bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-metastatic niche drives breast cancer invasion by modulating MSC homing and CAF differentiation
Authors: Saxena Neha , Bhardwaj Garvit , Jadhav Sameer , Zafar Hamim , Sen Shamik 
Published: January 2021

AbstractThe extent to which cancer-associated alterations in extracellular matrix stiffness influences the crosstalk between cancer cells and mesenchymal stem cells (MSCs) remains unclear. By analyzing multiple singlecell RNA sequencing datasets, we establish the existence of a cell sub-population co-expressing MSC and cancer associated fibroblast (CAF) markers in highly aggressive triple-negative breast cancers in primary tumor, secondary sites, and in circulatory tumor cell clusters. Using hydrogels of varying stiffness corresponding to different stages of cancer progression, we show that on pre-metastatic stroma mimetic 2 kPa gels, MDA-MB-231 breast cancer cell secreted conditioned media drives efficient MSC chemotaxis and induces stable CAF differentiation in a TGFβ/contractility-dependent manner. In addition to enhancing cancer cell proliferation, 2 kPa CAFs maximally boost local invasion and confer resistance to flow-induced shear stresses. Together, our results suggest that homing of MSCs at the pre-metastatic stage and their differentiation into CAFs actively drives breast cancer invasion and metastasis.
Endogenous feline leukemia virus siRNA transcription may interfere with exogenous FeLV infection
Authors: Chiu Elliott S. , VandeWoude Sue 
Published: January 2021

AbstractEndogenous retroviruses (ERVs) are increasingly recognized for biological impacts on host cell function and susceptibility to infectious agents, particularly in relation to interactions with exogenous retroviral progenitors (XRVs). ERVs can simultaneously promote and restrict XRV infections using different mechanisms that are virus- and host-specific. The majority of endogenous-exogenous retroviral interactions have been evaluated in experimental mouse or chicken systems which are limited in their ability to extend findings to naturally infected outbred animals. Feline leukemia virus (FeLV) has a relatively well-characterized endogenous retrovirus with a coexisting virulent exogenous counterpart and is endemic worldwide in domestic cats. We have previously documented an association between endogenous FeLV LTR copy number and abrogated exogenous FeLV in naturally infected cats and experimental infections in tissue culture. Analyses described here examine limited FeLV replication in experimentally infected peripheral blood mononuclear cells. We further examine NCBI Sequence Read Archive RNA transcripts to evaluate enFeLV transcripts and RNA interference precursors. We find that lymphoid-derived tissues, which are experimentally less permissive to exogenous FeLV infection, transcribe higher levels of enFeLV under basal conditions. Transcription of enFeLV-LTR segments is significantly greater than other enFeLV genes. We documented transcription of a 21-nt miRNA just 3′ to the enFeLV 5′-LTR in the feline miRNAome of all datasets evaluated (n=27). Our findings point to important biological functions of enFeLV transcription linked to solo LTRs distributed within the domestic cat genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis.ImportanceEndogenous retroviruses (ERVs) are increasingly implicated in host cellular processes and susceptibility to infectious agents, specifically regarding interactions with exogenous retroviral progenitors (XRVs). Exogenous feline leukemia virus (FeLV) and its endogenous counterpart (enFeLV) represent a well characterized, naturally occurring XRV-ERV dyad. We have previously documented an abrogated FeLV infection in both naturally infected cats and experimental fibroblast infections that harbor higher enFeLV proviral loads. Using anin silicoapproach, we provide evidence of miRNA-transcription that are produced in tissues most important for FeLV infection, replication, and transmission. Our findings point to important biological functions of enFeLV transcription linked to solo-LTRs distributed within the feline genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis. This body of work provides additional evidence of RNAi as a mechanism of viral interference and is a demonstration of ERV exaptation by the host to defend against related XRVs.
Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients
Authors: Crescenzo-Chaigne Bernadette , Behillil Sylvie , Enouf Vincent , Escriou Nicolas , Petres Stephane , Ungeheuer Marie Noelle , Ghosn Jade , Tubiana Sarah , Bouadma Lila , van der Werf Sylvie , Demeret Caroline ,   for the French COVID cohort study group
Published: January 2021

AbstractBackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.
A Vital Sign-based Prediction Algorithm for Differentiating COVID-19 Versus Seasonal Influenza in Hospitalized Patients
Authors: Yanamala Naveena , Krishna Nanda H. , Hathaway Quincy A. , Radhakrishnan Aditya , Sunkara Srinidhi , Patel Heenaben , Farjo Peter , Patel Brijesh , Sengupta Partho P 
Published: January 2021

