bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropogenically-induced range expansion as an invasion front in native species: An example in North American flying squirrels
Authors: Diggins Corinne A.
Published: March 2023

Biological invasions are typically framed as non-native species impacting the populations of native species or ecosystems. However, in a changing world, taxonomically similar native species that were previously parapatric or allopatric may become increasingly sympatric over short time periods (<100 years). In the context of climate change in the Northern Hemisphere, this may have a negative impact on northern species whose ranges are being invaded by southern species. To highlight factors that may influence invasion fronts in native species, I use two species of North American flying squirrels, small-bodied nocturnal arboreal Sciurids, as an example. I discuss what factors may enable or limit the expansion of southern flying squirrels (SFS; Glaucomys fuscus) into northern flying squirrel (NFS; Glaucomys sabrinus) habitat and potential impacts that anthropogenically-induced factors have on range shift dynamics. The range expansion of SFS may impact NFS via resource competition, hybridization, and parasite-mediation. Factors potentially enabling the expansion of SFS into NFS habitat include anthropogenic habitat disturbance and climate change, wherein historical land-use (i.e., logging) alters forest composition increasing habitat suitability for SFS and a warming climate allows SFS to expanded their ranges northward into colder regions. Shifts in forest species composition from historical logging may interact with a warming climate to enable SFS to quickly expand their range. Factors limiting SFS expansion include thermoregulation limitations and absence of potential food and denning resources. The factors influencing the dynamics between these two species may be applicable to the shifting ranges of other taxonomically and functionally similar native species in the context of a rapidly changing world in the Anthropocene.
Mediterranean university campuses enhance butterfly (Lepidoptera) and beetle (Coleoptera) diversity
Authors: Arjona José Manuel , Ibáñez-Álamo Juan Diego , Sanllorente Olivia
Published: March 2023

Human population growth is causing an expansion of urban areas, a phenomenon known to deeply impact on the Earth’s biodiversity. Therefore, it is key to understand how to conceal urban development with biodiversity conservation. In this context, university campuses can play an important role as they usually present a large array of different environments and green areas, crucial aspects for promoting urban biodiversity as well as human-nature interactions. Several studies have analyzed the biodiversity of university campuses, however, there are still important taxonomic (e.g., insects) and geographical biases (e.g., Mediterranean hotspot) in our current understanding of these urban areas. Insects are fundamental in many ecosystems as pollinators, prey, pest controllers or decomposers among others. This further increases the need to study this group in the urban context. In this study, we have investigated diurnal Lepidoptera and ground-dwelling Coleoptera in three university campuses and three non-campus areas of the city of Granada (Spain). We used spatial and temporal replicates for each area in order to explore whether university campuses hold higher levels of insect biodiversity (e.g., species richness or common species) than other nearby urban areas. In addition, we investigated the potential influence of several additional predictors on insect diversity such as type of land cover, vegetation origin, management intensity, and distance to the outskirts. Our results suggest that Lepidoptera species and Coleoptera families are more diverse in university campuses than in other urban areas, showing also a positive association with the proportion of bare soil and herbaceous cover. Furthermore, they also seem to be benefited from low vegetation management intensity whereas Coleoptera are favored by native vegetation providing clear management recommendations in order to promote such animal groups in cities. Our study indicates that university campuses are important urban areas to preserve insect biodiversity but also highlights the heterogeneity of response among insect groups.
Smooth Descent: A ploidy-aware algorithm to improve linkage mapping in the presence of genotyping errors
Authors: Thérèse Navarro Alejandro , Bourke Peter M. , van de Weg Eric , Clot Corentin R. , Arens Paul , Finkers Richard , Maliepaard Chris
Published: March 2023

Linkage mapping is an approach to order markers based on recombination events. Mapping algorithms cannot easily handle genotyping errors, which are common in high-throughput genotyping data. To solve this issue, strategies have been developed, aimed mostly at identifying and eliminating these errors. One such strategy is SMOOTH, an iterative algorithm to detect genotyping errors. Unlike other approaches, SMOOTH can also be used to impute the most probable alternative genotypes, but its application is limited to diploid species and to markers heterozygous in only one of the parents. In this study we adapted SMOOTH to expand its use to any marker type and to autopolyploids with the use of identity-by-descent probabilities, naming the updated algorithm Smooth Descent (SD). We applied SD to real and simulated data, showing that in the presence of genotyping errors this method produces better genetic maps in terms of marker order and map length. SD is particularly useful for error rates between 5% and 20% and when error rates are not homogeneous among markers or individuals. With a starting error rate of 10%, SD reduced it to ∼5% in diploids, ∼7% in tetraploids and ∼8.5% in hexaploids. Conversely, the correlation between true and estimated genetic maps increased by 0.03 in tetraploids and by 0.2 in hexaploids, while worsening slightly in diploids (∼0.0011). We also show that the combination of genotype curation and map re-estimation allowed us to obtain better genetic maps while correcting wrong genotypes. We have implemented this algorithm in the R package Smooth Descent.
Recapitulating essential pathophysiological characteristics in lung-on-a-chip for disease studies
Authors: Zhang Yanning , Wang Xuejiao , Yang Yaoqing , Yan Jing , Xiong Yanlu , Wang Wenchen , Lei Jie , Jiang Tao
Published: March 2023

