bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis
Authors: Seal Rishav , Schwab Lara S. U. , Chiarolla Cristina M. , Hundhausen Nadine , Klose Georg Heinrich , Reu-Hofer Simone , Rosenwald Andreas , Wiest Johannes , Berberich-Siebelt Friederike
Published: May 2023

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities.
Overcoming the immune suppressive nature of glioblastoma by leveraging the surgical intervention - current status and future perspectives
Authors: Duerinck Johnny , Tuyaerts Sandra , Movahedi Kiavash , Neyns Bart
Published: May 2023

Despite relentless efforts to improve outcome, the prognosis of glioblastoma (GBM) remains poor. Standard therapy at first diagnosis consists of maximal safe surgical resection followed by radiochemotherapy, but treatment options at recurrence are scarce and have limited efficacy. Immunotherapy is a broad term that covers several treatment strategies, including immune checkpoint inhibition (ICI). The successes of systemically administered therapeutic monoclonal antibodies that block the Programmed death receptor or ligand (PD-(L)1) and Cytotoxic T-Lymphocyte associated protein (CTLA)-4 immune checkpoints in other cancer types could not be reproduced in glioblastoma. This is considered to be related to the intrinsic low immunogenicity and strong immunosuppressive tumor microenvironment of glioblastoma, in addition to the presence of a blood-glioma and blood-brain barrier that limits many systemically administered therapeutic agents from reaching their target. In this mini-review, we address the specific aspects of immune suppression in glioblastoma and discuss potential strategies that could help to overcome it. The potential advantages of incorporating surgical resection in clinical trials of immunotherapy for glioblastoma, including window-of-opportunity studies, are highlighted. Combination strategies that include surgical resection, as well as local administration of therapeutic agents in the brain are discussed as a potential strategy to achieve an effective immunological response against glioblastoma.
Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis
Authors: Chen Anning , Sun Zhun , Sun Donglin , Huang Meiying , Fang Hongwei , Zhang Jinyuan , Qian Guojun
Published: May 2023

Background

Idiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood.

Methods

In this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF.

Results

We identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment.

Conclusion

Our findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.
An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design
Authors: Sheng Zizhang , Bimela Jude S. , Wang Maple , Li Zhiteng , Guo Yicheng , Ho David D.
Published: May 2023

Accurate identification of beneficial mutations is central to antibody design. Many knowledge-based (KB) computational approaches have been developed to predict beneficial mutations, but their accuracy leaves room for improvement. Thermodynamic integration (TI) is an alchemical free energy algorithm that offers an alternative technique for identifying beneficial mutations, but its performance has not been evaluated. In this study, we developed an efficient TI protocol with high accuracy for predicting binding free energy changes of antibody mutations. The improved TI method outperforms KB methods at identifying both beneficial and deleterious mutations. We observed that KB methods have higher accuracies in predicting deleterious mutations than beneficial mutations. A pipeline using KB methods to efficiently exclude deleterious mutations and TI to accurately identify beneficial mutations was developed for high-throughput mutation scanning. The pipeline was applied to optimize the binding affinity of a broadly sarbecovirus neutralizing antibody 10-40 against the circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant. Three identified beneficial mutations show strong synergy and improve both binding affinity and neutralization potency of antibody 10-40. Molecular dynamics simulation revealed that the three mutations improve the binding affinity of antibody 10-40 through the stabilization of an altered binding mode with increased polar and hydrophobic interactions. Above all, this study presents an accurate and efficient TI-based approach for optimizing antibodies and other biomolecules.
Performance of spectral flow cytometry and mass cytometry for the study of innate myeloid cell populations
Authors: van der Pan Kyra , Khatri Indu , de Jager Anniek L. , Louis Alesha , Kassem Sara , Naber Brigitta A.E. , de Laat Inge F. , Hameetman Marjolijn , Comans Suzanne E.T. , Orfao Alberto , van Dongen Jacques J.M. , Díez Paula , Teodosio Cristina
Published: May 2023

Introduction

Monitoring of innate myeloid cells (IMC) is broadly applied in basic and translational research, as well as in diagnostic patient care. Due to their immunophenotypic heterogeneity and biological plasticity, analysis of IMC populations typically requires large panels of markers. Currently, two cytometry-based techniques allow for the simultaneous detection of ≥40 markers: spectral flow cytometry (SFC) and mass cytometry (MC). However, little is known about the comparability of SFC and MC in studying IMC populations.

