bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term effect of a short pulse of dietary supplementation with algae on the quality of turbot (Scophthalmus maximus) frozen fillets
Authors: Sáez M. Isabel , Galafat Alba , Vizcaíno Antonio J. , Rodríguez Cristina , Hernández de Rojas Alma , Alarcón F. Javier , Martínez Tomás F.
Published: July 2022

This study raises the question of the potential long-term effects of a feeding pulse with diets containing algal biomass on the quality of frozen turbot (Scophthalmus maximus) fillets. A feeding trial was carried out with this aim, in which juvenile turbot were fed during 60 d with six different experimental diets, two of which were enriched with the macroalgaeUlva rigida(U diets), the other two with a microalgae blend (M diets), plus a non-supplemented control diet (CT), and finally, a commercial aquafeed (COM). Two inclusion levels were considered in algae-enriched diets (50 and 100 g kg-1) so that they were designed as U5 and U10 forU. rigida, and M5 and M10 for microalgae-enriched diets. The duration of the feeding pulse with the functional diets was 60 days, and then, all specimens were fed with a COM diet for a further 150-d period until reaching a body size close to the commercial standard (approximately 750 g). Subsequently, fish were sacrificed; fillets were removed from the pigmented flank and kept at -20 °C for 5 months. Then, fillets were thawed and the muscle proximal composition and fatty acid profile were analyzed, and fillet quality parameters were assessed during a 10-d co\ld storage period at 4°C. The possible deferred effects of algae-enriched diets on fillet quality were compared with a control diet without algae (CT) and with a commercial diet (COM). Roughly, the results obtained indicated that a 60-d administration pulse of algae-enriched diets induced some long-term changes in both the nutritional and organoleptic quality of turbot fillets. In this regard, the algae-enriched aquafeeds improved the muscle antioxidant response throughout the cold storage period, prolonging the shelf life of thawed turbot fillets. In addition, in terms of consumers’ acceptability, this feeding pulse on pre-growing stage of the productive cycle was able to modify the skin and muscle pigmentation of fish of commercial size. Namely, the U10 diet increased the protein content, improved muscle texture, reduced fillet total lipid content, and favored muscle selective retention of n-3 polyunsaturated fatty acids. On the other hand, the strategy based on the early administration of a diet rich in fishmeal (CT) for 60 d, followed by feeding with commercial feed, also affected positively the quality of fillets, with values comparable to U10 specimens. Thus, the results obtained indicate that a two-month feeding pulse with algae-supplemented diets during pre-growing phase may represent a promising strategy to improve the nutritional and organoleptic quality of frozen turbot fillet, as well as to extend their shelf life during the post-thawing cold storage.
Systemic immune effects of anesthetics and their intracellular targets in tumors
Authors: Luan Ting , Li Yi , Sun Lihui , Xu Siqi , Wang Haifeng , Wang Jiansong , Li Chong
Published: July 2022

According to the result released by the World Health Organization (WHO), non-communicable diseases have occupied four of the top 10 current causes for death in the world. Cancer is one of the significant factors that trigger complications and deaths; more than 80% cancer patients require surgical or palliative treatment. In this case, anesthetic treatment is indispensable. Since cancer is a heterogeneous disease, various types of interventions can activate oncogenes or mutate tumor suppressor genes. More and more researchers believe that anesthetics have a certain effect on the long-term recurrence and metastasis of tumors, but it is still controversial whether they promote or inhibit the progression of cancer. On this basis, a series of retrospective or prospective randomized clinical trials have been conducted, but it seems to be difficult to reach a conclusion within 5 years or longer. This article focuses on the effects of anesthetic drugs on immune function and cancer and reviews their latest targets on the tumor cells, in order to provide a theoretical basis for optimizing the selection of anesthetic drugs, exploring therapeutic targets, and improving the prognosis of cancer patients.
IPF Respiratory Symptoms Management — Current Evidence
Authors: Janowiak Piotr , Szymanowska-Narloch Amelia , Siemińska Alicja
Published: July 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic disease of the lungs which is characterized by heavy symptom burden, especially in the last year of life. Despite recently established anti-fibrotic treatment IPF prognosis is one of the worst among interstitial lung diseases. In this review available evidence regarding pharmacological and non-pharmacological management of the main IPF symptoms, dyspnea and cough, is presented.
Altered Lung Microbiome and Metabolome Profile in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease
Authors: Ma Runwei , Cheng Liming , Song Yi , Sun Yi , Gui Wenting , Deng Yao , Xie Chao , Liu Min
Published: July 2022

Backgrounds

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular functional and structural changes, resulting in increased pulmonary vascular resistance and eventually right heart failure and death. Congenital Left-to-Right shunts (LTRS) is one type of congenital heart disease (CHD) and PAH associated with the congenital Left-to-Right shunt (PAH-LTRS) is a severe disease in children. However, changes in the lung microbiome and their potential impact on PAH-LTRS have not been not fully studied. We hypothesized that lung microbiota and their derived metabolites have been disturbed in children with PAH-LTRS, which might contribute to the progression and outcomes of PAH-LTRS.

