bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response
Authors: Currenti Jennifer , Simmons Joshua , Oakes Jared , Gaudieri Silvana , Warren Christian M. , Gangula Rama , Alves Eric , Ram Ramesh , Leary Shay , Armitage Jesse D. , Smith Rita M. , Chopra Abha , Halasa Natasha B. , Pilkinton Mark A. , Kalams Spyros A. 
Published: March 2023

IntroductionA vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear.MethodsIn this study, we examined the T cell receptor (TCR) repertoire and transcriptional profile of vaccine-induced expanded cTfh cells in individuals who received sequential seasonal influenza vaccines. We measured the magnitude of cTfh and plasmablast cell activation from day 0 (d0) to d7 post-vaccination as an indicator of a vaccine response. To assess TCR diversity and T cell expansion we sorted activated and resting cTfh cells at d0 and d7 post-vaccination and performed TCR sequencing. We also single cell sorted activated and resting cTfh cells for TCR analysis and transcriptome sequencing.Results and discussionThe percent of activated cTfh cells significantly increased from d0 to d7 in each of the 2016-17 (p &lt; 0.0001) and 2017-18 (p = 0.015) vaccine seasons with the magnitude of cTfh activation increase positively correlated with the frequency of circulating plasmablast cells in the 2016-17 (p = 0.0001) and 2017-18 (p = 0.003) seasons. At d7 post-vaccination, higher magnitudes of cTfh activation were associated with increased clonality of cTfh TCR repertoire. The TCRs from vaccine-expanded clonotypes were identified and tracked longitudinally with several TCRs found to be present in both years. The transcriptomic profile of these expanded cTfh cells at the single cell level demonstrated overrepresentation of transcripts of genes involved in the type-I interferon pathway, pathways involved in gene expression, and antigen presentation and recognition. These results identify the expansion and transcriptomic profile of vaccine-induced cTfh cells important for B cell help.
γδ T cells recruitment and local proliferation in brain parenchyma benefit anti-neuroinflammation after cerebral microbleeds
Authors: Su Xin , Yang Shuxian , Li Yanxiang , Xiang Zongqin , Tao Qiao , Liu Shengde , Yin Zhinan , Zhong Liyun , Lv Xiaoxu , Zhou Libing 
Published: March 2023

BackgroundCerebral microbleeds (CMBs) are an early sign of many neurological disorders and accompanied by local neuroinflammation and brain damage. As important regulators of immune response and neuroinflammation, the biological behavior and role of γδ T cells after CMBs remain largely unknown.MethodsWe made a spot injury of microvessel in the somatosensory cortex to mimic the model of CMBs by two-photon laser and in vivo tracked dynamical behaviors of γδ T cells induced by CMBs using TCR-δGFP transgenic mice. Biological features of γδ T cells in the peri-CMBs parenchyma were decoded by flow cytometry and Raman spectra. In wildtype and γδ T cell-deficient mice, neuroinflammation and neurite degeneration in the peri-CMBs cortex were studied by RNAseq, immunostaining and in vivo imaging respectively.ResultsAfter CMBs, γδ T cells in the dural vessels were tracked to cross the meningeal structure and invade the brain parenchyma in a few days, where the division process of γδ T cells were captured. Parenchymal γδ T cells were highly expressed by CXCR6 and CCR6, similar to meningeal γδ T cells, positive for IL-17A and Ki67 (more than 98%), and they contained abundant substances for energy metabolism and nucleic acid synthesis. In γδ T cell-deficient mice, cortical samples showed the upregulation of neuroinflammatory signaling pathways, enhanced glial response and M1 microglial polarization, and earlier neuronal degeneration in the peri-CMBs brain parenchyma compared with wildtype mice.ConclusionCMBs induce the accumulation and local proliferation of γδ T cells in the brain parenchyma, and γδ T cells exert anti-neuroinflammatory and neuroprotective effects at the early stage of CMBs.
The macrophages regulate intestinal motility dysfunction through the PGE2 Ptger3 axis during Klebsiella pneumonia sepsis
Authors: Yao Hua , Fu Xin , Xu Qian , Li Tingting , Li Yao , Kang Yan , Wu Qin 
Published: March 2023