Methods

We evaluated the performance of two SFC and MC panels, which contained 21 common markers, for the identification and subsetting of blood IMC populations. Based on unsupervised clustering analysis, we systematically identified 24 leukocyte populations, including 21 IMC subsets, regardless of the cytometry technique.

Results

Overall, comparable results were observed between the two technologies regarding the relative distribution of these cell populations and the staining resolution of individual markers (Pearson’s ρ=0.99 and 0.55, respectively). However, minor differences were observed between the two techniques regarding intra-measurement variability (median coefficient of variation of 42.5% vs. 68.0% in SFC and MC, respectively; p<0.0001) and reproducibility, which were most likely due to the significantly longer acquisition times (median 16 min vs. 159 min) and lower recovery rates (median 53.1% vs. 26.8%) associated with SFC vs. MC.

Discussion

Altogether, our results show a good correlation between SFC and MC for the identification, enumeration and characterization of IMC in blood, based on large panels (>20) of antibody reagents.
The complement receptor C5aR2 regulates neutrophil activation and function contributing to neutrophil-driven epidermolysis bullosa acquisita
Authors: Seiler Daniel L. , Kähler Katja H. , Kleingarn Marie , Sadik Christian D. , Bieber Katja , Köhl Jörg , Ludwig Ralf J. , Karsten Christian M.
Published: May 2023

Introduction

The function of the second receptor for the complement cleavage product C5a, C5aR2, is poorly understood and often neglected in the immunological context. Using mice with a global deficiency of C5aR2, we have previously reported an important role of this receptor in the pathogenesis of the neutrophil-driven autoimmune disease epidermolysis bullosa acquisita (EBA). Based on in vitro analyses, we hypothesized that the absence of C5aR2 specifically on neutrophils is the cause of the observed differences. Here, we report the generation of a new mouse line with a LysM-specific deficiency of C5aR2.

Methods

LysM-specific deletion of C5aR2 was achieved by crossing LysMcre mice with tdTomato-C5ar2fl/fl mice in which the tdTomato-C5ar2 gene is flanked by loxP sites. Passive EBA was induced by subcutaneous injection of rabbit anti-mouse collagen type VII IgG. The effects of targeted deletion of C5ar2 on C5a-induced effector functions of neutrophils were examined in in vitro assays.

Results

We confirm the successful deletion of C5aR2 at both the genetic and protein levels in neutrophils. The mice appeared healthy and the expression of C5aR1 in bone marrow and blood neutrophils was not negatively affected by LysM-specific deletion of C5aR2. Using the antibody transfer mouse model of EBA, we found that the absence of C5aR2 in LysM-positive cells resulted in an overall amelioration of disease progression, similar to what we had previously found in mice with global deficiency of C5aR2. Neutrophils lacking C5aR2 showed decreased activation after C5a stimulation and increased expression of the inhibitory Fcγ receptor FcγRIIb.

Discussion

Overall, with the data presented here, we confirm and extend our previous findings and show that C5aR2 in neutrophils regulates their activation and function in response to C5a by potentially affecting the expression of Fcγ receptors and CD11b. Thus, C5aR2 regulates the finely tuned interaction network between immune complexes, Fcγ receptors, CD11b, and C5aR1 that is important for neutrophil recruitment and sustained activation. This underscores the importance of C5aR2 in the pathogenesis of neutrophil-mediated autoimmune diseases.
The urgency to expand the antiviral indications of general chronic hepatitis B patients
Authors: Fan Ping , Li Lan-Qing , Chen En-Qiang
Published: May 2023

In recent years, liver experts have conducted in-depth discussions on whether it is necessary to expand the indication of antiviral therapy for patients with chronic hepatitis B (CHB). Currently, the guidelines are too strict in treating CHB patients. With the deepening understanding of the natural history of hepatitis B virus infection, there is more and more evidence challenging the view that there is no disease progression and no treatment in the immune tolerance period and inactive period. As the price of antiviral agents for CHB has decreased significantly, the availability of antiviral agents for CHB has been considerably improved. Therefore, expanding the indications for antiviral treatment of CHB is of great significance in achieving the goal of eliminating the public health threat of viral hepatitis by 2030, as the World Health Organization has proposed.
Case report: Analysis of phage therapy failure in a patient with a Pseudomonas aeruginosa prosthetic vascular graft infection
Authors: Blasco Lucia , López-Hernández Inmaculada , Rodríguez-Fernández Miguel , Pérez-Florido Javier , Casimiro-Soriguer Carlos S. , Djebara Sarah , Merabishvili Maya , Pirnay Jean-Paul , Rodríguez-Baño Jesús , Tomás María , López Cortés Luis Eduardo
Published: May 2023

