bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Safety and Efficacy of Omalizumab in a 13-Year-Old Patient With Chronic Spontaneous Urticaria and Type 1 Diabetes
Authors: Del Barba Paolo , Del Tedesco Federica , Frontino Giulio , Guarneri Maria Pia , Bonfanti Riccardo , Barera Graziano
Published: April 2022

Chronic urticaria (CU) is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. CU is treated with second-generation antihistamines, increased up to four times the normal doses for second-line treatment. Omalizumab (a monoclonal antibody anti-IgE) may be recommended as third-line therapy in children aged over 12 years. Few reports have suggested that glucose homeostasis is impaired in some type 2 diabetic patients receiving omalizumab, and even in non-diabetic patients, fasting blood glucose and HOMA-IR values appeared to be significantly increased. We report the case of a 13-year-old girl with diabetes mellitus type 1 and chronic spontaneous urticaria (CSU) refractory to standard recommended therapy that we treated with omalizumab at a standard recommended dose of 300 mg every 4 weeks. We observed a rapid and complete remission of CSU after treatment with this humanized monoclonal antibody without detrimental effects on the patient’s glucose control especially in terms of HbA1c (glycated hemoglobin), time in glycemic range (TIR), and daily insulin needs.
Automated Plankton Classification With a Dynamic Optimization and Adaptation Cycle
Authors: Conradt Jan , Börner Gregor , López-Urrutia Ángel , Möllmann Christian , Moyano Marta
Published: April 2022

With recent advances in Machine Learning techniques based on Deep Neural Networks (DNNs), automated plankton image classification is becoming increasingly popular within the marine ecological sciences. Yet, while the most advanced methods can achieve human-level performance on the classification of everyday images, plankton image data possess properties that frequently require a final manual validation step. On the one hand, this is due to morphological properties manifesting in high intra-class and low inter-class variability, and, on the other hand is due to spatial-temporal changes in the composition and structure of the plankton community. Composition changes enforce a frequent updating of the classifier model via training with new user-generated training datasets. Here, we present a Dynamic Optimization Cycle (DOC), a processing pipeline that systematizes and streamlines the model adaptation process via an automatic updating of the training dataset based on manual-validation results. We find that frequent adaptation using the DOC pipeline yields strong maintenance of performance with respect to precision, recall and prediction of community composition, compared to more limited adaptation schemes. The DOC is therefore particularly useful when analyzing plankton at novel locations or time periods, where community differences are likely to occur. In order to enable an easy implementation of the DOC pipeline, we provide an end-to-end application with graphical user interface, as well as an initial dataset of training images. The DOC pipeline thus allows for high-throughput plankton classification and quick and systematized model adaptation, thus providing the means for highly-accelerated plankton analysis.
Differences of Macroalgal Consumption by Eight Herbivorous Coral Reef Fishes From the Xisha Islands, China
Authors: Wu Peng , Wang Teng , Liu Yong , Li Chunhou , Xiao Yayuan , Xu Shannan , Han Tingting , Lin Lin , Quan Qiumei
Published: April 2022

Herbivorous fishes play an important role in preventing the overabundance of macroalgae on coral reefs. Understanding the feeding selectivity and consumption of macroalgae by herbivorous fishes can be challenging in studies of their ecological role in the preservation and recovery of coral reefs. Coral reef decline, macroalgal overgrowth and overfishing are clearly visible in the Xisha Islands, China. However, there are seldom studies on the feeding behaviors of herbivorous fishes in this area. We used microscopy, 18S rRNA high-throughput sequencing, and stable isotope analyses to comprehensively examine the diet of eight herbivorous reef fish species common in the Xisha Islands, including one parrotfish, two chub, two unicorn fish, and three rabbitfish. Based on microscopic examination,Siganus argenteusfed on the highest number of macroalgae species (five species), followed byNaso unicornis(four species).Kyphosus cinerascens,K. vaigiensis,N. unicornisandS. punctatissimusfed on the entire macroalgal thallus, indicating their greater ecological importance compared with species that only consume algal fronds. According to the 18S rRNA high-throughput sequencing of fish intestinal contents, cluster analysis revealed that consumed macroalgae composition from the eight fishes always grouped together based on the fish species, but with low similarity.K. vaigiensisremoved the highest diversity of macroalgae species as well as the greatest quantity of macroalgae.Calotomus carolinuscan consume the red algaPneophyllum conicum, which is widely distributed on Indo-Pacific coral reefs and can overgrow and kill live corals.N. unicorniswas found to occupy the lowest trophic position based on stable isotope analysis. Multi-technique analyses revealed thatK. vaigiensis,N. unicornisandS. argenteusshowed a high consumption potential of macroalgae, suggesting that they are the key browsers that should receive priority protection in the Xisha Islands. A diverse herbivorous fish fauna is also very important in the Xisha coral reefs. These results not only demonstrated the various functions of different herbivorous fish species in macroalgal removal, but also provided insights into the management of herbivorous fishes on the coral reefs of the South China Sea.
Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study
Authors: Vieira Waldonio de Brito , Franco Karen Margarete Vieira da Silva , Dias Apio Ricardo Nazareth , Falcão Aline Semblano Carreira , Falcão Luiz Fábio Magno , Quaresma Juarez Antonio Simões , de Sousa Rita Catarina Medeiros
Published: April 2022