Methods

In this study, 68 age- and sex-matched children of three different groups (patients with PAH-LTRS cohort, patients with LTRS but have no pathologic features of PAH cohort, and healthy reference cohort) were enrolled in the current study. Bronchoalveolar lavage fluid samples from these participants were conducted for multi-omics analysis, including 16S rRNA sequencing and metabolomic profiling. Data progressing and integration analysis were performed to identify pulmonary microbial and metabolic characteristics of PAH-LTRS in children.

Results

We found that microbial community density was not significantly altered in PAH-LTRS based on α-diversity analysis. Microbial composition analysis indicated phylum of Bacteroidetes was that less abundant while Lactobacillus, Alicycliphilus, and Parapusillimonas were significantly altered and might contribute to PAH in children with LTRS. Moreover, metabolome profiling data showed that metabolites involved in Purine metabolism, Glycerophospholipid metabolism, Galactose metabolism, and Pyrimidine metabolism were also significantly disturbed in the PAH-LTRS cohort. Correlation analysis between microbes and metabolites indicated that alterations in the microbial composition from the lung microbiota could eventually result in the disturbance in certain metabolites, and might finally contribute to the pathology of PAH-LTRS.

Conclusion

Lung microbial density was not significantly altered in patients with PAH-LTRS. Composition analysis results showed that the relative microbiome abundance was different between groups. Metabolome profiling and correlation analysis with microbiota showed that metabolome also altered in children with PAH-LTRS. This study indicated that pulmonary microbes and metabolites disturbed in PAH-LTRS could be potentially effective biomarkers and provides valuable perspectives on clinical diagnosis, treatment, and prognosis of pediatric PAH-LTRS.
Severity of depressive but not anxiety symptoms impacts glucose metabolism among patients with type 2 diabetes in primary care
Authors: Hargittay Csenge , Eöry Ajándék , Márkus Bernadett , Mohos András , Ferenci Tamás , Vörös Krisztián , Rihmer Zoltán , Gonda Xenia , Torzsa Péter
Published: July 2022

Background

Data from primary care regarding the prevalence of symptoms of depression and anxiety, and their effect on glycemic control among people with diabetes is lacking in Hungary. The recently introduced Patient Health Record (PHR) requires family doctors to screen for depressive symptoms.

Objectives

We aimed to investigate the prevalence of depressive and anxiety symptoms among patients with type 2 diabetes in the general practice, and the relationship between these affective disorders and glycated hemoglobin (HbA1c) level.

Methods

We included 338 consecutive patients with type 2 diabetes from six primary care practices in this cross-sectional study. A self-administered questionnaire (patient history, anthropometric, socioeconomic, laboratory parameters), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A) were used.

Results

The mean age of the sample was 64.0 ± 11.5 (years ± SD), 61% of participants were female. The prevalence of depressive symptoms was 21%, mainly moderate/severe symptoms (13%). Anxiety symptoms were more common (35%). We found significant univariate association between the depressive symptoms and HbA1c (p = 0.001), suicide attempt (p < 0.001), anxiety (p < 0.001), micro- and macrovascular complication (p = 0.028 and p < 0.001), education (p = 0.001) and place of residence (p = 0.002). In multivariate analysis, however, only BDI score had significant (p = 0.03191) association with glycemic control.

