bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced phenylpropanoid metabolism underlies resistance to Fusarium oxysporum f. sp. vasinfectum race 4 infection in the cotton cultivar Pima-S6 (Gossypium barbadense L.)
Authors: Ojeda-Rivera Jonathan Odilón , Ulloa Mauricio , Pérez-Zavala Francisco G. , Nájera-González Héctor-Rogelio , Roberts Philip A. , Yong-Villalobos Lenin , Yadav Himanshu , Chávez Montes Ricardo A. , Herrera-Estrella Luis , Lopez-Arredondo Damar 
Published: January 2024

Introduction:Fusarium oxysporum f. sp. vasinfectum (FOV) race 4 (FOV4) is a highly pathogenic soil-borne fungus responsible for Fusarium wilt in cotton (Gossypium spp.) and represents a continuing threat to cotton production in the southwest states of the United States, including California, New Mexico, and Texas. Pima (G. barbadense L.) cotton, which is highly valued for its fiber quality, has been shown to be more susceptible to this pathogen than Upland (G. hirsutum L.) cotton. Still, some Pima cultivars present resistance to FOV4 infection.Methods: To gain insights into the FOV4-resistance mechanism, we performed comparative transcriptional and metabolomic analyses between FOV4-susceptible and FOV4-resistant Pima cotton entries. FOV4-resistant Pima-S6 and FOV4-susceptible Pima S-7 and Pima 3-79 cotton plants were infected with FOV4 in the greenhouse, and the roots harvested 11 days post-infection for further analysis.Results: We found that an enhanced root phenylpropanoid metabolism in the resistant Pima-S6 cultivar determines FOV4-resistance. Gene-ontology enrichment of phenylpropanoid biosynthesis and metabolism categories correlated with the accumulation of secondary metabolites in Pima-S6 roots. Specifically, we found esculetin, a coumarin, an inhibitor of Fusarium’s growth, accumulated in the roots of Pima-S6 even under non-infected conditions. Genes related to the phenylpropanoid biosynthesis and metabolism, including phenylalanine ammonia-lyase 2 (PAL2) and pleiotropic drug resistance 12 (PDR12) transporter, were found to be upregulated in Pima-S6 roots.Discussion: Our results highlight an essential role for the phenylpropanoid synthesis pathway in FOV4 resistance in Pima-S6 cotton. These genes represent attractive research prospects for FOV4-disease resistance and breeding approaches of other cotton cultivars of economic relevance.
nPCA: a linear dimensionality reduction method using a multilayer perceptron
Authors: Li Juzeng , Wang Yi 
Published: January 2024

Background: Linear dimensionality reduction techniques are widely used in many applications. The goal of dimensionality reduction is to eliminate the noise of data and extract the main features of data. Several dimension reduction methods have been developed, such as linear-based principal component analysis (PCA), nonlinear-based t-distributed stochastic neighbor embedding (t-SNE), and deep-learning-based autoencoder (AE). However, PCA only determines the projection direction with the highest variance, t-SNE is sometimes only suitable for visualization, and AE and nonlinear methods discard the linear projection.Results: To retain the linear projection of raw data and generate a better result of dimension reduction either for visualization or downstream analysis, we present neural principal component analysis (nPCA), an unsupervised deep learning approach capable of retaining richer information of raw data as a promising improvement to PCA. To evaluate the performance of the nPCA algorithm, we compare the performance of 10 public datasets and 6 single-cell RNA sequencing (scRNA-seq) datasets of the pancreas, benchmarking our method with other classic linear dimensionality reduction methods.Conclusion: We concluded that the nPCA method is a competitive alternative method for dimensionality reduction tasks.
Differential expression of miRNAs revealed by small RNA sequencing in traumatic tracheal stenosis
Authors: Li Wentao , Wei Jinmei , Huang Pingping , Wei Yuhui , Chang Li , Liu Guangnan 
Published: January 2024

