bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis on Experimental Performance of Hysteretic Behavior of Concrete-Filled Circular CFRP Steel Tubular Beam-Column
Authors: Qing-li Wang , Miao Chu , Kuan Peng
Published: February 2022

In order to study the test performance of the concrete-filled CFRP steel tubular (CF-CFRP-ST) beam-column under hysteretic load, 12 specimens were designed. During the test loading, the effects of axial compression ratio and longitudinal CFRP reinforcement coefficient on hysteric load were studied. Based on experimental research, a finite element method for establishing CF-CFRP-ST beam-column is proposed by FE simulation, and the influence of main parameters on performance is studied by this method. The test results show that CFRP and the steel tube can work together well, and the local buckling of specimens is delayed. In addition, the simulation results are in good agreement with the experimental results. Based on the experiment and finite element method, the influence of main parameters on the hysteretic behavior of specimens is studied.
A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)
Authors: Opfermann Philipp , Felli Alessia , Schlömmer Christine , Dworschak Martin , Bevilacqua Michele , Mouhieddine Mohamed , Zimpfer Daniel , Zuckermann Andreas , Steinlechner Barbara
Published: February 2022

Background

Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established.

Methods

We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons.

Results

7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = −0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (−0.7, p < 0.001), EXTEM MCF (ρ = −0.63; p < 0.001), EXTEM alpha (ρ = −0.67; p < 0.001), FIBTEM MCF (ρ = −0.41; p = 0.042), Fibrinogen (Clauss) (ρ = −0.5; p = 0.011), Anti-thrombin activity (ρ = −0.49; p = 0.013) and platelet count (ρ = −0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP—[31.5 IQR (17.25–43.5U) vs. 69 IQR (52.5–87U); p = 0.004], ASPI—[16.5 IQR (5.5–35.7U) vs. 39 IQR (24.5–62.5U); p = 0.038], ADP—[30 IQR (22–69U) vs. 12.5 IQR (8.7–21.5U); p = 0.01], EXTEM MCF—[63 IQR (57.7–63.7) vs. 67 IQR (65–75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75–74) vs. 79 IQR (78–80.5); p = 0.002] values before LVAD implantation.

Conclusion

Multiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.
Long-Term Persistence of Olfactory and Gustatory Disorders in COVID-19 Patients
Authors: Nguyen Nhu Ngoc , Hoang Van Thuan , Dao Thi Loi , Meddeb Line , Cortaredona Sébastien , Lagier Jean-Christophe , Million Matthieu , Raoult Didier , Gautret Philippe
Published: February 2022

Smell and taste disorders are frequent symptoms during acute COVID-19 and may persist long after the resolution of the initial phase. This study aims to estimate the proportion and risk factors for smell and/or taste disorders at the onset of symptoms and their persistence after more than 6 months of follow-up in COVID-19 patients. We analyzed a prospective cohort of COVID-19 patients admitted to our institute in Marseille, France in early 2020. After being discharged from the hospital, patients with smell and/or taste disorders were contacted for a telephone interview. Logistic regression analysis was performed to determine the risk factors for smell and/or taste disorders. A total of 3,737 patients were included, of whom 1,676 reported smell and/or taste disorders at the onset of symptoms. Taste and/or smell disorders were independently associated with being younger and female, a lower likelihood of suffering from diabetes, cardiovascular diseases and cancer, a longer delay between the onset of symptoms and consultation, and non-severe forms of COVID-19 at admission. Of the 605 patients with smell and/or taste disorders who were followed-up, 154 (25.5%) reported the persistence of symptoms for more than 6 months. At the time of follow-up, being female, having a chronic respiratory disease and using angiotensin-converting enzyme inhibitors (ACEis) were factors independently associated with the persistence of smell and/or taste disorders. In conclusion, the long-term persistence of olfactory and gustative disorders is frequent among COVID-19 patients, notably affecting female patients and patients who suffered from chronic respiratory diseases before infection. The role of ACEis needs to be further evaluated in larger numbers of patients.
Comparison of Clinical Characteristics and Short-Term Prognoses Within Hospitalized Chronic Obstructive Pulmonary Disease Patients Comorbid With Asthma, Bronchiectasis, and Their Overlaps: Findings From the ACURE Registry
Authors: Lei Jieping , Yang Ting , Liang Chen , Huang Ke , Wu Sinan , Wang Chen
Published: February 2022

Introduction

Real-world evidence and comparison among commonly seen chronic obstructive pulmonary disease (COPD) phenotypes, i.e., asthma–COPD overlap (ACO), bronchiectasis–COPD overlap (BCO), and their coexistence (ABCO) have not been fully depicted, especially in Chinese patients.

