bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62
Authors: Harnett Margaret M. , Lumb Felicity E. , Crowe Jenny , Doonan James , Buitrago Geraldine , Brown Stephanie , Thom Gillian , MacDonald Amy , Suckling Colin J. , Selman Colin , Harnett William
Published: November 2023

Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age. ES-62 also reduced gene expression of the cytokines IL-4 and IL-17 and in addition the TLR/IL-1R adaptor MyD88, in the lungs of male mice although HCD-induced increases in these inflammatory markers were not detected until between 340 and 500 days of age. A combination of two drug-like ES-62 PC-based small molecule analogues (SMAs), produced broadly similar protective effects in the lungs of male mice with respect to both lung pathology and inflammatory markers, in addition to a decrease in HCD-induced IL-5 expression. Overall, our data show that ES-62 and its SMAs offer protection against HCD-accelerated pathological changes in the lungs during ageing. Given the targeting of Th2 cytokines and IL-17, we discuss this protection in the context of ES-62’s previously described amelioration of airway hyper-responsiveness in mouse models of asthma.
Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy
Authors: Ma Minghua , Li Guo , Zhou Baoyong , Li Kaili , Wu Zhongjun , Kong Lingwang , Liu Maoyun , Liu Miao , Zhang Cheng , Yu Huarong , Wang Shuaiqi , Huang Zuotian , Zong Kezhen
Published: November 2023

Background

During clinical practice, routine blood tests are commonly performed following pancreaticoduodenectomy (PD). However, the relationship between blood cell counts, inflammation-related indices, and postoperative complications remains unclear.

Method

We conducted a retrospective study, including patients who underwent PD from October 2018 to July 2023 at the First Hospital of Chongqing Medical University, and compared baseline characteristics and clinical outcomes among different groups. Neutrophil count (NC), platelet count (PLT), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) were derived from postoperative blood test results. We investigated the association between these indicators and outcomes using multivariable logistic regression and restricted cubic spline analysis. The predictive performance of these indicators was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA).

Result

A total of 232 patients were included in this study. Multivariate logistic regression and restricted cubic spline analysis showed that all indicators, except for PLT, were associated with clinical postoperative pancreatic fistula (POPF). SII, NLR, and NC were linked to surgical site infection (SSI), while SII, NLR, and PLR were correlated with CD3 complication. PLT levels were related to postoperative hemorrhage. SII (AUC: 0.729), NLR (AUC: 0.713), and NC (AUC: 0.706) effectively predicted clinical POPF.

Conclusion

In patients undergoing PD, postoperative inflammation-related indices and blood cell counts are associated with various complications. NLR and PLT can serve as primary indicators post-surgery for monitoring complications.
Present drugs and future perspectives in treating soil-transmitted helminthiasis
Authors: Keiser Jennifer
Published: November 2023

Soil-transmitted helminthiases caused by Ascaris lumbricoides, Trichuris trichiura, and hookworm (Ancylostoma duodenale and Necator americanus) are responsible for the infection of approximately 1.5 billion people worldwide, mostly in tropical and subtropical regions. Preventive chemotherapy is the mainstay of control, which is the regular administration of anthelminthic drugs, mainly albendazole and mebendazole to at-risk populations. As benzimidazoles face a risk of developing drug resistance and have shortcomings in their therapeutic profile, efforts have been made to develop alternative anthelminthics. The aim of this review is to provide a state-of-the-art update on available treatments and ongoing efforts in Research and Development (R&D) for the three main soil-transmitted helminth infections. Recent findings on the use of drug combinations and advanced drug candidates such as oxantel pamoate and emodepside and how these drugs fulfill the target product profile will be reviewed. Lastly, progress in drug discovery will be summarized.
Assessing seasonal and interannual changes in carbonate chemistry across two time-series sites in the North Western Mediterranean Sea
Authors: Wimart-Rousseau Cathy , Wagener Thibaut , Bosse Anthony , Raimbault Patrick , Coppola Laurent , Fourrier Marine , Ulses Caroline , Lefèvre Dominique
Published: November 2023

