bluuebunny/crossref_metadata_2025 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

Introduction

Tuberculosis (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.

Methods

Using 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.

Results

Both 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.

Conclusions

The 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.
Viral infection impacts the 3D subcellular structure of the abundant marine diatom Guinardia delicatula
Authors: Walde Marie , Camplong Cyprien , de Vargas Colomban , Baudoux Anne-Claire , Simon Nathalie
Published: February 2023

Viruses are key players in marine ecosystems where they infect abundant marine microbes. RNA viruses are emerging as key members of the marine virosphere. They have recently been identified as a potential source of mortality in diatoms, a group of microalgae that accounts for roughly 40% of the primary production in the ocean. Despite their likely importance, their impacts on host populations and ecosystems remain difficult to assess. In this study, we introduce an innovative approach that combines automated 3D confocal microscopy with quantitative image analysis and physiological measurements to expand our understanding of viral infection. We followed different stages of infection of the bloom-forming diatom Guinardia delicatula by the RNA virus GdelRNAV-04 until the complete lysis of the host. From 20h after infection, we observed quantifiable changes in subcellular host morphology and biomass. Our microscopy monitoring also showed that viral infection of G. delicatula induced the formation of auxospores as a probable defense strategy against viruses. Our method enables the detection of discriminative morphological features on the subcellular scale and at high throughput for comparing populations, making it a promising approach for the quantification of viral infections in the field in the future.
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<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<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

Background

Interleukin 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.

Methods

Secondary 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.

Results

A 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 > 1.3 log10 copies/ml) and also in those with at least one IL6 > 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.

Conclusion

In 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

Background

Cardiovascular 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.

Methods

An 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.

Results

Comparable 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.

Conclusion

Predictive 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

Introduction

Arbuscular 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.

Methods

This 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.

Results

Pea 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.

Discussion

The 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.
Holistic view of biological nitrogen fixation and phosphorus mobilization in Azotobacter chroococcum NCIMB 8003
Authors: Biełło Karolina A. , Lucena Carlos , López-Tenllado Francisco J. , Hidalgo-Carrillo Jesús , Rodríguez-Caballero Gema , Cabello Purificación , Sáez Lara P. , Luque-Almagro Víctor , Roldán María Dolores , Moreno-Vivián Conrado , Olaya-Abril Alfonso
Published: February 2023

Nitrogen (N) and phosphorus (P) deficiencies are two of the most agronomic problems that cause significant decrease in crop yield and quality. N and P chemical fertilizers are widely used in current agriculture, causing environmental problems and increasing production costs. Therefore, the development of alternative strategies to reduce the use of chemical fertilizers while maintaining N and P inputs are being investigated. Although dinitrogen is an abundant gas in the atmosphere, it requires biological nitrogen fixation (BNF) to be transformed into ammonium, a nitrogen source assimilable by living organisms. This process is bioenergetically expensive and, therefore, highly regulated. Factors like availability of other essential elements, as phosphorus, strongly influence BNF. However, the molecular mechanisms of these interactions are unclear. In this work, a physiological characterization of BNF and phosphorus mobilization (PM) from an insoluble form (Ca3(PO4)2) in Azotobacter chroococcum NCIMB 8003 was carried out. These processes were analyzed by quantitative proteomics in order to detect their molecular requirements and interactions. BNF led to a metabolic change beyond the proteins strictly necessary to carry out the process, including the metabolism related to other elements, like phosphorus. Also, changes in cell mobility, heme group synthesis and oxidative stress responses were observed. This study also revealed two phosphatases that seem to have the main role in PM, an exopolyphosphatase and a non-specific alkaline phosphatase PhoX. When both BNF and PM processes take place simultaneously, the synthesis of nitrogenous bases and L-methionine were also affected. Thus, although the interdependence is still unknown, possible biotechnological applications of these processes should take into account the indicated factors.
Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity
Authors: Anderson Delaney M. , Jayanthi Lakshmi P. , Gosavi Shachi , Meiering Elizabeth M.
Published: February 2023

