bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESKAPEE pathogens newly released from biofilm residence by a targeted monoclonal are sensitized to killing by traditional antibiotics
Authors: Kurbatfinski Nikola , Kramer Cameron N. , Goodman Steven D. , Bakaletz Lauren O. 
Published: July 2023

IntroductionThe “silent” antimicrobial resistance (AMR) pandemic is responsible for nearly five million deaths annually, with a group of seven biofilm-forming pathogens, known as the ESKAPEE pathogens, responsible for 70% of these fatalities. Biofilm-resident bacteria, as they exist within the disease site, are canonically highly resistant to antibiotics. One strategy to counter AMR and improve disease resolution involves developing methods to disrupt biofilms. These methods aim to release bacteria from the protective biofilm matrix to facilitate their killing by antibiotics or immune effectors. Several laboratories working on such strategies have demonstrated that bacteria newly released from a biofilm display a transient phenotype of significantly increased susceptibility to antibiotics. Similarly, we developed an antibody-based approach for biofilm disruption directed against the two-membered DNABII family of bacterial DNA-binding proteins, which serve as linchpins to stabilize the biofilm matrix. The incubation of biofilms with α-DNABII antibodies rapidly collapses them to induce a population of newly released bacteria (NRel).MethodsIn this study, we used a humanized monoclonal antibody (HuTipMab) directed against protective epitopes of a DNABII protein to determine if we could disrupt biofilms formed by the high-priority ESKAPEE pathogens as visualized by confocal laser scanning microscopy (CLSM) and COMSTAT2 analysis. Then, we demonstrated the potentiated killing of the induced NRel by seven diverse classes of traditional antibiotics by comparative plate count.ResultsTo this end, ESKAPEE biofilms were disrupted by 50%−79% using a single tested dose and treatment period with HuTipMab. The NRel of each biofilm were significantly more sensitive to killing than their planktonically grown counterparts (heretofore, considered to be the most sensitive to antibiotic-mediated killing), even when tested at a fraction of the MIC (1/250–1/2 MIC). Moreover, the bacteria that remained within the biofilms of two representative ESKAPEE pathogens after HuTipMab disruption were also significantly more susceptible to killing by antibiotics.DiscussionNew data presented in this study support our continued development of a combinatorial therapy wherein HuTipMab is delivered to a patient with recalcitrant disease due to an ESKAPEE pathogen to disrupt a pathogenic biofilm, along with a co-delivered dose of an antibiotic whose ability to rapidly kill the induced NRel has been demonstrated. This novel regimen could provide a more successful clinical outcome to those with chronic, recurrent, or recalcitrant diseases, while limiting further contribution to AMR.
The halophilic bacteria Gracilibacillus dipsosauri GDHT17 alleviates salt stress on perennial ryegrass seedlings
Authors: Li Xiangying , Zheng Jinyuan , Wei Wei , Gong Zifan , Liu Zhenyu 
Published: July 2023