Sustained time-series measurements are crucial to understand changes in oceanic carbonate chemistry. In the North Western Mediterranean Sea, the temporal evolution of the carbonate system is here investigated based on two 10-year time-series (between January 2010 and December 2019) of monthly carbonate parameters measurements at two sampling sites in the Ligurian Sea (ANTARES and DYFAMED). At seasonal timescale, the seawater partial pressure of CO2 (pCO2) within the mixed layer is mostly driven by temperature at both sites, and biological processes as stated by the observed relationships between total inorganic carbon (CT), nitrate and temperature. This study suggests also that mixing and water masses advection could play a role in modulating the CT content. At decadal timescale, significant changes in ocean chemistry are observed with increasing trends in CT (+3.2 ± 0.9 µmol.kg−1.a−1 – ANTARES; +1.6 ± 0.8 µmol.kg−1.a−1 – DYFAMED), associated with increasing pCO2 trends and decreasing trends in pH. The magnitude of the increasing trend in CT at DYFAMED is consistent with the increase in atmospheric pCO2 and the anthropogenic carbon transport of water originating from the Atlantic Ocean, while the higher trends observed at the ANTARES site could be related to the hydrological variability induced by the variability of the Northern Current.
Randomized controlled trial on the effects of mindfulness-based respiratory decompression therapy in claustrophobic patients undergoing MRI inspection
Authors: Zhou Yi , Cao Yanqing , Xu Shan , Li Sijin , Liang Yidan , Zhang Wei , Xiao Yunping
Published: November 2023

Background

Claustrophobia is a psychological disease. It is estimated to occur in 2.1–14.3% of all magnetic resonance imaging (MRI) examinations. Mindfulness decompression is an effective means to treat and reduce fear and anxiety. There is a rare report on the application of mindfulness-based stress reduction therapy in the magnetic resonance examinations of patients with claustrophobia to date.

Purpose

The purpose of this study is to explore the intervention effect of mindfulness respiratory decompression therapy on the MRI inspection of patients with claustrophobia.

Methods

A total of 86 patients with claustrophobia requiring MRI in our hospital from January 2018 to December 2020 were divided into two groups. The control group was given routine psychological nursing, and the observation group was given a mindfulness breathing technique on the basis of the control group. Before and after the intervention, we compared the intervention effect, satisfaction with nurses’ psychological intervention technique, severe autonomic nervous symptoms during the examination, self-rating anxiety scale (SAS) scores, and profile of mood states revised (POMS-R) scores.

Results

The total effective rate of intervention in the observation group was 90.90%, which was significantly higher (χ2 = 6.857, p = 0.00004) than that in the control group (26.19%). Severe autonomic nervous symptoms in the observation group were significantly lower than those in the control group (p < 0.05). After the intervention, SAS scores and POMS-R scores in the observation group decreased with statistical significance (p < 0.05).

Conclusion

Mindfulness respiratory decompression therapy can effectively help claustrophobic patients complete an MRI examination, which may be worthy of wide promotion and application in the clinic.
The effectiveness of different immunotherapies in the treatment of condyloma acuminatum: a network meta-analysis of randomized clinical trials
Authors: Liu Xiaoye , Qi Manli
Published: November 2023

Background

The treatment of condyloma acuminatum (CA), especially the very persistent and recurrent CA, is currently the focus of our research. Immunotherapies have recently been shown to be well-tolerated and effective in treating warts, particularly refractory warts. However, there is still a lack of corresponding evidence-based medical evidence on the effectiveness of different immunotherapies in treating warts. The difference between network meta-analysis and meta-analysis is that network meta-analysis can be used to compare multiple treatments by combining direct and indirect evidence to assess the interrelationship between all treatments. We intend to compare the efficacy of different treatments for CA using a network meta-analysis.

Methods

PubMed, Cochrane Library and Embase from inception to June 1st, 2023 were searched using a computer. All articles on immunotherapies for CA were included. Stata MP17.0 software was used for data analyses.

Results

A total of 8 randomly-controlled trials involving 493 patients were included. Result showed that all treatment measures had a significant efficacy compared with the regular saline group (BCG (bacillus Calmette-Guérin vaccine) OR = 96.00, 95%CI: 10.35–890.58; MMR (measle, mumps and rubella vaccine) OR = 29.69, 95%CI: 7.47–118.04; Candida antigens OR = 27.34, 95%CI: 8.64–86.52; PPDs (purified protein derivatives) OR = 23.33, 95%CI: 6.75–80.60; VD3 OR = 21.36, 95%CI: 4.34–105.16 and purified protein derivatives (general) OR = 13.14, 95%CI: 3.38–51.12). The area under the curve (SUCRA) ranking results showed that the bacillus Calmette-Guérin vaccine had the highest total efficiency, which was 88.2%, with the rest in the order of measle, mumps and rubella vaccine, which was 68.9%, Candida antigens, which was 63.6%, purified protein derivatives, which was 52.9%, vitamin D3, which was 49.0%, purified protein derivatives (general), which was 27.4%, and saline, which was 0%.

