bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic virus infection results in CD8 T cell recruitment to the retina in the absence of local virus infection
Authors: Paskeviciute Egle , Chen Mei , Xu Heping , Honoré Bent , Vorum Henrik , Sørensen Torben Lykke , Christensen Jan Pravsgaard , Thomsen Allan Randrup , Nissen Mogens Holst , Steffensen Maria Abildgaard
Published: August 2023

During recent years, evidence has emerged that immune privileged sites such as the CNS and the retina may be more integrated in the systemic response to infection than was previously believed. In line with this, it was recently shown that a systemic acute virus infection leads to infiltration of CD8 T cells in the brains of immunocompetent mice. In this study, we extend these findings to the neurological tissue of the eye, namely the retina. We show that an acute systemic virus infection in mice leads to a transient CD8 T cell infiltration in the retina that is not directed by virus infection inside the retina. CD8 T cells were found throughout the retinal tissue, and had a high expression of CXCR6 and CXCR3, as also reported for tissue residing CD8 T cells in the lung and liver. We also show that the pigment epithelium lining the retina expresses CXCL16 (the ligand for CXCR6) similar to epithelial cells of the lung. Thus, our results suggest that the retina undergoes immune surveillance during a systemic infection, and that this surveillance appears to be directed by mechanisms similar to those described for non-privileged tissues.
The immune checkpoint VISTA is associated with prognosis in patients with malignant uveal melanoma
Authors: Issam Salah Nour el Imane , Marnissi Farida , Lakhdar Abdelhakim , Karkouri Mehdi , ElBelhadji Mohamed , Badou Abdallah
Published: August 2023

Introduction

Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.

Methods

Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.

Results and discussion

Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.
Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters
Authors: Strother Camilla A. , Brewer-Jensen Paul D. , Becker-Dreps Sylvia , Zepeda Omar , May Samantha , Gonzalez Fredman , Reyes Yaoska , McElvany Benjamin D. , Averill April M. , Mallory Michael L. , Montmayeur Anna M. , Costantini Verónica P. , Vinjé Jan , Baric Ralph S. , Bucardo Filemon , Lindesmith Lisa C. , Diehl Sean A.
Published: August 2023

Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb–infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection.
HMGB1: a double-edged sword and therapeutic target in the female reproductive system
Authors: Ren Yu , Zhu Damin , Han Xingxing , Zhang Qiqi , Chen Beili , Zhou Ping , Wei Zhaolian , Zhang Zhiguo , Cao Yunxia , Zou Huijuan
Published: August 2023

HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It is present in the nucleus of eukaryotes and can be actively secreted or passively released by kinds of cells. HMGB1 is important for maintaining DNA structure by binding to DNA and histones, protecting it from damage. It also regulates the interaction between histones and DNA, affecting chromatin packaging, and can influence gene expression by promoting nucleosome sliding. And as a DAMP, HMGB1 binding to RAGE and TLRs activates NF-κB, which triggers the expression of downstream genes like IL-18, IL-1β, and TNF-α. HMGB1 is known to be involved in numerous physiological and pathological processes. Recent studies have demonstrated the significance of HMGB1 as DAMPs in the female reproductive system. These findings have shed light on the potential role of HMGB1 in the pathogenesis of diseases in female reproductive system and the possibilities of HMGB1-targeted therapies for treating them. Such therapies can help reduce inflammation and metabolic dysfunction and alleviate the symptoms of reproductive system diseases. Overall, the identification of HMGB1 as a key player in disease of the female reproductive system represents a significant breakthrough in our understanding of these conditions and presents exciting opportunities for the development of novel therapies.
Initial immune response after exposure to Mycobacterium tuberculosis or to SARS-COV-2: similarities and differences
Authors: Aiello Alessandra , Najafi-Fard Saeid , Goletti Delia
Published: August 2023

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) and Coronavirus disease-2019 (COVID-19), whose etiologic agent is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are currently the two deadliest infectious diseases in humans, which together have caused about more than 11 million deaths worldwide in the past 3 years. TB and COVID-19 share several aspects including the droplet- and aerosol-borne transmissibility, the lungs as primary target, some symptoms, and diagnostic tools. However, these two infectious diseases differ in other aspects as their incubation period, immune cells involved, persistence and the immunopathological response. In this review, we highlight the similarities and differences between TB and COVID-19 focusing on the innate and adaptive immune response induced after the exposure to Mtb and SARS-CoV-2 and the pathological pathways linking the two infections. Moreover, we provide a brief overview of the immune response in case of TB-COVID-19 co-infection highlighting the similarities and differences of each individual infection. A comprehensive understanding of the immune response involved in TB and COVID-19 is of utmost importance for the design of effective therapeutic strategies and vaccines for both diseases.
Allium leafminer (Diptera: Agromyzidae) host preference: implications for developing a trap cropping strategy
Authors: Lai Pin-Chu , Sandhi Ramandeep Kaur , Nault Brian A.
Published: August 2023