IntroductionAdverse abiotic environmental conditions including excess salt in the soil, constantly challenge plants and disrupt the function of plants, even inflict damage on plants. Salt stress is one of the major limiting factors for agricultural productivity and severe restrictions on plant growth. One of the critical ways to improve plant salt tolerance is halotolerant bacteria application. However, few such halotolerant bacteria were known and should be explored furtherly.MethodsHalophilic bacterium strain was isolated from saline soil with serial dilution and identified with classical bacteriological tests and 16S rRNA analysis. Perennial ryegrass (Lolium perenne L) was used in this study to evaluate the potential effect of the bacteria.Results and discussionA halophilic bacterium strain GDHT17, was isolated from saline soil, which grows in the salinities media with 1.0%, 5.0%, and 10.0% (w/v) NaCl, and identified as Gracilibacillus dipsosauri. Inoculating GDHT17 can significantly promote ryegrass’s seedling height and stem diameter and increase the root length, diameter, and surface area at different salt concentrations, indicating the significant salt stress alleviating effect of GDHT17 on the growth of ryegrass. The alleviating effect on roots growth showed more effective, especially on the root length, which increased significantly by 26.39%, 42.59%, and 98.73% at salt stress of 100 mM, 200 mM, and 300 mM NaCl when the seedlings were inoculated with GDHT17. Inoculating GDHT17 also increases perennial ryegrass biomass, water content, chlorophyll and carotenoid content under salt stress. The contents of proline and malonaldehyde in the seedlings inoculated with GDHT17 increased by 83.50% and 6.87%, when treated with 300 mM NaCl; however, the contents of MDA and Pro did not show an apparent effect under salt stress of 100 mM or 200 mM NaCl. GDHT17-inoculating maintained the Na+/K+ ratio in the salt-stressed ryegrass. The Na+/K+ ratio decreased by 26.52%, 6.89%, and 29.92% in the GDHT17-inoculated seedling roots treated with 100 mM, 200 mM, and 300 mM NaCl, respectively. The GDHT17-inoculating increased the POD and SOD activity of ryegrass seedlings by 25.83% and 250.79%, respectively, at a salt stress of 300 mM NaCl, indicating the properties of GDHT17, improving the activity of antioxidant enzymes of ryegrass at the salt-stress condition. Our results suggest that G. dipsosauri GDHT17 may alleviate salt stress on ryegrass in multiple ways; hence it can be processed into microbial inoculants to increase salt tolerance of ryegrass, as well as other plants in saline soil.
Aerosolization inhalation of non-typeable Haemophilus influenzae outer membrane vesicles contributing to neutrophilic asthma
Authors: Zhang Ying , Wang Hongbo , Zhang Yanqiu , Zhao Peiliang , Li Yanan 
Published: July 2023

BackgroundNeutrophilic asthma is poorly responsive to corticosteroids, and the mechanism underlying its pathogenesis remains unclear. Non-typeable Haemophilus influenzae (NTHi) is the most common bacterium found in induced sputum from patients with neutrophilic asthma. NTHi can release outer membrane vesicles (OMVs), which transfer biomolecules to host cells and the external environment. However, the role and mechanisms of NTHi OMVs in the pathogenesis of neutrophilic asthma remain unclear.MethodsWe conducted assays to investigate whether NTHi OMVs can induce neutrophilic asthma when inhaled. We isolated and purified NTHi OMVs and administered them via a nebulizer to ovalbumin (OVA)-sensitized mice. We collected and sequenced serum, blood, bronchoalveolar lavage fluid, and lung tissue from each group and gathered lung function data.ResultsInhaled NTHi OMVs-induced neutrophilic asthma in OVA-sensitized mice. High-throughput sequencing revealed that NTHi OMV inhalation in OVA-sensitized mice significantly enriched inflammatory and immune-related signaling pathways. We found increased transcription and secretion of interleukin (IL)-1β and IL-17, which may contribute to neutrophilic asthma. Furthermore, we discovered that airway epithelium is the first receptor cell of NTHi OMVs and releases IL-1β. These findings suggest that NTHi OMVs could be a potential target for neutrophilic asthma therapy.
Effects of grazing prohibition on nirK- and nirS-type denitrifier communities in salt marshes
Authors: Li Niu , Li Jingrou , Nie Ming , Wu Ming , Wu Jihua 
Published: July 2023

IntroductionGrazing prohibition is an effective management practice to restore salt marsh functioning. However, the effects of grazing exclusion on denitrifying microbial communities and their controlling factors in salt marshes remain unclear.MethodsIn this study, we surveyed soil physicochemical properties and above- and below-ground biomass and using quantitative polymerase chain reaction and Illumina MiSeq high-throughput sequencing technology to determine the relative abundance, composition, and diversity of nitrite reductase nirS- and nirK-type denitrifying bacterial communities associated with grazing prohibition treatments and elevations.ResultsThe abundance of nirS-type denitrifiers increased with grazing prohibition time, whereas the abundance of nirK-type denitrifiers remained unaltered. Moreover, nirS-type denitrifiers were more abundant and diverse than nirK-type denitrifiers in all treatments. Grazing prohibition significantly altered the operational taxonomic unit richness, abundance-based coverage estimator, and Chao1 indices of the nirS-type denitrifying bacterial communities, whereas it only minimally affected the structure of the nirK-type denitrifying bacterial community.DiscussionThe results imply that the nirS community, rather than nirK, should be the first candidate for use as an indicator in the process of salt marsh restoration after grazing prohibition. Substances of concern, total nitrogen, and salinity were the key environmental factors affecting the abundance and community composition of nirS and nirK denitrifiers. The findings of this study provide novel insights into the influence of the length of grazing prohibition and elevation on nirS- and nirK-type denitrifying bacterial community composition in salt marshes.
Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study
Authors: Lee Ilju , Kim Dohyun , Kim Sehwan , Kim Hee Jung , Chung Un Sun , Lee Jung Jae 
Published: July 2023

