bluuebunny/crossref_metadata_2025 huggingface dataset:
Preservation of Titanium in a Naringin-Containing Solution to Enhance Osteogenic and Anti-inflammatory Activities In Vitro
Authors: Chen Wei , Zhu Wen-qing , Su Shan , Liu Yao , Qiu Jing
Published: April 2022

When exposed to air, the titanium implants undergo changes in surface characteristics and biological activity, which is known as biological aging. It is important to find a suitable storage method to slow down the biological aging of titanium. The purpose of this study was to develop a naringin-containing storage solution and evaluate the effects of this storage method on physicochemical properties as well as osteogenic and anti-inflammatory activities of commercial pure titanium (cp-Ti) and sandblasted with large grit and acid-etched titanium (SLA-Ti). Titanium surfaces stored in air and 0.9% NaCl solution for 4 weeks were served as control, and samples submerged in three different concentrations of naringin-containing solution for 4 weeks were used to investigate the new storage method. Surface topography images showed that nanostructures were observed on liquid-stored SLA-Ti surfaces. The storage condition did not influence the roughness of both cp-Ti and SLA-Ti. However, the wettability of titanium varied with the storage methods. Titanium stored in the naringin-containing solution exhibited lower contact angles. Samples stored in aqueous solution were less susceptible to hydrocarbon contamination. The preservation of titanium in the 10 μM naringin-containing solution enhanced the adhesion, proliferaton, and differentiation of osteoblasts. In addition, macrophages on samples stored in 10 μM and 100 μM naringin-containing solutions displayed better anti-inflammatory effect. In summary, the 10 μM naringin-containing solution could enhance osteogenic and anti-inflammatory activities of titanium and was proved to be an effective new storage condition.
Nomogram and Machine Learning Models Predict 1-Year Mortality Risk in Patients With Sepsis-Induced Cardiorenal Syndrome
Authors: Liu Yiguo , Zhang Yingying , Zhang Xiaoqin , Liu Xi , Zhou Yanfang , Jin Yun , Yu Chen
Published: April 2022

Objective

Early prediction of long-term outcomes in patients with sepsis-induced cardiorenal syndrome (CRS) remains a great challenge in clinical practice. Herein, we aimed to construct a nomogram and machine learning model for predicting the 1-year mortality risk in patients with sepsis-induced CRS.

Methods

This retrospective study enrolled 340 patients diagnosed with sepsis-induced CRS in Shanghai Tongji Hospital between January 2015 and May 2019, as a discovery cohort. Two predictive models, the nomogram and machine learning model, were used to predict 1-year mortality. The prognostic variables used to develop the nomogram were identified based on a forward stepwise binary logistic regression, and the predictive ability of the nomogram was evaluated by the areas under the receiver operating characteristic curve (AUC) and the calibration curve. Meanwhile, machine learning (ML) techniques, such as support vector machine, random forest (RF), and gradient boosted decision tree, were assessed mainly by accuracy and AUC. Feature ranking analysis was performed using the ML algorithm. Both nomogram and ML models were externally validated by an independent cohort of 103 patients diagnosed with sepsis-induced CRS between June 2019 and December 2020.

Results

Age, sequential sepsis-related organ failure score (SOFA), serum myoglobin (MYO), vasopressor use, and mechanical ventilation were identified as independent risk factors for 1-year mortality in the nomogram predictive model. In the discovery cohort, the nomogram yielded higher AUC for predicting mortality than did the SOFA score (0.855 [95% CI: 0.815–0.895] vs. 0.756 [95% CI: 0.705–0.808]). For ML, the model developed by RF showed the highest accuracy (0.765) and AUC (0.854). In feature ranking analysis, factors such as age, MYO, SOFA score, vasopressor use, and baseline serum creatinine were identified as important features affecting 1-year prognosis. Moreover, the nomogram and RF model both performed well in external validation, with an AUC of 0.877 and 0.863, respectively.

Conclusion

Our nomogram and ML models showed that age, SOFA score, serum MYO levels, and the use of vasopressors during hospitalization were the main factors influencing the risk of long-term mortality. Our models may serve as useful tools for assessing long-term prognosis in patients with sepsis-induced CRS.
Case Report: The Application of Dupilumab in Atopic Dermatitis Children Complicated With Nephrotic Syndrome
Authors: Yang Ya-Qi , Chen Hao , Qiu Li-Ru , Zhu Rong-Fei
Published: April 2022

Nephrotic syndrome (NS) tends to be more common in patients with history of allergies. Atopic dermatitis (AD) is one of the most common allergic diseases in children. Dupilumab, a dual IL-4 and IL-13 inhibitor, has been widely used to treat AD patients. However, the efficacy and safety of Dupilumab in NS is unclear. We reported two AD patients with NS comorbidities treated with Dupilumab. The outcomes showed the good control of NS and less systemic steroids and/or immunosuppressive agents use during the Dupilumab treatment period, accompanied by significant relief of AD symptoms. We suggest prospective pilot studies and randomized controlled trials could be carried out to validate the efficacy and safety of Dupilumab in the treatment of NS patients.
Emerging Infections Due to Shewanella spp.: A Case Series of 128 Cases Over 10 Years
Authors: Ng Wincy Wing-Sze , Shum Hoi-Ping , To Kelvin Kai-Wang , Sridhar Siddharth
Published: April 2022

Background

Shewanella species are emerging pathogens that can cause severe hepatobiliary, skin and soft tissue, gastrointestinal, respiratory infections, and bacteremia. Here we reported the largest case series of infections caused by Shewanella species.

