bluuebunny/crossref_metadata_2025 huggingface dataset:
Organogenesis of Ileal Peyer's Patches Is Initiated Prenatally and Accelerated Postnatally With Comprehensive Proliferation of B Cells in Pigs
Authors: Furukawa Mutsumi , Ito Shun , Suzuki Shunichi , Fuchimoto Daiichiro , Onishi Akira , Niimi Kanae , Usami Katsuki , Wu Guoyao , Bazer Fuller W. , Ogasawara Kouetsu , Watanabe Kouichi , Aso Hisashi , Nochi Tomonori
Published: December 2020

Morphogenesis and differentiation of organs is required for subsequent functional maturation. The morphological features of Peyer's patches vary among species. In pigs, they develop extensively in the ileum as ileal Peyer's patches (IPPs). However, the role of IPPs in the porcine immune system remains to be elucidated because of a lack of complete understanding of IPP organogenesis. Results of the present study revealed that development of porcine IPPs is initiated prenatally between embryonic days 76 and 91. The process of IPP organogenesis is concomitant with increased transcriptional patterns of CXCL13 and CCL19. IPPs undergo further development postnatally by forming central, marginal, and subepithelial zones. Importantly, a large number of proliferating B cells and apoptotic cells are found in porcine IPPs postnatally, but not prenatally. The expression level of IgM in proliferating B cells depends on the zone in which distinct B cells are separately localized after birth. Specifically, IgM+cells are predominantly found in the central zone, whereas IgM-/lowcells are abundant in the marginal zone. Importantly, the cellular feature of IPPs differs from that of mesenteric lymph nodes (MLNs) where such distinct zones are not formed both prenatally and postnatally. Our findings suggest that IPPs (not MLNs) in postnatal pigs are involved in complementing functions of the primary lymphoid tissue that promotes the differentiation and maturation of B cells.
Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience
Authors: Littera Roberto , Campagna Marcello , Deidda Silvia , Angioni Goffredo , Cipri Selene , Melis Maurizio , Firinu Davide , Santus Simonetta , Lai Alberto , Porcella Rita , Lai Sara , Rassu Stefania , Scioscia Rosetta , Meloni Federico , Schirru Daniele , Cordeddu William , Kowalik Marta Anna , Serra Maria , Ragatzu Paola , Carta Mauro Giovanni , Del Giacco Stefano , Restivo Angelo , Deidda Simona , Orrù Sandro , Palimodde Antonella , Perra Roberto , Orrù Germano , Conti Maria , Balestrieri Cinzia , Serra Giancarlo , Onali Simona , Marongiu Francesco , Perra Andrea , Chessa Luchino
Published: December 2020

Aim

SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.

Method and Materials

We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.

Results

Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].

Conclusion

The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
A Postural Assessment Utilizing Machine Learning Prospectively Identifies Older Adults at a High Risk of Falling
Authors: Forth Katharine E. , Wirfel Kelly L. , Adams Sasha D. , Rianon Nahid J. , Lieberman Aiden Erez , Madansingh Stefan I.
Published: December 2020

Introduction: Falls are the leading cause of accidental death in older adults. Each year, 28.7% of US adults over 65 years experience a fall resulting in over 300,000 hip fractures and $50 billion in medical costs. Annual fall risk assessments have become part of the standard care plan for older adults. However, the effectiveness of these assessments in identifying at-risk individuals remains limited. This study characterizes the performance of a commercially available, automated method, for assessing fall risk using machine learning.

Methods: Participants (N = 209) were recruited from eight senior living facilities and from adults living in the community (five local community centers in Houston, TX) to participate in a 12-month retrospective and a 12-month prospective cohort study. Upon enrollment, each participant stood for 60 s, with eyes open, on a commercial balance measurement platform which uses force-plate technology to capture center-of-pressure (60 Hz frequency). Linear and non-linear components of the center-of-pressure were analyzed using a machine-learning algorithm resulting in a postural stability (PS) score (range 1–10). A higher PS score indicated greater stability. Participants were contacted monthly for a year to track fall events and determine fall circumstances. Reliability among repeated trials, past and future fall prediction, as well as survival analyses, were assessed.

Results: Measurement reliability was found to be high (ICC(2,1) [95% CI]=0.78 [0.76–0.81]). Individuals in the high-risk range (1-3) were three times more likely to fall within a year than those in low-risk (7–10). They were also an order of magnitude more likely (12/104 vs. 1/105) to suffer a spontaneous fall i.e., a fall where no cause was self-reported. Survival analyses suggests a fall event within 9 months (median) for high risk individuals.

