bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Pichinde viral vector expressing tuberculosis antigens elicits strong T cell responses and protection in mice
Authors: Kirk Natalie M. , Huang Qinfeng , Vrba Sophia , Rahman Mizanur , Block Alisha M. , Murphy Hannah , White Dylan W. , Namugenyi Sarah B. , Ly Hinh , Tischler Anna D. , Liang Yuying 
Published: February 2023

IntroductionTuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a major global health threat. The only available vaccine Bacille Calmette-Guérin (BCG) does not prevent adult pulmonary TB. New effective TB vaccines should aim to stimulate robust T cell responses in the lung mucosa to achieve high protective efficacy. We have previously developed a novel viral vaccine vector based on recombinant Pichinde virus (PICV), a non-pathogenic arenavirus with low seroprevalence in humans, and have demonstrated its efficacy to induce strong vaccine immunity with undetectable anti-vector neutralization activity.MethodsUsing this tri-segmented PICV vector (rP18tri), we have generated viral vectored TB vaccines (TBvac-1, TBvac-2, and TBvac-10) encoding several known TB immunogens (Ag85B, EsxH, and ESAT-6/EsxA). A P2A linker sequence was used to allow for the expression of two proteins from one open-reading-frame (ORF) on the viral RNA segments. The immunogenicity of TBvac-2 and TBvac-10 and the protective efficacy of TBvac-1 and TBvac-2 were evaluated in mice.ResultsBoth viral vectored vaccines elicited strong antigen-specific CD4 and CD8 T cells through intramuscular (IM) and intranasal (IN) routes as evaluated by MHC-I and MHC-II tetramer analyses, respectively. The IN inoculation route helped to elicit strong lung T cell responses. The vaccine-induced antigen-specific CD4 T cells are functional, expressing multiple cytokines as detected by intracellular cytokine staining. Finally, immunization with TBvac-1 or TBvac-2, both expressing the same trivalent antigens (Ag85B, EsxH, ESAT6/EsxA), reduced Mtb lung tissue burden and dissemination in an aerosol challenge mouse model.ConclusionsThe novel PICV vector-based TB vaccine candidates can express more than two antigens via the use of P2A linker sequence and elicit strong systemic and lung T cell immunity with protective efficacy. Our study suggests the PICV vector as an attractive vaccine platform for the development of new and effective TB vaccine candidates.
Investigation and optimization of methane purification method for natural gas by two-column gas chromatography: A preliminary test for doubly substituted isotopologue (13CH3D) measurements
Authors: Sun Tiantian , Cao Jun , Qiu Haijun , Fu Piaoer , Lu Hailong , Ning Zijie , Chen Daohua , Deng Yinan , Yang Shengxiong 
Published: February 2023

In this study, optimization of the methane purification method by gas chromatography (GC) is described for the determination of methane clumped isotope compositions of natural gas. Methane was purified under the carrying of helium on the assembly line composed of a vacuum apparatus and two-column gas chromatography. Once methane was detected by the passive thermal conductivity detector (TCD) on the GC, it was collected through a silica trap immersed in liquid nitrogen. Optimum conditions of chromatographic column diameter (1/4 inch outside diameter), temperature (25 °C), and flow rate (50.8 ml min-1) have been determined. When N2/CH4 (by volume) is&lt;8.7%, the purification experiment can be undertaken once, while a double purification experiment is required when natural gas samples have an N2/CH4 of 8.7-78.0%. The purification method yielded a purity of 98.4-98.8% with a recovery of 97.3-98.7% on purified methane samples verified by GC determination. N2 was the main source that contributed to the loss of the purity, however, the N-bearing isobaric interferences (14NH3+ and 14NH4+) in purified samples presented&lt;1‰ intensity compared to the methane isotopologues (13CH4+ and 13CH3D+), thus we concluded that these interferences have no impact on clumped isotope determinations. The conventional δ13CVPDB and δDVSMOW values of purified methane samples were consistent with those of pure methane. A preliminary measurement of Δ13CH3D (working gas) of purified samples revealed differences of -0.27‰, which was within the internal precision of the measurement. The entire process of a single purification can be completed within two hours. Our proposed method could be used for the clumped isotope purification of natural gas with higher than ~50% methane.
Ginger Extract Decreases Susceptibility to Dextran Sulfate Sodium-Induced Colitis in Mice Following Early Antibiotic Exposure
Authors: Zhou Xinghong , Liu Xiaoyu , He Qiuxing , Wang Ming , Lu Hanqi , You Yanting , Chen Liqian , Cheng Jingru , Li Fei , Fu Xiuqiong , Kwan Hiu Yee , Zhou Lin , Zhao Xiaoshan 
Published: February 2023

