bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroacupuncture Alleviates LPS-Induced ARDS Through α7 Nicotinic Acetylcholine Receptor-Mediated Inhibition of Ferroptosis
Authors: Zhang Yiguo , Zheng Li , Deng Huimin , Feng Di , Hu Song , Zhu Lina , Xu Wenting , Zhou Wenyu , Wang Yu , Min Keting , Zhou Qing , Chen Yuanli , Zhou Huanping , Yang Hao , Lv Xin
Published: February 2022

Acute respiratory distress syndrome (ARDS) is an uncontrollable, progressive pulmonary inflammatory disease, and as a common clinical critical disease, there is no effective treatment available. Electroacupuncture (EA) therapy is a type of traditional Chinese medicine physiotherapy that can alleviate the inflammatory response. However, the potential mechanism of EA in the treatment of ARDS is not yet clear. Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation. Recently, emerging evidence has shown that ferroptosis is closely related to the occurrence and development of ARDS caused by various pathological factors. Here, we further investigated whether EA-mediated inhibition of ferroptosis in lung tissue could attenuate lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms. In this study, mice were administered LPS intraperitoneally to establish a model of LPS-induced ARDS. We found that EA stimulation could not only reduce the exudation of inflammatory cells and proteins in the alveolar lumen but also significantly alleviate the pathological changes of lung tissue, inhibit the production of proinflammatory cytokines and improve the survival rate of mice. Concurrently, we also found that ferroptosis events occurred in the lung tissue of LPS-induced ARDS mice, manifested by elevated iron levels, ROS production and lipid peroxidation. Intriguingly, our results showed that EA stimulation at the Zusanli (ST36) acupoint activated α7 nicotinic acetylcholine receptor (α7nAchR) in lung tissue mainly through the sciatic nerve and cervical vagus nerve, thus exerting anti-ferroptosis and pulmonary protective effects. Additionally, these effects were eliminated by methyllycaconitine (MLA), a selective antagonist of α7nAchR. In vitro experiments, activation of α7nAchR protected alveolar epithelial cells from LPS-induced ferroptosis. Furthermore, our experiments showed that the pulmonary protective effects of EA stimulation were effectively reversed by erastin, a ferroptosis activator. Collectively, we demonstrated that EA stimulation could alleviate LPS-induced ARDS by activating α7nAchR to inhibit LPS-induced ferroptosis in alveolar epithelial cells. Targeting and regulating ferroptosis in alveolar epithelial cells may be a potential intervention approach for the treatment of LPS-induced ALI/ARDS in the future.
T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy
Authors: Sim Malcolm J. W. , Sun Peter D.
Published: February 2022

In cancer, non-synonymous DNA base changes alter protein sequence and produce neoantigens that are detected by the immune system. For immune detection, neoantigens must first be presented on class I or II human leukocyte antigens (HLA) followed by recognition by peptide-specific receptors, exemplified by the T-cell receptor (TCR). Detection of neoantigens represents a unique challenge to the immune system due to their high similarity with endogenous ‘self’ proteins. Here, we review insights into how TCRs detect neoantigens from structural studies and delineate two broad mechanistic categories: 1) recognition of mutated ‘self’ peptides and 2) recognition of novel ‘non-self’ peptides generated through anchor residue modifications. While mutated ‘self’ peptides differ only by a single amino acid from an existing ‘self’ epitope, mutations that form anchor residues generate an entirely new epitope, hitherto unknown to the immune system. We review recent structural studies that highlight these structurally distinct mechanisms and discuss how they may lead to differential anti-tumor immune responses. We discuss how T cells specific for neoantigens derived from anchor mutations can be of high affinity and provide insights to their use in adoptive T cell transfer-based immunotherapy.
Research Progress of Biodegradable Polymers in Repairing Achilles Tendon Injury
Authors: Zhang Jinchi , Wang Wange , Zhang Xinan , Yang Liqun , Zhang JinChao
Published: February 2022

Achilles tendon injury has become a common sports injury clinically, and its treatment and rehabilitation are essential, while the regenerative capacity of the Achilles tendon in adult mammals is limited. Therefore, it is necessary to promote the repair and remodelling of the Achilles tendon through efficient interventions. Biodegradable polymer materials are one of the most popular in the treatment and repair of soft tissues, ligaments, muscles, and organs injured by organisms to enhance the function of their wounded sites. Thus, it plays a specific role in “compensation” and is widely used in clinical medicine and rehabilitation. This review summarized the progress of poly (ε-caprolactone), polylactic acid, poly (lactic-co-glycolic acid), poly (trimethylene carbonate) (PTMC), and polydioxanone (PDS) in repairing Achilles tendon injury, indicating that the biodegradable polymers have succeeded in improving and treating Achilles tendon injuries. However, some problems such as lack of good affinity with cells and uncontrollable degradation of the biodegradable polymers should be overcome in repairing Achilles tendon injury. Therefore, the development of modified biodegradable polymers to make them an ideal repair material that meets the requirements is vital in improving Achilles tendon injuries. With the continuous development and close cooperation of life sciences and material sciences, excellent materials for repairing Achilles tendon injuries will undoubtedly be produced. The treatment of Achilles tendon injuries will be more straightforward, which will be a boon for many athletes.
Predicting Severe Disease and Critical Illness on Initial Diagnosis of COVID-19: Simple Triage Tools
Authors: Kurban Lutfi Ali S. , AlDhaheri Sharina , Elkkari Abdulbaset , Khashkhusha Ramzi , AlEissaee Shaikha , AlZaabi Amna , Ismail Mohamed , Bakoush Omran
Published: February 2022

Rationale

This study was conducted to develop, validate, and compare prediction models for severe disease and critical illness among symptomatic patients with confirmed COVID-19.