Conclusions: We demonstrate that an easy-to-use, automated method for assessing fall risk can reliably predict falls a year in advance. Objective identification of at-risk patients will aid clinicians in providing individualized fall prevention care.
The Impact of the COVID-19 Pandemic on Incidences of Atrial Fibrillation and Electrical Cardioversion at a Tertiary Care Emergency Department: An Inter- and Intra-year Analysis
Authors: Schnaubelt Sebastian , Domanovits Hans , Niederdoeckl Jan , Schuetz Nikola , Cacioppo Filippo , Oppenauer Julia , Spiel Alexander O. , Laggner Anton N.
Published: December 2020

Background: National authorities have introduced measures as lockdowns against spreading of COVID-19 and documented incidences of multiple non-COVID-19 diseases have dropped. Yet, data on workload dynamics concerning atrial fibrillation and electrical cardioversion whilst a national lockdown are scarce and may assist in future planning.

Methods: Documented cases of atrial fibrillation and respective electrical cardioversion episodes at the Emergency Department of the Medical University of Vienna, Austria, from 01/01/2020 to 31/05/2020 were assessed. As reference groups, those incidences were calculated for the years 2017, 2018, and 2019. Inter- and intra-year analyses were conducted through Chi-square test and Poisson regression.

Results: A total of 2,310 atrial fibrillation-, and 511 electrical cardioversion episodes were included. We found no significant incidence differences in inter-year analyses of the time periods from January to May, or of the weeks pre- and post the national lockdown due to the COVID-19 pandemic. However, the intra-year analysis of the year 2020 showed a trend toward decreased atrial fibrillation incidences (rate-ratio 0.982, CI 0.964–1.001, p = 0.060), and significantly increased electrical cardioversion incidences in the post-lockdown period (rate ratio 1.051, CI 1.008–10.96, p = 0.020).

Conclusion: The decreased atrial fibrillation incidences are in line with international data. However, an increased demand of electrical cardioversions during the lockdown period was observed. A higher threshold to seek medical attention may produce a selected group with potentially more severe clinical courses. In addition, lifestyle modifications during isolation and a higher stress level may promote atrial fibrillation episodes to be refractory to other therapeutic approaches than electrical cardioversion.
Gene Expression Analysis of Three Putative Copper-Transporting ATPases in Copper-Tolerant Fibroporia radiculosa
Authors: Ohno Katie M. , Bishell Amy B. , Stanosz Glen R.
Published: December 2020

Copper tolerance of brown-rot basidiomycete decay fungi can lessen the efficacy of copper-containing wood preservatives for wood products in-service. The purpose of this study was to evaluate wood mass loss and differential expression of three genes that have putative annotations for copper-transporting ATPase pumps (FIBRA_00974, FIBRA_04716, and FIBRA_01430). Untreated southern pine (SP) and SP treated with three concentrations of ammoniacal copper citrate (CC, 0.6, 1.2, and 2.4%) were exposed to two copper-tolerant Fibroporia radiculosa isolates (FP-90848-T and L-9414-SP) and copper-sensitive Gloeophyllum trabeum isolate (MAD 617) in a 4-week-long standard decay test (AWPA E10-19). Decay of copper-treated wood was inhibited by G. trabeum (p = 0.001); however, there was no inhibition of decay with increasing copper concentrations by both F. radiculosa isolates. Initially, G. trabeum and one F. radiculosa isolate (L-9414-SP) highly upregulated FIBRA_00974 and FIBRA_04716 on copper-treated wood at week 1 (p = 0.005), but subsequent expression was either not detected or was similar to expression on untreated wood (p = 0.471). The other F. radiculosa isolate (FP-90848-T) downregulated FIBRA_00974 (p = 0.301) and FIBRA_04716 (p = 0.004) on copper-treated wood. FIBRA_01430 expression by G. trabeum was not detected, but was upregulated by both F. radiculosa FP-90848-T (p = 0.481) and L-9414-SP (p = 0.392). Results from this study suggest that all three test fungi utilized different mechanisms when decaying copper-treated wood. Additionally, results from this study do not provide support for the involvement of these putative gene annotations for copper-transporting ATPase pumps in the mechanism of copper-tolerance.
A Comparative Evaluation of Tools to Predict Metabolite Profiles From Microbiome Sequencing Data
Authors: Yin Xiaochen , Altman Tomer , Rutherford Erica , West Kiana A. , Wu Yonggan , Choi Jinlyung , Beck Paul L. , Kaplan Gilaad G. , Dabbagh Karim , DeSantis Todd Z. , Iwai Shoko
Published: December 2020

