bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate drivers of Southern Ocean phytoplankton community composition and potential impacts on higher trophic levels
Authors: Krumhardt Kristen M. , Long Matthew C. , Sylvester Zephyr T. , Petrik Colleen M.
Published: August 2022

Southern Ocean phytoplankton production supports rich Antarctic marine ecosystems comprising copepods, krill, fish, seals, penguins, and whales. Anthropogenic climate change, however, is likely to drive rearrangements in phytoplankton community composition with potential ramifications for the whole ecosystem. In general, phytoplankton communities dominated by large phytoplankton, i.e., diatoms, yield shorter, more efficient food chains than ecosystems supported by small phytoplankton. Guided by a large ensemble of Earth system model simulations run under a high emission scenario (RCP8.5), we present hypotheses for how anthropogenic climate change may drive shifts in phytoplankton community structure in two regions of the Southern Ocean: the Antarctic Circumpolar Current (ACC) region and the sea ice zone (SIZ). Though both Southern Ocean regions experience warmer ocean temperatures and increased advective iron flux under 21st century climate warming, the model simulates a proliferation of diatoms at the expense of small phytoplankton in the ACC, while the opposite patterns are evident in the SIZ. The primary drivers of simulated diatom increases in the ACC region include warming, increased iron supply, and reduced light from increased cloudiness. In contrast, simulated reductions in ice cover yield greater light penetration in the SIZ, generating a phenological advance in the bloom accompanied by a shift to more small phytoplankton that effectively consume available iron; the result is an overall increase in net primary production, but a decreasing proportion of diatoms. Changes of this nature may promote more efficient trophic energy transferviacopepods or krill in the ACC region, while ecosystem transfer efficiency in the SIZ may decline as small phytoplankton grow in dominance, possibly impacting marine food webs sustaining Antarctic marine predators. Despite the simplistic ecosystem representation in our model, our results point to a potential shift in the relative success of contrasting phytoplankton ecological strategies in different regions of the Southern Ocean, with ramifications for higher trophic levels.
Using citizen science to estimate surficial soil Blue Carbon stocks in Great British saltmarshes
Authors: Smeaton Craig , Burden Annette , Ruranska Paulina , Ladd Cai J. T. , Garbutt Angus , Jones Laurence , McMahon Lucy , Miller Lucy C. , Skov Martin W. , Austin William E. N.
Published: August 2022

A new saltmarsh soil dataset comprising of geochemical and physical property data from 752 soil samples collected through a sampling program supported by citizen scientists has been brought together with existing data to make the first national estimates of the surficial (top 10 cm) soil OC stock for Great British (GB) saltmarshes. To allow the inclusion of secondary data in the soil stock estimate a new bespoke organic matter to organic carbon conversion for GB saltmarsh soil was developed allowing organic matter data measured using loss-on-ignition to be convert to organic carbon content. The total GB surficial soil OC stock is 2.320 ± 0.470 Mt; English saltmarshes hold 1.601 ± 0.426 Mt OC, Scottish saltmarshes hold 0.368 ± 0.091 Mt OC, and Welsh saltmarshes hold 0.351 ± 0.082 Mt OC. The stocks were calculated within a Markov Chain Monte Carlo framework allowing robust uncertainty estimates to be derived for the first time. Spatial mapping tools are available to accompany these stock estimates at individual saltmarsh habitats throughout GB. This data will aid in the protection and management of saltmarshes and represents the first steps towards the inclusion of saltmarsh OC in the national inventory accounting of blue carbon ecosystems.
Staying close to home: Marine habitat selection by foraging yellow-eyed penguins using spatial distribution models
Authors: Hickcox Rachel P. , Mattern Thomas , Rodríguez-Recio Mariano , Young Melanie J. , van Heezik Yolanda , Seddon Philip J.
Published: August 2022

Endangered yellow-eyed penguins (Megadyptes antipodes) are central-place, benthic-diving foragers that search for prey in the productive marine areas off the coast of the South Island, New Zealand. Like other seabirds, they target specific, reliable areas of high prey abundance, which are often associated with oceanographic characteristics such as bathymetry, seafloor sediment type, and sea surface temperature. Employing GPS tracking data collected between 2003 and 2021, we created species distribution models using maximum entropy modelling (Maxent) to determine foraging space use and habitat suitability for yellow-eyed penguins across their entire South Island range and within five distinct subpopulations: Banks Peninsula, North Otago, Otago Peninsula, the Catlins, and Stewart Island. We quantified the importance of environmental variables for predicting foraging site selection during and outside the breeding season. Significant regional variation existed in predicted probability of penguin presence, and proximity to the nearest breeding area was a key predictor of suitable foraging habitat. When distance was not included in the models, dissolved oxygen concentration was the most important predictor in the overall South Island model and the North Otago, Otago Peninsula, and the Catlins subpopulation models, whereas water current speed and mean monthly turbidity were most important in Banks Peninsula and Stewart Island subpopulation models, respectively. Dynamic variables related to prey availability were often the most important variables in model predictions of the habitat selection of yellow-eyed penguins. Visualisations and findings from this study, particularly of the observed interactions between penguins and their marine habitat, can be used to direct conservation and resources during marine spatial planning and species management.
New approach for designing an underwater free-space optical communication system
Authors: Chen Yanhu , Zhang Luning , Ling Yucheng
Published: August 2022

