bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific T-cell subsets have a role in anti-viral immunity and pathogenesis but not viral dynamics or onwards vector transmission of an important livestock arbovirus
Authors: Newbrook Kerry , Khan Nakibul , Fisher Aimee , Chong Karen , Gubbins Simon , Davies William C. , Sanders Christopher , Busquets Marc Guimerà , Cooke Lyndsay , Corla Amanda , Ashby Martin , Flannery John , Batten Carrie , Stokes Jessica E. , Sanz-Bernardo Beatriz , Carpenter Simon , Moffat Katy , Darpel Karin E. 
Published: January 2024

IntroductionBluetongue virus (BTV) is an arthropod-borne Orbivirus that is almost solely transmitted by Culicoides biting midges and causes a globally important haemorrhagic disease, bluetongue (BT), in susceptible ruminants. Infection with BTV is characterised by immunosuppression and substantial lymphopenia at peak viraemia in the host.MethodsIn this study, the role of cell-mediated immunity and specific T-cell subsets in BTV pathogenesis, clinical outcome, viral dynamics, immune protection, and onwards transmission to a susceptible Culicoides vector is defined in unprecedented detail for the first time, using an in vivo arboviral infection model system that closely mirrors natural infection and transmission of BTV. Individual circulating CD4+, CD8+, or WC1+ γδ T-cell subsets in sheep were depleted through the administration of specific monoclonal antibodies.ResultsThe absence of cytotoxic CD8+ T cells was consistently associated with less severe clinical signs of BT, whilst the absence of CD4+ and WC1+ γδ T cells both resulted in an increased clinical severity. The absence of CD4+ T cells also impaired both a timely protective neutralising antibody response and the production of IgG antibodies targeting BTV non-structural protein, NS2, highlighting that the CD4+ T-cell subset is important for a timely protective immune response. T cells did not influence viral replication characteristics, including onset/dynamics of viraemia, shedding, or onwards transmission of BTV to Culicoides. We also highlight differences in T-cell dependency for the generation of immunoglobulin subclasses targeting BTV NS2 and the structural protein, VP7.DiscussionThis study identifies a diverse repertoire of T-cell functions during BTV infection in sheep, particularly in inducing specific anti-viral immune responses and disease manifestation, and will support more effective vaccination strategies.
The clinical efficacy and suitable implementation of two extracorporeal blood purification therapies: AN69-oXiris versus PMX-HP
Authors: Kim Hye Sung , Chung Yoon Ji , Lee Gyeo Ra , Kim Eun Young 
Published: January 2024

PurposeIn septic shock patients, pathogens and excessive endotoxins continuously overstimulate the host’s immune system with a cytokine storm that can lead to multi-organ failure and even mortality. Various types of extracorporeal blood purification treatments have recently been introduced to remove excessive endotoxins and cytokines. Herein, we compared the clinical efficacy of two blood purification methods, PMX-HP and AN69-oXiris, and discussed their detailed indications according to disease severity.Materials and methodsFrom December 2016 to April 2023, patients who underwent emergent surgery due to septic shock secondary to peritonitis and subsequently received blood purification treatment with AN69-oXiris or PMX-HP were enrolled. Propensity score (PS)-matching was conducted to adjust for baseline characteristics between the two groups, and the changes in clinical parameters and outcomes were compared. Clinical outcomes were assessed in subgroups of patients who underwent PMX-HP treatment divided according to SOFA scores into low (0–7), intermediate (8–13), and high (&gt; 13) disease severity groups.ResultsForty patients received blood purification therapy with either PMX-HP or AN69-oXiris during the study period. After 1:2 PS matching, six patients in the AN69-oXiris group and 12 patients in the PMX-HP group were finally analyzed. Vasoactive-inotropic scores (VISs) decreased in both groups after 48 h of treatment compared to the baseline values, but the change in VISs was more pronounced in the PMX-HP group {−57.6 [interquartile range (IQR) = −166.4 – (−10)] vs. -22.9 [IQR = −64–0], respectively, p = 0.041}. Decreases in cardiovascular SOFA scores were significantly pronounced in the PMX-HP group [−1.5 (IQR = −4 – 0) vs. 0 (IQR = −1 – 1), respectively, p = 0.035]. The 7-day mortality rate was significantly lower than the predicted mortality rate in a subgroup analysis of patients treated with PMX-HP in both the low disease severity group and the intermediate disease severity group.ConclusionPMX-HP and AN69-oXiris could be therapeutic options for refractory septic shock patients with intra-abdominal origins, especially after the surgical elimination of the infectious sources. A tailored modality choice that takes into account patient characteristics, such as disease severity and cost burden, could optimize the efficacy of this strategy.
Prevalence and molecular characteristics of Shewanella infection in diarrhea patients in Beijing, China 2017–2019
Authors: Kang Ying , Yu Keyi , Huang Zhenzhou , Pang Bo , Liu Shengtian , Peng Tao , Li Ying , Wang Duochun 
Published: January 2024