Coronavirus disease (COVID-19) is an infectious disease that can lead to pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death. This study aimed to verify the efficacy of chest computed tomography (CT) for the initial diagnosis of COVID-19. This observational, retrospective, cross-sectional study included 259 individuals who underwent clinical evaluation, blood collection, chest CT, and a reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during their course of treatment at a reference hospital in Belém, Pará, Brazil between April and June 2020. Inclusion criteria were flu-like symptoms in adults of both sexes. Individuals with an inconclusive COVID-19 molecular test or who had artifacts in the chest CT images were excluded. Parametric data were analyzed using Student-t-test and non-parametric data were analyzed using average test and Fisher exact test. Participants were divided into two groups: Group 1 (COVID-19 positive), n = 211 (124 males, 87 females), 51.8 ± 17.9 years old and Group 2 (COVID-19 negative), n = 48 (22 males, 26 females), 47.6 ± 18.6 years old. Most frequent symptoms were cough [Group 1 n = 199 (94%)/Group 2 n = 46 (95%)], fever [Group 1 n = 154 (72%)/Group 2 n = 28 (58%)], myalgia [Group 1 n = 172 (81%)/Group 2 n = 38 (79%)], dyspnoea [Group 1 n = 169 (80%) / Group 2 n = 37 (77%)], headache [Group 1 n = 163 (77%)/Group 2 n = 32 (66%)], and anosmia [Group 1 n = 154 (73%)/Group 2 n = 29 (60%)]. Group 1 had a higher proportion of ground-glass opacity [Group 1 n = 175 (83%)/Group 2 n = 24 (50%), 0.00], vascular enhancement sign [Group 1 n = 128 (60%)/Group 2 n = 15 (31%), 0.00], septal thickening [Group 1 n = 99 (47%)/Group 2 n = 13 (27%), 0.01], crazy-paving pattern [Group 1 n = 98 (46%) / Group 2 n = 13 (27%), 0.01], consolidations [Group 1 n = 92 (43%)/Group 2 n = 8 (16%), 0.00], and CO-RADS 4 and 5 [Group 1 n = 163 (77.25%)/Group 2 n = 24 (50%), 0.00] categories in chest CT. Chest CT, when available, was found to be an efficient method for the initial diagnosis and better management of individuals with COVID-19.
Dual RNA-Seq of H5N1 Avian Influenza Virus and Host Cell Transcriptomes Reveals Novel Insights Into Host-Pathogen Cross Talk
Authors: Wang Qiao , Wang Zixuan , Zhang Jin , Zhang Qi , Zheng Maiqing , Wen Jie , Zhao Guiping , Li Qinghe
Published: April 2022

H5N1 avian influenza virus (AIV) is a highly pathogenic influenza virus that poses a substantial threat to poultry production and public health. A comprehensive understanding of host–pathogen interactions for AIV requires knowledge of gene expression changes in both the pathogen and the host upon infection. We report the use of dual RNA sequencing technology to uncover trends in gene expression in H5N1 AIV and chickens (DF1 cells) during the course of infection. The expression of all viral genes increased continuously from 0 to 20 h post infection. We also identified 2,762 differentially expressed host genes during infection. Pathway analysis found that genes related to the signaling pathways of DNA replication, T cell activation, NF-kappa B signaling pathway, and RNA degradation were significantly enriched. We demonstrated that the cis-acting lncRNA MSTRG.14019.1 targeted CSE1L and may affect virus replication. This study provides a more comprehensive and detailed understanding of host-virus interactions at the RNA level during the course of H5N1 AIV infection.
Two Pathogenic Fungi Isolated From Chalkbrood Samples and Honey Bee Viruses They Carried
Authors: Cheng Xuefen , Zhang Li , Luo Ji , Yang Sa , Deng Yanchun , Li Jianghong , Hou Chunsheng
Published: April 2022

Ascosphaera apis and some Aspergillus species are the main pathogenic fungi of honey bee, and A. apis is the pathogen of chalkbrood disease. However, the infection mechanism of them is incompletely known and it is still unclear whether other factors impact their pathogenesis. In this study, Aspergillus tubingensis were obtained from the chalkbrood bee samples for the first time. Our results showed that A. tubingensis could promote the accumulation of the spores of A. apis. Pathogenicity test found that inoculation of the spores of the two fungi alone or their combination could induce disease characterization of chalkbrood and stonebrood but the extent was less than those in field. To further identify other pathogens impacted the pathogenesis, we found several honey bee viruses presented in the pathogenic fungi A. apis and A. tubingensis, which were different from previous reported. Our results indicated that acute bee paralysis virus (ABPV) and chronic bee paralysis virus (CBPV) could replicate in these two fungi and increased in titer with the going of cultivation time. In addition, CBPV could not only transmit vertically to the next generation by spores, but also spread horizontally to different fungi through hyphal anastomosis. These results suggested that the honey bee chalkbrood contained the other pathogenic fungi besides A. apis, the interactions between different pathogens of chalkbrood microbial communities may influence the prevalence of chalkbrood. Moreover, the discovery of honey bee viruses and their transmission mode in these two fungi enhanced the potential of exploring fungi virus as valuable factors that cause fungal disease outbreak.
High-Resolution Screening for Marine Prokaryotes and Eukaryotes With Selective Preference for Polyethylene and Polyethylene Terephthalate Surfaces
Authors: Marsay Katherine S. , Koucherov Yuri , Davidov Keren , Iankelevich-Kounio Evgenia , Itzahri Sheli , Salmon-Divon Mali , Oren Matan
Published: April 2022