Ocean observation system that involves multiple underwater vehicles and seafloor nodes plays an important role in better learning the ocean, where underwater wireless communication is mandatory for massive data interaction. Optical communication that has wide bandwidth and comprehensive working distance is the preferred method compared to acoustic and other methods. However, the presence of directionality makes the optical method difficult to use especially when the transceiver is equipped on a motive vehicle. In this study, an underwater free-space optical communication method of transmitting information is proposed. Characteristics of underwater optical transmission, as well as the photoelectric signal processing and modulation and demodulation algorithms, are studied and modeled. New approach for realizing underwater free-space optical communication is proposed and simulated. A prototype including a free-space optical transmitter and a receiver is developed; tests in different scenarios were carried out, and the results were observed: (1) by using the minimum number of LEDs, the effect of uniform lighting in space is achieved, and the transmitter coverage reaches 160°. (2) When the power of the transmitter is 10 W and the communication rate is 1 Mbps, the maximum communication distance reaches 13 m.
Sex hormones affect the pathogenesis and clinical characteristics of systemic lupus erythematosus
Authors: Kim Ji-Won , Kim Hyoun-Ah , Suh Chang-Hee , Jung Ju-Yang
Published: August 2022

Systemic lupus erythematosus (SLE) affects women more frequently than men, similar to the female predilection for other autoimmune diseases. Moreover, male patients with SLE exhibit different clinical features than female patients. Sex-associated differences in SLE required special considerations for disease management such as during pregnancy or hormone replacement therapy (HRT). Sex hormones, namely, estrogen and testosterone, are known to affect immune responses and autoimmunity. While estrogen and progesterone promote type I immune response, and testosterone enhances T-helper 1 response. Sex hormones also influence Toll-like receptor pathways, and estrogen receptor signaling is involved in the activation and tolerance of immune cells. Further, the clinical features of SLE vary according to hormonal changes in female patients. Alterations in sex hormones during pregnancy can alter the disease activity of SLE, which is associated with pregnancy outcomes. Additionally, HRT may change SLE status. Sex hormones affect the pathogenesis, clinical features, and management of SLE; thus, understanding the occurrence and exacerbation of disease caused by sex hormones is necessary to improve its management.
Exosomes secreted by Blastocystis subtypes affect the expression of proinflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10, IL-4)
Authors: Norouzi Mojtaba , Pirestani Majid , Arefian Ehsan , Dalimi Abdolhossein , Sadraei Javid , Mirjalali Hamed
Published: August 2022

Background

Blastocystissp. is a common intestinal parasite, possibly responsible for diarrhea, vomiting and nausea, abdominal pain, and irritable bowel syndrome. However, many studies focused on this issue due to the uncertainty of its pathogenic potential. The extracellular vesicles (EVs) are significant mediators for cellular communication, carrying biological molecules such as proteins, lipids, and nucleic acids. Compared with other parasites, little is known about theBlastocystisEVs. Hence the present investigation was done.

Methods

TheBlastocystisparasites were cultured in the DMEM medium, and a 550–585 bp fragment was amplified using PCR, and sequencing was done. A commercial kit was used for exosome extraction and dynamic light scattering (DLS), flow cytometry (CD63, CD81 markers), and electron microscopy tests to determine their morphology. The human leukemia monocytic cell line (THP-1) was exposed toBlastocystisEVs. Next, the expression of proinflammatory and anti-inflammatory cytokines, including IL-4, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α), were measured using quantitative PCR.

Results

Exosomes were extracted from ST1-3Blastocystissp. According to the DLS assay, the size of the exosomes was in the range of 30–100 nm. Electron microscopy images and CD63 and CD81 markers also confirmed the exosome's size, structure, and morphology. According to real-time PCR results, ST1-derived exosomes caused IL-6 and TNF-α upregulation and IL-10 and IL-4 downregulation, ST2- and ST3-derived exosomes downregulated IL-10, and ST3-derived exosomes caused IL-6 upregulation. There is a statistically significant difference (P≤ 0.05).

Conclusion

To our knowledge, this is the first report of the release of exosome-like vesicles by the human parasite,Blastocystis, and the provided information demonstrates the role of this parasite, particularly ST1 on proinflammatory and anti-inflammatory cytokines and navigating the host response.
Machine learning for predicting successful extubation in patients receiving mechanical ventilation
Authors: Igarashi Yutaka , Ogawa Kei , Nishimura Kan , Osawa Shuichiro , Ohwada Hayato , Yokobori Shoji
Published: August 2022