Metabolomic analyses of human gut microbiome samples can unveil the metabolic potential of host tissues and the numerous microorganisms they support, concurrently. As such, metabolomic information bears immense potential to improve disease diagnosis and therapeutic drug discovery. Unfortunately, as cohort sizes increase, comprehensive metabolomic profiling becomes costly and logistically difficult to perform at a large scale. To address these difficulties, we tested the feasibility of predicting the metabolites of a microbial community based solely on microbiome sequencing data. Paired microbiome sequencing (16S rRNA gene amplicons, shotgun metagenomics, and metatranscriptomics) and metabolome (mass spectrometry and nuclear magnetic resonance spectroscopy) datasets were collected from six independent studies spanning multiple diseases. We used these datasets to evaluate two reference-based gene-to-metabolite prediction pipelines and a machine-learning (ML) based metabolic profile prediction approach. With the pre-trained model on over 900 microbiome-metabolome paired samples, the ML approach yielded the most accurate predictions (i.e., highest F1 scores) of metabolite occurrences in the human gut and outperformed reference-based pipelines in predicting differential metabolites between case and control subjects. Our findings demonstrate the possibility of predicting metabolites from microbiome sequencing data, while highlighting certain limitations in detecting differential metabolites, and provide a framework to evaluate metabolite prediction pipelines, which will ultimately facilitate future investigations on microbial metabolites and human health.
Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources
Authors: Bazireh Homa , Shariati Parvin , Azimzadeh Jamalkandi Sadegh , Ahmadi Ali , Boroumand Mohammad Ali
Published: December 2020

Probiotics are non-pathogenic microorganisms that can interact with the gastrointestinal microbiota. They have numerous beneficial health effects that include enhancement of the host immune response, antiallergic, antimicrobial, anti-cancer, and anti-inflammatory properties. Probiotics are capable of restoring the impaired microbiome of a dysbiotic gut. They can be isolated from different environments. However, it is frequently suggested that probiotics for human use should come from human sources. The objective of this study was to isolate and characterize novel probiotic strains from the saliva and feces of healthy human individuals. To meet the criteria for probiotic attributes, the isolates were subjected to numerous standard morphological and biochemical tests. These tests included Gram staining, catalase tests, antibiotic susceptibility testing, hemolytic and antagonistic evaluation, tolerance tests involving temperature, NaCl levels, pH and bile salts, adherence ability assays, and genotypic characterization involving 16S rRNA gene sequencing. From 26 saliva and 11 stool samples, 185 microbial strains were isolated. Based on morphological and biochemical characteristics, 14 potential probiotic candidates were selected and identified genotypically. The new strains belonged to Lactobacillus fermentum, Enterococcus faecium, and Enterococcus hire. The selected strains were non-hemolytic, showed high tolerance to low pH and bile salts, and strong adherence abilities. Furthermore, the strains displayed a wide range of antimicrobial activities, particularly against antibiotic-resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA). Moreover, five of the selected isolates demonstrated antiproliferative features against human colon cancer cell line (Caco-2). The results of this investigation confirm the diversity of microbial populations in the human gut and saliva, and since these strains are of human origin, they will highly likely display maximal activities in food and drugs set for human use. Hence, the new strains of this study require additional in vivo experiments to assess their health-promoting effects.
Copy Number Heterogeneity in the Virulence Plasmid of Salmonella enterica
Authors: Sánchez-Romero María A. , Mérida-Floriano Ángela , Casadesús Josep
Published: December 2020

Quantitative PCR analysis shows that the virulence plasmid ofSalmonella entericaserovar Typhimurium (pSLT) is a low-copy-number plasmid, with 1–2 copies per chromosome. However, fluorescence microscopy observation of pSLT labeled with alacOfluorescent tag reveals cell-to-cell differences in the number of foci, which ranges from 1 to 8. As each focus must correspond to ≥1 plasmid copy, the number of foci can be expected to indicate the minimal number of pSLT copies per cell. A correlation is found between the number of foci and the bacterial cell volume. In contrast, heterogeneity in the number of foci appears to be independent of the cell volume and may have stochastic origin. As a consequence of copy number heterogeneity, expression of a pSLT-bone reporter gene shows high levels of cell-to-cell variation, especially in actively dividing cultures. These observations support the notion that low-copy-number plasmids can be a source of gene expression noise in bacterial populations.
Acetate Metabolism in Archaea: Characterization of an Acetate Transporter and of Enzymes Involved in Acetate Activation and Gluconeogenesis in Haloferax volcanii
Authors: Kuprat Tom , Johnsen Ulrike , Ortjohann Marius , Schönheit Peter
Published: December 2020