Conclusion

In summary, we found that the bacillus Calmette-Guérin vaccine was superior to other treatments in terms of efficacy according to the SUCRA value.
Association between the sarcopenia index and abnormal liver function in the adult population in the United States: a cross-sectional study
Authors: Xu Jian , Xu Zhi-Xiang , Yang Qi-Fan , Zhuang Jing , Zhu Xin , Yao Jun
Published: November 2023

Background

The objective of this study was to explore the association between the sarcopenia index and abnormal liver function in adult individuals in the United States.

Methodology

This study employed a rigorous cross-sectional analysis of data derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018. The primary objective was to investigate the correlation between the sarcopenia index and abnormal liver function. To achieve this, an advanced multivariate regression model was utilized, allowing for comprehensive analysis and meticulous adjustment of relevant variables. To ensure the robustness of the findings, a visually appealing smooth curve was constructed, and a two-stage regression model was applied for validation. Additionally, a detailed gender-stratified analysis was conducted to further explore the association between the sarcopenia index and abnormal liver function within distinct subgroups.

Results

Through our rigorous participant selection process, a total of 1756 individuals were included in the study. The meticulously adjusted multivariate regression model revealed a significant negative association between the sarcopenia index and abnormal liver function, with an adjusted odds ratio (OR) of 0.73 and a 95% confidence interval (CI) ranging from 0.63 to 0.86. The robustness of this association was further supported by the visually appealing smooth curve plot. Moreover, in the gender-stratified subgroup analysis, after meticulous adjustment for confounding factors, notable differences in this association emerged (males: OR = 0.8, 95% CI: 0.66–0.98; females: OR = 0.61, 95% CI: 0.47–0.79).

Conclusion

This cross-sectional study yields robust evidence indicating a negative correlation between the sarcopenia index and abnormal liver function, predominantly observed among females.
Vitamin D supplementation is beneficial in improving the prognosis of patients with acute respiratory failure in the intensive care unit: a retrospective study based on the MIMIC-IV database
Authors: Hu Song , He Qian , Xie Jun , Liu Hui , Zhou Rong , Li Chong
Published: November 2023

Background

Vitamin D plays a critical role in the regulation of multiple physiological pathways. Vitamin D deficiency may be a risk factor for life-threatening clinical conditions. Several studies have found that vitamin D supplementation in critically ill patients improves prognosis. The purpose of this study was to determine the association between vitamin D and the prognosis of patients with acute respiratory failure (ARF).

Methods

In this retrospective cohort study, we collected clinical information of ARF patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The outcome of this study was in-hospital mortality, intensive care unit (ICU) mortality. Patients were divided into the no-vitamin D and vitamin D groups according to whether they received supplementation or not. The correlation between vitamin D and outcome was examined using Kaplan–Meier (KM) survival curves, Cox proportional risk regression models and subgroup analyses. Propensity-score matching (PSM) was used to ensure the robustness of our findings.

Results

The study finally included 7,994 patients with ARF, comprising 6,926 and 1,068 in the no-vitamin D and vitamin D groups, respectively. The Kaplan–Meier survival curve indicated a significant difference in survival probability between the two groups. After adjustment for a series of confounders, the multivariate Cox proportional hazards models showed that the hazard ratio (95% confidence interval) values for in-hospital and ICU mortality in the no-vitamin D group were 1.67 (1.45, 1.93) and 1.64 (1.36, 1.98), respectively. The results of propensity score-matched (PSM) analysis were consistent with the original population. In the subgroup analysis, Vitamin D supplementation was associated with lower in-hospital mortality in patients with higher clinical scores (SOFA score ≥ 8, OASIS ≥ 38).

Conclusion

Our study concluded that Vitamin D supplementation may reduce in-hospital and ICU mortality in patients with ARF in the ICU. There may be a beneficial effect on in-hospital mortality in patients with higher clinical scores. Additional randomized controlled trials are needed to follow up to confirm the relationship between vitamin D supplementation and ARF.
Distribution, characterization, and evolution of heavy metal resistance genes and Tn7-like associated heavy metal resistance Gene Island of Burkholderia
Authors: Lan Yanhong , Liu Meijia , Song Yao , Cao Yu , Li Fosheng , Luo Dening , Qiao Dairong
Published: November 2023

Introduction

Burkholderia is a rod-shaped aerobic Gram-negative bacteria with considerable genetic and metabolic diversity, which can beused for bioremediation and production applications, and has great biotechnology potential. However, there are few studies on the heavy metal resistance of the Burkholderia genus.