IntroductionShewanella is an important opportunistic pathogen distributed in marine environments that has caused an increasing number of clinical infections. However, there are few reports on the distribution and characteristics of Shewanella in the diarrheal pathogen spectrum. In this study, we have systematically described the prevalence of Shewanella infections in diarrhea patients in Beijing, China 2017–2019, and genome characteristics and antimicrobial susceptibility of Shewanella isolates.MethodsStool samples were collected from diarrhea patients in a surveillance project from 2017 to 2019. Shewanella strains were isolated, and identified using VITEKR 2 COMPACT and MALDI-TOF MS. Average nucleotide identity (ANI) analysis, multi-locus sequence typing (MLST), phylogenetic analysis, virulence-associated genes and antimicrobial resistance genes analysis were used for genome characteristics description. The antibiotic susceptibility test was performed with microbroth dilution method.Results1104 fecal samples were collected, and the Shewanella detection rate was 2.36% (26/1104). The main manifestations of infection caused by Shewanella spp. were diarrhea (100%, 26/26), abdominal pain (65.38%, 17/26), and vomiting (38.46%, 10/26). The 26 isolates were classified into 3 species (S. algae (n = 18), S. indica (n = 5), and S. chilikensis (n = 3)) and 22 sequence types. Core genome single nucleotide polymorphism-based evolutionary tree identified three clone groups corresponding to three infection events in the same months in 2017 and 2019. The putative virulence-associated gene pool consisted of 56 potential virulence genes, including 19 virulence gene factors. The resistance rates of the 26 isolates to 17 antibiotics from high to low were as follows: polymyxin E (76.92%), cefotaxime (57.69%), ampicillin (50%), ampicillin-sulbactam (34.62%), nalidixic acid (15.38%), ciprofloxacin (11.54%), selectrin (3.846%,1/26), and tetracycline (3.846%, 1/26). The rate of multidrug resistance was 38.46% (10/26).DiscussionMonitoring for Shewanella spp. should be added to the routine surveillance of infectious diarrhea during the epidemic season.
Efficacy and feasibility of a digital speech therapy for post-stroke dysarthria: protocol for a randomized controlled trial
Authors: Kim Yuyoung , Kim Minjung , Kim Jinwoo , Song Tae-Jin 
Published: January 2024