Methods

Data were retrieved from an ongoing nationwide registry in hospitalized patients due to acute exacerbation of COPD in China (ACURE).

Results

Of the eligible 4,813 patients with COPD, 338 (7.02%), 492 (10.22%), and 63 (1.31%) were identified as ACO, BCO, and ABCO phenotypes, respectively. Relatively, the ABCO phenotype had a younger age with a median of 62.99 years [interquartile range (IQR): 55.93–69.48] and the COPD phenotype had an older age with a median of 70.15 years (IQR: 64.37–76.82). The BCO and COPD phenotypes were similar in body mass index with a median of 21.79 kg/m2 (IQR: 19.47–23.97) and 21.79 kg/m2 (IQR: 19.49–24.22), respectively. The COPD phenotype had more male gender (79.90%) and smokers (71.12%) with a longer history of smoking (median: 32.45 years, IQR: 0.00–43.91). The ACO and ABCO phenotypes suffered more prior allergic episodes with a proportion of 18.05 and 19.05%, respectively. The ACO phenotype exhibited a higher level of eosinophil and better lung reversibility. Moreover, the four phenotypes showed no significant difference neither in all-cause mortality, intensive care unit admission, length of hospital stay, and COPD Assessment Test score change during the index hospitalization, and nor in the day 30 outcomes, i.e., all-cause mortality, recurrence of exacerbation, all-cause, and exacerbation-related readmission.

Conclusions

The ACO, BCO, ABCO, and COPD phenotypes exhibited distinct clinical features but had no varied short-term prognoses. Further validation in a larger sample is warranted.
Acidic Electrolyzed Water Inhibits the Viability of Gardnerella spp. via Oxidative Stress Response
Authors: Zhao Chongyu , Chen Yu , Gao Lvfen , Huang Jue , Yang Xiurou , Pei Luowei , Ye Zhangying , Zhu Linyan
Published: February 2022

The vaginal microbiota, dominated by Lactobacilli, plays an important role in maintaining women's health. Disturbance of the vaginal microbiota allows infection by various pathogens such as Gardnerella spp. (GS) and related anaerobic bacteria resulting in bacterial vaginosis (BV). At present, the treatment options for BV are extremely limited. Treatment of antibacterial drugs and vaginal acidification are the two primary therapeutic methods. Acid electrolyzed water (AEW) is known to inactivate microorganisms and is considered a medical application in recent years. Studies have found that Lactobacillus acidophilus (LA) probiotics helps to inhibit GS-induced BV. Our study took GS and LA as the research object, which aims to explore AEW as a potential alternative therapy for BV and its underlying mechanisms. We first obtained the pH of AEW (3.71–4.22) close to normal vaginal pH (3.8–4.5) to maintain normal vaginal acidification conditions. Plate counting experiments showed that AEW (pH: 4.07, ORP: 890.67, ACC: 20 ppm) (20 ppm) could better inhibit the viability of GS but had a more negligible effect on LA. Then, we preliminarily explored the possible mechanism of AEW anti-GS using cell biology experiments and transmission electron microscopy. Results showed that the membrane permeability was significantly increased and the integrity of cell membrane was destroyed by AEW in GS than those in LA. AEW also caused protein leakage and cell lysis in GS without affecting LA. Meanwhile, AEW induced a number of reactive oxygen species (ROS) production in GS, with no obvious LA changes. Finally, we found that 20 ppm AEW exhibited excellent antibacterial effect on the vaginal secretions of women diagnosed with BV by Amsel criteria and sialic acid plum method. Taken together, our findings manifest that 20 ppm AEW has an excellent antibacterial effect in GS with less effect on LA, which might be expected to become a potential therapy for BV.
Increased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstructive Sleep Apnea
Authors: Cai Jingyao , Lyu Xing , Huang Peiying , Li Shisheng , Chen Ruohong , Chen Zhiyang , Sun Mei , Zeng Ling , Wu Fengxi , Hu Min
Published: February 2022

Background

Obstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell.

Methods

74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software.

Results

There was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression.

Conclusion

OSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.
Genetic Characterization of Antibiotic Resistant Enterobacteriaceae Isolates From Bovine Animals and the Environment in Nigeria
Authors: Jesumirhewe Christiana , Springer Burkhard , Allerberger Franz , Ruppitsch Werner
Published: February 2022

