bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and usability of the system for assessment and intervention of frailty for community-dwelling pre-frail older adults: A pilot study
Authors: Tan Ren Siang , Goh Eileen Fabia , Wang Di , Chan Robin Chung Leung , Zeng Zhiwei , Yeo Audrey , Pek Kalene , Kua Joanne , Wong Wei Chin , Shen Zhiqi , Lim Wee Shiong
Published: November 2022

Background

Effective multicomponent interventions in the community targeted at preventing frailty in at-risk older adults can promote healthy ageing. However, there is a lack of studies exploring the effectiveness of technology-enabled autonomous multi-domain community-based interventions for frailty. We developed a novel end-to-end System for Assessment and Intervention of Frailty (SAIF) with exercise, nutrition, and polypharmacy components. This pilot study aimed to explore SAIF’s effectiveness in improving frailty status, physical performance and strength, and its usability in pre-frail older adults.

Materials and methods

This is a single arm 8-week pilot study in 20 community-dwelling older adults who were pre-frail, defined using the Clinical Frailty Scale (CFS) as CFS 3 + (CFS 3 and FRAIL positive) or CFS 4. For outcomes, we assessed frailty status using the modified Fried Frailty Phenotype (FFP) and CFS; physical performance using Short Physical Performance Battery (SPPB); and Hand Grip Strength (HGS) at baseline and 8-week. User experience was explored using the System Usability Scale (SUS), interest-enjoyment subscale of the Intrinsic Motivation Inventory and open-ended questions. We analyzed effectiveness using repeated-measures tests on pre-post scores, and usability using a convergent mixed-method approach via thematic analysis of open-ended responses and descriptive statistics of usability/interest-enjoyment scales.

Results

Sixteen participants (71.8 ± 5.5 years) completed the 8-week study. There was a significant improvement in FFP score (−0.5, p < 0.05, effect size, r = 0.43), but not CFS (−1.0, p = 0.10, r = 0.29). Five (31.3%) improved in frailty status for both FFP and CFS. SPPB (+1.0, p < 0.05, r = 0.42) and HGS (+3.5, p < 0.05, r = 0.45) showed significant improvements. Three themes were identified: “Difficulty in module navigation” (barriers for SAIF interaction); “User engagement by gamification” (facilitators that encourage participation); and “Perceived benefits to physical health” (subjective improvements in physical well-being), which corroborated with SUS (68/100) and interest-enjoyment (3.9/5.0) scores. Taken together, user experience results cohere with the Senior Technology Acceptance and Adoption Model.

Conclusion

Our pilot study provides preliminary evidence of the effectiveness of SAIF in improving frailty status, physical performance and strength of pre-frail older adults, and offers user experience insights to plan the follow-up large-scale randomized controlled trial.
Changes of endophytic microbial community in Rhododendron simsii roots under heat stress and its correlation with leaf physiological indicators
Authors: Lin Wei , Liu Lei , Liang Jincheng , Tang Xuexiao , Shi Jie , Zhang Li , Wu Purui , Lan Siren , Wang Shusheng , Zhou Yan , Chen XiaoChou , Zhao Ying , Chen Xiang , Wu Binghua , Guo Lijin
Published: November 2022

Introduction

The response mechanism of Rhododendron simsii and its endophytic microorganism to heat stress is still unclear.

Methods

The light incubator was used to set the temperature gradients, and the control (CK) was (day/night: 14/10 h) 25/22°C, the moderate-heat-stress (MHS) was 35/30°C and the high-heat-stress (HHS) was 40/35°C.

Results

Compared with CK, MHS significantly increased the contents of malondialdehyde, hydrogen peroxide, proline, and soluble sugar, as well as the activities of catalase and peroxidase in leaf, while HHS increased the activities of ascorbate peroxidase, and decreased chlorophyll content. Compared with CK, MHS reduced soil available nitrogen (N) content. Both heat stress changed the endophytic microbial community structure in roots. MHS enriched Pezicula and Paracoccus, while HHS significantly enriched Acidothermus and Haliangium. The abundance of Pezicula positively correlated with the contents of chlorophyll a and proline in leaf, and negatively correlated with soil ammonium N content. The abundance of Pezicula and Haliangium positively correlated with soluble sugar and malondialdehyde contents, respectively.