Clinical case of a patient with a Pseudomonas aeruginosa multidrug-resistant prosthetic vascular graft infection which was treated with a cocktail of phages (PT07, 14/01, and PNM) in combination with ceftazidime-avibactam (CZA). After the application of the phage treatment and in absence of antimicrobial therapy, a new P. aeruginosa bloodstream infection (BSI) with a septic residual limb metastasis occurred, now involving a wild-type strain being susceptible to ß-lactams and quinolones. Clinical strains were analyzed by microbiology and whole genome sequencing techniques. In relation with phage administration, the clinical isolates of P. aeruginosa before phage therapy (HE2011471) and post phage therapy (HE2105886) showed a clonal relationship but with important genomic changes which could be involved in the resistance to this therapy. Finally, phenotypic studies showed a decrease in Minimum Inhibitory Concentration (MIC) to ß-lactams and quinolones as well as an increase of the biofilm production and phage resistant mutants in the clinical isolate of P. aeruginosa post phage therapy.
Identifying the Specific Root Microbiome of the Hyperaccumulator Noccaea brachypetala Growing in Non-metalliferous Soils
Authors: Martos Soledad , Busoms Sílvia , Pérez-Martín Laura , Llugany Mercè , Cabot Catalina , Poschenrieder Charlotte
Published: May 2023

Noccaea brachypetalais a close relative ofNoccaea caerulescens, a model plant species used in metal hyperaccumulation studies. In a previous survey in the Catalan Pyrenees, we found two occidental and two orientalN. brachypetalapopulations growing on non-metalliferous soils, with accumulated high concentrations of Cd and Zn. Our hypothesis was that the microbiome companion of the plant roots may influence the ability of these plants to absorb metals. We performed high-throughput sequencing of the bacterial and fungal communities in the rhizosphere soil and rhizoplane fractions. The rhizobiomes and shoot ionomes ofN. brachypetalaplants were analyzed along with those from other non-hyperaccumulator Brassicaceae species found at the same sampling locations. The analyses revealed that microbiome richness and relative abundance tended to increase inN. brachypetalaplants compared to non-hyperaccumulator species, regardless of plant location. We confirmed that the root compartment is a key factor in describing the community composition linked to the cohabiting Brassicaceae species, and the rhizoplane fraction contained the specific and rare taxa associated with each species.N. brachypetalaplants harbored a similar relative abundance of fungi compared to the other plant hosts, but there was a notable reduction in some specific taxa. Additionally, we observed an enrichment in the hyperaccumulator rhizoplane of previously described metal-tolerant bacteria and bacteria involved in nitrogen cycling. The bacteria involved in the nitrogen cycle could contribute indirectly to the hyperaccumulator phenotype by improving soil quality and fertility. Our results indicate thatN. brachypetalacaptures a particular prokaryotic community from the soil. This particular prokaryotic community may benefit the extraction of metal ions and/or improve plant nutrition. Our research identified satellite groups associated with the root niche of a hyperaccumulator plant that may assist in improving biological strategies in heavy metal remediation.
Therapeutic effect of demethylated hydroxylated phillygenin derivative on Helicobacter pylori infection
Authors: Li Ru-Jia , Xu Jia-yin , Wang Xue , Liao Li-juan , Wei Xian , Xie Ping , Xu Wen-yan , Xu Zhen-yi , Xie Shuo-hua , Jiang Yu-ying , Huang Liang , Wang Lu-yao , Huang Gan-rong , Huang Yan-Qiang
Published: May 2023

Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8–32 μg/mL in vitro, and the activity increased 2–8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it’s a good antioxidant for host cells.
Metagenomics reveals the effect of long-term fertilization on carbon cycle in the maize rhizosphere
Authors: Li Yanan , Wang Chengyu , Chang Hongyan , Zhang Yumang , Liu Shuxia , He Wentian
Published: May 2023