AbstractPatients with influenza and SARS-CoV2/Coronavirus disease 2019 (COVID-19) infections have different clinical course and outcomes. We developed and validated a supervised machine learning pipeline to distinguish the two viral infections using the available vital signs and demographic dataset from the first hospital/emergency room encounters of 3,883 patients who had confirmed diagnoses of influenza A/B, COVID-19 or negative laboratory test results. The models were able to achieve an area under the receiver operating characteristic curve (ROC AUC) of at least 97% using our multiclass classifier. The predictive models were externally validated on 15,697 encounters in 3,125 patients available on TrinetX database that contains patient-level data from different healthcare organizations. The influenza vs. COVID-19-positive model had an AUC of 98%, and 92% on the internal and external test sets, respectively. Our study illustrates the potentials of machine-learning models for accurately distinguishing the two viral infections. The code is made available at https://github.com/ynaveena/COVID-19-vs-Influenza and may be have utility as a frontline diagnostic tool to aid healthcare workers in triaging patients once the two viral infections start cocirculating in the communities.
Impact of training modules on physicians’ perspective of COVID-19: An online survey
Authors: Umar Badar Uddin , Alam Nazmun Nahar , Alam Tanbira , Mannan Mahmudul , Rahman S M Niazur 
Published: January 2021

AbstractBackgroundThe outbreak of COVID-19 has remained a massive challenge for healthcare workers specially physicians. Effective professional training has a crucial role in preparing doctors for responding to pandemics.ObjectiveTo assess the effectiveness of existing training modules on enhancing knowledge, ensuring safe practice, and improving behavior on COVID-19 among physicians.MethodsThis is a descriptive, cross-sectional, online survey; where a virtual questionnaire was used to collect data through online professional platforms. A pre-tested survey tool was employed to assess the impact of professional training on infection prevention and control.ResultsTotal 161 physicians participated in this survey from 15 different countries. Most of the respondents (72%) received training from various sources like the workplace (60%) and international agencies (21%), through the in-person or online format. Knowledge assessment revealed advanced (43%) and competent (40%) understanding by the participants. Improving knowledge progression was displayed by the cohort who received professional training (p<0.00). Physicians’ positive behavior and good practices were observed with the training modules.ConclusionIt became evident from this study, that professional training is effective in enhancing knowledge, improving behavior, and ensuring safe practices. Hence, designing such training modules for the physicians is warranted to tackle ongoing and future pandemics.
Unsupervised clustering reveals a unique Treg profile in slow progressors to type 1 diabetes
Authors: Boldison Joanne , Long Anna E , Aitken Rachel J , Wilson Isabel V , Megson Claire , Hanna Stephanie J , Wong F. Susan , Gillespie Kathleen M 
Published: January 2021

AbstractObjectiveTo profile CD4+ regulatory T cells (Tregs) in a well-characterised cohort of slow progressors to type 1 diabetes, individuals positive for multiple islet autoantibodies who remain diabetes-free for at least 10 years.Research Design and MethodsPeripheral blood samples were obtained from extreme slow progressor individuals (n=8), with up to 32 years follow-up, and age and gender-matched to healthy donors. One participant in this study was identified with a raised HbA1c at the time of assessment, and was individually evaluated in the data analysis. PBMCs were isolated, from donors, and to assess frequency, phenotype and function of Tregs, multi-parameter flow cytometry and T cell suppression assays were performed. Unsupervised clustering analysis, FlowSOM and CITRUS, was used to evaluate Treg phenotypes.ResultsTreg mediated suppression of CD4+ effector T cells, from slow progressors was significantly impaired, compared to healthy donors (P<0.05). Effector CD4 T cells, from slow progressors, were more responsive to Treg suppression, compared to healthy donors, demonstrated by increased suppression of CD25 expression on effector CD4 T cells (P<0.05). Unsupervised clustering on memory CD4 T cells, from slow progressors, showed an increased frequency of activated-memory CD4 Tregs associated with increased expression of GITR, compared to healthy donors (P<0.05). The participant with a raised HbA1c had a different Treg profile, compared to slow progressors and the matched controls.ConclusionsCD4+ Tregs from slow progressor individuals have a unique Treg signature. This report highlights the need for further study of Treg heterogeneity in individuals at-risk of developing type 1 diabetes.
Epidemiology and antibiotic resistance profile of Helicobacter pylori infection in Cameroon: a systematic review with meta-analysis
Authors: Ngnameko Corinne Raïssa , Noubiap Jean Jacques , Simo Nemg Freddy Brice , Galdima Mohamadou Abdou , Takuissu-Nguemto Guy Roussel , Ngo-Boumso Sophie , Njayou Frederic Nico , Moundipa Paul F. , Bigna Jean Joel 
Published: January 2021