There is a link between antibiotic resistance in humans, livestock and the environment. This study was carried out to characterize antibiotic resistant bovine and environmental Enterobacteriaceae isolates from Edo state, Nigeria. A total of 109 consecutive isolates of Enterobacteriaceae were isolated from March–May 2015 from 150 fecal samples of healthy bovine animals from three farms at slaughter in Edo state Nigeria. Similarly, 43 Enterobacteriaceae isolates were also obtained from a total of 100 environmental samples from different sources. Isolates were recovered and identified from samples using standard microbiological techniques. Recovered isolates were pre-identified by the Microbact Gram-Negative identification system and confirmed with Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and ribosomal multilocus sequence typing (rMLST). Antibiotic susceptibility testing was carried out by Kirby-Bauer method for 14 antibiotics. Whole genome sequencing (WGS) was carried out for isolate characterization and identification of resistance determinants. Out of 109 animal and 43 environmental Enterobacteriaceae isolates, 18 (17%) and 8 (19%) isolates based on selection criteria showed antibiotic resistance and were further investigated by whole genome sequencing (WGS). Resistance genes were detected in all (100%) of the resistant bovine and environmental Enterobacteriaceae isolates. The resistance determinants included β-lactamase genes, aminoglycoside modifying enzymes, qnr genes, sulfonamide, tetracycline and trimethoprim resistance genes, respectively. Out of the 18 and 8 resistant animal and environmental isolates 3 (17%) and 2 (25%) were multidrug resistant (MDR) and had resistance determinants which included efflux genes, regulatory systems modulating antibiotic efflux and antibiotic target alteration genes. Our study shows the dissemination of antibiotic resistance especially MDR strains among Nigerian bovine and environmental Enterobacteriaceae isolates. The presence of these resistant strains in animals and the environment constitute a serious health concern indicated by the difficult treatment options of the infections caused by these organisms. To the best of our knowledge we report the first detailed genomic characterization of antibiotic resistance in bovine and environmental Enterobacteriaceae isolates for Nigeria.
Membrane and Extracellular Matrix Glycopolymers of Colwellia psychrerythraea 34H: Structural Changes at Different Growth Temperatures
Authors: Casillo Angela , D’Angelo Caterina , Parrilli Ermenegilda , Tutino Maria Luisa , Corsaro Maria Michela
Published: February 2022

Colwellia psychrerythraea 34H is a marine Gram-negative psychrophile; it was isolated from Arctic marine sediments, but it is considered cosmopolitan in cold environments. This microorganism is considered a model to study adaptive strategies to sub-zero temperatures, and its lifestyle has been the object of numerous studies. In the last few years, we focused our studies on the glycoconjugates produced by C. psychrerythraea 34H at 4°C, resulting in the isolation and characterization of very interesting molecules. It produces an unusual lipooligosaccharide molecule and both capsular and medium released polysaccharides. In this study, we described the response of these glycoconjugates in terms of production and chemical structure produced by C. psychrerythraea 34H grown in planktonic conditions at −2, 4, and 8°C. The glycopolymers have been detected by chemical methods and spectroscopic analyses. Moreover, the glycopolymer content of the biofilm matrix of C. psychrerythraea 34H has been evaluated, through confocal microscopy and glycosyl analysis. The results highlighted that C. psychrerythraea 34H adjusts both the production and the typology of its glyconjugates in response to temperature fluctuations.
Effects of Escherichia coli Nissle 1917 on the Porcine Gut Microbiota, Intestinal Epithelium and Immune System in Early Life
Authors: Geervliet Mirelle , de Vries Hugo , Jansen Christine A. , Rutten Victor P. M. G. , van Hees Hubèrt , Wen Caifang , Skovgaard Kerstin , Antonello Giacomo , Savelkoul Huub F. J. , Smidt Hauke , Tijhaar Edwin , Wells Jerry M.
Published: February 2022

Early in life and particularly around weaning, piglets are susceptible to infections because of abrupt social, environmental, and dietary changes. Dietary interventions with probiotic bacteria have gained popularity because of the increased awareness of the direct link between diet and health. In this study, piglets received the probiotic strain Escherichia coli Nissle 1917 (EcN) or a control treatment perorally from day 2 after birth until 2 weeks post-weaning. To investigate spatio-temporal effects of EcN on the gut microbiota composition, intestinal epithelial gene expression and immune system, feces, digesta, blood, scraping material and mesenteric lymph node tissue were collected at different time points. In addition, oral vaccinations against Salmonella enterica serovar Typhimurium were administered on days 21 and 45 of the study to assess the immunocompetence. EcN-treated pigs showed a reduced diversity of taxa within the phylum Proteobacteria and a lower relative abundance of taxa within the genus Treponema during the pre-weaning period. Moreover, EcN induced T cell proliferation and Natural Killer cell activation in blood and enhanced IL-10 production in ex vivo stimulated mesenteric lymph node cells, the latter pointing toward a more regulatory or anti-inflammatory state of the local gut-associated immune system. These outcomes were primarily observed pre-weaning. No significant differences were observed between the treatment groups with regards to body weight, epithelial gene expression, and immune response upon vaccination. Differences observed during the post-weaning period between the treatment groups were modest. Overall, this study demonstrates that the pre-weaning period offers a ‘window of opportunity’ to modulate the porcine gut microbiota and immune system through dietary interventions such as EcN supplementation.
Associations of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Cognitive Impairment Among the Oldest-Old in China
Authors: Jin Xurui , Long Tingxi , Chen Huashuai , Zeng Yi , Zhang Xian , Yan Lijing , Wu Chenkai
Published: February 2022