Methods

In this paper, the distribution, characteristics and evolution of heavy metal resistance genes in Burkholderia and the gene island of Tn7-like transposable element associated with heavy metal resistance genes in Burkholderia were studied by comparative genomic method based on the characteristics of heavy metal resistance.

Results and discussion

The classification status of some species of the Burkholderia genus was improved, and it was found that Burkholderia dabaoshanensis and Burkholderia novacaledonica do not belong to the Burkholderia genus.Secondly, comparative genomics studies and pan-genome analysis found that the core genome of Burkholderia has alarger proportion of heavy metal resistance genes and a greater variety of heavy metalresistance genes than the subsidiary genome and strain specific genes. Heavy metal resistance genes are mostly distributed in the genome in the form of various gene clusters (for example, mer clusters, ars clusters, czc/cusABC clusters). At the same time, transposase, recombinase, integrase and other genes were foundupstream and downstream of heavy metal gene clusters, indicating that heavy metal resistance genes may beobtained through horizontal transfer. The analysis of natural selection pressure of heavy metal resistance genes showed that heavy metal resistance genes experienced strong purification selection under purification selection pressure in the genome.The Tn7 like transposable element of Burkholderia was associated with the heavy metal resistance gene island, and there were a large number of Tn7 transposable element insertion events in genomes. At the same time, BGI metal gene islands related to heavy metal resistance genes of Tn7 like transposable element were found, and these gene islands were only distributed in Burkholderia cepacia, Burkholderia polyvora, and Burkholderia contaminant.
Genetic diversity of Potato virus M (PVM) in the major potato growing region in the Indo-Gangetic plain and characterization of a distinct strain of PVM occurring in India
Authors: Kumar Alok , Katiyar Akshay , Jailani A. Abdul Kader , Chackraborty Ashis , Mandal Bikash
Published: November 2023

Potato virus M (PVM) is one of the most prevalent viruses infecting potatoes worldwide, showing a wide range of diversity in their populations; however, the diversity and genome information of PVM occurring in India is hardly known. The present study serologically detected the PVM in 22.8% of leaf samples collected from the potato fields, generated 13 coat protein (CP) genes and one complete genome sequence for the isolates from India, and identified four differential hosts confirming PVM-Del-144 as a distinct strain of PVM occurring in India. The phylogenetic analyses conducted based on the CP gene sequences (14 from India and 176 from other countries) suggested the existence of three evolutionary divergent lineages (PVM-o, PVM-d, and a new divergent group) in the PVM population, where isolates from India belong to only two clusters (PVM-o and PVM-d) within four sub-clusters. High levels of nucleotide diversity (0.124) and genetic distance (0.142) recorded among the isolates from India may be due to the deviation from the neutral evolution and experiencing population expansion in the past. The complete genome of the isolate Del-144 (KJ194171; 8,526 nucleotides) shared 92.2–93.9% nt sequence identity with the population of PVM-o, whereas it shared only 70.2–72.1% identity with PVM-d. In the phylogenetic analyses, Del-144 clustered with the isolates of PVM-o; however, it formed a separate branch away from all other isolates, indicating the diversity of the strain. Overall, this study revealed the diversity of the isolates of PVM from India and reported the first complete genome sequence of a distinct strain of PVM occurring in India.
Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages?
Authors: Bonnet Mehdi , Eckert Catherine , Tournebize Régis
Published: November 2023