Lung diseases have become a significant challenge to public healthcare worldwide, which stresses the necessity of developing effective biological models for pathophysiological and pharmacological studies of the human respiratory system. In recent years, lung-on-a-chip has been extensively developed as a potentially revolutionary respiratory model paradigm with high efficiency and improved accuracy, bridging the gap between cell culture and preclinical trials. The advantages of lung-on-a-chip technology derive from its capabilities in establishing 3D multicellular architectures and dynamic microphysiological environments. A critical issue in its development is utilizing such capabilities to recapitulate the essential components of the human respiratory system for effectively restoring physiological functions and illustrating disease progress. Here we present a review of lung-on-a-chip technology, highlighting various strategies for capturing lung physiological and pathological characteristics. The key pathophysiological characteristics of the lungs are examined, including the airways, alveoli, and alveolar septum. Accordingly, the strategies in lung-on-a-chip research to capture the essential components and functions of lungs are analyzed. Recent studies of pneumonia, lung cancer, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis based on lung-on-a-chip are surveyed. Finally, cross-disciplinary approaches are proposed to foster the future development of lung-on-a-chip technology.
Comprehensive analysis of the prognosis, tumor microenvironment, and immunotherapy response of SDHs in colon adenocarcinoma
Authors: Nan Han , Guo Pengkun , Fan Jianing , Zeng Wen , Hu Chonghan , Zheng Can , Pan Bujian , Cao Yu , Ge Yiwen , Xue Xiangyang , Li Wenshu , Lin Kezhi
Published: March 2023

Background

Succinate dehydrogenase (SDH), one of the key enzymes in the tricarboxylic acid cycle, is mainly found in the mitochondria. SDH consists of four subunits encoding SDHA, SDHB, SDHC, and SDHD. The biological function of SDH is significantly related to cancer progression. Colorectal cancer (CRC) is one of the most common malignant tumors globally, whose most common histological subtype is colon adenocarcinoma (COAD). However, the correlation between SDH factors and COAD remains unclear.

Methods

The data on pan-cancer was obtained from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis showed the prognostic ability of SDHs. The cBioPortal database reflected genetic variations of SDHs. The correlation analysis was conducted between SDHs and mitochondrial energy metabolism genes (MMGs) and the protein-protein interaction (PPI) network was built. Consequently, Univariate and Multivariate Cox Regression Analysis on SDHs and other clinical characteristics were conducted. A nomogram was established. The ssGSEA analysis visualized the association between SDHs and immune infiltration. Immunophenoscore (IPS) explored the correlation between SDHs and immunotherapy, and the correlation between SDHs and targeted therapy was investigated through Genomics of Drug Sensitivity in Cancer. Finally, qPCR and immunohistochemistry detected SDHs’ expression.

Results

After assessing SDHs differential expression in pan-cancer, we found that SDHB, SDHC, and SDHD benefit COAD patients. The cBioPortal database demonstrated that SDHA was the top gene in mutation frequency rank. Correlation analysis mirrored a strong link between SDHs and MMGs. We formulated a nomogram and found that SDHB, SDHC, SDHD, and clinical characteristics correlated with COAD patients’ survival. For T helper cells, Th2 cells, and Tem, SDHA, SDHB, SDHC, and SDHD were significantly enriched in the high expression group. Moreover, COAD patients with high SDHA expression were more suitable for immunotherapy. And COAD patients with different SDHs’ expression have different sensitivity to targeted drugs. Further verifying the gene and protein expression levels of SDHs, we found that the tissues were consistent with the bioinformatics analysis.

Conclusions

Our study analyzed the expression and prognostic value of SDHs in COAD, explored the pathway mechanisms involved, and the immune cell correlations, indicating that SDHs might be biomarkers for COAD patients.
Cross-reactive antibodies against Langat virus protect mice from lethal tick-borne encephalitis virus infection
Authors: Kubinski Mareike , Beicht Jana , Zdora Isabel , Saletti Giulietta , Kircher Magdalena , Petry-Gusmag Monique , Steffen Imke , Puff Christina , Jung Klaus , Baumgärtner Wolfgang , Rimmelzwaan Guus F. , Osterhaus Albert D. M. E. , Prajeeth Chittappen Kandiyil
Published: March 2023

Introduction

Naturally attenuated Langat virus (LGTV) and highly pathogenic tick-borne encephalitis virus (TBEV) share antigenically similar viral proteins and are grouped together in the same flavivirus serocomplex. In the early 1970s, this has encouraged the usage of LGTV as a potential live attenuated vaccine against tick-borne encephalitis (TBE) until cases of encephalitis were reported among vaccinees. Previously, we have shown in a mouse model that immunity induced against LGTV protects mice against lethal TBEV challenge infection. However, the immune correlates of this protection have not been studied.