The haloarchaeon Haloferax volcanii grows on acetate as sole carbon and energy source. The genes and proteins involved in uptake and activation of acetate and in gluconeogenesis were identified and analyzed by characterization of enzymes and by growth experiments with the respective deletion mutants. (i) An acetate transporter of the sodium: solute-symporter family (SSF) was characterized by kinetic analyses of acetate uptake into H. volcanii cells. The functional involvement of the transporter was proven with a Δssf mutant. (ii) Four paralogous AMP-forming acetyl-CoA synthetases that belong to different phylogenetic clades were shown to be functionally involved in acetate activation. (iii) The essential involvement of the glyoxylate cycle as an anaplerotic sequence was concluded from growth experiments with an isocitrate lyase knock-out mutant excluding the operation of the methylaspartate cycle reported for Haloarcula species. (iv) Enzymes involved in phosphoenolpyruvate synthesis from acetate, namely two malic enzymes and a phosphoenolpyruvate synthetase, were identified and characterized. Phylogenetic analyses of haloarchaeal malic enzymes indicate a separate evolutionary line distinct from other archaeal homologs. The exclusive function of phosphoenolpyruvate synthetase in gluconeogenesis was proven by the respective knock-out mutant. Together, this is a comprehensive study of acetate metabolism in archaea.
Advanced Hepatocellular Carcinoma With Hepatic Arterioportal Shunts: Combination Treatment of Transarterial Chemoembolization With Apatinib
Authors: Sun Tao , Ren Yanqiao , Kan Xuefeng , Chen Lei , Zhang Weihua , Yang Fan , Zheng Chuansheng
Published: December 2020

Object: This study aimed to compare the efficacy and safety of transarterial chemoembolization (TACE) combining with apatinib (TACE-apatinib) and TACE-alone for patients with advanced hepatocellular carcinoma (HCC) with hepatic arterioportal shunts (APS).

Materials and Methods: This retrospective study evaluated the medical records of patients with advanced HCC with APS who underwent TACE-apatinib or TACE-alone from June 2015 to January 2019. The occlusion of the shunt was performed during the TACE procedure. The time to tumor progression (TTP) and overall survival (OS) of study patients were evaluated. The modified Response Evaluation Criteria in solid tumors (mRECIST) was used to evaluate the treatment response. The apatinib-related adverse events were recorded.

Results: Fifty-eight patients were included in this study. Twenty-seven patients underwent the treatment of TACE-apatinib, and 31 received TACE-alone treatment. The median overall survival (OS) and median time of tumor progression (TTP) in the TACE-apatinib group were significantly longer than those of the TACE-alone group (OS: 12.0 vs. 9.0 months, P = 0.000; TTP: 9.0 vs. 5.0 months, P = 0.041). Multivariate analysis revealed that TACE-apatinib was a protective factor for OS, and there was no independent risk factor for TTP. In the TACE-apatinib group, the grade 3 apatinib-related adverse events occurred in four patients.

Conclusion: TACE-apatinib was an efficacious and safe treatment for patients with advanced HCC with APS, and apatinib improved the efficacy of TACE in the treatment of these patients.
The Influence of Aging, Hearing, and Tinnitus on the Morphology of Cortical Gray Matter, Amygdala, and Hippocampus
Authors: Profant Oliver , Škoch Antonín , Tintěra Jaroslav , Svobodová Veronika , Kuchárová Diana , Svobodová Burianová Jana , Syka Josef
Published: December 2020

Age related hearing loss (presbycusis) is a natural process represented by elevated auditory thresholds and decreased speech intelligibility, especially in noisy conditions. Tinnitus is a phantom sound that also potentially leads to cortical changes, with its highest occurrence coinciding with the clinical onset of presbycusis. The aim of our project was to identify age, hearing loss and tinnitus related structural changes, within the auditory system and associated structures. Groups of subjects with presbycusis and tinnitus (22 subjects), with only presbycusis (24 subjects), young tinnitus patients with normal hearing (10 subjects) and young controls (17 subjects), underwent an audiological examination to characterize hearing loss and tinnitus. In addition, MRI (3T MR system, analysis in Freesurfer software) scans were used to identify changes in the cortical and subcortical structures. The following areas of the brain were analyzed: Heschl gyrus (HG), planum temporale (PT), primary visual cortex (V1), gyrus parahippocampus (PH), anterior insula (Ins), amygdala (Amg), and hippocampus (HP). A statistical analysis was performed in R framework using linear mixed-effects models with explanatory variables: age, tinnitus, laterality and hearing. In all of the cortical structures, the gray matter thickness decreased significantly with aging without having an effect on laterality (differences between the left and right hemispheres). The decrease in the gray matter thickness was faster in the HG, PT and Ins in comparison with the PH and V1. Aging did not influence the surface of the cortical areas, however there were differences between the surface size of the reported regions in the left and right hemispheres. Hearing loss caused only a borderline decrease of the cortical surface in the HG. Tinnitus was accompanied by a borderline decrease of the Ins surface and led to an increase in the volume of Amy and HP. In summary, aging is accompanied by a decrease in the cortical gray matter thickness; hearing loss only has a limited effect on the structure of the investigated cortical areas and tinnitus causes structural changes which are predominantly within the limbic system and insula, with the structure of the auditory system only being minimally affected.
Complications and Pathophysiology of COVID-19 in the Nervous System
Authors: Yu Haiyang , Sun Tong , Feng Juan
Published: December 2020