Marine plastic debris serve as substrates for the colonization of a variety of prokaryote and eukaryote organisms. Of particular interest are the microorganisms that have adapted to thrive on plastic as they may contain genes, enzymes or pathways involved in the adhesion or metabolism of plastics. We implemented DNA metabarcoding with nanopore MinION sequencing to compare the 1-month-old biomes of hydrolyzable (polyethylene terephthalate) and non-hydrolyzable (polyethylene) plastics surfaces vs. those of glass and the surrounding water in a Mediterranean Sea marina. We sequenced longer 16S rRNA, 18S rRNA, and ITS barcode loci for a more comprehensive taxonomic profiling of the bacterial, protist, and fungal communities, respectively. Long read sequencing enabled high-resolution mapping to genera and species. Using previously established methods we performed differential abundance screening and identified 30 bacteria and five eukaryotic species, that were differentially abundant on plastic compared to glass. This approach will allow future studies to characterize the plastisphere communities and to screen for microorganisms with a plastic-metabolism potential.
HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir
Authors: Troyano-Hernáez Paloma , Reinosa Roberto , Holguín África
Published: April 2022

The HIV p24 capsid protein has an essential, structural, and functional role in the viral replication cycle, being an interesting target for vaccine design, diagnostic tests, and new antiretroviral drugs (ARVs). The HIV-1 variability poses a challenge for the accuracy and efficiency of diagnostic and treatment tools. This study analyzes p24 diversity among HIV-1 variants and within its secondary structure in HIV-1 M, O, P, and N groups. All available HIV-1 p24 nucleotide sequences were downloaded from the Los Alamos HIV Sequence Database, selecting 23,671 sequences belonging to groups O, N, P, and M (9 subtypes, 7 sub-sub types, and 109 circulating recombinant forms or CRFs). Using a bioinformatics tool developed in our laboratory (EpiMolBio program), we analyzed the amino acid conservation compared to the HXB2 subtype B reference sequence and the V-markers, or amino acid changes that were specific for each variant with at least 10 available sequences. We inferred the p24 consensus sequence for HIV-1 and for each group to analyze the overall conservation in p24 main structural regions, reporting the percentage of substitutions per variant affecting the capsid assembly and molecule-binding, including those associated with resistance to the new capsid-inhibitor lenacapavir, and the key residues involved in lenacapavir-p24 interaction, according to the bibliography. Although the overall structure of p24 was highly conserved, the conservation in the secondary structure varied between HIV-1 variants and the type of secondary structure. All HIV-1 variants presented >80% amino acid conservation vs. HXB2 reference sequence, except for group M sub-subtype F1 (69.27%). Mutants affecting the capsid assembly or lenacapavir capsid-binding were found in <1% of the p24 consensus sequence. Our study reports the HIV-1 variants carrying 14 unique single V-markers in 9/38 group M variants and the level of p24 conservation in each secondary structure region among the 4 HIV-1 groups and group M variants, revealing no natural resistance to lenacapavir in any HIV-1 variant. We present a thorough analysis of p24 variability among all HIV-1 variants circulating to date. Since p24 genetic variability can impact the viral replication cycle and the efficacy of new p24-based diagnostic, therapeutic, and vaccine strategies, conservation studies must consider all HIV-1 variants circulating worldwide.
Pathogenicity and Immunogenicity of a Serially Passaged Attenuated Genotype 2c Porcine Epidemic Diarrhea Virus Cultured in Suspended Vero Cells
Authors: Ge Fei-Fei , Kang Long-Shan , Shen Li-Ping , Shen Hai-Xiao , Yang De-Quan , Li Xin , Ju Hou-Bin , Zhao Hong-jin , Wang Jian
Published: April 2022

In this study, one G2c-subtype strain of porcine epidemic diarrhea virus (PEDV) (SHXX1902 strain) was isolated from clinical samples in suspended Vero cells, which was different from the genotype of the commercial AJ1102 vaccine. As a result, we determined the pathogenicity of different passages’ isolates (SHXX1902 strain) and compared the immunogenicity of G2c-subtype strain (SHXX1902 strain) with the commercial AJ1102 vaccine. The viral titer reached 107 50% tissue culture infectious dose (TCID50)/ml, which met the requirement for seed virus replication during vaccine development. Five-day-old piglets were orally infected with viruses from passages P5 and P35 to determine the pathogenicity and immunogenicity of different passages. Pregnant sows were immunized with inactivated SHXX1902-P5 or the commercial AJ1102 vaccine (first immunized with an attenuated vaccine and then boosted with an inactivated vaccine) to study the influence of the culture method on the immunogenicity of the strain. The median pig diarrhea dose (PDD50) and the median lethal dose (LD50) of the P5 virus were 102.00 and 102.84 TCID50/ml, respectively. All five piglets infected with the SHXX1902-P5 virus shed the virus 24 h after vaccination, whereas only two of the five piglets treated with the SHXX1902-P35 virus shed the virus 48 h after vaccination. The SHXX1902-P35 virus was partially attenuated in the 5-day-old piglets. Inactivated SHXX1902-P5 induced PEDV-specific immunoglobulin G (IgG) antibody responses equivalent to those induced by AJ1102 after infection in sow serum. However, the IgA titer induced by AJ1102 was much higher than that induced by inactivated SHXX1902-P5 since the boost immunization. On days 5 and 7 after farrowing, the IgA titers were similar among the immunized groups. Our study highlights that serial passage can lead to the attenuation of G2c-subtype strain. The immunogenicity of the inactivated strain was similar to the commercial vaccine. Our observation helped conceptualize appropriate study designs for the PEDV vaccine.
Size and Shape Directed Novel Green Synthesis of Plasmonic Nanoparticles Using Bacterial Metabolites and Their Anticancer Effects
Authors: Patil Snehal , Sastry Murali , Bharde Atul
Published: April 2022