Conclusions

Our results suggest that root endophytic microorganisms play an important role in helping Rhododendron resisting heat stress, mainly by regulating soil N content and plant physiological characteristics.
The hazard of carbapenemase (OXA-181)-producing Escherichia coli spreading in pig and veal calf holdings in Italy in the genomics era: Risk of spill over and spill back between humans and animals
Authors: Carfora Virginia , Diaconu Elena Lavinia , Ianzano Angela , Di Matteo Paola , Amoruso Roberta , Dell'Aira Elena , Sorbara Luigi , Bottoni Francesco , Guarneri Flavia , Campana Laura , Franco Alessia , Alba Patricia , Battisti Antonio
Published: November 2022

Carbapenemase-producing Enterobacterales (CPE) are considered a major public health issue. In the frame of the EU Harmonized AMR Monitoring program conducted in Italy in 2021, 21 epidemiological units of fattening pigs (6.98%; 95% CI 4.37–10.47%; 21/301) and four epidemiological units of bovines <12 months (1.29%; 95% CI 0.35–3.27%, 4/310) resulted positive to OXA-48-like-producing E. coli (n = 24 OXA-181, n = 1 OXA-48). Whole Genome Sequencing (WGS) for in-depth characterization, genomics and cluster analysis of OXA-181-(and one OXA-48) producing E. coli isolated, was performed. Tracing-back activities at: (a) the fattening holding of origin of one positive slaughter batch, (b) the breeding holding, and (c) one epidemiologically related dairy cattle holding, allowed detection of OXA-48-like-producing E. coli in different units and comparison of further human isolates from fecal samples of farm workers. The OXA-181-producing isolates were multidrug resistant (MDR), belonged to different Sequence Types (STs), harbored the IncX and IncF plasmid replicons and multiple virulence genes. Bioinformatics analysis of combined Oxford Nanopore Technologies (ONT) long reads and Illumina short reads identified blaOXA-181 as part of a transposon in IncX1, IncX3, and IncFII fully resolved plasmids from 16 selected E. coli, mostly belonging to ST5229, isolated during the survey at slaughter and tracing-back activities. Although human source could be the most likely cause for the introduction of the blaOXA-181-carrying IncX1 plasmid in the breeding holding, concerns arise from carbapenemase OXA-48-like-producing E. coli spreading in 2021 in Italian fattening pigs and, to a lesser extent, in veal calf holdings.
Evaluation of molecular typing for national surveillance of invasive clinical Haemophilus influenzae isolates from Denmark
Authors: Slotved Hans-Christian , Johannesen Thor Bech , Stegger Marc , Fuursted Kurt
Published: November 2022

Haemophilus influenzae is a gram-negative coccobacillus known to cause respiratory and invasive infections. It can possess a polysaccharide capsule that can be categorized into six different serotypes (i.e., Hia, Hib, Hic, Hid, Hie, and Hif) and non-encapsulated strains that are defined as non-typeable. Furthermore, H. influenzae can be characterized into eight biotypes (I–VIII). Traditionally, isolates have been serotyped and biotyped using phenotypic methods; however, these methods are not always reliable. In this study, we evaluate the use of whole-genome sequencing (WGS) for national surveillance and characterization of clinical Danish H. influenzae isolates. In Denmark, all clinical invasive isolates between 2014 and 2021 have been serotyped using a traditional phenotypic latex agglutination test as well as in silico serotyped using the in silico programs “hinfluenzae_capsule_characterization” and “hicap” to compare the subsequent serotypes. Moreover, isolates were also biotyped using a phenotypic enzyme test and the genomic data for the detection of the genes encoding ornithine, tryptophan, and urease. The results showed a 99–100% concordance between the two genotypic approaches and the phenotypic serotyping, respectively. The biotyping showed a 95% concordance between genotyping and phenotyping. In conclusion, our results show that in a clinical surveillance setting, in silico serotyping and WGS-based biotyping are a robust and reliable approach for typing clinical H. influenzae isolates.
Extracellular membrane vesicles from Limosilactobacillus reuteri strengthen the intestinal epithelial integrity, modulate cytokine responses and antagonize activation of TRPV1
Authors: Pang Yanhong , Ermann Lundberg Ludwig , Mata Forsberg Manuel , Ahl David , Bysell Helena , Pallin Anton , Sverremark-Ekström Eva , Karlsson Roger , Jonsson Hans , Roos Stefan
Published: November 2022