BackgroundDysarthria is a motor speech disorder caused by various neurological diseases, particularly stroke. Individuals with post-stroke dysarthria experience impaired speech intelligibility, communication difficulties, and a reduced quality of life. However, studies on the treatment of post-stroke dysarthria are lacking. Digital speech therapy applications have the advantages of being personalized and easily accessible. However, evidence for their efficacy is not rigorous. Moreover, no studies have investigated both the acute to subacute, and chronic phases of stroke. This study aims to investigate the efficacy and feasibility of digital speech therapy applications in addressing these gaps in dysarthria treatment.Methods and designThis study is a multicenter, prospective, randomized, evaluator-blinded non-inferiority trial. We aim to recruit 76 participants with post-stroke dysarthria. Eligible participants will be stratified based on the onset period of stroke into acute to subacute, and chronic phases. Participants will be randomized in a 1:1 to receive either a personalized digital speech therapy application or conventional therapy with a workbook for 60 min daily, 5 days a week, for 4 weeks. The primary outcome is the improvement in speech intelligibility. This will be measured by how accurately independent listeners can transcribe passages read by the participants. Secondary outcomes, which include speech function, will be evaluated remotely by speech-language pathologists. This includes the maximum phonation time, oral diadochokinetic rate, and percentage of consonants correct. Participants’ psychological well-being will also be assessed using self-report questionnaires, such as depressive symptoms (Patient Health Questionnaire-9) and quality of life (Quality of Life in the Dysarthric Speaker scale). The trial will also assess the feasibility, participant adherence, and usability of the application. Rigorous data collection and monitoring will be implemented to ensure patient safety.ConclusionThis trial aims to investigate the efficacy and feasibility of digital speech therapy applications for treating post-stroke dysarthria. The results could establish foundational evidence for future clinical trials with larger sample sizes.Clinical trial registrationClinicaltrials.gov, identifier: NCT05865106.
Study on the correlation between IL-12p70, IL-17A and migraine in children
Authors: Yang Fan , Liu Hai-zhen , Liu Jia-ai , Chen Yao-yao , Sun Su-zhen 
Published: January 2024

ObjectiveTo compare the serum levels of 12 cytokines in migraine group, encephalitis with headache symptoms group, pneumonia without headache symptoms group and migraine subgroups to explore the cytokines associated with migraine in children and their levels.MethodsA total of 44 children with migraine, 27 children in the encephalitis group with headache symptoms and 44 children in the pneumonia group without headache symptoms were selected from January 2022 to August 2023 in Hebei Children’s Hospital. They were all tested for serum cytokines by immunofluorescence assay. The migraine group was further divided into subgroups according to different age, gender, course of disease, and presence of coinfection. The differences of serum cytokine levels among the above groups were compared, and the correlation analysis was carried out.ResultsExcept IL-5, there were no significant differences in the expression levels of other 11 inflammatory cytokines between migraine subgroups. Compared with encephalitis with headache symptoms group and pneumonia without headache symptoms group the serum levels of IL-4, TNF-α, IL-17A, and IL-12p70 were higher in migraine group than in pneumonia group, and the levels of IL-12p70 were higher than those in encephalitis group (p &lt; 0.05). An increase in serum IL-12p70 (OR = 1.267, 95%CI 1.054–1.523, p = 0.012) and IL-17A (OR = 1.066, 95%CI 1.016–1.119, p = 0.010) levels had a significant effect on migraine.ConclusionElevated serum levels of IL-12p70 and IL-17A may increase the risk of migraine in children, which has certain diagnostic and predictive value.
Fecal supernatants from dogs with idiopathic epilepsy activate enteric neurons
Authors: Elfers Kristin , Watanangura Antja , Hoffmann Pascal , Suchodolski Jan S. , Khattab Mohammad R. , Pilla Rachel , Meller Sebastian , Volk Holger A. , Mazzuoli-Weber Gemma 
Published: January 2024

