bluuebunny/crossref_metadata_2025 huggingface dataset:
The detection and prediction of surgical site infections using multi-modal sensors and machine learning: Results in an animal model
Authors: Hughes Charmayne Mary Lee , Jeffers Andrew , Sethuraman Arun , Klum Michael , Tan Milly , Tan Valerie
Published: April 2023

Introduction

Surgical Site Infection (SSI) is a common healthcare-associated infection that imposes a considerable clinical and economic burden on healthcare systems. Advances in wearable sensors and digital technologies have unlocked the potential for the early detection and diagnosis of SSI, which can help reduce this healthcare burden and lower SSI-associated mortality rates.

Methods

In this study, we evaluated the ability of a multi-modal bio-signal system to predict current and developing superficial incisional infection in a porcine model infected with Methicillin Susceptible Staphylococcus Aureus (MSSA) using a bagged, stacked, and balanced ensemble logistic regression machine learning model.

Results

Results demonstrated that the expression levels of individual biomarkers (i.e., peri-wound tissue oxygen saturation, temperature, and bioimpedance) differed between non-infected and infected wounds across the study period, with cross-correlation analysis indicating that a change in bio-signal expression occurred 24 to 31 hours before this change was reflected by clinical wound scoring methods employed by trained veterinarians. Moreover, the multi-modal ensemble model indicated acceptable discriminability to detect the presence of a current superficial incisional SSI (AUC = 0.77), to predict an SSI 24 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.80), and to predict an SSI 48 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.74).

Discussion

In sum, the results of the current study indicate that non-invasive multi-modal sensor and signal analysis systems have the potential to detect and predict superficial incisional SSIs in porcine subjects under experimental conditions.
A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography
Authors: Ravagli Enrico , Ardell Jeffrey , Holder David , Aristovich Kirill
Published: April 2023

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies.
An Experimental Murine Model to Study Acquisition Dynamics of Tick-Borne Langat Virus in Ixodes scapularis
Authors: Ahmed Waqas , Rajendran Kundave V. , Neelakanta Girish , Sultana Hameeda
Published: April 2023

Graphical Abstract

Tick-borne virus acquisition study model.
Efficient detoxication of hydroxylamine and nitrite through heterotrophic nitrification and aerobic denitrification by Acinetobacter johnsonii EN-J1
Authors: Zhang Manman , He Tengxia , Wu Qifeng , Chen Mengping
Published: April 2023

The co-existence of hydroxylamine (NH2OH) and nitrite (NO2–-N) can aggravate the difficulty of wastewater treatment. The roles of hydroxylamine (NH2OH) and nitrite (NO2–-N) in accelerating the elimination of multiple nitrogen sources by a novel isolated strain of Acinetobacter johnsonii EN-J1 were investigated in this study. The results demonstrated that strain EN-J1 could eliminate 100.00% of NH2OH (22.73 mg/L) and 90.09% of NO2–-N (55.32 mg/L), with maximum consumption rates of 1.22 and 6.75 mg/L/h, respectively. Prominently, the toxic substances NH2OH and NO2–-N could both facilitate nitrogen removal rates. Compared with the control treatment, the elimination rates of nitrate (NO3–-N) and NO2–-N were enhanced by 3.44 and 2.36 mg/L/h after supplementation with 10.00 mg/L NH2OH, and those of ammonium (NH4+-N) and NO3–-N were improved by 0.65 and 1.00 mg/L/h after the addition of 50.00 mg/L NO2–-N. Furthermore, the nitrogen balance results indicated that over 55.00% of the initial total nitrogen was transformed into gaseous nitrogen by heterotrophic nitrification and aerobic denitrification (HN-AD). Ammonia monooxygenase (AMO), hydroxylamine oxidoreductase (HAO), nitrate reductase (NR), and nitrite reductase (NIR), which are essential for HN-AD, were detected at levels of 0.54, 0.15, 0.14, and 0.01 U/mg protein, respectively. All findings confirmed that strain EN-J1 could efficiently execute HN-AD, detoxify NH2OH and NO2–-N, and ultimately promote nitrogen removal rates.
Broadness and specificity: ArdB, ArdA, and Ocr against various restriction-modification systems
Authors: Kudryavtseva Anna A. , Cséfalvay Eva , Gnuchikh Evgeniy Yu , Yanovskaya Darya D. , Skutel Mikhail A. , Isaev Artem B. , Bazhenov Sergey V. , Utkina Anna A. , Manukhov Ilya V.
Published: April 2023