Methods

For development cohort, 433 symptomatic patients diagnosed with COVID-19 between April 15th 2020 and June 30th, 2020 presented to Tawam Public Hospital, Abu Dhabi, United Arab Emirates were included in this study. Our cohort included both severe and non-severe patients as all cases were admitted for purpose of isolation as per hospital policy. We examined 19 potential predictors of severe disease and critical illness that were recorded at the time of initial assessment. Univariate and multivariate logistic regression analyses were used to construct predictive models. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration and goodness of fit of the models were assessed. A cohort of 213 patients assessed at another public hospital in the country during the same period was used to validate the models.

Results

One hundred and eighty-six patients were classified as severe while the remaining 247 were categorized as non-severe. For prediction of progression to severe disease, the three independent predictive factors were age, serum lactate dehydrogenase (LDH) and serum albumin (ALA model). For progression to critical illness, the four independent predictive factors were age, serum LDH, kidney function (eGFR), and serum albumin (ALKA model). The AUC for the ALA and ALKA models were 0.88 (95% CI, 0.86–0.89) and 0.85 (95% CI, 0.83–0.86), respectively. Calibration of the two models showed good fit and the validation cohort showed excellent discrimination, with an AUC of 0.91 (95% CI, 0.83–0.99) for the ALA model and 0.89 (95% CI, 0.80–0.99) for the ALKA model. A free web-based risk calculator was developed.

Conclusions

The ALA and ALKA predictive models were developed and validated based on simple, readily available clinical and laboratory tests assessed at presentation. These models may help frontline clinicians to triage patients for admission or discharge, as well as for early identification of patients at risk of developing critical illness.
Comparison of Rumen Fermentation Parameters and Microbiota of Yaks From Different Altitude Regions in Tibet, China
Authors: Han Lulu , Xue Wanchao , Cao Hanwen , Chen Xiaoying , Qi Fasheng , Ma Tao , Tu Yan , Diao Qiyu , Zhang Chengfu , Cui Kai
Published: February 2022

Rumen microbiota are closely linked to feed utilization and environmental adaptability of ruminants. At present, little is known about the influence of different extreme environments on the rumen microbiota of yaks. In this study, 30 ruminal fluid samples from 30 healthy female yaks (average 280 kg of BW) in 5–8 years of life were collected from three regions in Tibet, China, and compared by gas chromatography and high-throughput sequencing. Results showed that propionic acid, butyric acid, and total volatile fatty acids were significantly (p < 0.05) higher, while microbial abundance and diversity were significantly (p < 0.05) lower, in the Nagqu (4,500 m altitude) compared with the Xigatse (4,800 m altitude) and Lhasa (3,800 m altitude) regions. Principal coordinate analysis revealed significant (p < 0.05) differences in rumen microbial composition of yaks from different regions. Specifically, Bacteroidetes and Firmicutes were identified by linear discriminant analysis effect size (LDA > 3) as being the signature phyla for Xigatse and Nagqu regions, respectively. In addition, the relative abundance of Rikenellaceae_RC9_gut_group, Quinella, Prevotellaceae_UCG-003, Lachnospiraceae_NK3A20_group, Papillibacter, Ruminococcaceae_UCG-010, Prevotellaceae_NK3B31_group, and Ruminococcaceae_UCG-005 correlated with altitude and rumen fermentation parameters (p < 0.05). Finally, the predicted function of rumen microbiota was found to differ between regions (p < 0.05). In summary, our results reveal that regions located at different altitudes influence microbiota composition and fermentation function of yaks’ rumen. The present findings can provide mechanistic insights on yak adaptation to high altitudes and improve the feeding efficiency of these animals in extreme regions.
Campylobacter in Wild Birds: Is It an Animal and Public Health Concern?
Authors: Ahmed Nejash A. , Gulhan Timur
Published: February 2022

Campylobacteriosis continues to be one of the leading causes of foodborne bacterial zoonotic infections worldwide. Despite its public health importance, the status of this disease in wild birds and the possibility of transmission from wild birds to domestic animals and humans have not been clearly elucidated yet. This article reviews the available literature with the aim of making a comprehensive manuscript on this disease status in wild birds and the possibility of interspecies transmission. Campylobacter has been isolated from various species of wild birds worldwide, with C. jejuni being the most commonly isolated species. The prevalence of Campylobacter in wild birds may vary depending on several factors like geographical location, season, the bird’s health status, bird species, sample type, the method used, and ecological factors. Molecular studies over the past two to three decades have characterized Campylobacter strains isolated from wild birds and have come up with results that fall into two categories. The first are those that report overlapping strains among human, domestic animal, and wild bird isolates. The results of the studies under this category emphasize that wild birds carry strains of Campylobacter, which are indistinguishable from domestic animals and humans and are therefore an important public and animal health concern. In contrast, the studies under the second category highlight significant differences in Campylobacter population structure among these hosts. Despite the controversiality and the inadequacy of current research to draw a full conclusion, the role of wild birds in the epidemiology of Campylobacter should not be undermined as drug-resistant strains, especially resistance to tetracycline and fluoroquinolones, are increasingly documented. In addition, source attribution studies have linked human cases of Campylobacter infections to wild birds. Therefore, the role of wild birds in the epidemiology of Campylobacter infection should not be neglected. However, in order to determine disease status in wild birds and the precise role of wild birds in domestic animals and human health, detail-oriented epidemiological investigations characterizing the genetic relatedness of isolates from the respective species and environment through one health approach are warranted.
One-Step Assembly of a Porcine Epidemic Diarrhea Virus Infectious cDNA Clone by Homologous Recombination in Yeast: Rapid Manipulation of Viral Genome With CRISPR/Cas9 Gene-Editing Technology
Authors: Zhou Yanyang , Li Chenxi , Ren Cicheng , Hu Jingbo , Song Changxu , Wang Xinjie , Li Yanhua
Published: February 2022