Allium leafminer (Phytomyza gymnostomaLoew) is an emerging invasive pest ofAlliumcrops and has been threateningAlliumcrop production in the eastern United States since its introduction in 2015.Phytomyza gymnostomacan cause substantial economic loss in leek crops when late instars tunnel into the lower portion of the plant, which often renders the crop unmarketable. With limited management tools that are cost-effective and practical, especially for leeks produced in organic systems, we examined the attractiveness of otherAlliumcrop species that might be considered in a trap cropping strategy. In 2021 and 2022, controlled environment choice tests and field trials were conducted to evaluate host preference ofP. gymnostomaamongAlliumcrop species including chives, scallion, an onion and scallion hybrid, and leek. We also assessed preference of P. gymnostoma for scallions that varied in size/age. Results from field trials indicated that only chives had more oviposition marks, cumulative numbers of eggs, and a higher density ofP. gymnostomalarvae and pupae than leeks. Larger/older scallions had more oviposition marks and higherP. gymnostomadensities than smaller ones in controlled environment choice tests, but this size/age preference was not evident in field trials. Based on our findings, chives could be considered as a potential trap crop for minimizingP. gymnostomadamage in leek crops.
Characterization of suspended sand concentrations in the Yangtze River Estuary and adjacent waters
Authors: Luan Kuifeng , Li Hui , Pan Yujia , Wang Zhenhua , Xu Hang , Zhu Weidong , Wang Jie , Wan Haixia , You Xinyi
Published: August 2023

Introduction

The study on the distribution characteristics of suspended sediment concentration (SSC) in estuaries is an important subject in the study of estuaries and coasts, which has important theoretical significance and practical value.

Methods

In order to fully understand the characteristics of SSC in the Yangtze River Estuary and its adjacent waters, this paper uses fixed vertical observation data and navigation type large area observation data as data sources to analyze the distribution characteristics of SSC in the Yangtze River Estuary and its adjacent waters under different tidal current states and its vertical profile characteristics. It discusses the impact of tidal current velocity on SSC and the changes of SSC in the Yangtze River Estuary and its adjacent waters from 2018 to 2020. And the applicability of the Rouse and Soulsby formulas in the Yangtze River Estuary and its adjacent waters was verified.

Results

It was found that the Rouse and Soulsby models have high applicability in the study area, and the prediction accuracy based on the Li’s Soulsby model is higher. This study provides effective support for carrying out marine forecasting, analysis and evaluation, and provides theoretical basis for carrying out analysis of the current situation of estuarine mudflat resources and prediction of the evolution trend. It plays an important role in scientific and comprehensive research and management of mudflat resources in Shanghai.

Discussion

However, this study only explored the characteristic patterns of SSC in the Yangtze River Estuary and its adjacent waters based on field observations, but SSC is a more complex water environment parameter that is influenced by a variety of factors. The effects of salinity, temperature and wind speed should be considered in subsequent studies.
Epistemology of ignorance: the contribution of philosophy to the science-policy interface of marine biosecurity
Authors: Schwenkenbecher Anne , Hewitt Chad L. , Heesen Remco , Campbell Marnie L. , Fritsch Oliver , Knight Andrew T. , Nash Erin
Published: August 2023

Marine ecosystems are under increasing pressure from human activity, yet successful management relies on knowledge. The evidence-based policy (EBP) approach has been promoted on the grounds that it provides greater transparency and consistency by relying on ‘high quality’ information. However, EBP also creates epistemic responsibilities. Decision-making where limited or no empirical evidence exists, such as is often the case in marine systems, creates epistemic obligations for new information acquisition. We argue that philosophical approaches can inform the science-policy interface. Using marine biosecurity examples, we specifically examine the epistemic challenges in the acquisition and acceptance of evidence to inform policy, discussing epistemic due care and biases in consideration of evidence.
Biomass accrual benefits of community-based marine protected areas outweigh their operational costs
Authors: Villaseñor-Derbez Juan Carlos , Fulton Stuart , Hernández-Velasco Arturo , Amador-Castro Imelda G.
Published: August 2023