ArdB, ArdA, and Ocr proteins inhibit the endonuclease activity of the type I restriction-modification enzymes (RMI). In this study, we evaluated the ability of ArdB, ArdA, and Ocr to inhibit different subtypes of Escherichia coli RMI systems (IA, IB, and IC) as well as two Bacillus licheniformis RMI systems. Furthermore we explored, the antirestriction activity of ArdA, ArdB, and Ocr against a type III restriction-modification system (RMIII) EcoPI and BREX. We found that DNA-mimic proteins, ArdA and Ocr exhibit different inhibition activity, depending on which RM system tested. This effect might be linked to the DNA mimicry nature of these proteins. In theory, DNA-mimic might competitively inhibit any DNA-binding proteins; however, the efficiency of inhibition depend on the ability to imitate the recognition site in DNA or its preferred conformation. In contrast, ArdB protein with an undescribed mechanism of action, demonstrated greater versatility against various RMI systems and provided similar antirestriction efficiency regardless of the recognition site. However, ArdB protein could not affect restriction systems that are radically different from the RMI such as BREX or RMIII. Thus, we assume that the structure of DNA-mimic proteins allows for selective inhibition of any DNA-binding proteins depending on the recognition site. In contrast, ArdB-like proteins inhibit RMI systems independently of the DNA recognition site.
Molecular and pathological investigation of avian reovirus (ARV) in Egypt with the assessment of the genetic variability of field strains compared to vaccine strains
Authors: Mosad Samah M. , Elmahallawy Ehab Kotb , Alghamdi Abeer M. , El-Khayat Fares , El-Khadragy Manal F. , Ali Lobna A. , Abdo Walied
Published: April 2023

Avian orthoreovirus (ARV) is among the important viruses that cause drastic economic losses in the Egyptian poultry industry. Despite regular vaccination of breeder birds, a high prevalence of ARV infection in broilers has been noted in recent years. However, no reports have revealed the genetic and antigenic characteristics of Egyptian field ARV and vaccines used against it. Thus, this study was conducted to detect the molecular nature of emerging ARV strains in broiler chickens suffering from arthritis and tenosynovitis in comparison to vaccine strains. Synovial fluid samples (n = 400) were collected from 40 commercial broiler flocks in the Gharbia governorate, Egypt, and then pooled to obtain 40 samples, which were then used to screen ARV using reverse transcriptase polymerase chain reaction (RT-PCR) with the partial amplification of ARV sigma C gene. The obtained RT-PCR products were then sequenced, and their nucleotide and deduced amino acid sequences were analyzed together with other ARV field and vaccine strains from GenBank. RT-PCR successfully amplified the predicted 940 bp PCR products from all tested samples. The phylogenetic tree revealed that the analyzed ARV strains were clustered into six genotypic clusters and six protein clusters, with high antigenic diversity between the genotypic clusters. Surprisingly, our isolates were genetically different from vaccine strains, which aligned in genotypic cluster I/protein cluster I, while our strains were aligned in genotypic cluster V/protein cluster V. More importantly, our strains were highly divergent from vaccine strains used in Egypt, with 55.09–56.23% diversity. Sequence analysis using BioEdit software revealed high genetic and protein diversity between our isolates and vaccine strains (397/797 nucleotide substitutions and 148-149/265 amino acid substitutions). This high genetic diversity explains the vaccination failure and recurrent circulation of ARV in Egypt. The present data highlight the need to formulate a new effective vaccine from locally isolated ARV strains after a thorough screening of the molecular nature of circulating ARV in Egypt.
Transcriptomic alterations in the sweet orange vasculature correlate with growth repression induced by a variant of citrus tristeza virus
Authors: Aknadibossian Vicken , Huguet-Tapia Jose C. , Golyaev Victor , Pooggin Mikhail M. , Folimonova Svetlana Y.
Published: April 2023