Conclusion

Among primary care patients with type 2 diabetes, the prevalence of depressive symptoms was less frequent than anxiety symptoms. More severe depressive symptoms were associated with worse glycemic control.
Influence of planting methods and organic amendments on rice yield and bacterial communities in the rhizosphere soil
Authors: Tang Zhiqiang , Zhang Liying , He Na , Liu Zhiqi , Ma Zuobin , Fu Liang , Wang Hui , Wang Changhua , Sui Guomin , Zheng Wenjing
Published: July 2022

A comprehensive understanding of rice cultivation techniques and organic amendments affecting soil quality, enzyme activities and bacterial community structure is crucial. We investigated two planting methods (direct seeding and transplanting) of paddy rice (Oryza sativa) and organic amendments with rice straw and biochar on crop yield and soil biological and physicochemical properties. Rhizosphere bacterial communities at the maturity stage of rice growth were characterized through high-throughput 16S rRNA sequencing. Soil biochemical properties and enzyme activity levels were analyzed. Grain yield of paddy rice with transplanting increased 10.6% more than that with direct seeding. The application of rice straw increased grain yield by 7.1 and 8.2%, more than with biochar and the control, respectively. Compared to biochar and the control, the application of rice straw significantly increased sucrase, cellulase, protease, organic carbon, available phosphorus, nitrate, and ammonium. The application of biochar increased microbial biomass nitrogen and carbon, urease, pH, available nitrogen, and available potassium compared to the application of rice straw and the control. Principal coordinate analysis and dissimilarity distances confirmed significant differences among the microbial communities associated with planting methods and organic amendments. Bacteroidetes, Nitrospirae, Firmicutes, and Gemmatimonadetes abundance increased with rice straw relative to biochar and the control. The biochar addition was associated with significant increases in Chloroflexi, Patescibacteria, Proteobacteria, and Actinobacteria abundance. Pearson’s correlation analyzes showed that Chloroflexi, Bacteroidetes and Nitrospirae abundance was positively correlated with grain yield. The relative abundance of these bacteria in soil may be beneficial for improving grain yield. These results suggest that planting methods and organic amendments impact soil biochemical characteristics, enzyme activity levels, and microbial community composition.
Spatio-Temporal Variation in the Phyllospheric Microbial Biodiversity of Alternaria Alternata-Infected Tobacco Foliage
Authors: Dai Yuan-feng , Wu Xiao-mao , Wang Han-cheng , Li Wen-hong , Cai Liu-ti , Li Ji-xin , Wang Feng , Sehar Shafaque , Shamsi Imran Haider
Published: July 2022

Phyllospheric microbial composition of tobacco (Nicotiana tabacum L.) is contingent upon certain factors, such as the growth stage of the plant, leaf position, and cultivar and its geographical location, which influence, either directly or indirectly, the growth, overall health, and production of the tobacco plant. To better understand the spatiotemporal variation of the community and the divergence of phyllospheric microflora, procured from healthy and diseased tobacco leaves infected by Alternaria alternata, the current study employed microbe culturing, high-throughput technique, and BIOLOG ECO. Microbe culturing resulted in the isolation of 153 culturable fungal isolates belonging to 33 genera and 99 bacterial isolates belonging to 15 genera. High-throughput sequencing revealed that the phyllosphere of tobacco was dominantly colonized by Ascomycota and Proteobacteria, whereas, the most abundant fungal and bacterial genera were Alternaria and Pseudomonas. The relative abundance of Alternaria increased in the upper and middle healthy groups from the first collection time to the third, whereas, the relative abundance of Pseudomonas, Sphingomonas, and Methylobacterium from the same positions increased during gradual leaf aging. Non-metric multi-dimensional scaling (NMDs) showed clustering of fungal communities in healthy samples, while bacterial communities of all diseased and healthy groups were found scattered. FUNGuild analysis, from the first collection stage to the third one in both groups, indicated an increase in the relative abundance of Pathotroph-Saprotroph, Pathotroph-Saprotroph-Symbiotroph, and Pathotroph-Symbiotroph. Inclusive of all samples, as per the PICRUSt analysis, the predominant pathway was metabolism function accounting for 50.03%. The average values of omnilog units (OUs) showed relatively higher utilization rates of carbon sources by the microbial flora of healthy leaves. According to the analysis of genus abundances, leaf growth and leaf position were the important drivers of change in structuring the microbial communities. The current findings revealed the complex ecological dynamics that occur in the phyllospheric microbial communities over the course of a spatiotemporal varying environment with the development of tobacco brown spots, highlighting the importance of community succession.
Unraveling the tripartite interaction of volatile compounds of Streptomyces rochei with grain mold pathogens infecting sorghum
Authors: Sudha A. , Durgadevi D. , Archana S. , Muthukumar A. , Suthin Raj T. , Nakkeeran S. , Poczai Peter , Nasif Omaima , Ansari Mohammad Javed , Sayyed R. Z.
Published: July 2022