Porcine epidemic diarrhea virus (PEDV), a swine enteric coronavirus causing acute diarrhea in piglets, is one of the major threatens to the pork industry globally. Reverse genetics is a valuable tool for the virological study and vaccine development for coronaviruses. Due to the large size and unstable problem in Escherichia coli of coronavirus genome, construction and manipulation of reverse genetics system for coronaviruses remain laborious and time-consuming. In this study, a reverse genetics system of the genotype II PEDV strain HM was generated using the transformation-associated recombination (TAR) technology in yeast within 1 week. The rescued virus (rPEDV) exhibited similar growth properties to the wild-type virus in vitro. With this PEDV infectious cDNA clone, CRISPR/Cas9 technology and homologous recombination were combined to generate a recombinant virus rPEDV-EGFP in which the ORF3 gene was swapped with an EGFP gene. The reporter virus displayed similar growth properties to the parental virus rPEDV and remained stable during serial passage in vitro. Of note, the strategies of construction and manipulation of PEDV infectious cDNA clone are extremely simple and efficient, which could be applied for other RNA viruses and DNA viruses.
The Complexity of SARS-CoV-2 Infection and the COVID-19 Pandemic
Authors: da Silva Torres Maria Karoliny , Bichara Carlos David Araújo , de Almeida Maria de Nazaré do Socorro , Vallinoto Mariana Cayres , Queiroz Maria Alice Freitas , Vallinoto Izaura Maria Vieira Cayres , dos Santos Eduardo José Melo , de Carvalho Carlos Alberto Marques , Vallinoto Antonio Carlos R.
Published: February 2022

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the death of millions of people worldwide and thousands more infected individuals developed sequelae due to the disease of the new coronavirus of 2019 (COVID-19). The development of several studies has contributed to the knowledge about the evolution of SARS-CoV2 infection and the disease to more severe forms. Despite this information being debated in the scientific literature, many mechanisms still need to be better understood in order to control the spread of the virus and treat clinical cases of COVID-19. In this article, we carried out an extensive literature review in order to bring together, in a single article, the biological, social, genetic, diagnostic, therapeutic, immunization, and even socioeconomic aspects that impact the SAR-CoV-2 pandemic. This information gathered in this article will enable a broad and consistent reading of the main aspects related to the current pandemic.
Cell Membrane Remodeling Mediates Polymyxin B Resistance in Klebsiella pneumoniae: An Integrated Proteomics and Metabolomics Study
Authors: Chen Xinyi , Tian Jingjing , Luo Can , Wang Xiaofan , Li Xianping , Wang Min
Published: February 2022

Polymyxin B (PB) is introduced into the clinic as the last-line therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). Unfortunately, increased resistance to PB in Klebsiella pneumoniae (K. pneumoniae) has threatened global health. Resistance of K. pneumoniae to PB was induced by passaging in serial concentrations of PB and determined by microbroth dilution method. Growth characteristics of induced strains including growth curve, reversibility of resistance, and biofilm formation (crystal violet staining method) were measured. This study employed TMT-labeled quantitative proteomics and LC-MS/MS metabolomics analysis to investigate the key biological processes associated with PB resistance in K. pneumoniae. A total of 315 differentially expressed proteins (DEPs) were identified, of which 133 were upregulated and 182 were downregulated in the PB-resistant K. pneumoniae. KEGG enrichment analysis revealed that the DEPs were mainly involved in ATP-binding cassette (ABC) transporters and cationic antimicrobial peptide (CAMP) resistance. Proteins related to central carbon metabolism were inhibited in the PB-resistant K. pneumoniae, but proteins mediating LPS modification were activated. Transcriptional levels of CAMP resistance-related proteins were significantly different between PB-susceptible and -resistant K. pneumoniae. PB treatment led to an increase in reactive oxygen species (ROS) levels of K. pneumoniae. Metabolomics data demonstrated that 23 metabolites were significantly upregulated in PB-resistant K. pneumoniae and 5 were downregulated. The differential metabolites were mainly lipids, including glycerophospholipids, sphingolipids, and fatty acids. Exposure to PB resulted in increased level of phospholipid transport gene mlaF in K. pneumoniae. Our study suggested that membrane remodeling and inhibited central carbon metabolism are conducive to the development of PB resistance in K. pneumoniae.
Multi-Omics Profiling Specifies Involvement of Alternative Ribosomal Proteins in Response to Zinc Limitation in Mycobacterium smegmatis
Authors: Dow Allexa , Burger Andrew , Marcantonio Endrei , Prisic Sladjana
Published: February 2022