Citrus tristeza virus (CTV, family Closteroviridae) is an economically important pathogen of citrus. CTV resides in the phloem of the infected plants and induces a range of disease phenotypes, including stem pitting and quick decline as well as a number of other deleterious syndromes. To uncover the biological processes underlying the poorly understood damaging symptoms of CTV, we profiled the transcriptome of sweet orange (Citrus sinensis) phloem-rich bark tissues of non-infected, mock-inoculated trees and trees singly infected with two distinct variants of CTV, T36 or T68-1. The T36 and T68-1 variants accumulated in the infected plants at similar titers. With that, young trees infected with T68-1 were markedly repressed in growth, while the growth rate of the trees infected with T36 was comparable to the mock-inoculated trees. Only a small number of differentially expressed genes (DEGs) were identified in the nearly asymptomatic T36-infected trees, whereas almost fourfold the number of DEGs were identified with the growth-restricting T68-1 infection. DEGs were validated using quantitative reverse transcription-PCR. While T36 did not induce many noteworthy changes, T68-1 altered the expression of numerous host mRNAs encoding proteins within significant biological pathways, including immunity and stress response proteins, papain-like cysteine proteases (PLCPs), cell-wall modifying enzymes, vascular development proteins and others. The transcriptomic alterations in the T68-1-infected trees, in particular, the strong and persistent increase in the expression levels of PLCPs, appear to contribute to the observed stem growth repression. On the other hand, analysis of the viral small interfering RNAs revealed that the host RNA silencing-based response to the infection by T36 and that by T68-1 was comparable, and thus, the induction of this antiviral mechanism may not contribute to the difference in the observed symptoms. The DEGs identified in this study promote our understanding of the underlying mechanisms of the yet unexplained growth repression induced by severe CTV isolates in sweet orange trees.
Evaluation of saliva and nasopharyngeal swab sampling for genomic detection of SARS-CoV-2 in children accessing a pediatric emergency department during the second pandemic wave
Authors: Diani Erica , Silvagni Davide , Lotti Virginia , Lagni Anna , Baggio Laura , Medaina Nicoletta , Biban Paolo , Gibellini Davide
Published: April 2023

SARS-CoV-2 infection is mainly detected by multiplex real-time RT-PCR from upper respiratory specimens, which is considered the gold-standard technique for SARS-CoV-2 infection diagnosis. A nasopharyngeal (NP) swab represents the clinical sample of choice, but NP swabbing can be uncomfortable to the patients, especially for pediatric-age participants, requires trained healthcare personnel, and may generate an aerosol, increasing the intrinsic exposure risk of healthcare workers. The objective of this study was to compare paired NP and saliva samples (SS) collected from pediatric patients to evaluate whether the saliva collection procedure may be considered a valuable alternative to the classical NP swab (NPS) sampling in children. In this study, we describe a SARS-CoV-2 multiplex real-time RT-PCR protocol for SS, comparing the results with the paired NPS specimens from 256 pediatric patients (mean age 4.24 ± 4.40 years) admitted to the hospital emergency room of Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, and randomly enrolled between September 2020 and December 2020. The saliva sampling demonstrated consistent results when compared to NPS use. The SARS-CoV-2 genome was detected in 16 out of 256 (6.25%) NP samples, among which 13 (5.07%) were positive even when paired SS were analyzed. Moreover, SARS-CoV-2-negative NPS and SS were consistent, and the overall concordances between NPS and SS were detected in 253 out of 256 samples (98.83%). Our results suggest that saliva samples may be considered a valuable alternative to NPS for SARS-CoV-2 direct diagnosis with multiplex real-time RT-PCR in pediatric patients.
Mammals’ sperm microbiome: current knowledge, challenges, and perspectives on metagenomics of seminal samples
Authors: Contreras María José , Núñez-Montero Kattia , Bruna Pablo , Zárate Ana , Pezo Felipe , García Matías , Leal Karla , Barrientos Leticia
Published: April 2023