Long-term fertilization can result in the changes in carbon (C) cycle in the maize rhizosphere soil. However, there have been few reports on the impacts of microbial regulatory mechanisms on the C cycle in soil. In the study, we analyzed the response of functional genes that regulate the C fixation, decomposition and methane (CH4) metabolism in maize rhizosphere soil to different fertilization treatments using metagenomics analysis. As the dominant C fixation pathway in maize rhizosphere soil, the abundance of the functional genes regulating the reductive citrate cycle (rTCA cycle) including korA, korB, and IHD1 was higher under the chemical nitrogen (N) fertilizer treatments [nitrogen fertilizer (N), compound chemical fertilization (NPK), the combination of compound chemical fertilizer with maize straw (NPKS)] than maize straw return treatments [maize straw return (S), the combination of phosphorus and potassium fertilizer with maize straw (PKS)]. The NPK treatment decreased the abundance of functional genes involved in 3-hydroxypropionate bicycle (3-HP cycle; porA, porB, and porD), which was one of the major C fixation pathways in soil aside from dicarboxylate-hydroxybutyrate (DC/4-HB cycle) and Calvin cycle. The abundance of functional genes related to C degradation was higher in S, PKS and NPKS treatments than N and NPK treatments, and chemical N fertilizer application had a significant effect on C degradation. The dominant Methanaogenesis pathway in maize rhizosphere soil, used acetate as a substrate, and was significantly promoted under chemical N fertilizer application. The functional genes that were related to CH4 oxidation (i.e., pmoA and pmoB) were reduced under N and NPK treatments. Moreover, soil chemical properties had a significant impact on the functional genes related to C fixation and degradation, with SOC (r2 = 0.79) and NO3−-N (r2 = 0.63) being the main regulators. These results implied that N fertilization rather than maize straw return had a greater influence on the C cycle in maize rhizosphere soil.
LysGR1, a novel thermostable endolysin from Geobacillus stearothermophilus bacteriophage GR1
Authors: Choi Dahee , Kong Minsuk
Published: May 2023

Geobacillus stearothermophilus is a highly thermophilic, spore-forming Gram-positive bacterium that causes flat sour spoilage in low-acid canned foods. To address this problem, we isolated G. stearothermophilus-infecting phage GR1 from the soil and characterized its endolysin LysGR1. Phage GR1 belongs to the Siphoviridae family and possesses a genome of 79,387 DNA bps with 108 putative open reading frames. GR1 demonstrated a very low degree of homology to previously reported phages, indicating that it is novel. The endolysin of GR1 (LysGR1) contains an N-terminal amidase domain as an enzymatically active domain (EAD) and two C-terminal LysM domains as a cell wall binding domain (CBD). Although GR1 is specific to certain strains of G. stearothermophilus, LysGR1 showed a much broader lytic range, killing all the tested strains of G. stearothermophilus and several foodborne pathogens, such as Clostridium perfringens, Listeria monocytogenes, and Escherichia coli O157:H7. LysGR1_EAD, alone, also exhibits lytic activity against a wide range of bacteria, including Bacillus cereus, which is not terminated by a full-length endolysin. Both LysGR1 and its EAD effectively remove the G. stearothermophilus biofilms and are highly thermostable, retaining about 70% of their lytic activity after a 15-min incubation at 70°C. Considering the high thermal stability, broad lytic activity, and biofilm reduction efficacy of LysGR1 and its EAD, we hypothesize that these enzymes could act as promising biocontrol agents against G. stearothermophilus and as foodborne pathogens.
Phylogeographic dynamics and molecular characteristics of Enterovirus 71 in China
Authors: Ma Zi-Hui , Nawal Bahoussi Amina , Tariq Shah Pir , Guo Yan-Yan , Dong Li , Wu Changxin , Xing Li
Published: May 2023

Enterovirus 71 (EV71) and coxsackievirus (CV-A16) are the major etiological agents of hand, foot and mouth disease (HFMD). This report reviewed the full-length genomic sequences of EV71 identified in different provinces of China between 1998 and 2019 (a total of 312) in addition to eight worldwide reference genomes to address the genomic evolution and genetic events. The main prevalent EV71 strians in China are C4 genotypes, co-circulating with a few A, B5, C1, and C2 subgenotypes. A new emerging subgenotype in China was identified and classified as B6 genotype. Phylogeographic analysis revealed multiple branches, where a Jiangsu strain 2006-52-9 (GenBank ID: KP266579.1) was linked to different subgenotypes through multiple long mutant branches, including the CV-A16 viruses through the A genotype. Furthermore, identification of 28 natural recombination events suggests that the emergence of new genotypes are associated with intratypic recombination involving EV71 strains and intertypic recombination between EV71 and CV-A16 strains. Compared with the structural proteins, the non-structural proteins of EV71 seem to be highly variable with the highest variable regions of peptidase C3 (3C protein), P2A, and the N-terminus of RNA-dependent RNA polymerase. This study updates the phylogenetic and phylogeographic information of EV71 and provides clues to the emergence of new genotypes of EV71 based on genetics.
FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC
Authors: Chi Hao , Gao Xinrui , Xia Zhijia , Yu Wanying , Yin Xisheng , Pan Yifan , Peng Gaoge , Mao Xinrui , Teichmann Alexander Tobias , Zhang Jing , Tran Lisa Jia , Jiang Tianxiao , Liu Yunfei , Yang Guanhu , Wang Qin
Published: May 2023

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients.

Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs.

Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy.

Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.
Progressive sleep disturbance in various transgenic mouse models of Alzheimer’s disease
Authors: Drew Victor J. , Wang Chanung , Kim Tae
Published: May 2023

Alzheimer’s disease (AD) is the leading cause of dementia. The relationship between AD and sleep dysfunction has received increased attention over the past decade. The use of genetically engineered mouse models with enhanced production of amyloid beta (Aβ) or hyperphosphorylated tau has played a critical role in the understanding of the pathophysiology of AD. However, their revelations regarding the progression of sleep impairment in AD have been highly dependent on the mouse model used and the specific techniques employed to examine sleep. Here, we discuss the sleep disturbances and general pathology of 15 mouse models of AD. Sleep disturbances covered in this review include changes to NREM and REM sleep duration, bout lengths, bout counts and power spectra. Our aim is to describe in detail the severity and chronology of sleep disturbances within individual mouse models of AD, as well as reveal broader trends of sleep deterioration that are shared among most models. This review also explores a variety of potential mechanisms relating Aβ accumulation and tau neurofibrillary tangles to the progressive deterioration of sleep observed in AD. Lastly, this review offers perspective on how study design might impact our current understanding of sleep disturbances in AD and provides strategies for future research.
The effects of proprioceptive weighting changes on posture control in patients with chronic low back pain: a cross-sectional study
Authors: Cheng Xue , Yang Jiajia , Hao Zengming , Li Yan , Fu Ruochen , Zu Yao , Ma Jinjin , Lo Wai Leung Ambrose , Yu Qiuhua , Zhang Guifang , Wang Chuhuai
Published: May 2023

Introduction

Patients with chronic low back pain (CLBP) exhibit changes in proprioceptive weighting and impaired postural control. This study aimed to investigate proprioceptive weighting changes in patients with CLBP and their influence on posture control.

Methods

Sixteen patients with CLBP and 16 healthy controls were recruited. All participants completed the joint reposition test sense (JRS) and threshold to detect passive motion test (TTDPM). The absolute errors (AE) of the reposition and perception angles were recorded. Proprioceptive postural control was tested by applying vibrations to the triceps surae or lumbar paravertebral muscles while standing on a stable or unstable force plate. Sway length and sway velocity along the anteroposterior (AP) and mediolateral (ML) directions were assessed. Relative proprioceptive weighting (RPW) was used to evaluate the proprioception reweighting ability. Higher values indicated increased reliance on calf proprioception.

Results

There was no significant difference in age, gender, and BMI between subjects with and without CLBP. The AE and motion perception angle in the CLBP group were significantly higher than those in the control group (JRS of 15°: 2.50 (2.50) vs. 1.50 (1.42), JRS of 35°: 3.83 (3.75) vs. 1.67 (2.00),pJRS< 0.01; 1.92 (1.18) vs. 0.68 (0.52),pTTDPM< 0.001). The CLBP group demonstrated a significantly higher RPW value than the healthy controls on an unstable surface (0.58 ± 0.21 vs. 0.41 ± 0.26,p< 0.05). Under the condition of triceps surae vibration, the sway length (pstable< 0.05;punstable< 0.001), AP velocity (pstable< 0.01;punstable< 0.001) and ML velocity (punstable< 0.05) had significant group main effects. Moreover, when the triceps surae vibrated under the unstable surface, the differences during vibration and post vibration in sway length and AP velocity between the groups were significantly higher in the CLBP group than in the healthy group (p< 0.05). However, under the condition of lumbar paravertebral muscle vibration, no significant group main effect was observed.

Conclusion

The patients with CLBP exhibited impaired dynamic postural control in response to disturbances, potentially linked to changes in proprioceptive weighting.
Effects of low-frequency rTMS combined with antidepressants on depression in patients with post-stroke depression: a systematic review and meta-analysis
Authors: Pan Juanhong , Li Hongpeng , Wang Yongshen , Lu Li , Wang Ying , Zhao Tianyu , Zhang Di , Jin Song
Published: May 2023

Objective

To evaluate the effect of low-frequency (≤1 Hz) repetitive transcranial magnetic stimulation (low-frequency rTMS) combined with antidepressants on depression and the levels of inflammatory factors IL-6 and TNF-α in patients with post-stroke depression (PSD).