Antimicrobial resistance is a major threat to human and animal health and accounted for up to 4.5 million deaths worldwide in 2019. Asymptomatic colonization of the digestive tract by multidrug resistant (multi-resistant) bacteria such as extended-spectrum beta-lactamase-, or carbapenemase- producing Enterobacterales is (i) a risk factor for infection by these multi-resistant bacteria, (ii) a risk factor of dissemination of these multi-resistant bacteria among patients and in the community, and (iii) allows the exchange of resistance genes between bacteria. Hence, decolonization or reduction of the gastrointestinal tract colonization of these multi-resistant bacteria needs to be urgently explored. Developing new non-antibiotic strategies to limit or eradicate multi-resistant bacteria carriage without globally disrupting the microbiota is considered a priority to fight against antibiotic resistance. Probiotics or Fecal Microbiota Transplantation are alternative strategies to antibiotics that have been considered to decolonize intestinal tract from MDR bacteria but there is currently no evidence demonstrating their efficacy. Lytic bacteriophages are viruses that kill bacteria and therefore could be considered as a promising strategy to combat antibiotic resistance. Successful decolonization by bacteriophages has already been observed clinically. Here, we discuss the current alternative strategies considered to decolonize the digestive tract of multidrug resistant bacteria, briefly describing probiotics and fecal microbiota transplantation approaches, and then detail the in vivo and in vitro studies using bacteriophages, while discussing their limits regarding the animal models used, the characteristics of phages used and their activity in regards of the gut anatomy.
Lactic acid bacterial surface display of scytovirin inhibitors for anti-ebolavirus infection
Authors: Wiggins Joshua , Nguyen Ngan , Wei Wenzhong , Wang Leah Liu , Hollingsead Olson Haley , Xiang Shi-Hua
Published: November 2023

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, this approach is also simple and cost-effective and can be easily applied in the regions of Ebola outbreaks in the developing countries.
Gut microbiota and risk of lower respiratory tract infections: a bidirectional two-sample Mendelian randomization study
Authors: Liu Wei , Wang Xinyan , Feng Ruizhi , Zhao Chen , Luo Jian , Zhang Xiawei , Liu Xuemei , Yang Mei , Min Jie , Mao Bing , Jiang Hongli
Published: November 2023

Introduction

Observational studies have reported the association between gut microbiota and the risk of lower respiratory tract infections (LRTIs). However, whether the association reflects a causal relationship remains obscure.

Methods

A bidirectional twosample Mendelian randomization (MR) analysis was conducted by assessing genome-wide association study (GWAS) summary statistics for gut microbiota taxa and five common LRTIs. MR methods including inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode were used to analyze the causality. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. Cochran’s Q test was used to check for heterogeneity. Leave-one-out analysis was used to assess the stability of effect sizes. Detected significant associations were validated by using an independent LRTI GWAS summary statistics dataset. An optional MR method of causal analysis using summary effect estimates (CAUSE) was further performed as a validation to avoid potential false-positive results.

Results

According to the MR-Egger estimates in forward MR analysis, a causal effect of gut Blautia on increased odds of bronchiectasis and pneumonia was suggested. MR-Egger regression pleiotropy intercept methods detected no significant horizontal pleiotropy between the instrumental variables of these associations. MR-PRESSO global test examined no potential horizontal pleiotropy. Cochran’s Q test showed that no heterogeneity biased the results. The leave-one-out sensitivity analyses suggested robust causality results. These associations with consistent effect direction were successfully replicated in IVW analysis by using the validation GWAS dataset. However, these evidence of causality did not survive after applying strict Bonferroni correction or CAUSE analysis. The reverse MR analysis failed to achieve consistent results in the effect of LRTIs on gut microbiota through comprehensive discovery and validation processes.

Discussion

This study established no strong causality between genetically predicted gut microbiome and the risk of lower respiratory tract infections. However, specific subtypes of microbial genera, such as Blautia, were identified as potential influencers and require further investigation, particularly at the species or strain levels.
The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees
Authors: Li Yiyuan , Zhang Yan , Luo Xi , Meng Yujie , Zhong Zhaopeng , Zheng Hao , Yang Yunsheng
Published: November 2023

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.
A genetic and virulence characterization of Brazilian strains of Mycoplasma hyopneumoniae
Authors: Toledo Leonardo Teófilo , de Souza Luiz Fernando Lino , Pereira Carlos Eduardo Real , Polveiro Richard Costa , Bressan Gustavo Costa , Yamatogi Ricardo Seiti , Jeong Kwangcheol Casey , Marks Fernanda Simone , Diamantino Caio Augustus , de Carvalho Victor Hugo Rabelo , Malcher Clarisse Sena , Petri Fernando Antônio Moreira , de Oliveira Luis Guilherme , Moreira Maria Aparecida Scatamburlo , Silva-Júnior Abelardo
Published: November 2023