Bacterial growth is highly detrimental to sperm quality and functionality. However, during the last few years, using sequencing techniques with a metagenomic approach, it has been possible to deepen the study of bacteria-sperm relationships and describe non-culturable species and synergistic and antagonistic relationships between the different species in mammalian animals. We compile the recent metagenomics studies performed on mammalian semen samples and provide updated evidence to understand the importance of the microbial communities in the results of sperm quality and sperm functionality of males, looking for future perspectives on how these technologies can collaborate in the development of andrological knowledge.
Genetic diversity and antimicrobial resistance profiles of Staphylococcus pseudintermedius associated with skin and soft-tissue infections in companion animals in Lisbon, Portugal
Authors: Morais Catarina , Costa Sofia Santos , Leal Marta , Ramos Bárbara , Andrade Mariana , Ferreira Carolina , Abrantes Patrícia , Pomba Constança , Couto Isabel
Published: April 2023

Staphylococcus pseudintermedius is the main bacterial pathogen of skin and soft-tissue infections (SSTIs) in companion animals. Antimicrobial resistance in this species is a growing public health concern. This study aims to characterize a collection of S. pseudintermedius causing SSTIs in companion animals, establishing the main clonal lineages and antimicrobial resistance traits. The collection corresponded to all S. pseudintermedius (n = 155) causing SSTIs in companion animals (dogs, cats and one rabbit) collected between 2014 and 2018 at two laboratories in Lisbon, Portugal. Susceptibility patterns were established by disk diffusion for 28 antimicrobials (15 classes). For antimicrobials without clinical breakpoints available, a cut-off value (COWT) was estimated, based on the distribution of the zones of inhibition. The blaZ and mecA genes were screened for the entire collection. Other resistance genes (e.g., erm, tet, aadD, vga(C), dfrA(S1)) were searched only for those isolates showing an intermediate/resistance phenotype. For fluoroquinolone resistance, we determined the chromosomal mutations in the target genes grlA and gyrA. All the isolates were typed by PFGE following SmaI macrorestriction and isolates representative of each PFGE type were further typed by MLST. Forty-eight out of the 155  S. pseudintermedius isolates (31.0%) were methicillin-resistant (mecA+, MRSP). Multidrug-resistant (MDR) phenotypes were detected for 95.8% of the MRSP and 22.4% of the methicillin-susceptible (MSSP) isolates. Of particular concern, only 19 isolates (12.3%) were susceptible to all antimicrobials tested. In total, 43 different antimicrobial resistance profiles were detected, mostly associated with the carriage of blaZ, mecA, erm(B), aph3-IIIa, aacA-aphD, catpC221, tet(M) and dfr(G) genes. The 155 isolates were distributed within 129 PFGE clusters, grouped by MLST in 42 clonal lineages, 25 of which correspond to new sequence types (STs). While ST71 remains the most frequent S. pseudintermedius lineage, other lineages that have been replacing ST71 in other countries were detected, including ST258, described for the first time in Portugal. This study revealed a high frequency of MRSP and MDR profiles among S. pseudintermedius associated with SSTIs in companion animals in our setting. Additionally, several clonal lineages with different resistance profiles were described, evidencing the importance of a correct diagnosis and selection of the therapy.
PHT427 as an effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1
Authors: Li Xiaohui , Wang Qian , Zheng Ji , Guan Yan , Liu Chennan , Han Jiangxue , Liu Sihan , Liu Tianjun , Xiao Chunling , Wang Xiao , Liu Yishuang
Published: April 2023

Introduction

With the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist β-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1.

Methods

We used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-blaNDM–1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays.

Results

PHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 μmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-blaNDM–1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay.

