bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages
Authors: Ochocka Natalia , Segit Pawel , Walentynowicz Kacper Adam , Wojnicki Kamil , Cyranowski Salwador , Swatler Julian , Mieczkowski Jakub , Kaminska Bozena 
Published: February 2021

AbstractMicroglia are resident myeloid cells in the central nervous system (CNS) that control homeostasis and protect CNS from damage and infections. Microglia and peripheral myeloid cells accumulate and adapt tumor supporting roles in human glioblastomas that show prevalence in men. Cell heterogeneity and functional phenotypes of myeloid subpopulations in gliomas remain elusive. Here we show single-cell RNA sequencing (scRNA-seq) of CD11b+ myeloid cells in naïve and GL261 glioma-bearing mice that reveal distinct profiles of microglia, infiltrating monocytes/macrophages and CNS border-associated macrophages. We demonstrate an unforeseen molecular heterogeneity among myeloid cells in naïve and glioma-bearing brains, validate selected marker proteins and show distinct spatial distribution of identified subsets in experimental gliomas. We find higher expression of MHCII encoding genes in glioma-activated male microglia, which was corroborated in bulk and scRNA-seq data from human diffuse gliomas. Our data suggest that sex-specific gene expression in glioma-activated microglia may be relevant to the incidence and outcomes of glioma patients.
Cre-Controlled CRISPR mutagenesis provides fast and easy conditional gene inactivation in zebrafish
Authors: Hans Stefan , Zöller Daniela , Hammer Juliane , Stucke Johanna , Spieß Sandra , Kesavan Gokul , Kroehne Volker , Eguiguren Juan Sebastian , Ezhkova Diana , Petzold Andreas , Dahl Andreas , Brand Michael 
Published: February 2021

AbstractConditional gene inactivation is a powerful tool to determine gene function when constitutive mutations result in detrimental effects. The most commonly used technique to achieve conditional gene inactivation employs the Cre/loxP system and its ability to delete DNA sequences flanked by two loxP sites. However, targeting a gene with two loxP sites is time and labor consuming. Here, we show Cre-Controlled CRISPR (3C) mutagenesis to circumvent these issues. 3C relies on gRNA and Cre-dependent Cas9-GFP expression from the same transgene. Exogenous or transgenic supply of Cre results in Cas9-GFP expression and subsequent mutagenesis of the gene of interest. The recombined cells become fluorescently visible enabling their isolation and subjection to various omics techniques. Hence, 3C mutagenesis provides a valuable alternative to the production of loxP-flanked alleles. It might even enable the conditional inactivation of multiple genes simultaneously and should be applicable to other model organisms amenable to single integration transgenesis.
Inequality is rising where social network segregation interacts with urban topology
Authors: Tóth Gergő , Wachs Johannes , Di Clemente Riccardo , Jakobi Ákos , Ságvári Bence , Kertész János , Lengyel Balázs 
Published: February 2021

AbstractSocial networks amplify inequalities by fundamental mechanisms of social tie formation such as homophily and triadic closure. These forces sharpen social segregation, which is reflected in fragmented social network structure. Geographical impediments such as distance and physical or administrative boundaries also reinforce social segregation. Yet, less is known about the joint relationships between social network structure, urban geography, and inequality. In this paper we analyze an online social network and find that the fragmentation of social networks is significantly higher in towns in which residential neighborhoods are divided by physical barriers such as rivers and railroads. Towns in which neighborhoods are relatively distant from the center of town and amenities are spatially concentrated are also more socially segregated. Using a two-stage model, we show that these urban geography features have significant relationships with income inequality via social network fragmentation. In other words, the geographic features of a place can compound economic inequalities via social networks.
An annotation-free whole-slide training approach to pathological classification of lung cancer types using deep learning
Authors: Chen Chi-Long , Chen Chi-Chung , Yu Wei-Hsiang , Chen Szu-Hua , Chang Yu-Chan , Hsu Tai-I , Hsiao Michael , Yeh Chao-Yuan , Chen Cheng-Yu 
Published: February 2021

AbstractDeep learning for digital pathology is hindered by the extremely high spatial resolution of whole-slide images (WSIs). Most studies have employed patch-based methods, which often require detailed annotation of image patches. This typically involves laborious free-hand contouring on WSIs. To alleviate the burden of such contouring and obtain benefits from scaling up training with numerous WSIs, we develop a method for training neural networks on entire WSIs using only slide-level diagnoses. Our method leverages the unified memory mechanism to overcome the memory constraint of compute accelerators. Experiments conducted on a data set of 9662 lung cancer WSIs reveal that the proposed method achieves areas under the receiver operating characteristic curve of 0.9594 and 0.9414 for adenocarcinoma and squamous cell carcinoma classification on the testing set, respectively. Furthermore, the method demonstrates higher classification performance than multiple-instance learning as well as strong localization results for small lesions through class activation mapping.
Long-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition
Authors: Zhang Bingfang , Wang Lei , Zhan Aisheng , Wang Min , Tian Lanxiang , Guo Weixiang , Pan Yongxin 
Published: February 2021

