bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
Authors: Castro Julia T. , Azevedo Patrick , Fumagalli Marcílio J. , Hojo-Souza Natalia S. , Salazar Natalia , Almeida Gregório G. , Oliveira Livia I. , Faustino Lídia , Antonelli Lis R. , Marçal Tomas G. , Augusto Marconi , Valiate Bruno , Fiorini Alex , Rattis Bruna , Ramos Simone G. , Piccin Mariela , Nonato Osvaldo Campos , Benevides Luciana , Magalhães Rubens , Cassaro Bruno , Burle Gabriela , Doro Daniel , Kalil Jorge , Durigon Edson , Salazar Andrés , Caballero Otávia , Santiago Helton , Machado Alexandre , Silva João S. , da Fonseca Flávio , Fernandes Ana Paula , Teixeira Santuza R. , Gazzinelli Ricardo T. 
Published: August 2022

AbstractBoth T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.
Mechanistic classification and benchmarking of polyolefin depolymerization over silica-alumina-based catalysts
Authors: Lee Wei-Tse , van Muyden Antoine , Bobbink Felix D. , Mensi Mounir D. , Carullo Jed R. , Dyson Paul J. 
Published: August 2022

AbstractCarbon-carbon bond cleavage mechanisms play a key role in the selective deconstruction of alkanes and polyolefins. Here, we show that the product distribution, which encompasses carbon range and formation of unsaturated and isomerization products, serves as a distinctive feature that allows the reaction pathways of different catalysts to be classified. Co, Ni, or Ru nanoparticles immobilized on amorphous silica-alumina, Zeo-Y and ZSM-5, were evaluated as catalysts in the deconstruction of n-hexadecane model substrate with hydrogen to delineate between different mechanisms, i.e., monofunctional- (acid site dominated) or bifunctional-hydrocracking (acid site & metal site) versus hydrogenolysis (metal site dominated), established from the product distributions. The ZSM-5-based catalysts were further studied in the depolymerization of polyethylene. Based on these studies, the catalysts are plotted on an activity-mechanism map that functions as an expandable basis to benchmark catalytic activity and to identify optimal catalysts that afford specific product distributions. The systematic approach reported here should facilitate the acceleration of catalyst discovery for polyolefin depolymerization.
Live-seq enables temporal transcriptomic recording of single cells
Authors: Chen Wanze , Guillaume-Gentil Orane , Rainer Pernille Yde , Gäbelein Christoph G. , Saelens Wouter , Gardeux Vincent , Klaeger Amanda , Dainese Riccardo , Zachara Magda , Zambelli Tomaso , Vorholt Julia A. , Deplancke Bart 
Published: August 2022

AbstractSingle-cell transcriptomics (scRNA-seq) has greatly advanced our ability to characterize cellular heterogeneity1. However, scRNA-seq requires lysing cells, which impedes further molecular or functional analyses on the same cells. Here, we established Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy2,3, thus allowing to couple a cell’s ground-state transcriptome to its downstream molecular or phenotypic behaviour. To benchmark Live-seq, we used cell growth, functional responses and whole-cell transcriptome read-outs to demonstrate that Live-seq can accurately stratify diverse cell types and states without inducing major cellular perturbations. As a proof of concept, we show that Live-seq can be used to directly map a cell’s trajectory by sequentially profiling the transcriptomes of individual macrophages before and after lipopolysaccharide (LPS) stimulation, and of adipose stromal cells pre- and post-differentiation. In addition, we demonstrate that Live-seq can function as a transcriptomic recorder by preregistering the transcriptomes of individual macrophages that were subsequently monitored by time-lapse imaging after LPS exposure. This enabled the unsupervised, genome-wide ranking of genes on the basis of their ability to affect macrophage LPS response heterogeneity, revealing basal Nfkbia expression level and cell cycle state as important phenotypic determinants, which we experimentally validated. Thus, Live-seq can address a broad range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.
Endocytosis in the axon initial segment maintains neuronal polarity
Authors: Eichel Kelsie , Uenaka Takeshi , Belapurkar Vivek , Lu Rui , Cheng Shouqiang , Pak Joseph S. , Taylor Caitlin A. , Südhof Thomas C. , Malenka Robert , Wernig Marius , Özkan Engin , Perrais David , Shen Kang 
Published: August 2022