Methods

We used the strategy of adoptive transfer of either serum or T cells from LGTV infected mice into naïve recipient mice and challenged them with lethal dose of TBEV.

Results

We show that mouse infection with LGTV induced both cross-reactive antibodies and T cells against TBEV. To identify correlates of protection, Monitoring the disease progression in these mice for 16 days post infection, showed that serum from LGTV infected mice efficiently protected from developing severe disease. On the other hand, adoptive transfer of T cells from LGTV infected mice failed to provide protection. Histopathological investigation of infected brains suggested a possible role of microglia and T cells in inflammatory processes within the brain.

Discussion

Our data provide key information regarding the immune correlates of protection induced by LGTV infection of mice which may help design better vaccines against TBEV.
Combining chemotherapy with CAR-T cell therapy in treating solid tumors
Authors: Wang Arthur Xuan , Ong Xiao Jing , D’Souza Criselle , Neeson Paul J. , Zhu Joe Jiang
Published: March 2023

Chemotherapy has long been a standard treatment for a wide range of malignancies, where patients typically undergo multiple rounds of chemotherapy regimens to control tumor growth. In the clinic, the chemotherapy drugs cyclophosphamide and fludarabine are commonly used prior to Chimeric Antigen Receptor T (CAR-T) cell therapy to lymphodeplete and improve CAR-T cell engraftment. In this review, we discuss the use of chemotherapy in combination with CAR-T cell therapy. We also show that chemotherapy can deplete immunosuppressive cells, promote a pro-inflammatory tumor microenvironment, disrupt tumor stroma, and improve CAR-T cell recruitment to the tumor. Although the combination of chemotherapy plus CAR-T cell therapy is promising, certain aspects of chemotherapy also pose a challenge. In addition, the combined therapeutic effect may be heavily dependent on the dose and the treatment schedule. Thus, we also discussed the obstacles to effective clinical outcomes of the combination therapy.
Human umbilical cord mesenchymal stem cell-derived exosomes promote murine skin wound healing by neutrophil and macrophage modulations revealed by single-cell RNA sequencing
Authors: Liu Yuanyuan , Zhang Mingwang , Liao Yong , Chen Hongbo , Su Dandan , Tao Yuandong , Li Jiangbo , Luo Kai , Wu Lihua , Zhang Xingyue , Yang Rongya
Published: March 2023

Introduction

Full-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing.

Methods

Utilizing single-cell RNA sequencing, the transcriptomic diversity of neutrophils and macrophages was analyzed in order to predict the cellular fate of these immune cells under the influence of hucMSC-Exosomes and to identify alterations of ligand-receptor interactions that may influence the wound microenvironment. The validity of the findings obtained from this analysis was subsequently corroborated by immunofluorescence, ELISA, and qRT-PCR. Neutrophil origins were characterized based on RNA velocity profiles.

Results

The expression of RETNLG and SLC2A3 was associated with migrating neutrophils, while BCL2A1B was linked to proliferating neutrophils. The hucMSC-Exosomes group exhibited significantly higher levels of M1 macrophages (215 vs 76, p < 0.00001), M2 macrophages (1231 vs 670, p < 0.00001), and neutrophils (930 vs 157, p < 0.00001) when compared to control group. Additionally, it was observed that hucMSC-Exosomes elicit alterations in the differentiation trajectories of macrophages towards more anti-inflammatory phenotypes, concomitant with changes in ligand-receptor interactions, thereby facilitating healing.

Discussion

This study has revealed the transcriptomic heterogeneity of neutrophils and macrophages in the context of skin wound repair following hucMSC-Exosomes interventions, providing a deeper understanding of cellular responses to hucMSC-Exosomes, a rising target of wound healing intervention.
Free-swimming fauna associated with influxes of pelagic sargassum: Implications for management and harvesting
Authors: Alleyne Kristie S. T. , Small Micaela , Corbin Makeda , Vallès Henri , Oxenford Hazel A.
Published: March 2023

Mass accumulations of pelagic sargassum (Sargassum natans and S. fluitans) in the Tropical Atlantic, across the Caribbean and off the coast of West Africa, are causing extensive ecological and socioeconomic harm. The extraordinary volumes of sargassum influxes could also provide a business opportunity if innovative ways are developed to utilise the raw material. In-water harvesting provides the best opportunity to collect substantial amounts of ‘fresh’ sargassum that can be used in a variety of applications. However, sargassum rafts are living and diverse ecosystems with a range of associated fauna including fish that are targeted by fishers. The consequences of in-water harvesting of sargassum on the biodiversity, including associated fishes, remain poorly understood. Characterisation of this biodiversity within nearshore and offshore environments is needed to help guide best harvest practices and assess possible impacts on fishing opportunities. We assessed the free-swimming fauna associated with sargassum rafts at various distances from shore with the use of underwater video recordings. Over a three-month period, a total of 35 underwater surveys were conducted off the eastern and southern coastline of Barbados. Thirteen species (12 fishes and one comb jelly) from 8 families were identified, with the family Carangidae representing the greatest number of species (n=6). Application of the MaxN metric (maximum number of individuals of a species seen during deployment) revealed significant correlations with raft characteristics notably raft volume, raft distance from shore and water depth. The three environmental variables accounted for 9% of the variation (adjusted R2) in the free-swimming community composition with raft volume being the major driver of species richness. This aligns with ecological theory and supports our hypothesis that larger rafts would host greater species richness. The results demonstrate a strong affiliation between pelagic sargassum rafts and species biodiversity and abundance that will need to be considered by managers when seeking a best compromise between protecting beaches from inundation by sargassum and protecting biodiversity and fishing opportunities.
Personalized displacement ventilation as an energy-efficient solution for airborne disease transmission control in offices
Authors: La Heij Lars , Gkantonas Savvas , Mastorakos Epaminondas
Published: March 2023