Sorghum is a major grain crop used in traditional meals and health drinks, and as an efficient fuel. However, its productivity, value, germination, and usability are affected by grain mold, which is a severe problem in sorghum production systems, which reduces the yield of harvested grains for consumer use. The organic approach to the management of the disease is essential and will increase consumer demand. Bioactive molecules like mVOC (volatile organic compound) identification are used to unravel the molecules responsible for antifungal activity. The Streptomyces rochei strain (ASH) has been reported to be a potential antagonist to many pathogens, with high levels of VOCs. The present study aimed to study the inhibitory effect of S. rochei on sorghum grain mold pathogens using a dual culture technique and via the production of microbial volatile organic compounds (mVOCs). mVOCs inhibited the mycelial growth of Fusarium moniliforme by 63.75 and Curvularia lunata by 68.52%. mVOCs suppressed mycelial growth and inhibited the production of spores by altering the structure of mycelia in tripartite plate assay. About 45 mVOCs were profiled when Streptomyces rochei interacted with these two pathogens. In the present study, several compounds were upregulated or downregulated by S. rochei, including 2-methyl-1-butanol, methanoazulene, and cedrene. S. rochei emitted novel terpenoid compounds with peak areas, such as myrcene (1.14%), cymene (6.41%), and ç-terpinene (7.32%) upon interaction with F. moniliforme and C. lunata. The peak area of some of the compounds, including furan 2-methyl (0.70%), benzene (1.84%), 1-butanol, 2-methyl-(8.25%), and myrcene (1.12)%, was increased during tripartite interaction with F. moniliforme and C. lunata, which resulted in furan 2-methyl (6.60%), benzene (4.43%), butanol, 2-methyl (18.67%), and myrcene (1.14%). These metabolites were implicated in the sesquiterpenoid and alkane biosynthetic pathways and the oxalic acid degradation pathway. The present study shows how S. rochei exhibits hyperparasitism, competition, and antibiosis via mVOCs. In addition to their antimicrobial functions, these metabolites could also enhance plant growth.
Dynamics of Viral Infection and Evolution of SARS-CoV-2 Variants in the Calabria Area of Southern Italy
Authors: De Marco Carmela , Veneziano Claudia , Massacci Alice , Pallocca Matteo , Marascio Nadia , Quirino Angela , Barreca Giorgio Settimo , Giancotti Aida , Gallo Luigia , Lamberti Angelo Giuseppe , Quaresima Barbara , Santamaria Gianluca , Biamonte Flavia , Scicchitano Stefania , Trecarichi Enrico Maria , Russo Alessandro , Torella Daniele , Quattrone Aldo , Torti Carlo , Matera Giovanni , De Filippo Caterina , Costanzo Francesco Saverio , Viglietto Giuseppe
Published: July 2022

In this study, we report on the results of SARS-CoV-2 surveillance performed in an area of Southern Italy for 12 months (from March 2021 to February 2022). To this study, we have sequenced RNA from 609 isolates. We have identified circulating VOCs by Sanger sequencing of the S gene and defined their genotypes by whole-genome NGS sequencing of 157 representative isolates. Our results indicated that B.1 and Alpha were the only circulating lineages in Calabria in March 2021; while Alpha remained the most common variant between April 2021 and May 2021 (90 and 73%, respectively), we observed a concomitant decrease in B.1 cases and appearance of Gamma cases (6 and 21%, respectively); C.36.3 and Delta appeared in June 2021 (6 and 3%, respectively); Delta became dominant in July 2021 while Alpha continued to reduce (46 and 48%, respectively). In August 2021, Delta became the only circulating variant until the end of December 2021. As of January 2022, Omicron emerged and took over Delta (72 and 28%, respectively). No patient carrying Beta, Iota, Mu, or Eta variants was identified in this survey. Among the genomes identified in this study, some were distributed all over Europe (B1_S477N, Alpha_L5F, Delta_T95, Delta_G181V, and Delta_A222V), some were distributed in the majority of Italian regions (B1_S477N, B1_Q675H, Delta_T95I and Delta_A222V), and some were present mainly in Calabria (B1_S477N_T29I, B1_S477N_T29I_E484Q, Alpha_A67S, Alpha_A701S, and Alpha_T724I). Prediction analysis of the effects of mutations on the immune response (i.e., binding to class I MHC and/or recognition of T cells) indicated that T29I in B.1 variant; A701S in Alpha variant; and T19R in Delta variant were predicted to impair binding to class I MHC whereas the mutations A67S identified in Alpha; E484K identified in Gamma; and E156G and ΔF157/R158 identified in Delta were predicted to impair recognition by T cells. In conclusion, we report on the results of SARS-CoV-2 surveillance in Regione Calabria in the period between March 2021 and February 2022, identified variants that were enriched mainly in Calabria, and predicted the effects of identified mutations on host immune response.
The landscape of antimicrobial resistance in the neonatal and multi-host pathogen group B Streptococcus: review from a One Health perspective
Authors: Oliveira Laura M. A. , Simões Leandro C. , Costa Natalia S. , Zadoks Ruth N. , Pinto Tatiana C. A.
Published: July 2022