The growing need for developing new synthesis methods of plasmonic nanoparticles (PNPs) stems from their various applications in nanotechnology. As a result, a variety of protocols have been developed for the synthesis of PNPs of different shapes, sizes, and compositions. Though widely practiced, the chemical synthesis of PNPs demands stringent control over the experimental conditions, often employs environmentally hazardous chemicals for surface stabilization, and is frequently energy-intensive. Additionally, chemically obtained PNPs require subsequent surface engineering steps for various optoelectronic and biomedicine applications to minimize the toxic effects and render them useful for targeted drug delivery, sensing, and imaging. Considering the pressing need to develop environmentally-friendly technology solutions, “greener” methods of nanoparticle synthesis are gaining importance. Here, we report on the biological synthesis of plasmonic nanoparticles using bacterial metabolites. A peptide-based siderophore pyoverdine and a blue-green pigment pyocyanin obtained from a marine strain of Pseudomonas aeruginosa rapidly produced plasmonic nanoparticles of gold and silver in an aqueous environment. The morphology of plasmonic nanoparticles could be modulated by tuning the concentration of these metabolites and the reaction time. The exposure of pyoverdine to chloroauric acid resulted in anisotropic gold nanoparticles. On the other hand, pyocyanin produced a highly monodispersed population of gold nanoparticles and anisotropic silver nanoparticles. Biologically obtained gold and silver nanoparticles retained pyoverdine and pyocyanin on the nanoparticle surface and were stable for an extended period of time. The biologically obtained gold and silver plasmonic nanoparticles displayed potent anticancer activities against metastatic lung cancer cells. Biogenic nanoparticles were rapidly internalized by cancer cells in high quantity to affect the cellular organization, and karyoplasmic ratio, indicating the potential of these nanoparticles for cancer nanomedicine.
Antofine Triggers the Resistance Against Penicillium italicum in Ponkan Fruit by Driving AsA-GSH Cycle and ROS-Scavenging System
Authors: Peng Xuan , Zhang Yanan , Wan Chunpeng , Gan Zengyu , Chen Chuying , Chen Jinyin
Published: April 2022

Postharvest fungal infection can accelerate the quality deterioration of Ponkan fruit and reduce its commodity value. Penicillium italicum is the causal pathogen of blue mold in harvested citrus fruits, not only causing huge fungal decay but also leading to quality deterioration. In our preliminary study, antofine (ATF) was found to have a great potential for significant in vitro suppression of P. italicum growth. However, the regulatory mechanism underpinning ATF-triggered resistance against P. italicum in citrus fruit remains unclear. Here, the protective effects of ATF treatment on blue mold development in harvested Ponkan fruit involving the enhancement of ROS-scavenging system were investigated. Results showed that ATF treatment delayed blue mold development and peel firmness loss. Moreover, the increase of electrolyte leakage, O2•– production, and malonyldialdehyde accumulation was significantly inhibited by ATF treatment. The ATF-treated Ponkan fruit maintained an elevated antioxidant capacity, as evidenced by inducted the increase in glutathione (GSH) content, delayed the declines of ascorbic acid (AsA) content and GSH/oxidized GSH ratio, and enhanced the activities of superoxide dismutase, catalase, peroxidase, and six key AsA-GSH cycle-related enzymes, along with their encoding gene expressions, thereby maintaining ROS homeostasis and reducing postharvest blue mold in harvested Ponkan fruit. Collectively, the current study revealed a control mechanism based on ATF-triggered resistance and maintenance of a higher redox state by driving AsA-GSH cycle and ROS-scavenging system in P. italicum-infected Ponkan fruit.
Identification of BgP, a Cutinase-Like Polyesterase From a Deep-Sea Sponge-Derived Actinobacterium
Authors: Carr Clodagh M. , de Oliveira Bruno Francesco Rodrigues , Jackson Stephen A. , Laport Marinella Silva , Clarke David J. , Dobson Alan D. W.
Published: April 2022