There is evidence to suggest that airborne droplets play an important role in the transmission of respiratory diseases. The highest risk of exposure to these pathogens is in indoor environments, where airflow control has been recognized as one of the most effective engineering means to combat its spread. However, this can contribute to a significant increase in energy costs, as conventional ventilation is often not designed to remove contaminants efficiently. In this study, Computational Fluid Dynamics simulations were used to analyze how a novel ventilation approach, called Personalized Displacement Ventilation (PerDiVent), can simultaneously reduce both pathogenic airborne transmission and reduce energy costs in an open office. In addition, thermal comfort and noise were investigated to assess the practicality of the concept. PerDiVent was found to reduce the risk of cross infection by a factor of 1.08–2.0 compared to mixing ventilation in the worst and best case scenarios analyzed, and lead to savings in mechanical power of at least 30%. Furthermore, there is great potential to further improve the system and to increase the stated numbers substantially with relatively simple alterations to the design. Tools that can be used to great advantage for such optimization are also proposed in this work. These include a simple integral model and analytical metrics to estimate the reduction in cross-infection risk and energy savings as a function of PerDiVent’s effectiveness in removing contaminants. Finally, the system has a modular and highly flexible arrangement, which makes it suitable for retrofitting purposes in various indoor environments and integration with current ventilation systems. The concept shows great promise for the future, where ventilation is required to create healthier and more sustainable environments.
Search, identification, and curation of cell and gene therapy product regulations using augmented intelligent systems
Authors: Schaut William , Shrivastav Akash , Ramakrishnan Srikanth , Bowden Robert
Published: March 2023

Background

Manually keeping up-to-date with regulations such as directives, guidance, laws, and ordinances related to cell and gene therapy is a labor-intensive process. We used machine learning (ML) algorithms to create an augmented intelligent system to optimize systematic screening of global regulations to improve efficiency and reduce overall labor and missed regulations.

Methods

Combining Boolean logic and artificial intelligence (i.e., augmented intelligence) for the search process, ML algorithms were used to identify and suggest relevant cell and gene therapy regulations. Suggested regulations were delivered to a landing page for further subject matter expert (SME) tagging of words/phrases to provide system relevance on functional words. Ongoing learning from the repository regulations continued to increase system reliability and performance. The automated ability to train and retrain the system allows for continued refinement and improvement of system accuracy. Automated daily searches for applicable regulations in global databases provide ongoing opportunities to update the repository.

Results

Compared to manual searching, which required 3–4 SMEs to review ~115 regulations, the current system performance, with continuous system learning, requires 1 full-time equivalent to process approximately 9,000 regulations/day. Currently, system performance has 86% overall accuracy, a recommend recall of 87%, and a reject recall of 84%. A conservative search strategy is intentionally used to permit SMEs to assess low-recommended regulations in order to prevent missing any applicable regulations.

Conclusion

Compared to manual searches, our custom automated search system greatly improves the management of cell and gene therapy regulations and is efficient, cost effective, and accurate.
Mechanisms regulating the CRISPR-Cas systems
Authors: Zakrzewska Marta , Burmistrz Michal
Published: March 2023

The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated proteins) is a prokaryotic system that enables sequence specific recognition and cleavage of nucleic acids. This is possible due to cooperation between CRISPR array which contains short fragments of DNA called spacers that are complimentary to the targeted nucleic acid and Cas proteins, which take part in processes of: acquisition of new spacers, processing them into their functional form as well as recognition and cleavage of targeted nucleic acids. The primary role of CRISPR-Cas systems is to provide their host with an adaptive and hereditary immunity against exogenous nucleic acids. This system is present in many variants in both Bacteria and Archea. Due to its modular structure, and programmability CRISPR-Cas system become attractive tool for modern molecular biology. Since their discovery and implementation, the CRISPR-Cas systems revolutionized areas of gene editing and regulation of gene expression. Although our knowledge on how CRISPR-Cas systems work has increased rapidly in recent years, there is still little information on how these systems are controlled and how they interact with other cellular mechanisms. Such regulation can be the result of both auto-regulatory mechanisms as well as exogenous proteins of phage origin. Better understanding of these interaction networks would be beneficial for optimization of current and development of new CRISPR-Cas-based tools. In this review we summarize current knowledge on the various molecular mechanisms that affect activity of CRISPR-Cas systems.
Discovery of a novel filamentous prophage in the genome of the Mimosa pudica microsymbiont Cupriavidus taiwanensis STM 6018
Authors: Klonowska Agnieszka , Ardley Julie , Moulin Lionel , Zandberg Jaco , Patrel Delphine , Gollagher Margaret , Marinova Dora , Reddy T. B. K. , Varghese Neha , Huntemann Marcel , Woyke Tanja , Seshadri Rekha , Ivanova Natalia , Kyrpides Nikos , Reeve Wayne
Published: March 2023