The costs and benefits of customary top-down Marine Protected Areas (MPAs) have been studied at length. But the costs and benefits of community-based MPAs –an increasingly common tool in conservation and fisheries management– remain understudied. Here, we quantify the operational costs of maintaining community-based MPA monitoring programs in nine small-scale fishing communities in Mexico. We then compare these costs to the potential extractive use value of invertebrate and fish biomass contained in the reserves. We find that the annual monitoring costs (median: 1,130 MXN/ha; range: 23-3,561 MXN/ha) represent between 0.3% and 55% of the extractive use value of the biomass contained in the reserves (median: 21.31 thousand MXN/ha; 5.22 - 49/12 thousand MXN/ha). These results suggest that the direct monetary benefits of community-based marine conservation can outweigh the costs of monitoring programs, providing further support for these types of management schemes. While further research should explore other mechanisms that would allow fishers to leverage the non-extractive use value of reserves (e.g., tourism) or the non-use value (i.e. existence value of biodiversity) to sustainably finance their conservation efforts, a stop-gap measure to ensuring long-term monitoring costs are covered might include limited extractive use of resources contained in the reserves.
Influence of seasonal variability on the trophic structure of pelagic communities
Authors: Iglesias Beñat , Louzao Maite , Bachiller Eneko , López-López Lucía , Santos María , Boyra Guillermo , Andonegi Eider , Cotano Unai , Preciado Izaskun
Published: August 2023

Seasonal variations in hydrodynamic conditions play a critical role in prey availability at the base of the food web and thus have implications for trophic interactions at higher trophic levels. Here we use the combination of stomach content analysis (SCA) and stable isotope analysis (SIA) to investigate predator-prey interactions and trophic structure of the pelagic fish community of the Bay of Biscay (BoB) in spring and late summer of 2020 and 2021. We found that trophic guilds were more influenced by intra-specific affinities rather than seasonal variability. Main prey for the pelagic fish comprised a set of species belonging to different trophic positions (TPs), from low TP class Thaliacea (salps) to mid TP Engraulis encrasicolus. Vertically migrating meso- and macrozooplankton (mainly copepods and krill) also played an important role as food source for the pelagic fish community showing high trophic overlap among most of species. No differences were detected between the trophic structure in spring and late summer with fish, squids and chaetognaths at the top TPs, whereas krill, meso-zooplankton and salps had the lowest values. However, the TPs estimated using both SCA and SIA approaches were consistently lower in spring, likely due to higher densities and, thus, low TP prey availability in spring. When analyzing ontogenic changes in TPs with predator’s size, significant and positive relationships were found when TP was estimated using SIA but not when using SCA. Overall, our results reveal new insights into the seasonal trophic dynamics of the pelagic fish community of the BoB.
Transcriptome and digital gene expression analysis reveal immune responses of mantle and visceral mass pearl culturing in Hyriopsis cumingii
Authors: Shen Xiaoya , Chen Yige , Jia Liang , He Wang , Chen Xiaofeng , Chen Yiwen , Xuan Xingrong , Li Jiale , Bai Zhiyi , Li Wenjuan
Published: August 2023

Biomineralization is a widespread phenomenon in marine mollusks and is responsible for the production of shells and pearls. However, the regulatory mechanisms governing the adaptive immune responses in the mollusk mantle and visceral mass during mineralization remain unclear. In this work, we examined the mantle and visceral mass immune responses of Hyriopsis cumingii during pearl culture using high-throughput sequencing techniques. A mantle transcriptome database was established using transcriptome sequencing technology and reference to the major databases. Digital gene expression profiling was used to identify the differentially expressed genes of mantle and visceral mass at different insertion periods. Moreover, quantitative real-time PCR was used to verify the expression of five immune-related genes. Transcriptome sequencing results showed 257,457 unigenes were identified. Digital gene expression profiles showed 1389, 3572, 1888, and 2613 differentially expressed genes (DEGs) in the mantle and visceral mass at 5, 20, 50, and 90 d after insertion, respectively, with the highest number at 20 d and the lowest at 5 d after insertion (q < 0.05). A cluster analysis of the DEGs showed similar clustering and expression features in the mantle to the control group, and at 5, 50 and 90 d, after mantle insertion. The DEGs in the visceral mass showed similar clustering and expression features to the control group and at 5, 20 and 50 d after insertion. We also screened 22 immune-related DEGs in the mantle and visceral mass during the same pearl culture period, including serine/threonine-protein kinase NLK, C-type lectin, and galectin. The greatest number of DEGs was found 90 d after insertion. Compared with the mantle, more immune-related DEGs were down-regulated than up-regulated in the visceral mass during pearl culture, indicating that the immune regulatory mechanisms in the visceral mass and the mantle differ during pearl culture, and that the visceral mass is liable to higher infection and mortality rates. Quantitative real-time PCR results showed that the expression of five immune-related genes was consistent with DGE results. Our findings will further knowledge of the immune systems that are present in the mantle and visceral mass during pearl culture.
How to calculate sample size in animal and human studies
Authors: Zhang Xinlian , Hartmann Phillipp
Published: August 2023