Many marine bacteria produce extracellular enzymes that degrade complex molecules to facilitate their growth in environmental conditions that are often harsh and low in nutrients. Marine bacteria, including those inhabiting sea sponges, have previously been reported to be a promising source of polyesterase enzymes, which have received recent attention due to their potential ability to degrade polyethylene terephthalate (PET) plastic. During the screening of 51 marine bacterial isolates for hydrolytic activities targeting ester and polyester substrates, a Brachybacterium ginsengisoli B129SM11 isolate from the deep-sea sponge Pheronema sp. was identified as a polyesterase producer. Sequence analysis of genomic DNA from strain B129SM11, coupled with a genome “mining” strategy, allowed the identification of potential polyesterases, using a custom database of enzymes that had previously been reported to hydrolyze PET or other synthetic polyesters. This resulted in the identification of a putative PET hydrolase gene, encoding a polyesterase-type enzyme which we named BgP that shared high overall similarity with three well-characterized PET hydrolases—LCC, TfCut2, and Cut190, all of which are key enzymes currently under investigation for the biological recycling of PET. In silico protein analyses and homology protein modeling offered structural and functional insights into BgP, and a detailed comparison with Cut190 revealed highly conserved features with implications for both catalysis and substrate binding. Polyesterase activity was confirmed using an agar-based polycaprolactone (PCL) clearing assay, following heterologous expression of BgP in Escherichia coli. This is the first report of a polyesterase being identified from a deep-sea sponge bacterium such as Brachybacterium ginsengisoli and provides further insights into marine-derived polyesterases, an important family of enzymes for PET plastic hydrolysis. Microorganisms living in association with sponges are likely to have increased exposure to plastics and microplastics given the wide-scale contamination of marine ecosystems with these plastics, and thus they may represent a worthwhile source of enzymes for use in new plastic waste management systems. This study adds to the growing knowledge of microbial polyesterases and endorses further exploration of marine host-associated microorganisms as a potentially valuable source of this family of enzymes for PET plastic hydrolysis.
Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress
Authors: Lin Fan , Liao Chengcheng , Zhang Jinsheng , Sun Yun , Lu Weiwei , Bai Yu , Liao Yixuan , Li Minxia , Qi Yongfen , Chen Yahong
Published: April 2022

Epithelial mesenchymal transition (EMT) is a contributing factor in remodeling events of chronic obstructive pulmonary disease (COPD). Hydrogen sulfide (H2S) has been implicated in the pathogenesis of COPD, but the effect of H2S in regulating EMT and the underlying mechanisms is not clear. In this study, we assessed endoplasmic reticulum (ER) stress markers, EMT markers and associated signal molecules in rat lungs, bronchial epithelial cells, and human peripheral lung tissues to investigate the effect of H2S in regulating EMT and the underlying mechanisms. We found that EMT and ER stress occurred in lung epithelial cells, especially in the bronchial epithelial cells of smokers and COPD patients. In cigarette smoke (CS)-exposed rats, intraperitoneal injection of NaHS significantly alleviated CS-induced lung tissue damage, small airway fibrosis, ER stress, and EMT, while intraperitoneal injection of propargylglycine (cystathionine-gamma-lyase inhibitor) aggravated these effects induced by CS. In the nicotine-exposed 16HBE cells, an appropriate concentration of H2S donor not only inhibited nicotine-induced ER stress, but also inhibited nicotine-induced enhancement of cell migration ability and EMT. ER stress nonspecific inhibitors taurine and 4-phenyl butyric acid also inhibited nicotine-induced enhancement of cell migration ability and EMT. Both H2S and inositol-requiring enzyme 1 (IRE1) activation inhibitor 4μ8C inhibited nicotine-induced activation of IRE1, Smad2/3 and EMT. These results suggest that H2S inhibits CS- or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The IRE1 signal pathway and Smad2/3 may be responsible for the inhibitory effect of H2S.
The Relationships of Fibrinogen and C-Reactive Protein With Gait Performance: A 20-Year Longitudinal Study
Authors: Heumann Zohar , Youssim Iaroslav , Kizony Rachel , Friedlander Yechiel , Shochat Tamar , Weiss Ram , Hochner Hagit , Agmon Maayan
Published: April 2022

Background

Gait speed, a central marker of aging, has been linked to various health outcomes, such as cognitive and physical functions in middle-aged adults. Although long-term systemic low-grade inflammation is considered a mechanism underlying a variety of aging-related risk factors, the longitudinal associations between inflammation markers and gait speed are yet to be fully investigated.

Objective

To explore the associations of CRP and fibrinogen levels, measured two decades ago, with gait speed among community dwelling adults, considering the contribution of cardio-metabolic factors and cognition.

Methods

Study participants took part in two phases of the of the “Kibbutzim Family Study” (i.e., Phase II, 1999–2000 and Phase III, 2017–2019). Blood samples collected in Phase II (baseline) were used to determine level of inflammatory markers. Gait speed was assessed under single-task (ST) and dual-task (DT) conditions in Phase III. Demographic, anthropometric and clinical data were collected in both phases. Linear regression models were used to assess the adjusted associations of inflammation and gait speed.

Results

A total of 373 individuals aged 34–99 (mean 64 ± 13 years) in Phase III were included in the study. Gait speed under ST was negatively associated with baseline levels of fibrinogen (b per standard deviation (SD) = −0.053, p = 0.0007) and CRP (b per SD = −0.043, p = 0.010), after adjusting for baseline and concurrent cardiometabolic risk factors. Accounting for executive functions, associations of fibrinogen with gait under ST were somewhat attenuated, yet associations remained statistically significant (p < 0.05). Associations with CRP were attenuated to the null. In contrast, there were no associations between inflammation markers and gait under DT.