Integrated virus genomes (prophages) are commonly found in sequenced bacterial genomes but have rarely been described in detail for rhizobial genomes. Cupriavidus taiwanensis STM 6018 is a rhizobial Betaproteobacteria strain that was isolated in 2006 from a root nodule of a Mimosa pudica host in French Guiana, South America. Here we describe features of the genome of STM 6018, focusing on the characterization of two different types of prophages that have been identified in its genome. The draft genome of STM 6018 is 6,553,639 bp, and consists of 80 scaffolds, containing 5,864 protein-coding genes and 61 RNA genes. STM 6018 contains all the nodulation and nitrogen fixation gene clusters common to symbiotic Cupriavidus species; sharing >99.97% bp identity homology to the nod/nif/noeM gene clusters from C. taiwanensis LMG19424T and “Cupriavidus neocalidonicus” STM 6070. The STM 6018 genome contains the genomes of two prophages: one complete Mu-like capsular phage and one filamentous phage, which integrates into a putative dif site. This is the first characterization of a filamentous phage found within the genome of a rhizobial strain. Further examination of sequenced rhizobial genomes identified filamentous prophage sequences in several Beta-rhizobial strains but not in any Alphaproteobacterial rhizobia.
Phenotypic and genotypic characterization of Shiga toxin-producing Escherichia coli strains recovered from bovine carcasses in Uruguay
Authors: Mussio Paula , Martínez Inés , Luzardo Santiago , Navarro Armando , Leotta Gerardo , Varela Gustavo
Published: March 2023

Introduction

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen that cause food-borne diseases in humans. Cattle and derived foodstuffs play a known role as reservoir and vehicles, respectively. In Uruguay, information about the characteristics of circulating STEC in meat productive chain is scarce. The aim was to characterize STEC strains recovered from 800 bovine carcasses of different slaughterhouses.

Methods

To characterize STEC strains we use classical microbiological procedures, Whole Genome Sequencing (WGS) and FAO/WHO risk criteria.

Results

We analyzed 39 STEC isolated from 20 establishments. They belonged to 21 different O-groups and 13 different H-types. Only one O157:H7 strain was characterized and the serotypes O130:H11(6), O174:H28(5), and O22:H8(5) prevailed. One strain showed resistance in vitro to tetracycline and genes for doxycycline, sulfonamide, streptomycin and fosfomycin resistance were detected. Thirty-three strains (84.6%) carried the subtypes Stx2a, Stx2c, or Stx2d. The gene eae was detected only in two strains (O157:H7, O182:H25). The most prevalent virulence genes found were lpfA (n = 38), ompA (n = 39), ompT (n = 39), iss (n = 38), and terC (n = 39). Within the set of STEC analyzed, the majority (81.5%) belonged to FAO/WHO’s risk classification levels 4 and 5 (lower risk). Besides, we detected STEC serotypes O22:H8, O113:H21, O130:H11, and O174:H21 belonged to level risk 2 associate with diarrhea, hemorrhagic colitis or Hemolytic-Uremic Syndrome (HUS). The only O157:H7 strain analyzed belonged to ST11. Thirty-eight isolates belonged to the Clermont type B1, while the O157:H7 was classified as E.

Discussion

The analyzed STEC showed high genomic diversity and harbor several genetic determinants associated with virulence, underlining the important role of WGS for a complete typing. In this set we did not detect non-O157 STEC previously isolated from local HUS cases. However, when interpreting this findings, the low number of isolates analyzed and some methodological limitations must be taken into account. Obtained data suggest that cattle constitute a local reservoir of non-O157 serotypes associated with severe diseases. Other studies are needed to assess the role of the local meat chain in the spread of STEC, especially those associated with severe diseases in humans.
A whole cell fluorescence quenching-based approach for the investigation of polyethyleneimine functionalized silver nanoparticles interaction with Candida albicans
Authors: Tiwari Atul Kumar , Gupta Munesh Kumar , Narayan Roger J. , Pandey Prem C.
Published: March 2023