Background: Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years.Methods: A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels.Results: Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family Peptococcaceae and Helicobacter species to modulate microbiota structure and composition adversely affected by early antibiotic exposure.Conclusion: Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life.
SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort
Authors: Roy-Vallejo Emilia , Cardeñoso Laura , Triguero-Martínez Ana , Chicot Llano Marta , Zurita Nelly , Ávalos Elena , Barrios Ana , Hernando Julia , Ortiz Javier , Rodríguez-García Sebastián C. , Ciudad Sañudo Marianela , Marcos Celeste , García Castillo Elena , Fontán García-Rodrigo Leticia , González Begoña , Méndez Rosa , Iturrate Isabel , Sanz-García Ancor , Villa Almudena , Sánchez-Azofra Ana , Quicios Begoña , Arribas David , Álvarez Rodríguez Jesús , Patiño Pablo , Trigueros Marina , Uriarte Miren , Martín-Ramírez Alexandra , Arévalo Román Cristina , Galván-Román José María , García-Vicuña Rosario , Ancochea Julio , Muñoz-Calleja Cecilia , Fernández-Ruiz Elena , de la Cámara Rafael , Suárez Fernández Carmen , González-Álvaro Isidoro , Rodríguez-Serrano Diego A. ,   the PREDINMUN-COVID Group
Published: February 2023

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with &gt; 1.3 log10 copies/ml) and also in those with at least one IL6 &gt; 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.
Decision-making support systems on extended hospital length of stay: Validation and recalibration of a model for patients with AMI
Authors: Xavier Joana , Seringa Joana , Pinto Fausto José , Magalhães Teresa 
Published: February 2023

BackgroundCardiovascular diseases are still a significant cause of death and hospitalization. In 2019, circulatory diseases were responsible for 29.9% of deaths in Portugal. These diseases have a significant impact on the hospital length of stay. Length of stay predictive models is an efficient way to aid decision-making in health. This study aimed to validate a predictive model on the extended length of stay in patients with acute myocardial infarction at the time of admission.MethodsAn analysis was conducted to test and recalibrate a previously developed model in the prediction of prolonged length of stay, for a new set of population. The study was conducted based on administrative and laboratory data of patients admitted for acute myocardial infarction events from a public hospital in Portugal from 2013 to 2015.ResultsComparable performance measures were observed upon the validation and recalibration of the predictive model of extended length of stay. Comorbidities such as shock, diabetes with complications, dysrhythmia, pulmonary edema, and respiratory infections were the common variables found between the previous model and the validated and recalibrated model for acute myocardial infarction.ConclusionPredictive models for the extended length of stay can be applied in clinical practice since they are recalibrated and modeled to the relevant population characteristics.
Arbuscular mycorrhizal fungus changes alfalfa response to pathogen infection activated by pea aphid infestation
Authors: Wang Yajie , Li Yingde , Duan Tingyu 
Published: February 2023