AbstractNeurons are highly polarized cells that face the fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly1. The axon initial segment (AIS) is a specialized domain that separates a neuron’s morphologically, biochemically and functionally distinct axon and dendrite compartments2,3. How the AIS maintains polarity between these compartments is not fully understood. Here we find that in Caenorhabditis elegans, mouse, rat and human neurons, dendritically and axonally polarized transmembrane proteins are recognized by endocytic machinery in the AIS, robustly endocytosed and targeted to late endosomes for degradation. Forcing receptor interaction with the AIS master organizer, ankyrinG, antagonizes receptor endocytosis in the AIS, causes receptor accumulation in the AIS, and leads to polarity deficits with subsequent morphological and behavioural defects. Therefore, endocytic removal of polarized receptors that diffuse into the AIS serves as a membrane-clearance mechanism that is likely to work in conjunction with the known AIS diffusion-barrier mechanism to maintain neuronal polarity on the plasma membrane. Our results reveal a conserved endocytic clearance mechanism in the AIS to maintain neuronal polarity by reinforcing axonal and dendritic compartment membrane boundaries.
Spatial profiling of chromatin accessibility in mouse and human tissues
Authors: Deng Yanxiang , Bartosovic Marek , Ma Sai , Zhang Di , Kukanja Petra , Xiao Yang , Su Graham , Liu Yang , Qin Xiaoyu , Rosoklija Gorazd B. , Dwork Andrew J. , Mann J. John , Xu Mina L. , Halene Stephanie , Craft Joseph E. , Leong Kam W. , Boldrini Maura , Castelo-Branco Gonçalo , Fan Rong 
Published: August 2022

AbstractCellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context1. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping2–5, but the ability to capture spatial epigenetic information of tissue at the cellular level and genome scale is lacking. Here we describe a method for spatially resolved chromatin accessibility profiling of tissue sections using next-generation sequencing (spatial-ATAC-seq) by combining in situ Tn5 transposition chemistry6 and microfluidic deterministic barcoding5. Profiling mouse embryos using spatial-ATAC-seq delineated tissue-region-specific epigenetic landscapes and identified gene regulators involved in the development of the central nervous system. Mapping the accessible genome in the mouse and human brain revealed the intricate arealization of brain regions. Applying spatial-ATAC-seq to tonsil tissue resolved the spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology progresses spatial biology by enabling spatially resolved chromatin accessibility profiling to improve our understanding of cell identity, cell state and cell fate decision in relation to epigenetic underpinnings in development and disease.
MYB orchestrates T cell exhaustion and response to checkpoint inhibition
Authors: Tsui Carlson , Kretschmer Lorenz , Rapelius Svenja , Gabriel Sarah S. , Chisanga David , Knöpper Konrad , Utzschneider Daniel T. , Nüssing Simone , Liao Yang , Mason Teisha , Torres Santiago Valle , Wilcox Stephen A. , Kanev Krystian , Jarosch Sebastian , Leube Justin , Nutt Stephen L. , Zehn Dietmar , Parish Ian A. , Kastenmüller Wolfgang , Shi Wei , Buchholz Veit R. , Kallies Axel 
Published: August 2022

