bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Omics Analysis Reveals the Systematic Relationship Between Oral Homeostasis and Chronic Sleep Deprivation in Rats
Authors: Chen Pan , Wu Hao , Yao Hongliang , Zhang Jiashuo , Fan Weiyang , Chen Zhen , Su Weiwei , Wang Yonggang , Li Peibo
Published: March 2022

Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.
Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
Authors: Ziemssen Tjalf , Arnold Douglas L. , Alvarez Enrique , Cross Anne H. , Willi Roman , Li Bingbing , Kukkaro Petra , Kropshofer Harald , Ramanathan Krishnan , Merschhemke Martin , Kieseier Bernd , Su Wendy , Häring Dieter A. , Hauser Stephen L. , Kappos Ludwig , Kuhle Jens
Published: March 2022

Objective

This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS).

Background

Previous post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment.

Design/Methods

In this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (>median) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup.

Results

High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p<0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, −0.32% vs. −0.24%, p=0.044, and teriflunomide, −0.43% vs. −0.29%, p=0.002), thalamic volume (−0.56% vs. −0.31%, p=0.047 and −0.94% vs. −0.49%, p<0.001), and WM volume (−0.30% vs. −0.19%, p=0.083 and −0.38% vs. −0.18%, p=0.003) but not of cGM volume (−0.39% vs. −0.32%, p=0.337 and −0.49% vs. −0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients.

Conclusion

This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients.
The Ups and Downs of Using Active Acoustic Technologies to Study Fish at Tidal Energy Sites
Authors: Viehman Haley A. , Hasselman Daniel J. , Douglas Jessica , Boucher Tyler
Published: March 2022

Active acoustic instruments (echosounders) are well-suited for collecting high-resolution information on fish abundance and distribution in the areas targeted for tidal energy development, which is necessary for understanding the potential risks tidal energy devices pose to fish. However, a large proportion of echosounder data must often be omitted due to high levels of backscatter from air entrained into the water column. To effectively use these instruments at tidal energy sites, we need a better understanding of this data loss and how it may affect estimates of fish abundance and vertical distribution. We examined entrained air contamination in echosounder data from the Fundy Ocean Research Center for Energy (FORCE) tidal energy test site in Minas Passage, Nova Scotia, where current speeds can exceed 5 m·s-1. Entrained air depth was highly variable and increased with current speed, and contamination was lowest during neap tides. The lower 70% of the water column and current speeds <3 m·s-1were generally well-represented in the dataset. However, under-sampling of the upper water column and faster speeds strongly affected simulated fish abundance estimates, with error highly dependent on the underlying vertical distribution of fish. Complementary sensing technologies, such as acoustic telemetry and optical instruments, could be used concurrently with echosounders to fill gaps in active acoustic datasets and to maximize what can be learned about fish abundance and distribution at tidal energy sites.
Catalyzing Remote Collaboration During the COVID-19 Pandemic and Beyond: Early Career Oceanographers Adopt Hybrid Open Science Framework
Authors: Rudzin Johna E. , Soule Dax C. , Whitaker Justine , Berger Halle , Clayton Sophie , Fogaren Kristen E.
Published: March 2022

The COVID-19 pandemic introduced many challenges for research scientists: reduction of lab and field observation collection and in-person meetings. These new constraints forced researchers to remote work and virtual networking, dramatically influencing scientific inquiry. Such challenges are compounded for those in early stages of their career, where data collection and networking are vital to be seen as productive. However, during this trying time of remote work, we, as a collective of early-career oceanographers, were actively developing and improving on an already-existent hybrid community of practice. Through our experiences, we believe this type of framework can enhance virtual collaboration to the point that it outlasts the pandemic and helps create new synergies that will diversify and enhance scientific inquiry within the ocean science community. We describe a hybrid community of practice and an example workflow that models effective collaboration. We have found that three components to this model are necessary for effective collaboration, inspiration, and communication: 1) openly accessible data, 2) software, computational, and professional-development resources, and 3) a team science approach. In our experience, both the in-person and remote aspects of the model are important. In person collaboration is key to expanding the community of practice and invigorating those already within the community. Remote collaboration has been critical for effective collaborations between in-person activities and has proven to maximize outputs during in-person collaborations. While the three components of this model are not new to the scientific community, we believe that utilizing them strategically post-pandemic will diversify and expand scientific collaboration in oceanography.
Compressive Behavior of Corroded RC Columns Strengthened With Ultra-High Performance Jacket
Authors: Chen Jun , Wang Zongshan , Xu Anqi , Zhou Jianting
Published: March 2022