Recent literature suggested that ALDH2 mutation is associated with alcohol metabolism, and ethanol intake might jointly increase the risk of Alzheimer’s disease (AD) in mice. However, it is unclear whether this synergistic effect exists among humans. We examined the associations of four single nucleotide polymorphisms (SNPs) on aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) genes (i.e., ALDH2 rs671, ADH1B rs1229984, ADH1B rs1042026, and ADH1C rs1693482) and cognitive impairment among the oldest-old. We also investigated whether this association was modified by ethanol intake from alcohol consumption. Data were from the Chinese Longitudinal Healthy Longevity Survey genetic sub-study, including 1,949 participants aged over 90 years. Participants with a Mini-Mental State Examination (MMSE) score of < 18 were considered cognitively impaired. Alcohol consumption was categorized as heavy, moderate, or never drinkers. With the dominant model, carrying A allele on rs671, C allele on rs1229984, and T allele on rs1042026 was associated with 33% (95% confidence interval [CI]: 5%, 69%), 33% (95% CI: 2%, 75%), and 29% (95% CI: 3%, 62%) higher odds of cognitive impairment in the multivariable-adjusted logistic model, respectively. We did not observe a significant interaction between those SNPs and alcohol consumption. Among the oldest-old, carrying ALDH2 rs671 mutation was associated with higher odds of cognitive impairment independent of alcohol consumption.
Association of Age and Structural Brain Changes With Functional Connectivity and Executive Function in a Middle-Aged to Older Population-Based Cohort
Authors: Schulz Maximilian , Mayer Carola , Schlemm Eckhard , Frey Benedikt M. , Malherbe Caroline , Petersen Marvin , Gallinat Jürgen , Kühn Simone , Fiehler Jens , Hanning Uta , Twerenbold Raphael , Gerloff Christian , Cheng Bastian , Thomalla Götz
Published: February 2022

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45–74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.
Inhibition of miR-128 Enhances Vocal Sequence Organization in Juvenile Songbirds
Authors: Aamodt Caitlin M. , White Stephanie A.
Published: February 2022

The molecular mechanisms underlying learned vocal communication are not well characterized. This is a major barrier for developing treatments for conditions affecting social communication, such as autism spectrum disorder (ASD). Our group previously generated an activity-dependent gene expression network in the striatopallidal song control nucleus, Area X, in adult zebra finches to identify master regulators of learned vocal behavior. This dataset revealed that the two host genes for microRNA-128, ARPP21 and R3HDM1, are among the top genes whose expression correlates to how much birds sing. Here we examined whether miR-128 itself is behaviorally regulated in Area X and found that its levels decline with singing. We hypothesized that reducing miR-128 during the critical period for vocal plasticity would enhance vocal learning. To test this, we bilaterally injected an antisense miR-128 construct (AS miR-128) or a control scrambled sequence into Area X at post-hatch day 30 (30 d) using sibling-matched experimental and control pupils. The juveniles were then returned to their home cage and raised with their tutors. Strikingly, inhibition of miR-128 in young birds enhanced the organization of learned vocal sequences. Tutor and pupil stereotypy scores were positively correlated, though the correlation was stronger between tutors and control pupils compared to tutors and AS miR-128 pupils. This difference was driven by AS miR-128 pupils achieving higher stereotypy scores despite their tutors’ lower syntax scores. AS miR-128 birds with tutors on the higher end of the stereotypy spectrum were more likely to produce songs with faster tempos relative to sibling controls. Our results suggest that low levels of miR-128 facilitate vocal sequence stereotypy. By analogy, reducing miR-128 could enhance the capacity to learn to speak in patients with non-verbal ASD. To our knowledge, this study is the first to directly link miR-128 to learned vocal communication and provides support for miR-128 as a potential therapeutic target for ASD.
Research Progress on the Role of Microglia Membrane Proteins or Receptors in Neuroinflammation and Degeneration
Authors: Zhao Jun-Feng , Ren Tong , Li Xiang-Yu , Guo Tian-Lin , Liu Chun-Hui , Wang Xun
Published: February 2022