AbstractAdult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.
Fecal microbiota transplantation in HIV: A pilot placebo-controlled study
Authors: Serrano-Villar Sergio , Talavera-Rodríguez Alba , Gosalbes María José , Madrid Nadia , Pérez-Molina José A. , Elliott Ryan J. , Navia Beatriz , Lanza Val F. , Vallejo Alejandro , Osman Majdi , Dronda Fernando , Budree Shrish , Zamora Javier , Gutiérrez Carolina , Manzano Mónica , Vivancos María Jesús , Ron Raquel , Martínez-Sanz Javier , Herrera Sabina , Ansa Uxua , Moya Andrés , Moreno Santiago 
Published: February 2021

AbstractChanges in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.
Calculating metalation in cells reveals CobW acquires CoII for vitamin B12 biosynthesis while related proteins prefer ZnII
Authors: Young Tessa R. , Martini Maria Alessandra , Foster Andrew W. , Glasfeld Arthur , Osman Deenah , Morton Richard J. , Deery Evelyne , Warren Martin J. , Robinson Nigel J. 
Published: February 2021

AbstractProtein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. We use the calculator to understand the function and mechanism of GTPase CobW, a predicted CoII-chaperone for vitamin B12. Upon binding nucleotide (GTP) and MgII, CobW assembles a high-affinity site that can obtain CoII or ZnII from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables CoII to outcompete ZnII for binding CobW. Thus, CoII is the cognate metal. However, after growth in different [CoII], CoII-occupancy ranges from 10 to 97% which matches CobW-dependent B12 synthesis. The calculator also reveals that related GTPases with comparable ZnII affinities to CobW, preferentially acquire ZnII due to their relatively weaker CoII affinities. The calculator is made available here for use with other proteins.
Characterization of oral virome and microbiome revealed distinctive microbiome disruptions in paediatric patients with hand, foot and mouth disease
Authors: Ho Si Xian , Min Nyo , Wong Emmerie Phaik Yen , Chong Chia Yin , Chu Justin Jang Hann 
Published: February 2021

AbstractWhile the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.
Faecal pollution source tracking in the holy Bagmati River by portable 16S rRNA gene sequencing
Authors: Pantha Kalyan , Acharya Kishor , Mohapatra Sanjeeb , Khanal Santosh , Amatya Niroj , Ospina-Betancourth Carolina , Butte Giacomo , Shrestha Suman Dhun , Rajbhandari Prajwal , Werner David 
Published: February 2021

AbstractA suitcase laboratory was used for 16S rRNA amplicon sequencing to assess microbial water quality in the holy Bagmati River, Kathmandu, Nepal. SourceTracker analysis and Volcano plots revealed that microbial communities in the downstream part of the river were mainly contributed by untreated sewage. Seasonal variability in the sewage microbiome was reflected in the downstream river water quality. The bacterial genera Acidovorax, Geobacillus and Caulobacter predominated in the upstream sites, while genera containing putative human pathogens and gut bacteria, such as Clostridium, Prevotella, Arcobacter, Lactobacillus, Enterococcus and Streptococcus become prominent in the downstream sites. Marker gene qPCR assays for total bacteria, total coliforms, Human E. coli, Arcobacter butzleri and Vibrio cholerae confirmed the sequencing data trends. Even though basic sanitation provision is nowadays near universal in Nepal, our findings show how inadequate wastewater management may turn an urban river into an open sewer, which poses a public health risk.
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis
Authors: Mosleth Ellen F. , Vedeler Christian Alexander , Liland Kristian Hovde , McLeod Anette , Bringeland Gerd Haga , Kroondijk Liesbeth , Berven Frode Steingrimsen , Lysenko Artem , Rawlings Christopher J. , Eid Karim El-Hajj , Opsahl Jill Anette , Gjertsen Bjørn Tore , Myhr Kjell-Morten , Gavasso Sonia 
Published: February 2021

AbstractDespite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease.
Key factors leading to fatal outcomes in COVID-19 patients with cardiac injury
Authors: He Yiyu , Zheng Xiaoxin , Li Xiaoyan , Jiang Xuejun 
Published: February 2021

AbstractCardiac injury among patients with COVID-19 has been reported and is associated with a high risk of mortality, but cardiac injury may not be the leading factor related to death. The factors related to poor prognosis among COVID-19 patients with myocardial injury are still unclear. This study aimed to explore the potential key factors leading to in-hospital death among COVID-19 patients with cardiac injury. This retrospective single-center study was conducted at Renmin Hospital of Wuhan University, from January 20, 2020 to April 10, 2020, in Wuhan, China. All inpatients with confirmed COVID-19 (≥ 18 years old) and cardiac injury who had died or were discharged by April 10, 2020 were included. Demographic data and clinical and laboratory findings were collected and compared between survivors and nonsurvivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with mortality in COVID-19 patients with cardiac injury. A total of 173 COVID-19 patients with cardiac injury were included in this study, 86 were discharged and 87 died in the hospital. Multivariable regression showed increased odds of in-hospital death were associated with advanced age (odds ratio 1.12, 95% CI 1.05–1.18, per year increase; p < 0.001), coagulopathy (2.54, 1.26–5.12; p = 0·009), acute respiratory distress syndrome (16.56, 6.66–41.2; p < 0.001), and elevated hypersensitive troponin I (4.54, 1.79–11.48; p = 0.001). A high risk of in-hospital death was observed among COVID-19 patients with cardiac injury in this study. The factors related to death include advanced age, coagulopathy, acute respiratory distress syndrome and elevated levels of hypersensitive troponin I.
New combination approaches to combat methicillin-resistant Staphylococcus aureus (MRSA)
Authors: Sharaf Mohamed H. , El-Sherbiny Gamal M. , Moghannem Saad A. , Abdelmonem Mohamed , Elsehemy Islam A. , Metwaly Ahmed M. , Kalaba Mohamed H. 
Published: February 2021