Ventilator liberation is one of the most critical decisions in the intensive care unit; however, prediction of extubation failure is difficult, and the proportion thereof remains high. Machine learning can potentially provide a breakthrough in the prediction of extubation success. A total of seven studies on the prediction of extubation success using machine learning have been published. These machine learning models were developed using data from electronic health records, 8–78 features, and algorithms such as artificial neural network, LightGBM, and XGBoost. Sensitivity ranged from 0.64 to 0.96, specificity ranged from 0.73 to 0.85, and area under the receiver operating characteristic curve ranged from 0.70 to 0.98. The features deemed most important included duration of mechanical ventilation, PaO2, blood urea nitrogen, heart rate, and Glasgow Coma Scale score. Although the studies had limitations, prediction of extubation success by machine learning has the potential to be a powerful tool. Further studies are needed to assess whether machine learning prediction reduces the incidence of extubation failure or prolongs the duration of ventilator use, thereby increasing tracheostomy and ventilator-related complications and mortality.
Rapamycin inhibits hepatitis B virus covalently closed circular DNA transcription by enhancing the ubiquitination of HBx
Authors: Zhang Yuan , Li Liang , Cheng Sheng-Tao , Qin Yi-Ping , He Xin , Li Fan , Wu Dai-Qing , Ren Fang , Yu Hai-Bo , Liu Jing , Chen Juan , Ren Ji-Hua , Zhang Zhen-Zhen
Published: August 2022

Hepatitis B virus (HBV) infection is still a serious public health problem worldwide. Antiviral therapies such as interferon and nucleos(t)ide analogs efficiently control HBV replication, but they cannot eradicate chronic hepatitis B (CHB) because of their incapacity to eliminate endocellular covalently closed circular DNA (cccDNA). Thus, there is a necessity to develop new strategies for targeting cccDNA. As cccDNA is difficult to clear, transcriptional silencing of cccDNA is a possible effective strategy. HBx plays a vitally important role in maintaining the transcriptional activity of cccDNA and it could be a target for blocking the transcription of cccDNA. To screen new drugs that may contribute to antiviral therapy, the ability of 2,000 small-molecule compounds to inhibit HBx was examined by the HiBiT lytic detection system. We found that the macrolide compound rapamycin, which is clinically used to prevent acute rejection after organ transplantation, could significantly reduce HBx protein expression. Mechanistic studies demonstrated that rapamycin decreased the stability of the HBx protein by promoting its degradation via the ubiquitin-proteasome system. Moreover, rapamycin inhibited HBV RNA, HBV DNA, and cccDNA transcription levels in HBV-infected cells. In addition, HBx deficiency abrogated the inhibition of cccDNA transcription induced by rapamycin. Similar results were also confirmed in a recombinant cccDNA mouse model. In summary, we report a new small-molecule, rapamycin, which targets HBx to block HBV cccDNA transcription and inhibit HBV replication. This approach can identify new strategies to cure CHB.
World Health Organization critical priority Escherichia coli clone ST648 in magnificent frigatebird (Fregata magnificens) of an uninhabited insular environment
Authors: Ewbank Ana Carolina , Fuentes-Castillo Danny , Sacristán Carlos , Esposito Fernanda , Fuga Bruna , Cardoso Brenda , Godoy Silvia Neri , Zamana Roberta Ramblas , Gattamorta Marco Aurélio , Catão-Dias José Luiz , Lincopan Nilton
Published: August 2022

Antimicrobial resistance is an ancient natural phenomenon increasingly pressured by anthropogenic activities. Escherichia coli has been used as markers of environmental contamination and human-related activity. Seabirds may be bioindicators of clinically relevant bacterial pathogens and their antimicrobial resistance genes, including extended-spectrum-beta-lactamase (ESBL) and/or plasmid-encoded AmpC (pAmpC), in anthropized and remote areas. We evaluated cloacal swabs of 20 wild magnificent frigatebirds (Fregata magnificens) of the Alcatrazes Archipelago, the biggest breeding colony of magnificent frigatebirds in the southern Atlantic and a natural protected area with no history of human occupation, located in the anthropized southeastern Brazilian coast. We characterized a highly virulent multidrug-resistant ST648 (O153:H9) pandemic clone, harboring blaCTX–M–2, blaCMY–2, qnrB, tetB, sul1, sul2, aadA1, aac(3)-VIa and mdfA, and virulence genes characteristic of avian pathogenic (APEC) (hlyF, iroN, iss, iutA, and ompT) and other extraintestinal E. coli (ExPEC) (chuA, kpsMII, and papC). To our knowledge, this is the first report of ST648 E. coli co-producing ESBL and pAmpC in wild birds inhabiting insular environments. We suggest this potentially zoonotic and pathogenic lineage was likely acquired through indirect anthropogenic contamination of the marine environment, ingestion of contaminated seafood, or by intra and/or interspecific contact. Our findings reinforce the role of wild birds as anthropization sentinels in insular environments and the importance of wildlife surveillance studies on pathogens of critical priority classified by the World Health Organization.
Mucosal immune cell populations and the bacteriome of adenoids and tonsils from people living with HIV on suppressive antiretroviral therapy
Authors: Briceño Olivia , Gónzalez-Navarro Mauricio , Montufar Nadia , Chávez-Torres Monserrat , Abato Indira , Espinosa-Sosa Ariana , Ablanedo-Terrazas Yuria , Luna-Villalobos Yara , Ávila-Ríos Santiago , Reyes-Terán Gustavo , Pinto-Cardoso Sandra
Published: August 2022