IntroductionGut motility dysfunction, the most common complication of post-septic organ dysfunction, depends on immune and neuronal cells. This study aimed to investigate the mechanisms that activate these cells and the contribution of macrophages to the recovery of intestinal motility dysfunction after sepsis.Materials and methodsPostoperative gut motility dysfunction was induced by establishing Klebsiella pneumonia sepsis in mice with selective deletion of neutrophils and macrophages in the gut. The distribution of orally administered fluorescein isothiocyanate-dextran and carmine excretion time was used to determine the severity of small bowel disease. The effect of macrophages on intestinal motility was evaluated after prostaglandin E2 therapy.ResultsWe found that muscular neutrophil infiltration leading to neuronal loss in the intestine muscle triggered intestinal motility dysfunction after pneumonia sepsis; however, reduced neutrophil infiltration did not improve intestinal motility dysfunction. Moreover, macrophage depletion aggravated gut motility dysfunction. The addition of macrophages directly to a smooth muscle was responsible for the recovery of intestinal motility.ConclusionOur results suggest that a direct interaction between macrophages and smooth muscle is neurologically independent of the restoration of intestinal dysmotility.
Impact of initial chemotherapy cycles and clinical characteristics on outcomes for HIV-associated diffuse large B cell lymphoma patients: The Central and Western China AIDS Lymphoma League 001 study (CALL-001 study)
Authors: Wang Chaoyu , Wu Yan , Liu Jun , Min Haiyan , Huang Yunhong , Wei Guo , Zhang Wei , Wang Min , Tang Xiaoqiong , Zhou Hui , Chen Yaokai , Liu Yao 
Published: March 2023

IntroductionLittle is known about the first line induction chemotherapy cycles for HIV-associated diffuse large B-cell lymphoma (DLBCL) as these are less common than HIV-negative lymphoma. Currently, the optimal treatment cycles option remains undefined. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-associated DLBCL patients in different treatment modes in China.MethodsTotally 273 newly diagnosed HIV-associated DLBCL patients at eleven large academic centers from October 2008 to October 2021, were analyzed.ResultsIn the entire cohort, the median age was 47 years (range, 21-90) at lymphoma diagnosis, and 223 patients were male (81.7%). One hundred and ninety-four (71.1%) patients were germinal center B-cell-like lymphoma (GCB) subtype. Most patients (65.2%, 178/273) had elevated lactate dehydrogenase (LDH), and advanced Ann Arbor stage (78.9% 213/273) at diagnosis. High international prognostic index (IPI) score (3-5) at diagnosis was found in 65.2% (178/273) of patients. One hundred and fifty-five patients (56.8%) had extranodal involvement. The median CD4 cell count was 168/μl (range, 2-1067), of whom 174 (63.7%) had a CD4 cell count below 200/μl. The median follow‐up of our cohort was 10.1 (0.1-160) months. The overall 2-year OS rates 58.0%. Median OS times in the 0, 1-3, 4-6, and &gt;6 cycles chemotherapy cohort were 7.1 months, 20.0 months, not reached, and not reached, respectively (Hazard Ratio (HR)=0.549, 95% Confidence interval (CI) 0.451-0.667; p&lt;0.001). Cox multivariate analysis showed that age ≥60 (HR=2.207, 95%CI 1.321-3.690; p=0.003), high IPI score (3-5) (HR=2.926, 95% CI 1.716-4.988; p&lt;0.001), B symptoms (HR=1.928, 95%CI 1.192-3.119; p=0.007), elevated LDH (HR=1.696, 95%CI 1.031-2.791; p=0.038) and received less than 4 cycles chemotherapy (HR=0.520, 95%CI 0.424-0.637; p&lt;0.001) were independent risk factor for adverse prognosis based on overall survival (OS).DiscussionThese results demonstrated that 4-6 cycles chemotherapy were significantly associated with improved outcomes in HIV-associated DLBCL patients. However, &gt;6 cycles chemotherapy did not further improve the survival of patients.
Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome
Authors: Roufosse Florence , Butterfield Joseph , Steinfeld Jonathan , Bentley Jane H. , von Maltzahn Robyn , Kwon Namhee , Nelsen Linda 
Published: March 2023

BackgroundHypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems.ObjectivesTo assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES.MethodsEach of the six HES-related symptoms were rated (0–10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo.ResultsMepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms.ConclusionThese data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients.
Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis
Authors: Mousavi Soraya , Weschka Dennis , Bereswill Stefan , Heimesaat Markus M. 
Published: March 2023

IntroductionGiven the worldwide increasing prevalence of human Campylobacter jejuni infections and the emergence of multi-drug resistant enteropathogenic strains, antibiotic-independent approaches applying non-toxic natural compounds for the treatment and prophylaxis of campylobacteriosis appear utmost desirable. In our placebo-controlled intervention study, we surveyed potential disease-alleviating including anti-pathogenic and immune-modulatory effects upon prophylactic oral application of lemon-essential oil (LEM-EO) and coriander-essential oil (COR-EO) in acute experimental campylobacteriosis.MethodsTherefore, secondary abiotic IL-10−/− mice were orally challenged with either LEM-EO or COR-EO starting seven days prior to peroral C. jejuni infection.Results and discussionSix days post-infection, slightly lower pathogen loads were assessed in the colon of mice from the LEM-EO as opposed to the COR-EO cohort if compared to placebo counterparts. Prophylactic application of both EOs improved the clinical outcome of acute campylobacteriosis which was paralleled by less distinct pathogen-induced colonic epithelial cell apoptosis. Moreover, mice subjected to LEM-EO and COR-EO prophylaxis displayed lower colonic numbers of macrophages/monocytes and of T lymphocytes, respectively, whereas in both verum groups, basal IL-6 and IFN-γ concentrations were measured in mesenteric lymph nodes on day 6 post-infection. The oral challenge with either EOs resulted in diminished secretion of distinct pro-inflammatory mediators in the kidney as well as serum samples derived from the infected mice. In conclusion, the results from our preclinical in vivo study provide evidence that LEM-EO and COR-EO constitute promising prophylactic measures to prevent severe campylobacteriosis which may help to reduce the risk for development of post-infectious sequelae in C. jejuni infected individuals.
DNA accelerates the protease inhibition of a bacterial serpin chloropin
Authors: Xu Jiawei , Ye Wei , Yang Ting Ting , Yan Teng , Cai Haiyan , Zhou Aiwu , Yang Yufeng 
Published: March 2023

Serine protease inhibitors (Serpins) are the most widely distributed protease inhibitors in nature and have been identified from all kingdoms of life. Eukaryotic serpins are most abundant with their activities often subject to modulation by cofactors; however, little is known about the regulation of prokaryotic serpins. To address this, here we prepared a recombinant bacteria serpin, termed chloropin, derived from green sulfur bacteria Chlorobium limicola and solved its crystal structure at 2.2 Å resolution. This showed a canonical inhibitory serpin conformation of native chloropin with a surface-exposed reactive loop and a large central beta-sheet. Enzyme activity analysis showed that chloropin could inhibit multiple proteases, such as thrombin and KLK7 with second order inhibition rate constants at 2.5×104 M−1s−1 and 4.5×104 M−1s−1 respectively, consistent with its P1 arginine residue. Heparin could accelerate the thrombin inhibition by ∼17-fold with a bell-shaped dose-dependent curve as seen with heparin-mediated thrombin inhibition by antithrombin. Interestingly, supercoiled DNA could accelerate the inhibition of thrombin by chloropin by 74-fold, while linear DNA accelerated the reaction by 142-fold through a heparin-like template mechanism. In contrast, DNA did not affect the inhibition of thrombin by antithrombin. These results indicate that DNA is likely a natural modulator of chloropin protecting the cell from endogenous or exogenous environmental proteases, and prokaryotic serpins have diverged during evolution to use different surface subsites for activity modulation.
A rapid direct-differential agglutination assay for Brucella detection using antibodies conjugated with functionalized gold nanoparticles
Authors: Hans Richa , Yadav Pranjal Kumar , Zaman M. Burhanuz , Poolla Rajaram , Thavaselvam Duraipandian 
Published: March 2023