Zinc ion (Zn2+) is an essential micronutrient and a potent antioxidant. However, Zn2+ is often limited in the environment. Upon Zn2+ limitation, Mycolicibacterium (basonym: Mycobacterium) smegmatis (Msm) undergoes a morphogenesis, which relies on alternative ribosomal proteins (AltRPs); i.e., Zn2+-independent paralogues of Zn2+-dependent ribosomal proteins. However, the underlying physiological changes triggered by Zn2+ limitation and how AltRPs contribute to these changes were not known. In this study, we expand the knowledge of mechanisms utilized by Msm to endure Zn2+ limitation, by comparing the transcriptomes and proteomes of Zn2+-limited and Zn2+-replete Msm. We further compare, corroborate and contrast our results to those reported for the pathogenic mycobacterium, M. tuberculosis, which highlighted conservation of the upregulated oxidative stress response when Zn2+ is limited in both mycobacteria. By comparing the multi-omics analysis of a knockout mutant lacking AltRPs (ΔaltRP) to the Msm wild type strain, we specify the involvement of AltRPs in the response to Zn2+ limitation. Our results show that AltRP expression in Msm does not affect the conserved oxidative stress response during Zn2+ limitation observed in mycobacteria, but AltRPs do significantly impact expression patterns of numerous genes that may be involved in morphogenesis or other adaptive responses. We conclude that AltRPs are not only important as functional replacements for their Zn2+-dependent paralogues; they are also involved in the transcriptomic response to the Zn2+-limited environment.
Diversity in the Characteristics of Klebsiella pneumoniae ST101 of Human, Environmental, and Animal Origin
Authors: De Koster Sien , Rodriguez Ruiz Juan Pablo , Rajakani Sahaya Glingston , Lammens Christine , Glupczynski Youri , Goossens Herman , Xavier Basil Britto
Published: February 2022

Background

Klebsiella pneumoniae ST101 is an emerging high-risk clone which exhibits extensive drug resistance. Bacterial strains residing in multiple hosts show unique signatures related to host adaptation. In this study, we assess the genetic relationship of K. pneumoniae ST101 isolated from hospital samples, the environment, community, and livestock using whole genome sequencing (WGS).

Materials and Methods

We selected ten K. pneumoniae ST101 strains from hospitalized patients in Italy (n = 3) (2014) and Spain (n = 5) (2015–2016) as well as Belgian livestock animals (n = 2) (2017–2018). WGS was performed with 2 × 250 bp paired-end sequencing (Nextera XT) sample preparation kit and MiSeq (Illumina Inc.). Long-read sequencing (Pacbio Sequel I) was used to sequence the two livestock strains and three Italian hospital-associated strains. Furthermore, a public ST101 sequence collection of 586 strains (566 hospital-associated strains, 12 environmental strains, six strains from healthy individuals, one food-associated strain and one pig strain) was obtained. BacPipe and Kleborate were used to conduct genome analysis. ISFinder was used to find IS elements, and PHASTER was utilized to identify prophages. A phylogenetic tree was constructed to illustrate genetic relatedness.

Results

Hospital-associated K. pneumoniae ST101 showed higher resistance scores than non-clinical isolates from healthy individuals, the environment, food and livestock (1.85 ± 0.72 in hospital-associated isolates vs. 1.14 ± 1.13 in non-clinical isolates, p < 0.01). Importantly, the lack of integrative conjugative elements ICEKp bearing iron-scavenging yersiniabactin siderophores (ybt) in livestock-associated strains suggests a lower pathogenicity potential than hospital-associated strains. Mobile genetic elements (MGE) appear to be an important source of diversity in K. pneumoniae ST101 strains from different origins, with a highly stable genome and few recombination events outside the prophage-containing regions. Core genome MLST based analysis revealed a distinct genetic clustering between human and livestock-associated isolates.

Conclusion

The study of K. pneumoniae ST101 hospital-associated and strains from healthy individuals and animals revealed a genetic diversity between these two groups, allowing us to identify the presence of yersiniabactin siderophores in hospital-associated isolates. Resistance and virulence levels in livestock-associated strains were considerably lower than hospital-associated strains, implying that the public health risk remains low. The introduction of an ICEKp into animal strains, on the other hand, might pose a public threat over time.
The Hidden Enemy Within: Non-canonical Peptides in Virus-Induced Autoimmunity
Authors: Lodha Manivel , Erhard Florian , Dölken Lars , Prusty Bhupesh K.
Published: February 2022