This paper performed compressive tests on corroded reinforced concrete (RC) columns with externally confined ultra-high performance concrete (UHPC) jacket. The studied parameters in this testing program was the corrosion ratio of specimens. The influences of this parameter on the compressive behavior of concrete columns confined by UHPC jacket was reported and discussed. The test results revealed that when the rust rate was less than 20%, axial cracking was the typical failure mode of unreinforced specimens, and the cracks in the rusted area gradually increased with the increase of the rust rate. When the corrosion rate reached 30%, the concrete of the protective layer fell off significantly, and the longitudinal reinforcement also yielded. The ultimate load and peak displacement of the specimens reinforced with UHPC were significantly improved, and the improvement rates of the two were more than 80% and 30%, respectively. The failure mode of the specimen with a corrosion rate of 30% also changed to longitudinal cracking of the UHPC layer. An analytical model was proposed to predict the ultimate load of RC columns with externally strengthening UHPC jacket. The validations of the predictions against the reported test results confirmed the accuracy of the analytical model.
Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis
Authors: Chen Xuejing , Wang Yu , Yu Xiaojuan , Wang Suxia , Zhao Minghui
Published: March 2022

Background

Complement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.

Methods

Patients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.

Results

Fifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24–138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR (r = 0.341, p = 0.013), sclerotic/ischemic glomerular lesions (r = –0.364, p = 0.008) and PTC density (r = 0.426, p = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition (r = –0.174, p = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen (r = 0.330, p = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.

Conclusion

Our findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis.
Association Between Urinary Protein-to-Creatinine Ratio and Chronic Kidney Disease Progression: A Secondary Analysis of a Prospective Cohort Study
Authors: Qin Xun , Hu Haofei , Cen Ji , Wang Xiaoyu , Wan Qijun , Wei Zhe
Published: March 2022

Objective

Studies on the association between urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression are limited. This study aimed to investigate the relationship between UPCR and CKD progression in a Japanese population.

Methods

The present research was a secondary analysis of a prospective cohort study. Eight hundred and ninety-six subjects from the research of CKD-ROUTE in Japan were included. All the patients were new visitors or first referred to the participating centers of nephrology between October 2010 and December 2011. The target-independent variable was UPCR measured at baseline. The dependent variable was CKD progression and the estimated glomerular filtration rate (eGFR) changes during follow-up. We used Cox proportional hazards regression to investigate the association between UPCR and CKD progression risk. To address UPCR and CKD progression's non-linearity, a multivariate Cox proportional hazards regression analysis with cubic spline functions model and smooth curve fitting (penalized spline method) were conducted. We further used a generalized linear mixed model to explore the relationship between UPCR and the changes of eGFR.

Result

The mean age of the included patients was 67.2 ± 13.4 years old. Two hundred and thirty-four people occurred CKD progression during follow-up. The present study showed that UPCR was independently associated with CKD progression in the multivariate analysis [HR = 1.164, 95% CI (1.116, 1.215)]. The non-linear relationship between UPCR and CKD progression was explored in a dose-dependent manner, with an obvious inflection point of 1.699. Furthermore, our findings indicated that the tendency of the effect sizes on both the left and right sides of the inflection point was not consistent [left HR: 4.377, 95% CI (2.956, 6.483); right HR: 1.100, 95% CI (1.049–1.153)]. Using the linear mixed-effects regression model, we found that UPCR was an independent predictor of the longitudinal changes in eGFR (p < 0.001 for the interaction term with time).

Conclusion

This study demonstrates a nonlinear positive relationship between UPCR and CKD progression in the Japanese population. UPCR is also an independent predictor of the longitudinal changes in eGFR.
Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease
Authors: Sun Qing-Feng , Tang Liang-Jie , Wang Ming-Jie , Zhu Pei-Wu , Li Yang-Yang , Ma Hong-Lei , Huang Ou-Yang , Hong Liang , Li Gang , Byrne Christopher D. , Targher Giovanni , Liu Wen-Yue , Lu Yan , Ding Ji-Guang , Zheng Ming-Hua
Published: March 2022

Background and objective

This pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

Methods

We included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0–1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes.

Results

The two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3′-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p < 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p < 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p < 0.05).

