bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid- and strain-specific factors drive variation in ESBL-plasmid spread in vitro and in vivo
Authors: Benz Fabienne , Huisman Jana S , Bakkeren Erik , Herter Joana A , Stadler Tanja , Ackermann Martin , Diard Médéric , Egli Adrian , Hall Alex R , Hardt Wolf-Dietrich , Bonhoeffer Sebastian 
Published: November 2020

Abstract
Horizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global rise of antibiotic resistance. However, the relative contributions of factors that underlie the spread of plasmids and their roles in conjugation in vivo are unclear. To address this, we investigated the spread of clinical Extended Spectrum Beta-Lactamase (ESBL)-producing plasmids in the absence of antibiotics in vitro and in the mouse intestine. We hypothesised that plasmid properties would be the primary determinants of plasmid spread and that bacterial strain identity would also contribute. We found clinical Escherichia coli strains natively associated with ESBL-plasmids conjugated to three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain. Final transconjugant frequencies varied across plasmid, donor, and recipient combinations, with qualitative consistency when comparing transfer in vitro and in vivo in mice. In both environments, transconjugant frequencies for these natural strains and plasmids covaried with the presence/absence of transfer genes on ESBL-plasmids and were affected by plasmid incompatibility. By moving ESBL-plasmids out of their native hosts, we showed that donor and recipient strains also modulated transconjugant frequencies. This suggests that plasmid spread in the complex gut environment of animals and humans can be predicted based on in vitro testing and genetic data.
Skin fungal assemblages of bats vary based on susceptibility to white-nose syndrome
Authors: Vanderwolf Karen J , Campbell Lewis J , Goldberg Tony L , Blehert David S , Lorch Jeffrey M 
Published: November 2020

Abstract
Microbial skin assemblages, including fungal communities, can influence host resistance to infectious diseases. The diversity-invasibility hypothesis predicts that high-diversity communities are less easily invaded than species-poor communities, and thus diverse microbial communities may prevent pathogens from colonizing a host. To explore the hypothesis that host fungal communities mediate resistance to infection by fungal pathogens, we investigated characteristics of bat skin fungal communities as they relate to susceptibility to the emerging disease white-nose syndrome (WNS). Using a culture-based approach, we compared skin fungal assemblage characteristics of 10 bat species that differ in susceptibility to WNS across 10 eastern U.S. states. The fungal assemblages on WNS-susceptible bat species had significantly lower alpha diversity and abundance compared to WNS-resistant species. Overall fungal assemblage structure did not vary based on WNS-susceptibility, but several yeast species were differentially abundant on WNS-resistant bat species. One yeast species inhibited Pseudogymnoascus destructans (Pd), the causative agent on WNS, in vitro under certain conditions, suggesting a possible role in host protection. Further exploration of interactions between Pd and constituents of skin fungal assemblages may prove useful for predicting susceptibility of bat populations to WNS and for developing effective mitigation strategies.
Candida albicans promotes tooth decay by inducing oral microbial dysbiosis
Authors: Du Qian , Ren Biao , He Jinzhi , Peng Xian , Guo Qiang , Zheng Liwei , Li Jiyao , Dai Huanqin , Chen Vivian , Zhang Lixin , Zhou Xuedong , Xu Xin 
Published: November 2020

Abstract
Candida albicans has been detected in root carious lesions. The current study aimed to explore the action of this fungal species on the microbial ecology and the pathogenesis of root caries. Here, by analyzing C. albicans in supragingival dental plaque collected from root carious lesions and sound root surfaces of root-caries subjects as well as caries-free individuals, we observed significantly increased colonization of C. albicans in root carious lesions. Further in vitro and animal studies showed that C. albicans colonization increased the cariogenicity of oral biofilm by altering its microbial ecology, leading to a polymicrobial biofilm with enhanced acidogenicity, and consequently exacerbated tooth demineralization and carious lesion severity. More importantly, we demonstrated that the cariogenicity-promoting activity of C. albicans was dependent on PHR2. Deletion of PHR2 restored microbial equilibrium and led to a less cariogenic biofilm as demonstrated by in vitro artificial caries model or in vivo root-caries rat model. Our data indicate the critical role of C. albicans infection in the occurrence of root caries. PHR2 is the major factor that determines the ecological impact and caries-promoting activity of C. albicans in a mixed microbial consortium.
Widespread transcriptional disruption of the microRNA biogenesis machinery in brain and peripheral tissues of individuals with schizophrenia
Authors: Rey Romain , Suaud-Chagny Marie-Françoise , Dorey Jean-Michel , Teyssier Jean-Raymond , d’Amato Thierry 
Published: November 2020