Group B Streptococcus (GBS) stands out as a major agent of pediatric disease in humans, being responsible for 392,000 invasive disease cases and 91,000 deaths in infants each year across the world. Moreover, GBS, also known as Streptococcus agalactiae, is an important agent of infections in animal hosts, notably cattle and fish. GBS population structure is composed of multiple clades that differ in virulence, antimicrobial resistance (AMR), and niche adaptation; however, there is growing evidence of interspecies transmission, both from evolutionary analysis and from disease investigations. The prevention of GBS infections through vaccination is desirable in humans as well as animals because it reduces the burden of GBS disease and reduces our reliance on antimicrobials, and the risk of adverse reactions or selection for AMR. In this perspective article, we navigate through the landscape of AMR in the pediatric and multi-host pathogen GBS under the One Health perspective and discuss the use of antimicrobials to control GBS disease, the evolution of AMR in the GBS population, and the future perspectives of resistant GBS infections in the post-pandemic era.
β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway
Authors: Hao Meng-Jiao , Chen Pei-Nan , Li Hou-Jin , Wu Feng , Zhang Guang-Yu , Shao Zong-Ze , Liu Xiu-Pian , Ma Wen-Zhe , Xu Jun , Mahmud Taifo , Lan Wen-Jian
Published: July 2022

Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (–)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents.
The cell wall and the response and tolerance to stresses of biotechnological relevance in yeasts
Authors: Ribeiro Ricardo A. , Bourbon-Melo Nuno , Sá-Correia Isabel
Published: July 2022

In industrial settings and processes, yeasts may face multiple adverse environmental conditions. These include exposure to non-optimal temperatures or pH, osmotic stress, and deleterious concentrations of diverse inhibitory compounds. These toxic chemicals may result from the desired accumulation of added-value bio-products, yeast metabolism, or be present or derive from the pre-treatment of feedstocks, as in lignocellulosic biomass hydrolysates. Adaptation and tolerance to industrially relevant stress factors involve highly complex and coordinated molecular mechanisms occurring in the yeast cell with repercussions on the performance and economy of bioprocesses, or on the microbiological stability and conservation of foods, beverages, and other goods. To sense, survive, and adapt to different stresses, yeasts rely on a network of signaling pathways to modulate the global transcriptional response and elicit coordinated changes in the cell. These pathways cooperate and tightly regulate the composition, organization and biophysical properties of the cell wall. The intricacy of the underlying regulatory networks reflects the major role of the cell wall as the first line of defense against a wide range of environmental stresses. However, the involvement of cell wall in the adaptation and tolerance of yeasts to multiple stresses of biotechnological relevance has not received the deserved attention. This article provides an overview of the molecular mechanisms involved in fine-tuning cell wall physicochemical properties during the stress response of Saccharomyces cerevisiae and their implication in stress tolerance. The available information for non-conventional yeast species is also included. These non-Saccharomyces species have recently been on the focus of very active research to better explore or control their biotechnological potential envisaging the transition to a sustainable circular bioeconomy.
Next-generation sequencing and PCR technologies in monitoring the hospital microbiome and its drug resistance
Authors: Cason Carolina , D’Accolti Maria , Soffritti Irene , Mazzacane Sante , Comar Manola , Caselli Elisabetta
Published: July 2022

The hospital environment significantly contributes to the onset of healthcare-associated infections (HAIs), which represent one of the most frequent complications occurring in healthcare facilities worldwide. Moreover, the increased antimicrobial resistance (AMR) characterizing HAI-associated microbes is one of the human health’s main concerns, requiring the characterization of the contaminating microbial population in the hospital environment. The monitoring of surface microbiota in hospitals is generally addressed by microbial cultural isolation. However, this has some important limitations mainly relating to the inability to define the whole drug-resistance profile of the contaminating microbiota and to the long time period required to obtain the results. Hence, there is an urgent need to implement environmental surveillance systems using more effective methods. Molecular approaches, including next-generation sequencing and PCR assays, may be useful and effective tools to monitor microbial contamination, especially the growing AMR of HAI-associated pathogens. Herein, we summarize the results of our recent studies using culture-based and molecular analyses in 12 hospitals for adults and children over a 5-year period, highlighting the advantages and disadvantages of the techniques used.
ObReco-2: Two-step validation of a tool to assess memory deficits using 360° videos
Authors: Bruni Francesca , Mancuso Valentina , Stramba-Badiale Chiara , Greci Luca , Cavallo Marco , Borghesi Francesca , Riva Giuseppe , Cipresso Pietro , Stramba-Badiale Marco , Pedroli Elisa
Published: July 2022