Conclusion

BDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.
Difference of Bacterial Community Structure in the Meadow, Maize, and Continuous Cropped Alfalfa in Northeast China
Authors: Yang Zhao , Xu Yanxia , Li Hong , Li Shasha , Wang Xiaolong , Chai Hua
Published: March 2022

Maize and alfalfa (Medicago sativa L.) have been used extensively in the animal husbandry to compensate for the lack of livestock and fodder yields in the chilly northeast of China. Little is known, however, about the impact on soil characteristics of consecutive plantings in various crops and alfalfa. In this research, the soil characteristics, bacterial community diversity, and structure of the meadow, maize, and alfalfa continuous cropping fields (i.e., 6, 10, 14, 20, and 30 years) were measured. The results showed that maize cropping and continuous cropping of alfalfa increased the soil bacterial alpha diversity compared with meadow cropping, and alpha diversity of alfalfa increased with the continuous planting years. Soil pH, total phosphorus (TP), available P, total potassium (TK), and nitrate nitrogen (NO3–) content were soil variables significantly impacting the structure of soil bacterial communities in different plant types and different alfalfa continuous cropping systems. In addition, the relative abundance of some beneficial microbial species, such as Arthrobacter and Gaiellales, in the cropping maize and continuous cropping of alfalfa was much higher than that in the meadow field. Moreover, the networks differ among different plant types, and also differ among different continuous cropping years of alfalfa, and topologies of the networks suggested that continuous planting of alfalfa promotes cooperation between bacteria, which facilitates the long growth of alfalfa and is beneficial to the soil.
Identifying the Sources of Intestinal Colonization With Extended-Spectrum β-Lactamase-Producing Escherichia coli in Healthy Infants in the Community
Authors: Amin Mohammed Badrul , Hoque Kazi Injamamul , Roy Subarna , Saha Sumita Rani , Islam Md. Rayhanul , Julian Timothy R. , Islam Mohammad Aminul
Published: March 2022

The prevalence of fecal colonization with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) among children in low- and middle-income countries is alarmingly high. This study aimed to identify the sources of ESBL-Ec colonization in children < 1 year old through comparative analysis of E. coli isolates from child stool, child’s mother stool, and point-of-use drinking water from 46 rural households in Bangladesh. The pairwise similarity in antibiotic susceptibility of E. coli from all three sources was evaluated, followed by phylogenetic clustering using enterobacterial repetitive intergenic consensus polymerase chain reaction and whole-genome sequence analysis of the isolates. Matching antibiotic susceptibility and enterobacterial repetitive intergenic consensus polymerase chain reaction patterns were found among ESBL-Ec isolates from child–mother dyads of 24 and 11 households, respectively, from child–water dyads of 5 and 4 households, respectively, and from child–mother–water triads of 3 and 4 households, respectively. Whole-genome sequence analysis of 30 isolates from 10 households revealed that ESBL-Ec from children in five households (50%) was clonally related to ESBL-Ec either from their mothers (2 households), drinking water sources (2 households), or both mother and drinking-water sources (1 household) based on serotype, phylogroup, sequence type, antibiotic resistance genes, mobile genetic elements, core single-nucleotide polymorphisms, and whole-genome multilocus sequence typing. Overall, this study provides empirical evidence that ESBL-Ec colonization in children is linked to the colonization status of mothers and exposure to the household environments contaminated with ESBL-Ec. Interventions such as improved hygiene practices and a safe drinking water supply may help reduce the transmission of ESBL-Ec at the household level.
Genetic Basis of High-Pressure Tolerance of a Vibrio parahaemolyticus Mutant and Its Pathogenicity
Authors: Feng Lifang , Xu Minhui , Zhu Junli , Lu Haixia
Published: March 2022

Foodborne pathogens with high-pressure processing (HPP) tolerance and their pathogenicity have gained considerable attention in the field of food safety. However, tolerance to pressure treatment varies among microorganisms and growth phases, and the mechanism by which Vibrio parahaemolyticus can become tolerant of HPP is currently not known. In this study, 183 strains of V. parahaemolyticus were isolated from seafood products, and one strain, C4, carried a thermostable direct hemolysin (tdh) gene. A strain, N11, which was acquired from the C4 strain through adaptive laboratory evolution under HPP stress, could tolerate up to 200 MPa for 10 min. Compared with the C4 strain, the catalase and Na+/K+-ATPase activities in N11 strain were increased by about 2–3 times, and the cells maintained an intact cell membrane structure under HPP treatment. As shown by murine infection trials, the C4 and N11 strains impacted the physiological activities of mice and damaged liver and spleen cells. Comparative genomic analysis showed that 19 nucleotides were mutated in the N11 strain, which led to sustained high expression of mlaC and mlaD genes in this strain. Knockout of these genes confirmed that they were involved in the high-pressure stress response, and also related to pathogenicity of V. parahaemolyticus. Thereby, our findings revealed a HPP tolerance mechanism of V. parahaemolyticus, and the high-pressure-tolerant strain still retained pathogenicity in mice with skin and fur pleating and lethargy, indicating the pressure-tolerant foodborne pathogens present health risks.
Characterization of Agarolytic Pathway in a Terrestrial Bacterium Cohnella sp. LGH
Authors: Li Gen , Guo Rui , Wu Shuqi , Cheng Si , Li Jiaqi , Liu Zhenzhen , Xie Wangliang , Sun Xiaolin , Zhang Qiuyi , Li Zihan , Xu JiaZheng , Wu Jun , Wei Zhong , Hu Feng
Published: March 2022

