bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferritin Light Chain: A Candidate Autoantigen in Immuno-Related Pancytopenia
Authors: Zhang Yang , Hao Shanfeng , Xiao Na , Zhang Yu , Wang Huaquan , Li Lijuan , Fu Rong , Shao Zonghong
Published: April 2022

The characteristic feature of immune-related pancytopenia (IRP) is autoantibody-mediated bone marrow (BM) damage and peripheral blood cytopenia. We found that the potential antigen of IRP was Ferritin light chain (FTL) by SEREX (serological analysis of recombinant cDNA expression libraries) in the previous study. In this study, we tried to explore the antigenic epitopes of FTL and verify its antigenicity in IRP. We found the possible FTL epitope: VNLYLQASYTYLSLG by phage random peptide library. Through ELISPOT, it was found that peptide VNLYLQASYTYLSLG can significantly stimulate the production of interleukin-4 and cannot stimulate the production of interferon-γ, which suggested that the peptide can obviously activate Th2 cells. Peptide–major histocompatibility complex tetramer elicited antigen-specific T cell responses. The expression levels of FTL were significantly increased in the patients with untreated IRP (P < 0.05). In conclusion, we found that FTL is the target antigen for some patients with IRP. The peptide of VNLYLQASYTYLSLG is an epitope of the target antigen. The target antigen is abnormally overexpressed on the membrane of BM cells, especially on the surface of CD34+ BM cells of patients with IRP. In addition, it is related to the severity of disease. These results provide a possible new target for the treatment of IRP in the future.
The SARS-CoV-2 B.1.351 Variant Can Transmit in Rats But Not in Mice
Authors: Zhang Cheng , Cui Huan , Li Entao , Guo Zhendong , Wang Tiecheng , Yan Fang , Liu Lina , Li Yuanguo , Chen Di , Meng Keyin , Li Nan , Qin Chengfeng , Liu Juxiang , Gao Yuwei , Zhang Chunmao
Published: April 2022

Previous studies have shown that B.1.351 and other variants have extended the host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to mice. Sustained transmission is a prerequisite for viral maintenance in a population. However, no evidence of natural transmission of SARS-CoV-2 in wild mice has been documented to date. Here, we evaluated the replication and contact transmission of the B.1.351 variant in mice and rats. The B.1.351 variant could infect and replicate efficiently in the airways of mice and rats. Furthermore, the B.1.351 variant could not be transmitted in BALB/c or C57BL/6 mice but could be transmitted with moderate efficiency in rats by direct contact. Additionally, the B.1.351 variant did not transmit from inoculated Syrian hamsters to BALB/c mice. Moreover, the mouse-adapted SARS-CoV-2 strain C57MA14 did not transmit in mice. In summary, the risk of B.1.351 variant transmission in mice is extremely low, but the transmission risk in rats should not be neglected. We should pay more attention to the potential natural transmission of SARS-CoV-2 variants in rats and their possible spillback to humans.
PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome
Authors: Guo Huidong , Wang Ming , Wang Bixia , Guo Liping , Cheng Yifei , Wang Zhidong , Sun Yu-Qian , Wang Yu , Chang Ying-Jun , Huang Xiao-Jun
Published: April 2022

T cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Here, we found low expression of PRDM1 in T cells from donor and recipients both related to the occurrence of acute graft-versus-host disease (aGVHD). Our systematic multiomics analysis found that the transcription factor PRDM1 acts as a master regulator during inducing human primary T cell hyporesponsiveness. PRDM1-overexpression in primary T cells expanded Treg cell subset and increased the expression level of FOXP3, while decreased expression had the opposite effects. Moreover, the binding motifs of key T cell function regulators, such as FOS, JUN and AP-1, were enriched in PRDM1 binding sites and that PRDM1 altered the chromatin accessibility of these regions. Multiomics analysis showed that PRDM1 directly upregulated T cell inhibitory genes such as KLF2 and KLRD1 and downregulated the T cell activation gene IL2, indicating that PRDM1 could promote a tolerant transcriptional profile. Further analysis showed that PRDM1 upregulated FOXP3 expression level directly by binding to FOXP3 upstream enhancer region and indirectly by upregulating KLF2. These results indicated that PRDM1 is sufficient for inducing human primary T cell hyporesponsiveness by transcriptomic and epigenetic manners.
The Forgotten Azores Current: A Long-Term Perspective
Authors: Frazão Helena C. , Prien Ralf D. , Schulz-Bull Detlef E. , Seidov Dan , Waniek Joanna J.
Published: April 2022

The Atlantic Meridional Overturning Circulation (AMOC) and its surface limb, the Gulf Stream, are in their weakest state since the last millennium. The consequences of this weakening in the Northeast Atlantic are not yet known. We show that the slowdown of the Gulf Stream in the 1960s, 1970s, and after 2000 may have caused a delayed weakening of the Azores Current. Concurrently, the Azores Front associated with the Azores Current migrated northward since the 1970s due to gradual changes in the Atlantic Multidecadal Oscillation and ocean heat content. We argue that the AMOC slowdown is also detectable in the low-energy region of the Northeast Atlantic and that the dynamics of Azores Current tightly connects to that of the dynamics of the Gulf Stream and AMOC on decadal and longer time scales.
Gonad Transcriptome and Whole-Genome DNA Methylation Analyses Reveal Potential Sex Determination/Differentiation Mechanisms of the Deep-Sea Mussel Gigantidas platifrons
Authors: Zhong Zhaoshan , Wang Minxiao , Chen Hao , Wang Hao , Zhang Huan , Zhou Li , Sun Yan , Cao Lei , Lian Chao , Li Mengna , Li Chaolun
Published: April 2022