Ear, nose, and throat (ENT) conditions are prevalent in people living with HIV (PLWH) and occur at all strata of CD4 counts and despite antiretroviral therapy (ART). ENT conditions are underreported in PLWH. Also, little is known about the adenotonsillar microbiota and its relation to resident adaptive and innate immune cells. To bridge this gap, we characterized immune cell populations and the bacterial microbiota of two anatomical sites (adenoids, tonsils) and the oral cavity. Adenoids and tonsils were obtained from PLWH (n = 23) and HIV-seronegative individuals (SN, n = 16) after nasal surgery and tonsillectomy and processed for flow cytometry. Nasopharyngeal, oropharyngeal swabs, and oral rinses were collected prior to surgery for 16S sequencing. Wilcoxon rank sum test, principal coordinate analysis, permutational multivariate analysis of variance, and linear discriminant analysis (LEfSe) were used to assess differences between PLWH and SN. Spearman’s correlations were performed to explore interactions between the bacteriome and mucosal immune cells. Of the 39 individuals included, 30 (77%) were men; the median age was 32 years. All PLWH were on ART, with a median CD4 of 723 cells. ENT conditions were classified as inflammatory or obstructive, with no differences observed between PLWH and SN. PLWH had higher frequencies of activated CD4+ and CD8+ T cells, increased T helper (Th)1 and decreased Th2 cells; no differences were observed for B cells and innate immune cells. Alpha diversity was comparable between PLWH and SN at all 3 anatomical sites (adenoids, tonsils, and oral cavity). The impact of HIV infection on the bacterial community structure at each site, as determined by Permutational multivariate analysis of variance, was minor and not significant. Two discriminant genera were identified in adenoids using LEfSe: Staphylococcus for PLWH and Corynebacterium for SN. No discriminant genera were identified in the oropharynx and oral cavity. Niche-specific differences in microbial diversity and communities were observed. PLWH shared less of a core microbiota than SN. In the oropharynx, correlation analysis revealed that Th17 cells were inversely correlated with bacterial richness and diversity, Filifactor, Actinomyces and Treponema; and positively correlated with Streptococcus. Our study contributes toward understanding the role of the adenotonsillar microbiota in the pathophysiology of ENT conditions.
Prevalence and distribution of extended-spectrum β-lactamase and AmpC-producing Escherichia coli in two New Zealand dairy farm environments
Authors: Collis Rose M. , Biggs Patrick J. , Burgess Sara A. , Midwinter Anne C. , Brightwell Gale , Cookson Adrian L.
Published: August 2022

Antimicrobial resistance (AMR) is a global threat to human and animal health, with the misuse and overuse of antimicrobials being suggested as the main driver of resistance. In a global context, New Zealand (NZ) is a relatively low user of antimicrobials in animal production. However, the role antimicrobial usage on pasture-based dairy farms, such as those in NZ, plays in driving the spread of AMR within the dairy farm environment remains equivocal. Culture-based methods were used to determine the prevalence and distribution of extended-spectrum β-lactamase (ESBL)- and AmpC-producing Escherichia coli from farm environmental samples collected over a 15-month period from two NZ dairy farms with contrasting management practices. Whole genome sequencing was utilised to understand the genomic epidemiology and antimicrobial resistance gene repertoire of a subset of third-generation cephalosporin resistant E. coli isolated in this study. There was a low sample level prevalence of ESBL-producing E. coli (faeces 1.7%; farm dairy effluent, 6.7% from Dairy 4 and none from Dairy 1) but AmpC-producing E. coli were more frequently isolated across both farms (faeces 3.3% and 8.3%; farm dairy effluent 38.4%, 6.7% from Dairy 1 and Dairy 4, respectively). ESBL- and AmpC-producing E. coli were isolated from faeces and farm dairy effluent in spring and summer, during months with varying levels of antimicrobial use, but no ESBL- or AmpC-producing E. coli were isolated from bulk tank milk or soil from recently grazed paddocks. Hybrid assemblies using short- and long-read sequence data from a subset of ESBL- and AmpC-producing E. coli enabled the assembly and annotation of nine plasmids from six E. coli, including one plasmid co-harbouring 12 antimicrobial resistance genes. ESBL-producing E. coli were infrequently identified from faeces and farm dairy effluent on the two NZ dairy farms, suggesting they are present at a low prevalence on these farms. Plasmids harbouring several antimicrobial resistance genes were identified, and bacteria carrying such plasmids are a concern for both animal and public health. AMR is a burden for human, animal and environmental health and requires a holistic “One Health” approach to address.
Towards Reverse Vaccinology for Bovine TB: High Throughput Expression of Full Length Recombinant Mycobacterium bovis Proteins
Authors: Paliwal Deepa , Thom Michelle , Hussein Areej , Ravishankar Divyashree , Wilkes Alex , Charleston Bryan , Jones Ian M.
Published: August 2022