The antimicrobial activity of metal nanoparticles can be considered a two-step process. In the first step, nanoparticles interact with the cell surface; the second step involves the implementation of the microbicidal processes. Silver nanoparticles have been widely explored for their antimicrobial activity against many pathogens. The interaction dynamics of functionalized silver nanoparticles at the biological interface must be better understood to develop surface-tuned biocompatible nanomaterial-containing formulations with selective antimicrobial activity. Herein, this study used the intrinsic fluorescence of whole C. albicans cells as a molecular probe to understand the cell surface interaction dynamics of polyethyleneimine-functionalized silver nanoparticles and antifungal mechanism of the same. The results demonstrated that synthesized PEI-f-Ag-NPs were ~ 5.6 ± 1.2 nm in size and exhibited a crystalline structure. Furthermore, the recorded zeta potential (+18.2 mV) was associated with the stability of NPS and shown a strong electrostatic interaction tendency between the negatively charged cell surface. Thus, rapid killing kinetics was observed, with a remarkably low MIC value of 5 μg/mL. PEI-f-Ag-NPs quenched the intrinsic fluorescence of C. albicans cells with increasing incubation time and concentration and have shown saturation effect within 120 min. The calculated binding constant (Kb = 1 × 105 M−1, n = 1.01) indicated strong binding tendency of PEI-f-Ag-NPs with C. albicans surface. It should also be noted that the silver nanoparticles interacted more selectively with the tyrosine-rich proteins in the fungal cell. However, calcofluor white fluorescence quenching showed non-specific binding on the cell surface. Thus, the antifungal mechanisms of PEI-f-Ag-NPs were observed as reactive oxygen species (ROS) overproduction and cell wall pit formation. This study demonstrated the utility of fluorescence spectroscopy for qualitative analysis of polyethyleneimine-functionalized silver nanoparticle interaction/binding with C. albicans cell surface biomolecules. Although, a quantitative approach is needed to better understand the interaction dynamics in order to formulate selective surface tuned nanoparticle for selective antifungal activity.
Development of the thin film solid phase microextraction (TF-SPME) method for metabolomics profiling of steroidal hormones from urine samples using LC-QTOF/MS
Authors: Struck-Lewicka Wiktoria , Karpińska Beata , Rodzaj Wojciech , Nasal Antoni , Wielgomas Bartosz , Markuszewski Michał Jan , Siluk Danuta
Published: March 2023

In the present study, the development and optimization of a thin film solid phase microextraction method (TF-SPME) was conducted for metabolomics profiling of eight steroid compounds (androsterone, dihydrotestosterone, dihydroepiandrosterone, estradiol, hydroxyprogesterone, pregnenolone, progesterone and testosterone) from urine samples. For optimization of extraction method, two extraction sorbents (PAN-C18 and PS-DVB) were used as they are known to be effective for isolation of low-polarity analytes. The stages of sample extraction and analyte desorption were considered as the most crucial steps in the process. Regarding the selection of the most suitable desorption solution, six different mixtures were analyzed. As a result, the mixture of ACN: MeOH (1:1, v/v) was chosen in terms of the highest analytes’ abundances that were achieved using the chosen solvent. Besides other factors were examined such as the volume of desorption solvent and the time of both extraction and desorption processes. The analytical determination was carried out using the ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry detection in electrospray ionization and positive polarity in a scan mode (UHPLC-ESI-QTOF/MS). The developed and optimized TF-SPME method was validated in terms of such parameters as extraction efficiency, recovery as well as matrix effect. As a result, the extraction efficiency and recovery were in a range from 79.3% to 99.2% and from 88.8% to 111.8%, respectively. Matrix effect, calculated as coefficient of variation was less than 15% and was in a range from 1.4% to 11.1%. The values of both validation parameters (recovery and matrix effect) were acceptable in terms of EMA criteria. The proposed TF-SPME method was used successfully for isolation of steroids hormones from pooled urine samples before and after enzymatic hydrolysis of analytes.
Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm
Authors: Metz Lisa Maria , Feige Tobias , de Biasi Larissa , Ehrenberg Agnes , Mulorz Joscha , Toska Laura Mara , Reusswig Friedrich , Quast Christine , Gerdes Norbert , Kelm Malte , Schelzig Hubert , Elvers Margitta
Published: March 2023

Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in abdominal aortic aneurysm formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP) VI. Since platelets play a role in cardiovascular diseases including abdominal aortic aneurysm, we analyzed the contribution of platelet Panx1 in the progression of abdominal aortic aneurysm. We detected enhanced Panx1 plasma levels in abdominal aortic aneurysm patients. In experimental abdominal aortic aneurysm using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect abdominal aortic aneurysm formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in abdominal aortic aneurysm via Panx1 channels and adds important knowledge about the significance of platelets in abdominal aortic aneurysm pathology important for the establishment of an anti-platelet therapy for abdominal aortic aneurysm patients.
Neuroprotective effect of angiotensin II receptor blockers on the risk of incident Alzheimer’s disease: A nationwide population-based cohort study
Authors: Lee Hyun Woo , Kim Seungyeon , Jo Youngkwon , Kim Youjin , Ye Byoung Seok , Yu Yun Mi
Published: March 2023

Background

Recent studies on renin-angiotensin system (RAS) inhibitors have reported a reduced risk of Alzheimer’s disease (AD). Nevertheless, the effect of RAS inhibitor type and blood–brain barrier (BBB) permeability on the risk of AD is still unknown.