One of the most important statistical analyses when designing animal and human studies is the calculation of the required sample size. In this review, we define central terms in the context of sample size determination, including mean, standard deviation, statistical hypothesis testing, type I/II error, power, direction of effect, effect size, expected attrition, corrected sample size, and allocation ratio. We also provide practical examples of sample size calculations for animal and human studies based on pilot studies, larger studies similar to the proposed study—or if no previous studies are available—estimated magnitudes of the effect size per Cohen and Sawilowsky.
Reviewing the state of biosensors and lab-on-a- chip technologies: opportunities for extreme environments and space exploration
Authors: Cinti Stefano , Singh Sima , Covone Giovanni , Tonietti Luca , Ricciardelli Annarita , Cordone Angelina , Iacono Roberta , Mazzoli Arianna , Moracci Marco , Rotundi Alessandra , Giovannelli Donato
Published: August 2023

The space race is entering a new era of exploration, in which the number of robotic and human missions to various places in our solar system is rapidly increasing. Despite the recent advances in propulsion and life support technologies, there is a growing need to perform analytical measurements and laboratory experiments across diverse domains of science, while keeping low payload requirements. In this context, lab-on-a-chip nanobiosensors appear to be an emerging technology capable of revolutionizing space exploration, given their low footprint, high accuracy, and low payload requirements. To date, only some approaches for monitoring astronaut health in spacecraft environments have been reported. Although non-invasive molecular diagnostics, like lab-on-a-chip technology, are expected to improve the quality of long-term space missions, their application to monitor microbiological and environmental variables is rarely reported, even for analogous extreme environments on Earth. The possibility of evaluating the occurrence of unknown or unexpected species, identifying redox gradients relevant to microbial metabolism, or testing for specific possible biosignatures, will play a key role in the future of space microbiology. In this review, we will examine the current and potential roles of lab-on-a-chip technology in space exploration and in extreme environment investigation, reporting what has been tested so far, and clarifying the direction toward which the newly developed technologies of portable lab-on-a-chip sensors are heading for exploration in extreme environments and in space.
Microbiota is structured by gut regions, life stage, and diet in the Black Soldier Fly (Hermetia illucens)
Authors: Auger Laurence , Deschamps Marie-Hélène , Vandenberg Grant , Derome Nicolas
Published: August 2023