IntroductionAlterations in the composition and function of the gut microbiome have been reported in idiopathic epilepsy (IE), however, interactions of gut microbes with the enteric nervous system (ENS) in this context require further study. This pilot study examined how gastrointestinal microbiota (GIM), their metabolites, and nutrients contained in intestinal contents communicate with the ENS.MethodsFecal supernatants (FS) from healthy dogs and dogs with IE, including drug-naïve, phenobarbital (PB) responsive, and PB non-responsive dogs, were applied to cultured myenteric neurons to test their activation using voltage-sensitive dye neuroimaging. Additionally, the concentrations of short-chain fatty acids (SCFAs) in the FS were quantified.ResultsOur findings indicate that FS from all examined groups elicited neuronal activation. Notably, FS from PB non-responsive dogs with IE induced action potential discharge in a higher proportion of enteric neurons compared to healthy controls, which exhibited the lowest burst frequency overall. Furthermore, the highest burst frequency in enteric neurons was observed upon exposure to FS from drug-naïve dogs with IE. This frequency was significantly higher compared to that observed in PB non-responsive dogs with IE and showed a tendency to surpass that of healthy controls.DiscussionAlthough observed disparities in SCFA concentrations across the various FS samples might be associated with the induced neuronal activity, a direct correlation remains elusive at this point. The obtained results hint at an involvement of the ENS in canine IE and set the basis for future studies.
Primary gastrinoma of the gallbladder: a case report and review of the literature
Authors: Liu Yao-Ge , Jiang Shi-Tao , Zhou Yang , Zhang Jun-Wei , Sang Xin-Ting , Zhang Lei , Lu Xin , Xu Yi-Yao 
Published: January 2024

BackgroundPrimary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported.Case presentationWe report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient’s symptoms disappeared after the surgery with a follow-up of 6 months.ConclusionsThis case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.
Adenovirus and Mycoplasma pneumoniae co-infection as a risk factor for severe community-acquired pneumonia in children
Authors: Chen Qihong , Lin Lihua , Zhang Ning , Yang Yungang 
Published: January 2024

BackgroundTo investigate the pathogenic characteristics and risk factors of pediatric severe community-acquired pneumonia (CAP).MethodsWe retrospectively analyzed the clinical data of hospitalized children with severe CAP from April 2014 to June 2019 in China. Data of age, sex and pathogenic results were collected: bacterial and fungal cultures, respiratory viruses from sputum or bronchoalveolar lavage fluid (BALF), serum Mycoplasma pneumoniae (MP)-IgM and Chlamydia Pneumoniae-IgM, and BALF or blood (1-3)-β-D-glucan/galactomannan test.ResultsA total of 679 children with severe CAP were included in the analysis. The number of cases infected with MP was higher in males than in females. There were significant differences between the ≤1-year and &gt;1-year groups in terms of pathogen. The top three bacteria cultured were Haemophilus influenzae (57/679, 8.4%), Streptococcus pneumoniae (50/679, 7.4%), and Pseudomonas aeruginosa (25/679, 3.7%). The top three viruses detected were adenovirus (AdV, 124/679, 18.3%), respiratory syncytial virus (24/679, 3.5%), and parainfluenza virus (21/679, 3.1%). AdV and MP were the leading pathogens, detected in 18.3% and 32.6% cases, respectively. MP infection increased the risk of AdV infection (OR 3.77, p &lt; 0.0001). MP infection was a risk factor for severe AdV-infected pneumonia, while sex, age, bacteria, Chlamydia Pneumoniae, fungal, and AdV infections were risk factors for severe MP-infected pneumonia.ConclusionsAdV and MP were dominant pathogens in children with severe CAP. AdV and MP infection predisposed each other to develop severe illness. AdV-MP co-infection may lead to severe pneumonia.
Tolerability, safety, and pharmacokinetics of a single intravenous administration of a novel recombinant humanized anti-interleukin-6 receptor monoclonal antibody in healthy Chinese volunteers
Authors: Jiang Xin , Lin Pingping , Sun Feifei , Xu Yi , Tao Ye , Shi Ping , Liu Yanping , Li Xin , Liu Shuqin , Gao Xiaomeng , Wang Chenjing , Cao Yu 
Published: January 2024