Previously, we have reported that an endo-type β-agarase AgaW was responsible for the hydrolysis of agarose into the major product neoagarotetraose in a terrestrial agar-degrading bacterium Cohnella sp. LGH. Here, we identify and characterize the following depolymerization pathway in strain LGH through the genomic and enzymatic analysis. In the pathway, neoagarotetraose was depolymerized by a novel α-neoagarooligosaccharide (NAOS) hydrolase CL5012 into 3,6-anhydro-α-L-galactose (L-AHG) and agarotriose; Agarotriose was further depolymerized by a novel agarolytic β-galactosidase CL4994 into D-galactose and neoagarobiose; Neoagarobiose was finally depolymerized by CL5012 into L-AHG and D-galactose. Although α-agarase has not been identified in strain LGH, the combined action of CL5012 and CL4994 unexpectedly plays a critical role in the depolymerization of agarotetraose, one theoretical product of α-agarase hydrolysis of agarose. In this pathway, agarotetraose was depolymerized by CL4994 into D-galactose and neoagarotriose; Neoagarotriose was then depolymerized by CL5012 into L-AHG and agarobiose. Furthermore, another novel endo-type β-agarase CL5055 was identified as an isozyme of AgaW with different pH preference in the hydrolysis of agarose into α-NAOSs. Strain LGH seemed to lack a common exo-type β-agarase responsible for the direct depolymerization of agarose or neoagarooligosaccharide into neoagarobiose. These results highlight the diversity of agarolytic manner in bacteria and provide a novel insight on the diversity of agarolytic pathways.
Identification of Zinc-Binding Inhibitors of Matrix Metalloproteinase-9 to Prevent Cancer Through Deep Learning and Molecular Dynamics Simulation Approach
Authors: Mathpal Shalini , Sharma Priyanka , Joshi Tushar , Pande Veena , Mahmud Shafi , Jeong Mi-Kyung , Obaidullah Ahmad J. , Chandra Subhash , Kim Bonglee
Published: March 2022

The overexpression of matrix metalloproteinase-9 (MMP-9) is associated with tumor development and angiogenesis, and hence, it has been considered an attractive drug target for anticancer therapy. To assist in drug design endeavors for MMP-9 targets, an in silico study was presented to investigate whether our compounds inhibit MMP-9 by binding to the catalytic domain, similar to their inhibitor or not. For that, in the initial stage, a deep-learning algorithm was used for the predictive modeling of the CHEMBL321 dataset of MMP-9 inhibitors. Several regression models were built and evaluated based on R2, MAE MSE, RMSE, and Loss. The best model was utilized to screen the drug bank database containing 9,102 compounds to seek novel compounds as MMP-9 inhibitors. Then top high score compounds were selected for molecular docking based on the comparison between the score of the reference molecule. Furthermore, molecules having the highest docking scores were selected, and interaction mechanisms with respect to S1 pocket and catalytic zinc ion of these compounds were also discussed. Those compounds, involving binding to the catalytic zinc ion and the S1 pocket of MMP-9, were considered preferentially for molecular dynamics studies (100 ns) and an MM-PBSA (last 30 ns) analysis. Based on the results, we proposed several novel compounds as potential candidates for MMP-9 inhibition and investigated their binding properties with MMP-9. The findings suggested that these compounds may be useful in the design and development of MMP-9 inhibitors in the future.
mRNA Translation Is Dynamically Regulated to Instruct Stem Cell Fate
Authors: Wang Ruoxu , Amoyel Marc
Published: March 2022