Design

PubMed, Embase, Web of Science, Cochrane Library (CBM), China National Knowledge Infrastructure, Technology Periodical Database, and Wanfang Database were searched until October 2022 for randomized controlled trials.

Participants

Patients with post-stroke depression (PSD) participated in the study.

Results

A total of 16 randomized controlled trials (RCTs) involving 1,463 patients with PSD were included. According to the Physiotherapy Evidence Database (PEDro) quality assessment, three studies received high quality (eight scores) and 13 RCTs received moderate quality (six scores) results. The meta-analysis showed that low-rTMS combined with an antidepressant significantly reduced the Hamilton Depression Scale (HAMD) score and the National Institutes of Health Stroke Scale (NIHSS) score, reduced IL-6 and TNF-α levels, and improved the MMSE score in PSD compared to an antidepressant alone.

Conclusion

The results of this meta-analysis evidenced the efficacy and safety of low-rTMS combined with antidepressants in the treatment of depression in PSD patients. The combined therapy could reduce The depression state and the levels of IL-6 and TNF-α, and enhance the cognitive function of patients. In addition, low-rTMS had fewer adverse effects, proving safety. However, there are shortcomings, such as a lack of long-term follow-up, different intervention sites of low-rTMS, and different intervention frequencies (0.5 or 1 Hz). Thus, in the future, RCTs with a larger sample size and longer-term observation are required to verify the efectiveness of low-rTMS combined therapy on PSD. Meantime, a new meta-analysis could be analysized, which intervention sites and frequency are more effective in treating PSD.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022376845.
Diffusion-weighted MRI of the spinal cord in cervical spondylotic myelopathy after instrumented fusion
Authors: Koch Kevin M. , Nencka Andrew S. , Klein Andrew , Wang Marjorie , Kurpad Shekar , Vedantam Aditya , Budde Matthew
Published: May 2023

Introduction

This study investigated tissue diffusion properties within the spinal cord of individuals treated for cervical spondylotic myelopathy (CSM) using post-decompression stabilization hardware. While previous research has indicated the potential of diffusion-weighted MRI (DW-MRI) markers of CSM, the metallic implants often used to stabilize the decompressed spine hamper conventional DW-MRI.

Methods

Utilizing recent developments in DW-MRI metal-artifact suppression technologies, imaging data was acquired from 38 CSM study participants who had undergone instrumented fusion, as well as asymptomatic (non-instrumented) control participants. Apparent diffusion coefficients were determined in axial slice sections and split into four categories: a) instrumented levels, b) non-instrumented CSM levels, c) adjacent-segment (to instrumentation) CSM levels, and d) non-instrumented control levels. Multi-linear regression models accounting for age, sex, and body mass index were used to investigate ADC measures within each category. Furthermore, the cord diffusivity within CSM subjects was correlated with symptom scores and the duration since fusion procedures.

Results

ADC measures of the spinal cord in CSM subjects were globally reduced relative to control subjects (p = 0.005). In addition, instrumented levels within the CSM subjects showed reduced diffusivity relative to controls (p = 0.003), while ADC within non-instrumented CSM levels did not statistically deviate from control levels (p = 0.107).

Discussion

Multi-spectral DW-MRI technology can be effectively employed to evaluate cord diffusivity near fusion hardware in subjects who have undergone surgery for CSM. Leveraging this advanced technology, this study had identified significant reductions in cord diffusivity, relative to control subjects, in CSM patients treated with conventional metallic fusion instrumentation.
Role of white matter hyperintensity in effects of apolipoprotein E on cognitive injury
Authors: Raber Jacob , Silbert Lisa C.
Published: May 2023