Gigantidas platifrons is one of the most dominant deep-sea mussels in cold seeps ecosystems in the South China sea. Studies have shown that deep-sea mussels are a gonochoristic species, however, little is known about the molecular mechanisms of sex determination in G. platifrons. In this study, RNA-seq and WGBS methylation analysis were performed on adult G. platifrons gonads to identify potential sex-related genes and generate a comprehensive analysis of sex determination in deep-sea mussels. A total of 5923 genes were identified as differentially expressed between the ovaries and testes, of which 2711 were female-biased and 3212 were male-biased. Among them, 161 genes may participate in the sex determination, and we found that DMRT2 may play an important role in male sex determination, and FOXL2, Wnt7, and β-catenin may have impact on female sex determination. Moreover, common expression patterns were found in majority of the sex-related genes such as FOXL2, β-catenin, and genes in SOX family, suggesting the sex determination mechanisms of mussels in different habitats were conserved. The 5mC levels of transcription start sites (TSS2K) were significantly higher in sex-related genes than other DEGs in both gonads. Positive correlation was observed between sex-related genes expression and methylation in male, however, the effects of the DNA methylation on gene expression were complex in female. In short, we argue that sex determination mechanisms of deep-sea mussel G. platifrons is mainly controlled by genetic, and the methylation may have a regulation role on male sex determination or differentiation.
Modified Surface Composition and Biocompatibility of Core-Shell Nitinol Nanoparticles Fabricated via Laser Ablation of Differently Passivized Targets
Authors: Dahiya Ujjwal Ranjan , Singh Sonu , Garg Chetan Kumar , Rai Aakansha , Kalyanasundaram Dinesh
Published: April 2022

Nitinol is a versatile alloy known for its shape memory effect and thus finds multiple applications in biomedical devices and implants. The biomedical applications of nitinol-based devices are, however, limited because of concerns related to leaching and its associated cytotoxicity. In particular, nitinol nanoparticles (NPs), despite being highly promising for biomedical applications such as nano-actuators and biomolecular delivery agents are not explored, owing to the same concerns. Moreover, nitinol nanoparticles and their biological interactions are not fully characterized, and the available literature on their toxicity portrays a divided picture. Surface passivation of nitinol using multiple methods has been explored in the past to reduce the leaching of nickel in implants while also improving the thrombogenic properties. In this work, we reported the preparation of passivized nitinol NPs by laser ablation of nitinol targets, followed by different surface treatments. The effect of different treatments in reducing nickel leaching and its influence on biocompatibility were studied. The biocompatibility and multi-faceted interaction of nitinol NPs with osteoblast cells and associated toxicity were explored. Homogenous nitinol NPs were found to be generated at 25 W of laser power. Also, surface modification using hydrogen peroxide, anodization, and acid etching was found to be effective in waning the nickel leaching and improving biocompatibility. In view of the observed results of cellular interactions, we discussed the possible routes of cellular toxicity of these NPs. The prospective applications of such passivized NPs in the biomedical field are also discussed in this work.
Synthesis and Reactivities of Conducting Hexathienylbenzene-Co-Poly(3-Hexylthiophene) Star-Branched Copolymer as Donor Material for Organic Photovoltaic Cell
Authors: Ramoroka Morongwa E. , Mdluli Siyabonga B. , John-Denk Vivian S. , Januarie Kaylin C. , Modibane Kwena D. , Nwambaekwe Kelechi C. , Yussuf Sodiq T. , Mokwebo Kefilwe V. , Williams Avril R. , Iwuoha Emmanuel I.
Published: April 2022

The hexathienylbenzene-co-poly(3-hexylthiophene-2,5diyl) (HTB-co-P3HT) conducting polymer was synthesized by oxidative co-polymerization of hexathienylbenzene (HTB) and 3-hexylthiophene using iron chloride (FeCl3) as an oxidant. The effect of chlorobenzene, toluene and chloroform on the optoelectronic characteristics of the polymer was investigated. The study revealed that spectroscopic and electrochemical responses of HTB-co-P3HT are affected by the nature of the solvent. The lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels of HTB-co-P3HT were determined from cyclic voltammetry (CV) and were compared to those of (6,6)-Phenyl C71 butyric acid methyl ester (PC71BM) and it was found that the LUMO energy levels of HTB-co-P3HT in toluene were lower than those for chlorobenzene and chloroform. The electrochemical impedance spectroscopy (EIS) analysis also revealed the thin film of HTB-co-P3HT prepared using toluene as the most conductive. However, the photovoltaic parameters of the HTB-co-P3HT organic photovoltaic cells (OPVs) departed from the favored toluene and noted chlorobenzene as being the advantageous solvent. We obtained a power conversion efficiency (PCE) of 0.48%, fill factor (FF) of 27.84%, current density (JSC) of 4.93 mA.cm−2 and open circuit voltage (VOC) of 0.35 V in chlorobenzene, a PCE of 0.30%, FF of 26.08%, JSC of 5.00 mA.cm−2 and VOC of 0.23 V in chloroform and finally, a PCE of 0.33%, FF of 25.45%, JSC of 5.70 mA.cm−2 and VOC of 0.23 V in toluene.
Comparison Between Magnetic Resonance Imaging and Computed Tomography in the Detection and Volumetric Assessment of Lung Nodules: A Prospective Study
Authors: Darçot Emeline , Jreige Mario , Rotzinger David C. , Gidoin Tuyet Van Stacey , Casutt Alessio , Delacoste Jean , Simons Julien , Long Olivier , Buela Flore , Ledoux Jean-Baptiste , Prior John O. , Lovis Alban , Beigelman-Aubry Catherine
Published: April 2022