Aim

To identify the clinical features and risk factors predisposing to Shewanella infections. To evaluate resistance pattern of Shewanella species and appropriateness of antibiotic use in the study cohort.

Methods

Patients admitted to a regional hospital in Hong Kong with Shewanella species infection from April 1, 2010 to December 31, 2020 were included. Demographics, antibiotics, microbiology, and outcomes were retrospectively analyzed.

Findings

Over the 10 years, we identified 128 patients with Shewanella species infection. 61.7% were male with a median age of 78 (IQR 65–87). Important underlying diseases included hepatobiliary diseases (63.3%), malignancy (26.6%), chronic kidney disease or end-stage renal failure (25.8%), and diabetes mellitus (22.7%). Hepatobiliary infections (60.4%) were the most common clinical manifestation. Majority (92.2%) were infected with Shewanella algae, while 7.8% were infected with Shewanella putrefaciens. The identified organisms were usually susceptible to ceftazidime (98.7%), gentamicin (97.4%), cefoperazone-sulbactam (93.5%) and ciprofloxacin (90.3%). Imipenem-susceptible strains were only present in 76.6% of isolates.

Conclusion

This largest case series suggested that Shewanella infections are commonly associated with underlying comorbidities, especially with hepatobiliary diseases and malignancy. Although Shewanella species remained largely susceptible to third and fourth generation cephalosporins and aminoglycosides, carbapenem resistance has been on a significant rise.
Clinical Outcome of Viral Respiratory Tract Infections in Hospitalized Adults in Norway: High Degree of Inflammation and Need of Emergency Care for Cases With Respiratory Syncytial Virus
Authors: Debes Sara , Haug Jon Birger , de Blasio Birgitte Freiesleben , Lindstrøm Jonas Christoffer , Jonassen Christine Monceyron , Dudman Susanne Gjeruldsen
Published: April 2022

Background

The clinical features and outcomes of viral respiratory tract infections (RTIs) in adults have not been thoroughly studied, especially the respiratory syncytial virus (RSV) disease burden. It has become apparent that outbreaks of RSV in the elderly are associated with increased hospitalization rates. However, little data exists on the severity of such viral RTIs in adults, particularly the need for hospitalization, respiratory support and intensive care.

Methods

We conducted a retrospective observational single-center study at Østfold Hospital Trust, Norway, during three winter seasons 2015–2018. Patients ≥18 years with either influenza A, influenza B, RSV A/B, human metapneumovirus, parainfluenza virus 1–4 or adenovirus detected in respiratory specimens were included, if they were hospitalized 14 days prior or following the detection date, with signs of RTI. Hospital records on treatment and outcome were investigated, as well as mortality of all causes up to 30 days from discharge.

Results

Of the 1222 infection events that were included, influenza A was the most frequent virus detected (39%), while 179 infection events (14.6%) were due to RSV. Influenza B counted for 24% of the infection events, human metapneumovirus 13%, parainfluenza virus 9% and adenovirus 1%. Patients admitted with RSV more often suffered from COPD and congestive heart failure than patients with influenza A. In addition, RSV patients were overrepresented in the urgent response NEWS score (National Early Warning Score) category ≥5. RSV patients also showed signs of more severe inflammation, with WBC ≥11.1 × 109/L and CRP >100 mg/L, and they were more often treated with antibiotic agents during their hospital stay. However, we found no differences in the need for ICU admission or mortality.

Conclusion

Patients with RSV had more often high values for markers of inflammation and elevated NEWS score when compared to patients hospitalized with other common respiratory viruses. Taken into account that they suffered more frequently from comorbidities like COPD, these patients needed hospitalization more urgently. These findings highlight the need for further investigations on RSV disease in adults and the elderly.
Matrix Effectors in the Pathogenesis of Keratinocyte-Derived Carcinomas
Authors: Kavasi Rafaela-Maria , Neagu Monica , Constantin Carolina , Munteanu Adriana , Surcel Mihaela , Tsatsakis Aristidis , Tzanakakis George N. , Nikitovic Dragana
Published: April 2022

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), referred to as keratinocyte carcinomas, are skin cancer with the highest incidence. BCCs, rarely metastasize; whereas, though generally not characterized by high lethality, approximately 2–4% of primary cSCCs metastasize with patients exhibiting poor prognosis. The extracellular matrix (ECM) serves as a scaffold that provides structural and biological support to cells in all human tissues. The main components of the ECM, including fibrillar proteins, proteoglycans (PGs), glycosaminoglycans (GAGs), and adhesion proteins such as fibronectin, are secreted by the cells in a tissue-specific manner, critical for the proper function of each organ. The skin compartmentalization to the epidermis and dermis compartments is based on a basement membrane (BM), a highly specialized network of ECM proteins that separate and unify the two compartments. The stiffness and assembly of BM and tensile forces affect tumor progenitors' invasion at the stratified epithelium's stromal border. Likewise, the mechanical properties of the stroma, e.g., stiffness, are directly correlated to the pathogenesis of the keratinocyte carcinomas. Since the ECM is a pool for various growth factors, cytokines, and chemokines, its' intense remodeling in the aberrant cancer tissue milieu affects biological functions, such as angiogenesis, adhesion, proliferation, or cell motility by regulating specific signaling pathways. This review discusses the structural and functional modulations of the keratinocyte carcinoma microenvironment. Furthermore, we debate how ECM remodeling affects the pathogenesis of these skin cancers.
Anti-factor Xa Activity Is Not Associated With Venous Thromboembolism in Critically Ill Patients Receiving Enoxaparin for Thromboprophylaxis: A Retrospective Observational Study
Authors: Dibiasi Christoph , Gratz Johannes , Wiegele Marion , Baierl Andreas , Schaden Eva
Published: April 2022

Background

Anti-factor Xa activity has been suggested as a surrogate parameter for judging the effectiveness of pharmacological thromboprophylaxis with low molecular weight heparins in critically ill patients. However, this practice is not supported by evidence associating low anti-factor Xa activity with venous thromboembolism.