IntroductionMild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI.MethodsNear-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants.ResultsCompared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance.ConclusionOur results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.
Mind the gap: trajectory of cognitive development in young individuals with sickle cell disease: a cross-sectional study
Authors: Koelbel Melanie , Hamdule Shifa , Kirkham Fenella J. , Stotesbury Hanne , Hood Anna Marie , Dimitriou Dagmara 
Published: July 2023

Study objectivesCompared to typically developing children and young adults (CYA-TD), those living with Sickle Cell Disease (CYA-SCD) experience more cognitive difficulties, particularly with executive function. Few studies have examined the relative importance of silent cerebral infarction (SCI), haemoglobin and arterial oxygen content on age-related cognitive changes using cross-sectional or longitudinal (developmental trajectory) data. This study presents cohort data from a single timepoint to inform studies with multiple timepoints.MethodsWe compared cross-sectional raw and scaled scores as age-related changes in cognition (trajectories) in CYA-SCD and age-and ethnicity-matched CYA-TD. We also compared cross-sectional age-related changes in cognition (trajectories) in CYA-SCD with and without SCI to CYA-TD. General cognitive abilities were assessed using Wechsler Intelligence Scales, including the Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) underpinning IQ. Executive function was evaluated using the Delis-Kaplan Executive Function System (D-KEFS) Tower subtest and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. SCI were identified from contemporaneous 3 T MRI; participants with overt stroke were excluded. Recent haemoglobin was available and oxygen saturation (SpO2) was measured on the day of the MRI.ResultsData were available for 120 CYA-SCD [62 male; age = 16.78 ± 4.79 years; 42 (35%) with SCI] and 53 CYA-TD (23 male; age = 17.36 ± 5.16). Compared with CYA-TD, CYA-SCD experienced a delayed onset in VCI and slower rate of development for BRIEF Global Executive Composite, Metacognition Index (MI), and Behaviour Regulation Index. The rate of executive function development for the BRIEF MI differed significantly between CYA-TD and CYA-SCD, with those with SCI showing a 26% delay compared with CYA-TD. For CYA-SCD with SCI, arterial oxygen content explained 22% of the variance in VCI and 37% in PRI, while haemoglobin explained 29% of the variance in PRI.ConclusionAge-related cognitive trajectories of CYA-SCD may not be impaired but may progress more slowly. Longitudinal studies are required, using tests unaffected by practice. In addition to initiation of medical treatment, including measures to improve arterial oxygen content, early cognitive intervention, educational support, and delivery of extracurricular activities could support cognitive development for CYA-SCD.
Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019
Authors: Ye Yang , Zhu Yu-Tian , Zhang Jia-Cheng , Zhang Hao-Lin , Fan Rui-Wen , Jin Yu-Xin , Hu Hang-Qi , Xin Xi-Yan , Li Dong 
Published: July 2023

BackgroundThe epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019.MethodsThis is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed.ResultsFrom 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China.ConclusionOur study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.
Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies
Authors: Amberntsson Anna , Bärebring Linnea , Winkvist Anna , Lissner Lauren , Meltzer Helle Margrete , Brantsæter Anne Lise , Papadopoulou Eleni , Augustin Hanna 
Published: July 2023

IntroductionMaternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child’s body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations.MethodsData sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child’s documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child’s BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset.ResultsIn the pooled analysis, maternal 25OHD &lt;30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI ≥25 kg/m2.ConclusionLow maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.
Evaluation of oncofertility care in childhood cancer patients: the EU-Horizon 2020 twinning project TREL initiative
Authors: Stukaite-Ruibiene Egle , van der Perk M. E. Madeleine , Vaitkeviciene Goda Elizabeta , Bos Annelies M. E. , Bumbuliene Zana , van den Heuvel-Eibrink Marry M. , Rascon Jelena 
Published: July 2023

BackgroundThe 5-year survival rate of childhood cancer exceeds 80%, however, many survivors develop late effects including infertility. The aim of this study was to evaluate the current status of oncofertility care at Vilnius University Hospital Santaros Klinikos (VULSK) within the framework of the EU-Horizon 2020 TREL project.MethodsAll parents or patients aged 12–17.9 years treated from July 1, 2021 until July 1, 2022 were invited to complete an oncofertility-care-evaluation questionnaire. After completing the questionnaire, patients were triaged to low-risk (LR) or high-risk (HR) of gonadal damage using a risk stratification tool (triage). Data was assessed using descriptive statistics.ResultsQuestionnaires were completed by 48 parents and 13 children triaged as 36 (59%) LR and 25 (41%) HR patients. Most HR respondents (21/25, 84%) were not counseled by a fertility specialist. Six boys (4 HR, 2 LR) were counseled, none of the girls was counseled. Three HR boys underwent sperm cryopreservation. Only 17 (27.9%, 9 HR, 8 LR) respondents correctly estimated their risk. All counseled boys (n = 6) agreed the risk for fertility impairment had been mentioned as compared to 49.1% (n = 27) of uncounseled. All counseled respondents agreed they knew enough about fertility (vs. 42%).ConclusionsRespondents counseled by a fertility specialist were provided more information on fertility than uncounseled. HR patients were not sufficiently counseled by a fertility specialist. Based on the current experience oncofertility care at VULSK will be improved.
The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer
Authors: Lu Tingting , Huang Yufan , Cai Zhongjie , Lin Wangchun , Chen Xiaoxiao , Chen Ruijia , Hu Yingying 
Published: July 2023

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system.Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs’ costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes.Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model’s results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT.Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.
Transcriptome analysis of mRNAs, lncRNAs, and miRNAs in the skeletal muscle of Tibetan chickens at different developmental stages
Authors: Li Jie , Chen Chuwen , Zhao Ruipeng , Wu Jinbo , Li Zhixiong 
Published: July 2023

Introduction: As a valuable genetic resource, native birds can contribute to the sustainable development of animal production. Tibetan chickens, known for their special flavor, are one of the important local poultry breeds in the Qinghai–Tibet Plateau. However, Tibetan chickens have a slow growth rate and poor carcass traits compared with broilers. Although most of the research on Tibetan chickens focused on their hypoxic adaptation, there were fewer studies related to skeletal muscle development.Methods: Here, we performed the transcriptional sequencing of leg muscles from Tibetan chicken embryos at E (embryonic)10, E14, and E18.Results: In total, 1,600, 4,610, and 2,166 DE (differentially expressed) mRNAs, 210, 573, and 234 DE lncRNAs (long non-coding RNAs), and 52, 137, and 33 DE miRNAs (microRNAs) were detected between E10 and E14, E10 and E18, and E14 and E18, respectively. Functional prediction showed several DE mRNAs and the target mRNAs of DE lncRNAs and DE miRNAs were significantly enriched in sarcomere organization, actin cytoskeleton organization, myofibril, muscle fiber development, and other terms and pathways related to muscle growth and development. Finally, a lncRNA–miRNA–mRNA ceRNA (competing endogenous RNA) network associated with muscle growth and development, which contained 6 DE lncRNAs, 13 DE miRNAs, and 50 DE mRNAs, was constructed based on the screened DE RNAs by Gene Ontology (GO) enrichment. These DE RNAs may play a critical regulatory role in the skeletal muscle development of chickens.Discussion: The results provide a genomic resource for mRNAs, lncRNAs, and miRNAs potentially involved in the skeletal muscle development of chickens, which lay the foundation for further studies of the molecular mechanisms underlying skeletal muscle growth and development in Tibetan chickens.