Stem cells preserve tissue homeostasis by replacing the cells lost through damage or natural turnover. Thus, stem cells and their daughters can adopt two identities, characterized by different programs of gene expression and metabolic activity. The composition and regulation of these programs have been extensively studied, particularly by identifying transcription factor networks that define cellular identity and the epigenetic changes that underlie the progressive restriction in gene expression potential. However, there is increasing evidence that post-transcriptional mechanisms influence gene expression in stem cells and their progeny, in particular through the control of mRNA translation. Here, we review the described roles of translational regulation in controlling all aspects of stem cell biology, from the decision to enter or exit quiescence to maintaining self-renewal and promoting differentiation. We focus on mechanisms controlling global translation rates in cells, mTOR signaling, eIF2ɑ phosphorylation, and ribosome biogenesis and how they allow stem cells to rapidly change their gene expression in response to tissue needs or environmental changes. These studies emphasize that translation acts as an additional layer of control in regulating gene expression in stem cells and that understanding this regulation is critical to gaining a full understanding of the mechanisms that underlie fate decisions in stem cells.
Anti-platelet Therapy Is Associated With Lower Risk of Dementia in Patients With Cerebral Small Vessel Disease
Authors: Pan Dong , Rong Xiaoming , Li Honghong , Deng Zhenhong , Wang Jia , Liu Xiaohuan , He Lei , Xu Yongteng , Tang Yamei
Published: March 2022

Introduction

Cerebral small vessel disease (CSVD) is common among older people and it could lead to dementia. Whether anti-platelet therapy (APT) could retard the cognitive decline of CSVD is unclear. The aim of the study was to evaluate, in newly diagnosed CSVD patients without dementia, the association between the APT and dementia during follow-up.

Methods

We conducted a nested case-control study within a CSVD cohort. Dementia cases, such as vascular dementia (VaD), Alzheimer’s disease (AD), and unspecified dementia (UD), were individually matched (1:1) to controls by age, sex, and follow-up time. Conditional logistic regression models were used to estimate the odds ratios (ORs) between APT and dementia.

Results

Of 9,991 patients in a cohort screened from January 2009 to December 2019 and followed-up until November 2020, 131 dementia cases were finally included and successfully matched to 131 controls. Among 262 patients with CSVD, the mean [standard deviation (SD)] age was 73.9 (7.9) years and 126 (48.1%) were men. The median [interquartile range (IQR)] follow-up periods were 4.73 (2.70–6.57) years in the control group and 2.94 (1.34–4.89) years in the case group. According to MRI at baseline, the case group showed higher CSVD burden in lacune(s) (p = 0.001), moderate-to-severe white matter hyperintensities (WMHs) (p = 0.015), enlarged perivascular spaces (EPVSs) in basal ganglia (p = 0.005), and brain atrophy (p < 0.001). The APT was associated with the lower overall dementia risk and the matched OR was statistically significant (aOR 0.15, 95% CI 0.05–0.45, p = 0.001), and clopidogrel showed protective effects on overall dementia (aOR 0.30, 95% CI 0.14–0.62, p = 0.001).

Conclusion

Among newly diagnosed CSVD patients without dementia, APT was associated with a lower risk of dementia and clopidogrel might be an appropriate candidate in preventing dementia.
Abnormal Default Mode Network Homogeneity in Major Depressive Disorder With Gastrointestinal Symptoms at Rest
Authors: Yan Meiqi , Chen Jindong , Liu Feng , Li Huabing , Zhao Jingping , Guo Wenbin
Published: March 2022

Background

Gastrointestinal (GI) symptoms are prominent in many patients with major depressive disorder (MDD). However, it remains unclear whether MDD patients with GI symptoms have brain imaging alterations in the default mode network (DMN) regions.

Methods

A total of 35 MDD patients with GI symptoms, 17 MDD patients without GI symptoms, and 28 healthy controls (HCs) were recruited. All participants underwent resting-state functional magnetic resonance imaging scans. Network homogeneity (NH) and support vector machine (SVM) methods were used to analyze the imaging data.

Results

Gastrointestinal group showed higher 17-item Hamilton Rating Scale for Depression total scores and factor scores than the non-GI group. Compared with the non-GI group and HCs, the GI group showed decreased NH in the right middle temporal gyrus (MTG) and increased NH in the right precuneus (PCu). The SVM results showed that a combination of NH values of the right PCu and the right MTG exhibited the highest accuracy of 88.46% (46/52) to discriminate MDD patients with GI symptoms from those without GI symptoms.