Kinetic stability, defined as the rate of protein unfolding, is central to determining the functional lifetime of proteins, both in nature and in wide-ranging medical and biotechnological applications. Further, high kinetic stability is generally correlated with high resistance against chemical and thermal denaturation, as well as proteolytic degradation. Despite its significance, specific mechanisms governing kinetic stability remain largely unknown, and few studies address the rational design of kinetic stability. Here, we describe a method for designing protein kinetic stability that uses protein long-range order, absolute contact order, and simulated free energy barriers of unfolding to quantitatively analyze and predict unfolding kinetics. We analyze two β-trefoil proteins: hisactophilin, a quasi-three-fold symmetric natural protein with moderate stability, and ThreeFoil, a designed three-fold symmetric protein with extremely high kinetic stability. The quantitative analysis identifies marked differences in long-range interactions across the protein hydrophobic cores that partially account for the differences in kinetic stability. Swapping the core interactions of ThreeFoil into hisactophilin increases kinetic stability with close agreement between predicted and experimentally measured unfolding rates. These results demonstrate the predictive power of readily applied measures of protein topology for altering kinetic stability and recommend core engineering as a tractable target for rationally designing kinetic stability that may be widely applicable.
Polarization multiplexing multichannel high-Q terahertz sensing system
Authors: Wang Xiuyu , Wang Xiaoman , Ren Qun , Cai Haocheng , Xin Jihong , Lang Yuxin , Xiao Xiaofei , Lan Zhihao , You Jian Wei , Sha Wei E. I.
Published: February 2023

Terahertz functional devices with high-Q factor play an important role in spectral sensing, security imaging, and wireless communication. The reported terahertz devices based on the electromagnetic induction transparency (EIT) effect cannot meet the needs of high-Q in practical applications due to the low-Q factor. Therefore, to increase the Q-factor of resonance, researchers introduced the concept of bound state in the continuum (BIC). In the quasi-BIC state, the metasurface can be excited by the incident wave and provide resonance with a high-Q factor because the condition that the resonant state of the BIC state is orthogonal is not satisfied. The split ring resonator (SRR) is one of the most representative artificial microstructures in the metasurface field, and it shows great potential in BIC. In this paper, based on the classical single-SRR array structure, we combine the large and small SRR and change the resonance mode of the inner and outer SRR by changing the outer radius of the inner SRR. The metasurface based on parameter-tuned BIC verified that the continuous modulation of parameters in a system could make a pair of resonant states strongly coupled, and the coherent cancellation of the resonant states will cause the linewidth of one of the resonant states to disappear, thus forming BIC. Compared with the single-SRR array metasurface based on symmetry-protected BIC, the dual-SRR array metasurface designed in this paper has multiple accidental BICs and realizes multichannel multiplexing of X-polarization and Y-polarization. It provides a brilliant platform for high-sensitivity optical sensor array, low threshold laser and efficient optical harmonic generation.
Research progress on the protective mechanism of a novel soluble epoxide hydrolase inhibitor TPPU on ischemic stroke
Authors: Huang Pan
Published: February 2023

Arachidonic Acid (AA) is the precursor of cerebrovascular active substances in the human body, and its metabolites are closely associated with the pathogenesis of cerebrovascular diseases. In recent years, the cytochrome P450 (CYP) metabolic pathway of AA has become a research hotspot. Furthermore, the CYP metabolic pathway of AA is regulated by soluble epoxide hydrolase (sEH). 1-trifluoromethoxyphenyl-3(1-propionylpiperidin-4-yl) urea (TPPU) is a novel sEH inhibitor that exerts cerebrovascular protective activity. This article reviews the mechanism of TPPU's protective effect on ischemic stroke disease.
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

Introduction

Brachial 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.

Methods

We 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.

Results

Pain 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.

Conclusion

Our 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

Introduction

A 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).

Methods

Our 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.

Results

A 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 < 0.001 and 531.93 (377.55–797.12) vs. 397.23 (263.32–577.65), P < 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 < 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).

Conclusions

Higher 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

Introduction

Spiking 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.

Methods

In 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.

Results

We 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.
Read the clonotype: Next-generation sequencing-based lymphocyte clonality analysis and perspectives for application in pathology
Authors: Groenen Patricia J. T. A. , van den Brand Michiel , Kroeze Leonie I. , Amir Avital L. , Hebeda Konnie M.
Published: February 2023

Clonality assessment using the unique rearrangements of immunoglobulin (IG) and T-cell receptor (TR) genes in lymphocytes is a widely applied supplementary test for the diagnosis of B-cell and T-cell lymphoma. To enable a more sensitive detection and a more precise comparison of clones compared with conventional clonality analysis based on fragment analysis, the EuroClonality NGS Working Group developed and validated a next-generation sequencing (NGS)-based clonality assay for detection of the IG heavy and kappa light chain and TR gene rearrangements for formalin-fixed and paraffin-embedded tissues. We outline the features and advantages of NGS-based clonality detection and discuss potential applications for NGS-based clonality testing in pathology, including site specific lymphoproliferations, immunodeficiency and autoimmune disease and primary and relapsed lymphomas. Also, we briefly discuss the role of T-cell repertoire of reactive lymphocytic infiltrations in solid tumors and B-lymphoma.
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

Purpose

To develop and assess a deep convolutional neural network (DCNN) model for the automatic detection of bone metastases from lung cancer on computed tomography (CT)

Methods

In 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.

Results

The 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).