Viruses play a key role in explaining the pathogenesis of various autoimmune disorders, whose underlying principle is defined by the activation of autoreactive T-cells. In many cases, T-cells escape self-tolerance due to the failure in encountering certain MHC-I self-peptide complexes at substantial levels, whose peptides remain invisible from the immune system. Over the years, contribution of unstable defective ribosomal products (DRiPs) in immunosurveillance has gained prominence. A class of unstable products emerge from non-canonical translation and processing of unannotated mammalian and viral ORFs and their peptides are cryptic in nature. Indeed, high throughput sequencing and proteomics have revealed that a substantial portion of our genomes comprise of non-canonical ORFs, whose generation is significantly modulated during disease. Many of these ORFs comprise short ORFs (sORFs) and upstream ORFs (uORFs) that resemble DRiPs and may hence be preferentially presented. Here, we discuss how such products, normally “hidden” from the immune system, become abundant in viral infections activating autoimmune T-cells, by discussing their emerging role in infection and disease. Finally, we provide a perspective on how these mechanisms can explain several autoimmune disorders in the wake of the COVID-19 pandemic.
The Neuropsychiatric Changes After COVID-19 Quarantine in Patients With Cognitive Impairment and Their Caregivers in Chongqing, China: A Cohort Study
Authors: Yuan Shiyun , Zhang Wenbo , Yao Qiang , Lü Wenqi , Yu Wuhan , Zhong Fuxin , Wang Yan , Xing Dianxia , Wang Xiaoqin , Song Jiaqi , Huang Hong , Chen Chenxi , Liu Junjin , Yu Weihua , Lü Yang
Published: February 2022

Background

The follow-up study on neuropsychiatric changes after the lifting of coronavirus disease 2019 (COVID-19) quarantine in patients with cognitive impairment and their caregivers is still lacking, and relative information is needed to formulate more comprehensive healthcare prevention measures worldwide.

Aims

To provide data on the changes in neuropsychiatric performance after the lifting of COVID-19 quarantine in patients with cognitive disorders and their caregivers.

Methods

Two surveys in Chongqing, China were conducted via telephonic interview with 531 patients and their caregivers. The baseline survey was performed from February 11 to 23, 2020, and the follow-up was from October 24 to November 9, 2020. The data of neuropsychiatric symptoms (NPSs), sleep, nutrition, and chronic diseases of patients, as well as the burden of care, anxiety, and depression of caregivers were evaluated.

Results

Significant alleviation of NPSs after the lifting of COVID-19 quarantine was observed in patients with mild cognitive impairment (MCI) and dementia (both P < 0.05). Compared with baseline, the prevalence for NPSs of all participants dropped from 57.94 to 38.82%. Among NPS subdomains, apathy displayed the biggest decline at follow-up by 10.72%, followed by nighttime behavior by 8.65%. Mixed effect generalized estimation equation analysis showed significant amelioration in hallucination, depression, apathy, irritability, aberrant motor behavior, and nighttime behavior (all P < 0.05), with the most prominent changes in nighttime behavior and apathy. Among the patients with unsatisfactory control of chronic disease, the medication adherence rate dropped by approximately 30% after the lifting of quarantine. More importantly, around 13% increase of care burden was observed among the caregivers at follow-up, with both depression and anxiety rising by nearly 4%.

Conclusion

The prolonged quarantine may exacerbate NPS in patients with memory disorders, while the care burden and mental stability of the caregivers after the pandemic should also be concerned.
Cannabis Use and Resting State Functional Connectivity in the Aging Brain
Authors: Watson Karli K. , Bryan Angela D. , Thayer Rachel E. , Ellingson Jarrod M. , Skrzynski Carillon J. , Hutchison Kent E.
Published: February 2022

Several lines of evidence suggest that older adults (aged 65+) sharply increased their cannabis use over the last decade, highlighting a need to understand the effects of cannabis in this age group. Pre-clinical models suggest that cannabinoids affect the brain and cognition in an age-dependent fashion, having generally beneficial effects on older animals and deleterious effects on younger ones. However, there is little research on how cannabis affects the brains of older adults or how older adults differ from younger adults who use cannabis. Resting state functional connectivity (rsFC) measures provide sensitive metrics of age-related cognitive decline. Here we compared rsFC in older adults who are either regular users of cannabis or non-users. We found stronger connectivity between sources in the hippocampus and parahippocampal cortex, and targets in the anterior lobes of the cerebellum in older adult cannabis users relative to non-users. A similar pattern of strengthened connectivity between hippocampal and cerebellar structures was also present in 25–35 year old non-users in comparison to 60–88 year old non-users. These findings suggest that future studies should examine both the potential risks of cannabinoids, as well as a potential benefits, on cognition and brain health for older adults.
Gender-Related Differences in Regional Cerebral Glucose Metabolism in Normal Aging Brain
Authors: Feng Bei , Cao Jiang , Yu YaPing , Yang HaiYan , Jiang YangHongYan , Liu Ying , Wang Rong , Zhao Qian
Published: February 2022

Objectives: This study was aimed to investigate the gender-related differences of regional cerebral glucose metabolism in healthy people along the age using 18F-FDG PET/CT.

Methods: We recruited 344 healthy volunteers, including 217 males and 127 females (age range: 40–89 years old). All subjects underwent fluorine-18 fluorodeoxyglucose(18F-FDG) positron emission tomography (PET). All the data were divided into four groups for every 10 years old. Each participant was carefully screened from PET, MR, and other examinations in order to exclude the abnormalities, such as neurodegenerative or psychiatric disorders, alcohol/abuse, cerebral vascular disorders, metabolic diseases like diabetes mellitus and hyperthyroidism, and other systemic malignancies. The 40–50 years old group was set as the baseline group. Statistical parametric mapping (SPM) analysis was employed to illustrate the differences among groups.

Results: Compared to the baseline group, whether in a cohort or different gender groups, the decrease of brain glucose metabolism was shown in the bilateral frontal lobe, anterior cingulate gyrus, and the bilateral temporal lobe. In males, the regions of decreased metabolism were bilateral frontal lobe, caudate nucleus, and cingulate gyrus, whereas that of females were left occipital lobe, cerebellum, and the thalamus. However, the overall decrease of brain metabolism in men and women began from the age of 60s, an aggravated decrease from 70s was only observed in males.