Discussion

This is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.
Effects of Bacillus subtilis or Lentilactobacillus buchneri on aerobic stability, and the microbial community in aerobic exposure of whole plant corn silage
Authors: Yin Hang , Zhao Meirong , Pan Gang , Zhang Hongyu , Yang Rui , Sun Juanjuan , Yu Zhu , Bai Chunsheng , Xue Yanlin
Published: April 2023

This study aimed to evaluate the effects of Bacillus subtilis or Lentilactobacillus buchneri on the fermentation quality, aerobic stability, and bacterial and fungal communities of whole plant corn silage during aerobic exposure. Whole plant corn was harvested at the wax maturity stage, which chopped to a length of approximately 1 cm, and treated with the following: distilled sterile water control, 2.0 × 105 CFU/g of Lentilactobacillus buchneri (LB) or 2.0 × 105 CFU/g of Bacillus subtilis (BS) for 42 days silage. Then, the samples were exposed to air (23–28°C) after opening and sampled at 0, 18 and 60 h, to investigate fermentation quality, bacterial and fungal communities, and aerobic stability. Inoculation with LB or BS increased the pH value, acetic acid, and ammonia nitrogen content of silage (P < 0.05), but it was still far below the threshold of inferior silage, the yield of ethanol was reduced (P < 0.05), and satisfactory fermentation quality was achieved. With the extension of the aerobic exposure time, inoculation with LB or BS prolonged the aerobic stabilization time of silage, attenuated the trend of pH increase during aerobic exposure, and increased the residues of lactic acid and acetic acid. The bacterial and fungal alpha diversity indices gradually declined, and the relative abundance of Basidiomycota and Kazachstania gradually increased. The relative abundance of Weissella and unclassified_f_Enterobacteria was higher and the relative abundance of Kazachstania was lower after inoculation with BS compared to the CK group. According to the correlation analysis, Bacillus and Kazachstania are bacteria and fungi that are more closely related to aerobic spoilage and inoculation with LB or BS could inhibit spoilage. The FUNGuild predictive analysis indicated that the higher relative abundance of fungal parasite-undefined saprotroph in the LB or BS groups at AS2, may account for its good aerobic stability. In conclusion, silage inoculated with LB or BS had better fermentation quality and improved aerobic stability by effectively inhibiting the microorganisms that induce aerobic spoilage.
Discovery and excavation of lichen bioactive natural products
Authors: Ren Meirong , Jiang Shuhua , Wang Yanyan , Pan Xinhua , Pan Feng , Wei Xinli
Published: April 2023

Lichen natural products are a tremendous source of new bioactive chemical entities for drug discovery. The ability to survive in harsh conditions can be directly correlated with the production of some unique lichen metabolites. Despite the potential applications, these unique metabolites have been underutilized by pharmaceutical and agrochemical industries due to their slow growth, low biomass availability, and technical challenges involved in their artificial cultivation. At the same time, DNA sequence data have revealed that the number of encoded biosynthetic gene clusters in a lichen is much higher than in natural products, and the majority of them are silent or poorly expressed. To meet these challenges, the one strain many compounds (OSMAC) strategy, as a comprehensive and powerful tool, has been developed to stimulate the activation of silent or cryptic biosynthetic gene clusters and exploit interesting lichen compounds for industrial applications. Furthermore, the development of molecular network techniques, modern bioinformatics, and genetic tools is opening up a new opportunity for the mining, modification, and production of lichen metabolites, rather than merely using traditional separation and purification techniques to obtain small amounts of chemical compounds. Heterologous expressed lichen-derived biosynthetic gene clusters in a cultivatable host offer a promising means for a sustainable supply of specialized metabolites. In this review, we summarized the known lichen bioactive metabolites and highlighted the application of OSMAC, molecular network, and genome mining-based strategies in lichen-forming fungi for the discovery of new cryptic lichen compounds.
Network analysis of the associations between personality traits, cognitive functioning, and inflammatory markers in elderly individuals without dementia
Authors: Bastelica Thomas , Lespine Louis-Ferdinand , Rouch Isabelle , Tadri Myriam , Dorey Jean-Michel , Strippoli Marie-Pierre F. , d'Amato Thierry , von Gunten Armin , Preisig Martin , Rey Romain
Published: April 2023

Introduction

Lower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia.

Methods

This study utilizes a network analysis approach, a statistical method that allows visualization of the data’s unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test.

Results

Openness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified.

