yu Kanchao , Wang Lianxia , Wang Shurong , Xiang Hao , Wen Ronghui , Nian Hai , Lian Tengxiang
Published: September 2021

The continuous planting of soybeans leads to soil acidification, aggravation of soil-borne diseases, reduction in soil enzyme activity, and accumulation of toxins in the soil. Microorganisms in the rhizosphere play a very important role in maintaining the sustainability of the soil ecosystem and plant health. In this study, two soybean genotypes, one bred for continuous cropping and the other not, were grown in a Mollisol in northeast China under continuous cropping for 7 and 36years in comparison with soybean–maize rotation, and microbial communities in the rhizosphere composition were assessed using high-throughput sequencing technology. The results showed that short- or long-term continuous cropping had no significant effect on the rhizosphere soil bacterial alpha diversity. Short-term continuous planting increased the number of soybean cyst nematode (Heterodera glycines), while long-term continuous planting reduced these numbers. There were less soybean cyst nematodes in the rhizosphere of the tolerant genotypes than sensitive genotypes. In addition, continuous cropping significantly increased the potential beneficial bacterial populations, such as Pseudoxanthomonas, Nitrospira, and Streptomyces compared to rotation and short-term continuous cropping, suggesting that long-term continuous cropping of soybean shifts the microbial community toward a healthy crop rotation system. Soybean genotypes that are tolerant to soybean might recruit some microorganisms that enhance the resistance of soybeans to long-term continuous cropping. Moreover, the network of the two genotypes responded differently to continuous cropping. The tolerant genotype responded positively to continuous cropping, while for the sensitive genotype, topology analyses on the instability of microbial community in the rhizosphere suggested that short periods of continuous planting can have a detrimental effect on microbial community stability, although this effect could be alleviated with increasing periods of continuous planting.
Effects of DC Magnetic Fields on Magnetoliposomes
Authors: Nuñez-Magos L. , Lira-Escobedo J. , Rodríguez-López R. , Muñoz-Navia M. , Castillo-Rivera F. , Viveros-Méndez P. X. , Araujo E. , Encinas A. , Saucedo-Anaya S. A. , Aranda-Espinoza S.
Published: September 2021

The potential use of magnetic nanoparticles (MNPs) in biomedicine as magnetic resonance, drug delivery, imagenology, hyperthermia, biosensors, and biological separation has been studied in different laboratories. One of the challenges on MNP elaboration for biological applications is the size, biocompatibility, heat efficiency, stabilization in physiological conditions, and surface coating. Magnetoliposome (ML), a lipid bilayer of phospholipids encapsulating MNPs, is a system used to reduce toxicity. Encapsulated MNPs can be used as a potential drug and a gene delivery system, and in the presence of magnetic fields, MLs can be accumulated in a target tissue by a strong gradient magnetic field. Here, we present a study of the effects of DC magnetic fields on encapsulated MNPs inside liposomes. Despite their widespread applications in biotechnology and environmental, biomedical, and materials science, the effects of magnetic fields on MLs are unclear. We use a modified coprecipitation method to synthesize superparamagnetic nanoparticles (SNPs) in aqueous solutions. The SNPs are encapsulated inside phospholipid liposomes to study the interaction between phospholipids and SNPs. Material characterization of SNPs reveals round-shaped nanoparticles with an average size of 12 nm, mainly magnetite. MLs were prepared by the rehydration method. After formation, we found two types of MLs: one type is tense with SNPs encapsulated and the other is a floppy vesicle that does not show the presence of SNPs. To study the response of MLs to an applied DC magnetic field, we used a homemade chamber. Digitalized images show encapsulated SNPs assembled in chain formation when a DC magnetic field is applied. When the magnetic field is switched off, it completely disperses SNPs. Floppy MLs deform along the direction of the external applied magnetic field. Solving the relevant magnetostatic equations, we present a theoretical model to explain the ML deformations by analyzing the forces exerted by the magnetic field over the surface of the spheroidal liposome. Tangential magnetic forces acting on the ML surface result in a press force deforming MLs. The type of deformations will depend on the magnetic properties of the mediums inside and outside the MLs. The model predicts a coexistence region of oblate–prolate deformation in the zone where χ = 1. We can understand the chain formation in terms of a dipole–dipole interaction of SNP.
Targeting M2 Macrophages Alleviates Airway Inflammation and Remodeling in Asthmatic Mice via miR-378a-3p/GRB2 Pathway
Authors: Wang Qiujie , Hong Luna , Chen Ming , Shi Jiangting , Lin Xiaoling , Huang Linjie , Tang Tiantian , Guo Yimin , Yuan Xiaoqing , Jiang Shanping
Published: September 2021