IntroductionArbuscular mycorrhizal (AM) fungi are important for the resistance of plants to insect infestation and diseases. However, the effect of AM fungal colonization of plants response to pathogen infection activated by pea aphid infestation is unknown. Pea aphid (Acyrthosiphon pisum) and the fungal pathogen Phoma medicaginis severely limit alfalfa production worldwide.MethodsThis study established an alfalfa (Medicago sativa)–AM fungus (Rhizophagus intraradices)–pea aphid–P. medicaginis experimental system to clarify the effects of an AM fungus on the host plant response to insect infestation and subsequent fungal pathogen infection.ResultsPea aphid increased the disease incidence of P. medicaginis by 24.94%. The AM fungus decreased the disease index by 22.37% and enhanced alfalfa growth by increasing the uptake of total nitrogen and total phosphorus. The aphid induced polyphenol oxidase activity of alfalfa, and the AM fungus enhanced plant-defense enzyme activity against aphid infestation and subsequent P. medicaginis infection. In addition, the AM fungus increased the contents of jasmonic acid and abscisic acid in plants exposed to aphid infestation or pathogen infection. Abscisic acid and genes associated with the gene ontology term “hormone binding” were upregulated in aphid-infested or pathogen-infected alfalfa.DiscussionThe results demonstrate that an AM fungus enhances plant defense and signaling components induced by aphid infestation, which may contribute to improved defense against subsequent pathogen infection.
Brachial plexus avulsion induced changes in gut microbiota promotes pain related anxiety-like behavior in mice
Authors: Zhang Jian-lei , Xian Hang , Zhao Rui , Luo Ceng , Xie Rou-gang , Tian Tong , Cong Rui 
Published: February 2023

IntroductionBrachial plexus avulsion (BPA) injury develops frequent and intense neuropathic pain, involving in both peripheral and central nervous systems. The incidence of anxiety or depression caused by BPA-induced neuropathic pain is high, but the underlying mechanism remains unclear.MethodsWe established a BPA mice model and assessed its negative emotions through behavioral tests. To further explore the role of the microbiota-gut-brain axis in the unique emotional behavior after BPA, we performed intestinal fecal 16s and metabolomics assays. Psychobiotics (PB) supplementation was administered to BPA mice to check the probiotics effects on BPA-induced anxiety behaviors.ResultsPain related anxiety-like behavior was observed at the early stage after BPA (7 days), while no depression-like behavior was detected. Intriguingly, gut microbiota diversity was increased in BPA mice, and the most abundant probiotics, Lactobacillus, showed obvious changes. Lactobacillus_reuteri was significantly decreased in BPA mice. Metabolomics analysis showed that Lactobacillus_reuteri-related bile acid pathway and some neurotransmitter amino acids were significantly altered. Further PB (dominated by Lactobacillus_reuteri) supplementation could significantly relieve BPA-induced anxiety-like behaviors in mice.ConclusionOur study suggests that pathological neuralgia after BPA could alter intestinal microbiota diversity, especially Lactobacillus, and the changes in neurotransmitter amino acid metabolites may be the key reason for the onset of anxiety-like behaviors in BPA mice.
Systemic inflammation response index predicts 3-month outcome in patients with mild acute ischemic stroke receiving intravenous thrombolysis
Authors: Chu Min , Luo Yunhe , Wang Daosheng , Liu Yang , Wang Delong , Wang Yong , Zhao Jing 
Published: February 2023

IntroductionA crucial aspect of stroke progression is the inflammatory response. As novel inflammatory and prognostic markers, the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI) have recently been studied. The objective of our study was to evaluate the prognostic value of SII and SIRI in mild acute ischemic stroke (AIS) patients following intravenous thrombolysis (IVT).MethodsOur study screened the clinical data of patients with mild AIS admitted to the Minhang Hospital of Fudan University for retrospective analysis. The SIRI and SII were examined by the emergency laboratory before IVT. Functional outcome was evaluated 3 months after the onset of stroke using the modified Rankin Scale (mRS). mRS ≥ 2 was defined as an unfavorable outcome. The relationship between SIRI and SII and the 3-month prognosis was determined using both univariate and multivariate analysis. Receiver operating characteristic curve was performed to evaluate the predictive value of SIRI for AIS prognosis.ResultsA total of 240 patients were included in this study. Both SIRI and SII were higher in the unfavorable outcome group than in the favorable outcome group [1.28 (0.70–1.88) vs. 0.79 (0.51–1.08), P &lt; 0.001 and 531.93 (377.55–797.12) vs. 397.23 (263.32–577.65), P &lt; 0.001]. Multivariate logistic regression analyses showed that SIRI was significantly associated with 3-month unfavorable outcome of mild AIS patients [odds ratio (OR) = 2.938, 95% confidence interval (CI) = 1.805–4.782, P &lt; 0.001], conversely, SII had no prognostic value. When SIRI combined with the established clinical factors, the area under the curve (AUC) showed a significant improvement (0.773 vs. 0.683, P for comparison = 0.0017).ConclusionsHigher SIRI could be valuable in predicting poor clinical outcomes for patients with mild AIS following IVT.
EXODUS: Stable and efficient training of spiking neural networks
Authors: Bauer Felix C. , Lenz Gregor , Haghighatshoar Saeid , Sheik Sadique 
Published: February 2023