AbstractCD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and by the impaired production of cytokines. This state of restrained functionality—which is referred to as T cell exhaustion1,2—is maintained by precursors of exhausted T (TPEX) cells that express the transcription factor T cell factor 1 (TCF1), self-renew and give rise to TCF1− exhausted effector T cells3–6. Here we show that the long-term proliferative potential, multipotency and repopulation capacity of exhausted T cells during chronic infection are selectively preserved in a small population of transcriptionally distinct CD62L+ TPEX cells. The transcription factor MYB is not only essential for the development of CD62L+ TPEX cells and maintenance of the antiviral CD8+ T cell response, but also induces functional exhaustion and thereby prevents lethal immunopathology. Furthermore, the proliferative burst in response to PD-1 checkpoint inhibition originates exclusively from CD62L+ TPEX cells and depends on MYB. Our findings identify CD62L+ TPEX cells as a stem-like population that is central to the maintenance of long-term antiviral immunity and responsiveness to immunotherapy. Moreover, they show that MYB is a transcriptional orchestrator of two fundamental aspects of exhausted T cell responses: the downregulation of effector function and the long-term preservation of self-renewal capacity.
Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits
Authors: Sheweita Salah A. , El-dafrawi Yassmin A. , El-ghalid Osama A. , Ghoneim Alaa A. , Wahid Ahmed 
Published: August 2022

AbstractTramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadol-treated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.
Cervical cancer prognosis and related risk factors for patients with cervical cancer: a long-term retrospective cohort study
Authors: Li Jina , Liu Gaoming , Luo Jiayou , Yan Shipeng , Ye Ping , Wang Jie , Luo Miyang 
Published: August 2022

AbstractThis study aims to explore the recurrence rate and overall survival for patients with cervical cancer after the first treatment and the related risk factors. A retrospective cohort study was conducted on cervical cancer patients enrolled in a cancer specialist hospital in Hunan Province, China from January 1992 to December 2005 and followed up until December 2010. Kaplan–Meier survival analysis was used to estimate the cumulative recurrence rate, and Cox proportional hazards model was utilized to identify risk factors associated with prognosis. A total of 4358 patients were enrolled with a median follow-up of 7.4 years (range 5–19 years), and 372 (8.5%) patients had cancer recurrence. The cumulative recurrence rate showed a rapid increase from 3.8% in the first year after discharge to 8.0% in the fifth year, and the recurrence rate remained relatively stable afterward reaching 9.7% and 10.8% in the 10th and the 15th year, respectively. The median time to recurrence was 15.5 months with an IQR of 5.5–40.0 months. The Cox regression showed that miscarriage, clinical stage, and treatment received were significantly associated with cervical cancer recurrence after adjustment for confounders. Patients with recurrence showed a significantly higher risk for mortality than those without recurrence (HR 2.79, 95% CI 2.42–3.22). This study depicted the long-term recurrence rate and survival after recurrence for patients with cervical cancer after the first treatment, and reported time to recurrence and risk factors related to recurrence. These findings may provide important evidence for designing targeted interventions for the treatment of cervical cancer.
Association between prognostic factors and the clinical deterioration of preterm neonates with necrotizing enterocolitis
Authors: Ibrohim Ibnu Sina , Pratama Henggar Allest , Fauzi Aditya Rifqi , Iskandar Kristy , Agustriani Nunik , Gunadi  
Published: August 2022

AbstractNecrotizing enterocolitis (NEC) is responsible for most morbidity and mortality in neonates. Early recognition of the clinical deterioration in newborns with NEC is essential to enhance the referral and management and potentially improve the outcomes. Here, we aimed to identify the prognostic factors and associate them with the clinical deterioration of preterm neonates with NEC. We analyzed the medical records of neonates with NEC admitted to our hospital from 2016 to 2021. We ascertained 214 neonates with NEC. The area under the receiver operating characteristic (ROC) curve and cut-off level of age at onset, C-reactive protein (CRP), leukocyte count, and platelet count for the clinical deterioration of preterm neonates with NEC was 0.644 and 10.5 days old, 0.694 and 4.5 mg/L, 0.513 and 12,200/mm3, and 0.418 and 79,500/mm3, respectively. Late-onset, history of blood transfusion, thrombocytopenia, and elevated CRP were significantly associated with the clinical deterioration of neonates with NEC (p =  < 0.001, 0.017, 0.001, and < 0.001, respectively), while leukocytosis, gestational age, and birth weight were not (p = 0.073, 0.274, and 0.637, respectively). Multivariate analysis revealed that late-onset and elevated CRP were strongly associated with the clinical deterioration of neonates with NEC, with an odds ratio of 3.25 (95% CI = 1.49–7.09; p = 0.003) and 3.53 (95% CI = 1.57–7.95; p = 0.002), respectively. We reveal that late-onset and elevated CRP are the independent prognostic factor for the clinical deterioration of preterm neonates with NEC. Our findings suggest that we should closely monitor preterm neonates with NEC, particularly those with late-onset of the disease and those with an elevated CRP, to prevent further clinical deterioration and intervene earlier if necessary.
Breast cancer patient characterisation and visualisation using deep learning and fisher information networks
Authors: Ortega-Martorell Sandra , Riley Patrick , Olier Ivan , Raidou Renata G. , Casana-Eslava Raul , Rea Marc , Shen Li , Lisboa Paulo J. G. , Palmieri Carlo 
Published: August 2022