Rationale and Objectives

Computed tomography (CT) lung nodule assessment is routinely performed and appears very promising for lung cancer screening. However, the radiation exposure through time remains a concern. With the overall goal of an optimal management of indeterminate lung nodules, the objective of this prospective study was therefore to evaluate the potential of optimized ultra-short echo time (UTE) MRI for lung nodule detection and volumetric assessment.

Materials and Methods

Eight (54.9 ± 13.2 years) patients with at least 1 non-calcified nodule ≥4 mm were included. UTE under high-frequency non-invasive ventilation (UTE-HF-NIV) and in free-breathing at tidal volume (UTE-FB) were investigated along with volumetric interpolated breath-hold examination at full inspiration (VIBE-BH). Three experienced readers assessed the detection rate of nodules ≥4 mm and ≥6 mm, and reported their location, 2D-measurements and solid/subsolid nature. Volumes were measured by two experienced readers. Subsequently, two readers assessed the detection and volume measurements of lung nodules ≥4mm in gold-standard CT images with soft and lung kernel reconstructions. Volumetry was performed with lesion management software (Carestream, Rochester, New York, USA).

Results

UTE-HF-NIV provided the highest detection rate for nodules ≥4 mm (n = 66) and ≥6 mm (n = 32) (35 and 50%, respectively). No dependencies were found between nodule detection and their location in the lung with UTE-HF-NIV (p > 0.4), such a dependency was observed for two readers with VIBE-BH (p = 0.002 and 0.03). Dependencies between the nodule's detection and their size were noticed among readers and techniques (p < 0.02). When comparing nodule volume measurements, an excellent concordance was observed between CT and UTE-HF-NIV, with an overestimation of 13.2% by UTE-HF-NIV, <25%-threshold used for nodule's growth, conversely to VIBE-BH that overestimated the nodule volume by 28.8%.

Conclusion

UTE-HF-NIV is not ready to replace low-dose CT for lung nodule detection, but could be used for follow-up studies, alternating with CT, based on its volumetric accuracy.
Analysis of Pan-Cancer Revealed the Immunological and Prognostic Potential of CBX3 in Human Tumors
Authors: Xu Haitao , Jiang Caihong , Chen Dangui , Wu Youzhi , Lu Jia , Zhong Long , Yao Fusheng
Published: April 2022

Chromobox protein homolog 3 (CBX3) has been recognized as a member of the heterochromatin protein 1 family and participate in transcriptional activation or inhibition, cell differentiation and growth. Despite more and more evidence shows that CBX3 has a critical function in the development of some tumors, no systematic extensive analysis of CBX3 has been reported. Thus, we intended to examine the prognostic significance of CBX3 in 33 tumors and investigate its potential immune function. We employed several bioinformatics methods to explore the potential carcinogenic impact of CBX3 premised on the data sets collected from tumor genome maps, human protein maps, cBioPortal, and genotype tissue expression. The approaches include assessing the link between CBX3 and prognosis of different tumors, immune cell infiltration, micro-satellite instability (MSI), DNA methylation, and tumor mutational burden (TMB). The outcomes illustrated that CBX3 was increasingly expressed in 29 tumors. Moreover, CBX3 exhibited a negative correlation with the prognosis of many tumors. The expression of CBX3 was linked to MSI in 12 tumors and TMB in 16 tumors. In 24 tumors, the expression of CBX3 was linked to DNA methylation. Moreover, the CBX3 expression exhibited a negative relationship with the infiltration level of the majority of immune cells, but showed a positive link to T gamma delta cells, central memory T cells, and T helper cells, especially when invading breast carcinoma, thymic carcinoma, colon carcinoma, cutaneous melanoma, endometrial carcinoma, and lung squamous carcinoma. Our research indicates that CBX3 might be used as a prognostic indicator for different malignant tumors due to its function in tumor genesis as well as tumor immunity.
Severe Disease in Patients With Recent-Onset Psoriatic Arthritis. Prediction Model Based on Machine Learning
Authors: Queiro Rubén , Seoane-Mato Daniel , Laiz Ana , Galindez Agirregoikoa Eva , Montilla Carlos , Park Hye Sang , Pinto Tasende Jose A. , Bethencourt Baute Juan José , Joven Ibáñez Beatriz , Toniolo Elide , Ramírez Julio , Pruenza García-Hinojosa Cristina
Published: April 2022

Objectives

To identify patient- and disease-related characteristics that make it possible to predict higher disease severity in recent-onset PsA.