AbstractIn schizophrenia, altered transcription in brain and peripheral tissues may be due to altered expression of the microRNA biogenesis machinery genes. In this study, we explore the expression of these genes both at the cerebral and peripheral levels. We usedshinyGEO application to analyze gene expression from ten Gene Expression Omnibus datasets, in order to perform differential expression analyses for eight genes encoding the microRNA biogenesis machinery. First, we compared expression of the candidate genes between control subjects and individuals with schizophrenia in postmortem cerebral samples from seven different brain regions. Then, we compared the expression of the candidate genes between control subjects and individuals with schizophrenia in three peripheral tissues. In brain and peripheral tissues of individuals with schizophrenia, we report distinct altered expression patterns of the microRNA biogenesis machinery genes. In the dorsolateral prefrontal cortex, associative striatum and cerebellum of individuals with schizophrenia, we observed an overexpression pattern of some candidate genes suggesting a heightened miRNA production in these brain regions. Additionally, mixed transcriptional abnormalities were identified in the hippocampus. Moreover, in the blood and olfactory epithelium of individuals with schizophrenia, we observed distinct aberrant transcription patterns of the candidate genes. Remarkably, in individuals with schizophrenia, we report DICER1 overexpression in the dorsolateral prefrontal cortex, hippocampus and cerebellum as well as a congruent DICER1 upregulation in the blood compartment suggesting that it may represent a peripheral marker. Transcriptional disruption of the miRNA biogenesis machinery may contribute to schizophrenia pathogenesis both in brain and peripheral tissues.
Anti-bacterial antibodies in multiple myeloma patients at disease presentation, in response to therapy and in remission: implications for patient management
Authors: Chicca Ilaria J. , Heaney Jennifer L. J. , Iqbal Gulnaz , Dunn Janet A. , Bowcock Stella , Pratt Guy , Yong Kwee L. , Planche Timothy D. , Richter Alex , Drayson Mark T. 
Published: November 2020

AbstractMultiple myeloma (MM) is associated with increased risk of infection, but little is known regarding antibody levels against specific bacteria. We assessed levels of polyclonal immunoglobulin and antibacterial antibodies in patients recruited to the TEAMM trial, a randomised trial of antibiotic prophylaxis at the start of anti-myeloma treatment. Polyclonal IgG, IgA and IgM levels were below the reference range in 71%, 83% and 90% of 838 MM patients at diagnosis. Anti-vaccine targeted tetanus toxoid antibodies were protective in 95% of 193 healthy controls but only 41% of myeloma patients. In healthy controls, protective antibodies against 6/12 pneumococcal serotypes, haemophilus and meningococcus A were present in 67%, 41% and 56% compared to just 15%, 21% and 17% of myeloma patients. By 1 year, myeloma patients IgG levels had recovered for 57% of patients whilst the proportion with protective levels of IgG against thymus-dependent protein antigen tetanus toxoid had changed little. In contrast the proportions of patients with protective levels against thymus independent polysaccharide antigens pneumococcus, haemophilus and meningococcus had fallen from 15 to 7%, 21 to 0% and 17 to 11%. Findings highlight the need for strategies to protect patients against bacterial infections during therapy and vaccination programmes during remission.
Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX
Authors: Kaufman Jonathan L. , Dimopoulos Meletios A. , White Darrell , Benboubker Lotfi , Cook Gordon , Leiba Merav , Morton James , Joy Ho P. , Kim Kihyun , Takezako Naoki , Moreau Philippe , Sutherland Heather J. , Magen Hila , Iida Shinsuke , Kim Jin Seok , Miles Prince H. , Cochrane Tara , Oriol Albert , Bahlis Nizar J. , Chari Ajai , O’Rourke Lisa , Trivedi Sonali , Casneuf Tineke , Krevvata Maria , Ukropec Jon , Kobos Rachel , Avet-Loiseau Hervé , Usmani Saad Z. , San-Miguel Jesus 
Published: November 2020

AbstractHigh cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.
Carfilzomib-associated renal toxicity is common and unpredictable: a comprehensive analysis of 114 multiple myeloma patients
Authors: Fotiou Despina , Roussou Maria , Gakiopoulou Charikleia , Psimenou Erasmia , Gavriatopoulou Maria , Migkou Magdalini , Kanellias Nikolaos , Dialoupi Ioanna , Eleutherakis-Papaiakovou Evangelos , Giannouli Stavroula , Delavinia Christina , Efstathiou Kostantinos , Kontogiannis Sofoklis , Terpos Evangelos , Dimopoulos Meletios A. , Kastritis Efstathios 
Published: November 2020

AbstractCarfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed and refractory myeloma (RRMM). Its use has been associated with cardiovascular toxicity but although recently a signal of clinically significant renal complications has also been identified, it is less extensively investigated. We analyzed data of 114 consecutive patients with RRMM who received CFZ-based regimens. Renal complications not related to MM progression were observed in 19 (17%) patients; thrombotic microangiopathy (TMA) was seen in 6 (5%) patients, albuminuria >1 gr/day in 7 patients (6%) and at least grade 3 acute kidney injury (AKI) which could not be otherwise explained in 6 patients (5%). A total of 15 patients discontinued CFZ and dosing was reinitiated at a lower level in one patient with AKI. Albuminuria was associated with focal segmental glomerulosclerosis in the renal biopsy (performed in a total of 6 patients). Renal complications during CFZ therapy are common, occur mostly early and are unpredictable. A potential effect of CFZ on the renal endothelium could be implicated in the pathogenesis of these complications and may also share common pathophysiology with cardiovascular effects of CFZ.
Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer
Authors: Dwyer Amy R. , Truong Thu H. , Kerkvliet Carlos Perez , Paul Kiran V. , Kabos Peter , Sartorius Carol A. , Lange Carol A. 
Published: November 2020

Abstract
Background
Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action.

Methods
The transcriptomes of primary tumours and metastases in mice harbouring ER+ breast cancer patient-derived xenografts (PDXs) were analysed following single-cell RNAseq. In vitro assays were employed to delineate mechanisms of endocrine resistance and stemness.

Results
A 16-gene phospho-Ser294 PR (p-PR) signature predicted poor outcome in ER+ breast cancer. Relative to primary PDX tumours, metastatic lesions expressed abundant p-PR and exhibited an activated PR gene programme with elevated expression of PGR and IRS-1. Breast cancer models of activated PR lost the expression of IGF1R and acquired insulin hypersensitivity with tamoxifen insensitivity. Activated p-PR+ breast cancer cells formed increased tumourspheres with enlarged ALDH+ and CD24−/CD44 populations. E2 induced PR/IRS-1 interaction and exchange of IGF1Rβ for IRS-1 in p-PR-containing transcriptional complexes. Inhibition of IRS-1 or IR and inducible IRS-1 knockdown reduced tumourspheres. Endocrine-resistant models of luminal B breast cancer induced p-PR in 3D cultures and required PR and IRS-1 for tumoursphere formation.

Conclusions
Phospho-PR-B cooperates with IRS-1 to promote outgrowth of endocrine-resistant and stem-like breast cancer cells. Targeting phospho-PR/IRS-1 crosstalk may block the emergence of endocrine resistance.
Effects of social distancing and isolation on epidemic spreading modeled via dynamical density functional theory
Authors: te Vrugt Michael , Bickmann Jens , Wittkowski Raphael 
Published: November 2020

AbstractFor preventing the spread of epidemics such as the coronavirus disease COVID-19, social distancing and the isolation of infected persons are crucial. However, existing reaction-diffusion equations for epidemic spreading are incapable of describing these effects. In this work, we present an extended model for disease spread based on combining a susceptible-infected-recovered model with a dynamical density functional theory where social distancing and isolation of infected persons are explicitly taken into account. We show that the model exhibits interesting transient phase separation associated with a reduction of the number of infections, and allows for new insights into the control of pandemics.
Site-specific spectroscopic measurement of spin and charge in (LuFeO3)m/(LuFe2O4)1 multiferroic superlattices
Authors: Fan Shiyu , Das Hena , Rébola Alejandro , Smith Kevin A. , Mundy Julia , Brooks Charles , Holtz Megan E. , Muller David A. , Fennie Craig J. , Ramesh Ramamoorthy , Schlom Darrell G. , McGill Stephen , Musfeldt Janice L. 
Published: November 2020