Traditional neuropsychological evaluations are usually carried out using psychometric paper and pencil tests. Nevertheless, there is a continuous discussion concerning their efficacy to capture life-like abilities. The introduction of new technologies, such as Virtual Reality (VR) and 360° spherical photos and videos, has improved the ecological validity of the neuropsychological assessment. The possibility of simulating realistic environments and situations allows clinicians to evaluate patients in realistic activities. Moreover, 360° photos and videos seem to provide higher levels of graphical realism and technical user-friendliness compared to standard VR, regardless of their limitations in terms of interactivity. We developed a novel 360° tool, ObReco-2 (Object Recognition version 2), for the assessment of visual memory which simulates a daily situation in a virtual house. More precisely, patients are asked to memorize some objects that need to be moved for a relocation. After this phase, they are asked to recall them after 15 min and later to recognize them in the same environment. Here we present a first study about the usability of ObReco-2, and a second one exploring its clinical efficacy and updated usability data. We focused on Free Recall and Recognition scores, comparing the performances obtained by the participants in the standard and the 360° test. The preliminary results support the use of 360° technology for enhancing the ecological value of standard memory assessment tests.
Impact of aging on animal models of Parkinson's disease
Authors: Klæstrup Ida Hyllen , Just Mie Kristine , Holm Karina Lassen , Alstrup Aage Kristian Olsen , Romero-Ramos Marina , Borghammer Per , Van Den Berge Nathalie
Published: July 2022

Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.
Enlarged perivascular spaces and white matter hyperintensities in patients with frontotemporal lobar degeneration syndromes
Authors: Wang Ming-Liang , Sun Zheng , Li Wen-Bin , Zou Qiao-Qiao , Li Peng-Yang , Wu Xue , Li Yue-Hua ,   the 4-Repeat Tau Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative
Published: July 2022

Objective

The aim of this study was to investigate the distribution characteristics of enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) and their associations with disease severity across the frontotemporal lobar degeneration (FTLD) syndromes spectrum.

Methods

This study included 73 controls, 39 progressive supranuclear palsy Richardson’s syndrome (PSP-RS), 31 corticobasal syndrome (CBS), 47 behavioral variant frontotemporal dementia (bvFTD), 36 non-fluent variant primary progressive aphasia (nfvPPA), and 50 semantic variant primary progressive aphasia (svPPA). All subjects had brain magnetic resonance imaging (MRI) and neuropsychological tests, including progressive supranuclear palsy rating scale (PSPRS) and FTLD modified clinical dementia rating sum of boxes (FTLD-CDR). EPVS number and grade were rated on MRI in the centrum semiovale (CSO-EPVS), basal ganglia (BG-EPVS), and brain stem (BS-EPVS). Periventricular (PWMH) and deep (DWMH) were also graded on MRI. The distribution characteristics of EPVS and WMH were compared between control and disease groups. Multivariable linear regression analysis was performed to evaluate the association of EPVS and WMH with disease severity.

Results

Compared with control subjects, PSP-RS and CBS had more BS-EPVS; CBS, bvFTD, and nfvPPA had less CSO-EPVS; all disease groups except CBS had higher PWMH (p < 0.05). BS-EPVS was associated with PSPRS in PSP-RS (β = 2.395, 95% CI 0.888–3.901) and CBS (β = 3.115, 95% CI 1.584–4.647). PWMH was associated with FTLD-CDR in bvFTD (β = 1.823, 95% CI 0.752–2.895), nfvPPA (β = 0.971, 95% CI 0.030–1.912), and svPPA (OR: 1.330, 95% CI 0.457–2.204).

Conclusion

BS-EPVS could be a promising indicator of disease severity in PSP-RS and CBS, while PWMH could reflect the severity of bvFTD, nfvPPA, and svPPA.
Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease
Authors: Lai Yongxing , Lin Chunjin , Lin Xing , Wu Lijuan , Zhao Yinan , Lin Fan
Published: July 2022

Introduction

Alzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model.