Conclusion

Our findings demonstrate that in a sample including younger to older adults, higher systemic inflammatory activity was linked with gait 20 years later, beyond age and cardiometabolic health, and to a certain extent, beyond executive functions. Thus, systemic inflammation may serve as an early marker to identify individuals at risk for gait decline.
Rehabilitation at the Time of Pandemic: Patient Journey Recommendations
Authors: Negm Ahmed M. , Salopek Adrian , Zaide Mashal , Meng Victoria J. , Prada Carlos , Chang Yaping , Zanwar Preeti , Santos Flavia H. , Philippou Elena , Rosario Emily R. , Faieta Julie , Pinto Shanti M. , Falvey Jason R. , Kumar Amit , Reistetter Timothy A. , Dal Bello-Haas Vanina , Bhandari Mohit , Bean Jonathan F. , Heyn Patricia C.
Published: April 2022

Purpose

The World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic in March 2020, causing almost 3.5 million coronavirus disease (COVID-19) related deaths worldwide. The COVID-19 pandemic has imposed a significant burden on healthcare systems, economies, and social systems in many countries around the world. The access and delivery of rehabilitation care were severely disrupted, and patients have faced several challenges during the COVID-19 outbreak. These challenges include addressing new functional impairments faced by survivors of COVID-19 and infection prevention to avoid the virus spread to healthcare workers and other patients not infected with COVID-19. In this scoping review, we aim to develop rehabilitation recommendations during the COVID-19 pandemic across the continuum of rehabilitation care.

Materials and Methods

Established frameworks were used to guide the scoping review methodology. Medline, Embase, Pubmed, CINAHL databases from inception to August 1, 2020, and prominent rehabilitation organizations’ websites were searched.

Study Selection

We included articles and reports if they were focused on rehabilitation recommendations for COVID-19 survivors or the general population at the time of the COVID-19 pandemic.

Data Extraction

Two of our team members used the pre-tested data extraction form to extract data from included full-text articles. The strength and the quality of the extracted recommendations were evaluated by two reviewers using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Results

We retrieved 6,468 citations, of which 2,086 were eligible after removing duplicates. We excluded 1,980 citations based on the title and the abstract. Of the screened full-text articles, we included 106 studies. We present recommendations based on the patient journey at the time of the pandemic. We assessed the evidence to be of overall fair quality and strong for the recommendations.

Conclusion

We have combined the latest research results and accumulated expert opinions on rehabilitation to develop acute and post-acute rehabilitation recommendations in response to the global COVID-19 pandemic. Further updates are warranted in order to incorporate the emerging evidence into rehabilitation guidelines.
Working Memory Training Coupled With Transcranial Direct Current Stimulation in Older Adults: A Randomized Controlled Experiment
Authors: Teixeira-Santos Ana C. , Moreira Célia S. , Pereira Diana R. , Pinal Diego , Fregni Felipe , Leite Jorge , Carvalho Sandra , Sampaio Adriana
Published: April 2022

Background

Transcranial direct current stimulation (tDCS) has been employed to boost working memory training (WMT) effects. Nevertheless, there is limited evidence on the efficacy of this combination in older adults. The present study is aimed to assess the delayed transfer effects of tDCS coupled with WMT in older adults in a 15-day follow-up. We explored if general cognitive ability, age, and educational level predicted the effects.

Methods

In this single-center, double-blind randomized sham-controlled experiment, 54 older adults were randomized into three groups: anodal-tDCS (atDCS)+WMT, sham-tDCS (stDCS)+WMT, and double-sham. Five sessions of tDCS (2 mA) were applied over the left dorsolateral prefrontal cortex (DLPFC). Far transfer was measured by Raven’s Advanced Progressive Matrices (RAPM), while the near transfer effects were assessed through Digit Span. A frequentist linear mixed model (LMM) was complemented by a Bayesian approach in data analysis.

Results

Working memory training improved dual n-back performance in both groups submitted to this intervention but only the group that received atDCS+WMT displayed a significant improvement from pretest to follow-up in transfer measures of reasoning (RAPM) and short-term memory (forward Digit Span). Near transfer improvements predicted gains in far transfer, demonstrating that the far transfer is due to an improvement in the trained construct of working memory. Age, formal education, and vocabulary score seem to predict the gains in reasoning. However, Bayesian results do not provide substantial evidence to support this claim.

Conclusion

This study will help to consolidate the incipient but auspicious field of cognitive training coupled with tDCS in healthy older adults. Our findings demonstrated that atDCS may potentialize WMT by promoting transfer effects in short-term memory and reasoning in older adults, which are observed especially at follow-up.
Novel Non-invasive Transcranial Electrical Stimulation for Parkinson’s Disease
Authors: Ni Rui , Yuan Ye , Yang Li , Meng Qiujian , Zhu Ying , Zhong Yiya , Cao Zhenqian , Zhang Shengzhao , Yao Wenjun , Lv Daping , Chen Xin , Chen Xianwen , Bu Junjie
Published: April 2022