Methods

We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥ 18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. Severe disease was defined at each visit as fulfillment of at least 1 of the following criteria: need for systemic treatment, Health Assessment Questionnaire (HAQ) > 0.5, polyarthritis. The dataset contained data for the independent variables from the baseline visit and follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a logistic regression model and random forest–type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis.

Results

The sample comprised 158 patients. At the first follow-up visit, 78.2% of the patients who attended the clinic had severe disease. This percentage decreased to 76.4% at the second visit. The variables predicting severe disease were patient global pain, treatment with synthetic DMARDs, clinical form at diagnosis, high CRP, arterial hypertension, and psoriasis affecting the gluteal cleft and/or perianal area. The mean values of the measures of validity of the machine learning algorithms were all ≥ 80%.

Conclusion

Our prediction model of severe disease advocates rigorous control of pain and inflammation, also addressing cardiometabolic comorbidities, in addition to actively searching for hidden psoriasis.
Exposure to Antibacterial Chemicals Is Associated With Altered Composition of Oral Microbiome
Authors: Vindenes Hilde Kristin , Lin Huang , Shigdel Rajesh , Ringel-Kulka Tamar , Real Francisco Gomez , Svanes Cecilie , Peddada Shyamal D. , Bertelsen Randi J.
Published: April 2022

Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18–47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (<25th percentile). High exposure to ethylparaben was associated with a higher abundance of Paracoccus. High urine levels of bisphenol A were associated with a lower abundance of Streptococcus and exposure to another environmental chemical, 2,4-DCP, was associated with a lower abundance of Treponema, Fretibacterium, and Bacteroidales [G-2]. High exposure to antibacterial and environmental chemicals was associated with an altered composition of gingiva bacteria; mostly commensal bacteria in the oral cavity. Our results highlight a need for a better understanding of how antimicrobial chemical exposure influences the human microbiome.
Functional Analysis of the Endopeptidase and Holin From Planktothrix agardhii Cyanophage PaV-LD
Authors: Meng Li-Hui , Ke Fei , Zhang Qi-Ya , Zhao Zhe
Published: April 2022

A cyanophage PaV-LD, previously isolated from harmful filamentous cyanobacteriumPlanktothrix agardhii, was sequenced, and co-expression of its two ORFs in tandem, ORF123 and ORF124, inhibited growth on the model cyanobacteriumSynechocystissp. PCC6803 cells. However, the mechanism of action of ORF123 and ORF124 alone remains to be elucidated. In this study, we aimed to study the individual function of ORF123 or ORF124 from PaV-LD. Our data showed that the ORF123 encoded an endopeptidase, which harbored an M23 family peptidase domain and a transmembrane region. The expression of the endopeptidase inEscherichia colialone revealed that the protein exhibited remarkable bacteriostatic activity, as evidenced by observation of growth inhibition, membrane damage, and leakage of the intracellular enzyme. Similarly, the holin, a membrane-associated protein encoded by the ORF124, showed weak bacteriostatic activity onE. coli. Moreover, deletion mutations indicated that the transmembrane domains of endopeptidase and holin were indispensable for their bacteriostatic activity. Meanwhile, the bacteriostatic functions of endopeptidase and holin on cyanobacteria cells were confirmed by expressing them in the cyanobacteriumSynechocystissp. PCC6803. Collectively, our study revealed the individual role of endopeptidase or holin and their synergistic bacteriolytic effect, which would contribute to a better understanding of the lytic mechanism of cyanophage PaV-LD.
Detection and Characterization of Carbapenemases in Enterobacterales With a New Rapid and Simplified Carbapenemase Detection Method Called rsCDM
Authors: Liao Quanfeng , Yuan Yu , Zhang Weili , Deng Jin , Wu Siying , Liu Ya , Xiao Yuling , Kang Mei
Published: April 2022

Objective

This study aimed to develop a new rapid and simplified carbapenemase detection method (rsCDM) for detection and characterization of carbapenemase with 3-aminophenylboronic acid (APBA), ethylenediaminetetraacetic acid (EDTA), and cloxacillin (CLO) β-lactamase inhibitors.

Methods

A panel of 182 carbapenem-resistant Enterobacterales (CRE) strains with blaKPC (88), blaNDM (60), blaIMP (10), blaVIM (3), blaOXA-181 (5), blaKPC, and blaNDM (7), porin changes in combination with an extended-spectrum β-lactamase (ESBL) (3) or AmpC hyper-production (6) and 43 carbapenem-susceptible Enterobacterales isolates were used to evaluate the performance of rsCDM and EDTA-carbapenem inactivation method (eCIM). Carbapenemase class was determined with specific inhibitors at 4, 6, and 18 h by rsCDM, and the difference between imipenem (IMI) and meropenem (MEM) disks was simultaneously compared.