Conclusions

The proposed DCNN model for automatic lung cancer bone metastases detection can improve diagnostic efficiency and reduce the diagnosis time and workload of junior radiologists.
Incoherent color holography lattice light-sheet for subcellular imaging of dynamic structures
Authors: Alford Simon , Mann Christopher , Art Jonathan , Potcoava Mariana
Published: February 2023

The purpose of the article is to explore the need and advantages of using the incoherent color holography lattice light-sheet (ICHLLS) to provide multiwavelength quantitative monitoring of 3D cellular dynamics in live tissue to further understand complex functions of cells and cellular compartments. We have explored the use of incoherent color holography lattice light-sheet to investigate colocalization of fluorescent markers in live cells in intact tissue. Neuronal structures provide an attractive target for incoherent color holography lattice light-sheet. The cells show a complex architecture in 3D space in which signaling both between cells and within subcellular structures requires colocalization of proteins and lipids to function. During activity and over long periods it is important in understanding these signaling functions in Parkinson’s, Alzheimer’s and motoneuron diseases within live cells in intact tissue. As a proof of concept this article recalls the key aspects in lattice light-sheet imaging and provides a description of the incoherent detection system configuration to actively control dual diffractive lenses phase-shifting at multiple excitation wavelengths sequentially, and per each z-galvo scanning level, with extended field-of-view. The incoherent color holography lattice light-sheet system will allow simultaneous recording of multidimensional object waves that contain intensity in 3D space, phase, and wavelength information. We measure colocalization of fluorescence indicators introduced into live cells in intact neural tissue.
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.
IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes
Authors: Sánchez-Aguilera Pablo , López-Crisosto Camila , Norambuena-Soto Ignacio , Penannen Christian , Zhu Jumo , Bomer Nils , Hoes Matijn F. , Van Der Meer Peter , Chiong Mario , Westenbrink B. Daan , Lavandero Sergio
Published: February 2023

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.
Genetic modulation of Valencia sweet orange field performance by 50 rootstocks under huanglongbing-endemic conditions
Authors: Bowman Kim D. , McCollum Greg , Seymour Danelle K.
Published: February 2023

Although the citrus scion cultivar primarily determines the characteristics of the fruit, the rootstock cultivar of the graft combination has a major role in determining the horticultural performance of the tree. The disease huanglongbing (HLB) is particularly devastating to citrus, and the rootstock has been demonstrated to modulate tree tolerance. However, no existing rootstock is entirely suitable in the HLB-endemic environment, and citrus rootstocks are particularly challenging to breed because of a long life cycle and several biological characteristics that interfere with breeding and commercial use. This study with Valencia sweet orange scion documents the multi-season performance of 50 new hybrid rootstocks and commercial standards in one trial that forms the first wave of a new breeding strategy, with the aim of identifying superior rootstocks for commercial use now, and mapping important traits to be used in selection for the next generation of outstanding rootstocks. A large assortment of traits were quantified for all trees in the study, including traits associated with tree size, health, cropping, and fruit quality. Among the quantitative traits compared between rootstock clones, all except one were observed to have significant rootstock influence. Multiple progeny from eight different parental combinations were included in the trial study, and significant differences between parental combinations of the rootstocks were observed for 27 of the 32 traits compared. Pedigree information was integrated with quantitative trait measurements to dissect the genetic components of rootstock-mediated tree performance. Results suggest there is a significant genetic component underlying rootstock-mediated tolerance to HLB and other critical traits, and that integration of pedigree-based genetic information with quantitative phenotypic data from trials should enable marker-based breeding approaches for the rapid selection of next-generation rootstocks with superior combinations of traits that are needed for commercial success. The current generation of new rootstocks included in this trial is a step toward this goal. Based on results from this trial, the new hybrids US-1649, US-1688, US-1709, and US-2338 were considered the four most promising new rootstocks. Release of these rootstocks for commercial use is being considered, pending the evaluation of continuing performance in this trial and the results from other trials.
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

Introduction

The 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 Discussion

The 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.
Relocation of bioclimatic suitability of Portuguese grapevine varieties under climate change scenarios
Authors: Adão Filipe , Campos João C. , Santos João A. , Malheiro Aureliano C. , Fraga Hélder
Published: February 2023

Introduction

Climate change has been driving warming trends and changes in precipitation patterns and regimes throughout Europe. Future projections indicate a continuation of these trends in the next decades. This situation is challenging the sustainability of viniculture and, thus, significant efforts towards adaptation should be then carried out by local winegrowers.