AbstractThe herbal products proved to be more promising antimicrobials even though their antimicrobial activity is milder than commercially available antibiotics. Moreover, herbal drugs may act synergistically with antibiotics to kill microbes. In this study, we aimed to enhance the activity of penicillin against MRSA through combination with the active saponin fraction isolated from theZygophyllum albumplant. Three different types of metabolites (saponins, sterols, and phenolics) have been extracted fromZygophyllum albumwith ethanol and purified using different chromatographic techniques. The antibacterial activity of crude extract and the separated metabolites were checked against MRSA isolates, Saponin fraction (ZA-S) was only the active one followed by the crude extract. Therefore, the compounds in this fraction were identified using ultra-high-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) operated in positive and negative ionization modes. UHPLC/QTOF-MS revealed the presence of major six ursane-type tritepenoidal saponins (Quinovic acid, Quinovic acid 3β-O-β-D-quinovopyranoside, Zygophylloside C, Zygophylloside G, Zygophylloside K and Ursolic acid), in addition to Oleanolic acid. Interaction studies between saponin fraction and penicillin against MRSA were performed through the checkerboard method and time-kill assay. According to checkerboard results, only three combinations showed a fractional inhibitory concentration index less than 0.5 at concentrations of (62.5 + 312.5, 62.5 + 156.25, and 62.5 + 78.125 of penicillin and ZA-S, respectively). Time kill assay results showed that the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h occurred by 3.7 at concentrations of 62.5 + 312.5 (µg/µg)/ml of penicillin and ZA-S, respectively. Thus, the combination between saponin fraction ofZygophyllum albumand penicillin with these concentrations could be a potential agent against MRSA that can serve as possible model for new antibacterial drug.
Effects of maoto (ma-huang-tang) on host lipid mediator and transcriptome signature in influenza virus infection
Authors: Nishi Akinori , Kaifuchi Noriko , Shimobori Chika , Ohbuchi Katsuya , Iizuka Seiichi , Sugiyama Aiko , Ogura Keisuke , Yamamoto Masahiro , Kuroki Haruo , Nabeshima Shigeki , Yachie Ayako , Matsuoka Yukiko , Kitano Hiroaki 
Published: February 2021

AbstractMaoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. In this study, we evaluated the effects of maoto as an herbal multi-compound medicine on host responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus [A/PR/8/34 (H1N1)], maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host’s inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza.
The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution
Authors: Eriksson Peter R. , Clark David J. 
Published: February 2021

AbstractIsw1 and Chd1 are ATP-dependent nucleosome-spacing enzymes required to establish regular arrays of phased nucleosomes near transcription start sites of yeast genes. Cells lacking both Isw1 and Chd1 have extremely disrupted chromatin, with weak phasing, irregular spacing and a propensity to form close-packed dinucleosomes. The Isw1 ATPase subunit occurs in two different remodeling complexes: ISW1a (composed of Isw1 and Ioc3) and ISW1b (composed of Isw1, Ioc2 and Ioc4). The Ioc4 subunit of ISW1b binds preferentially to the H3-K36me3 mark. Here we show that ISW1b is primarily responsible for setting nucleosome spacing and resolving close-packed dinucleosomes, whereas ISW1a plays only a minor role. ISW1b and Chd1 make additive contributions to dinucleosome resolution, such that neither enzyme is capable of resolving all dinucleosomes on its own. Loss of the Set2 H3-K36 methyltransferase partly phenocopies loss of Ioc4, resulting in increased dinucleosome levels with only a weak effect on nucleosome spacing, suggesting that Set2-mediated H3-K36 trimethylation contributes to ISW1b-mediated dinucleosome separation. The H4 tail domain is required for normal nucleosome spacing but not for dinucleosome resolution. We conclude that the nucleosome spacing and dinucleosome resolving activities of ISW1b and Chd1 are critical for normal global chromatin organisation.
Causes of death and comorbidities in hospitalized patients with COVID-19
Authors: Elezkurtaj Sefer , Greuel Selina , Ihlow Jana , Michaelis Edward Georg , Bischoff Philip , Kunze Catarina Alisa , Sinn Bruno Valentin , Gerhold Manuela , Hauptmann Kathrin , Ingold-Heppner Barbara , Miller Florian , Herbst Hermann , Corman Victor Max , Martin Hubert , Radbruch Helena , Heppner Frank L. , Horst David 
Published: February 2021

AbstractInfection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.