The larvae of the Black Soldier Fly (Hermetia illucens) provide numerous ecological benefits, leading to significant commercial advancements. These benefits include the bioconversion of low-value waste into high-value feed and soil amendments. Understanding how the bacterial and eukaryotic microbiota communities affect host performance becomes vital for the optimization and specialization of industrial-scale rearing. This study investigates H. illucens-associated microbiota taxonomic composition and dynamics across the developmental cycle (eggs, neonates, larvae, prepupae, and imago X0 to second generation X1) when reared on two substrates: (i) plant-based (Housefly Gainesville diet) and (ii) animal-based (poultry hatchery waste). By using the 16S gene amplicon metataxonomic approach, we found that the results revealed that bacterial microbiota inherited from parents reared on a different substrate may have induced dysbiosis in the progeny. Specifically, the interaction networks of individuals reared on hatchery waste showed a high prevalence of negative interactions and low connectivity. Proteobacteria (39–92%), Firmicutes (4–39%), Bacteroidota (1–38%), and Actinobacteria (1–33%). In animal feed-reared individuals, Firmicutes reached the highest relative abundance (10–80%), followed by Proteobacteria (6–55%), Actinobacteria (1–31%), and Bacteroidota (0–22%). The rearing substrate was the main driver of microbiota composition, while the developmental stage influenced only the whole individual's bacterial microbiota composition. Gut regions were associated with distinct bacterial composition and richness, with diversity decreasing along the digestive tract. For the first time, microeukaryotes of the microbiota other than Fungi were investigated using 18S genetic marker amplicon sequencing with novel blocking primers specific to the Black Soldier Fly. Microeukaryotes are a neglected part of multitrophic microbiota communities that can have similar effects on their hosts as bacterial microbiota. Microeukaryotes from seven orders were identified in black soldier flies, including potential pathogens (e.g., Aplicomplexa group). Nucletmycea were the dominant class throughout development, followed by Holozoa and Stramenophiles. The eukaryote microbiota was structured by developmental stages but not by gut regions. Insights from this study are a stepping stone toward the microbiological optimization of black soldier flies for industrial rearing, highlighting how a synthetic microbiota assembly should be tailored to the rearing environment of the larvae at a targeted developmental stage.
Responses of soil microbial communities and enzyme activities under nitrogen addition in fluvo-aquic and black soil of North China
Authors: Ullah Sami , Raza Muhammad Mohsin , Abbas Tanveer , Guan Xian , Zhou Wei , He Ping
Published: August 2023

This research investigates the impact of long-term nitrogen (N) addition on fluvo-aquic and black soils in north China, with a focus on soil microbial communities and enzyme activities. In each site, there were three N fertilization treatments, i.e., control, moderate-N, and high-N. Phospholipid Fatty Acid Analysis was employed to analyze the microbial community composition, and enzyme activities related to N, carbon (C), and phosphorus (P) cycling were assessed. The results showed that increasing N fertilization levels led to higher soil organic carbon (SOC) and total N (TN) concentrations, indicating enhanced nutrient availability. N fertilization reduced soil pH across both soils, with a more pronounced acidification effect observed in the black soil. Across both soils, N addition increased maize yield, but the higher crop yield was attained in moderate-N rate compared with high-N rate. Microbial community composition analysis revealed that N fertilization induced shifts in the relative abundances of specific microbial groups. The black soil exhibited pronounced shifts in the microbial groups compared to the fluvo-aquic soil, i.e., decreased fungal abundance and fungi: bacteria ratio in response to N input. In addition, the application of N fertilizer led to an elevated ratio of gram-positive to gram-negative (GP:GN) bacteria, but this effect was observed only in black soil. N fertilization had an impact on the enzyme activities related to C, N, and P cycling in both soil types, but black soil showed more pronounced changes in enzyme activities. Permutational multivariate analysis of variance indicated that soil types rather than N fertilization mediated the response of the soil microbial community and enzyme activities. Partial least square path modeling demonstrated that soil pH was the only key driver impacting soil microbial groups and enzyme activities in both soils. In conclusion, our findings highlighted that N fertilization exerted more pronounced impacts on soil biochemical properties, microbial community composition, and enzyme activities in black soil furthermore, moderate N rate resulted in higher crop productivity over high N rate.
Improved connectivity and cognition due to cognitive stimulation in Alzheimer’s disease
Authors: Behfar Qumars , Richter Nils , Kural Merve , Clemens Anne , Behfar Stefan Kambiz , Folkerts Ann-Kristin , Fassbender Ronja , Kalbe Elke , Fink Gereon R. , Onur Oezguer A.
Published: August 2023

Background

Due to the increasing prevalence of Alzheimer’s disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise.

Objectives

Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST.

Methods

Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15).

Results

After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus.

Conclusion

Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.
Effects of a 10-week musical instrument training on cognitive function in healthy older adults: implications for desirable tests and period of training
Authors: Wang Xueyan , Soshi Takahiro , Yamashita Masatoshi , Kakihara Marcelo , Tsutsumi Takanobu , Iwasaki Shoko , Sekiyama Kaoru
Published: August 2023

Introduction

Previous studies have shown that musical instrument training programs of 16 or more weeks improve verbal memory (Logical Memory Test delayed recall), processing speed (Digit Symbol Coding Test), and executive function (Trail Making Test Part B) of musically untrained healthy older adults. However, it is unclear whether shorter-period instrument training can yield similar effects. We sought to (1) verify those results and (2) clarify if intervention effects could be detected using other measures such as reaction time.