AbstractBreast cancer is the most commonly diagnosed female malignancy globally, with better survival rates if diagnosed early. Mammography is the gold standard in screening programmes for breast cancer, but despite technological advances, high error rates are still reported. Machine learning techniques, and in particular deep learning (DL), have been successfully used for breast cancer detection and classification. However, the added complexity that makes DL models so successful reduces their ability to explain which features are relevant to the model, or whether the model is biased. The main aim of this study is to propose a novel visualisation to help characterise breast cancer patients using Fisher Information Networks on features extracted from mammograms using a DL model. In the proposed visualisation, patients are mapped out according to their similarities and can be used to study new patients as a ‘patient-like-me’ approach. When applied to the CBIS-DDSM dataset, it was shown that it is a competitive methodology that can (i) facilitate the analysis and decision-making process in breast cancer diagnosis with the assistance of the FIN visualisations and ‘patient-like-me’ analysis, and (ii) help improve diagnostic accuracy and reduce overdiagnosis by identifying the most likely diagnosis based on clinical similarities with neighbouring patients.
Fluoride varnish, ozone and octenidine reduce the incidence of white spot lesions and caries during orthodontic treatment: randomized controlled trial
Authors: Grocholewicz Katarzyna , Mikłasz Paulina , Zawiślak Alicja , Sobolewska Ewa , Janiszewska-Olszowska Joanna 
Published: August 2022

AbstractThis randomized, parallel, controlled trial assessed the effect of fluoride varnish, ozone and octenidine on white spot lesions (WSLs) and caries during orthodontic treatment. Patients were enrolled between 1st September 2017 and 31st August 2020 at initiation of orthodontic treatment in Department of Interdisciplinary Dentistry Pomeranian Medical University in Szczecin, Poland. All participants were randomly assigned to four study and one control groups using number random generator. However, investigators were not blinded due to the nature of the study. Groups I, II, III, IV had professional cleaning and varnishing (5% NaF) every 4 weeks. Groups II and IV had in-office ozone therapy before varnishing, groups III and IV received domestic octenidine mouthrinse. Group K had no professional hygienic or prophylactic procedures. WSLs were assessed at T0 and then every 4 weeks (T1–T4) and caries—at T0 and T4. The specific objective was to assess the influence of fluoride varnish, ozone and octenidine on the incidence of white spot lesions and caries during orthodontic treatment. The primary outcome of this report was the highest number of WSLs in group K and the lowest percentage of patients with WSLs in group IV. Each group comprised 30 randomized participants; they were all analyzed. No WSLs were found at T0, but they were stated in all groups at T4. The numbers of patients with WSLs significantly increased between T0-T4 in groups I and K. Group IV had the lowest percentage of patients with WSLs in T1-T4. WSLs in group IV were found no earlier than at T2. Group K had the highest percentage of WSLs at T4: 26%. At T0 all the groups had DMFs above 0 with a significant increase at T4. No side effects of the introduced prophylaxis were observed in any group. Caries is an important problem of fixed orthodontic treatment. Even an extremely intensive prophylaxis could not completely prevent WSLs and caries. Simultaneous application of fluoride varnish, ozone gas exposure and octenidine appears to have a beneficial effect in limiting the development of WSLs.Trial registration: NCT04992481.