Objectives

To assess the effects of RAS inhibitors on the risk of AD based on the type and BBB permeability and investigate the cumulative duration-response relationship.

Methods

This was a population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database records from 2008 to 2019. The data of patients diagnosed with ischemic heart disease between January 2009 and June 2009 were identified for inclusion in the analyses. Propensity score matching was used to balance RAS inhibitor users with non-users. The association between the use of RAS inhibitors and incident AD was evaluated using a multivariate Cox proportional hazard regression model. The results are presented in adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results

Among the 57,420 matched individuals, 7,303 developed AD within the follow-up period. While the use of angiotensin-converting enzyme inhibitors (ACEIs) was not significantly associated with AD risk, the use of angiotensin II receptor blockers (ARBs) showed a significant association with reduced risk of incident AD (aHR = 0.94; 95% CI = 0.90–0.99). Furthermore, the use of BBB-crossing ARBs was associated with a lower risk of AD (aHR = 0.83; 95% CI = 0.78–0.88) with a cumulative duration-response relationship. A higher cumulative dose or duration of BBB-crossing ARBs was associated with a gradual decrease in AD risk (P for trend < 0.001). No significant association between the use of ACEIs and the risk of AD was observed regardless of BBB permeability.

Conclusion

Long-term use of BBB-crossing ARBs significantly reduced the risk of AD development. The finding may provide valuable insight into disease-modifying drug options for preventing AD in patients with cardiovascular diseases.
Descriptive analysis of post-stroke patients in a neurological physical therapy unit
Authors: Paniagua-Monrobel Mercedes , Escobio-Prieto Isabel , Magni Eleonora , Galan-Mercant Alejandro , Lucena-Anton David , Pinero-Pinto Elena , Luque-Moreno Carlos
Published: March 2023

Introduction

Physical therapy (PT) is the mainstay treatment in functional recovery after suffering a stroke. It is important in the acute phase of hospitalization after a stroke and later in the ambulatory phase.

Patients and methods

The present study aimed to analyze the data provided by the clinical history (CH) of people with stroke (pwS) who received PT treatment in order to establish a “preferential patient profile” (PPP) that may benefit more from an early PT treatment. This was an observational, descriptive, and cross-sectional study. A total of 137 pwS who had been treated with PT were selected. Information provided age, gender, stroke type and localization, and start and end dates of the different PT treatments. A descriptive analysis of the variables was conducted using absolute frequencies and percentages for the qualitative variables. Student's t-test or the Mann–Whitney U-test was used to determine the relationship between the time and variables “stroke type,” “outpatient,” and “occupational therapy.” The Kruskal–Wallis H-test was applied for the “localization” variable.

Results

Of the entire sample, 57.7% were men, 65% had an ischemic stroke, and 48.9% had a stroke on the left side. The patients with hemorrhagic stroke had an increased number of hospital PT sessions (p = 0.01) and were younger (59.58 years) than patients with ischemic stroke (65.90 years) (p = 0.04).

Discussion and conclusion

Our results do not show significant differences between the persons < 65 years and the number of outpatient physiotherapy sessions performed, although the resulting values are close to significance. Our results suggest that the PPP is a young person, with a hemorrhagic and left or bilateral stroke.
Ethiopians' knowledge of and attitudes toward epilepsy: A systematic review and meta-analysis
Authors: Woldegeorgis Beshada Zerfu , Anjajo Eyosiyas Abreham , Korga Tesfalem Israel , Yigezu Berhanu Lijalem , Bogino Efa Ambaw , Tema Habtamu Tieka , Alemu Henok Berhanu , Boda Tesfalem Israel , Daba Dugo Angasa , Gobena Negeso , Obsa Mohammed Suleiman
Published: March 2023

Background

Epilepsy remains one of the world's most common neurological diseases, but it appears to be widely misunderstood, particularly in under-resourced countries like Ethiopia. Improving individuals' knowledge and attitude toward epilepsy is critical for reducing the multifaceted impacts of epilepsy. Therefore, in this study, we sought to estimate the pooled levels of good knowledge and a favorable attitude toward epilepsy and also identify the associated factors using available data collected from different segments of the population.

Methods

Articles were searched in international electronic databases. A standardized Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was used to write this report. The random-effect meta-analysis model was used to estimate Der Simonian-Laird's pooled effect. Statistical heterogeneity of the meta-analysis was checked via Higgins and Thompson's I2 statistics (0–100%), and Cochran's Q test at P < 0.10. Subgroups, based on the study regions, and sensitivity analyses were also performed. Publication bias was examined subjectively using funnel plots and objectively using the nonparametric rank correlation test of Begg and the regression-based test of Egger for small study effects with P < 0.05 considered to indicate potential publication bias. Furthermore, the Trim-and-fill method of Duval and Tweedie was used to explore sources of publication bias for the favorable level of attitudes toward epilepsy.