Methods

Healthy older adults (mean age = 73.28 years) were pseudo-randomly assigned to an untrained control group (n= 30) or an intervention group (n= 30) that received a weekly 10-session musical instrument training program (using melodica). We conducted neuropsychological tests on which intervention effects or association with musical training were reported in previous studies. We newly included two reaction time tasks to assess verbal working memory (Sternberg task) and rhythm entrainment (timing task). Intervention effects were determined using a “group × time” analysis of variance (ANOVA).

Results

The intervention effects were detected on the reaction time in Sternberg task and phonological verbal fluency. Although intervention effects had been reported on Logical Memory test, Digit Symbol Coding Test and Trail Making Test in previous studies with longer training periods, the present study did not show such effects. Instead, the test-retest practice effect, indicated by significant improvement in the control group, was significant on these tests.

Discussion

The present results indicated the usefulness of working memory assessments (Verbal Fluency Test and Sternberg task) in detecting the effects of short-term melodica training in healthy older adults. The practice effect detected on those three tasks may be due to the shorter interval between pre- and post-intervention assessments and may have obscured intervention effects. Additionally, the findings suggested the requirement for an extended interval between pre- and post-tests to capture rigorous intervention effects, although this should be justified by a manipulation of training period.
A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease
Authors: Devi Gayatri
Published: August 2023

Article purpose

The clinical approach to Alzheimer's disease (AD) is challenging, particularly in high-functioning individuals. Accurate diagnosis is crucial, especially given the significant side effects, including brain hemorrhage, of newer monoclonal antibodies approved for treating earlier stages of Alzheimer's. Although early treatment is more effective, early diagnosis is also more difficult. Several clinical mimickers of AD exist either separately, or in conjunction with AD pathology, adding to the diagnostic complexity. To illustrate the clinical decision-making process, this study includes de-identified cases and reviews of the underlying etiology and pathology of Alzheimer's and available therapies to exemplify diagnostic and treatment subtleties.

Problem

The clinical presentation of Alzheimer's is complex and varied. Multiple other primary brain pathologies present with clinical phenotypes that can be difficult to distinguish from AD. Furthermore, Alzheimer's rarely exists in isolation, as almost all patients also show evidence of other primary brain pathologies, including Lewy body disease and argyrophilic grain disease. The phenotype and progression of AD can vary based on the brain regions affected by pathology, the coexistence and severity of other brain pathologies, the presence and severity of systemic comorbidities such as cardiac disease, the common co-occurrence with psychiatric diagnoses, and genetic risk factors. Additionally, symptoms and progression are influenced by an individual's brain reserve and cognitive reserve, as well as the timing of the diagnosis, which depends on the demographics of both the patient and the diagnosing physician, as well as the availability of biomarkers.

Methods

The optimal clinical and biomarker strategy for accurately diagnosing AD, common neuropathologic co-morbidities and mimickers, and available medication and non-medication-based treatments are discussed. Real-life examples of cognitive loss illustrate the diagnostic and treatment decision-making process as well as illustrative treatment responses.

Implications

AD is best considered a syndromic disorder, influenced by a multitude of patient and environmental characteristics. Additionally, AD existing alone is a unicorn, as there are nearly always coexisting other brain pathologies. Accurate diagnosis with biomarkers is essential. Treatment response is affected by the variables involved, and the effective treatment of Alzheimer's disease, as well as its prevention, requires an individualized, precision medicine strategy.
Macroscopic brain gray matter staining: historical protocol overview and neuroanatomy learning applications in second-year medical students
Authors: Villegas-Gomez Gustavo Adolfo , Figueredo Luisa F. , Ramirez A. D. , Quiroga-Padilla Pedro Jose , Rueda-Esteban Roberto
Published: August 2023