Mycoplasma hyopneumoniae(M. hyopneumoniae) is considered the primary causative agent of porcine enzootic pneumonia (EP), a chronic contagious respiratory disease that causes economic losses. Obtaining new pathogenic isolates and studying the genome and virulence factors are necessary. This study performed a complete sequencing analysis of two Brazilian strains, UFV01 and UFV02, aiming to characterize the isolates in terms of the virulence factors and sequence type. The complete genome analysis revealed the main virulence genes (mhp385,mhp271,MHP_RS03455,p102,p97,p216,MHP_RS00555,mhp107) and ST-123, the presence of three toxin-related genes (tlyC,PLDc_2andhcnC), and some genetic groups specific to these two isolates. Subsequently, the pathogenicity of the isolates was evaluated via an experimental infection conducted in a swine model. The study was divided into three groups, namely a negative control group (n = 4) and two test groups (n = 8), totaling 20 animals. They were challenged at 35 days of age with 107CCU (Color Changing Units)M. hyopneumoniaevia the intratracheal route. The UFV01 group showed earlier and higher seroconversion (IgG) (100%), while only 50% of the UFV02 group seroconverted. The same trend was observed when analyzing the presence of IgA in the bronchoalveolar lavage fluid (BALF) at 35 days post-infection (dpi). The UFV01 group had a mean macroscopic lesion score of 11.75% at 35 dpi, while UFV02 had 3.125%. Microscopic lesions were more severe in the UFV01 group. Based on laryngeal swab samples evaluated by qPCR, and the detection began at 14 days. The UFV01 group showed 75% positivity at 14 dpi. The UFV02 group also started excreting at 14 dpi, with a positivity rate of 37.5%. The results indicate that the UFV01 isolate exhibits higher virulence than UFV02. These findings may aid in developing new vaccines and diagnostic kits and establishing experimental models for testing.
Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study
Authors: Fang Haiming , Yao Tingting , Li Wanli , Pan Na , Xu Hang , Zhao Qian , Su Yuan , Xiong Kangwei , Wang Jiajia
Published: November 2023

Objective

To assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia.

Methods

Patients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4 weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed.

Results

Forty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N = 17) and non-insomnia group (N = 16). Compared to baseline, FMT significantly ameliorated the ISI (17.31 ± 5.12 vs. 5.38 ± 5.99), PSQI (14.56 ± 2.13 vs. 6.63 ± 4.67), SAS (54.25 ± 8.90 vs. 43.68 ± 10.64) and SDS (57.43 ± 10.96 vs. 50.68 ± 15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients.

Conclusion

Eggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.
National Danish surveillance of invasive clinical Haemophilus influenzae isolates and their resistance profile
Authors: Slotved Hans-Christian , Johannesen Thor Bech , Stegger Marc , Dalby Tine , Fuursted Kurt
Published: November 2023

Introduction

This study aimed to investigate the epidemiology, serotype distribution, phenotypical antibiogram, and molecular resistance gene characteristics of invasive Haemophilus influenzae infections in Denmark from 2014 to 2022. Additionally, the potential impact of outdoor temperature and COVID-19 restrictions on the epidemiology of H. influenzae was assessed.

Materials and methods

Invasive H. influenzae isolates were received from patients with positive culture results from cerebrospinal fluid, blood, or other sterile sites. Sample data were obtained from the Danish laboratory surveillance system/MiBa database, and whole-genome sequencing (WGS) was performed on the isolates. The incidence rates and distribution of H. influenzae cases were analyzed, and antibiotic susceptibility were assessed.

Results

A total of 1,007 invasive H. influenzae cases were identified, with serotyping conducted for 752 (74.7%) isolates. The median incidence per year of H. influenzae was 2.0 cases per 100,000, with the highest incidence in 2014 and the lowest in 2020. The majority of H. influenzae isolates were non-typeable H. influenzae (NTHi), while the most prominent serotypes were serotype f followed by serotype b. Bacteremia cases accounted for the majority (88.6%) of occurrences, although meningitis cases showed an increasing trend during the time period. The age group 85+ exhibited the highest incidence. The implementation of COVID-19 preventive interventions in 2020 resulted in a significant reduction in H. influenzae incidence, which returned to pre-COVID levels in 2021. A negative correlation was observed between monthly H. influenzae cases and outdoor temperature. An overall level of genetic beta-lactamase resistance of 26.3% was observed divided into 10.6% beta-lactamase-positive ampicillin-resistant (gBLPAR), 13.6% beta-lactamase-negative ampicillin-resistant (gBLNAR) and 2.1% beta-lactamase-positive amoxicillin clavulanate-resistant (gBLPACR). Other non-beta-lactam resistance traits were detected in 7.6% of isolates (primarily aminoglycoside-modifying enzymes).