Conventional transcranial electrical stimulation (tES) is a non-invasive method to modulate brain activity and has been extensively used in the treatment of Parkinson’s disease (PD). Despite promising prospects, the efficacy of conventional tES in PD treatment is highly variable across different studies. Therefore, many have tried to optimize tES for an improved therapeutic efficacy by developing novel tES intervention strategies. Until now, these novel clinical interventions have not been discussed or reviewed in the context of PD therapy. In this review, we focused on the efficacy of these novel strategies in PD mitigation, classified them into three categories based on their distinct technical approach to circumvent conventional tES problems. The first category has novel stimulation modes to target different modulating mechanisms, expanding the rang of stimulation choices hence enabling the ability to modulate complex brain circuit or functional networks. The second category applies tES as a supplementary intervention for PD hence amplifies neurological or behavioral improvements. Lastly, the closed loop tES stimulation can provide self-adaptive individualized stimulation, which enables a more specialized intervention. In summary, these novel tES have validated potential in both alleviating PD symptoms and improving understanding of the pathophysiological mechanisms of PD. However, to assure wide clinical used of tES therapy for PD patients, further large-scale trials are required.
Higher Peripheral Inflammation Is Associated With Lower Orbitofrontal Gamma Power in Chronic Tinnitus
Authors: Becker Linda , Keck Antonia , Rohleder Nicolas , Müller-Voggel Nadia
Published: April 2022

Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom, for which the underlying pathology has not yet been fully understood. It is associated with neurophysiological alterations in the central nervous system and chronic stress, which can be related with a disinhibition of the inflammatory system. We here investigated the association between resting-state oscillatory activity assessed with Magnetoencephalography (MEG), and peripheral inflammation assessed by C-reactive protein (CRP) in a group of patients with chronic tinnitus (N = 21, nine males, mean age: 40.6 ± 14.6 years). Additionally, CRP was assessed in an age- and sex-matched healthy control group (N = 21, nine males, mean age: 40.9 ± 15.2 years). No MEG data was available for the control group. We found a significant negative correlation between CRP and gamma power in the orbitofrontal cortex in tinnitus patients (p < 0.001), pointing to a deactivation of the orbitofrontal cortex when CRP was high. No significant clusters were found for other frequency bands. Moreover, CRP levels were significantly higher in the tinnitus group than in the healthy controls (p = 0.045). Our results can be interpreted based on findings from previous studies having disclosed the orbitofrontal cortex as part of the tinnitus distress network. We suggest that higher CRP levels and the associated deactivation of the orbitofrontal cortex in chronic tinnitus patients is maintaining the tinnitus percept through disinhibition of the auditory cortex and attentional or emotional top-down processes. Although the direction of the association (i.e., causation) between CRP levels and orbitofrontal gamma power in chronic tinnitus is not yet known, inflammation reducing interventions are promising candidates when developing treatments for tinnitus patients. Overall, our study highlights the importance of considering immune-brain communication in tinnitus research.
The Time Course of Monocytes Infiltration After Acoustic Overstimulation
Authors: Shin Seung Ho , Jung Jinsei , Park Haeng Ran , Sim Nam Suk , Choi Jae Young , Bae Seong Hoon
Published: April 2022

Cochlea macrophages regulate cochlea inflammation and may harbors the potentials to protect hearing function from injury, including acoustic overstimulation. Cochlea macrophage numbers increase at 3–7 days after acoustic stimulation. However, the exact timing of macrophage infiltration and maturation from inflammatory monocytes is unclear. Furthermore, neutrophils may also be involved in this process. Therefore, in this study, we investigated time-dependent immune cell infiltration, macrophage transformation, and neutrophil involvement following acoustic stimulation. Flow cytometry and immunofluorescence were conducted in C-X3-C motif chemokine receptor 1 (CX3CR1)+/GFPmice after acoustic overstimulation (at baseline and at 1, 2, 3, and 5 days after exposure to 120 dB for 1 h) to identify inflammatory monocytes in the cochlea. RNA-sequencing and quantitative polymerase chain reaction were performed to identify differentially expressed genes. Inflammatory monocytes infiltrated into the lower portion of the lateral wall within 2 days after acoustic overstimulation (dpn), followed by transformation into macrophages at 3–5 dpnviaCX3CR1 upregulation and Ly6C downregulation. In addition, inflammatory monocytes were aggregated inside the collecting venule only at 1 dpn. Neutrophils were not a major type of phagocyte during this response. The gene encoding C-C motif chemokine ligand 2 gene was significantly upregulated as early as 3 h after acoustic overstimulation. Given these results, treatment to control immune response after a noise-induced hearing loss should be applied as soon as possible.
Repetitive Transcranial Magnetic Stimulation Improves Neurological Function and Promotes the Anti-inflammatory Polarization of Microglia in Ischemic Rats
Authors: Luo Jing , Feng Yuan , Li Mingyue , Yin Mingyu , Qin Feng , Hu Xiquan
Published: April 2022

Ischemic stroke (IS) is a severe neurological disease that is difficult to recovery. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic approach, while the exact therapy mechanisms of rTMS in improving neural functional recovery remain unclear. Furthermore, the inflammatory environment may influence the rehabilitation efficacy. Our study shows that long-term rTMS stimulation will significantly promote neurogenesis, inhibit apoptosis, and control inflammation. rTMS inhibits the activation of transcription factors nuclear factor kappa b (NF-κB) and signal transducer and activator of transcription 6 (STAT6) and promotes the anti-inflammatory polarization of microglia. Obvious promotion of anti-inflammatory cytokines production is observed both in vitro and in vivo through rTMS stimulation on microglia. In addition, neural stem cells (NSCs) cultured in conditioned medium (CM) from microglia treated with rTMS showed downregulation of apoptosis and upregulation of neuronal differentiation. Overall, our results illustrate that rTMS can modulate microglia with anti-inflammatory polarization variation, promote neurogenesis, and improve neural function recovery.
AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System
Authors: Marino Marika , Holt Matthew G.
Published: April 2022