Methods

We performed a retrospective observational study including 1,352 critically ill patients admitted to 6 intensive care units of the Medical University of Vienna, Austria between 01/2015 and 12/2018. Included patients received prophylactically dosed enoxaparin (≤100 IU/kg body weight per day). We analyzed median peak, 12-h trough and 24-h trough anti-factor Xa activity per patient and compared anti-factor Xa activity between patients without vs. with venous thromboembolic events.

Results

19 patients (1.4%) developed a total of 22 venous thromboembolic events. We did not observe a difference of median (IQR) anti-factor Xa activity between patients without venous thromboembolism [peak 0.22 IU/mL (0.14–0.32); 12-h trough 0.1 IU/mL (<0.1–0.17), 24-h trough < 0.1 IU/mL (<0.1– <0.1)] vs. patients with venous thromboembolism [peak 0.33 IU/mL (0.14–0.34); 12-h trough 0.12 IU/mL (<0.1–0.26); 24-h trough < 0.1 IU/mL (<0.1–<0.1)].

Conclusion

Patients who developed venous thromboembolism had anti-factor Xa activities comparable to those who did not suffer from venous thromboembolism.
Metagenomics Reveals the Microbial Community Responsible for Producing Biogenic Amines During Mustard [Brassica juncea (L.)] Fermentation
Authors: Yu Yangyang , Li Lu , Xu Yujuan , Li Hong , Yu Yuanshan , Xu Zhenlin
Published: April 2022

Biogenic amines (BAs) are considered potential hazards produced during fermented food processing, and the production of BAs is closely related to microbial metabolism. In this work, the changes of BA content were analyzed during mustard fermentation, and microbes and gene abundance responsible for producing BAs were revealed by metagenomic analyses. The results showed that cadaverine, putrescine, tyramine, and histamine were generated during mustard fermentation, which mainly accumulate in the first 6 days of fermentation. According to the metagenome sequencing, the predominant genus was Bacillus (64.78%), followed by Lactobacillus (11.67%), Weissella (8.88%), and Leuconostoc (1.71%) in the initial fermentation stage (second day), while Lactobacillus (76.03%) became the most dominant genus in the late stage. In addition, the gene abundance of BA production enzymes was the highest in the second day and decreased continuously as fermentation progressed. By tracking the source of the enzyme in the KEGG database, both Bacillus and Delftia closely correlated to the generation of putrescine. Besides, Bacillus also correlated to the generation of tyramine and spermidine, and Delftia also correlated to the generation of cadaverine and spermine. In the processes of fermentation, the pH of fermented mustard showed slower decrease compared with other similar fermented vegetables, which may allow Bacillus to grow at high levels before the pH <4. This study reveals the change of BA content and microbes involved in BA formation during mustard fermentation.
Comparative Transcriptome Analysis of Fungal Pathogen Bipolaris maydis to Understand Pathogenicity Behavior on Resistant and Susceptible Non-CMS Maize Genotypes
Authors: Meshram Shweta , Gogoi Robin , Bashyal Bishnu Maya , Kumar Aundy , Mandal Pranab Kumar , Hossain Firoz
Published: April 2022

Bipolaris maydis is pathogen of maize which causes maydis leaf blight disease. In India major losses occur due to the B. maydis race “O” pathogen, whereas in other parts of the world, major losses are due to the race “T” pathogen. In the present study, we conducted an in planta transcriptomics study of the B. maydis race “O” pathogen after infection on non-CMS maize resistant and susceptible genotypes by mRNA sequencing to understand the molecular basis of pathogenicity for better management of the pathogen. Approximately 23.4 GB of mRNA-seq data of B. maydis were obtained from both resistant and susceptible maize backgrounds for fungus. Differentially expressed genes (DEGs) analysis of B. maydis in two different genetic backgrounds suggested that the majority of highly DEGs were associated with mitochondrial, cell wall and chitin synthesis, sugar metabolism, peroxidase activity, mitogen-activated protein kinase (MAPK) activity, and shikimate dehydrogenase. KEGG analysis showed that the biosynthetic pathways for secondary metabolism, antibiotics, and carbon metabolism of fungus were highly enriched, respectively, in susceptible backgrounds during infection. Previous studies in other host pathogen systems suggest that these genes play a vital role in causing disease in their host plants. Our study is probably the first transcriptome study of the B. maydis race “O” pathogen and provides in-depth insight of pathogenicity on the host.
Differences in the Composition of the Rumen Microbiota of Finishing Beef Cattle Divergently Ranked for Residual Methane Emissions
Authors: Smith Paul E. , Kelly Alan K. , Kenny David A. , Waters Sinéad M.
Published: April 2022