Discussion

In elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively.
Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals
Authors: Tobe Mayuna , Nobukawa Sou , Mizukami Kimiko , Kawaguchi Megumi , Higashima Masato , Tanaka Yuji , Yamanishi Teruya , Takahashi Tetsuya
Published: April 2023

Introduction

Maintaining high cognitive functions is desirable for “wellbeing” in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the “hub” node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals.

Method

To test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score.

Results

We found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network.

Discussion

The hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.
Influence of goals on modular brain network organization during working memory
Authors: Gallen Courtney L. , Hwang Kai , Chen Anthony J.-W. , Jacobs Emily G. , Lee Taraz G. , D’Esposito Mark
Published: April 2023

Introduction

Top-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM.

Methods

Here, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity–a measure of brain sub-network segregation–that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant).

Results

First, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance.

Discussion

These results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM.
C9ORF72 knockdown triggers FTD-like symptoms and cell pathology in mice
Authors: Lopez-Herdoiza Maria-Belen , Bauché Stephanie , Wilmet Baptiste , Le Duigou Caroline , Roussel Delphine , Frah Magali , Béal Jonas , Devely Gabin , Boluda Susana , Frick Petra , Bouteiller Delphine , Dussaud Sébastien , Guillabert Pierre , Dalle Carine , Dumont Magali , Camuzat Agnes , Saracino Dario , Barbier Mathieu , Bruneteau Gaelle , Ravassard Phillippe , Neumann Manuela , Nicole Sophie , Le Ber Isabelle , Brice Alexis , Latouche Morwena
Published: April 2023

The GGGGCC intronic repeat expansion within C9ORF72 is the most common genetic cause of ALS and FTD. This mutation results in toxic gain of function through accumulation of expanded RNA foci and aggregation of abnormally translated dipeptide repeat proteins, as well as loss of function due to impaired transcription of C9ORF72. A number of in vivo and in vitro models of gain and loss of function effects have suggested that both mechanisms synergize to cause the disease. However, the contribution of the loss of function mechanism remains poorly understood. We have generated C9ORF72 knockdown mice to mimic C9-FTD/ALS patients haploinsufficiency and investigate the role of this loss of function in the pathogenesis. We found that decreasing C9ORF72 leads to anomalies of the autophagy/lysosomal pathway, cytoplasmic accumulation of TDP-43 and decreased synaptic density in the cortex. Knockdown mice also developed FTD-like behavioral deficits and mild motor phenotypes at a later stage. These findings show that C9ORF72 partial loss of function contributes to the damaging events leading to C9-FTD/ALS.
Symmetric data-driven fusion of diffusion tensor MRI: Age differences in white matter
Authors: Mendez Colmenares Andrea , Hefner Michelle B. , Calhoun Vince D. , Salerno Elizabeth A. , Fanning Jason , Gothe Neha P. , McAuley Edward , Kramer Arthur F. , Burzynska Agnieszka Z.
Published: April 2023

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20–33, n = 51 and age 60–79, n = 170). Four-way mCCA + jICA yielded one high-stability modality-shared component with co-variant patterns of age differences in RD and AD in the corpus callosum, internal capsule, and prefrontal WM. The mixing coefficients (or loading parameters) showed correlations with processing speed and fluid abilities that were not detected by unimodal analyses. In sum, mCCA + jICA allows data-driven identification of cognitively relevant multimodal components within the WM. The presented method should be further extended to clinical samples and other MR techniques (e.g., myelin water imaging) to test the potential of mCCA+jICA to discriminate between different WM disease etiologies and improve the diagnostic classification of WM diseases.
Secondary hyperperfusion injury following surgical evacuation for acute isolated epidural hematoma with concurrent cerebral herniation
Authors: Huang Wei , Li Jun , Wang Wen-hao , Zhang Yuan , Luo Fei , Hu Lian-Shui , Lin Jun-Ming
Published: April 2023

Objective

Hemispherical cerebral swelling or even encephalocele after head trauma is a common complication and has been well elucidated previously. However, few studies have focused on the secondary brain hemorrhage or edema occurring regionally but not hemispherically in the cerebral parenchyma just underneath the surgically evacuated hematoma during or at a very early stage post-surgery.

