bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant hemagglutinin displaying on yeast reshapes congenital lymphocyte subsets to prompt optimized systemic immune protection against avian influenza infection
Authors: Zhang Han , Li Zexing , Zhang Huixia , Guo Yanyu , Zhang Xinyi , Zhang Lilin , Yang Liu , Li Shujun , Li Changyan , Cui Daqing , Xie Ruyu , Li Yongqing , Huang Jinhai 
Published: May 2023

IntroductionProphylactic vaccination is regarded as the most effective means to control avian flu infection. Currently, there is a need for a universal vaccine that provides broad and long-lasting protection against influenza virus. Meanwhile, although yeast-based vaccines have been used in clinic, studies are still required to further understand the molecular mechanism of yeast-based vaccines under physiological conditions.MethodsWe generated a yeast-based vaccine against influenza hemagglutinin (HA) of H5, H7 and H9 using surface displaying technology and evaluated the protective efficacy of chickens after exposure to H9N2 influenza virus.ResultsOral yeast vaccine provided less clinical syndrome, reduced viral loading and alleviated airway damage significantly. Compared to the commercial inactivated vaccine, yeast vaccine stimulated the activation of splenic NK and APCs cells and boosted TLR7-IRF7-IFN signaling in spleen. Meanwhile, γδ T cells in the bursa of Fabricius were activated and the innate lymphoid cells (ILCs) in the bursa of Fabricius promoted the CILPs to differentiate to ILC3 cells in oral yeast birds. Moreover, the reshaped gut microbiota and a suppressed Th17-IL17-mediated inflammation in intestine was observed in oral yeast chickens, which might facilitate the recovery of intestinal mucosal immunity upon virus infection. Collectively, our findings suggest that oral yeast based multivalent bird flu vaccines provide an attractive strategy to update host defense function via reshapes of multi-systemic immune homeostasis.
CREB5 hypermethylation involved in the ganglioside GM1 therapy of Parkinson’s disease
Authors: Wang Rui , Tong Shanshan , Wang Mengdi , Zou Junjie , Wang Nan , Sun Fengjiao , Zhou Xiaosheng , Chen Jinbo , Wang Hongcai 
Published: May 2023

IntroductionThe treatment with monosialotetrahexosylganglioside (GM1) improves the symptoms of Parkinson’s disease (PD). The alteration of DNA methylation in the blood was examined to investigate epigenetic modification by GM1 treatment.MethodsAfter a 28-day continuous intravenous infusion of GM1 (100mg), the motor and non-motor symptoms were evaluated by UPDRS III, Mini-mental state examination (MMSE) scores, FS-14, SCOPA-AUT, and PDQ-8. Moreover, blood samples were collected and PBMC was isolated. Genome-wide DNA methylation was performed by an 850K BeadChip. RNA levels and apoptosis were examined by RT-PCR and flow cytometry in rotenone-based cell models. The CREB5 plasmid was transfected by electroporation into SH-SY5Y cells. We also identified 235 methylation variable positions achieving genome-wide significance in 717558 differentially methylated positions (DMPs) (P = 0.0003) in comparison of pre-treatment with post-treatment measurements (statistical analysis paired-samples t-test).ResultsBy searching the Gene Expression Omnibus (GEO) dataset and GWAS, 23 methylation variable positions were screened. Moreover, there are 7 hypomethylated methylation variable positions correlated with the scores of motor symptoms (UPDRS III scale). According to KEGG pathways enrichment analysis, the methylated genes CACNA1B (hypomethylated), CREB5 (hypermethylated), GNB4 (hypomethylated), and PPP2R5A (hypomethylated) were enriched in the dopaminergic synapse pathway. Pretreated with GM1 (80 μM) for 1 h, cell apoptosis and impaired neurite outgrowth were inhibited in rotenone-induced PD cell models. The RNA expression of CREB5 was increased in rotenone-treated SH-SY5Y cells. GM1 treatment decreased rotenone-induced CREB5 gene expression. The enhancement of CREB5 gene expression suppressed the protective role of GM1 in rotenone-induced cell apoptosis.DiscussionThe application of GM1 improves the motor and non-motor symptoms of PD associated with the decreased CREB5 expression and the hypermethylation of CREB5.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=120582t, identifier ChiCTR2100042537.
The Use of Different Components of Brain Oxygenation for the Assessment of Cerebral Haemodynamics: A Prospective Observational Study on COVID-19 Patients
Authors: Robba Chiara , Cardim Danilo , Ball Lorenzo , Battaglini Denise , Dabrowski Wojciech , Bassetti Matteo , Giacobbe Daniele Roberto , Czosnyka Marek , Badenes Rafael , Pelosi Paolo , Matta Basil ,   The GeCovid group
Published: May 2023