Conclusion: (1) An obviously decreased brain metabolism was found from 60 years old, especially in the bilateral frontal lobe, bilateral temporal lobe, and inferior cingulate gyrus; (2) We found specific brain metabolic differences between genders, including the caudate nucleus region in males and the occipital lobe region in females; and (3) The aging trend is different between genders.
Retinal Nerve Fiber Layer Thickness and Associations With Cognitive Impairment in Parkinson’s Disease
Authors: Chang Zihan , Xie Fen , Li Hualing , Yuan Feilan , Zeng Lina , Shi Lin , Zhu Shuzhen , Lu Xiaohe , Wei Xiaobo , Wang Qing
Published: February 2022

Objective

This study intended to investigate whether retinal nerve fiber layer (RNFL) thickness could become a potential marker in patients with Parkinson’s disease with cognitive impairment (PD-CI).

Methods

Fifty-seven PD patients and 45 age-matched healthy controls (HCs) were recruited in our cross-sectional study and completed optical coherence tomography (OCT) evaluations. PD with normal cognition (PD-NC) and cognitive impairment (PD-CI) patients were divided following the 2015 Movement Disorder Society criteria. RNFL thickness was quantified in subfields of the 3.0-mm circle surrounding the optic disk; while a battery of neuropsychiatric assessments was conducted to estimate the Parkinsonism severity. General linear models and one-way ANOVA were adopted to assess RNFL thickness between subgroups with different cognitive statuses; logistic regression analyses were applied to determine the relation between RNFL and PD-CI cases.

Results

Compared with HCs, more thinning of the RNFL was observed in the inferior and temporal sectors in PD patients, especially in the PD-CI group. Inferior RNFL thickness was reduced in PD-CI compared with PD-NC patients. Logistic regression analysis found that inferior RNFL thickness was independently associated with PD-CI cases (odds ratio = 0.923,p= 0.014). Receiver operating characteristic analysis showed that the RNFL-involved combined model provided a high accuracy in screening cognitive deficiency in PD cases (area under the curve = 0.85,p< 0.001).

Conclusion

Reduced RNFL thickness especially in the inferior sector is independently associated with PD-CI patients. Our study present new perspectives into verifying possible indicators for neuropathological processes or disease severity in Parkinsonians with cognitive dysfunction.
Cellular and Molecular Gradients in the Ventral Horns With Increasing Distance From the Injury Site After Spinal Cord Contusion
Authors: Kabdesh Ilyas M. , Mukhamedshina Yana O. , Arkhipova Svetlana S. , Sabirov Davran K. , Kuznecov Maxim S. , Vyshtakalyuk Alexandra B. , Rizvanov Albert A. , James Victoria , Chelyshev Yuri A.
Published: February 2022

To identify cellular and molecular gradients following spinal cord injury (SCI), a rat contusion model of severe SCI was used to investigate the expression of NG2 and molecules that identify astrocytes and axons of the ventral horns (VH) at different distances on 7 and 30 days post-injury (dpi). A gradient of expression of NG2+/Olig2+ cells was determined, with the highest concentrations focused close to the injury site. A decrease in NG2 mean intensity correlates with a decrease in the number of NG2+ cells more distally. Immunoelectron microscopy subsequently revealed the presence of NG2 in connection with the membrane and within the cytoplasm of NG2+ glial cells and in large amounts within myelin membranes. Analysis of the astrocyte marker GFAP showed increased expression local to injury site from 7 dpi, this increase in expression spread more distally from the injury site by 30 dpi. Paradoxically, astrocyte perisynaptic processes marker GLT-1 was only increased in expression in areas remote from the epicenter, which was traced both at 7 and 30 dpi. Confocal microscopy showed a significant decrease in the number of 5-HT+ axons at a distance from the epicenter in the caudal direction, which is consistent with a decrease in β3-tubulin in these areas. The results indicate significant cellular and molecular reactions not only in the area of the gray matter damage but also in adjacent and remote areas, which is important for assessing the possibility of long-distance axonal growth.
Impact of Dose of Combined Conventional and Robotic Therapy on Upper Limb Motor Impairments and Costs in Subacute Stroke Patients: A Retrospective Study
Authors: Pila Ophélie , Koeppel Typhaine , Grosmaire Anne-Gaëlle , Duret Christophe
Published: February 2022

Introduction

Robot-based training integrated into usual care might optimize therapy productivity and increase treatment dose. This retrospective study compared two doses of an upper limb rehabilitation program combining robot-assisted therapy and occupational therapy on motor recovery and costs after stroke.

Methods

Thirty-six subacute stroke patients [Fugl-Meyer Assessment (FMA) score 32 ± 12 points; mean ± SD] underwent a combined program of 29 ± 3 sessions of robot-assisted therapy and occupational therapy. Scheduled session time for the higher dose group (HG) was 90 min (two 45-min sessions;n= 14) and for the lower dose group (LG) was 60 min (two 30-min sessions;n= 22). Pre-/post-treatment change in FMA score (ΔFMA, %), actual active time (min), number of movements and number of movements per minute per robot-assisted therapy session were compared between groups. The costs of the combined programs were also analyzed.