Bovine tuberculosis caused by Mycobacterium bovis, is a significant global pathogen causing economic loss in livestock and zoonotic TB in man. Several vaccine approaches are in development including reverse vaccinology which uses an unbiased approach to select open reading frames (ORF) of potential vaccine candidates, produce them as recombinant proteins and assesses their immunogenicity by direct immunization. To provide feasibility data for this approach we have cloned and expressed 123 ORFs from the M. bovis genome, using a mixture of E. coli and insect cell expression. We used a concatenated open reading frames design to reduce the number of clones required and single chain fusion proteins for protein pairs known to interact, such as the members of the PPE-PE family. Over 60% of clones showed soluble expression in one or the other host and most allowed rapid purification of the tagged bTB protein from the host cell background. The catalogue of recombinant proteins represents a resource that may be suitable for test immunisations in the development of an effective bTB vaccine.
Genomic reconstruction of short-chain fatty acid production by the human gut microbiota
Authors: Frolova Maria S. , Suvorova Inna A. , Iablokov Stanislav N. , Petrov Sergei N. , Rodionov Dmitry A.
Published: August 2022

Short-chain fatty acids (SCFAs) including acetate, formate, propionate, and butyrate are the end products of dietary fiber and host glycan fermentation by the human gut microbiota (HGM). SCFAs produced in the column are of utmost importance for host physiology and health. Butyrate and propionate improve gut health and play a key role in the neuroendocrine and immune systems. Prediction of HGM metabolic potential is important for understanding the influence of diet and HGM-produced metabolites on human health. We conducted a detailed metabolic reconstruction of pathways for the synthesis of SCFAs and L- and D-lactate, as additional fermentation products, in a reference set of 2,856 bacterial genomes representing strains of >800 known HGM species. The reconstructed butyrate and propionate pathways included four and three pathway variants, respectively, that start from different metabolic precursors. Altogether, we identified 48 metabolic enzymes, including five alternative enzymes in propionate pathways, and propagated their occurrences across all studied genomes. We established genomic signatures for reconstructed pathways and classified genomes according to their simplified binary phenotypes encoding the ability (“1”) or inability (“0”) of a given organism to produce SCFAs. The resulting binary phenotypes combined into a binary phenotype matrix were used to assess the SCFA synthesis potential of HGM samples from several public metagenomic studies. We report baseline and variance for Community Phenotype Indices calculated for SCFAs production capabilities in 16S metagenomic samples of intestinal microbiota from two large national cohorts (American Gut Project, UK twins), the Hadza hunter-gatherers, and the young children cohort of infants with high-risk for type 1 diabetes. We further linked the predicted SCFA metabolic capabilities with available SCFA concentrations both for in vivo fecal samples and in vitro fermentation samples from previous studies. Finally, we analyzed differential representation of individual SCFA pathway genes across several WGS metagenomic datasets. The obtained collection of SCFA pathway genes and phenotypes enables the predictive metabolic phenotype profiling of HGM datasets and enhances the in silico methodology to study cross-feeding interactions in the gut microbiomes.
Scientific literature landscape analysis of researches on oxidative stress in intervertebral disc degeneration in web of science
Authors: Cheng Yunzhong , Yang Honghao , Hai Yong , Zhou Lijin
Published: August 2022

Oxidative stress plays a significant role in the development of disc degeneration and has attracted widespread attention since it was first researched in 2007. Our study aims to analyze the scientific output of oxidative stress in intervertebral disc degeneration (IDD) and drive future research into new publications. Publications focused on this topic were retrieved from the SCI-EXPANDED (SCI-E) of the Web of Science (WOS) core collection database and were screened according to the inclusion criteria. Bibliometric website, VOSviewer, and Citespace software were used to evaluate and visualize the results, including annual publications, citations, authors, organizations, countries, research directions, funds, and journals. As of 16 February 2022, a total of 289 original articles and reviews were included, and the overall trend of the number of publications rapidly increased. China and the United States were the leading countries for research production in worldwide. The retrieved 289 publications received 5,979 citations, with an average of 20.67 citations and an H-index of 40. The most high-yield author, organization, country, research direction, fund, and journal were Wang K from Tongji Medical College, Huazhong University of Science Technology, China, Cell Biology, National Natural Science Foundation of China, Oxidative Medicine and Cellular Longevity, respectively. The majority of most common keywords were related to the mechanisms and regulatory networks of oxidative stress. Furthermore, with accumulating evidence that demonstrates the role of oxidative stress in IDD, “mitochondria” and “senescence” are becoming the new research focus that should be paid more attention to.
RETRACTED: QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics
Authors: Arora Deepshi , Bhatt Shailendra , Kumar Manish , Verma Ravinder , Taneja Yugam , Kaushal Nikita , Tiwari Abhishek , Tiwari Varsha , Alexiou Athanasios , Albogami Sarah , Alotaibi Saqer S. , Mittal Vineet , Singla Rajeev K. , Kaushik Deepak , Batiha Gaber El-Saber
Published: August 2022

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310–3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.
Altered pattern analysis and identification of subjective cognitive decline based on morphological brain network
Authors: Xu Xiaowen , Chen Peiying , Xiang Yongsheng , Xie Zhongfeng , Yu Qiang , Zhou Xiang , Wang Peijun
Published: August 2022