Microglia are intrinsic immune cells of the central nervous system and play a dual role (pro-inflammatory and anti-inflammatory) in the homeostasis of the nervous system. Neuroinflammation mediated by microglia serves as an important stage of ischemic hypoxic brain injury, cerebral hemorrhage disease, neurodegeneration and neurotumor of the nervous system and is present through the whole course of these diseases. Microglial membrane protein or receptor is the basis of mediating microglia to play the inflammatory role and they have been found to be upregulated by recognizing associated ligands or sensing changes in the nervous system microenvironment. They can then allosterically activate the downstream signal transduction and produce a series of complex cascade reactions that can activate microglia, promote microglia chemotactic migration and stimulate the release of proinflammatory factor such as TNF-α, IL-β to effectively damage the nervous system and cause apoptosis of neurons. In this paper, several representative membrane proteins or receptors present on the surface of microglia are systematically reviewed and information about their structures, functions and specific roles in one or more neurological diseases. And on this basis, some prospects for the treatment of novel coronavirus neurological complications are presented.
Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis
Authors: Perdaens Océane , van Pesch Vincent
Published: February 2022

Aging is characterized, amongst other features, by a complex process of cellular senescence involving both innate and adaptive immunity, called immunosenescence and associated to inflammaging, a low-grade chronic inflammation. Both processes fuel each other and partially explain increasing incidence of cancers, infections, age-related autoimmunity, and vascular disease as well as a reduced response to vaccination. Multiple sclerosis (MS) is a lifelong disease, for which considerable progress in disease-modifying therapies (DMTs) and management has improved long-term survival. However, disability progression, increasing with age and disease duration, remains. Neurologists are now involved in caring for elderly MS patients, with increasing comorbidities. Aging of the immune system therefore has relevant implications for MS pathogenesis, response to DMTs and the risks mediated by these treatments. We propose to review current evidence regarding markers and molecular mechanisms of immunosenescence and their relevance to understanding MS pathogenesis. We will focus on age-related changes in the innate and adaptive immune system in MS and other auto-immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. The consequences of these immune changes on MS pathology, in interaction with the intrinsic aging process of central nervous system resident cells will be discussed. Finally, the impact of immunosenescence on disease evolution and on the safety and efficacy of current DMTs will be presented.
Weighted Blind Source Separation Can Decompose the Frequency Mismatch Response by Deviant Concatenation: An MEG Study
Authors: Matsubara Teppei , Stufflebeam Steven , Khan Sheraz , Ahveninen Jyrki , Hämäläinen Matti , Goto Yoshinobu , Maekawa Toshihiko , Tobimatsu Shozo , Kishida Kuniharu
Published: February 2022

The mismatch response (MMR) is thought to be a neurophysiological measure of novel auditory detection that could serve as a translational biomarker of various neurological diseases. When recorded with electroencephalography (EEG) or magnetoencephalography (MEG), the MMR is traditionally extracted by subtracting the event-related potential/field (ERP/ERF) elicited in response to “deviant” sounds that occur randomly within a train of repetitive “standard” sounds. However, there are several problems with such a subtraction, which include increased noise and the neural adaptation problem. On the basis of the original theory underlying MMR (i.e., the memory-comparison process), the MMR should be present only in deviant epochs. Therefore, we proposed a novel method called weighted-BSST/k, which uses only the deviant response to derive the MMR. Deviant concatenation and weight assignment are the primary procedures of weighted-BSST/k, which maximize the benefits of time-delayed correlation. We hypothesized that this novel weighted-BSST/k method highlights responses related to the detection of the deviant stimulus and is more sensitive than independent component analysis (ICA). To test this hypothesis and the validity and efficacy of the weighted-BSST/k in comparison with ICA (infomax), we evaluated the methods in 12 healthy adults. Auditory stimuli were presented at a constant rate of 2 Hz. Frequency MMRs at a sensor level were obtained from the bilateral temporal lobes with the subtraction approach at 96–276 ms (the MMR time range), defined based on spatio-temporal cluster permutation analysis. In the application of the weighted-BSST/k, the deviant responses were given a constant weight using a rectangular window on the MMR time range. The ERF elicited by the weighted deviant responses demonstrated one or a few dominant components representing the MMR that fitted well with that of the sensor space analysis using the conventional subtraction approach. In contrast, infomax or weighted-infomax revealed many minor or pseudo components as constituents of the MMR. Our single-trial, contrast-free approach may assist in using the MMR in basic and clinical research, and it opens a new and potentially useful way to analyze event-related MEG/EEG data.
Disentangling the Relationship Between Chronic Kidney Disease and Cognitive Disorders
Authors: Kelly Dearbhla M. , Rothwell Peter M.
Published: February 2022