Results

ΔFMA did not differ significantly between groups; the HG improved by 16 ± 13 % and the LG by 11 ± 8%. A between-group difference was found for actual active time (p= 1.06E−13) and number of movements (p= 4.42E−2) but not for number of movements per minute during robot-assisted therapy: the HG performed 1,023 ± 344 movements over 36 ± 3 min and the LG performed 796 ± 301 movements over 29 ± 1 min. Both groups performed 28 movements per minute. The combined program cost was €2017 and €1162 for HG and LG, respectively.

Conclusions

Similar motor improvements were observed following two doses of movement-based training. The reduction in scheduled session time did not affect the intensity of the practice and met economic constraints.
Plaque Characteristics in Young Adults With Symptomatic Intracranial Atherosclerotic Stenosis: A Preliminary Study
Authors: Li Ling , Tang Min , Yan Xuejiao , Gao Jie , Ma Niane , Shi Xiaorui , Niu Yaxin , Wen Yu , Ai Kai , Lei Xiaoyan , Zhang Xiaoling
Published: February 2022

Purpose

To determine how intracranial vascular wall and atherosclerosis plaque characteristics differ between young and old adults with sICAS.

Methods

Eighty-four consecutive patients with sICAS who underwent high-resolution magnetic resonance imaging (HRMRI) from December 2017 to July 2020 were retrospectively collected. These participants were divided into young adult group (18–50 years, n = 28) and old adult group (>50 years, n = 56). Reviewers were blinded to any clinical information and HRMRI scans were analyzed for qualitative and quantitative indicators of vascular walls and plaque at the maximal lumen narrowing site using the independent-sample t-test, Mann–Whitney U-test, chi-square test or Fisher exact test, and logistic regression analysis.

Results

Young patients with sICAS had significantly smaller maximum wall thickness (1.45 ± 0.38 vs.1.75 ± 0.51 mm2, P = 0.003), higher prevalence of positive remodeling (53.57 vs. 21.43%, P = 0.003), and lower prevalence of diabetes mellitus (14.29 vs. 35.71%, P = 0.04) than old patients. Plaque burden and other plaque features were comparable between young and old patients.

Conclusion

Young patients with sICAS have smaller maximum wall thickness and greater ability to reconstruct, and are more likely to show positive remodeling, which may lead to some atherosclerotic lesions being missed. Young patients with evidence of vessel narrowing should be carefully examined for presence of high-risk atherosclerotic plaque.
Viability Study of Machine Learning-Based Prediction of COVID-19 Pandemic Impact in Obsessive-Compulsive Disorder Patients
Authors: Tubío-Fungueiriño María , Cernadas Eva , Gonçalves Óscar F. , Segalas Cinto , Bertolín Sara , Mar-Barrutia Lorea , Real Eva , Fernández-Delgado Manuel , Menchón Jose M. , Carvalho Sandra , Alonso Pino , Carracedo Angel , Fernández-Prieto Montse
Published: February 2022

Background

Machine learning modeling can provide valuable support in different areas of mental health, because it enables to make rapid predictions and therefore support the decision making, based on valuable data. However, few studies have applied this method to predict symptoms’ worsening, based on sociodemographic, contextual, and clinical data. Thus, we applied machine learning techniques to identify predictors of symptomatologic changes in a Spanish cohort of OCD patients during the initial phase of the COVID-19 pandemic.

Methods

127 OCD patients were assessed using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured clinical interview during the COVID-19 pandemic. Machine learning models for classification (LDA and SVM) and regression (linear regression and SVR) were constructed to predict each symptom based on patient’s sociodemographic, clinical and contextual information.

Results

A Y-BOCS score prediction model was generated with 100% reliability at a score threshold of ± 6. Reliability of 100% was reached for obsessions and/or compulsions related to COVID-19. Symptoms of anxiety and depression were predicted with less reliability (correlation R of 0.58 and 0.68, respectively). The suicidal thoughts are predicted with a sensitivity of 79% and specificity of 88%. The best results are achieved by SVM and SVR.

Conclusion

Our findings reveal that sociodemographic and clinical data can be used to predict changes in OCD symptomatology. Machine learning may be valuable tool for helping clinicians to rapidly identify patients at higher risk and therefore provide optimized care, especially in future pandemics. However, further validation of these models is required to ensure greater reliability of the algorithms for clinical implementation to specific objectives of interest.
A Speech-Level–Based Segmented Model to Decode the Dynamic Auditory Attention States in the Competing Speaker Scenes
Authors: Wang Lei , Wang Yihan , Liu Zhixing , Wu Ed X. , Chen Fei
Published: February 2022