Background:Asthma is a complex respiratory disease characterized by airway inflammation and remodeling. MicroRNAs (miRNAs) mediate various cellular processes including macrophage polarization and play an important role in the pathogenesis of asthma. In present study, we aimed to screen miRNA profiling involved in macrophage polarization and investigate its possible functions and mechanisms.

Methods:An OVA-sensitized mouse model was established and 2-chloroadenosine (2-CA) was used to interfere with macrophages. The airway inflammation and remodeling were assessed. The identification and function of M2 alveolar macrophages were assessed by flow cytometry, RT-qPCR, arginase activity and co-culture experiment. Microarray screening was used to select miRNAs which were related to macrophage polarization and RNA interference (RNAi) technique was performed to confirm the function of the selected miRNA and its target gene.

Results:Alveolar macrophages of asthmatic mice showed significant M2 polarization. 2-CA alleviated airway inflammation and remodeling as well as M2 polarization.In vitro, IL-4-induced M2 macrophages promoted the proliferation of α-SMA-positive cells. And miRNA profiling showed a remarkable increased expression of miR-378a-3p in IL-4 induced M2 macrophages. Dual luciferase reporter assay confirmed growth factor receptor binding protein 2 (GRB2) was a target gene of miR-378a-3p. A miR-378a-3p inhibitor and knockdown of GRB2 repolarized alveolar macrophages from M1 to M2 phenotype.

Conclusion:Our findings suggest that miR-378a-3p/GRB2 pathway regulates the polarization of alveolar macrophages which acts as a potential therapeutic target for airway inflammation and remodeling in asthma.
Risk of Post-stroke Epilepsy Following Stroke-Associated Acute Symptomatic Seizures
Authors: Lin Ru , Yu Yaoyao , Wang Yi , Foster Emma , Kwan Patrick , Lin Mengqi , Xia Niange , Xu Huiqin , Xie Chenglong , Yang Yunjun , Wang Xinshi
Published: September 2021

Objective: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8–34.3% of these patients will go on to develop PSE. Identifying these “high risk” individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures.

Participants and Methods: This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview.

Results: Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 [hazard ratio (HR) 2.98, 95% CI 1.57–5.67], longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke) (HR 2.51, 95% CI 1.37–4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58–9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49–15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73.

Conclusion: More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.
Early Functional and Cognitive Declines Measured by Auditory-Evoked Cortical Potentials in Mice With Alzheimer’s Disease
Authors: Mei Ling , Liu Li-Man , Chen Kaitian , Zhao Hong-Bo
Published: September 2021