Introduction: The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate the role of the integral components of regional cerebral oxygenation (rSO2) measured by NIRS [i.e., arterial-oxyhemoglobin (O2Hbi) and venous-deoxyhemoglobin (HHbi)-components], as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD).Methods: Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO2 and its components [relative changes in O2Hbi, HHbi, and total haemoglobin (cHbi)] were compared with TCD (cerebral blood flow velocity, CBFV). Changes (Δ) in CBFV and rSO2, ΔO2Hbi, ΔHHbi, and ΔcHbi after systemic arterial blood pressure (MAP) modifications induced by different manoeuvres (e.g., rescue therapies and haemodynamic manipulation) were assessed using mixed-effect linear regression analysis and repeated measures correlation coefficients. All values were normalised as percentage changes from the baseline (Δ%).Results: One hundred and four measurements from 25 patients were included. Significant effects of Δ%MAP on Δ%CBF were observed after rescue manoeuvres for CBFV, ΔcHbi, and ΔO2Hbi. The highest correlation was found between ΔCBFV and ΔΔO2Hbi (R = 0.88, p &lt; 0.0001), and the poorest between ΔCBFV and ΔΔHHbi (R = 0.34, p = 0.002).Conclusions: ΔO2Hbi had the highest accuracy to assess CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. The use of indexes derived from the different components of rSO2 can be useful for the bedside evaluation of cerebral haemodynamics in mechanically ventilated patients with COVID-19.
Effects of community ambulation training with 3D-printed ankle–foot orthosis on gait and functional improvements: a case series of three stroke survivors
Authors: Cho Ji-Eun , Seo Kyeong-Jun , Ha Sunghe , Kim Hogene 
Published: May 2023

IntroductionMany of the patients using ankle–foot orthoses (AFOs) experience poor fit, pain, discomfort, dislike of the aesthetics of the device, and excessive range of motion restrictions, which diminish the use of AFOs. Although 3D-printed ankle–foot orthoses (3D-AFOs) affect patient satisfaction and overall gait functions such as ankle moment, joint range of motion (ROM), and temporal-spatial parameters, the material properties and manufacturing process of 3D-AFOs are still diverse; the clinical effects of community ambulation using 3D-AFOs and satisfaction in patients with stroke are poorly understood.Case descriptionCase 1: A 30-year-old man, with a history of right basal ganglia hemorrhage, presented with marked foot drop and genu recurvatum. Case 2: A 58-year-old man, with a history of multifocal scattered infarction, presented with an asymmetrical gait pattern due to abnormal pelvic movement. Case 3: A 47-year-old man, with a history of right putamen hemorrhage, presented with recent poor balance and a prominent asymmetrical gait pattern due to increased ankle spasticity and tremor. All patients could walk independently with AFOs.Interventions and outcomesGait was assessed under three walking (even, uneven, and stair ascent/descent) and four AFO (no shoes, only shoes, shoes with AFOs, and shoes with 3D-AFOs) conditions. After 4 weeks of community ambulation training with 3D-AFO or AFO, the patients were followed up. Spatiotemporal parameters; joint kinematics; muscle efficiency; clinical evaluations including impairments, limitations, and participation; and patient satisfaction with wearing 3D-AFO were evaluated.Results and conclusion3D-AFOs were suitable for community ambulation of patients with chronic stroke and effective on step length, stride width, symmetry, ankle range of motion, and muscle efficiency during even surface walking and stair ascent in patients with chronic stroke. The 4-week community ambulation training with 3D-AFOs did not promote patient participation; however, it increased ankle muscle strength, balance, gait symmetry, and gait endurance and reduced depression among patients with a history of stroke. The participants were satisfied with 3D-AFO's thinness, lightweight, comfortable feeling with wearing shoes, and gait adjustability.
Vertigoheel promotes rodent cognitive performance in multiple memory tests
Authors: Ott Kerstin , Heikkinen Taneli , Lehtimäki Kimmo K. , Paldanius Kaisa , Puoliväli Jukka , Pussinen Raimo , Andriambeloson Emile , Huyard Bertrand , Wagner Stéphanie , Schnack Cathrin , Wahler Anke , von Einem Bjoern , von Arnim Christine A. F. , Burmeister Yvonne , Weyer Kathrin , Seilheimer Bernd 
Published: May 2023

IntroductionCognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made ofAmbra grisea,Anamirta cocculus L.,Conium maculatum, andPetroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.MethodsIn the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neuronsin vitroand mRNA expression of synaptophysin in the hippocampus.ResultsAdministration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experimentsin vitroshowed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.DiscussionOur findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.
Parent-reported child appetite moderates relationships between child genetic obesity risk and parental feeding practices
Authors: Jansen Elena , Naymik Marcus , Thapaliya Gita , Huentelman Matt , Beauchemin Jennifer , D'Sa Viren , Lewis Candace R. , Deoni Sean ,   RESONANCE consortium, Carnell Susan 
Published: May 2023

BackgroundFood parenting practices are associated with child weight. Such associations may reflect the effects of parents' practices on children's food intake and weight. However, longitudinal, qualitative, and behavioral genetic evidence suggests these associations could, in some cases, reflect parents' response to children's genetic risk for obesity, an instance of gene–environment correlation. We tested for gene–environment correlations across multiple domains of food parenting practices and explored the role of parent-reported child appetite in these relationships.Materials and methodsData on relevant variables were available for N = 197 parent–child dyads (7.54 ± 2.67 years; 44.4% girls) participating in RESONANCE, an ongoing pediatric cohort study. Children's body mass index (BMI) polygenic risk score (PRS) were derived based on adult GWAS data. Parents reported on their feeding practices (Comprehensive Feeding Practices Questionnaire) and their child's eating behavior (Child Eating Behavior Questionnaire). Moderation effects of child eating behaviors on associations between child BMI PRS and parental feeding practices were examined, adjusting for relevant covariates.ResultsOf the 12 parental feeding practices, 2 were associated with child BMI PRS, namely, restriction for weight control (β = 0.182, p = 0.011) and teaching about nutrition (β = −0.217, p = 0.003). Moderation analyses demonstrated that when children had high genetic obesity risk and showed moderate/high (vs. low) food responsiveness, parents were more likely to restrict food intake to control weight.ConclusionOur results indicate that parents may adjust their feeding practices in response to a child's genetic propensity toward higher or lower bodyweight, and the adoption of food restriction to control weight may depend on parental perceptions of the child's appetite. Research using prospective data on child weight and appetite and food parenting from infancy is needed to further investigate how gene–environment relationships evolve through development.
Determinants of morbidity and mortality related to health care-associated primary bloodstream infections in neonatal intensive care units: a prospective cohort study from the SEPREVEN trial
Authors: Jaloustre Morgane , Cohen Robert , Biran Valérie , Decobert Fabrice , Layese Richard , Audureau Etienne , Le Saché Nolwenn , Chevallier Marie , Boukhris Mohamed Riadh , Bolot Pascal , Caeymaex Laurence , Tauzin Manon ,   with the SEPREVEN study Group
Published: May 2023

BackgroundHealth care-associated primary bloodstream infections (BSIs), defined as not secondary to an infection at another body site, including central line-associated BSI, are a leading cause of morbidity and mortality in patients in neonatal intensive care units (NICUs). Our objective was to identify factors associated with severe morbidity and mortality after these infections in neonates in NICUs.MethodsThis ancillary study of the SEPREVEN trial included neonates hospitalized ≥2 days in one of 12 French NICUs and with ≥ 1 BSI during the 20-month study period. BSIs (all primary and health care-associated) were diagnosed in infants with symptoms suggestive of infection and classified prospectively as possible (one coagulase-negative staphylococci (CoNS)-growing blood culture) or proven (two same CoNS, or ≥1 recognized pathogen-growing blood culture). BSI consequences were collected prospectively as moderate morbidity (antibiotic treatment alone) or severe morbidity/mortality (life-saving procedure, permanent damage, prolonged hospitalization, and/or death).ResultsOf 557 BSIs identified in 494 patients, CoNS accounted for 378/557 (67.8%) and recognized bacterial or fungal pathogens for 179/557 (32.1%). Severe morbidity/mortality was reported in 148/557 (26.6%) BSIs. Independent factors associated with severe morbidity/mortality were corrected gestational age &lt;28 weeks (CGA) at infection (P &lt; .01), fetal growth restriction (FGR) (P = .04), and proven pathogen-related BSI vs. CoNS-related BSI (P &lt; .01). There were no differences in severe morbidity and mortality between proven and possible CoNS BSIs. In possible BSI, S. epidermidis was associated with a lower risk of severe morbidity than other CoNS (P &lt; .01), notably S. capitis and S. haemolyticus.ConclusionsIn BSIs in the NICU, severe morbidity/mortality was associated with low CGA at infection, FGR, and proven pathogen-related BSIs. When only one blood culture was positive, severe morbidity/mortality were less frequent if it grew with S. epidermidis compared to other CoNS. Further studies to help distinguish real CoNS BSIs from contaminations are needed.Study registrationClinicalTrials.gov (NCT02598609).
Critical shortage of capacity to deliver safe paediatric surgery in sub-Saharan Africa: evidence from 67 hospitals in Malawi, Zambia, and Tanzania
Authors: Gajewski Jakub , Pittalis Chiara , Borgstein Eric , Bijlmakers Leon , Mwapasa Gerald , Cheelo Mweene , Juma Adinan , Sardana Muskan , Brugha Ruairi 
Published: May 2023