Aim: VDJ001 is a novel recombinant humanized monoclonal antibody against the anti-interleukin-6 receptor. As an analog of tocilizumab, it exhibited improved affinity and in vitro activity. Based on preclinical studies, a first-in-human clinical study was conducted to evaluate the safety, tolerability, and pharmacokinetics of VDJ001.Methods: This is a single-center, randomized, double-blinded, placebo-controlled phase I dose-escalation study conducted in healthy Chinese volunteers. Four cohorts were designed with dosages ranging from 1 to 8 mg/kg. There were equal numbers of female and male volunteers in each cohort. Enrolled subjects randomly received a single intravenous administration of VDJ001 or placebo (VDJ001: placebo = 4:1 in both female and male volunteers). Three sentinel volunteers in the 1 mg/kg cohort were first administered, and the treatment of the other seven volunteers was carried out after a safety assessment on D15. The following cohort was conducted only when the safety profile was evaluated as acceptable on D29 of the previous cohort. Samples for pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity were collected at specified time points and analyzed through validated methods. Adverse events and the results of the examination and laboratory were analyzed to assess the safety profile.Results: All cohorts were carried out according to the protocol. With the escalation of dosage, Cmax increased linearly, and AUC0-t and AUC0-∞ increased in a non-linear manner, while clearance decreased and t1/2 prolonged. Six volunteers who received VDJ001 tested ADA-positive, among whom one participant tested Nab-positive on D57. One volunteer in the placebo group tested ADA-positive but Nab-negative. CRP concentrations were not found to be correlated with the dosage. Both IL-6 and sIL-6R concentrations increased after the administration of VDJ001. All adverse events were mild to moderate in severity. No serious adverse events were reported in this study. No unexpected or clinically significant safety issues were found.Conclusion: The safety and tolerability of VDJ001 are acceptable with a single intravenous dosage of 1∼8 mg/kg. Further clinical trials are warranted.
Pulmonary nitric oxide in astronauts before and during long-term spaceflight
Authors: Karlsson Lars L. , Gustafsson Lars E. , Linnarsson Dag 
Published: January 2024

Introduction: During exploratory space flights astronauts risk exposure to toxic planetary dust. Exhaled nitric oxide partial pressure (PENO) is a simple method to monitor lung health by detecting airway inflammation after dust inhalation. The turnover of NO in the lungs is dependent on several factors which will be altered during planetary exploration such as gravity (G) and gas density. To investigate the impacts of these factors on normal PENO, we took measurements before and during a stay at the International Space Station, at both normal and reduced atmospheric pressures. We expected stable PENO levels during the preflight and inflight periods, with lower values inflight. With reduced pressure we expected no net changes of PENO.Material and methods: Ten astronauts were studied during the pre-flight (1 G) and inflight (µG) periods at normal pressure [1.0 ata (atmospheres absolute)], with six of them also monitored at reduced (0.7 ata) pressure and gas density. The average observation period was from 191 days before launch until 105 days after launch. PENO was measured together with estimates of alveolar NO and the airway contribution to the exhaled NO flux.Results: The levels of PENO at 50 mL/s (PENO50) were not stable during the preflight and inflight periods respectively but decreased with time (p = 0.0284) at a rate of 0.55 (0.24) [mean (SD)] mPa per 180 days throughout the observation period, so that there was a significant difference (p &lt; 0.01, N = 10) between gravity conditions. Thus, PENO50 averaged 2.28 (0.70) mPa at 1 G and 1.65 (0.51) mPa during µG (−27%). Reduced atmospheric pressure had no net impact on PENO50 but increased the airway contribution to exhaled NO.Discussion: The time courses of PENO50 suggest an initial airway inflammation, which gradually subsided. Our previous hypothesis of an increased uptake of NO to the blood by means of an expanded gas-blood interface in µG leading to decreased PENO50 is neither supported nor contradicted by the present findings. Baseline PENO50 values for lung health monitoring in astronauts should be obtained not only on ground but also during the relevant gravity conditions and before the possibility of inhaling toxic planetary dust.