Methods

In order to explore the characteristics, hemodynamic mechanisms, and optimized treatment of a novel peri-operative complication in patients with isolated acute epidural hematoma (EDH), clinical data of 157 patients with acute-isolated EDH who underwent surgical intervention were reviewed retrospectively. Risk factors including demographic characteristics, admission Glasgow Coma Score, preoperative hemorrhagic shock, anatomical location, and morphological parameters of epidural hematoma, as well as the extent and duration of cerebral herniation on physical examination and radiographic evaluation were considered.

Results

It suggested that secondary intracerebral hemorrhage or edema was determined in 12 of 157 patients within 6 h after surgical hematoma evacuation. It was featured by remarkable, regional hyperperfusion on the computed tomography (CT) perfusion images and associated with a relatively poor neurological prognosis. In addition to concurrent cerebral herniation, which was found to be a prerequisite for the development of this novel complication, multivariate logistic regression further showed four independent risk factors contributing to this type of secondary hyperperfusion injury: cerebral herniation that lasted longer than 2 h, hematomas that were located in the non-temporal region, hematomas that were thicker than 40 mm, and hematomas occurring in pediatric and elderly patients.

Conclusion

Secondary brain hemorrhage or edema occurring within an early perioperative period of hematoma-evacuation craniotomy for acute-isolated EDH is a rarely described hyperperfusion injury. Because it plays an important prognostic influence on patients’ neurological recovery, optimized treatment should be given to block or reduce the consequent secondary brain injuries.
Design and evaluation of a rodent-specific focal transcranial magnetic stimulation coil with the custom shielding application in rats
Authors: Liu Li , Ding Ming , Wu Junfa , Zhang Yuwen , Guo Shaoqian , Wang Nianhong , Wang He , Yu Kewei , Weng Yuanfeng , Luo Lu , Zhang Jingjun , Zhang Quan , Qiu Kai , Wu Yi , Xiao Xiao , Zhang Qun
Published: April 2023

Repetitive TMS has been used as an alternative treatment for various neurological disorders. However, most TMS mechanism studies in rodents have been based on the whole brain stimulation, the lack of rodent-specific focal TMS coils restricts the proper translation of human TMS protocols to animal models. In this study, we designed a new shielding device, which was made of high magnetic permeability material, to enhance the spatial focus of animal-use TMS coils. With the finite element method, we analyzed the electromagnetic field of the coil with and without the shielding device. Furthermore, to assess the shielding effect in rodents, we compared the c-fos expression, the ALFF and ReHo values in different groups following a 15 min 5 Hz rTMS paradigm. We found that a smaller focality with an identical core stimulation intensity was achieved in the shielding device. The 1 T magnetic field was reduced from 19.1 mm to 13 mm in diameter, and 7.5 to 5.6 mm in depth. However, the core magnetic field over 1.5 T was almost the same. Meanwhile, the area of electric field was reduced from 4.68 cm2 to 4.19 cm2, and 3.8 mm to 2.6 mm in depth. Similar to this biomimetic data, the c-fos expression, the ALFF and ReHo values showed more limited cortex activation with the use of the shielding device. However, compared to the rTMS group without the shielding application, more subcortical regions, like the striatum (CPu), the hippocampus, the thalamus, and the hypothalamus were also activated in the shielding group. This indicated that more deep stimulation may be achieved by the shielding device. Generally, compared with the commercial rodents’ TMS coil (15 mm in diameter), TMS coils with the shielding device achieved a better focality (~6 mm in diameter) by reducing at least 30% of the magnetic and electric field. This shielding device may provide a useful tool for further TMS studies in rodents, especially for more specific brain area stimulation.
Incomplete spectrum QSM using support information
Authors: Fuchs Patrick , Shmueli Karin
Published: April 2023

Introduction

Reconstructing a bounded object from incomplete k-space data is a well posed problem, and it was recently shown that this incomplete spectrum approach can be used to reconstruct undersampled MRI images with similar quality to compressed sensing approaches. Here, we apply this incomplete spectrum approach to the field-to-source inverse problem encountered in quantitative magnetic susceptibility mapping (QSM). The field-to-source problem is an ill-posed problem because of conical regions in frequency space where the dipole kernel is zero or very small, which leads to the kernel's inverse being ill-defined. These “ill-posed” regions typically lead to streaking artifacts in QSM reconstructions. In contrast to compressed sensing, our approach relies on knowledge of the image-space support, more commonly referred to as the mask, of our object as well as the region in k-space with ill-defined values. In the QSM case, this mask is usually available, as it is required for most QSM background field removal and reconstruction methods.