Conclusion

Major depressive disorder patients with GI symptoms have more severe depressive symptoms than those without GI symptoms. Distinctive NH patterns in the DMN exist in MDD patients with GI symptoms, which can be applied as a potential brain imaging marker to discriminate MDD patients with GI symptoms from those without GI symptoms.
Systemic-Immune-Inflammation Index as a Promising Biomarker for Predicting Perioperative Ischemic Stroke in Older Patients Who Underwent Non-cardiac Surgery
Authors: Zhang Faqiang , Niu Mu , Wang Long , Liu Yanhong , Shi Likai , Cao Jiangbei , Mi Weidong , Ma Yulong , Liu Jing
Published: March 2022

Objective

This study aimed to investigate the clinical prognostic values of the preoperative systemic-immune-inflammation index (SII) in older patients undergoing non-cardiac surgery, using perioperative ischemic stroke as the primary outcome.

Methods

This retrospective cohort study included older patients who underwent non-cardiac surgery between January 2008 and August 2019. The patients were divided into SII < 583 and SII ≥ 583 group according to the optimal SII cut-off value. The outcome of interest was ischemic stroke within 30 days after surgery. Primary, sensitivity, and subgroup analyses were performed to confirm that preoperative SII qualifies as a promising, independent prognostic indicator. Propensity score matching (PSM) analysis was further applied to address the potential residual confounding effect of covariates to examine the robustness of our results.

Results

Among the 40,670 included patients with a median age of 70 years (interquartile range: 67, 74), 237 (0.58%) experienced an ischemic stroke within 30 days after surgery. SII ≥ 583 was associated with an increased risk of perioperative ischemic stroke in multivariate regression analysis [odds ratio (OR), 1.843; 95% confidence interval (CI), 1.369–2.480; P < 0.001]. After PSM adjustment, all covariates were well balanced between the two groups. The correlation between the SII and perioperative ischemic stroke remained significantly robust (OR: 2.195; 95% CI: 1.574–3.106; P < 0.001) in the PSM analysis.

Conclusion

Preoperative SII, which includes neutrophil, platelet, and lymphocyte counts obtained from routine blood analysis, was a potential prognostic biomarker for predicting perioperative ischemic stroke after non-cardiac surgery in older patients. An elevated SII, based on an optimal cut-off value of 583, was an independent risk factor for perioperative ischemic stroke.
Exploring Sex-Related Differences in Microglia May Be a Game-Changer in Precision Medicine
Authors: Lynch Marina A.
Published: March 2022

One area of microglial biology that has been relatively neglected until recently is sex differences and this is in spite of the fact that sex is a risk factor in several diseases that are characterized by neuroinflammation and, by extension, microglial activation. Why these sex differences exist is not known but the panoply of differences extend to microglial number, genotype and phenotype. Significantly, several of these sex-related differences are also evident in health and change during life emphasizing the dynamic and plastic nature of microglia. This review will consider how age impacts on sex-related differences in microglia and ask whether the advancement of personalized medicine demands that a greater focus is placed on studying sex-related differences in microglia in Alzheimer’s disease, Parkinson’s disease and models of inflammatory stress and trauma in order to make true progress in dealing with these conditions.
Areas of Convergence and Divergence in Adolescent Social Isolation and Binge Drinking: A Review
Authors: Lodha Jyoti , Brocato Emily , Wolstenholme Jennifer T.
Published: March 2022

Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation of synaptic connections throughout the brain. Adolescents spend more time interacting with peers than any other age group and display heightened reward sensitivity, impulsivity and diminished inhibitory self-control, which contribute to increased risky behaviors, including the initiation and progression of alcohol use. Compared to adults, adolescents are less susceptible to the negative effects of ethanol, but are more susceptible to the negative effects of stress, particularly social stress. Juvenile exposure to social isolation or binge ethanol disrupts synaptic connections, dendritic spine morphology, and myelin remodeling in the frontal cortex. These structural effects may underlie the behavioral and cognitive deficits seen later in life, including social and memory deficits, increased anxiety-like behavior and risk for alcohol use disorders (AUD). Although the alcohol and social stress fields are actively investigating the mechanisms through which these effects occur, significant gaps in our understanding exist, particularly in the intersection of the two fields. This review will highlight the areas of convergence and divergence in the fields of adolescent social stress and ethanol exposure. We will focus on how ethanol exposure or social isolation stress can impact the development of the frontal cortex and lead to lasting behavioral changes in adulthood. We call attention to the need for more mechanistic studies and the inclusion of the evaluation of sex differences in these molecular, structural, and behavioral responses.
Extracellular Matrix Recycling as a Novel Plasticity Mechanism With a Potential Role in Disease
Authors: Dankovich Tal M. , Rizzoli Silvio O.
Published: March 2022