Result

A total of 12 studies with 6,373 study participants and 10 studies with 5,336 study participants were included to estimate the pooled level of good epilepsy knowledge and favorable attitudes respectively. The overall estimated levels of good epilepsy knowledge and favorable attitudes toward epilepsy among Ethiopians were 47.37% [(95% CI: 35.00, 59.74), I2 = 99.2, P < 0.001] and 46.83%[(95% CI: 32.75, 60.90), I2 = 99.2, P < 0.001] respectively. Subgroup analysis revealed that the pooled level of good epilepsy knowledge was 48.51% [(95% CI: 38.95, 58.06), I2 = 95.6%, P < 0.001] in the Amhara region.

Conclusion

In the current review, we found out that there is a huge knowledge gap and an unfavorable level of attitudes towardepilepsy, which demand immediate public health action as well as a targeted policy intervention.
Pipeline embolization devices for the treatment of nonsaccular aneurysms in pediatric patients
Authors: Han Jintao , Liang Fei , Zhang Yuxiang , Zhang Yupeng , Liang Shikai , Zhu Haoyu , Chang Yuzhou , Ma Chao , Liu Lian , Jia Zichang , Jiang Chuhan
Published: March 2023

Objective

Pediatric nonsaccular aneurysms are rare but challenging lesions; pipeline embolization devices (PEDs) are their potential treatment option. In this study, we aimed to evaluate the safety and efficacy of PEDs for treatment of these aneurysms.

Methods

We retrospectively selected pediatric patients with nonsaccular aneurysms treated using PEDs between June 2015 and July 2021 from our prospectively maintained database. For each patient, demographics, aneurysm characteristics, procedure details, and clinical and angiographic follow-up data were collected and summarized.

Results

This study included 16 pediatric patients with 16 nonsaccular aneurysms treated with PEDs. A median clinical follow-up time of 1,376 days was achieved in 93.75% of the patients. The complication rate of the included patients was 25%, with two patients developing mass effect, one patient undergoing major ischemic stroke, and one patient experiencing stent foreshortening after the procedure. The complete occlusion rate of aneurysms without any neurologic sequelae was 93.33%, with a median angiographic follow-up period of 246 days. The mortality rate was 6.25%.

Conclusions

The use of PEDs to treat pediatric nonsaccular aneurysms is feasible, with a high rate of complete occlusion of the aneurysm and favorable follow-up outcomes.
Online adaptive group-wise sparse Penalized Recursive Exponentially Weighted N-way Partial Least Square for epidural intracranial BCI
Authors: Moly Alexandre , Aksenov Alexandre , Martel Félix , Aksenova Tetiana
Published: March 2023

Introduction

Motor Brain–Computer Interfaces (BCIs) create new communication pathways between the brain and external effectors for patients with severe motor impairments. Control of complex effectors such as robotic arms or exoskeletons is generally based on the real-time decoding of high-resolution neural signals. However, high-dimensional and noisy brain signals pose challenges, such as limitations in the generalization ability of the decoding model and increased computational demands.

Methods

The use of sparse decoders may offer a way to address these challenges. A sparsity-promoting penalization is a common approach to obtaining a sparse solution. BCI features are naturally structured and grouped according to spatial (electrodes), frequency, and temporal dimensions. Applying group-wise sparsity, where the coefficients of a group are set to zero simultaneously, has the potential to decrease computational time and memory usage, as well as simplify data transfer. Additionally, online closed-loop decoder adaptation (CLDA) is known to be an efficient procedure for BCI decoder training, taking into account neuronal feedback. In this study, we propose a new algorithm for online closed-loop training of group-wise sparse multilinear decoders using Lp-Penalized Recursive Exponentially Weighted N-way Partial Least Square (PREW-NPLS). Three types of sparsity-promoting penalization were explored using Lpwith p = 0., 0.5, and 1.

Results

The algorithms were tested offline in a pseudo-online manner for features grouped by spatial dimension. A comparison study was conducted using an epidural ECoG dataset recorded from a tetraplegic individual during long-term BCI experiments for controlling a virtual avatar (left/right-hand 3D translation). Novel algorithms showed comparable or better decoding performance than conventional REW-NPLS, which was achieved with sparse models. The proposed algorithms are compatible with real-time CLDA.

Discussion

The proposed algorithm demonstrated good performance while drastically reducing the computational load and the memory consumption. However, the current study is limited to offline computation on data recorded with a single patient, with penalization restricted to the spatial domain only.
Vestibular paroxysmia associated with congenital vascular malformation: A case report
Authors: Liu Fei , Zhang Zheng , Wei Wan , Jiang Lin
Published: March 2023

Vestibular paroxysmia (VP) is an uncommon paroxysmal disease, characterized by vertigo, tinnitus, and postural unsteadiness. The main reason of VP is neurovascular cross compression, while few cases of VP accompanied with congenital vascular malformation were reported. Here, we describe a 22-year-old patient with VP caused by congenital anterior inferior cerebellar artery (AICA) malformation who completely recovered after taking oral medicine. This report shows that VP caused by congenital vascular malformation can occur in adults and that oral medication is effective.