With the advent of high throughput technology, it is now feasible to study the complex relationship of the rumen microbiota with methanogenesis in large populations of ruminant livestock divergently ranked for enteric emissions. Recently, the residual methane emissions (RME) concept has been identified as the optimal phenotype for assessing the methanogenic potential of ruminant livestock due to the trait’s independence from animal productivity but strong correlation with daily methane emissions. However, there is currently a dearth of data available on the bacterial and archaeal microbial communities residing in the rumens of animals divergently ranked for RME. Therefore, the objective of this study was to investigate the relationship between the rumen microbiota and RME in a population of finishing beef cattle. Methane emissions were estimated from individual animals using the GreenFeed Emissions Monitoring system for 21 days over a mean feed intake measurement period of 91 days. Residual methane emissions were calculated for 282 crossbred finishing beef cattle, following which a ∼30% difference in all expressions of methane emissions was observed between high and low RME ranked animals. Rumen fluid samples were successfully obtained from 268 animals during the final week of the methane measurement period using a trans-oesophageal sampling device. Rumen microbial DNA was extracted and subjected to 16S rRNA amplicon sequencing. Animals ranked as low RME had the highest relative abundances (P < 0.05) of lactic-acid-producing bacteria (Intestinibaculum, Sharpea, and Olsenella) and Selenomonas, and the lowest (P < 0.05) proportions of Pseudobutyrivibrio, Butyrivibrio, and Mogibacterium. Within the rumen methanogen community, an increased abundance (P < 0.05) of the genus Methanosphaera and Methanobrevibacter RO clade was observed in low RME animals. The relative abundances of both Intestinibaculum and Olsenella were negatively correlated (P < 0.05) with RME and positively correlated with ruminal propionate. A similar relationship was observed for the abundance of Methanosphaera and the Methanobrevibacter RO clade. Findings from this study highlight the ruminal abundance of bacterial genera associated with the synthesis of propionate via the acrylate pathway, as well as the methanogens Methanosphaera and members of the Methanobrevibacter RO clade as potential microbial biomarkers of the methanogenic potential of beef cattle.
Bioherder Generated by Rhodococcus erythropolis as a Marine Oil Spill Treating Agent
Authors: Yu Miao , Zhu Zhiwen , Chen Bing , Cao Yiqi , Zhang Baiyu
Published: April 2022

There is an urgent call for contingency planning with effective and eco-friendly oil spill cleanup responses. In situ burning, if properly applied, could greatly mitigate oil in water and minimize the adverse environmental impacts of the spilled oil. Chemical herders have been commonly used along with in situ burning to increase the thickness of spilled oil at sea and facilitate combustion. These chemical surfactant-based agents can be applied to the edges of the oil slick and increase its thickness by reducing the water–oil interfacial tension. Biosurfactants have recently been developed as the next generation of herds with a smaller environmental footprint. In this study, the biosurfactant produced by Rhodococcus erythropolis M25 was evaluated and demonstrated as an effective herding agent. The impact of environmental and operational factors (e.g., temperature, herder dose, spilled oil amount, water salinity, and operation location) on its performance was investigated. A five-factor fractional design was applied to examine the importance of these factors and their impact on herding effectiveness and efficiency. The results of this study showed that higher temperature and a higher dose of herder could result in an increased oil slick thickness changing rate. Differences in water salinity at the same temperature led to the same trend, that is, the herding process effectively goes up with increasing herder–oil ratio (HOR). Further large-scale testing needs to be conducted for evaluating the applicability of the developed bioherder in the field.
Grocott Methenamine Silver Staining Is the Optimal Approach to Histological Diagnosis of Pulmonary Cryptococcosis
Authors: Wang Suijing , Lai Jieyi , Wu Ruibin , Zhang Lihong , Huang Mayan , Xiao Yongbo , Zhang Xinke , Chen Jiewei
Published: April 2022

Background

Histological staining methods for Cryptococcus identification vary in accuracy. This study aimed to investigate the clinical value of Grocott methenamine silver (GMS), periodic acid-Schiff (PAS), and Alcian blue (AB) staining in the diagnosis of pulmonary cryptococcosis (PC).

Methods

From April 2004 to June 2021, the clinical and pathological data of 152 patients with PC were collected from the Department of Pathology, Sun Yat-sen University Cancer Center. The sensitivity and identifiability of GMS, PAS, and AB staining for histological diagnosis were systematically evaluated using statistical methods combined with the microscopic characteristics of PC cases.

Results

Statistical analysis showed that the detection rates of GMS, PAS, and AB staining were 100.0% (152/152), 94.7% (144/152), and 81.6% (124/152), respectively. McNemar’s test showed that the sensitivity of GMS was significantly higher than those of PAS (P = 0.008) and AB stains (P < 0.001). Both PAS and AB stains had obvious non-specific staining, which interfered with the detection of Cryptococcus, and increased diagnostic difficulties. In contrast, in GMS staining, Cryptococcus spores were prominent with a clean background and were clearly observed at low or medium power magnification, with the identifiability significantly better than those of PAS or AB staining.

Conclusion

GMS staining had sensitivity up to 100%, and identifiability that was better than those of PAS and AB staining. GMS is the best method for histological diagnosis of PC.
Aerospace Technology Improves Fermentation Potential of Microorganisms
Authors: Chi Yan , Wang Xuejiang , Li Feng , Zhang Zhikai , Tan Peiwen
Published: April 2022

It is highly possible to obtain high-quality microbial products in appreciable amounts, as aerospace technology is advancing continuously. Genome-wide genetic variations in microorganisms can be triggered by space microgravity and radiation. Mutation rate is high, mutant range is wide, and final mutant character is stable. Therefore, space microorganism breeding is growing to be a new and promising area in microbial science and has greatly propelled the development of fermentation technology. Numerous studies have discovered the following improvements of fermentation potential in microorganisms after exposure to space: (1) reduction in fermentation cycle and increase in growth rate; (2) improvement of mixed fermentation species; (3) increase in bacterial conjugation efficiency and motility; (4) improvement of the bioactivity of various key enzymes and product quality; (5) enhancement of multiple adverse stress resistance; (6) improvement of fermentation metabolites, flavor, appearance, and stability. Aerospace fermentation technology predominantly contributes to bioprocessing in a microgravity environment. Unlike terrestrial fermentation, aerospace fermentation keeps cells suspended in the fluid medium without significant shear forces. Space radiation and microgravity have physical, chemical, and biological effects on mutant microorganisms by causing alternation in fluid dynamics and genome, transcriptome, proteome, and metabolome levels.
Evidence of Omics, Immune Infiltration, and Pharmacogenomics for BATF in a Pan-Cancer Cohort
Authors: Jia Chenguang , Ma Yihui , Wang Mengyang , Liu Wen , Tang Feng , Chen Jincao
Published: April 2022