Conclusion

The overall incidence of H. influenzae in Denmark returned to stable levels after the COVID-19 epidemic, with NTHi strains dominating. The COVID-19 preventive interventions led to a major reduction in incidence. A significant negative correlation between the incidence of H. influenzae and temperature was observed. The study revealed an overall genetic beta-lactam resistance rate of 26.3%, and the concordance between genotypic and phenotypic beta-lactam resistance was high (98.2%).
SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids
Authors: Stewart Romal , Yan Kexin , Ellis Sevannah A. , Bishop Cameron R. , Dumenil Troy , Tang Bing , Nguyen Wilson , Larcher Thibaut , Parry Rhys , Sng Julian De Jun , Khromykh Alexander A. , Sullivan Robert K. P. , Lor Mary , Meunier Frédéric A. , Rawle Daniel J. , Suhrbier Andreas
Published: November 2023

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neurotropic potential, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. The results herein suggest that evolving omicron variants may have increasing neurotropic potential.
Cellular senescence in brain aging and cognitive decline
Authors: Shafqat Areez , Khan Saifullah , Omer Mohamed H. , Niaz Mahnoor , Albalkhi Ibrahem , AlKattan Khaled , Yaqinuddin Ahmed , Tchkonia Tamara , Kirkland James L. , Hashmi Shahrukh K.
Published: November 2023

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden.
LGNN: a novel linear graph neural network algorithm
Authors: Cao Shujuan , Wang Xiaoming , Ye Zhonglin , Li Mingyuan , Zhao Haixing
Published: November 2023

The emergence of deep learning has not only brought great changes in the field of image recognition, but also achieved excellent node classification performance in graph neural networks. However, the existing graph neural network framework often uses methods based on spatial domain or spectral domain to capture network structure features. This process captures the local structural characteristics of graph data, and the convolution process has a large amount of calculation. It is necessary to use multi-channel or deep neural network structure to achieve the goal of modeling the high-order structural characteristics of the network. Therefore, this paper proposes a linear graph neural network framework [Linear Graph Neural Network (LGNN)] with superior performance. The model first preprocesses the input graph, and uses symmetric normalization and feature normalization to remove deviations in the structure and features. Then, by designing a high-order adjacency matrix propagation mechanism, LGNN enables nodes to iteratively aggregate and learn the feature information of high-order neighbors. After obtaining the node representation of the network structure, LGNN uses a simple linear mapping to maintain computational efficiency and obtain the final node representation. The experimental results show that the performance of the LGNN algorithm in some tasks is slightly worse than that of the existing mainstream graph neural network algorithms, but it shows or exceeds the machine learning performance of the existing algorithms in most graph neural network performance evaluation tasks, especially on sparse networks.
Chronic interleukin-6 mediated neuroinflammation decreases anxiety, and impaires spatial memory in aged female mice
Authors: Wagnon Ingrid Marguerite , Jabur Lillian Jocelyn , Niedermayer Garry , Münch Gerald , Karl Tim , Chesworth Rose , Gyengesi Erika
Published: November 2023

Introduction

Neuroinflammation is a common feature of many psychiatric disorders as well as a common underlying mechanism of neurodegenerative diseases. Sex has been shown to strongly influence the development as well as the clinical expression of these pathologies. However, there is still a neglect regarding the consideration of sex effects in rodent experiments, and a substantial underrepresentation of females in studies. This work set out to expand our knowledge of neuroinflammatory mechanisms in female mice, at both a behavioral and molecular level.

Methods

This study used GFAP-IL6 mice, a model of chronic neuroinflammation, in which interleukin-6 (IL6) is overexpressed in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter. We evaluated aged (11-15-month-old) wild type-like (WT) and GFAP-IL6 female mice in behavioral tests assessing anxiety (elevated plus-maze, EPM, Light/dark box), and spatial learning and memory (Y-maze, YM and Barnes Maze, BM) and associative learning (fear conditioning, FC). We also examined gene expression of markers linked to neuroinflammation, neurodegeneration and neurotransmission via RT-qPCR in brain regions involved in motor control, anxiety, learning and memory.