Chronic kidney disease (CKD) is a rapidly rising global health burden that affects nearly 40% of older adults. Epidemiologic data suggest that individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia, and thus represent a vulnerable population. It is currently unknown to what extent this risk may be attributable to a clustering of traditional risk factors such as hypertension and diabetes mellitus leading to a high prevalence of both symptomatic and subclinical ischaemic cerebrovascular lesions, or whether other potential mechanisms, including direct neuronal injury by uraemic toxins or dialysis-specific factors could also be involved. These knowledge gaps may lead to suboptimal prevention and treatment strategies being implemented in this group. In this review, we explore the mechanisms of susceptibility and risk in the relationship between CKD and cognitive disorders.
The Effect of Pedaling at Different Cadence on Attentional Resources
Authors: Akaiwa Mayu , Iwata Koki , Saito Hidekazu , Shibata Eriko , Sasaki Takeshi , Sugawara Kazuhiro
Published: February 2022

We investigated the relationship between attentional resources and pedaling cadence using electroencephalography (EEG) to measure P300 amplitudes and latencies. Twenty-five healthy volunteers performed the oddball task while pedaling on a stationary bike or relaxing (i.e., no pedaling). We set them four conditions, namely, (1) performing only the oddball task (i.e., control), (2) performing the oddball task while pedaling at optimal cadence (i.e., optimal), (3) performing the oddball task while pedaling faster than optimal cadence (i.e., fast), and (4) performing the oddball task while pedaling slower than optimal cadence (i.e., slow). P300 amplitudes at Cz and Pz electrodes under optimal, fast, and slow conditions were significantly lower than those under control conditions. P300 amplitudes at Pz under fast and slow conditions were significantly lower than those under the optimal condition. No significant changes in P300 latency at any electrode were observed under any condition. Our findings revealed that pedaling at non-optimal cadence results in less attention being paid to external stimuli compared with pedaling at optimal cadence.
Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders
Authors: Padhi Piyush , Worth Carter , Zenitsky Gary , Jin Huajun , Sambamurti Kumar , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G.
Published: February 2022

The human gut microbiota is a complex, dynamic, and highly diverse community of microorganisms. Beginning as early as in utero fetal development and continuing through birth to late-stage adulthood, the crosstalk between the gut microbiome and brain is essential for modulating various metabolic, neurodevelopmental, and immune-related pathways. Conversely, microbial dysbiosis – defined as alterations in richness and relative abundances – of the gut is implicated in the pathogenesis of several chronic neurological and neurodegenerative disorders. Evidence from large-population cohort studies suggests that individuals with neurodegenerative conditions have an altered gut microbial composition as well as microbial and serum metabolomic profiles distinct from those in the healthy population. Dysbiosis is also linked to psychiatric and gastrointestinal complications – comorbidities often associated with the prodromal phase of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Studies have identified potential mediators that link gut dysbiosis and neurological disorders. Recent findings have also elucidated the potential mechanisms of disease pathology in the enteric nervous system prior to the onset of neurodegeneration. This review highlights the functional pathways and mechanisms, particularly gut microbe-induced chronic inflammation, protein misfolding, propagation of disease-specific pathology, defective protein clearance, and autoimmune dysregulation, linking gut microbial dysbiosis and neurodegeneration. In addition, we also discuss how pathogenic transformation of microbial composition leads to increased endotoxin production and fewer beneficial metabolites, both of which could trigger immune cell activation and enteric neuronal dysfunction. These can further disrupt intestinal barrier permeability, aggravate the systemic pro-inflammatory state, impair blood–brain barrier permeability and recruit immune mediators leading to neuroinflammation and neurodegeneration. Continued biomedical advances in understanding the microbiota-gut-brain axis will extend the frontier of neurodegenerative disorders and enable the utilization of novel diagnostic and therapeutic strategies to mitigate the pathological burden of these diseases.
Effects of Immunonutrition in Head and Neck Cancer Patients Undergoing Cancer Treatment – A Systematic Review
Authors: Tan Sing Ean , Abdul Satar Nur Fadhlina , Majid Hazreen Abdul
Published: February 2022

Background and Aims

Malnutrition is prevalent among head and neck cancer (HNC) patients and leads to undesirable outcomes such as reduced treatment response and increased treatment-related side effects. This systematic review summarizes the recent evidence regarding the effect of immunonutrition in HNC patients undergoing radiotherapy and chemotherapy.

Methods

A literature search was conducted of the CENTRAL, ProQuest, MEDLINE, EBSCOhost, Web of Science and CINAHL databases; and further supplemented with internet and manual searches. Studies published between January 2011 and May 2021 were identified, screened, retrieved, and data extraction was performed.

Results

Twenty studies involving 1535 patients were included, 15 were randomized controlled trials (RCTs), three were retrospective study and two were comparative cohort studies. Five out of seven studies reported improvement or maintenance of nutrition status with continuous supplementation using immunonutrient-enriched formula. Three studies reported functional status as an outcome, with one study reporting significant improvement, one study reporting maintenance, and another study reporting no difference in the functional status of patients supplemented with immunonutrient-enriched formulas. Supplementation with glutamine did not reduce the overall incidence of mucositis but delayed the onset of oral mucositis and had significantly less incidence of severe oral mucositis.