Background: Cytotoxic CD8+ T-cell exhaustion is the major barrier for immunotherapy in tumors. Recent studies have reported that the basic leucine zipper activating transcription factor–like transcription factor (BATF) is responsible for countering cytotoxic CD8+ T-cell exhaustion. Nevertheless, the expression and roles of BATF in tumors have been poorly explored.

Methods: In the present study, we conducted a multi-omics analysis, including gene expression, methylation status, DNA alterations, pharmacogenomics, and survival status based on data from the Cancer Genome Atlas (TCGA) database to discern expression patterns and prognostic roles of BATF in tumors. We also explored potential roles of BATF in a pan-cancer cohort by performing immune infiltration, Gene Ontology (GO) enrichment, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In vitro assay was also performed to explore roles of BATF in tumor cells.

Results: We found that BATF was aberrantly upregulated in 27 types of tumors with respect to the corresponding normal tissues. Abnormal BATF expression in tumors predicted survival times of patients in a tissue-dependent manner. The results of GO, immune infiltration, and KEGG analysis revealed that increased BATF expression in tumors participated in modulating immune cell infiltration via immune-related pathways. BATF expression could also predict immunotherapeutic and chemotherapy responses in cancers. Moreover, knockdown of BATF suppresses tumor cell viability.

Conclusion: Our present study reports the vital roles of BATF in tumors and provides a theoretical basis for targeting BATF therapy.
Multi-Omics Integration in Mice With Parkinson’s Disease and the Intervention Effect of Cyanidin-3-O-Glucoside
Authors: Wang Wang , Zhu Guoxue , Wang Yuwen , Li Wei , Yi Shilin , Wang Kai , Fan Lu , Tang Juanjuan , Chen Ruini
Published: April 2022

Background

Parkinson’s disease (PD) is a multifactorial degenerative disease of the central nervous system, which affects mostly older adults. To date, research has focused on the progression of PD. Simultaneously, it was confirmed that the imbalances in gut microbiota are associated with the onset and progression of PD. Accurate diagnosis and precise treatment of PD are currently deficient due to the absence of effective biomarkers.

Methods

In this study, the pharmacodynamic study of cyanidin-3-O-glucoside in PD mice was used. It intends to use the “imbalance” and “balance” of intestinal microecology as the starting point to investigate the “gut-to-brain” hypothesis using metabolomic-combined 16S rRNA gene sequencing methods. Simultaneously, metabolomic analysis was implemented to acquire differential metabolites, and microbiome analysis was performed to analyze the composition and filter the remarkably altered gut microbiota at the phylum/genera level. Afterward, metabolic pathway and functional prediction analysis of the screened differential metabolites and gut microbiota were applied using the MetaboAnalyst database. In addition, Pearson’s correlation analysis was used for the differential metabolites and gut microbiota. We found that cyanidin-3-O-glucoside could protect 1-methyl-4-phenyl-1,2,3,6− tetrahydropy ridine (MPTP)-induced PD mice.

Results

Metabolomic analysis showed that MPTP-induced dysbiosis of the gut microbiota significantly altered sixty-seven metabolites. The present studies have also shown that MPTP-induced PD is related to lipid metabolism, amino acid metabolism, and so on. The 16S rRNA sequencing analysis indicated that 5 phyla and 22 genera were significantly altered. Furthermore, the differential gut microbiota was interrelated with amino acid metabolism, and so on. The metabolites and gut microbiota network diagram revealed significant correlations between 11 genera and 8 differential metabolites.

Conclusion

In combination, this study offers potential molecular biomarkers that should be validated for future translation into clinical applications for more accurately diagnosing PD. Simultaneously, the results of this study lay a basis for further study of the association between host metabolisms, gut microbiota, and PD.
Polymorphisms of Cytochromes P450 and Glutathione S-Transferases Synergistically Modulate Risk for Parkinson’s Disease
Authors: Fan Hui-Hui , Li Bao-Qing , Wu Ke-Yun , Yan Hai-Dan , Gu Meng-Jie , Yao Xing-Hao , Dong Hao-Jia , Zhang Xiong , Zhu Jian-Hong
Published: April 2022

Background

Environmental substances such as pesticides are well-known in link with Parkinson’s disease (PD) risk. Enzymes including cytochromes P450 (CYPs), esterases and glutathione S-transferases (GSTs) are responsible for the xenobiotic metabolism and may functionally compensate each other for subtypes in the same class. We hypothesize that the genetic effects of each class modulate PD risk stronger in a synergistic way than individually.

Methods

We selected 14 polymorphic loci out of 13 genes which encode enzymes in the classes of CYP, esterase, and GST, and recruited a cohort of 1,026 PD and control subjects from eastern China. The genotypes were identified using improved multiplex ligation detection reaction and analyzed using multiple models.