AbstractObjectivesAlthough global epidemiology of Helicobacter pylori (HP) infection is well characterized, country-specific figure is more accurate for context-specific tailored interventions. The aim was to determine the prevalence, factors associated with infection, antibiotic resistance profile, and genotypes of HP in Cameroon.DesignA systematic review with meta-analysis.ParticipantsPeople living in Cameroon regardless of their clinical profile.Data sources and synthesisObservational studies published in PubMed, EMBASE, African Index Medicus, African Journals Online, and Health Sciences and Diseases up to October 12th, 2020. Study selection, data extraction, and methodological quality assessment were done by two independent authors. Random-effect meta-analysis served to pool prevalence data.ResultsFifteen studies were included. None investigated the genotypes of HP. Among symptomatic patients, the most common used test, urea breath test on gastric biopsy, yielded a prevalence 57.8% (95% confidence interval (CI): 34.3-79.5) of HP infection. This prevalence significantly varied between 47.0% (95%CI: 43.0-51.0) for antigen test in stool samples and 71.2% (95%CI: 59.1-81.9) for Giemsa on gastric biopsy; p = 0.0006. One study in asymptomatic children reported the prevalence of 52.3% (95%CI: 44.9-59.6) using antigen test for stool samples. Among the six studies investigating factors associated with HP infection, one performed a multivariable model and identified being student as protective factor compared to being employed (Odds ratio: 0.09; 95%CI: 0.02–0.49). For antibiotics used for first line treatment, HP was resistant to amoxicillin (85.6-97.1%), metronidazole (93.2-97.9%), and clarithromycin (13.6-44.7%) as reported in two studies.LimitationData were from six of the ten regions of Cameroon, hindering the generalizability of the findings to the country.ConclusionThis study depicted a high prevalence of HP infection and a worrying resistance profile to first-line antibiotics. When waiting for well-conducted studies, updated guidelines are needed for clinical practice for first-line antibiotic treatment.RegistrationPROSPERO, CRD42020220084.Strengths and limitations of this studyNot all the 10 regions of the country were represented in this study, hindering the generalizability of the findings.We were not able to substantially investigate sources of heterogeneity in the prevalence of Helicobacter pylori infection due to scarcity of data.Evidence investigating factors associated with Helicobacter pylori infection are weak and there was scarcity on data exploring antibiotic resistance profile of Helicobacter pylori.This study is the first to provide an estimate of the epidemiology and resistance profile of Helicobacter pylori in Cameroon.
Automated Bias Reduction in Deep Learning Based Melanoma Diagnosis using a Semi-Supervised Algorithm
Authors: Das Sauman 
Published: January 2021

AbstractMelanoma is one of the most fatal forms of skin cancer and is often very difficult to differentiate from other benign skin lesions. However, if detected at its early stages, it can almost always be cured. Researchers and data scientists have studied this disease in-depth with the help of large datasets containing high-quality dermascopic images, such as those assembled by the International Skin Imaging Collaboration (ISIC). However, these images often lack diversity and over-represent patients with very common skin features such as light skin and having no visible body hair. In this study, we introduce a novel architecture called LatentNet which automatically detects over-represented features and reduces their weights during training. We tested our model on four distinct categories - three skin color levels corresponding to Type I, II, and III on the Fitzpatrick Scale, and images containing visible hair. We then compared the accuracy against the conventional Deep Convolutional Neural Network (DCNN) model trained using the standard approach (i.e. without detecting over-represented features) and containing the same hyper-parameters as the LatentNet. LatentNet showed significant performance improvement over the standard DCNN model with accuracy of 89.52%, 79.05%, 64.31%, and 64.35% compared to the DCNN accuracy of 90.41%, 70.82%, 45.28%, 56.52% in the corresponding categories, respectively. Differences in the average performance between the models were statistically significant (p < 0.05), suggesting that the proposed model successfully reduced bias amongst the tested categories. LatentNet is the first architecture that addresses racial bias (and other sources of bias) in deep-learning based Melanoma diagnosis.
Astrocyte-derived ApoE is Required for the Maturation of Injury-induced Hippocampal Neurons and Regulates Cognitive Recovery After Traumatic Brain Injury
Authors: Yu Tzong-Shiue , Tensaouti Yacine , Stephanz Elizabeth P. , Rafikian Elizabeth E. , Yang Mu , Kernie Steven G. 
Published: January 2021