Methods

Based on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency.

Results

The dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity.

Conclusion

Our study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients.
Neurogenic mechanisms for locomotor-respiratory coordination in mammals
Authors: Juvin Laurent , Colnot Eloïse , Barrière Grégory , Thoby-Brisson Muriel , Morin Didier
Published: July 2022

Central motor rhythm-generating networks controlling different functions are generally considered to operate mostly independently from one another, each controlling the specific behavioral task to which it is assigned. However, under certain physiological circumstances, central pattern generators (CPGs) can exhibit strong uni- or bidirectional interactions that render them closely inter-dependent. One of the best illustrations of such an inter-CPG interaction is the functional relationship that may occur between rhythmic locomotor and respiratory functions. It is well known that in vertebrates, lung ventilatory rates accelerate at the onset of physical exercise in order to satisfy the accompanying rapid increase in metabolism. Part of this acceleration is sustained by a coupling between locomotion and ventilation, which most often results in a periodic drive of the respiratory cycle by the locomotor rhythm. In terrestrial vertebrates, the likely physiological significance of this coordination is that it serves to reduce the mechanical interference between the two motor systems, thereby producing an energetic benefit and ultimately, enabling sustained aerobic activity. Several decades of studies have shown that locomotor-respiratory coupling is present in most species, independent of the mode of locomotion employed. The present article aims to review and discuss mechanisms engaged in shaping locomotor-respiratory coupling (LRC), with an emphasis on the role of sensory feedback inputs, the direct influences between CPG networks themselves, and finally on spinal cellular candidates that are potentially involved in the coupling of these two vital motor functions.
Dynamic balance of a bipedal robot using neural network training with simulated annealing
Authors: Angeles-García Yoqsan , Calvo Hiram , Sossa Humberto , Anzueto-Ríos Álvaro
Published: July 2022

This work proposes using an evolutionary optimization method known as simulated annealing to train artificial neural networks. These neural networks are used to control posture stabilization of a humanoid robot in a simulation. A total of eight multilayer perceptron neural networks are used. Although the control is used mainly for posture stabilization and not displacement, we propose a posture set to achieve this, including right leg lift in sagittal plane and right leg lift in frontal plane. At the beginning, tests are carried out only considering gravitational force and reaction force between the floor and the humanoid; then tests are carried out with two disturbances: tilted ground and adding a mass to the humanoid. We found that using simulated annealing the robot maintains its stability at all times, decreasing the number of epochs needed to converge, and also, showing flexibility and adaptability to disturbances. The way neural networks learn is analyzed; videos of the movements made, and the model for further experimentation are provided.
Impact of Perineuronal Net Removal in the Rat Medial Prefrontal Cortex on Parvalbumin Interneurons After Reinstatement of Cocaine Conditioned Place Preference
Authors: Gonzalez Angela E. , Jorgensen Emily T. , Ramos Jonathan D. , Harkness John H. , Aadland Jake A. , Brown Travis E. , Sorg Barbara A.
Published: July 2022

Parvalbumin (PV)-positive cells are GABAergic fast-spiking interneurons that modulate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) and their output to brain areas associated with learning and memory. The majority of PV cells within the mPFC are surrounded by a specialized extracellular matrix structure called the perineuronal net (PNN). We have shown that removal of PNNs with the enzyme chondroitinase-ABC (Ch-ABC) in the mPFC prevents the consolidation and reconsolidation of cocaine-associated conditioned place preference (CPP) memories. Here we examined the extent to which retrieval of a CPP memory during cocaine-primed reinstatement altered the levels and function of PV neurons and their surrounding PNNs during the reconsolidation period. We further determined the extent to which PNN removal prior to reinstatement altered PV intensity levels and PV cell function. Male Sprague-Dawley rats were trained for cocaine-induced conditioned place preference (CPP) followed by extinction training, microinjection of Ch-ABC in the prelimbic PFC, and cocaine-induced reinstatement. Rats were sacrificed immediately prior to reinstatement or at 2 h, 6 h, or 48 h after reinstatement for immunohistochemistry or 2 h later for electrophysiology. Our findings indicate that PNN removal only partially diminished reinstatement. Cocaine-primed reinstatement produced only minor changes in PNN or PV intensity in vehicle controls. However, after PNN removal, the intensity of remaining PNN-surrounded PV cells was decreased at all times except at 2 h post-reinstatement, at which time cocaine increased PV intensity. Consistent with this, in vehicle controls, PV neurons naturally devoid of PNNs showed a similar pattern to Ch-ABC-treated rats prior to and after cocaine reinstatement, suggesting a protective effect of PNNs on cocaine-induced changes in PV intensity. Using whole-cell patch-clamp, cocaine-primed reinstatement in Ch-ABC-treated rats decreased the number of elicited action potentials but increased excitatory synaptic transmission, which may have been compensatory. These findings suggest that without PNNs, cocaine-induced reinstatement produces rapid changes in PV intensity and PV cell excitability, which may in turn regulate output of the mPFC post-memory retrieval and diminish the maintenance of cocaine memory during reconsolidation.
Efficacy of electroacupuncture with different frequencies in the treatment of chemotherapy-induced peripheral neuropathy: A study protocol for a randomized controlled trial
Authors: Lu Chao , Bao Wenlong , Deng Dehou , Li Rongrong , Li Guangliang , Zou Shanlin , Wang Yan
Published: July 2022