The extracellular matrix (ECM) stabilizes neural circuits and synapses in the healthy brain, while also retaining the ability to be remodeled, to allow synapses to be plastic. A well-described mechanism for ECM remodeling is through the regulated secretion of proteolytic enzymes at the synapse, together with the synthesis of new ECM molecules. The importance of this process is evidenced by the large number of brain disorders that are associated with a dysregulation of ECM-cleaving protease activity. While most of the brain ECM molecules are indeed stable for remarkable time periods, evidence in other cell types, as cancer cells, suggests that at least a proportion of the ECM molecules may be endocytosed regularly, and could even be recycled back to the ECM. In this review, we discuss the involvement of such a mechanism in the brain, under physiological activity conditions and in relation to synapse and brain disease.
The Application of the Omaha System in Community Rehabilitation Nursing for Patients With Stroke and Previous Falls
Authors: Fang Xiaoqun , Jia Shulei , Wang Qiuyan , Liu Huifang , Zhou Yumei , Zhang Lingling , Dai Tanghua , Luo Hui , Peng Hui , Yuan Jun , Zhou Huyan
Published: March 2022

Objective

This study aimed to explore the use of the Omaha System in rehabilitation and nursing methods and the effects on patients within the community who had experienced stroke and previous falls.

Methods

This study enrolled 42 patients who had experienced stroke and previous falls and had returned to the community after being discharged from the Department of Neurology and Rehabilitation of the Affiliated Hospital of Nanchang University from January to July 2018. The patients were randomly divided into two groups: an experimental group (n = 21) and a control group (n = 21). Patients in the control group received routine community rehabilitation care, and patients in the experimental group received community rehabilitation care on the basis of the Omaha System. Intervention lasted for 1 year. The Omaha outcome score, the ability to perform activities of daily living (ADL) (measured via the Modified Barthel Index [MBI]), and the incidence of falls for each group were compared before and after the intervention.

Results

After 1 year of intervention, the Omaha outcome score and MBI of both groups were higher than before; the Omaha outcome score and MBI of the experimental group were higher than those of the control group; the differences were statistically significant (P < 0.05). No fall occurred in either of the two groups.

Conclusion

The Omaha System can comprehensively evaluate the health problems of patients, guide nursing intervention, and quantitatively evaluate the effect of nursing intervention; it is therefore worthy of promotion.
γδ T Cell in Cerebral Ischemic Stroke: Characteristic, Immunity-Inflammatory Role, and Therapy
Authors: Wang Li , Yao Chengye , Chen Jiayi , Ge Yangyang , Wang Chenchen , Wang Yu , Wang Fuquan , Sun Yan , Dai Maosha , Lin Yun , Yao Shanglong
Published: March 2022

Gamma-delta (γδ) T cells are a small subset of T cells that are reported to have a proinflammatory role in the pathophysiology of cerebral ischemia stroke (CIS). Upon activation by interleukin-1 beta (IL-1β), IL-23 and IL-18, γδ T cells are stimulated to secrete various cytokines, such as IL-17a, IL-21, IL-22, and interferon-gamma (IFN-γ). In addition, they all play a pivotal role in the inflammatory and immune responses in ischemia. Nevertheless, the exact mechanisms responsible for γδ T cell proinflammatory functions remain poorly understood, and more effective therapies targeting at γδ T cells and cytokines they release remain to be explored, particularly in the context of CIS. CIS is the second most common cause of death and the major cause of permanent disability in adults worldwide. In this review, we focus on the neuroinflammatory and immune functions of γδ T cells and related cytokines, intending to understand their roles in CIS, which may be crucial for the development of novel effective clinical applications.
Can an Online Reading Camp Teach 5-Year-Old Children to Read?
Authors: Weiss Yael , Yeatman Jason D. , Ender Suzanne , Gijbels Liesbeth , Loop Hailley , Mizrahi Julia C. , Woo Bo Y. , Kuhl Patricia K.
Published: March 2022