Method

Ecological Niche Models were built, using the ensemble modelling approach, to estimate the bioclimatic suitability of four main wine-producing European countries, namely France, Italy, Portugal, and Spain, in the recent past (1989–2005), for the cultivation of twelve Portuguese grape varieties. The models were then used to project the bioclimatic suitability to two future periods (2021– 2050 and 2051–2080) to better understand the potential shifts related to climate change (modeled after Intergovernmental Panel on Climate Change’s Representative Concentration Pathways 4.5 and 8.5 scenarios). The models were obtained with the modeling platform BIOMOD2, using four bioclimatic indices, namely the “Huglin Index”, the “Cool Night index”, the “Growing Season Precipitation index”, and the “Temperature Range during Ripening index” as predictor variables, as well as the current locations of the chosen grape varieties in Portugal.

Results

All models performed with high statistical accuracy (AUC > 0.9) and were able to discriminate several suitable bioclimatic areas for the different grape varieties, in and around where they are currently located but also in other parts of the study area. The distribution of the bioclimatic suitability changed, however, when looking at future projections. For both climatic scenarios, projected bioclimatic suitability suffered a considerable shift to the north of Spain and France. In some cases, bioclimatic suitability also moved towards areas of higher elevation. Portugal and Italy barely retained any of the initially projected varietal areas. These shifts were mainly due to the overall rise in thermal accumulation and lower accumulated precipitation in the southern regions projected for the future.

Conclusion

Ensemble models of Ecological Niche Models were shown to be valid tools for winegrowers who want to adapt to a changing climate. The long-term sustainability of viniculture in southern Europe will most likely have to go through a process of mitigation of the effects of increasing temperatures and decreasing precipitation.
The impact of political ideology, knowledge and participation on electoral conspiracy endorsement
Authors: Jiang Yanru
Published: February 2023

From voting fraud to Russian interference, electoral conspiracy theories have circulated on social media since the 2016 United States presidential election with alarming magnitude. Previous conspiracy studies have primarily focused on psychological causes that contribute to the conspiracy mentality, and the discussion on political antecedents of conspiracy endorsement remains lacking. This study selects popular conspiracies reflecting various political ideologies and conducts multiple survey rounds (n = 500) to compare and contrast the effect of partisan affiliations on conspiracy endorsement. Drawing from the extant literature from psychology, communication, and political science and using two-way and three-way interaction models, this study examines three political antecedents—political ideology, knowledge, and participation—and their interactive effects on conspiracy endorsement. The results indicate that individuals with higher levels of political affiliation and knowledge illustrate stronger conspiracy endorsement, and this effect is stronger for conservatives than liberals. Additionally, increased political participation reduces the endorsement of conservative conspiracies and heightens the endorsement of liberal ones among both conservatives and liberals.
Understanding the consumers’ multi-competing brand community engagement: A mix method approach
Authors: He Kai , Liao Junyun , Li Fengyan , Sun Hongguang
Published: February 2023

Introduction

Participating in multiple competing brand communities simultaneously is common for consumers, which brings challenges for companies to manage brand communities and build strong brand-consumer relationships. Although previous studies have widely examined the drivers and outcomes of consumers’ engagement in an individual community, little is known about the multi-competing brand community engagement.

Methods

This paper explores the manifestation, categories, motivational drivers, and consequences of consumers’ MBCE through two studies using two different methodologies to fill this gap.

Results

By using netnography, study 1 shows that MBCE behaviors manifest in various ways, and can be classified into three categories: information-oriented MBCE, social-oriented MBCE, and oppositional MBCE. Study 2 indicates through a consumer survey that one reason that motivates consumers to participate in other competing brand communities is because of the attractiveness of other competing brands. Also, the results indicate that consumers’ product knowledge is positively associated with MBCE. Finally, the number of competing brand community engagements is positively related to brand switching intention.

Discussion

This article enriches the brand community literature and provides important implications on managing brand communities in a competing environment.
Do we need a strong captain to navigate the COVID-19 pandemic? Social identification, conspiracy theory beliefs, and the wish for a strong leader
Authors: Moscatelli Silvia , Graziani Anna Rita , Botindari Lucia , Ciaffoni Stefano , Menegatti Michela
Published: February 2023

Introduction

In times of great uncertainty and hardship, calls for a strong leader tend to arise. The present study delved into this issue by examining possible sociopsychological antecedents of the wish for a strong leader during the COVID-19 crisis.

Methods

We examined the role of social identification, belief in conspiracy theories related to COVID-19, and trust in various relevant social actors in a sample of 350 Italian citizens.

Results

Structural equation modeling analyses showed that identification with Italians was related to a lower wish for a strong leader through the mediation of trust. Identification with Europeans had a direct and negative association with the wish for a strong leader. Finally, greater endorsement of conspiracy beliefs was related to a greater wish for a strong leader, directly and through diminished trust.

Discussion

These findings suggest that belief in conspiracy theories might drive individuals to depart from democratic principles, whereas relying on meaningful social identities can effectively contrast possible authoritarian turns brought about by a global societal crisis, such as the coronavirus outbreak.