Bacterial extracellular membrane vesicles (MV) are potent mediators of microbe-host signals, and they are not only important in host-pathogen interactions but also for the interactions between mutualistic bacteria and their hosts. Studies of MV derived from probiotics could enhance the understanding of these universal signal entities, and here we have studied MV derived from Limosilactobacillus reuteri DSM 17938 and BG-R46. The production of MV increased with cultivation time and after oxygen stress. Mass spectrometry-based proteomics analyses revealed that the MV carried a large number of bacterial cell surface proteins, several predicted to be involved in host-bacteria interactions. A 5′-nucleotidase, which catalyze the conversion of AMP into the signal molecule adenosine, was one of these and analysis of enzymatic activity showed that L. reuteri BG-R46 derived MV exhibited the highest activity. We also detected the TLR2 activator lipoteichoic acid on the MV. In models for host interactions, we first observed that L. reuteri MV were internalized by Caco-2/HT29-MTX epithelial cells, and in a dose-dependent manner decreased the leakage caused by enterotoxigenic Escherichia coli by up to 65%. Furthermore, the MV upregulated IL-1β and IL-6 from peripheral blood mononuclear cells (PBMC), but also dampened IFN-γ and TNF-α responses in PBMC challenged with Staphylococcus aureus. Finally, we showed that MV from the L. reuteri strains have an antagonistic effect on the pain receptor transient receptor potential vanilloid 1 in a model with primary dorsal root ganglion cells from rats. In summary, we have shown that these mobile nanometer scale MV reproduce several biological effects of L. reuteri cells and that the production parameters and selection of strain have an impact on the activity of the MV. This could potentially provide key information for development of innovative and more efficient probiotic products.
Development of sequencing-based methodologies to distinguish viable from non-viable cells in a bovine milk matrix: A pilot study
Authors: Yap Min , O’Sullivan Orla , O’Toole Paul W. , Cotter Paul D.
Published: November 2022

Although high-throughput DNA sequencing-based methods have been of great value for determining the composition of microbial communities in various environments, there is the potential for inaccuracies arising from the sequencing of DNA from dead microorganisms. In this pilot study, we compared different sequencing-based methods to assess their relative accuracy with respect to distinguishing between viable and non-viable cells, using a live and heat-inactivated model community spiked into bovine milk. The methods used were shotgun metagenomics with and without propidium monoazide (PMA) treatment, RNA-based 16S rRNA sequencing and metatranscriptomics. The results showed that methods were generally accurate, though significant differences were found depending on the library types and sequencing technologies. Different molecular targets were the basis for variations in the results generated using different library types, while differences in the derived composition data from Oxford Nanopore Technologies-and Illumina-based sequencing likely reflect a combination of different sequencing depths, error rates and bioinformatics pipelines. Although PMA was successfully applied in this study, further optimisation is required before it can be applied in a more universal context for complex microbiomes. Overall, these methods show promise and represent another important step towards the ultimate establishment of approaches that can be applied to accurately identify live microorganisms in milk and other food niches.
Impact of early empirical antifungal therapy on prognosis of sepsis patients with positive yeast culture: A retrospective study from the MIMIC-IV database
Authors: Zou Zhi-ye , Sun Kai-jun , Fu Guang , Huang Jia-jia , Yang Zhen-jia , Zhou Zhi-peng , Ma Shao-lin , Zhu Feng , Wu Ming
Published: November 2022

Background

Mortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy.

Methods

A retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician’s experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed.

Results

This study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p < 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI: 1.16–3.91, p = 0.015) or urinary tract infection groups (OR 3.24, 95% CI: 1.48–7.11, p = 0.003).

Conclusion

Culture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU.
Volatile organic compounds emitted by Burkholderia pyrrocinia CNUC9 trigger induced systemic salt tolerance in Arabidopsis thaliana
Authors: Luo Huan , Riu Myoungjoo , Ryu Choong-Min , Yu Jun Myoung
Published: November 2022