Results

A total of 13 polymorphisms remained after Hardy-Weinberg equilibrium analysis. None of the polymorphisms were independently associated with PD risk after Bonferroni correction either by logistic regression or genetic models. In contrast, interaction analyses detected increased resistance to PD risk in individuals carrying the rs12441817/CC (CYP1A1) and rs2070676/GG + GC (CYP2E1) genotypes (P = 0.002, OR = 0.393, 95% CI = 0.216–0.715), or carrying the GSTM1-present, GSTT1-null, rs156697/AG + GG (GSTO2) and rs1695/AA (GSTP1) genotypes (P = 0.003, OR = 0.348, 95% CI = 0.171–0.706). The synergistic effect of GSTs on PD was primarily present in females (P = 0.003). No synergistic effect was observed within genotypes of esterases.

Conclusion

We demonstrate a presence of synergistic but not individual impact on PD susceptibility in polymorphisms of CYPs and GSTs. The results indicate that the genetic interplay leads the way to PD development for xenobiotic metabolizing enzymes.
The Foot Fault Scoring System to Assess Skilled Walking in Rodents: A Reliability Study
Authors: Martins Lucas Athaydes , Schiavo Aniuska , Xavier Léder Leal , Mestriner Régis Gemerasca
Published: April 2022

The foot fault scoring system of the ladder rung walking test (LRWT) is used to assess skilled walking in rodents. However, the reliability of the LRWT foot fault score has not been properly addressed. This study was designed to address this issue. Two independent and blinded raters analyzed 20 rats and 20 mice videos. Each video was analyzed twice by the same rater (80 analyses per rater). The intraclass correlation coefficient (ICC) and the Kappa coefficient were employed to check the accuracy of agreement and reliability in the intra- and inter-rater analyses of the LRWT outcomes. Excellent intra- and inter-rater agreements were found for the forelimb, hindlimb, and both limbs combined in rats and mice. The agreement level was also excellent for total crossing time, total time stopped, and the number of stops during the walking path. Rating individual scores in the foot fault score system (0–6) ranged from satisfactory to excellent, in terms of the intraclass correlation indexes. Moreover, we showed that experienced and inexperienced raters can obtain reliable results if supervised training is provided. We concluded that the LRWT is a reliable and useful tool to study skilled walking in rodents and can help researchers address walking-related neurobiological questions.
A Robot-Assisted Therapy to Increase Muscle Strength in Hemiplegic Gait Rehabilitation
Authors: Gil-Castillo Javier , Barria Patricio , Aguilar Cárdenas Rolando , Baleta Abarza Karim , Andrade Gallardo Asterio , Biskupovic Mancilla Angel , Azorín José M. , Moreno Juan C.
Published: April 2022

This study examines the feasibility of using a robot-assisted therapy methodology based on the Bobath concept to perform exercises applied in conventional therapy for gait rehabilitation in stroke patients. The aim of the therapy is to improve postural control and movement through exercises based on repetitive active-assisted joint mobilization, which is expected to produce strength changes in the lower limbs. As therapy progresses, robotic assistance is gradually reduced and the patient's burden increases with the goal of achieving a certain degree of independence. The relationship between force and range of motion led to the analysis of both parameters of interest. The study included 23 volunteers who performed 24 sessions, 2 sessions per week for 12 weeks, each lasting about 1 h. The results showed a significant increase in hip abduction and knee flexion strength on both sides, although there was a general trend of increased strength in all joints. However, the range of motion at the hip and ankle joints was reduced. The usefulness of this platform for transferring exercises from conventional to robot-assisted therapies was demonstrated, as well as the benefits that can be obtained in muscle strength training. However, it is suggested to complement the applied therapy with exercises for the maintenance and improvement of the range of motion.
A Model of Pattern Separation by Single Neurons
Authors: Löffler Hubert , Gupta Daya Shankar
Published: April 2022

For efficient processing, spatiotemporal spike patterns representing similar input must be able to transform into a less similar output. A new computational model with physiologically plausible parameters shows how the neuronal process referred to as “pattern separation” can be very well achieved by single neurons if the temporal qualities of the output patterns are considered. Spike patterns generated by a varying number of neurons firing with fixed different frequencies within a gamma range are used as input. The temporal and spatial summation of dendritic input combined with theta-oscillating excitability in the output neuron by subthreshold membrane potential oscillations (SMOs) lead to high temporal separation by different delays of output spikes of similar input patterns. A Winner Takes All (WTA) mechanism with backward inhibition suffices to transform the spatial overlap of input patterns to much less temporal overlap of the output patterns. The conversion of spatial patterns input into an output with differently delayed spikes enables high separation effects. Incomplete random connectivity spreads the times up to the first spike across a spatially expanded ensemble of output neurons. With the expansion, random connectivity becomes the spatial distribution mechanism of temporal features. Additionally, a “synfire chain” circuit is proposed to reconvert temporal differences into spatial ones.
Efficacy of Cognitive-Behavioral Therapy for the Prophylaxis of Migraine in Adults: A Three-Armed Randomized Controlled Trial
Authors: Klan Timo , Gaul Charly , Liesering-Latta Eva , Both Bernhard , Held Isabella , Hennemann Severin , Witthöft Michael
Published: April 2022

Background

Behavioral approaches are central to the preventive treatment of migraine but empirical evidence regarding efficacy and effectiveness is still sparse. This study aimed to evaluate the efficacy of a newly developed migraine-specific, integrative cognitive-behavioral therapy program (miCBT) combining several approaches (trigger and stress management, coping with fear of attacks, relaxation training) by comparing it with a single behavioral approach (relaxation training, RLX) as an active control group and a waiting-list control group (WLC).