Results

The sensitivity of rsCDM using IMI was 97.1% at the three time points, with a specificity of 100%, independent of the culture duration. Similar to IPM, MEM disk also showed high sensitivity (97.1%) and specificity (100%) at 6 h. And the sensitivity of eCIM was 95.4% and the specificity was 100%. Based on a decision algorithm, the characterization number of IMI and MEM in KPC-producing isolates was 88 vs. 87, metallo-β-lactamases (MBLs) was 73 vs. 72, KPC and NDM carbapenemase was 7 vs. 7 at 4 h, respectively. After 6 h, the category number changed insignificantly except for isolates with combined AmpC overproduction and porin changes, showing an increase in IMI (6) and MEM (2), and there was no difference in the results between 6 and 18 h for the two tablets. OXA-181-producing strains can’t be distinguished by rsCDM. For eCIM, the characterization number in KPC-, OXA- 181-, and MBLs-producing strains was 88, 5, and 72, but it failed to detect multi-enzyme-producing isolates (KPC and NDM).

Conclusion

rsCDM accurately discriminated carbapenemase within 4 h and could differentiate multi-enzyme (KPC and NDM) and AmpC in conjunction with porin changes strains. Hence, rsCDM represents a rapid, simple, easy readout, and accurate tool that can be used without any specialized equipment.
Retinal Microvascular Changes in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Yeh Tsai-Chu , Kuo Chun-Tung , Chou Yu-Bai
Published: April 2022

Background

The remarkable increase in prevalence and significant morbidity of neurodegenerative diseases pose a tremendous burden for the health care system. Changes in retinal microvasculature metrics associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may provide opportunities for early diagnosis and intervention. However, the role of retinal vascular biomarkers remains controversial. We aim to perform a systematic review, meta-analysis and meta-regression to evaluate the comprehensive retinal microvasculature changes in patients with AD and MCI.

Methods

We conducted a literature search on PubMed, MEDLINE, and EMBASE to identify studies published before May 2021 which assessed the measurements of optical coherence tomography angiography (OCTA) between AD, MCI with healthy control eyes, including foveal avascular zone (FAZ), vessel density (VD) of peripapillary, superficial and deep capillary plexus, and choroidal thickness using a random-effect model. We also performed meta-regression and subgroup analysis and assessed heterogeneity and publication bias to evaluate potential sources of bias.

Results

Compared with control eyes, VD of superficial capillary plexus was significantly lower in AD [standardized mean difference (SMD): −0.48; 95% CI (−0.70 to −0.27); p = 0.04] and MCI eyes [SMD: −0.42; 95% CI (−0.81 to −0.03); p = 0.03], as well as reduced VD of deep capillary plexus [SMD: −1.19; 95% CI (−2.00 to −0.38]; p < 0.001], [SMD: −0.53; 95% CI (−0.85 to −0.22); p < 0.001]. FAZ was significantly enlarged in AD eyes [SMD: 0.54; 95% CI (0.09 to 0.99); p = 0.02]. The meta-regression analysis showed that the OCTA machine type and macular scan size significantly influenced the variation of VD and FAZ between AD and control eyes (p < 0.05).

Conclusion

Our results highlight the potential of OCTA as a biomarker to detect early microvasculature deficits in AD and MCI. Notably, the macular scan size and different OCTA machine type could explain the heterogeneity observed in literatures. This information might be useful for future longitudinal study design to evaluate the role of OCTA in monitoring disease progression and treatment efficacy.
Pathophysiological Mechanisms Underlying Idiopathic Normal Pressure Hydrocephalus: A Review of Recent Insights
Authors: Bonney Phillip A. , Briggs Robert G. , Wu Kevin , Choi Wooseong , Khahera Anadjeet , Ojogho Brandon , Shao Xingfeng , Zhao Zhen , Borzage Matthew , Wang Danny J. J. , Liu Charles , Lee Darrin J.
Published: April 2022

The pathophysiologic mechanisms underpinning idiopathic normal pressure hydrocephalus (iNPH), a clinically diagnosed dementia-causing disorder, continue to be explored. An increasing body of evidence implicates multiple systems in the pathogenesis of this condition, though a unifying causative etiology remains elusive. Increased knowledge of the aberrations involved has shed light on the iNPH phenotype and has helped to guide prognostication for treatment with cerebrospinal fluid diversion. In this review, we highlight the central role of the cerebrovasculature in pathogenesis, from hydrocephalus formation to cerebral blood flow derangements, blood-brain barrier breakdown, and glymphatic pathway dysfunction. We offer potential avenues for increasing our understanding of how this disease occurs.
Beyond Systematic and Unsystematic Responding: Latent Class Mixture Models to Characterize Response Patterns in Discounting Research
Authors: Gilroy Shawn P. , Strickland Justin C. , Naudé Gideon P. , Johnson Matthew W. , Amlung Michael , Reed Derek D.
Published: April 2022

Operant behavioral economic methods are increasingly used in basic research on the efficacy of reinforcers as well as in large-scale applied research (e.g., evaluation of empirical public policy). Various methods and strategies have been put forward to assist discounting researchers in conducting large-scale research and detecting irregular response patterns. Although rule-based approaches are based on well-established behavioral patterns, these methods for screening discounting data make assumptions about decision-making patterns that may not hold in all cases and across different types of choices. Without methods well-suited to the observed data, valid data could be omitted or invalid data could be included in study analyses, which subsequently affects study power, the precision of estimates, and the generality of effects. This review and demonstration explore existing approaches for characterizing discounting and presents a novel, data-driven approach based on Latent Class Analysis. This approach (Latent Class Mixed Modeling) characterizes longitudinal patterns of choice into classes, the goal of which is to classify groups of responders that differ characteristically from the overall sample of discounters. In the absence of responders whose behavior is characteristically distinct from the greater sample, modern approaches such as mixed-effects models are robust to less-systematic data series. This approach is discussed, demonstrated with a publicly available dataset, and reviewed as a potential supplement to existing methods for inspecting and screening discounting data.
Embodied Metarepresentations
Authors: Hinrichs Nicolás , Foradi Maryam , Yousef Tariq , Hartmann Elisa , Triesch Susanne , Kaßel Jan , Pein Johannes
Published: April 2022