Literacy is an essential skill. Learning to read is a requirement for becoming a self-providing human being. However, while spoken language is acquired naturally with exposure to language without explicit instruction, reading and writing need to be taught explicitly. Decades of research have shown that well-structured teaching of phonological awareness, letter knowledge, and letter-to-sound mapping is crucial in building solid foundations for the acquisition of reading. During the COVID-19 pandemic, children worldwide did not have access to consistent and structured teaching and are, as a consequence, predicted to be behind in the development of their reading skills. Subsequent evidence confirms this prediction. With the best evidence-based practice in mind, we developed an online version of a well-structured early literacy training program (Reading Camp) for 5-year-old children. This 2-week online Reading Camp program is designed for pre-K children. It incorporates critical components of the fundamental skills essential to learning to read and is taught online in an interactive, multi-sensory, and peer-learning environment. We measure the participants’ literacy skills and other related skills before and after participating in the online Reading Camp and compare the results to no-treatment controls. Results show that children who participated in the online Reading Camp improved significantly on all parameters in relation to controls. Our results demonstrate that a well-structured evidence-based reading instruction program, even if online and short-term, benefits 5-year-old children in learning to read. With the potential to scale up this online program, the evidence presented here, alongside previous evidence for the efficacy of the in-person program, indicates that the online Reading Camp program is effective and can be used to tackle a variety of questions regarding structural and functional plasticity in the early stages of reading acquisition.
Effects of Ordered Grasping Movement on Brain Function in the Performance Virtual Reality Task: A Near-Infrared Spectroscopy Study
Authors: Li Xiangyang , Yin Jiahui , Li Huiyuan , Xu Gongcheng , Huo Congcong , Xie Hui , Li Wenhao , Liu Jizhong , Li Zengyong
Published: March 2022

Objective

Virtual reality (VR) grasping exercise training helps patients participate actively in their recovery and is a critical approach to the rehabilitation of hand dysfunction. This study aimed to explore the effects of active participation and VR grasping on brain function combined with the kinematic information obtained during VR exercises.

Methods

The cerebral oxygenation signals of the prefrontal cortex (LPFC/RPFC), the motor cortex (LMC/RMC), and the occipital cortex (LOC/ROC) were measured by functional near-infrared spectroscopy (fNIRS) in 18 young people during the resting state, grasping movements, and VR grasping movements. The EPPlus plug-in was used to collect the hand motion data during simulated interactive grasping. The wavelet amplitude (WA) of each cerebral cortex and the wavelet phase coherence (WPCO) of each pair of channels were calculated by wavelet analysis. The total difference in acceleration difference of the hand in the VR grasping movements was calculated to acquire kinematic characteristics (KCs). The cortical activation and brain functional connectivity (FC) of each brain region were compared and analyzed, and a significant correlation was found between VR grasping movements and brain region activation.

Results

Compared with the resting state, the WA values of LPFC, RPFC, LMC, RMC, and ROC increased during the grasping movements and the VR grasping movements, these changes were significant in LPFC (p = 0.0093) and LMC (p = 0.0007). The WA values of LMC (p = 0.0057) in the VR grasping movements were significantly higher than those in the grasping movements. The WPCO of the cerebral cortex increased during grasping exercise compared with the resting state. Nevertheless, the number of significant functional connections during VR grasping decreased significantly, and only the WPCO strength between the LPFC and LMC was enhanced. The increased WA of the LPFC, RPFC, LMC, and RMC during VR grasping movements compared with the resting state showed a significant negative correlation with KCs (p < 0.001).

Conclusion

The VR grasping movements can improve the activation and FC intensity of the ipsilateral brain region, inhibit the FC of the contralateral brain region, and reduce the quantity of brain resources allocated to the task. Thus, ordered grasping exercises can enhance active participation in rehabilitation and help to improve brain function.
A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
Authors: Goldwaser Eric L. , Swanson Randel L. , Arroyo Edgardo J. , Venkataraman Venkat , Kosciuk Mary C. , Nagele Robert G. , Hong L. Elliot , Acharya Nimish K.
Published: March 2022

Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway(s) responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier (BBB) function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing. In this preliminary study, we used immunohistochemistry and serum immunoglobulin G (IgG) antibodies to investigate the state of BBB function in formalin-fixed postmortem samples from the hippocampus and surrounding temporal cortex of patients with schizophrenia (n = 25) and controls without schizophrenia (n = 27) matched for age, sex, and race. Since a functional BBB prevents the extravasation of IgGs, detection of IgGs in the parenchyma is used as direct evidence of BBB breakdown. We also developed a semi-quantitative approach to quantify the extent of IgG leak and therein BBB breach. Analysis of our immunohistochemistry data demonstrated a significantly higher incidence of IgG leak in patients with schizophrenia compared to controls. Further, BBB permeability was significantly higher in advanced-age patients with schizophrenia than both advanced-age controls and middle-aged patients with schizophrenia. Male patients with schizophrenia also demonstrated a significant increase in IgG permeability compared to control males. Interestingly, the extravasated IgGs also demonstrated selective immunoreactivity for neurons. Based on these observations, we suggest that BBB dysfunction and IgG autoantibodies could be two key missing pathoetiological links underwriting schizophrenia hippocampal damage.