Results

Female GFAP-IL6 mice exhibited reduced anxiety-like behavior in the EPM, and hypolocomotion in the light-dark test and EPM. Short-term memory impairment was evident in the YM but associative learning in FC was intact in GFAP-IL6 mice, suggesting domain-specific cognitive deficits in female GFAP-IL6 mice. In the BM, all mice showed intact learning and memory, but GFAP-IL6 mice exhibited higher latencies to enter the escape hole than WT mice. We analyzed the search strategy and found differences in the way GFAP-IL6 mice searched for the escape hole compared to WTs. RT-qPCR showed increased mRNA levels for molecules involved in pro-inflammatory pathways in the cerebellum, motor cortex, hippocampus, and amygdala in GFAP-IL6 mice. Of the regions examined, the cerebellum and the hippocampus showed upregulation of neuroinflammatory makers as well as dysregulation of glutamatergic and GABAergic neurotransmission gene expression in GFAP-IL6 mice compared to WTs.

Conclusion

In conclusion, we showed that chronic neuroinflammation via IL6 overexpression in aged female mice led to a less anxious-like phenotype, hypolocomotion and impaired intermediate-term spatial learning and memory in the YM.
The effect of EEG and fNIRS in the digital assessment and digital therapy of Alzheimer’s disease: a systematic review
Authors: Zhang Yucheng , Zhang Yue , Jiang Zhouhao , Xu Mengxue , Qing Kunqiang
Published: November 2023

In the context of population aging, the growing problem of Alzheimer’s disease (AD) poses a great challenge to mankind. Although there has been considerable progress in exploring the etiology of AD, i.e., the important role of amyloid plaques and neurofibrillary tangles in the progression of AD has been widely accepted by the scientific community, traditional treatment and monitoring modalities have significant limitations. Therefore novel evaluation and treatment modalities for Alzheimer’s disease are called for emergence. In this research, we sought to review the effectiveness of digital treatment based on monitoring using functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). This work searched four electronic databases using a keyword approach and focused on journals focusing on AD and geriatric cognition. Finally, 21 articles were included. The progress of digital therapy and outcome monitoring in AD was reviewed, including digital therapy approaches on different platforms and different neuromonitoring techniques. Because biomarkers such as theta coherence, alpha and beta rhythms, and oxyhemoglobin are effective in monitoring the cognitive level of AD patients, and thus the efficacy of digital therapies, this review particularly focuses on the biomarker validation results of digital therapies. The results show that digital treatment based on biomarker monitoring has good effectiveness. And the effectiveness is reflected in the numerical changes of biomarker indicators monitored by EEG and fNIRS before and after digital treatment. Increases or decreases in the values of these indicators collectively point to improvements in cognitive function (mostly moderate to large effect sizes). The study is the first to examine the state of digital therapy in AD from the perspective of multimodal monitoring, which broadens the research perspective on the effectiveness of AD and gives clinical therapists a “reference list” of treatment options. They can select a specific protocol from this “reference list” in order to tailor digital therapy to the needs of individual patients.
A quantization algorithm of visual fatigue based on underdamped second order stochastic resonance for steady state visual evoked potentials
Authors: Tian Peiyuan , Xu Guanghua , Han Chengcheng , Zhang Xun , Zheng Xiaowei , Wei Fan , Zhang Sicong , Zhao Zhe
Published: November 2023

Introduction

In recent years, more and more attention has been paid to the visual fatigue caused by steady state visual evoked potential (SSVEP) paradigm. It is well known that the large-scale application of brain-computer interface is closely related to SSVEP, and the fatigue caused by SSVEP paradigm leads to the reduction of application effect. At present, the mainstream method of objectively quantifying visual fatigue in SSVEP paradigm is based on traditional canonical correlation analysis (CCA).

Methods

In this paper, we propose a new SSVEP paradigm visual fatigue quantification algorithm based on underdamped second-order stochastic resonance (USSR) to accurately quantify visual fatigue caused by SSVEP paradigm in different working modes using single-channel electroencephalogram (EEG) signals. This scheme uses the fixed-step energy parameter optimization algorithm we designed, combined with the USSR model, to significantly improve the signal-to-noise ratio of the processed signal at the target characteristic frequency. We not only compared the new algorithm with CCA, but also with the traditional subjective quantitative visual fatigue gold standard Likert fatigue scale.

Results

There was no significant difference (p = 0.090) between the quantitative value of paradigm fatigue obtained by the single channel SSVEP processed by the new algorithm and the gold standard of subjective fatigue quantification, while there was a significant difference (p < 0.001***) between the quantitative value of paradigm fatigue obtained by the traditional multi-channel CCA algorithm and the gold standard of subjective fatigue quantification.

Discussion

The conclusion shows that the quantization value obtained by the new algorithm can better match the subjective gold standard score, which also shows that the new algorithm is more reliable, which reflects the superiority of the new algorithm.