In the last four decades, monoclonal antibodies and their derivatives have emerged as a powerful class of therapeutics, largely due to their exquisite targeting specificity. Several clinical areas, most notably oncology and autoimmune disorders, have seen the successful introduction of monoclonal-based therapeutics. However, their adoption for treatment of Central Nervous System diseases has been comparatively slow, largely due to issues of efficient delivery resulting from limited permeability of the Blood Brain Barrier. Nevertheless, CNS diseases are becoming increasingly prevalent as societies age, accounting for ~6.5 million fatalities worldwide per year. Therefore, harnessing the full therapeutic potential of monoclonal antibodies (and their derivatives) in this clinical area has become a priority. Adeno-associated virus-based vectors (AAVs) are a potential solution to this problem. Preclinical studies have shown that AAV vector-mediated antibody delivery provides protection against a broad range of peripheral diseases, such as the human immunodeficiency virus (HIV), influenza and malaria. The parallel identification and optimization of AAV vector platforms which cross the Blood Brain Barrier with high efficiency, widely transducing the Central Nervous System and allowing high levels of local transgene production, has now opened a number of interesting scenarios for the development of AAV vector-mediated antibody delivery strategies to target Central Nervous System proteinopathies.
Does Prefrontal Glutamate Index Cognitive Changes in Parkinson’s Disease?
Authors: Buard Isabelle , Lopez-Esquibel Natalie , Carey Finnuella J. , Brown Mark S. , Medina Luis D. , Kronberg Eugene , Martin Christine S. , Rogers Sarah , Holden Samantha K. , Greher Michael R. , Kluger Benzi M.
Published: April 2022

Introduction

Cognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease (PD). A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex (PFC), a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.

Methods

Proton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD (CTL), as well as PD participants with either normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD). Ratios to Creatine (Cre) resonance were obtained for glutamate (Glu), glutamine and glutamate combined (Glx), N-acetylaspartate (NAA), myoinositol (mI), and total choline (Cho), and correlated with cognitive scores across multiple domains (executive function, learning and memory, language, attention, visuospatial function, and global cognition) administered to the PD participants only.

Results

When individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.

Conclusion

These preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups.
Bioinformatics Analysis of Stem Cell circ-ASB3 Signaling Pathway and Its Affection on Glioma Biological Characteristics
Authors: Guowei Li , Yanping Jin
Published: April 2022

Objective

In our research we try to explore whether glioma stem cell containing circRNAs signal pathway could regulate glioma malignant progression and elaborate its possible mechanism.

Methods

In this study, we used biological information analysis to build an RNA regulatory network and then proceeded RT-PCR to screen target RNAs, after that we clarified the targeting relationship between circRNA-miRNA-mRNA through double luciferase gene assay, RNA pull down experiment, PCR and Western Blot. Finally we adopted RNA transfection to identify its impact on glioma cell proliferation, invasion, migration, apoptosis and cell cycle.

Results

circ-ASB3 was significantly up-regulated in glioma stem cells compared with glioma cells. The circ-ASB3/miR-543/Twist1 axis was discovered to be a possible regulatory pathway in glioma, circ-ASB3 could adsorb and targeted bind to miR-543, down-regulate miR-543 expression, thus release its targeted inhibition to Twist1. Circ-ASB3 was shown to increase glioma cell proliferation, invasion, and migration in vitro via miR-543/Twist1 axis. Meanwhile glioma cell apoptosis could be inhibited, and cell cycle arrest could be induced through this signaling pathway.

Conclusion

circ-ASB3 could enhance glioma malignancy via miR-543/Twist1 axis, resulting in the discovery of new biomarkers and possible therapeutic targets for these patients.
Quantitative Hemodynamic Measurements in Cortical Vessels Using Functional Ultrasound Imaging
Authors: Brunner Clément , Macé Emilie , Montaldo Gabriel , Urban Alan
Published: April 2022

Red blood cell velocity (RBCv), cerebral blood flow (CBF), and volume (CBV) are three key parameters when describing brain hemodynamics. Functional ultrasound imaging is a Doppler-based method allowing for real-time measurement of relative CBV at high spatiotemporal resolution (100 × 110 × 300 μm3, up to 10 Hz) and large scale. Nevertheless, the measure of RBCv and CBF in small cortical vessels with functional ultrasound imaging remains challenging because of their orientation and size, which impairs the ability to perform precise measurements. We designed a directional flow filter to overpass these limitations allowing us to measure RBCv in single vessels using a standard functional ultrasound imaging system without contrast agents (e.g., microbubbles). This method allows to quickly extract the number of vessels in the cortex that was estimated to be approximately 650/cm3 in adult rats, with a 55–45% ratio for penetrating arterioles versus ascending venules. Then, we analyzed the changes in RBCv in these vessels during forepaw stimulation. We observed that ∼40 vessels located in the primary somatosensory forelimb cortex display a significant increase of the RBCv (median ΔRBCv ∼15%, maximal ΔRBCv ∼60%). As expected, we show that RBCv was higher for penetrating arterioles located in the center than in the periphery of the activated area. The proposed approach extends the capabilities of functional ultrasound imaging, which may contribute to a better understanding of the neurovascular coupling at the brain-wide scale.