Magnetic Resonance Imaging (MRI) T2-weighted white matter hyperintensity (WMH) is a marker of small vessel cerebrovascular pathology and is of ischemic origin. The prevalence and severity of WMH is associated with cardiovascular risk factors, aging, and cognitive injury in mild cognitive impairment (MCI), vascular dementia, and Alzheimer’s disease (AD). WMH especially affects executive function, with additional effects on memory and global cognition. Apolipoprotein E (apoE) plays a role in cholesterol metabolism and neuronal repair after injury. Human and animal studies support a role for apoE in maintaining white matter integrity. In humans, there are three major human apoE isoforms, E2, E3, and E4. Human apoE isoforms differ in risk to develop AD and in association with WMH. In this Mini Review, we propose an increased focus on the role of WMH in cognitive health and cognitive injury and the likely role of apoE and apoE isoform in modulating these effects. We hypothesize that apoE and apoE isoforms play a role in modulating WMH via apoE isoform-dependent effects on oxylipins and 7-ketocholesterol, as well as amyloid related vascular injury, as seen in cerebral amyloid angiopathy.
Clinical, radiological, therapeutic and prognostic differences between MOG-seropositive and MOG-seronegative pediatric acute disseminated encephalomyelitis patients: a retrospective cohort study
Authors: Dong Xueshan , Jiang Yan , Yuan Ping , Fan Xiao , Ma Jiannan , Wu Peng , Jiang Li , Li Xiujuan
Published: May 2023

Objective

This study aimed to compare the clinical, radiological, therapeutic, and prognostic differences between pediatric patients showing acute disseminated encephalomyelitis (ADEM) with and without myelin oligodendrocyte glycoprotein (MOG) antibodies.

Methods

We retrospectively collected all available data of children diagnosed with ADEM and tested for serum MOG antibodies at the Children's Hospital of Chongqing Medical University from January 2017 to May 2021.

Results

A total of 62 patients were included in our cohort, of which 35 were MOG-seropositive and 27 were MOG-seronegative. MOG-seropositive ADEM children presented with significantly lower rates of seizures (P = 0.038) and cranial nerve (III–XII) palsy (P = 0.003). Isolated leukocytosis in the blood was more common in ADEM children with MOG antibodies (P < 0.001). The two groups showed no significant differences in the distributions and extent of the MRI lesions as well as the appearance of typical/atypical magnetic resonance imaging (MRI) features. MOG-seropositive children were more likely to relapse (P = 0.017) despite having slower oral prednisolone tapering after acute treatments (P = 0.028). In scoring performed on the basis of two neurological function scoring systems, MOG-seropositive children showed milder neurological disability status at onset (P = 0.017 and 0.025, respectively) but showed no difference during follow-up.

Conclusion

In summary, the differences in the clinical manifestations and auxiliary examination findings for MOG-seropositive and MOG-seronegative ADEM children lacked significance and specificity, making early identification difficult. MOG-seropositive children were more likely to relapse and showed slower steroid tapering. Moreover, MOG-seronegative children tended to have more severe neurological impairments at onset with no difference during follow-up.
Muscle synergy analysis of eight inter-limb coordination modes during human hands-knees crawling movement
Authors: Li Chengxiang , Chen Xiang , Zhang Xu , Chen Xun , Wu De
Published: May 2023

In order to reveal in-depth the neuromuscular control mechanism of human crawling, this study carries out muscle synergy extraction and analysis on human hands-knees crawling under eight specific inter-limb coordination modes, which are defined according to the swing sequence of limbs and includes two-limb swing crawling modes and six single-limb swing crawling modes. Ten healthy adults participate in crawling data collection, and surface electromyography (sEMG) signals are recorded from 30 muscles of limbs and trunk. Non-negative matrix factorization (NNMF) algorithm is adopted for muscle synergy extraction, and a three-step muscle synergy analysis scheme is implemented by using the hierarchical clustering method. Based on results of muscle synergy extraction, 4 to 7 synergies are extracted from each participant in each inter-limb coordination mode, which supports the muscle synergy hypothesis to some extent, namely, central nervous system (CNS) controls the inter-limb coordination modes during crawling movement by recruiting a certain amount of muscle synergies, rather than a single muscle. In addition, when different participants crawl in the same inter-limb coordination mode, they share more temporal features in recruiting muscle synergies. Further, by extracting and analyzing intra-mode shared synergies among participants and inter-mode shared synergies among the eight inter-limb coordination modes, the CNS is found to realize single-limb swing crawling modes by recruiting the four inter-mode shared synergy structures related to the swing function of each limb in different orders, and realize the two-limb swing crawling modes by recruiting synchronously two intra-mode shared synergy structures. The research results of the muscle synergy analysis on the eight specific inter-limb coordination modes, on the one hand, provide a basis for muscle synergy hypothesis from the perspective of crawling motion, on the other hand, also provide a possible explanation for the choice of the inter-limb coordination mode in human crawling.
Transnasal targeted delivery of therapeutics in central nervous system diseases: a narrative review
Authors: Won Seoyeon , An Jeongyeon , Song Hwayoung , Im Subin , You Geunho , Lee Seungho , Koo Kyo-in , Hwang Chang Ho
Published: May 2023