Salinity is among the most significant abiotic stresses that negatively affects plant growth and agricultural productivity worldwide. One ecofriendly tool for broadly improving plant tolerance to salt stress is the use of bio-inoculum with plant growth-promoting rhizobacteria (PGPR). In this study, a bacterium strain CNUC9, which was isolated from maize rhizosphere, showed several plant growth-promoting characteristics including the production of 1-aminocyclopropane-1-carboxylate deaminase, indole acetic acid, siderophore, and phosphate solubilization. Based on 16S rRNA and recA gene sequence analysis, we identified strain CNUC9 as Burkholderia pyrrocinia. Out of bacterial determinants to elicit plant physiological changes, we investigated the effects of volatile organic compounds (VOCs) produced by B. pyrrocinia CNUC9 on growth promotion and salinity tolerance in Arabidopsis thaliana. Higher germination and survival rates were observed after CNUC9 VOCs exposure under 100 mM NaCl stress. CNUC9 VOCs altered the root system architecture and total leaf area of A. thaliana compared to the control. A. thaliana exposed to VOCs induced salt tolerance by increasing its total soluble sugar and chlorophyll content. In addition, lower levels of reactive oxygen species, proline, and malondialdehyde were detected in CNUC9 VOCs-treated A. thaliana seedlings under stress conditions, indicating that VOCs emitted by CNUC9 protected the plant from oxidative damage induced by salt stress. VOC profiles were obtained through solid-phase microextraction and analyzed by gas chromatography coupled with mass spectrometry. Dimethyl disulfide (DMDS), methyl thioacetate, and 2-undecanone were identified as products of CNUC9. Our results indicate that optimal concentrations of DMDS and 2-undecanone promoted growth in A. thaliana seedlings. Our findings provide greater insight into the salt stress alleviation of VOCs produced by B. pyrrocinia CNUC9, as well as potential sustainable agriculture applications.
Correlation analysis between gut microbiota characteristics and melasma
Authors: Liu Cong , He Dan , Yu Anye , Deng Yaru , Wang Li , Song Zhiqi
Published: November 2022

In recent years, many studies have shown that the gut microbiota can affect the occurrence and development of a variety of human diseases. A variety of skin diseases are related to the regulation of the gut–skin axis, such as psoriasis, atopic dermatitis, and acne. Gut microbial dysbiosis can promote the development of these diseases. The gut microbiota can affect estrogen metabolism, β-glucuronidase secreted by the gut microbiota can promote the reabsorption of estrogen by the gut, and estrogen is transported to other parts of the body through the circulatory system. The occurrence and development of melasma are closely related to abnormal metabolism of estrogen. The relationship between the structure of the gut microbiota and melasma remains unclear. Epidemiological surveys were conducted in patients with melasma and healthy subjects (control group) in this study. The feces were collected for 16S rRNA sequencing analysis of the gut microbiota. To compare the similarities and differences in species diversity of the gut microbiota between these two groups, we calculated the α-diversity and β-diversity indices and analyzed the differences between them. We found that the abundance of Collinsella spp., Actinomyces spp. (belonging to Actinobacteria), Parabacteroides spp., Bacteroides spp., Paraprevotella spp. (belonging to Bacteroidetes), Blautia spp., and Roseburia spp. (belonging to Firmicutes) in the melasma group were significantly different compared with that in the healthy group. The largest difference was found in Actinobacteria (p < 0.05), and there were also significant differences in the abundance of Coriobacteriia, Actinobacteria, Coriobacteriales, Coriobacteriaceae, and Collinsella spp. between the two groups (all p < 0.05). Many of these differences in the microbiota were closely related to the production of β-glucuronidase and the regulation of estrogen synthesis or metabolism. Changes in the gut microbiota structure and the biological effects of Collinsella spp. in the microbiota in patients with melasma can play an important role in the occurrence and development of melasma by affecting the body’s estrogen metabolism. This study provides a theoretical basis and experimental data reference for future studies on the relationship between the gut microbiota and melasma, and may be helpful for the prevention and treatment of melasma.
Case report: Whole genome sequence of Clostridium perfringens JUM001 causing acute emphysematous cholecystitis
Authors: Tohya Mari , Otsuka Tomohiro , Yoshimoto Jiro , Ishizaki Yoichi , Kirikae Teruo , Watanabe Shin
Published: November 2022