Meaning has been established pervasively as a central concept throughout disciplines that were involved in cognitive revolution. Its metaphoric usage comes to be, first and foremost, through the interpreter's constraint: representational relationships and contents are considered to be in the “eye” or mind of the observer and shared properties among observers themselves are knowable through interlinguistic phenomena, such as translation. Despite the instability of meaning in relation to its underdetermination by reference, it can be atertium comparationisor “third comparator” for extended human cognition if gauged through invariants that exist in transfer processes such as translation, as all languages and cultures are rooted in pan-human experience and, thus, share and express species-specific ontology. Meaning, seen as a cognitive competence, does not stop outside of the body but extends, depends, and partners with other agents and the environment. A novel approach for exploring the transfer properties of some constituent items of the original natural semantic metalanguage in English, that is, semantic primitives, is presented: FrameNet's semantic frames, evoked by the primes SEE and FEEL, were extracted from EuroParl, a parallel corpus that allows for the automatic word alignment of items with their synonyms. Large Ontology Multilingual Extraction was used. Afterward, following the Semantic Mirrors Method, a procedure that consists back-translating into source language, a translatological examination of translated and original versions of items was performed. A fully automated pipeline was designed and tested, with the purpose of exploring associated frame shifts and, thus, beginning a research agenda on their alleged universality as linguistic features of translation, which will be complemented with and contrasted against further massive feedback through a citizen science approach, as well as cognitive and neurophysiological examinations. Additionally, an embodied account of frame semantics is proposed.
TAT-HSP27 Peptide Improves Neurologic Deficits via Reducing Apoptosis After Experimental Subarachnoid Hemorrhage
Authors: Zhou Xiao-yan , Sun Jing-yi , Wang Wei-qi , Li Shu-xian , Li Han-xia , Yang Hui-juan , Yang Ming-feng , Yuan Hui , Zhang Zong-yong , Sun Bao-liang , Han Jin-Xiang
Published: April 2022

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765−90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765−90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765−90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.
Current Insights Into Oligodendrocyte Metabolism and Its Power to Sculpt the Myelin Landscape
Authors: Narine Mohanlall , Colognato Holly
Published: April 2022

Once believed to be part of the nervenkitt or “nerve glue” network in the central nervous system (CNS), oligodendroglial cells now have established roles in key neurological functions such as myelination, neuroprotection, and motor learning. More recently, oligodendroglia has become the subject of intense investigations aimed at understanding the contributions of its energetics to CNS physiology and pathology. In this review, we discuss the current understanding of oligodendroglial metabolism in regulating key stages of oligodendroglial development and health, its role in providing energy to neighboring cells such as neurons, as well as how alterations in oligodendroglial bioenergetics contribute to disease states. Importantly, we highlight how certain inputs can regulate oligodendroglial metabolism, including extrinsic and intrinsic mediators of cellular signaling, pharmacological compounds, and even dietary interventions. Lastly, we discuss emerging studies aimed at discovering the therapeutic potential of targeting components within oligodendroglial bioenergetic pathways.
Can Old Animals Reveal New Targets? The Aging and Degenerating Brain as a New Precision Medicine Opportunity for Epilepsy
Authors: del Pozo Aaron , Lehmann Leanne , Knox Kevin M. , Barker-Haliski Melissa
Published: April 2022

Older people represent the fastest growing group with epilepsy diagnosis. For example, cerebrovascular disease may underlie roughly 30–50% of epilepsy in older adults and seizures are also an underrecognized comorbidity of Alzheimer's disease (AD). As a result, up to 10% of nursing home residents may take antiseizure medicines (ASMs). Despite the greater incidence of epilepsy in older individuals and increased risk of comorbid seizures in people with AD, aged animals with seizures are strikingly underrepresented in epilepsy drug discovery practice. Increased integration of aged animals into preclinical epilepsy drug discovery could better inform the potential tolerability and pharmacokinetic interactions in aged individuals as the global population becomes increasingly older. Quite simply, the ASMs on the market today were brought forth based on efficacy in young adult, neurologically intact rodents; preclinical information concerning the efficacy and safety of promising ASMs is not routinely evaluated in aged animals. Integrating aged animals more often into basic epilepsy research may also uncover novel treatments for hyperexcitability. For example, cannabidiol and fenfluramine demonstrated clear efficacy in syndrome-specific pediatric models that led to a paradigm shift in the perceived value of pediatric models for ASM discovery practice; aged rodents with seizures or rodents with aging-related neuropathology represent an untapped resource that could similarly change epilepsy drug discovery. This review, therefore, summarizes how aged rodent models have thus far been used for epilepsy research, what studies have been conducted to assess ASM efficacy in aged rodent seizure and epilepsy models, and lastly to identify remaining gaps to engage aging-related neurological disease models for ASM discovery, which may simultaneously reveal novel mechanisms associated with epilepsy.
Brain–Heart Interaction and the Experience of Flow While Playing a Video Game
Authors: Khoshnoud Shiva , Alvarez Igarzábal Federico , Wittmann Marc
Published: April 2022