IntroductionPaediatric surgical care is a significant challenge in Sub-Saharan Africa (SSA), where 42% of the population are children. Building paediatric surgical capacity to meet SSA country needs is a priority. This study aimed to assess district hospital paediatric surgical capacity in three countries: Malawi, Tanzania and Zambia (MTZ).MethodsData from 67 district-level hospitals in MTZ were collected using a PediPIPES survey tool. Its five components are procedures, personnel, infrastructure, equipment, and supplies. A PediPIPES Index was calculated for each country, and a two-tailed analysis of variance test was used to explore cross-country comparisons.ResultsSimilar paediatric surgical capacity index scores and shortages were observed across countries, greater in Malawi and less in Tanzania. Almost all hospitals reported the capacity to perform common minor surgical procedures and less complex resuscitation interventions. Capacity to undertake common abdominal, orthopaedic and urogenital procedures varied—more often reported in Malawi and less often in Tanzania. There were no paediatric or general surgeons or anaesthesiologists at district hospitals. General medical officers with some training to do surgery on children were present (more often in Zambia). Paediatric surgical equipment and supplies were poor in all three countries. Malawi district hospitals had the poorest supply of electricity and water.ConclusionsWith no specialists in district hospitals in MTZ, access to safe paediatric surgery is compromised, aggravated by shortages of infrastructure, equipment and supplies. Significant investments are required to address these shortfalls. SSA countries need to define what procedures are appropriate to national, referral and district hospital levels and ensure that an appropriate paediatric surgical workforce is in place at district hospitals, trained and supervised to undertake these essential surgical procedures so as to meet population needs.
Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children
Authors: Shi Jianrong , He Lin , Zheng Huiwen , Li Wei , Huang Shuangshuang , Li Yunling , Tao Ran 
Published: May 2023

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P &lt; 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).ConclusionsOur findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children.
The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan
Authors: Huang Yu-Hua , Pan Mei-Hung , Yang Hwai-I 
Published: May 2023

Objective: Previous studies have shown that gabapentin or pregabalin use is associated with cognitive decline. Herein, we aimed to evaluate the association between gabapentin or pregabalin use and the risk of dementia.Methods: In this retrospective, population-based matched cohort study, all research data were collected from the 2005 Longitudinal Health Insurance Database, which contains data of 2 million people randomly selected from the National Health Insurance Research Database of Taiwan in 2005. The study extracted data from 1 January 2000, to 31 December 2017. Adult patients taking gabapentin or pregabalin were included in the exposure group, and patients not using gabapentin or pregabalin matched to exposure subjects in a 1:5 ratio by propensity scores composed of age, sex and index date were included in the non-exposure group.Results: A total of 206,802 patients were enrolled in the study. Of them, 34,467 gabapentin- or pregabalin-exposure and 172,335 non-exposure patients were used for analysis. The mean follow-up day (±standard deviation) after the index date was 1724.76 (±1282.32) and 1881.45 (±1303.69) in the exposure and non-exposure groups, respectively; the incidence rates of dementia were 980.60 and 605.48 per 100,000 person-years, respectively. The multivariate-adjusted hazard ratio of risk of dementia for gabapentin or pregabalin exposure versus the matched non-exposed group was 1.45 (95% confidence interval [CI], 1.36–1.55). The risk of dementia increased with higher cumulative defined daily doses during the follow-up period. Moreover, the stratification analysis revealed that the risk of dementia associated with gabapentin or pregabalin exposure was significant in all age subgroups; however, it was higher in younger patients (age &lt;50) than in the older patients (hazard ratio, 3.16; 95% CI, 2.23–4.47).Conclusion: Patients treated with gabapentin or pregabalin had an increased risk of dementia. Therefore, these drugs should be used with caution, particularly in susceptible individuals.