Macroscopic staining in anatomical samples of the central nervous system is a technique that has been used for decades to achieve better differentiation of multiple gray matter structures, such as the cortex, basal ganglia, and cerebellar nuclei. Staining methods are based on using the different components of the brain, mainly the lipids present in the white matter. These techniques have been progressively forgotten while computer renderings are increasing; however, as a primary exposure to surgical anatomy, stained brain specimens are considered a helpful tool. We aim to summarize different staining techniques, their principles, and their current applications for neuroanatomy learning purposes. In total, four gray matter staining protocol descriptions (Mulligan's, Roberts's, Alston's, and Prussian Blue) were performed, as well as Likert scale surveys of second-year medical students about their perceptions of the stained sections. The results showed that the different macroscopic stains for brain tissue are based on lipid and reactant interactions, intending to increase the white matter (WM) and gray matter (GM) contrast. The search also showed that most staining protocols would take 2 days to develop. Efficient preservation options include submerging the sections in formaldehyde solutions, formaldehyde-free solutions, ethanol, or applying plastination techniques. Based on the student's perspective, the stained slices seem to be a valuable alternative to facilitate the study and identification of the basal ganglia and their relationships with the white matter (from 51.2 to 72% based on the Likert scale) compared with the non-stained sections. In conclusion, macroscopic staining of brain tissue continues to be a valuable tool for comprehensively studying the brain. Further research is needed to determine the efficacy of stained specimens as teaching tools.
Thrombectomy with and without computed tomography perfusion imaging for large-vessel occlusion stroke in the extended time window: a meta-analysis of randomized clinical trials
Authors: Zhan Zheng , Gu Feng , Ji Yi , Zhang Yu , Ge Yi , Wang Zhong
Published: August 2023

Objective

In recent years, several studies have used computed tomography perfusion (CTP) to assess whether mechanical thrombectomy can be performed in patients with large-vessel occlusion (LVO) stroke in an extended time window. However, it has the disadvantage of being time-consuming and expensive. This study aimed to compare the impact of the CTP group with the non-CTP group [non-contrast CT (NCCT) ± CT angiography (CTA)] on the prognosis of this patient population.

Methods

A search of PubMed, EMBASE, and the Cochrane Library databases was conducted to collect randomized controlled trials (RCTs) comparing the two strategies. Outcome indicators and factors influencing prognosis were summarized by standardized mean differences, ratios, and relative risks with 95% confidence intervals using a random-effects model.

Results

A total of two RCTs were included in the combined analysis. There were no significant differences in the main outcome indicators (modified Rankin Scale score at 90 days, successful postoperative reperfusion rate) or the incidence of adverse events (90-day mortality and symptomatic intracranial hemorrhage) between the NCCT ± CTA and CTP groups. The time from the last puncture appeared to be significantly shorter in the NCCT ± CTA group than in the CTP group (SMD: −0.14; 95% CI: −0.24, −0.04). Among them, age (OR: 0.96; 95% CI: 0.94, 0.98), ASPECTS (OR: 1.18; 95% CI: 1.12, 1.24), NIHSS score (OR: 0.90; 95% CI: 0.89, 0.91), and diabetes (OR: 0.69; 95% CI: 0.54, 0.88) were associated with a 90-day independent functional outcome.

Conclusion

These findings suggest that the choice of NCCT ± CTA (without CTP) for the assessment of mechanical thrombectomy within 6–24 h after LVO in the anterior circulation is not significantly different from CTP; instead, the choice of NCCT ± CTA significantly reduces the time from onset to arterial puncture.
Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome
Authors: Boldrini Vinícius Oliveira , Brito Mariana Rabelo , Quintiliano Raphael Patrício Silva , Scárdua Silva Lucas , Yasuda Clarissa Lin , Cendes Fernando , Farias Alessandro Santos , Damasceno Alfredo
Published: August 2023

Background

The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.

Case presentation

Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells.

Conclusions

Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.
Cognitive impairment in essential tremor assessed by the cerebellar cognitive affective syndrome scale
Authors: Destrebecq Virginie , Naeije Gilles
Published: August 2023

Background

Essential tremor (ET) is a movement disorder characterized by cerebellar neurodegenerative changes. ET is also associated with non-motor symptoms including cognitive impairment. The neuropsychologic profile of a patient with ET could relate to cerebellar cognitive affective syndrome (CCAS).

Objective

This study aimed to assess the prevalence of cognitive impairment in patients with ET and identify whether the cognitive impairment in ET corresponds to a CCAS.

Methods

Cognitive functions were evaluated with the CCAS-Scale (CCAS-S) in 20 patients with ET and 20 controls matched for age, sex, and level of education. The results of the CCAS-S were compared between patients and controls. The underlying determinant of CCAS inpatients with ET was identified through the correlation between the results of the CCAS-S and age at onset of symptoms, disease duration, and the Essential Tremor Rating Assessment Scale (TETRAS).

Results

On a group level, ET patients performed significantly worse than matched controls. In total, 13 individuals with ET had a definite CCAS (CCAS-S failed items ≥ 3). ASO and TETRAS scores significantly correlated with CCAS-S performances in ET patients.