IntroductionSpiking Neural Networks (SNNs) are gaining significant traction in machine learning tasks where energy-efficiency is of utmost importance. Training such networks using the state-of-the-art back-propagation through time (BPTT) is, however, very time-consuming. Previous work employs an efficient GPU-accelerated backpropagation algorithm called SLAYER, which speeds up training considerably. SLAYER, however, does not take into account the neuron reset mechanism while computing the gradients, which we argue to be the source of numerical instability. To counteract this, SLAYER introduces a gradient scale hyper parameter across layers, which needs manual tuning.MethodsIn this paper, we modify SLAYER and design an algorithm called EXODUS, that accounts for the neuron reset mechanism and applies the Implicit Function Theorem (IFT) to calculate the correct gradients (equivalent to those computed by BPTT). We furthermore eliminate the need for ad-hoc scaling of gradients, thus, reducing the training complexity tremendously.ResultsWe demonstrate, via computer simulations, that EXODUS is numerically stable and achieves comparable or better performance than SLAYER especially in various tasks with SNNs that rely on temporal features.
Deep learning-based algorithm improves radiologists’ performance in lung cancer bone metastases detection on computed tomography
Authors: Huo Tongtong , Xie Yi , Fang Ying , Wang Ziyi , Liu Pengran , Duan Yuyu , Zhang Jiayao , Wang Honglin , Xue Mingdi , Liu Songxiang , Ye Zhewei 
Published: February 2023

PurposeTo develop and assess a deep convolutional neural network (DCNN) model for the automatic detection of bone metastases from lung cancer on computed tomography (CT)MethodsIn this retrospective study, CT scans acquired from a single institution from June 2012 to May 2022 were included. In total, 126 patients were assigned to a training cohort (n = 76), a validation cohort (n = 12), and a testing cohort (n = 38). We trained and developed a DCNN model based on positive scans with bone metastases and negative scans without bone metastases to detect and segment the bone metastases of lung cancer on CT. We evaluated the clinical efficacy of the DCNN model in an observer study with five board-certified radiologists and three junior radiologists. The receiver operator characteristic curve was used to assess the sensitivity and false positives of the detection performance; the intersection-over-union and dice coefficient were used to evaluate the segmentation performance of predicted lung cancer bone metastases.ResultsThe DCNN model achieved a detection sensitivity of 0.894, with 5.24 average false positives per case, and a segmentation dice coefficient of 0.856 in the testing cohort. Through the radiologists-DCNN model collaboration, the detection accuracy of the three junior radiologists improved from 0.617 to 0.879 and the sensitivity from 0.680 to 0.902. Furthermore, the mean interpretation time per case of the junior radiologists was reduced by 228 s (p = 0.045).ConclusionsThe proposed DCNN model for automatic lung cancer bone metastases detection can improve diagnostic efficiency and reduce the diagnosis time and workload of junior radiologists.
The superior cervical ganglion is involved in chronic chemoreflex sensitization during recovery from acute lung injury
Authors: Kamra Kajal , Karpuk Nikolay , Zucker Irving H. , Schultz Harold D. , Wang Han-Jun 
Published: February 2023