Methods

In a three-armed open-label randomized controlled trial, 121 adults with migraine were assigned to either miCBT, RLX or WLC. The outpatient group therapy (miCBT or RLX) consisted of seven sessions each 90 min. Participants who completed the WLC were subsequently randomized to one of the two treatment groups. Primary outcomes were headache days, headache-related disability, emotional distress, and self-efficacy. The baseline was compared to post-treatment, and followed by assessments 4- and 12-months post-treatment to compare miCBT and RLX.

Results

Mixed-model analyses (intention-to-treat sample, 106 participants) showed significantly stronger pre-post improvements in self-efficacy (assessed by the Headache Management Self-Efficacy Scale, HMSE-G-SF) in both treatment groups compared to the WLC (mean difference at post; miCBT: 4.67 [0.55–8.78], p = 0.027; RLX: 4.42 [0.38 to 8.46], p = 0.032), whereas no other significant between-group differences were observed. The follow-up analyses revealed significant within-group improvements from baseline to 12-month follow-up in all four primary outcomes for both treatments. However, between-group effects (miCBT vs. RLX) were not significant at follow-up.

Conclusion

The miCBT has no better treatment effects compared to RLX in migraine-prophylaxis. Both treatments effectively increase patients' self-efficacy.

Trial Registration

German Clinical Trials Register (www.drks.de; DRKS-ID: DRKS00011111).
Accuracy of Calf Circumference Measurement, SARC-F Questionnaire, and Ishii's Score for Screening Stroke-Related Sarcopenia
Authors: Yao Ruihong , Yao Liqing , Yuan Changli , Gao Bu-Lang
Published: April 2022

Objective

The purpose of this study was to investigate the accuracy of sarcopenia diagnosis in patients with stroke using calf circumference (CC), SARC-F questionnaire, and Ishii's score in comparison with the Asian Working Group for Sarcopenia 2019 (AWGS) sarcopenia diagnostic criteria.

Materials and Methods

In this cross-sectional study, a total of 364 consecutive patients with stroke were enrolled and evaluated with the CC measurement, SARC-F questionnaire, and Ishii's score. The diagnostic accuracy was analyzed.

Results

Based on the AWGS criteria, sarcopenia was present in 180 (49.5%) patients, with an age range of 49–74 (mean 63 ± 14.7) years. In all patients, the cutoff value of CC in the accuracy of diagnosing sarcopenia was 30.5 cm, with an AUC of 0.85, sensitivity of 81.8%, specificity of 90.1%, Kappa value of 0.72, and Youden index of 0.72. In the accuracy of diagnosing sarcopenia in all patients, Ishii's score had a cutoff value of 118, AUC of 0.78, sensitivity of 90.1%, specificity of 36.0%, Kappa value of 0.4, and Youden index of 0.55. For accuracy of diagnosing sarcopenia, the SARC-F questionnaire had a cutoff value of 5, AUC of 0.731, sensitivity of 94.7%, specificity of 40%, Kappa value of 0.34, and Youden index of 0.41.

Conclusions

Based on the AWGS criteria, calf circumference measurement has the optimal performance in screening stroke-related sarcopenia compared with the SARC-F questionnaire and Ishii's score. In patients with stroke, the cutoff value of calf circumference for sarcopenia is < 31 cm in men and 30 cm in women, and with an AUC of 0.85.
Regional Brain Fusion: Graph Convolutional Network for Alzheimer's Disease Prediction and Analysis
Authors: Li Wenchao , Zhao Jiaqi , Shen Chenyu , Zhang Jingwen , Hu Ji , Xiao Mang , Zhang Jiyong , Chen Minghan
Published: April 2022

Alzheimer's disease (AD) has raised extensive concern in healthcare and academia as one of the most prevalent health threats to the elderly. Due to the irreversible nature of AD, early and accurate diagnoses are significant for effective prevention and treatment. However, diverse clinical symptoms and limited neuroimaging accuracy make diagnoses challenging. In this article, we built a brain network for each subject, which assembles several commonly used neuroimaging data simply and reasonably, including structural magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and amyloid positron emission tomography (PET). Based on some existing research results, we applied statistical methods to analyze (i) the distinct affinity of AD burden on each brain region, (ii) the topological lateralization between left and right hemispheric sub-networks, and (iii) the asymmetry of the AD attacks on the left and right hemispheres. In the light of advances in graph convolutional networks for graph classifications and summarized characteristics of brain networks and AD pathologies, we proposed a regional brain fusion-graph convolutional network (RBF-GCN), which is constructed with an RBF framework mainly, including three sub-modules, namely, hemispheric network generation module, multichannel GCN module, and feature fusion module. In the multichannel GCN module, the improved GCN by our proposed adaptive native node attribute (ANNA) unit embeds within each channel independently. We not only fully verified the effectiveness of the RBF framework and ANNA unit but also achieved competitive results in multiple sets of AD stages' classification tasks using hundreds of experiments over the ADNI clinical dataset.
Cerebellar Gray Matter Volume in Tinnitus
Authors: Mennink Lilian M. , Koops Elouise A. , Langers Dave R. M. , Aalbers Marlien W. , van Dijk J. Marc C. , van Dijk Pim
Published: April 2022