Brucellosis is the most widespread and serious zoonotic disease worldwide which affects livestock, sylvatic wildlife, marine dwellers, and humans. It is acquired through Alphaproteobacteria which belong to the genus Brucella and is categorized as a potential bio-threat agent. In this study, we developed a rapid and direct differential whole cell (WC) agglutination-based assay for its on-field detection. The recombinant outer membrane (rOmp28) protein-derived specific mice IgG polyclonal antibodies (pAbs) of Brucella were purified using affinity chromatography and conjugated with functionalized gold nanoparticles (AuNPs) for rapid agglutination. A positive blot of 32 kDa protein revealed specific immuno-reactivity of rOmp28-pAbs using immunoblot analysis. For the synthesis of AuNPs, the conventional “Turkevich method” was optimized at a concentration &lt; 1 mM of gold precursor for obtaining 50-nm-sized particles. Also, their physico-chemical characteristics were analyzed using UV-visible spectrophotometry, Fourier transform infra-red spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential (ζ, ZP), and fluorescence spectroscopy. Furthermore, these AuNPs were functionalized with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to prepare modified carboxylated AuNPs. For bioconjugation with Brucella rOmp28 IgG pAbs, antibody-conjugated functionalized AuNP constructs were prepared and characterized using FT-IR analysis with strong N–H deformations. Subsequently, these bioconjugated AuNPs were used to develop a direct-differential slide agglutination assay with a detection limit of 104 CFU mL−1. The sensitivity of this assay was compared with standard double-antibody sandwich ELISA (S-ELISA) using rOmp28 IgG pAbs with an LOD of 103 CFU mL−1 and a detection range of 102–108 CFU mL−1. No intraspecies cross-reactivity was observed based on evaluation of its specificity with a battery of closely related bacterial species. In conclusion, the increased sensitivity and specificity of the developed agglutination assay obtained using bioconjugated functionalized AuNPs is ≥ 98% for the detection of Brucella. Therefore, it can be used as an alternate rapid method of direct WC detection of bacteria as it is simple, robust, and cost-effective, with minimal time of reaction in the case of early disease diagnosis.
Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro
Authors: Adams Alexandra A. , Li Ying , Kim Haesun A. , Pfister Bryan J. 
Published: March 2023

Introduction:In vitro models of traumatic brain injury (TBI) commonly use neurons isolated from the central nervous system. Limitations with primary cortical cultures, however, can pose challenges to replicating some aspects of neuronal injury associated with closed head TBI. The known mechanisms of axonal degeneration from mechanical injury in TBI are in many ways similar to degenerative disease, ischemia, and spinal cord injury. It is therefore possible that the mechanisms that result in axonal degeneration in isolated cortical axons after in vitro stretch injury are shared with injured axons from different neuronal types. Dorsal root ganglia neurons (DRGN) are another neuronal source that may overcome some current limitations including remaining healthy in culture for long periods of time, ability to be isolated from adult sources, and myelinated in vitro.Methods: The current study sought to characterize the differential responses between cortical and DRGN axons to mechanical stretch injury associated with TBI. Using an in vitro model of traumatic axonal stretch injury, cortical and DRGN neurons were injured at a moderate (40% strain) and severe stretch (60% strain) and acute alterations in axonal morphology and calcium homeostasis were measured.Results: DRGN and cortical axons immediately form undulations in response to severe injury, experience similar elongation and recovery within 20 min after the initial injury, and had a similar pattern of degeneration over the first 24 h after injury. Additionally, both types of axons experienced comparable degrees of calcium influx after both moderate and severe injury that was prevented through pre-treatment with tetrodotoxin in cortical neurons and lidocaine in DRGNs. Similar to cortical axons, stretch injury also causes calcium activated proteolysis of sodium channel in DRGN axons that is prevented by treatment with lidocaine or protease inhibitors.Discussion: These findings suggest that DRGN axons share the early response of cortical neurons to a rapid stretch injury and the associated secondary injury mechanisms. The utility of a DRGN in vitro TBI model may allow future studies to explore TBI injury progression in myelinated and adult neurons.
Spatial CT perfusion data helpful in automatically locating vessel occlusions for acute ischemic stroke patients
Authors: Peerlings Daan , de Jong Hugo W. A. M. , Bennink Edwin , Dankbaar Jan W. , Velthuis Birgitta K. , Emmer Bart J. , Majoie Charles B. L. M. , Marquering Henk A. 
Published: March 2023