A strain of Clostridium perfringens was isolated from the bile sample of a patient with emphysematous cholecystitis who underwent a laparoscopic cholecystectomy, followed by treatment with meropenem and recovery. Metagenomic analysis of the bile sample showed that 99.73% of the bile microbiota consisted of C. perfringens, indicating that C. perfringens JUM001 was the causative pathogen of acute emphysematous cholecystitis in this patient. Complete genome sequencing showed that C. perfringens JUM001 contained a circular chromosome of 3,231,023 bp and two circular plasmids, pJUM001-1 of 49,289 bp and pJUM001-2 of 47,855 bp. JUM001 was found to possess a typing toxin gene, plc, but no other typing toxin genes, indicating that its toxinotype is type A. The plasmids pJUM001-1 and pJUM001-2 belonged to the pCP13-like and pCW3-like families of plasmids, respectively, which are characteristic conjugative and archetypical plasmids of C. perfringens. Phylogenetic analysis showed that JUM001 was closely related to C. perfringens strain JXNC-DD isolated from a dog in China. To our knowledge, this is the first report of whole-genome sequences of a clinical isolate of C. perfringens causing acute emphysematous cholecystitis.
Variations in leaf phyllosphere microbial communities and development of tobacco brown spot before and after fungicide application
Authors: Xiang Li-Gang , Wang Han-Cheng , Cai Liu-Ti , Guo Tao , Luo Fei , Hsiang Tom , Yu Zhi-He
Published: November 2022

In recent years, STROBY (50% Kresoxim-methyl) has been widely used to control tobacco brown spot in Guizhou Province, China. As a broad-spectrum fungicide, STROBY targets not only phytopathogens, but also affects many other microorganisms including those pathogenic, beneficial, or neutral to the plant hosts. To understand the effects of STROBY on the phyllosphere microbial communities of tobacco leaves during the development of tobacco brown spot, the fungal and bacterial communities of symptomatic and asymptomatic leaves at four time points, before spraying (August 29) and after spraying (September 3, 8, and 13), were investigated using the Illumina high-throughput sequencing. The results showed that STROBY had significant effects on the phyllosphere microbial communities of tobacco leaves. Microbial communities in asymptomatic leaves were more greatly affected than their counterparts in symptomatic leaves, and fungal communities were more sensitive than bacterial communities. Throughout the experiment, the most common genera in symptomatic leaves were Alternaria, Pseudomonas, Pantoea, and Sphingomonas, and in asymptomatic leaves, these were Golubevia and Pantoea. After spraying, the alpha diversity of fungal communities increased in symptomatic leaves and decreased in asymptomatic leaves, while the alpha diversity of bacteria increased in both types of leaves. Beta diversity showed that in asymptomatic leaves, the fungal communities in the first stage was significantly different from the remaining three stages. In contrast, the fungal communities in symptomatic leaves and the bacterial communities in all leaves did not fluctuate significantly during the four stages. Before spraying (August 29), the dominant functions of the fungal community were animal pathogen, endophyte, plant pathogen, and wood saprotroph. Whereas after spraying (September 3, 8, and 13), the proportion of the above fungal functions decreased and the unassigned functions increased, especially in asymptomatic leaves. This study describes the effects of STROBY application and tobacco brown spot presence in shaping the leaf phyllosphere microbial communities, and provides insights into the microbial community effects on tobacco leaves of a strobilurin fungicide.
Key players in syntrophic propionate oxidation revealed by metagenome-assembled genomes from anaerobic digesters bioaugmented with propionic acid enriched microbial consortia
Authors: Kim Minjae , Rhee Chaeyoung , Wells Michael , Shin Juhee , Lee Joonyeob , Shin Seung Gu
Published: November 2022

Propionic acid (HPr) is frequently accumulated in anaerobic digesters due to its thermodynamically unfavorable degradation reaction. Here, we identify key players in HPr oxidation and organic overloading recovery from metagenome-assembled genomes (MAGs) recovered from anaerobic digesters inoculated with HPr-enriched microbial consortia before initiating organic overloading. Two independent HPr-enrichment cultures commonly selected two uncultured microorganisms represented with high relative abundance: Methanoculleus sp002497965 and JABUEY01 sp013314815 (a member of the Syntrophobacteraceae family). The relative abundance of JABUEY01 sp013314815 was 60 times higher in bioaugmented bioreactors compared to their unaugmented counterparts after recovery from organic overloading. Genomic analysis of JABUEY01 sp013314815 revealed its metabolic potential for syntrophic propionate degradation when partnered with hydrogenotrophic methanogens (e.g., Methanoculleus sp002497965) via the methylmalonyl-CoA pathway. Our results identified at least two key species that are responsible for efficient propionate removal and demonstrate their potential applications as microbial cocktails for stable AD operation.
Metabolomic exploration of the effects of habituation to livestock trailer and extended transportation in goats
Authors: Batchu Phaneendra , Naldurtiker Aditya , Kouakou Brou , Terrill Thomas H. , McCommon George W. , Kannan Govind
Published: November 2022