The flow state – an experience of complete absorption in an activity – is linked with less self-referential processing and increased arousal. We used the heart-evoked potential (HEP), an index representing brain–heart interaction, as well as indices of peripheral physiology to assess the state of flow in individuals playing a video game. 22 gamers and 21 non-gamers played the video game Thumper for 25 min while their brain and cardiorespiratory signals were simultaneously recorded. The more participants were absorbed in the game, the less they thought about time and the faster time passed subjectively. On the cortical level, the fronto-central HEP amplitude was significantly lower while playing the game compared to resting states before and after the game, reflecting less self-referential processing while playing. This HEP effect corresponded with lower activity during gameplay in brain regions contributing to interoceptive processing. The HEP amplitude predicted the level of absorption in the game. While the HEP amplitude was overall lower during the gaming session than during the resting states, within the gaming session the amplitude of HEP was positively associated with absorption. Since higher absorption was related to higher performance in the game, the higher HEP in more absorbed individuals reflects more efficient brain–heart interaction, which is necessary for efficient game play. On the physiological level, a higher level of flow was associated with increased overall sympathetic activity and less inhibited parasympathetic activity toward the end of the game. These results are building blocks for future neurophysiological assessments of flow.
Comparative Aroma Profile Analysis and Development of a Sensory Aroma Lexicon of Seven Different Varieties of Flammulina velutipes
Authors: Wang Ruijuan , Zhang Yueyan , Lu Huan , Liu Jianyu , Song Chunyan , Xu Zhen , Yang Hui , Shang Xiaodong , Feng Tao
Published: April 2022

Flammulina Velutipes (F. velutipes) is widely planted all over the world and is rich in nutrients, which is of great benefit to the human body. However, the research on the aroma of F. velutipes is relatively rare, which limits the application of F. velutipes in deep processing, resulting in a single product and edible method of F. velutipes. The purpose of this study was to find out the aroma compounds contributing to the sensory properties of F. velutipes to promote the application of different varieties of F. velutipes in deep processing. Aromas of 7 species of F. velutipes were described and evaluated by sensory evaluation experiment. The volatile compounds in seven kinds of F. velutipes were detected by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (GC-MS). A total of 74 volatile compounds were found, including 23 alcohols, 5 aldehydes, 2 phenols, 1 acid, 16 esters, 7 ketones, 1 ether, 13 hydrocarbons, 1 sulfide, 1 acyl compound, and 4 heterocyclic compounds. It was also found that the sensory evaluation results of sample F, C, and E had a high correlation with the content of compound, and the correlation between sample B and sample A was also high. A lexicon for describing aroma attributes of F. velutipes was developed and they could be grouped into categories, such as fruity (apple-like, banana-like, cucumber-like, citrus-like and berry-like), alcoholic (whisky-like, fermented fruit-like), milky (creamy-like), floral (hyacinth-like, phoenix-like, iris-like and mint-like), sulfurous (onion-like), and musty (mud-like). This research will provide a theoretical basis for the future study of F. velutipes aroma and the development and application of F. velutipes products.
The Interaction of Dried Distillers Grains With Solubles (DDGS) Type and Level on Growth Performance, Health, Texture, and Muscle-Related Gene Expression in Grass Carp (Ctenopharyngodon idellus)
Authors: Abouel Azm Fatma Ragab , Kong Fanshuang , Wang Xiaoyu , Zhu Wenhuan , Yu Haojie , Long Xianmei , Tan Qingsong
Published: April 2022

The aim of this study was to estimate the possible synergetic effects of the two levels of dietary dried distillers grains with solubles (DDGS) from different sources (US-imported and native) on the growth, health status, muscle texture, and muscle growth-related gene expression of juvenile grass carp. Four treatments of fish were fed with 4 isonitrogenous diets, namely, native DDGS20, native DDGS30, US-imported DDGS20, and US-imported DDGS30 for 60 days. The US-imported DDGS30 group showed the better growth and feed efficiency. Additionally, we observed a significant increase in hepatopancreatic total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in native DDGS groups. Moreover, raw muscle collagen increases considerably in the US-imported DDGS30 compared with the native DDGS30 group. In comparison with the native DDGS groups, the US-imported DDGS groups showed significantly decrease in all textural properties and fiber density, while increased fiber diameter. Dietary native DDGS inclusion significantly showed the upregulation of myog, myhc, and fgf6a expression in muscle, while the downregulation of the expression of myod and myf5. Overall, US-imported DDGS30 had a beneficial influence on growth via regulating genes involved in myogenesis and hypertrophy, the formation of collagen, but had negative impacts on antioxidant capacity and cooked muscle texture.
Effect of Response Surface Methodology-Optimized Ultrasound-Assisted Pretreatment Extraction on the Composition of Essential Oil Released From Tribute citrus Peels
Authors: Li Guoqiang , Liu Shuxun , Zhou Qingqing , Han Jiarun , Qian Cheng , Li Yongquan , Meng Xia , Gao Xin , Zhou Tao , Li Ping , Gu Qing
Published: April 2022