Tinnitus is the perception of sound without an external source. The flocculus (FL) and paraflocculus (PFL), which are small lobules of the cerebellum, have recently been implicated in its pathophysiology. In a previous study, the volume of the (P)FL-complex correlated with tinnitus severity in patients that had undergone cerebellopontine angle (CPA) tumor removal. In this study, the relation between tinnitus and gray matter volume (GMV) of the (P)FL-complex, GMV of the other cerebellar lobules and GMV of the cerebellar nuclei is investigated in otherwise healthy participants. Data was processed using the SUIT toolbox, which is dedicated to analysis of imaging data of the human cerebellum. GMV of all cerebellar lobules and nuclei were similar between tinnitus and non-tinnitus participants. Moreover, no relation was present between tinnitus severity, as measured by the Tinnitus Handicap Inventory, and (P)FL-complex GMV, tonsil GMV, or total cerebellar cortical GMV. These results suggest that in otherwise healthy participants, in contrast to participants after CPA tumor removal, no relation between the GMV of neither the (P)FL-complex nor other cerebellar lobules and tinnitus presence and severity exists. These findings indicate that a relation only exists when the (P)FL-complex is damaged, for instance by a CPA tumor. Alternatively, it is possible that differences in (P)FL-complex GMVs are too small to detect with a voxel-based morphometry study. Therefore, the role of the (P)FL-complex in tinnitus remains to be further studied.
The Overexpression of Insulin-Like Growth Factor-1 and Neurotrophin-3 Promote Functional Recovery and Alleviate Spasticity After Spinal Cord Injury
Authors: Talifu Zuliyaer , Qin Chuan , Xin Zhang , Chen Yixin , Liu Jiayi , Dangol Subarna , Ma Xiaodong , Gong Han , Pei Zhisheng , Yu Yan , Li Jianjun , Du Liangjie
Published: April 2022

Objective

This study was conducted to investigate the effects of the exogenous overexpression of nerve growth factors NT-3 and IGF-1 on the recovery of nerve function after spinal cord injury (SCI) and identify the potential mechanism involved.

Methods

Sixty-four female SD rats were randomly divided into four groups: an SCI group, an adeno-associated viral (AAV)-RFP and AAV-GFP injection group, an AAV-IGF-1 and AAV-NT-3 injection group, and a Sham group. After grouping, the rats were subjected to a 10-week electrophysiological and behavioral evaluation to comprehensively evaluate the effects of the intervention on motor function, spasticity, mechanical pain, and thermal pain. Ten weeks later, samples were taken for immunofluorescence (IF) staining and Western blot (WB) detection, focusing on the expression of KCC2, 5-HT2A, and 5-HT2C receptors in motor neurons and the spinal cord.

Results

Electrophysiological and behavioral data indicated that the AAV-IGF-1 and AAV-NT-3 groups showed better recovery of motor function (P < 0.05 from D14 compared with the AAV-RFP + AAV-GFP group; P < 0.05 from D42 compared with SCI group) and less spasticity (4–10 weeks, at 5 Hz all P < 0.05 compared with SCI group and AAV- RFP + AAV-GFP group) but with a trend for more pain sensitivity. Compared with the SCI group, the von Frey value result of the AAV-IGF-1 and AAV-NT-3 groups showed a lower pain threshold (P < 0.05 at 4–8 weeks), and shorter thermal pain threshold (P < 0.05 at 8–10 weeks). IF staining further suggested that compared with the SCI group, the overexpression of NT-3 and IGF-1 in the SCI-R + G group led to increased levels of KCC2 (p < 0.05), 5-HT2A (p < 0.05), and 5-HT2C (p < 0.001) in motor neurons. WB results showed that compared with the SCI group, the SCI-R + G group exhibited higher expression levels of CHAT (p < 0.01), 5-HT2A (p < 0.05), and 5-HT2C (p < 0.05) proteins in the L2-L6 lumbar enlargement.

Conclusion

Data analysis showed that the overexpression of NT-3 and IGF-1 may improve motor function after SCI and alleviate spasms in a rat model; however, these animals were more sensitive to mechanical pain and thermal pain. These behavioral changes may be related to increased numbers of KCC2, 5-HT2A, and 5-HT2C receptors in the spinal cord tissue. The results of this study may provide a new theoretical basis for the clinical treatment of SCI.
Depression Classification Using Frequent Subgraph Mining Based on Pattern Growth of Frequent Edge in Functional Magnetic Resonance Imaging Uncertain Network
Authors: Li Yao , Zhou Zihao , Li Qifan , Li Tao , Julian Ibegbu Nnamdi , Guo Hao , Chen Junjie
Published: April 2022

The brain network structure is highly uncertain due to the noise in imaging signals and evaluation methods. Recent works have shown that uncertain brain networks could capture uncertain information with regards to functional connections. Most of the existing research studies covering uncertain brain networks used graph mining methods for analysis; for example, the mining uncertain subgraph patterns (MUSE) method was used to mine frequent subgraphs and the discriminative feature selection for uncertain graph classification (DUG) method was used to select discriminant subgraphs. However, these methods led to a lack of effective discriminative information; this reduced the classification accuracy for brain diseases. Therefore, considering these problems, we propose an approximate frequent subgraph mining algorithm based on pattern growth of frequent edge (unFEPG) for uncertain brain networks and a novel discriminative feature selection method based on statistical index (dfsSI) to perform graph mining and selection. Results showed that compared with the conventional methods, the unFEPG and dfsSI methods achieved a higher classification accuracy. Furthermore, to demonstrate the efficacy of the proposed method, we used consistent discriminative subgraph patterns based on thresholding and weighting approaches to compare the classification performance of uncertain networks and certain networks in a bidirectional manner. Results showed that classification performance of the uncertain network was superior to that of the certain network within a defined sparsity range. This indicated that if a better classification performance is to be achieved, it is necessary to select a certain brain network with a higher threshold or an uncertain brain network model. Moreover, if the uncertain brain network model was selected, it is necessary to make full use of the uncertain information of its functional connection.