Goats raised for meat production are often transported long distances. Twelve-month-old male Spanish goats were used to determine the effects of habituation to trailers on plasma metabolomic profiles when transported for extended periods. In a split-plot design, 168 goats were separated into two treatment (TRT; whole plot) groups and maintained on two different paddocks. Concentrate supplement was fed to one group inside two livestock trailers (habituated group, H), while the other group received the same quantity of concentrate, but not inside the trailers (non-habituated, NH). Goats were subjected to a 10-h transportation stress in 4 replicates (n = 21 goats/replicate/TRT) after 4 weeks of habituation period. Blood samples were collected prior to loading, 20 min after loading (0 h), and at 2, 4, 6, 8, and 10 h of transportation (Time; subplot). A targeted quantitative metabolomics approach was employed to analyze the samples. The data were analyzed using R software and MIXED procedures in SAS. Several amino acids (alanine, serine, glycine, histidine, glutamate, trans-hydroxyproline, asparagine, threonine, methylhistidine, ornithine, proline, leucine, tryptophan) were higher (p < 0.05) in the H group compared to the NH group. Six long-chain acylcarnitines were higher (p < 0.05), while free (C0) and short-chain (C3, C5) carnitines were lower (p < 0.05) in the NH goats compared to the H goats. In general, amino acid concentrations decreased and long-chain acylcarnitine (>C10) levels increased with transportation time (p < 0.05). Butyric acid, α-ketoglutaric acid, and α-aminoadipic acid concentrations were lower (p < 0.05) and β-hydroxybutyric acid concentrations were higher in the NH goats compared to the H goats. Plasma glucose, non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly influenced by Time (p < 0.01). Plasma NEFA concentrations were significantly lower (p < 0.01) in the H group than the NH group. Habituation to trailers can be beneficial in enhancing stress coping abilities in goats due to higher concentrations of metabolites such as butyrate and certain amino acids that support antioxidant activities and immune function. Plasma long-chain acylcarnitines may be good indicators of stress during long-distance transportation in goats.
Computational study of nitro-benzylidene phenazine as dengue virus-2 NS2B-NS3 protease inhibitor
Authors: Salin Nurul Hanim , Hariono Maywan , Khalili Nur Sarah Dyana , Zakaria Iffah Izzati , Saqallah Fadi G. , Mohamad Taib Mohamad Nurul Azmi , Kamarulzaman Ezatul Ezleen , Wahab Habibah A. , Khawory Muhammad Hidhir
Published: November 2022

According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5-bis((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits’ free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52–55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds’ toxicity and mutagenicity.
Association of cerebral spinal fluid copper imbalance in amyotrophic lateral sclerosis
Authors: Chen Qiao Yi , Wu Peng , Wen Ting , Qin Xing , Zhang Ronghua , Jia Rui , Jin Jiaoting , Hu Fangfang , Xie Xiaoge , Dang Jingxia
Published: November 2022

A plethora of environmental risk factors has been persistently implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), including metal/metalloids. This study aimed to examine potential associations between cerebral spinal fluid (CSF) metal/metalloids and ALS risks. CSF concentrations of copper (Cu), nickel (Ni), mercury (Hg), arsenic (As), manganese (Mn), and iron (Fe) in ALS (spinal- and bulbar-onset) patients and controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results from this study revealed marked differences between control, spinal-onset, and bulbar-onset groups. We report that Cu levels were lower in the ALS and spinal-onset groups compared to the control group. Ni level were higher in the spinal-onset group compared to the control and bulbar-onset groups. In addition, associations between CSF metal/metalloid levels with disease severity, sex, and serum triglycerides were also examined to broach the potential relevance of neurotoxic metal/metalloids in ALS disease heterogeneity.
The heterogeneity of astrocytes in glaucoma
Authors: Tang Yunjing , Chen Yongjiang , Chen Danian
Published: November 2022