Conclusion

CCAS is highly prevalent in patients with ET which supports the cerebellar pathophysiology of associated cognitive impairment and supports a more systematic use of the CCAS-S to cognitively assessed patients with ET.
A review of experimental task design in psychophysical eye tracking research
Authors: Lima Diego da Silva , Ventura Dora Fix
Published: August 2023

While eye tracking is a technique commonly used in the experimental study of higher-level perceptual processes such as visual search, working memory, reading, and scene exploration, its use for the quantification of basic visual functions (visual acuity, contrast sensitivity, color vision, motion detection) is less explored. The use of eye movement features as dependent variables in a psychophysical investigation can serve multiple roles. They can be central in studies with neurological patients or infants that cannot comply with verbal instructions, understand task demands, and/or emit manual responses. The technique may also serve a complementary role, determining the conditions under which a manual or verbal response is given, such as stimulus position in the visual field, or it can afford the analysis of new dependent variables, such as the time interval between oculomotor and manual responses. Our objective is to review the literature that applied the eye tracking technique to psychophysical problems. The two questions our review raises are: can eye movements (reflex or voluntary) be an objective index of stimulus detection in psychophysical tasks? If so, under what conditions, and how does it compare with traditional paradigms requiring manual responses? Our (non-systematic) methodological review selected studies that used video-oculography as the technique of choice and had a basic visual function as their primary object of investigation. Studies satisfying those criteria were then categorized into four broad classes reflecting their main research interest: (1) stimulus detection and threshold estimation, (2) the effects of stimulus properties on fixational eye movements, (3) the effects of eye movements on perception, and (4) visual field assessment. The reviewed studies support the idea that eye tracking is a valuable technique for the study of basic perceptual processes. We discuss methodological characteristics within each of the proposed classification area, with the objective of informing future task design.
Longitudinal early epigenomic signatures inform molecular paths of therapy response and remission in depressed patients
Authors: Van Assche Evelien , Hohoff Christa , Zang Johannes , Knight Matthew J. , Baune Bernhard T.
Published: August 2023

Introduction

The etiology of major depressive disorder (MDD) involves the interaction between genes and environment, including treatment. Early molecular signatures for treatment response and remission are relevant in a context of personalized medicine and stratification and reduce the time-to-decision. Therefore, we focused the analyses on patients that responded or remitted following a cognitive intervention of 8 weeks.

Methods

We used data from a randomized controlled trial (RCT) with MDD patients (N = 112) receiving a cognitive intervention. At baseline and 8 weeks, blood for DNA methylation (Illumina Infinium MethylationEPIC 850k BeadChip) was collected, as well as MADRS. First, responders (N = 24; MADRS-reduction of at least 50%) were compared with non-responders (N = 60). Then, we performed longitudinal within-individual analyses, for response (N = 21) and for remission (N = 18; MADRS smaller or equal to 9 and higher than 9 at baseline), respectively, as well as patients with no change in MADRS over time. At 8 weeks the sample comprised 84 individuals; 73 patients had DNA methylation for both time-points. The RnBeads package (R) was used for data cleaning, quality control, and differential DNA-methylation (limma). The within-individual paired longitudinal analysis was performed using Welch’s t-test. Subsequently gene-ontology (GO) pathway analyses were performed.

Results

No CpG was genome-wide significant CpG (p < 5 × 10–8). The most significant CpG in the differential methylation analysis comparing response versus non-response was in the IQSEC1 gene (cg01601845; p = 1.53 × 10–6), linked to neurotransmission. The most significant GO-terms were linked to telomeres. The longitudinal response analysis returned 67 GO pathways with a p < 0.05. Two of the three most significant pathways were linked to sodium transport. The analysis for remission returned 46 GO terms with a p-value smaller than 0.05 with pathways linked to phosphatase regulation and synaptic functioning. The analysis with stable patients returned mainly GO-terms linked to basic cellular processes.

Discussion

Our result suggest that DNA methylation can be suitable to capture early signs of treatment response and remission following a cognitive intervention in depression. Despite not being genome-wide significant, the CpG locations and GO-terms returned by our analysis comparing patients with and without cognitive impairment, are in line with prior knowledge on pathways and genes relevant for depression treatment and cognition. Our analysis provides new hypotheses for the understanding of how treatment for depression can act through DNA methylation and induce response and remission.