The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global public health threat. Majority of the patients with COVID-19 have fever, cough, and fatigue. Critically ill patients can develop dyspnea and acute respiratory distress syndrome. In addition to respiratory symptoms, neurological damage also occurs in some patients. However, the mechanisms by which SARS-CoV-2 invades the nervous system have not been elucidated yet. In order to provide some reference for designing optimal therapeutic strategies, we have discussed the complications and potential mechanisms of COVID-19 in the nervous system in this review.
Resting-State Electroencephalography for Prognosis in Disorders of Consciousness Following Traumatic Brain Injury
Authors: Pauli Ruth , O'Donnell Alice , Cruse Damian
Published: December 2020

Although the majority of patients recover consciousness after a traumatic brain injury (TBI), a minority develop a prolonged disorder of consciousness, which may never fully resolve. For these patients, accurate prognostication is essential to treatment decisions and long-term care planning. In this review, we evaluate the use of resting-state electroencephalography (EEG) as a prognostic measure in disorders of consciousness following TBI. We highlight that routine clinical EEG recordings have prognostic utility in the short to medium term. In particular, measures of alpha power and variability are indicative of relatively better functional outcomes within the first year post-TBI. This is hypothesized to reflect intact thalamocortical loops, and thus the potential for recovery of consciousness even in the apparent absence of current consciousness. However, there is a lack of research into the use of resting-state EEG for predicting longer-term recovery following TBI. We conclude that, given the potential for patients to demonstrate improvements in consciousness and functional capacity even years after TBI, a research focus on EEG-augmented prognostication in very long-term disorders of consciousness is now required.
Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma
Authors: Cui Yong , Zeng Wei , Jiang Haihui , Ren Xiaohui , Lin Song , Fan Yanzhu , Liu Yapeng , Zhao Jizong
Published: December 2020

Objective: To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS).

Methods: The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis and Cox regression model were used to identify parameters correlated with progression-free survival (PFS) and overall survival (OS).

Results: Compared with the contralateral normal brain region, postoperative PEZ showed a lower ratio of NAA/Cr (1.20 ± 0.42 vs. 1.81 ± 0.48, P < 0.001), and higher ratios of Cho/Cr and Cho/NAA (1.36 ± 0.44 vs. 1.02 ± 0.27, P < 0.001 and 1.32 ± 0.59 vs. 0.57 ± 0.14, P < 0.001). Both the ratios of Cho/NAA and NAA/Cr were identified as prognostic factors in univariate analysis (P < 0.05), while only Cho/NAA ≥ 1.31 was further confirmed as an independent risk factor for early recurrence in the Cox regression model (P < 0.01). According to the factors of MGMT promoter unmethylation, without radiotherapy and Cho/NAA ≥ 1.31, a prognostic scoring scale for GBM was established, which could divide patients into low-risk, moderate-risk, and high-risk groups. There was a significant difference of survival rate between the three groups (P < 0.001).

Conclusions: Higher Cho/NAA ratio in the postoperative PEZ of GBM predicts earlier recurrence and is associated with poor prognosis. The prognostic scoring scale based on clinical, molecular and metabolic parameters of patients with GBM can help doctors to make more precise prediction of survival time and to adjust therapeutic regimens.
Recovery of Theta Frequency Oscillations in Rats Following Lateral Fluid Percussion Corresponds With a Mild Cognitive Phenotype
Authors: Ondek Katelynn , Pevzner Aleksandr , Tercovich Kayleen , Schedlbauer Amber M. , Izadi Ali , Ekstrom Arne D. , Cowen Stephen L. , Shahlaie Kiarash , Gurkoff Gene G.
Published: December 2020

Whether from a fall, sports concussion, or even combat injury, there is a critical need to identify when an individual is able to return to play or work following traumatic brain injury (TBI). Electroencephalogram (EEG) and local field potentials (LFP) represent potential tools to monitor circuit-level abnormalities related to learning and memory: specifically, theta oscillations can be readily observed and play a critical role in cognition. Following moderate traumatic brain injury in the rat, lasting changes in theta oscillations coincide with deficits in spatial learning. We hypothesized, therefore, that theta oscillations can be used as an objective biomarker of recovery, with a return of oscillatory activity corresponding with improved spatial learning. In the current study, LFP were recorded from dorsal hippocampus and anterior cingulate in awake, behaving adult Sprague Dawley rats in both a novel environment on post-injury days 3 and 7, and Barnes maze spatial navigation on post-injury days 8–11. Theta oscillations, as measured by power, theta-delta ratio, peak theta frequency, and phase coherence, were significantly altered on day 3, but had largely recovered by day 7 post-injury. Injured rats had a mild behavioral phenotype and were not different from shams on the Barnes maze, as measured by escape latency. Injured rats did use suboptimal search strategies. Combined with our previous findings that demonstrated a correlation between persistent alterations in theta oscillations and spatial learning deficits, these new data suggest that neural oscillations, and particularly theta oscillations, have potential as a biomarker to monitor recovery of brain function following TBI. Specifically, we now demonstrate that oscillations are depressed following injury, but as oscillations recover, so does behavior.
Patient Stratification of Clear Cell Renal Cell Carcinoma Using the Global Transcription Factor Activity Landscape Derived From RNA-Seq Data
Authors: Zhu Yanyan , Cang Shundong , Chen Bowang , Gu Yue , Jiang Miaomiao , Yan Junya , Shao Fengmin , Huang Xiaoyun
Published: December 2020