Glaucoma is a leading cause of blindness with progressive degeneration of retinal ganglion cells. Aging and increased intraocular pressure (IOP) are major risk factors. Lowering IOP does not always stop the disease progression. Alternative ways of protecting the optic nerve are intensively studied in glaucoma. Astrocytes are macroglia residing in the retina, optic nerve head (ONH), and visual brain, which keep neuronal homeostasis, regulate neuronal activities and are part of the immune responses to the retina and brain insults. In this brief review, we discuss the activation and heterogeneity of astrocytes in the retina, optic nerve head, and visual brain of glaucoma patients and animal models. We also discuss some recent transgenic and gene knockout studies using glaucoma mouse models to clarify the role of astrocytes in the pathogenesis of glaucoma. Astrocytes are heterogeneous and play crucial roles in the pathogenesis of glaucoma, especially in the process of neuroinflammation and mitochondrial dysfunction. In astrocytes, overexpression of Stat3 or knockdown of IκKβ/p65, caspase-8, and mitochondrial uncoupling proteins (Ucp2) can reduce ganglion cell loss in glaucoma mouse models. Based on these studies, therapeutic strategies targeting the heterogeneity of reactive astrocytes by enhancing their beneficial reactivity or suppressing their detrimental reactivity are alternative options for glaucoma treatment in the future.
Attenuated iron stress and oxidative stress may participate in anti-seizure and neuroprotective roles of xenon in pentylenetetrazole-induced epileptogenesis
Authors: Zhang Mengdi , Cheng Yao , Zhai Yujie , Yuan Yi , Hu Haoran , Meng Xianfeng , Fan Xuemeng , Sun Hongliu , Li Shucui
Published: November 2022

The previous studies have demonstrated the excellent neuroprotective effects of xenon. In this study, we verified the anti-seizure and neuroprotective roles of xenon in epileptogenesis and evaluated the involvement of oxidative stress and iron accumulation in the protective roles of xenon. Epileptogenesis was induced by pentylenetetrazole (PTZ) treatment in Sprague-Dawley rats. During epileptogenesis, we found increased levels of iron and oxidative stress accompanied by elevated levels of divalent metal transporter protein 1 and iron regulatory protein 1, which are closely associated with iron accumulation. Meanwhile, the levels of autophagy and mitophagy increased, alongside significant neuronal damage and cognitive deficits. Xenon treatment reversed these effects: oxidative stress and iron stress were reduced, neuronal injury and seizure severity were attenuated, and learning and memory deficits were improved. Thus, our results confirmed the neuroprotective and anti-seizure effects of xenon treatment in PTZ-induced epileptogenesis. The reduction in oxidative and iron stress may be the main mechanisms underlying xenon treatment. Thus, this study provides a potential intervention strategy for epileptogenesis.
Integrating ankle and hip strategies for the stabilization of upright standing: An intermittent control model
Authors: Morasso Pietro
Published: November 2022

Even in unperturbed upright standing of healthy young adults, body sway involves concurrent oscillations of ankle and hip joints, thus suggesting to using biomechanical models with at least two degrees of freedom, namely, a double inverted pendulum (DIP) framework. However, in a previous study, it was demonstrated that the observed coordinated ankle–hip patterns do not necessarily require the independent active control of the two joints but can be explained by a simpler hybrid control system, with a single active component (intermittent, delayed sensory feedback of the ongoing sway) applied to the ankle joint and a passive component (stiffness control) applied to the hip joint. In particular, the proposed active component was based on the internal representation of a virtual inverted pendulum (VIP) that links the ankle to the current position of the global center of mass (CoM). This hybrid control system, which can also be described as an ankle strategy, is consistent with the known kinematics of the DIP and, in particular, with the anti-phase correlation of the acceleration profiles of the two joints. The purpose of this study is to extend the hybrid control model in order to apply to both the ankle and hip strategy, clarifying as well the rationale of mixed strategies. The extension consists of applying the hybrid control scheme to both joints: a passive stiffness component and an active intermittent component, based on the same feedback signals derived from the common VIP but with independent parameter gains for the two joints. Thus, the hip gains are null in the pure ankle strategy, the ankle gains are null in the pure hip strategy, and both ankle and hip gains are specifically tuned in mixed strategies. The simulation of such an extended model shows that it can reproduce both strategies; moreover, the pure ankle strategy is more robust than the hip strategy, because the range of variation (RoV) of the intermittent control gains is larger in the former case than in the latter, and the pure ankle strategy is also more energy efficient. Generally, the simulations suggest that there is no advantage to employ mixed strategies, except in borderline situations in which the control gains are just outside the RoV that provides stable control for either pure strategy: in this case, a stable mixed strategy can emerge from the combination of two marginally unstable pure strategies.
Management of epilepsy in pregnancy in eastern China: A survey from the Zhejiang association against epilepsy
Authors: Xu Zheng-Yan-Ran , Qian Ping , Cai Meng-Ting , Ding Mei-ping , Guo Yi
Published: November 2022

Objective

We aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE.