The traditional hydrodistillation (HD) and ultrasound-assisted pretreatment extraction (UAPE) methods were proposed to obtain essential oil (EO) from Tribute citrus (TC) peels. The Box-Behnken design was employed to optimize the HD and UAPE procedures. Moreover, gas chromatography-mass spectrometry (GC-MS) and electronic nose (E-nose) were applied to identify the discrepancy of the extraction methods. The yield of EO extracted by UAPE (114.02 mg/g) was significantly higher than that by HD (85.67 mg/g) (p < 0.01) undergoing 40 min short time-consuming UPAE. A total of 28 compounds were extracted from the TC peels as terpenes were the predominant components. d-Limonene was the most vital compound in the T. citrus essential oil (TCEO), accounting for 86.38% of the total volatile concentration in HD and 86.75% in UAPE, respectively, followed by α-pinene, sabinene, γ-myrcene, and β-phellandrene. The chart of radar and graphic of the principal component analysis by E-nose displayed no significance, which was similar to the GC-MS results. This study demonstrated that UAPE is an efficient and short time-consuming method for TCEO extraction, which provides a promising method for the separation of EO from aromatic plant materials.
Changes in Phytochemical Profiles and Biological Activity of Olive Leaves Treated by Two Drying Methods
Authors: Zhang Chengcheng , Zhang Jianming , Xin Xiaoting , Zhu Shenlong , Niu Erli , Wu Qinghang , Li Ting , Liu Daqun
Published: April 2022

Olive leaves, which are the most abundant byproducts of the olive industry, offer multiple health benefits. The investigation of the phytochemical profiles and relevant biological activities is an essential step toward transforming these low-value byproducts into value-added ones. This study systematically investigated the phytochemical profiles, antioxidant capacity, and inhibition rates of olive leaves from four cultivars on the α-glucosidase, α-amylase, and angiotensin-converting enzyme (ACE). The leaves were prepared using two common drying methods, namely, hot air-drying and freeze-drying. A total of 33 bioactive compounds were identified in the olive leaves, namely, 19 flavonoids, 2 phenylethanoids, 2 coumarins, 2 hydroxycinnamic acids, 2 iridoids, and 6 triterpenic acids. Quantification of the bioactive compounds revealed high amounts of polyphenols, especially flavonoids [2,027–8,055 mg/kg dry weight (DW)], iridoids (566–22,096 mg/kg DW), and triterpenic acids (13,824–19,056 mg/kg DW) in the olive leaves. The hot air-dried leaves showed significantly (P < 0.05) higher iridoid (oleuropein and secoxyloganin) content than the fresh leaves, while freeze-drying resulted in significantly (P < 0.05) higher flavonoid aglycone and hydroxytyrosol content. Additionally, freeze-drying led to samples with the highest radical scavenging, α-amylase, α-glucosidase, and ACE inhibition abilities. The flavonoid (e.g., quercetin, luteolin, eriodictyol, kaempferol-7-O-glucoside, and luteolin-7-O-glucoside), hydroxytyrosol, and oleanolic acid contents in the olive leaves were positively correlated (P < 0.05) with their bioactive potentials.
Macrominerals and Trace Minerals in Commercial Infant Formulas Marketed in Brazil: Compliance With Established Minimum and Maximum Requirements, Label Statements, and Estimated Daily Intake
Authors: Almeida Cristine Couto , Baião Diego dos Santos , Rodrigues Paloma de Almeida , Saint'Pierre Tatiana Dillenburg , Hauser-Davis Rachel Ann , Leandro Katia Christina , Paschoalin Vania Margaret Flosi , Costa Marion Pereira da , Conte-Junior Carlos Adam
Published: April 2022

Infant formulas are the main nutritional source for infants when breastfeeding is not possible or recommended. The daily need for specific nutrients, such as essential minerals, in early stages of a child's life is high because of rapid infant growth and development, which impose metabolic flux increases on these pathways to support growth, physical activity, and defense against infections. In this context, this research aimed to determine macromineral and trace mineral contents in starting (phase 1) and follow-up (phase 2) infant formulas marketed in Brazil (n = 30) by inductively coupled plasma-mass spectrometry, calculate estimated daily intakes, and compare them to reference values regarding adequate intake and tolerable upper intake levels. The highest concentrations of macrominerals were observed in Ca, K, P, and Na, and trace minerals in Fe, Zn, Mn, and Cu. Certain homogeneity only to trace mineral contents was observed when analyzing inter-batch values from same manufacturers. In general, all phase 1 and phase 2 infant formula brands and batches met or exceeded Fe, Zn, Cu, Mo, and Se contents when compared to maximum limits established by Codex Alimentarius. In addition, Zn contents in eight phase 1 and in four phase 2 infant formulas were above the contents established by the tolerable upper intake level for children aged 0–6 and/or 7–12 months, respectively. These findings highlight the need to expand regular infant formula inspection concerning nutritional quality, as some composition aspects of these foods must be improved to follow international guidelines, since ideal requirements for infant formula composition, quality, and safety interfere in child development and adult health.