Conclusion

Supplementation with immunonutrient-enriched formulas in HNC patients during radiotherapy and chemotherapy may improve or maintain nutrition status. Supplementation with glutamine during HNC radiotherapy and chemotherapy may delay the onset of oral mucositis and reduce incidences of severe oral mucositis. Further investigations are required, focusing on the timing, dosage, and duration of immunonutrition.

Systematic Review Registration: PROSPERO, identifier CRD42021241817.
Associations of Serum and Red Blood Cell Folate With All-Cause and Cardiovascular Mortality Among Hypertensive Patients With Elevated Homocysteine
Authors: Zhou Long , Huang Hui , Wen Xiaoxiao , Chen Yu , Liao Jie , Chen Fuli , Zhao Liancheng , Liu Mingjiang , Tao Jianhong , Li Gang
Published: February 2022

Objectives

This study aims to explore the associations between serum and red blood cell (RBC) folate as indicators of short- and long-term folate status, respectively, and all-cause as well as CVD mortality among hypertensive patients with elevated homocysteine.

Methods

A prospective cohort study of the National Health and Nutrition Examination Survey (1999–2006) and 2015 Linked Mortality File was performed. All-cause and CVD mortality risk estimated using Cox proportional hazards models with adjusting for multiple potential covariates.

Results

A total of 1,753 hypertensive patients with elevated homocysteine [mean (SD) age, 68.5 (13.1)] were included in the analysis. During a median follow-up of 10.0 years, a total of 899 all-cause and 257 CVD deaths occurred. Compared the highest with the lowest quartile of RBC folate, the multivariable adjusted hazard ratios and 95% confidence intervals for all-cause and CVD death were 1.13 (0.92–1.39) and 1.47 (1.01–2.16) respectively. There was a significant and positive trend between RBC folate and the risk of CVD death (p for trend = 0.0196). No significant association was found between serum folate and mortality risk among the study sample.

Conclusions

High level of RBC folate is associated with an increased risk of cardiovascular mortality among hypertensive patients with elevated homocysteine while serum folate has no such effects.
Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells
Authors: Jiang Wen , Li Fanglin , Jiang Yang , Li Shengli , Liu Xiaoli , Xu Yaqi , Li Binggen , Feng Xiaoli , Zheng Chengyun
Published: February 2022

Multiple myeloma (MM) is still an incurable plasma cell tumor. Natural killer (NK) cells are characterized by efficient anti-tumor activity, and their activity is one basis of cancer immunotherapeutic strategies. Tim-3, one of the immune checkpoint molecules, negatively regulates NK cell activity. To evaluate roles of the Tim-3 pathway blocking in the regulation of NK cell mediated- anti-MM activity in vitro and in vivo, anti-Tim-3 and/or anti-its ligand (HMGB1, CEACAM1 or Galetin-9) antibodies were applied respectively to block the Tim-3 pathway in the present study. Our results showed that Tim-3 was highly expressed on NK cells, in particular on in vitro expanded NK (exNK) cells. NK cells with Tim-3 blockade displayed a significantly higher degranulation and cytolytic activity against both human MM cell lines and primary MM cells, compared to the isotype control antibody-treated NK cells. The increased NK cell cytolytic activity by Tim-3 blocking was associated with up-regulation of cytotoxicity-related molecules, including perforin, granzyme B, TNF-α and IFN-γ. Ligand (HMGB1, CEACAM1 or Galetin-9) expression on MM cells was at different levels, and accordingly, the improvement in NK cell-mediated killing activity by different ligand blocking were also varying. Tim-3 blocking showed much more efficient enhancement of NK cell cytolytic activity than its ligand blockings. More importantly, exNK cells with Tim-3 blockade significantly inhibited MM tumor growth and prolonged the survival of MM-bearing NOD/SCID mice. Our results also showed that NK cells from peripheral blood and bone marrow of MM patients expressed much higher levels of Tim-3 than their counterparts from controls. Taken together, Tim-3 may be an important target molecule used for developing an antibody and/or NK cell based immunotherapeutic strategies for MM.
A Radiosensitivity Prediction Model Developed Based on Weighted Correlation Network Analysis of Hypoxia Genes for Lower-Grade Glioma
Authors: Du Zixuan , Liu Hanshan , Bai Lu , Yan Derui , Li Huijun , Peng Sun , Cao JianPing , Liu Song-Bai , Tang Zaixiang
Published: February 2022

Background and Purpose

Hypoxia is one of the basic characteristics of the physical microenvironment of solid tumors. The relationship between radiotherapy and hypoxia is complex. However, there is no radiosensitivity prediction model based on hypoxia genes. We attempted to construct a radiosensitivity prediction model developed based on hypoxia genes for lower-grade glioma (LGG) by using weighted correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (Lasso).