Subjective cognitive decline (SCD) is considered the first stage of Alzheimer’s disease (AD). Accurate diagnosis and the exploration of the pathological mechanism of SCD are extremely valuable for targeted AD prevention. However, there is little knowledge of the specific altered morphological network patterns in SCD individuals. In this present study, 36 SCD cases and 34 paired-matched normal controls (NCs) were recruited. The Jensen-Shannon distance-based similarity (JSS) method was implemented to construct and derive the attributes of multiple brain connectomes (i.e., morphological brain connections and global and nodal graph metrics) of individual morphological brain networks. A t-test was used to discriminate between the selected nodal graph metrics, while the leave-one-out cross-validation (LOOCV) was used to obtain consensus connections. Comparisons were performed to explore the altered patterns of connectome features. Further, the multiple kernel support vector machine (MK-SVM) was used for combining brain connectomes and differentiating SCD from NCs. We showed that the consensus connections and nodal graph metrics with the most discriminative ability were mostly found in the frontal, limbic, and parietal lobes, corresponding to the default mode network (DMN) and frontoparietal task control (FTC) network. Altered pattern analysis demonstrated that SCD cases had a tendency for modularity and local efficiency enhancement. Additionally, using the MK-SVM to combine the features of multiple brain connectomes was associated with optimal classification performance [area under the curve (AUC): 0.9510, sensitivity: 97.22%, specificity: 85.29%, and accuracy: 91.43%]. Therefore, our study highlighted the combination of multiple connectome attributes based on morphological brain networks and offered a valuable method for distinguishing SCD individuals from NCs. Moreover, the altered patterns of multidimensional connectome attributes provided a promising insight into the neuroimaging mechanism and early intervention in SCD subjects.
Management of dysphagia and gastroparesis in Parkinson’s disease in real-world clinical practice – Balancing pharmacological and non-pharmacological approaches
Authors: Bhidayasiri Roongroj , Phuenpathom Warongporn , Tan Ai Huey , Leta Valentina , Phumphid Saisamorn , Chaudhuri K. Ray , Pal Pramod Kumar
Published: August 2022

Gastrointestinal (GI) issues are commonly experienced by patients with Parkinson’s disease (PD). Those that affect the lower GI tract, such as constipation, are the most frequently reported GI problems among patients with PD. Upper GI issues, such as swallowing dysfunction (dysphagia) and delayed gastric emptying (gastroparesis), are also common in PD but are less well recognized by both patients and clinicians and, therefore, often overlooked. These GI issues may also be perceived by the healthcare team as less of a priority than management of PD motor symptoms. However, if left untreated, both dysphagia and gastroparesis can have a significant impact on the quality of life of patients with PD and on the effectiveness on oral PD medications, with negative consequences for motor control. Holistic management of PD should therefore include timely and effective management of upper GI issues by utilizing both non-pharmacological and pharmacological approaches. This dual approach is key as many pharmacological strategies have limited efficacy in this setting, so non-pharmacological approaches are often the best option. Although a multidisciplinary approach to the management of GI issues in PD is ideal, resource constraints may mean this is not always feasible. In ‘real-world’ practice, neurologists and PD care teams often need to make initial assessments and treatment or referral recommendations for their patients with PD who are experiencing these problems. To provide guidance in these cases, this article reviews the published evidence for diagnostic and therapeutic management of dysphagia and gastroparesis, including recommendations for timely and appropriate referral to GI specialists when needed and guidance on the development of an effective management plan.
Motor cortex outputs evoked by long-duration microstimulation encode synergistic muscle activation patterns not controlled movement trajectories
Authors: Capaday Charles
Published: August 2022

The effects of intracortical microstimulation (ICMS) parameters on the evoked electromyographic (EMG) responses and resulting limb movement were investigated. In ketamine-anesthetized cats, paw movement kinematics in 3D and EMG activity from 8 to 12 forelimb muscles evoked by ICMS applied to the forelimb area of the cat motor cortex (MCx) were recorded. The EMG responses evoked by ICMS were also compared to those evoked by focal ictal bursts induced by the iontophoretic ejection of the GABAA receptor antagonist bicuculline methochloride (BIC) at the same cortical point. The effects of different initial limb starting positions on movement trajectories resulting from long-duration ICMS were also studied. The ICMS duration did not affect the evoked muscle activation pattern (MAP). Short (50 ms) and long (500 ms) stimulus trains activated the same muscles in the same proportions. MAPs could, however, be modified by gradually increasing the stimulus intensity. MAPs evoked by focal ictal bursts were also highly correlated with those obtained by ICMS at the same cortical point. Varying the initial position of the forelimb did not change the MAPs evoked from a cortical point. Consequently, the evoked movements reached nearly the same final end point and posture, with variability. However, the movement trajectories were quite different depending on the initial limb configuration and starting position of the paw. The evoked movement trajectory was most natural when the forelimb lay pendant ~ perpendicular to the ground (i.e., in equilibrium with the gravitational force). From other starting positions, the movements did not appear natural. These observations demonstrate that while the output of the cortical point evokes a seemingly coordinated limb movement from a rest position, it does not specify a particular movement direction or a controlled trajectory from other initial positions.
Outcomes of reconstructive endovascular treatment of vertebrobasilar dissecting aneurysms with intramural hematoma
Authors: Zhang Yisen , Peng Qichen , Zhou Yangyang , Wang Chao , Zhang Longhui , Yang Xinjian , Mu Shiqing
Published: August 2022

Background

Vertebrobasilar dissecting aneurysms (VBDAs) with an intramural hematoma (IMH) usually cause symptoms because of mass effect and grow in size over time. Clinical outcomes are generally poor.