Methods

A cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE.

Results

This survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest difficulty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management.

Conclusion

Our study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication.
Machine learning can predict mild cognitive impairment in Parkinson's disease
Authors: Amboni Marianna , Ricciardi Carlo , Adamo Sarah , Nicolai Emanuele , Volzone Antonio , Erro Roberto , Cuoco Sofia , Cesarelli Giuseppe , Basso Luca , D'Addio Giovanni , Salvatore Marco , Pace Leonardo , Barone Paolo
Published: November 2022

Background

Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI).

Aim

Finding significant features associated with PD-MCI through a machine learning approach.

Patients and methods

Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model.

Results

Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2.

Conclusions

This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.
Segmentation and differentiation of periventricular and deep white matter hyperintensities in 2D T2-FLAIR MRI based on a cascade U-net
Authors: Gong Tan , Han Hualu , Tan Zheng , Ning Zihan , Qiao Huiyu , Yu Miaoxin , Zhao Xihai , Tang Xiaoying , Liu Gaifen , Shang Fei , Liu Shuai
Published: November 2022

Background

White matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images.

Methods

A total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted.

Results

Compared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001).

Conclusion

Cascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.
Identifying longitudinal patterns of CPAP treatment in OSA using growth mixture modeling: Disease characteristics and psychological determinants
Authors: Yi Huijie , Dong Xiaosong , Shang Shaomei , Zhang Chi , Xu Liyue , Han Fang
Published: November 2022

In this study, we aim to identify the distinct subtypes of continuous positive airway pressure (CPAP) user profiles based on the telemedicine management platform and to determine clinical and psychological predictors of various patterns of adherence. A total of 301 patients used auto-CPAP (Autoset 10, Resmed Inc.) during the treatment period. Four categories of potential predictors for CPAP adherence were examined: (1) demographic and clinical characteristics, (2) disease severity and comorbidities, (3) sleep-related health issues, and (4) psychological evaluation. Then, growth mixture modeling was conducted using Mplus 8.0 to identify the unique trajectories of adherence over time. Adherence data were collected from the telemedicine management platform (Airview, Resmed Inc.) during the treatment. Three novel subgroups were identified and labeled “adherers” (53.8% of samples, intercept = 385, slope = −51, high mean value, negative slope and moderate decline), “Improvers” (18.6%, intercept = 256, slope = 50, moderate mean value, positive slope and moderate growth) and “non-adherers” (27.6%, intercept = 176, slope = −31, low mean value, negative slope and slight decline). The comorbidities associated with OSA and the apnea–hypopnea index (AHI), which reflects the objective severity of the disease, did not differ significantly among the subgroups. However, “improvers” showed higher levels of daytime sleepiness (8.1 ± 6.0 vs. 12.1 ± 7.0 vs. 8.0 ± 6.1 in SWIFT, p = 0.01), reduced daytime function (4.6 ± 1.6 vs. 3.8 ± 1.6 vs. 4.2 ± 1.8 in QSQ daytime symptoms, p = 0.02), and characteristics of positive coping style (1.8 ± 0.5 vs. 1.9 ± 0.5 vs. 1.7 ± 0.5 in SCSQ positive coping index, p = 0.02). Negative emotion was more pronounced in patients with “non-adherers” (12.9 ± 3.8 vs. 13.7 ± 3.3 vs. 14.6 ± 3.5, p = 0.02 in the HADS depression dimension; 9.0 ± 6.1 vs. 9.8 ± 5.1 vs. 11.5 ± 6.3, p = 0.01 with Negative Affectivity in DS14, and 9.3 ± 6.1 vs. 10.3 ± 5.1 vs. 11.7 ± 6.5, p = 0.01 with Social Inhibition in DS14). Overall, our study demonstrated that CPAP therapy may present distinct trajectories of adherence over time in addition to the traditional binary classification. Self-reported sleep health issues (diurnal sleepiness and daytime dysfunction) as well as psychological characteristics (negative emotions and coping style) were predictors of different adherence subtypes in patients with OSA. Understanding CPAP use profiles and their predictors enable the identification of those who may require additional intervention to improve adherence and further enhance the therapeutic effect in OSA patients.