Introduction: Traumatic tracheal stenosis (TTS) is a major cause of complex difficult airways, without clinically definitive efficacious drugs available. The aim of this study was to provide a general view of interactions between micro and messenger ribonucleic acids (miRNAs and mRNAs) and many potential mechanisms in TTS via small RNA sequencing.Methods: In this study, the identification of miRNAs was completed using small RNA sequencing and samples from four TTS patients and four normal control cases. By using bioinformatics tools, such as miRanda and RNAhybrid, for identifying the candidate target genes of miRNAs with differential expression in each sample, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were employed for enriching the predicted target genes of miRNAs with differential expression based on the correspondence between miRNAs and their target genes. We detected the expression of the candidate miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR).Results: Twenty-four miRNAs with significant differential expression were identified, including 13 upregulated and 11 downregulated ones. Bioinformation technology was adopted to predict 2,496 target genes. These miRNA-target genes were shown to be primarily enriched in cells and organelles with catalytic activity and binding function, such as binding proteins, small molecules, and nucleotides. Finally, they were observed to process into TTS through the intercellular and signal regulation of related inflammatory signaling and fibrosis signaling pathways. QRT-PCR confirmed the upregulation of miR21-5p and miR214-3p and the downregulation of miR141-3p and miR29b-3p, which was expected to become a high-specific miRNA for TTS.Conclusion: Among all the miRNAs detected, 24 miRNAs demonstrated differential expression between the TTS and normal control groups. A total of 2,496 target genes were predicted by bioinformation technology and enriched in inflammatory and fibrotic signaling pathways. These results provide new ideas for further studies and the selection of targets for TTS in the future.
Feasibility and acceptability of an HPV self-testing strategy: lessons from a research context to assess for ability to implement into primary care at a national level in Botswana
Authors: Luckett Rebecca , Ramogola-Masire Doreen , Harris Devon A. , Gompers Annika , Gaborone Kelebogile , Mochoba Lorato , Ntshese Lapelo , Mathoma Anikie , Kula Maduke , Shapiro Roger , Larson Elysia 
Published: January 2024

BackgroundThe WHO strategy for cervical cancer elimination strives to achieve 70% coverage with high-performance cervical screening. While few low- and middle-income countries have achieved this, high-risk human papillomavirus (hrHPV) self-testing creates the possibility to rapidly upscale access to high-performance cervical screening across resource settings. However, effective hrHPV screening requires linkage to follow-up, which has been variable in prior studies. This study developed and tested an implementation strategy aimed at improving screening and linkage to follow-up care in South East District in Botswana.MethodsThis study performed primary hrHPV self-testing; those with positive results were referred for a triage visit. Withdrawals for any reason, loss-to follow-up between hrHPV test and triage visit, and number of call attempts to give hrHPV results were also documented. Acceptability of the program to patients was measured as the proportion of patients who completed a triage visit when indicated, meeting the a priori threshold of 80%. Feasibility was defined as the proportion of participants receiving the results and attending follow-up. To assess the associations between participant characteristics and loss-to-follow-up we used log-binomial regressions to estimate risk ratios and 95% confidence intervals (CI).ResultsEnrollment of 3,000 women occurred from February 2021 to August 2022. In total, 10 participants withdrew and an additional 33 were determined ineligible after consent, leaving a final cohort of 2,957 participants who underwent self-swab hrHPV testing. Half (50%) of participants tested positive for hrHPV and nearly all (98%) of participants received their hrHPV results, primarily via telephone.  Few calls to participants were required to communicate results: 2,397 (82%) required one call, 386 (13%) required 2 calls, and only 151 (5%) required 3–5 calls. The median time from specimen collection to participant receiving results was 44 days (IQR, 27–65). Of all hrHPV positive participants, 1,328 (90%) attended a triage visit.DiscussionIn a large cohort we had low loss-to-follow-up of 10%, indicating that the strategy is acceptable. Telephonic results reporting was associated with high screening completion, required few calls to participants, and supports the feasibility of hrHPV self-testing in primary care followed by interval triage.
COVID-19 infection characteristics, risk factors and its potential impacts on Takayasu arteritis: a web-based survey in a large cohort
Authors: Kong Xiufang , Wang Jinghua , Fan Guihua , Huang Huijing , Sun Ying , Chen Huiyong , Ma Lili , Li Yanshan , Jiang Lindi 
Published: January 2024