Objective

This study aimed to examine outcomes of reconstructive endovascular treatment (EVT) in patients with VBDAs with IMH. Safety and effectiveness were compared between flow diverters (FDs) and conventional stents.

Methods

We retrospectively analyzed the clinical and radiological data of 36 VBDAs with IMH in 36 patients who underwent EVT with either FDs or conventional stents from January 2012 to December 2020 at our institution.

Results

Among the 36 study patients, 20 were treated with FDs and 16 with conventional stents. Incidence of procedure-related complications did not significantly differ between the two stents. IMH growth occurred after EVT in a significantly higher proportion of conventional stent group aneurysms (zero vs. 31.3% [5/16]; p = 0.012). Among the five aneurysms with IMHs that grew, all recurred. Change in IMH size after EVT was significantly lower in the FD group (−2.7 vs. +8.1%, p = 0.036). However, after the recurrent aneurysms were removed from the conventional stent group, change in IMH size did not significantly differ between the two groups (−2.7 vs. +1.0%, p = 0.332). The proportion of patients who experienced an improvement in mRS score after EVT was significantly higher in the FD group (60 vs. 25%, p = 0.036).

Conclusion

IMHs in VBDAs stop growing after successful reconstructive EVT. Although both FD and conventional stent treatment are effective, FD treatment may be superior based on clinical outcomes and effect on IMH size.
The radiological and electrophysiological characteristics of Hirayama disease with proximal involvement: A retrospective study
Authors: Wang Hongwei , Tian Ye , Wu Jianwei , Sun Chi , Nie Cong , Zheng Chaojun , Zou Fei , Xia Xinlei , Ma Xiaosheng , Lyu Feizhou , Jiang Jianyuan , Wang Hongli
Published: August 2022

Purpose

Hirayama disease (HD) has been largely believed to affect only distal muscles. However, the proximal upper extremities have been affected in some cases, which can be confused with motor neuron diseases.

Methods

Baseline data, deep tendon reflex, Hoffmann sign, cervical curvature, sagittal Cobb angle, atrophied spinal cord, high signal intensity, loss of attachment, and affected muscles and segments on electromyography (EMG) were retrospectively obtained and compared between patients with HD with proximal involvement and patients with simple distal HD in one center from September 2007 to April 2022.

Results

In this study, fifteen patients with proximal HD and 30 patients with simple distal HD were included. The proximal group had a larger proportion of patients with decreased biceps reflex, decreased triceps reflex, brisk or hyperactive knee reflex, positive Hoffmann sign, and cervical kyphosis. The curvatures of the upper part of the cervical spine (C2-4) were lost to a greater degree in the proximal group. More affected segments were observed on magnetic resonance imaging (MRI) and electromyography in the proximal group.

Conclusion

The injured segments were longer and the upper curvature of the cervical spine was poorer in patients with HD with proximal involvement. These findings indicated that proximal involvement may indicate more serious HD.
Cerebral small vessel disease combined with cerebral collaterals to predict the prognosis of patients with acute large artery atherosclerotic stroke
Authors: Wei Cunsheng , Shen Tingwen , Tang Xuelian , Gao Yuanyuan , Yu Xiaorong , Chen Xuemei
Published: August 2022

Background and purpose

Besides cerebral collaterals, few studies have examined other additional factors affecting the prognosis of patients with large artery atherosclerotic (LAA) stroke. Our study aims to explore the effect of the cerebral small vessel disease (SVD) and the effects of its interaction with cerebral collaterals on the prognosis of patients with acute LAA stroke.

Method

Patients aged 18 years or older with LAA stroke within 24 h after stroke onset were consecutively enrolled. The functional outcome was determined using the modified Rankin Scale (mRS) at 3 months after stroke onset. Logistic multivariate analyses were used to identify the risk factors for stroke prognosis. Receiver operating characteristic (ROC) curves were constructed to compare the effects of cerebral collaterals and SVD on predicting the prognosis.