Clear cell renal cell carcinoma represents the most common type of kidney cancer. Precision medicine approach to ccRCC requires an accurate stratification of patients that can predict prognosis and guide therapeutic decision. Transcription factors are implicated in the initiation and progression of human carcinogenesis. However, no comprehensive analysis of transcription factor activity has been proposed so far to realize patient stratification. Here we propose a novel approach to determine the subtypes of ccRCC patients based on global transcription factor activity landscape. Using the TCGA cohort dataset, we identified different subtypes that have distinct up-regulated biomarkers and altered biological pathways. More important, this subtype information can be used to predict the overall survival of ccRCC patients. Our results suggest that transcription factor activity can be harnessed to perform patient stratification.
CXCL12 and IL7R as Novel Therapeutic Targets for Liver Hepatocellular Carcinoma Are Correlated With Somatic Mutations and the Tumor Immunological Microenvironment
Authors: He Ke , Liu Shuai , Xia Yong , Xu Jianguo , Liu Fei , Xiao Jing , Li Yong , Ding Qianshan , Lu Ligong , Xiang Guoan , Zhan Meixiao
Published: December 2020

The mechanism of liver hepatocellular carcinoma (LIHC) development in correlation with tumor microenvironments and somatic mutations is still being elucidated. This study aims to identify the potential molecular mechanisms and candidate biomarkers in response to tumor microenvironments and somatic mutations. Multiple bioinformatics analysis methods were applied to assess the tumor immunological microenvironment, differentially expressed genes, genetic function enrichment, immunocyte infiltration, regulatory network construction, and tumor mutational burden, and to identify DNA methylation sites. The immunological microenvironment features of ESTIMATE score (OS: p = 0.017, HR = 0.64; RFS: HR = 0.43, p < 0.001) have an important impact on the prognosis of LIHC patients. Cut-off by ESTIMATE score and prognostic information identified 666 DEGs (45 downregulated and 621 upregulated) that were linked with leukocyte migration and lymphocyte activation. In immunocyte infiltration analysis, NK cells (resting), M1 macrophages, CD8+ T cells, and regulatory T cells (Tregs), which are considered core immunoregulatory cells, exhibited significant differences between higher and lower ESTIMATE scores (overall survival and recurrence-free survival p-values < 0.01). Subsequently, further analysis of immunocyte-hub gene identification illustrated that the expression levels of CXCL12 and IL7R significantly correlated with core immunoregulatory cells and somatic mutations (CXCL12: p = 2.1E-06; IL7R: p = 0.001). This study provides new insight into our understanding of the mechanisms of immunocyte regulation and microenvironment involved in LIHC development as well as the effective biomarkers of CXCL12 and IL7R and core immunoregulatory cells, which may emerge as novel therapies for LIHC patients.
Accuracy of Endoscopic Diagnosis of Helicobacter pylori Based on the Kyoto Classification of Gastritis: A Multicenter Study
Authors: Zhao Jing , Xu Shaoxian , Gao Yuan , Lei Yali , Zou Baicang , Zhou Mimi , Chang Danyan , Dong Lei , Qin Bin
Published: December 2020

Background

There is lack of clinical evidence supporting the value of the Kyoto classification of gastritis for the diagnosis of Helicobacter pylori (H. pylori) infection in Chinese patients, and there aren’t enough specific features for the endoscopic diagnosis of past infections, which is of special significance for the prevention of early gastric cancer (GC).

Methods

This was a prospective and multicenter study with 650 Chinese patients. The H. pylori status and gastric mucosal features, including 17 characteristics based on the Kyoto classification and two newly-defined features unclear atrophy boundary (UAB) and RAC reappearance in atrophic mucosa (RAC reappearance) were recorded in a blind fashion. The clinical characteristics of the subjects were analyzed, and the diagnostic odds ratio (DOR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristics curve (ROC/AUC), and 95% confidence intervals were calculated for the different features, individually, and in combination.