ObjectivesTo investigate the characteristics of COVID-19 and its impact on patients with Takayasu’s arteritis (TAK).MethodsA web-based survey was administered to a TAK cohort and their co-residents in China during January 2023. Infection symptoms, post-acute sequelae of COVID-19 (PASC), potential impacts of COVID-19 on patients’ disease condition, treatment and immune-related parameters were analyzed. In addition, risk factors for COVID-19 and disease relapse after infection were explored.ResultsThe infection rate was significantly lower in patients with TAK than in co-residents (79.13% vs 90.67%, p=0.025). TAK patients were more prone to gastrointestinal symptoms (17.78% vs 5.88%, p=0.024), sleep problems (25.15% vs 10.29%, p=0.011), and symptoms involving more than 2 organs (58.90% vs 35.29%, p=0.001) after infection. Although only 2.45% of TAK patients were hospitalized and none progressed to life-threatening conditions, they were more likely to suffer from PASC (26.38% vs 13.24%, p=0.029), especially active patients. Active disease after the pandemic was significantly lower in infected patients than uninfected patients (21/163, 12.88% vs. 11/43, 25.58%, p=0.041). The presence of multiple system symptoms was a risk factor for active TAK after infection [OR: 3.62 (95% CI 1.06-12.31), p=0.040]. Moreover, csDMARDs treatment was a risk factor for COVID-19 infection [OR: 3.68 (95% CI 1.56-8.66), p=0.002].ConclusionAlthough TAK patients with COVID-19 have more acute and post-acute symptoms, there is no adverse outcome and the risk of disease relapse does not increase. Patients treated with csDMARDs may be at higher risk of infection and deserve more clinical attention.
Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD20 therapy
Authors: Priddey Ashley , Chen-Xu Michael Xin Hua , Cooper Daniel James , MacMillan Serena , Meisl Georg , Xu Catherine K. , Hosmillo Myra , Goodfellow Ian G. , Kollyfas Rafael , Doffinger Rainer , Bradley John R. , Mohorianu Irina I. , Jones Rachel , Knowles Tuomas P. J. , Smith Rona , Kosmoliaptsis Vasilis 
Published: January 2024

BackgroundPatients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients.MethodsWe performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30).ResultsRituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7–38.8) nM vs. 4.6 (2.3–44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45–1.84) nM vs. 20.25 (13.2–38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination.DiscussionOur results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.
Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model
Authors: Curran Colleen S. , Cui Xizhong , Li Yan , Jeakle Mark , Sun Junfeng , Demirkale Cumhur Y. , Minkove Samuel , Hoffmann Victoria , Dhamapurkar Rhea , Chumbris Symya , Bolyard Cameron , Iheanacho Akunna , Eichacker Peter Q. , Torabi-Parizi Parizad 
Published: January 2024

IntroductionBecause prior immune checkpoint inhibitor (ICI) therapy in cancer patients presenting with COVID-19 may affect outcomes, we investigated the beta-coronavirus, murine hepatitis virus (MHV)-1, in a lethal pneumonia model in the absence (Study 1) or presence of prior programmed cell death ligand-1 (PD-L1) antibody (PD-L1mAb) treatment (Study 2). MethodsIn Study 1, animals were inoculated intratracheally with MHV-1 or vehicle and evaluated at day 2, 5, and 10 after infection. In Study 2, uninfected or MHV-1-infected animals were pretreated intraperitoneally with control or PD-L1-blocking antibodies (PD-L1mAb) and evaluated at day 2 and 5 after infection. Each study examined survival, physiologic and histologic parameters, viral titers, lung immunophenotypes, and mediator production.ResultsStudy 1 results recapitulated the pathogenesis of COVID-19 and revealed increased cell surface expression of checkpoint molecules (PD-L1, PD-1), higher expression of the immune activation marker angiotensin converting enzyme (ACE), but reduced detection of the MHV-1 receptor CD66a on immune cells in the lung, liver, and spleen. In addition to reduced detection of PD-L1 on all immune cells assayed, PD-L1 blockade was associated with increased cell surface expression of PD-1 and ACE, decreased cell surface detection of CD66a, and improved oxygen saturation despite reduced blood glucose levels and increased signs of tissue hypoxia. In the lung, PD-L1mAb promoted S100A9 but inhibited ACE2 production concomitantly with pAKT activation and reduced FOXO1 levels. PD-L1mAb promoted interferon-γ but inhibited IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production, contributing to reduced bronchoalveolar lavage levels of eosinophils and neutrophils. In the liver, PD-L1mAb increased viral clearance in association with increased macrophage and lymphocyte recruitment and liver injury. PD-L1mAb increased the production of virally induced mediators of injury, angiogenesis, and neuronal activity that may play role in COVID-19 and ICI-related neurotoxicity. PD-L1mAb did not affect survival in this murine model. DiscussionIn Study 1 and Study 2, ACE was upregulated and CD66a and ACE2 were downregulated by either MHV-1 or PD-L1mAb. CD66a is not only the MHV-1 receptor but also an identified immune checkpoint and a negative regulator of ACE. Crosstalk between CD66a and PD-L1 or ACE/ACE2 may provide insight into ICI therapies. These networks may also play role in the increased production of S100A9 and neurological mediators in response to MHV-1 and/or PD-L1mAb, which warrant further study. Overall, these findings support observational data suggesting that prior ICI treatment does not alter survival in patients presenting with COVID-19.
Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers
Authors: Chagovets Vitaliy , Starodubtseva Natalia , Tokareva Alisa , Novoselova Anastasia , Patysheva Marina , Larionova Irina , Prostakishina Elizaveta , Rakina Militsa , Kazakova Anna , Topolnitskiy Evgenii , Shefer Nikolay , Kzhyshkowska Julia , Frankevich Vladimir , Sukhikh Gennadiy 
Published: January 2024

IntroductionImmunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer.MethodsMonocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts. The targeted analysis of 26 amino acids was conducted by LCMS/MS on an Agilent 6460 triple quadrupole mass spectrometer equipped with an electrospray ionization source and an Agilent 1260 II liquid chromatograph.ResultsComparison of monocytes of cancer patients with monocytes of healthy control individuals demonstrated that in breast cancer most pronounced changes were identified for tryptophan (AUC = 0.76); for ovarian cancer, aminobutyric acid was significantly elevated (AUC= 1.00); for lung cancer significant changes we indented for citrulline (AUC = 0.70). In order to identify key amino acids that are characteristic for monocytes in specific cancer types, we compared each individual cancer with other 3 types of cancer. We found, that aspartic acid and citrulline are specific for monocytes of patients with colorectal cancer (p&lt;0.001, FC = 1.40 and p=0.003, FC = 1.42 respectively). Citrulline, sarcosine and glutamic acid are ovarian cancer-specific amino acids (p = 0.003, FC = 0.78, p = 0.003, FC = 0.62, p = 0.02, FC = 0.78 respectively). Glutamine, methionine and phenylalanine (p = 0.048, FC = 1.39. p = 0.03, FC = 1.27 and p = 0.02, FC = 1.41) are lung cancer-specific amino acids. Ornithine in monocytes demonstrated strong positive correlation (r = 0.63) with lymph node metastasis incidence in breast cancer patients. Methyl histidine and cysteine in monocytes had strong negative correlation with lymph node metastasis in ovarian cancer patients (r = -0.95 and r = -0.95 respectively). Arginine, citrulline and ornithine have strong negative correlation with tumor size (r = -0.78, citrulline) and lymph node metastasis (r = -0.63 for arginine and r = -0.66 for ornithine).DiscussionThese alterations in monocyte amino acid metabolism can reflect the reaction of systemic innate immunity on the growing tumor. Our data indicate that this metabolic programming is cancer specific and can be inhibiting cancer progression. Cancer-specific differences in citrulline, as molecular link between metabolic pathways and epigenetic programing, provide new option for the development and validation of anti-cancer therapies using inhibitors of enzymes catalyzing citrullination.
Low-dose radiotherapy promotes the formation of tertiary lymphoid structures in lung adenocarcinoma
Authors: Wang Duo , Huang Liuying , Qian Danqi , Cao Yulin , Wu Xiaohan , Xu Peiwen , Ming Liang , Tang Junhui , Huang Zhaohui , Yin Yuan , Zhou Leyuan 
Published: January 2024

PurposeA tertiary lymphoid structure (TLS) refers to an organized infiltration of immune cells that is linked to a positive prognosis and improved response to immunotherapy. However, methods that promote TLS formation are limited and challenging to implement in clinical settings. In this study, we aimed to promote the formation and maturation of TLSs in lung adenocarcinoma (LUAD) by combining low-dose radiotherapy (LDRT) with immunotherapy.MethodsTissue sections from 198 patients who had undergone surgery were examined. Risk factors for patient survival were assessed, and the relationship between TLSs and five-year survival was analyzed. The Kras-LSL-G12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. LDRT combined with anti-PD-1 was used to promote the formation and maturation of TLSs.ResultsTLS+, TLSHigh, TLS+GC+ and CD8High within TLS+ were associated with a favorable prognosis. LDRT increased the formation of early TLSs in the Kras-LSL-G12D lung cancer mouse model. In addition, LDRT combined with anti-PD-1 treatment can significantly improve the maturity of TLSs in mouse LUAD, resulting in greater antitumor effects. This antitumor effect was strongly associated with the number of CD8+ T cells within the TLSs.ConclusionWe successfully applied LDRT combined with PD-1 inhibitor therapy for the first time, which increased both the quantity and maturity of TLSs in lung cancer. This approach achieved a promising antitumor effect.