In the competing speaker environments, human listeners need to focus or switch their auditory attention according to dynamic intentions. The reliable cortical tracking ability to the speech envelope is an effective feature for decoding the target speech from the neural signals. Moreover, previous studies revealed that the root mean square (RMS)–level–based speech segmentation made a great contribution to the target speech perception with the modulation of sustained auditory attention. This study further investigated the effect of the RMS-level–based speech segmentation on the auditory attention decoding (AAD) performance with both sustained and switched attention in the competing speaker auditory scenes. Objective biomarkers derived from the cortical activities were also developed to index the dynamic auditory attention states. In the current study, subjects were asked to concentrate or switch their attention between two competing speaker streams. The neural responses to the higher- and lower-RMS-level speech segments were analyzed via the linear temporal response function (TRF) before and after the attention switching from one to the other speaker stream. Furthermore, the AAD performance decoded by the unified TRF decoding model was compared to that by the speech-RMS-level–based segmented decoding model with the dynamic change of the auditory attention states. The results showed that the weight of the typical TRF component approximately 100-ms time lag was sensitive to the switching of the auditory attention. Compared to the unified AAD model, the segmented AAD model improved attention decoding performance under both the sustained and switched auditory attention modulations in a wide range of signal-to-masker ratios (SMRs). In the competing speaker scenes, the TRF weight and AAD accuracy could be used as effective indicators to detect the changes of the auditory attention. In addition, with a wide range of SMRs (i.e., from 6 to –6 dB in this study), the segmented AAD model showed the robust decoding performance even with short decision window length, suggesting that this speech-RMS-level–based model has the potential to decode dynamic attention states in the realistic auditory scenarios.
Traumatic Brain Injury Is Associated With Both Hemorrhagic Stroke and Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Qu Donghao , Li Wenchen , Zhang Shuyan , Li Ri , Wang Haifeng , Chen Bo
Published: February 2022

Background

Traumatic brain injury (TBI) is considered a risk factor for the development of stroke (Hemorrhagic Stroke and Ischemic Stroke). We performed this systemic review and meta-analysis to determine the association of prior TBI with the subsequent diagnosis of stroke.

Methods

We systematically searched PubMed, EMBASE, and the Cochrane Library for cohort studies involving TBI patients who subsequently developed stroke. Study selection, data extraction, and quality assessment were performed by two separate researchers. Data were analyzed with random-effects models, and a secondary analysis stratified by the type of stroke was performed.

Results

Of the 741 identified studies, 6 studies were eligible for inclusion, with more than 2,200,000 participants. TBI predicted the occurrence of stroke in the random-effect model, with a relative risk of 2.14 (95% CI 1.97–2.32, P < 0.001). Furthermore, in the analysis of each type of stroke, TBI was associated with the incidence of ischemic stroke (RR 1.351 95% CI 1.212–1.506, P < 0.001), and TBI was associated with an even greater increase in the incidence of hemorrhagic stroke (RR 6.118 95% CI 5.265–7.108, P < 0.001).

Conclusion

Our meta-analysis showed that TBI was associated with a more than two-fold increase in the risk of stroke. However, owing to the high degree of heterogeneity, decisions should be made on a patient-by-patient basis. The occurrence of TBI is associated with the development of both hemorrhagic and ischemic stroke, and the risk of hemorrhagic stroke is much higher than that of ischemic stroke in TBI patients.
Using Collagen Peptides From the Skin of Monkfish (Lophius litulon) to Ameliorate Kidney Damage in High-Fat Diet Fed Mice by Regulating the Nrf2 Pathway and NLRP3 Signaling
Authors: Miao Bingtao , Zheng Jiawen , Zheng Guoping , Tian Xiaoxiao , Zhang Wen , Yuan Falei , Yang Zuisu
Published: February 2022

Background

Oxidative stress and inflammation play important roles in high-fat diet (HFD) induced kidney damage. Previous studies show that the collagen extracted from the skin of monkfish (Lophius litulon) with pepsin (pepsin-solubilized collagen, PSC) exhibits good biological activities. This study investigates the protective effect of PSCP against chronic kidney injury in HFD-fed mice.

Methods

Pepsin-solubilized collagen was further hydrolyzed into collagen peptides, and the compound with the best 2,2-diphenyl-1-picrylhydrazyl (DPPH) clearance rate was named pepsin-solubilized collagen peptide (PSCP). A group of mice were fed an HFD for 4 weeks, and then for another 6 weeks PSCP was added to their diet at the amount of either 100 or 200 mg/kg.

Results

Pepsin-solubilized collagen peptide treatment (200 mg/kg) reduced the mice's serum levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) by 27, 20, and 37%, respectively. This treatment also remarkably improved renal histopathology. Moreover, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were increased by 96, 52, and 74%, respectively, and decreased the malondialdehyde (MDA) level by 36%. Additionally, PSCP activated the Nrf2 pathway and inhibited NLRP3 signaling to significantly reduce the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α.

Conclusions

Our results indicate that compound PSCP has the potential to prevent or control chronic kidney damage.
Dairy as a Source of Iodine and Protein in the UK: Implications for Human Health Across the Life Course, and Future Policy and Research
Authors: Witard Oliver C. , Bath Sarah C. , Dineva Mariana , Sellem Laury , Mulet-Cabero Ana-Isabel , Dongen Laura H. van , Zheng Ju-Sheng , Valenzuela Carina , Smeuninx Benoit
Published: February 2022

This narrative review summarizes key concepts in dairy nutrition for supporting human health throughout the life course. Milk and dairy products have been a staple component of our diet for thousands of years and provide a wide range of important nutrients that are otherwise difficult to obtain from dairy-free diets. In this review, we provide a broad perspective on the nutritional roles of iodine and dairy protein in supporting human health during pregnancy and early life, childhood and adolescence, mid- and later-life. New methodologies to identify biomarkers of dairy intake via high-throughput mass spectrometry are discussed, and new concepts such as the role of the food matrix in dairy nutrition are introduced. Finally, future policy and research related to the consumption of dairy and non-dairy alternatives for health are discussed with a view to improving nutritional status across the lifespan.