Introduction: Acute lung injury (ALI) initiates an inflammatory cascade that impairs gas exchange, induces hypoxemia, and causes an increase in respiratory rate (fR). This stimulates the carotid body (CB) chemoreflex, a fundamental protective reflex that maintains oxygen homeostasis. Our previous study indicated that the chemoreflex is sensitized during the recovery from ALI. The superior cervical ganglion (SCG) is known to innervate the CB, and its electrical stimulation has been shown to significantly sensitize the chemoreflex in hypertensive and normotensive rats. We hypothesized that the SCG is involved in the chemoreflex sensitization post-ALI.Methods: We performed a bilateral SCG ganglionectomy (SCGx) or sham-SCGx (Sx) in male Sprague Dawley rats 2 weeks before inducing ALI (Week −2 i.e., W-2). ALI was induced using a single intra-tracheal instillation of bleomycin (bleo) (day 1). Resting-fR, Vt (Tidal Volume), and V̇ E (Minute Ventilation) were measured. The chemoreflex response to hypoxia (10% O2, 0% CO2) and normoxic-hypercapnia (21% O2, 5% CO2) were measured before surgery on W (−3), before bleo administration on W0 and on W4 post-bleo using whole-body plethysmography (WBP).Results: SCGx did not affect resting fR, Vt and V̇E as well as the chemoreflex responses to hypoxia and normoxic hypercapnia in either group prior to bleo. There was no significant difference in ALI-induced increase in resting fR between Sx and SCGx rats at W1 post-bleo. At W4 post-bleo, there were no significant differences in resting fR, Vt, and V̇E between Sx and SCGx rats. Consistent with our previous study, we observed a sensitized chemoreflex (delta fR) in response to hypoxia and normoxic hypercapnia in Sx rats at W4 post-bleo. However, at the same time, compared to Sx rats, the chemoreflex sensitivity was significantly less in SCGx rats in response to either hypoxia or normoxic hypercapnia.Discussion: These data suggest that SCG is involved in the chemoreflex sensitization during ALI recovery. Further understanding of the underlying mechanism will provide important information for the long-term goal of developing novel targeted therapeutic approaches to pulmonary diseases to improve clinical outcomes.
Effects on stone cell development and lignin deposition in pears by different pollinators
Authors: Yan Chongchong , Zhang Nan , Xu Chao , Jin Qing , Qi Yongjie , Cai Yongping 
Published: February 2023

IntroductionThe pear pulp is formed by the development of the ovary wall, which is the somatic cell of the female parent, and its genetic traits are identical to those of the female parent, so that its phenotypic traits should also be identical to those of the female parent. However, the pulp quality of most pears, especially the stone cell clusters (SCCs) number and degree of polymerization (DP), were significantly affected by the paternal type. Stone cells are formed by the deposition of lignin in parenchymal cell (PC) walls. Studies on the effect of pollination on lignin deposition and stone cell formation in pear fruit have not been reported. Methods: In this study, 'Dangshan Su' (P. bretschneideri Rehd.) was selected as the mother tree, while 'Yali' (P. bretschneideri Rehd.) and 'Wonhwang' (P. pyrifolia Nakai.) were used as the father trees to perform cross-pollination. We investigated the effects of different parents on SCCs number and DP, and lignin deposition by microscopic and ultramicroscopic observation.Results and DiscussionThe results showed that the formation of SCCs proceeds was consistent in DY and DW, but the SCC number and DP in DY were higher than that in DW. Ultramicroscopy revealed that the lignification process of DY and DW were all from corner to rest regions of the compound middle lamella and the secondary wall, with lignin particles deposited along the cellulose microfibrils. They were alternatively arranged until they filled up the whole cell cavity to culminate in the formation of stone cells. However, the compactness of the wall layer of cell wall was significantly higher in DY than in DW. We also found that the pit of stone cell was predominantly single pit pair, they transported degraded material from the PCs that were beginning to lignify out of the cells. Stone cell formation and lignin deposition in pollinated pear fruit from different parents were consistent, but the DP of SCCs and the compactness of the wall layer were higher in DY than that in DW. Therefore, DY SCC had a higher ability to resist the expansion pressure of PC.