IntroductionLocating a vessel occlusion is important for clinical decision support in stroke healthcare. The advent of endovascular thrombectomy beyond proximal large vessel occlusions spurs alternative approaches to locate vessel occlusions. We explore whether CT perfusion (CTP) data can help to automatically locate vessel occlusions.MethodsWe composed an atlas with the downstream regions of particular vessel segments. Occlusion of these segments should result in the hypoperfusion of the corresponding downstream region. We differentiated between seven-vessel occlusion locations (ICA, proximal M1, distal M1, M2, M3, ACA, and posterior circulation). We included 596 patients from the DUtch acute STroke (DUST) multicenter study. Each patient CTP data set was processed with perfusion software to determine the hypoperfused region. The downstream region with the highest overlap with the hypoperfused region was considered to indicate the vessel occlusion location. We assessed the indications from CTP against expert annotations from CTA.ResultsOur atlas-based model had a mean accuracy of 86% and could achieve substantial agreement with the annotations from CTA according to Cohen's kappa coefficient (up to 0.68). In particular, anterior large vessel occlusions and occlusions in the posterior circulation could be located with an accuracy of 80 and 92%, respectively.ConclusionThe spatial layout of the hypoperfused region can help to automatically indicate the vessel occlusion location for acute ischemic stroke patients. However, variations in vessel architecture between patients seemed to limit the capacity of CTP data to distinguish between vessel occlusion locations more accurately.
Global research on cancer and sleep: A bibliometric and visual analysis of the last two decades
Authors: Sun Jiaru , Wang Caihua , Hui Zhaozhao , Han Wenjin , Wang Xiaoqin , Wang Mingxu 
Published: March 2023

ObjectiveThe study aimed to analyze the research status, hotspots, and frontiers of global research on cancer and sleep through bibliometrics and provide references and guidance for future research.MethodsThe literature regarding cancer and sleep from 2002 to 2022 was searched from the Web of Science Core Collection (WoSCC) database. CiteSpace 5.6.R3 was performed for visualization analysis.ResultsA total of 1,172 publications were identified. The number of publications in the field has gradually increased over the past two decades. The United States had the most prominent contributions. Taipei Medical University and the University of California, San Francisco, and David Gozal were the most prolific institutions and author, respectively. The most published academic journal was Supportive Care in Cancer. The research hotspots can be summarized into the symptom cluster intervention for cancer survivors and the association between cancer and melatonin and/or obstructive sleep apnea (OSA). The complex interaction between cancer and sleep disruption and the influencing factors of sleep quality may be the emerging trends of research.ConclusionThis study systematically analyzed the hotspots and frontiers in the field of cancer and sleep and called for strengthening cooperation among countries, institutions, and authors. In addition, intervention measures for the cancer symptom cluster, the bioavailability of exogenous melatonin, the causal relationship between OSA and cancer, the mechanism of tumor-induced sleep disruption, the dose–response relationship between sleep duration and cancer risk, and the path relationship between sleep quality influencing factors may be the focus of future research.