AbstractPolymorphisms in the apolipoprotein E (ApoE) gene confer a major genetic risk for the development of late-onset Alzheimer’s disease (AD) and are predictive of outcome following traumatic brain injury (TBI). Alterations in adult hippocampal neurogenesis have long been associated with both the development of AD and recovery following TBI, and ApoE is known to play a role in this process. In order to determine how ApoE might influence hippocampal injury-induced neurogenesis, we developed a novel conditional system whereby functional ApoE from astrocytes was ablated just prior to injury. While successfully ablating 90% of astrocytic ApoE just prior to a closed cortical impact injury in mice, we observed an attenuation in the development of newly born neurons using a GFP-expressing retrovirus, but not in existing hippocampal neurons visualized with a Golgi stain. Intriguingly, animals with a “double-hit”, i.e. injury and ApoE conditionally inactivated in astrocytes, demonstrated the most pronounced impairments in the hippocampal-dependent Morris water maze test, failing to exhibit spatial memory after both acquisition and reversal training trials. In comparison, conditional knockout mice without injury displayed impairments but only in the reversal phase of the test, suggesting accumulative effects of astrocytic ApoE deficiency and traumatic brain injury on AD-like phenotypes. Together, these findings demonstrate that astrocytic ApoE is required for functional injury-induced neurogenesis following traumatic brain injury.Significance StatementApoE has long been implicated in the development of Alzheimer’s disease and recovery from traumatic brain injury via unknown mechanisms. Using a novel conditional ablation model of mouse ApoE and subsequent tracing of individual hippocampal neurons, we demonstrate its requirement in injury-induced neurogenesis for proper dendritic arborization and cognitive function in hippocampal-dependent learning and memory tasks.
Nanobody Mediated Macromolecular Crowding Induces Membrane Fission and Remodeling in the African Trypanosome
Authors: Hempelmann Alexander , Hartleb Laura , van Straaten Monique , Hashemi Hamidreza , Zeelen Johan P. , Papavasiliou F. Nina , Engstler Markus , Stebbins C. Erec , Jones Nicola G. 
Published: January 2021

AbstractThe dense Variant Surface Glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generated anti-VSG nanobodies and combined high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody caused rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endo-and exocytosis is mechanistically linked toT. bruceipropulsion and whose density is required for survival. Electron microscopy studies demonstrated that this loss of motility was accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.
Colletotrichum higginsianumeffectors exhibit cell to cell hypermobility in plant tissues and modulate intercellular connectivity amongst a variety of cellular processes
Authors: Ohtsu Mina , Jennings Joanna , Johnston Matthew , Liu Xiaokun , Hughes Aoife , Stark Kara , Morris Richard J. , de Keijzer Jeroen , Faulkner Christine 
Published: January 2021

SummaryMulticellular organisms exchange information and resources between cells to co-ordinate growth and responses. In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. Some plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion. However, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To begin to investigate this and identify which effectors are cell-to-cell mobile, we performed a live imaging-based screen and identified 15 cell-to-cell mobile effectors of the fungal pathogenColletotrichum higginsianum. Of these, 6 are “hypermobile”, showing cell-to-cell mobility greater than expected for a protein of its size. We further identified 3 effectors that can indirectly modify plasmodesmal aperture. Transcriptional profiling of plants expressing hypermobile effectors implicate them in a variety of processes including senescence, glucosinolate production, cell wall integrity, growth and iron metabolism. However, not all effectors had an independent effect on virulence. This suggests a wide range of benefits to infection gained by the mobility ofC. higginsianumeffectors that likely interact in a complex way during infection.
Anti-CoVid19 plasmid DNA vaccine induces a potent immune response in rodents by Pyro-drive Jet Injector intradermal inoculation
Authors: Nishikawa Tomoyuki , Chang Chin Yang , Tai Jiayu A , Hayashi Hiroki , Sun Jiao , Torii Shiho , Ono Chikako , Matsuura Yoshiharu , Ide Ryoko , Mineno Junichi , Sasai Miwa , Yamamoto Masahiro , Nakagami Hironori , Yamashita Kunihiko 
Published: January 2021

AbstractThere is an urgent need to limit and stop the worldwide coronavirus disease 2019 (COVID-19) pandemic via quick development of efficient and safe vaccination methods. Plasmid DNA vaccines are one of the most remarkable vaccines that can be developed in a short term. pVAX1-SARS-CoV2-co, which is a plasmid DNA vaccine, was designed to express severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. The produced antibodies lead to Immunoreactions against S protein, anti-receptor-binding-domain, and neutralizing action of pVAX1-SARS-CoV2-co, as confirmed in a previous study. To promote the efficacy of the pVAX1-SARS-CoV2-co vaccine, a pyro-drive jet injector (PJI) was employed. PJI is an injection device that can adjust the injection pressure depending on various target tissues. Intradermally-adjusted PJI demonstrated that pVAX1-SARS-CoV2-co vaccine injection caused a strong production of anti-S protein antibodies, triggered immunoreactions and neutralizing actions against SARS-CoV-2. Moreover, a high dose of pVAX1-SARS-CoV2-co intradermal injection via PJI did not cause any serious disorders in the rat model. Finally, virus infection challenge in mice, confirmed that intradermally immunized (via PJI) mice were potently protected from COVID-19 infection. Thus, pVAX1-SARS-CoV2-co intradermal injection via PJI is a safe and promising vaccination method to overcome the COVID-19 pandemic.