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive decline. However, the assessment of AD-associated functional and cognitive changes is still a big challenge. Auditory-evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex (AC) but also cognitive activity in the brain. In this study, we used the subdermal needle electrodes with the same electrode setting as the auditory brainstem response (ABR) recording and recorded AECP in normal aging CBA/CaJ mice and APP/PS1 AD mice. AECP in mice usually appeared as three positive peaks, i.e., P1, P2, and P3, and three corresponding negative peaks, i.e., N1, N2, and N3. In normal aging CBA mice, the early sensory peaks P1, N1, and P2 were reduced as age increased, whereas the later cognitive peaks N2, P3, and N3 were increased or had no changes with aging. Moreover, the latency of the P1 peak was increased as age increased, although the latencies of later peaks had a significant reduction with aging. In AD mice, peak P1 was significantly reduced in comparison with wild-type (WT) littermates at young ages, proceeding AD phenotype presentation. In particular, the later cognitive peak P3 was diminished after 3 months old, different from the normal aging effect. However, the latencies of AECP peaks in AD mice generally had no significant delay or changes with aging. Finally, consistent with AECP changes, the accumulation of amyloid precursor protein (APP) at the AC was visible in AD mice as early as 2 months old. These data suggest that AECP could serve as an early, non-invasive, and objective biomarker for detecting AD and AD-related dementia (ADRD).
Chronic Distress in Male Mice Impairs Motivation Compromising Both Effort and Reward Processing With Altered Anterior Insular Cortex and Basolateral Amygdala Neural Activation
Authors: Cabeza Lidia , Ramadan Bahrie , Cramoisy Stephanie , Houdayer Christophe , Haffen Emmanuel , Risold Pierre-Yves , Fellmann Dominique , Peterschmitt Yvan
Published: September 2021

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contributes to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward-processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from novelty suppressed feeding, operant effort-based choice, free feeding, and sucrose preference tasks) collectively show that behavioural initiation, effort allocation, and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlights CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how effort and reward processing contribute to adjust the motivational threshold triggering goal-directed behaviours in versatile environments.
Three-Dimensional Volumetric Measurement of Endolymphatic Hydrops in Meniere's Disease
Authors: Noh Tae-Soo , Park Moo Kyun , Lee Jun Ho , Oh Seung Ha , Kim Ji-Hoon , Song In Chan , Suh Myung-Whan
Published: September 2021

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages.

Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods.

Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear.

Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.
Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach
Authors: van Lonkhuizen Pearl J. C. , Vegt Niko J. H. , Meijer Eline , van Duijn Erik , de Bot Susanne T. , Klempíř Jiří , Frank Wiebke , Landwehrmeyer G. Bernhard , Mühlbäck Alzbeta , Hoblyn Jennifer , Squitieri Ferdinando , Foley Peter , Chavannes Niels H. , Heemskerk Anne-Wil
Published: September 2021

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home.

Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts.

Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD.
Seizure Susceptibility Prediction in Uncontrolled Epilepsy
Authors: Truong Nhan Duy , Yang Yikai , Maher Christina , Kuhlmann Levin , McEwan Alistair , Nikpour Armin , Kavehei Omid
Published: September 2021

Epileptic seizure forecasting, combined with the delivery of preventative therapies, holds the potential to greatly improve the quality of life for epilepsy patients and their caregivers. Forecasting seizures could prevent some potentially catastrophic consequences such as injury and death in addition to several potential clinical benefits it may provide for patient care in hospitals. The challenge of seizure forecasting lies within the seemingly unpredictable transitions of brain dynamics into the ictal state. The main body of computational research on determining seizure risk has been focused solely on prediction algorithms, which involves a challenging issue of balancing sensitivity and false alarms. There have been some studies on identifying potential biomarkers for seizure forecasting; however, the questions of “What are the true biomarkers for seizure prediction” or even “Is there a valid biomarker for seizure prediction?” are yet to be fully answered. In this paper, we introduce a tool to facilitate the exploration of the potential biomarkers. We confirm using our tool that interictal slowing activities are a promising biomarker for epileptic seizure susceptibility prediction.
Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants—A Potential Novel Biomarker of Disease Activity
Authors: Stascheit Frauke , Hotter Benjamin , Klose Sarah , Meisel Christian , Meisel Andreas , Klehmet Juliane
Published: September 2021

Background: In chronic inflammatory demyelinating polyneuropathy (CIDP), there is an urgent need for biomarkers to monitor ongoing disease activity. Serum calprotectin (CLP) induces signaling pathways involved in inflammatory processes and has been shown to correlate with markers of disease activity in other autoimmune disorders. Thus, we wanted to study the potential value of CLP in comparison to serum neurofilament light chain (sNfl) to monitor disease activity.