Results

Of the 274 enrolled patients, 174 (63.50%) were identified as having a favorable prognosis, and 100 (36.50%) were identified as having an unfavorable prognosis. After adjusting for covariates, the logistic regression analysis identified that unfavorable prognosis was related to the total SVD score (Model 1, adjusted odds ratio = 1.73, 95% CI: 1.15–2.61, P < 0.01; Model 2, adjusted odds ratio = 1.85, 95% CI: 1.23–2.79, P < 0.01) and Tan score (Model 1, adjusted odds ratio = 0.38, 95% CI: 0.23–0.64, P < 0.01; Model 2, adjusted odds ratio = 0.52, 95% CI: 0.33–0.82, P < 0.01). Compared with cerebral collaterals (AUC = 0.59; 95% CI: 0.52–0.67; P < 0.01) or SVD (AUC = 0.62; 95% CI: 0.56–0.69; P < 0.01) alone, the combination of collaterals and SVD (AUC = 0.66; 95% CI: 0.59–0.73; P < 0.01) had higher diagnostic value for an unfavorable prognosis, and the optimal sensitivity and specificity were 77.01 and 53.00%, respectively.

Conclusions

The total SVD burden was related to the prognosis of patients with LAA stroke. Compared with cerebral collaterals or SVD alone, cerebral collaterals combined with total SVD burden are better at predicting the prognosis of patients with acute LAA stroke.
Misophonia: Analysis of the neuroanatomic patterns at the basis of psychiatric symptoms and changes of the orthosympathetic/ parasympathetic balance
Authors: Grossini Elena , Stecco Alessandro , Gramaglia Carla , De Zanet Daniel , Cantello Roberto , Gori Benedetta , Negroni Davide , Azzolina Danila , Ferrante Daniela , Feggi Alessandro , Carriero Alessandro , Zeppegno Patrizia
Published: August 2022

Background/Aim

Misophonia is a disorder characterized by reduced tolerance to specific sounds or stimuli known as “triggers,” which tend to evoke negative emotional, physiological, and behavioral responses. In this study, we aimed to better characterize participants with misophonia through the evaluation of the response of the autonomic nervous system to “trigger sounds,” a psychometric assessment, and the analysis of the neurological pathways.

Materials and methods

Participants included 11 adults presenting with misophonic disturbance and 44 sex-matched healthy controls (HCs). Following recently proposed diagnostic criteria, the participants listened to six “trigger sounds” and a “general annoyance” sound (baby crying) during a series of physiological tests. The effects were examined through functional magnetic resonance imaging (fMRI), the analysis of heart rate variability (HRV), and of galvanic skin conductance (GSC). The fMRI was performed on a 3T Scanner. The HRV was obtained through the analysis of electrocardiogram, whereas the GSC was examined through the positioning of silver-chloride electrodes on fingers. Furthermore, the psychometric assessment included questionnaires focused on misophonia, psychopathology, resilience, anger, and motivation.

Results

Participants with misophonia showed patterns of increased sympathetic activation in response to trigger sounds and a general annoyance sound, the low frequency (LF) component of HRV, the sympathetic index, and the number of significant GSC over the threshold, where the amplitude/phasic response of GSC was higher. The fMRI analysis provided evidence for the activation of the temporal cortex, the limbic area, the ventromedial prefrontal/premotor/cingulate cortex, and the cerebellum in participants with misophonia. In addition, the psychometric assessment seemed to differentiate misophonia as a construct independent from general psychopathology.

Conclusion

These results suggest the activation of a specific auditory-insula-limbic pathway at the basis of the sympathetic activation observed in participants with misophonia in response to “trigger and general annoyance sounds.” Further studies should disentangle the complex issue of whether misophonia represents a new clinical disorder or a non-pathological condition. These results could help to build diagnostic tests to recognize and better classify this disorder. The relevance of this question goes beyond purely theoretical issues, as in the first case, participants with misophonia should receive a diagnosis and a targeted treatment, while in the second case, they should not.
Genetic variant rs11136000 upregulates clusterin expression and reduces Alzheimer’s disease risk
Authors: Ma Jin , Qiu Shizheng
Published: August 2022

Clusterin (CLU) is an extracellular chaperone involved in reducing amyloid beta (Aβ) toxicity and aggregation. Although previous genome-wide association studies (GWAS) have reported a potential protective effect of CLU on Alzheimer’s disease (AD) patients, how intron-located rs11136000 (CLU) affects AD risk by regulating CLU expression remains unknown. In this study, we integrated multiple omics data to construct the regulated pathway of rs11136000-CLU-AD. In step 1, we investigated the effects of variant rs11136000 on AD risk with different genders and diagnostic methods using GWAS summary statistics for AD from International Genomics of Alzheimer’s Project (IGAP) and UK Biobank. In step 2, we assessed the regulation of rs11136000 on CLU expression in AD brain samples from Mayo clinic and controls from Genotype-Tissue Expression (GTEx). In step 3, we investigated the differential gene/protein expression of CLU in AD and controls from four large cohorts. The results showed that rs11136000 T allele reduced AD risk in either clinically diagnosed or proxy AD patients. By using expression quantitative trait loci (eQTL) analysis, rs11136000 variant downregulated CLU expression in 13 normal brain tissues, but upregulated CLU expression in cerebellum and temporal cortex of AD samples. Importantly, CLU was significantly differentially expressed in temporal cortex, dorsolateral prefrontal cortex and anterior prefrontal cortex of AD patients compared with normal controls. Together, rs11136000 may reduce AD risk by regulating CLU expression, which may provide important information about the biological mechanism of rs9848497 in AD progress.