Currently, neurointervention, surgery, medication, and central nervous system (CNS) stimulation are the main treatments used in CNS diseases. These approaches are used to overcome the blood brain barrier (BBB), but they have limitations that necessitate the development of targeted delivery methods. Thus, recent research has focused on spatiotemporally direct and indirect targeted delivery methods because they decrease the effect on nontarget cells, thus minimizing side effects and increasing the patient’s quality of life. Methods that enable therapeutics to be directly passed through the BBB to facilitate delivery to target cells include the use of nanomedicine (nanoparticles and extracellular vesicles), and magnetic field-mediated delivery. Nanoparticles are divided into organic, inorganic types depending on their outer shell composition. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes. Magnetic field-mediated delivery methods include magnetic field-mediated passive/actively-assisted navigation, magnetotactic bacteria, magnetic resonance navigation, and magnetic nanobots—in developmental chronological order of when they were developed. Indirect methods increase the BBB permeability, allowing therapeutics to reach the CNS, and include chemical delivery and mechanical delivery (focused ultrasound and LASER therapy). Chemical methods (chemical permeation enhancers) include mannitol, a prevalent BBB permeabilizer, and other chemicals—bradykinin and 1-O-pentylglycerol—to resolve the limitations of mannitol. Focused ultrasound is in either high intensity or low intensity. LASER therapies includes three types: laser interstitial therapy, photodynamic therapy, and photobiomodulation therapy. The combination of direct and indirect methods is not as common as their individual use but represents an area for further research in the field. This review aims to analyze the advantages and disadvantages of these methods, describe the combined use of direct and indirect deliveries, and provide the future prospects of each targeted delivery method. We conclude that the most promising method is the nose-to-CNS delivery of hybrid nanomedicine, multiple combination of organic, inorganic nanoparticles and exosomes, via magnetic resonance navigation following preconditioning treatment with photobiomodulation therapy or focused ultrasound in low intensity as a strategy for differentiating this review from others on targeted CNS delivery; however, additional studies are needed to demonstrate the application of this approach in more complex in vivo pathways.
A neurophysiological approach to the distinction between motor and cognitive skills: a functional magnetic resonance imaging study
Authors: Lu Yunhang , Kim Jingu , Kim Teri
Published: May 2023

This study investigated the neurophysiological differences underpinning motor and cognitive skills by measuring the brain activity via functional magnetic resonance imaging. Twenty-five healthy adults (11 women, 25.8 ± 3.5 years of age) participated in the study. We developed three types of tasks, namely, simple motor task (SMT), complex motor task (CMT), and cognitive task (CT), using two-dimensional images of Gomoku, a traditional game known as five in a row. When shown the stimulus, participants were instructed to identify the best spot to win the game and to perform motor imagery of placing the stone for the SMT and CMT but not for the CT. Accordingly, we found significant activation from the CMT minus SMT contrast in the dorsolateral prefrontal cortex, posterior parietal cortex, precentral gyrus, and superior frontal cortex, which reflected increased visuospatial attention, working memory, and motor planning. From the CT minus SMT contrast, we observed significant activation in the left caudate nucleus, right medial prefrontal cortex, and right primary somatosensory cortex, responsible for visuospatial working memory, error detection, and cognitive imagery, respectively. The present findings indicate that adopting a conventional classification of cognitive and motor tasks focused on the extent of decision making and motor control involved in task performance might not be ideal.
3D shape reconstruction with a multiple-constraint estimation approach
Authors: Chen Xia , Sun Zhan-Li , Zhang Ying
Published: May 2023

In this study, a multiple-constraint estimation algorithm is presented to estimate the 3D shape of a 2D image sequence. Given the training data, a sparse representation model with an elastic net, i.e., l1−norm and l2−norm constraints, is devised to extract the shape bases. In the sparse model, the l1−norm and l2−norm constraints are enforced to regulate the sparsity and scale of coefficients, respectively. After obtaining the shape bases, a penalized least-square model is formulated to estimate 3D shape and motion, by considering the orthogonal constraint of the transformation matrix, and the similarity constraint between the 2D observations and the shape bases. Moreover, an Augmented Lagrange Multipliers (ALM) iterative algorithm is adopted to solve the optimization of the proposed approach. Experimental results on the well-known CMU image sequences demonstrate the effectiveness and feasibility of the proposed model.