Materials and Methods: Sera from 63 typical and atypical CIDP and 6 MMN patients with varying degrees of disease activity were analyzed in comparison with 40 healthy controls (HC) in a cross-sectional design. Association of CLP and sNfl levels with socio-demographics, disease duration, CIDP disease activity scale (CDAS), and impairment status [medical research council-sum score (MRC-SS), the inflammatory neuropathy cause and treatment disability score (INCAT-DS), grip strength, and maximum walking distance], patient-reported outcome (PRO) parameters [SF-36 questionnaire, Beck's depression index (BDI), and fatigue severity scale (FSS)], as well as treatment regime were investigated using uni- and multivariate analysis.

Results: CLP and sNfl levels were significantly higher in all CIDP patients compared to HC (p = 0.0009). Multivariate analysis adjusted for age and gender revealed that CLP acts as an independent predictor for CIDP and MMN. CLP was significantly associated with active disease course according to CDAS and correlated with MRC-SS, whereas sNfl correlated with parameters of disease impairment. There was no correlation with PRO, except for sNfl and the mental health composite score. Subgroup analysis revealed no differences between typical CIDP and atypical variants.

Conclusions: CLP was elevated in CIDP and variants and was associated with active disease course, whereas sNfl shows further potential as biomarker of axonal degeneration. Thus, CLP might be a suitable additive biomarker for measurement of ongoing inflammation, which is greatly needed to guide better patient care in CIDP.
Influence of Augmented Visual Feedback on Balance Control in Unilateral Transfemoral Amputees
Authors: Fuchs Katharina , Krauskopf Thomas , Lauck Torben B. , Klein Lukas , Mueller Marc , Herget Georg W. , Von Tscharner Vinzenz , Stutzig Norman , Stieglitz Thomas , Pasluosta Cristian
Published: September 2021

Patients with a lower limb amputation rely more on visual feedback to maintain balance than able-bodied individuals. Altering this sensory modality in amputees thus results in a disrupted postural control. However, little is known about how lower limb amputees cope with augmented visual information during balance tasks. In this study, we investigated how unilateral transfemoral amputees incorporate visual feedback of their center of pressure (CoP) position during quiet standing. Ten transfemoral amputees and ten age-matched able-bodied participants were provided with real-time visual feedback of the position of their CoP while standing on a pressure platform. Their task was to keep their CoP within a small circle in the center of a computer screen placed at eye level, which could be achieved by minimizing their postural sway. The visual feedback was then delayed by 250 and 500 ms and was combined with a two- and five-fold amplification of the CoP displacements. Trials with eyes open without augmented visual feedback as well as with eyes closed were further performed. The overall performance was measured by computing the sway area. We further quantified the dynamics of the CoP adjustments using the entropic half-life (EnHL) to study possible physiological mechanisms behind postural control. Amputees showed an increased sway area compared to the control group. The EnHL values of the amputated leg were significantly higher than those of the intact leg and the dominant and non-dominant leg of controls. This indicates lower dynamics in the CoP adjustments of the amputated leg, which was compensated by increasing the dynamics of the CoP adjustments of the intact leg. Receiving real-time visual feedback of the CoP position did not significantly reduce the sway area neither in amputees nor in controls when comparing with the eyes open condition without visual feedback of the CoP position. Further, with increasing delay and amplification, both groups were able to compensate for small visual perturbations, yet their dynamics were significantly lower when additional information was not received in a physiologically relevant time frame. These findings may be used for future design of neurorehabilitation programs to restore sensory feedback in lower limb amputees.