Methods

We tuned the incomplete spectrum method (mask and band-limit) for QSM on a simulated dataset from the most recent QSM challenge and validated the QSM reconstruction results on brain images acquired in five healthy volunteers, comparing incomplete spectrum QSM to current state-of-the art-methods: FANSI, nonlinear dipole inversion, and conventional thresholded k-space division.

Results

Without additional regularization, incomplete spectrum QSM performs slightly better than direct QSM reconstruction methods such as thresholded k-space division (PSNR of 39.9 vs. 39.4 of TKD on a simulated dataset) and provides susceptibility values in key iron-rich regions similar or slightly lower than state-of-the-art algorithms, but did not improve the PSNR in comparison to FANSI or nonlinear dipole inversion. With added (ℓ1-wavelet based) regularization the new approach produces results similar to compressed sensing based reconstructions (at sufficiently high levels of regularization).

Discussion

Incomplete spectrum QSM provides a new approach to handle the “ill-posed” regions in the frequency-space data input to QSM.
Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer’s disease and controls
Authors: Chen Chih-Hao , Khnaijer Mary Klir , Beaudin Andrew E. , McCreary Cheryl R. , Gee Myrlene , Saad Feryal , Frayne Richard , Ismail Zahinoor , Pike G. Bruce , Camicioli Richard , Smith Eric E.
Published: April 2023

Background

Previous reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.

Methods

The study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.

Results

Participants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.

Conclusion

In contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.
A call to leverage a health equity lens to accelerate human neuroscience research
Authors: Rebello Vida , Uban Kristina A.
Published: April 2023

Investigation of health inequities tend to be examined, in human neurosciences, as biological factors at the level of the individual. In actuality, health inequities arise, due largely in part, to deep-seated structural factors. Structural inequality refers to the systemic disadvantage of one social group compared to others with whom they coexist. The term encompasses policy, law, governance, and culture and relates to race, ethnicity, gender or gender identity, class, sexual orientation, and other domains. These structural inequalities include but are not limited to social segregation, the intergenerational effects of colonialism and the consequent distribution of power and privilege. Principles to address inequities influenced by structural factors are increasingly prevalent in a subfield of the neurosciences, i.e., cultural neurosciences. Cultural neuroscience articulates the bidirectional relationship between biology and environmental contextual factors surrounding research participants. However, the operationalization of these principles may not have the intended spillover effect on the majority of human neurosciences: this limitation is the overarching focus of the present piece. Here, we provide our perspective that these principles are missing and very much needed in all human neuroscience subdisciplines to accelerate our understanding of the human brain. Furthermore, we provide an outline of two key tenets of a health equity lens necessary for achieving research equity in human neurosciences: the social determinants of health (SDoH) framework and how to deal with confounders using counterfactual thinking. We argue that these tenets should be prioritized across future human neuroscience research more generally, and doing so is a pathway to further gain an understanding of contextual background intertwined with the human brain, thus improving the rigor and inclusivity of human neuroscience research.
Astaxanthin From Haematococcus pluvialis Prevents High-Fat Diet-Induced Hepatic Steatosis and Oxidative Stress in Mice by Gut-Liver Axis Modulating Properties
Authors: Wang Meng , Xu Wenxin , Yu Jie , Liu Yingying , Ma Haotian , Ji Chunli , Zhang Chunhui , Xue Jinai , Li Runzhi , Cui Hongli
Published: April 2023

Graphical Abstract

Astaxanthin (ATX) preventive effects on lipid metabolic disorders, hepatic steatosis, and oxidative stress in high-fat diet-induced mice.