Results

For past infection, the DOR of UAB was 7.69 (95%CI:3.11−19.1), second only to map-like redness (7.78 (95%CI: 3.43−17.7)). RAC reappearance showed the highest ROC/AUC (0.583). In cases in which at least one of these three specific features of past infection was considered positive, the ROC/AUC reached 0.643. For current infection, nodularity showed the highest DOR (11.7 (95%CI: 2.65−51.2)), followed by diffuse redness (10.5 (95%CI: 4.87−22.6)). Mucosal swelling showed the highest ROC/AUC (0.726). Regular arrangement of collecting venules (RAC) was specific for no infection.

Conclusions

This study provides evidence of the clinical accuracy and robustness of the Kyoto classification of gastritis for the diagnosis of H. pylori in Chinese patients, and confirms UAB and RAC reappearance partly supplement it for the diagnosis of past infections, which is of great benefit to the early prevention of GC.
A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach
Authors: Hu Luanqian , Chen Yuqi , Chen Tingting , Huang Dan , Li Shihua , Cui Shuna
Published: December 2020

Objective: To investigate the mechanism of Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson (SC) and Patrinia scabiosifolia (PS) against Pelvic Inflammatory Disease with Dampness-Heat Stasis Syndrome via network pharmacological approach and experimental validation.

Methods: The active compounds with OB ≥ 30% and DL ≥ 0.18 were obtained from TCMSP database and further confirmed by literature research. The targets of the compounds and disease were acquired from multiple databases, such as GeneCards, CTD and TCMSP database. The intersection targets were identified by Venny software. Cytoscape 3.7.0 was employed to construct the protein-protein interaction (PPI) network and compound-target network. Moreover, GO enrichment and KEGG pathway analysis were analyzed by DAVID database. Finally, CCK-8, Griess assay and a cytometric bead array (CBA) immunoassay were used for experimental validation by detecting the influence of the active compounds on proliferation of macrophage, release of NO and TNF-α after LPS treatment.

Results: 9 bioactive compounds were identified from SC and PS. Those compounds corresponded to 134 targets of pelvic inflammatory disease with dampness-heat stasis syndrome. The targets include vascular endothelial growth factor A (VEGFA), von willebrand factor (VWF), interleukin 6 (IL6), tumor necrosis factor (TNF) and nuclear transcription factor 1 (NFκB1). They act on the signaling pathways like advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE), focal adhesion (FA), Toll-like receptor (TLR) and nuclear transcription factor κB (NF-κB). In addition, by in vitro validation, the selected active components of SC and PS such as acacetin, kaempferol, linarin, isovitexin, sinoacutine could significantly inhibit the release of NO induced by LPS, respectively. Moreover, different dose of acacetin, kaempferol, isovitexin and sinoacutine significantly inhibits the TNF-α production.

Conclusion: This study provides solid evidence for the anti-inflammatory mechanism of SC and PS against pelvic inflammatory disease with dampness-heat stasis syndrome, which will provide a preliminary evidence and novelty ideas for future research on the two herbs.
Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease
Authors: Zhu Shenghu , Guan Linshu , Tan Xuemei , Li Guoquan , Sun Changjie , Gao Meng , Zhang Bao , Xu Lina
Published: December 2020

Aromatic vinegar with abundant bioactive components can be used as a food additive to assist the treatment of various diseases. However, its effect on non-alcoholic fatty liver disease (NAFLD) is still unknown. The purpose of this study was to investigate the mechanism of Hengshun aromatic vinegar in preventing NAFLD in vivo and in vitro. Aromatic vinegar treatment was applied to rats fed with a high-fat diet (HFD) and HepG2 cells challenged with palmitic acid (PA). Our results showed that aromatic vinegar markedly improved cell viabilities and attenuated cell damage in vitro. The levels of TC, TG, FFA, AST, ALT, and malondialdehyde (MDA) in HFD-induced rats were significantly decreased by aromatic vinegar. Mechanism investigation revealed that aromatic vinegar markedly up-regulated the level of silent information regulator of transcription 1 (Sirt1), and thereby inhibited inflammation of the pathway through down-regulating the expressions of high mobility group box 1, toll-likereceptor-4, nuclear transcription factor-κB, tumor necrosis factor receptor-associated factor-6, and inflammatory factors. Aromatic vinegar simultaneously increased the expression of farnesoid X receptor and suppressed expressions of lipogenesis related proteins, including fatty acid synthase, acetyl-CoA carboxylase-1, sterol regulatory element binding transcription factor 1, and stearoyl-CoA desaturase-1. These results were further validated by knockdown of Sirt1 using siRNAs silencing in vitro. In conclusion, Hengshun aromatic vinegar showed protective effects against NAFLD by enhancing the activity of SIRT1 and thereby inhibiting lipogenesis and inflammation pathways, which is expected to become a new assistant strategy for NAFLD therapy in the future.
Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice
Authors: Coles Madilyn , Watt Georgia , Kreilaus Fabian , Karl Tim
Published: December 2020

Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APPSwe/PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.
Recent Advances and Prospects in the Research of Nascent Adhesions
Authors: Henning Stumpf Bernd , Ambriović-Ristov Andreja , Radenovic Aleksandra , Smith Ana-Sunčana
Published: December 2020

Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signaling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
Towards a Model of Valued Human Cognitive Abilities: An African Perspective Based on a Systematic Review
Authors: Oppong Seth
Published: December 2020

Studies that investigate cognitive ability in African children and estimate the general cognitive abilities of African adults tend to work with existing models of intelligence. However, African philosophy and empirical studies in cross-cultural psychology have demonstrated that conceptualizations of human cognitive ability vary with location. This paper begins with the assumption that the existing Anglo-American models of cognitive abilities are valuable but limited in their capacity to account for the various conceptualizations of valued cognitive abilities in different human societies. On the basis of this assumption, I employ extant empirical evidence generated through ethnographic studies across Africa to formulate what an African model of valued human cognitive ability ought to be. The output of this formulation has been so christened a model of valued cognitive ability in order to draw attention to the fact that models of cognitive abilities have currency and values in each human society. This value allocation is expected to influence which elements of cognitive ability each human society will promote and develop. In addition, implications for theory, research and praxes are discussed.
Is Red the New Black? A Quasi-Experimental Study Comparing Perceptions of Differently Coloured Cycle Lanes
Authors: Karlsen Katrine , Fyhri Aslak
Published: December 2020

Cities and road authorities in many countries have started colouring their cycle lanes. Some road authorities choose red, some blue, and some green. The reasoning behind this choice is not clear, and it is uncertain whether some colours are superior to others. The current study aims to examine whether coloured cycle lanes are viewed more positively than uncoloured lanes, and whether one of the typically chosen colours is perceived as safer and more inviting to cyclists or more deterring to motorists. Participants were invited to respond to a web survey. Respondents (N= 560) were from the four largest cities in Norway, both genders (42.1% women), and of a wide age range (79.6% between 30 and 70). Depending on cycling frequency, respondents were categorised as either motorist (n= 354) or cyclist (n= 206). All respondents rated different cycle lanes (uncoloured, blue, green, and red) on different attributes. The uncoloured lane was consistently rated least positively, with the lowest scores on visibility, perceived safety for both motorists and cyclist and how inviting it seemed to cycle in the lane. It was also estimated to be the lane that would experience the greatest degree of violation from motorists, in terms of driving or stopping in the cycle lane. The green and red lanes were consistently rated more positively than the blue lane, but whether green or red was preferred depended on whether the respondent had lived a place with coloured cycle lanes. People familiar with coloured cycle lanes, which in Norway are red, rated the red lane more positively than the green lane, while the opposite was true for people who were not used to coloured cycle lanes. The difference in ratings between different colours were similar to, or greater than, the difference from uncoloured to coloured, which implies that it not only mattersthata lane is coloured, but alsowhich colourit has.
A Systematic Review of Normative Studies Using Images of Common Objects
Authors: Souza Cristiane , Garrido Margarida V. , Carmo Joana C.
Published: December 2020

Common objects comprise living and non-living things people interact with in their daily-lives. Images depicting common objects are extensively used in different fields of research and intervention, such as linguistics, psychology, and education. Nevertheless, their adequate use requires the consideration of several factors (e.g., item-differences, cultural-context and confounding correlated variables), and careful validation procedures. The current study presents a systematic review of the available published norms for images of common objects. A systematic search using PRISMA guidelines indicated that despite their extensive use, the production of norms for such stimuli with adult populations is quite limited (N = 55), particularly for more ecological images, such as photos (N = 14). Among the several dimensions in which the items were assessed, the most commonly referred in our sample were familiarity, visual complexity and name agreement, illustrating some consistency across the reported dimensions while also indicating the limited examination of other potentially relevant dimensions for image processing. The lack of normative studies simultaneously examining affective, perceptive and semantic dimensions was also documented. The number of such normative studies has been increasing in the last years and published in relevant peer-reviewed journals. Moreover, their datasets and norms have been complying with current open science practices. Nevertheless, they are still scarcely cited and replicated in different linguistic and cultural contexts. The current study brings important theoretical contributions by characterizing images of common objects stimuli and their culturally-based norms while highlighting several important features that are likely to be relevant for future stimuli selection and evaluative procedures. The systematic scrutiny of these normative studies is likely to stimulate the production of new, robust and contextually-relevant normative datasets and to provide tools for enhancing the quality of future research and intervention.