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication in patients with cancer during chemotherapy. It mainly leads to severe numbness of the hands and feet and causes great pain in patients. Electroacupuncture (EA) is considered to be beneficial in improving peripheral neuropathy and relieving numbness of the hands and feet. This trial aims to evaluate the therapeutic effect of different frequencies of EA on CIPN in patients with cancer.

Methods and analysis

This study is a randomized controlled trial. In total, 160 eligible CIPN patients are randomly assigned to the 2 Hz EA group, 100 Hz EA group, 2/100 Hz EA group, and control group in the ratio of 1:1:1:1. All patients in the EA treatment groups receive treatment with EA three times a week for 4 weeks and following up for 4 weeks. The patients in the control group are given Mecobalamin (MeCbl) tablets orally, one tablet at a time, three times a day, for 4 weeks, and following up for 4 weeks. The primary outcome measures are the participant neurotoxicity questionnaire (PNQ) and the peripheral neurotoxicity assessment rating (NCI CTCAE V5.0). Secondary outcomes are the quality of life scale (EORTC QLQ-C30) and the measurement of peripheral nerve conduction velocity (NCV). The results are evaluated at baseline, post-treatment phase, and following up for 4 weeks. All major analyses are based on the intention to treat principle.

Ethics/dissemination

This protocol was approved by the Medical Ethics Committee of the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) on 7 December 2021. The license number is IRB-2021-458. This study provides clinical efficacy data of different frequencies of EA in the treatment of CIPN. The results help to prove whether EA is an effective therapy for CIPN and optimize the frequency of EA for CIPN. The results of this study are shared with health care professionals, the public, and relevant organizations through the publication of manuscripts and conference reports.

Trial registration number

ChiCTR2100054458.
The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage–A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms
Authors: Bründl Elisabeth , Proescholdt Martin , Störr Eva-Maria , Schödel Petra , Bele Sylvia , Zeman Florian , Hohenberger Christoph , Kieninger Martin , Schmidt Nils Ole , Schebesch Karl-Michael
Published: July 2022

Background

The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL.

Methods

Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11–35) and at the FU (t2).

Results

During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2.

Conclusion

Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing.
The relationship between red blood cell distribution width at admission and post-stroke fatigue in the acute phase of acute ischemic stroke
Authors: Peng Meidi , Chen Yupei , Chen Yan , Feng Koulan , Shen Haiyan , Huang Hongtao , Zhao Wenxuan , Zou Hua , Ji Jianan
Published: July 2022

Introduction

Post-stroke fatigue (PSF) is a common complication in the patients with acute ischemic stroke (AIS). This prospective study aimed to investigate the relationship between red blood cell distribution width (RDW) at admission and PSF in the acute phase.

Methods

The AIS patients were enrolled in Nantong Third People's Hospital, consecutively. PSF in the acute phase was scored according to the Fatigue Severity Scale. Levels of RDW were measured at admission. The associations were analyzed using multivariate regression and restricted cubic splines (RCS).

Results

From April 2021 to March 2022, a total of 206 AIS patients (mean age, 69.3 ± 10.7 years; 52.9% men) were recruited. After the adjustment for potential confounding factors, RDW at admission remained the independent associated factor with PSF in the acute phase (OR [odds ratio], 1.635; 95% CI [confidence interval], 1.153–2.318; P = 0.006). The linear dose-response associations of RDW with PSF in the acute phase were found, based on the RCS model (P for non-linearity = 0.372; P for linearity = 0.037). These results remained significant in other models.

Conclusions

RDW at admission could serve as a novel biomarker of PSF in the acute phase of AIS.