Methods

In this research, radiotherapy-related module genes were selected after WGCNA. Then, Lasso was performed to select genes in patients who received radiotherapy. Finally, 12 genes (AGK, ETV4, PARD6A, PTP4A2, RIOK3, SIGMAR1, SLC34A2, SMURF1, STK33, TCEAL1, TFPI, and UROS) were included in the model. A radiosensitivity-related risk score model was established based on the overall rate of The Cancer Genome Atlas (TCGA) dataset in patients who received radiotherapy. The model was validated in TCGA dataset and two Chinese Glioma Genome Atlas (CGGA) datasets. A novel nomogram was developed to predict the overall survival of LGG patients.

Results

We developed and verified a radiosensitivity-related risk score model based on hypoxia genes. The radiosensitivity-related risk score served as an independent prognostic indicator. This radiosensitivity-related risk score model has prognostic prediction ability. Moreover, a nomogram integrating risk score with age and tumor grade was established to perform better for predicting 1-, 3-, and 5-year survival rates.

Conclusions

We developed and validated a radiosensitivity prediction model that can be used by clinicians and researchers to predict patient survival rates and achieve personalized treatment of LGG.
Endoscopic Ultrasound-Guided Versus Percutaneous Transhepatic Biliary Drainage in Patients With Malignant Biliary Obstruction: Which Is the Optimal Cost-Saving Strategy After Failed ERCP?
Authors: Yoon Won Jae , Shah Eric D. , Lee Tae Hoon , Jang Sunguk , Law Ryan , Park Do Hyun
Published: February 2022

Background and Aim

Although endoscopic ultrasound-guided biliary drainage (EUS-BD) after failed primary ERCP in malignant distal biliary obstruction has similar clinical outcomes compared to percutaneous transhepatic biliary drainage (PTBD), little is known about optimal cost-saving strategy after failed ERCP. We performed a cost analysis of EUS-BD and PTBD after failed ERCP in two countries with different health care systems in the East and West.

Methods

From an unpublished database nested in a randomized controlled trial, we compared the cost between EUS-BD and PTBD in Korea. The total cost was defined as the sum of the total biliary drainage costs plus the cost of hospital stay to manage adverse events. We also performed a cost-minimization analysis using a decision-analytic model of a US Medicare population.

Results

In Korea, the median total costs for the biliary intervention ($1,203.36 for EUS-BD vs. $1,517.83 for PTBD; P=.0015) and the median total costs for the entire treatment were significantly higher in PTBD ($4,175.53 for EUS-BD vs. $5,391.87 for PTBD; P=.0496) due to higher re-intervention rate in PTBD. In cost-minimization analysis of US Medicare population, EUS-BD would cost $9,497.03 and PTBD $13,878.44 from a Medicare insurance perspective (average cost-savings in choosing EUS-BD of $4,381.41 in the US). In sensitivity analysis, EUS-BD was favored over PTBD regardless of the expected re-intervention rate in EUS-BD and PTBD.

Conclusions

EUS-BD may have an impact on cost-savings due to better clinical outcomes profile compared to PTBD after failed ERCP, even in different medical insurance programs.
Case Report: Sequential Liver After Kidney Transplantation in a Patient With Sensenbrenner Syndrome (Cranioectodermal Dysplasia)
Authors: Ryżko Joanna , Walczak-Sztulpa Joanna , Czubkowski Piotr , Latos-Bieleńska Anna , Kowalski Adam , Stefanowicz Marek , Jarmużek Wioletta , Grenda Ryszard , Pawłowska Joanna
Published: February 2022

Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a rare ciliopathy clinically characterized by congenital craniofacial, skeletal, and ectodermal defects. Chronic kidney and liver insufficiency are also present in this disorder. Cranioectodermal dysplasia is an autosomal recessive and heterogeneous genetic disease. Six genes (IFT122, WDR35, IFT140, IFT43, IFT52, and WDR19) are known to be associated with this syndrome. Until 2021 more than 70 patients have been reported with CED, however, an orthotopic liver transplantation has been reported only in one case. Here, we present a case report of sequential liver-after-kidney transplantation in a male patient affected by CED. The kidney and liver transplantation was performed at the age of 7 and 12 years, respectively. Patients with Sensenbrenner syndrome require a multidisciplinary medical management and should regularly be followed-up by hepatologists and nephrologists, as the liver and kidney diseases are the major cause of morbidity and mortality.