AbstractInterface materials offer a means to achieve electrical control of ferrimagnetism at room temperature as was recently demonstrated in (LuFeO3)m/(LuFe2O4)1 superlattices. A challenge to understanding the inner workings of these complex magnetoelectric multiferroics is the multitude of distinct Fe centres and their associated environments. This is because macroscopic techniques characterize average responses rather than the role of individual iron centres. Here, we combine optical absorption, magnetic circular dichroism and first-principles calculations to uncover the origin of high-temperature magnetism in these superlattices and the charge-ordering pattern in the m = 3 member. In a significant conceptual advance, interface spectra establish how Lu-layer distortion selectively enhances the Fe2+ → Fe3+ charge-transfer contribution in the spin-up channel, strengthens the exchange interactions and increases the Curie temperature. Comparison of predicted and measured spectra also identifies a non-polar charge ordering arrangement in the LuFe2O4 layer. This site-specific spectroscopic approach opens the door to understanding engineered materials with multiple metal centres and strong entanglement.
Common schizophrenia risk variants are enriched in open chromatin regions of human glutamatergic neurons
Authors: Hauberg Mads E. , Creus-Muncunill Jordi , Bendl Jaroslav , Kozlenkov Alexey , Zeng Biao , Corwin Chuhyon , Chowdhury Sarah , Kranz Harald , Hurd Yasmin L. , Wegner Michael , Børglum Anders D. , Dracheva Stella , Ehrlich Michelle E. , Fullard John F. , Roussos Panos 
Published: November 2020

AbstractThe chromatin landscape of human brain cells encompasses key information to understanding brain function. Here we use ATAC-seq to profile the chromatin structure in four distinct populations of cells (glutamatergic neurons, GABAergic neurons, oligodendrocytes, and microglia/astrocytes) from three different brain regions (anterior cingulate cortex, dorsolateral prefrontal cortex, and primary visual cortex) in human postmortem brain samples. We find that chromatin accessibility varies greatly by cell type and, more moderately, by brain region, with glutamatergic neurons showing the largest regional variability. Transcription factor footprinting implicates cell-specific transcriptional regulators and infers cell-specific regulation of protein-coding genes, long intergenic noncoding RNAs and microRNAs. In vivo transgenic mouse experiments validate the cell type specificity of several of these human-derived regulatory sequences. We find that open chromatin regions in glutamatergic neurons are enriched for neuropsychiatric risk variants, particularly those associated with schizophrenia. Integration of cell-specific chromatin data with a bulk tissue study of schizophrenia brains increases statistical power and confirms that glutamatergic neurons are most affected. These findings illustrate the utility of studying the cell-type-specific epigenome in complex tissues like the human brain, and the potential of such approaches to better understand the genetic basis of human brain function.
Distance makes a difference in crystalline photoluminescence
Authors: Gan Zibao , Liu Yungui , Wang Lin , Jiang Shuqing , Xia Nan , Yan Zhipeng , Wu Xiang , Zhang Junran , Gu Wanmiao , He Lizhong , Dong Jingwu , Ma Xuedan , Kim Jaeyong , Wu Zhongyan , Xu Yixuan , Li Yanchun , Wu Zhikun 
Published: November 2020

AbstractCrystallization-induced photoluminescence weakening was recently revealed in ultrasmall metal nanoparticles. However, the fundamentals of the phenomenon are not understood yet. By obtaining conformational isomer crystals of gold nanoclusters, we investigate crystallization-induced photoluminescence weakening and reveal that the shortening of interparticle distance decreases photoluminescence, which is further supported by high-pressure photoluminescence experiments. To interpret this, we propose a distance-dependent non-radiative transfer model of excitation electrons and support it with additional theoretical and experimental results. This model can also explain both aggregation-induced quenching and aggregation-induced emission phenomena. This work improves our understanding of aggregated-state photoluminescence, contributes to the concept of conformational isomerism in nanoclusters, and demonstrates the utility of high pressure studies in nanochemistry.
Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial
Authors: Balle Christina , Konstantinus Iyaloo N. , Jaumdally Shameem Z. , Havyarimana Enock , Lennard Katie , Esra Rachel , Barnabas Shaun L. , Happel Anna-Ursula , Moodie Zoe , Gill Katherine , Pidwell Tanya , Karaoz Ulas , Brodie Eoin , Maseko Venessa , Gamieldien Hoyam , Bosinger Steven E. , Myer Landon , Bekker Linda-Gail , Passmore Jo-Ann S. , Jaspan Heather B. 
Published: November 2020

AbstractYoung women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.
Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis
Authors: Moreira-Teixeira Lúcia , Stimpson Philippa J. , Stavropoulos Evangelos , Hadebe Sabelo , Chakravarty Probir , Ioannou Marianna , Aramburu Iker Valle , Herbert Eleanor , Priestnall Simon L. , Suarez-Bonnet Alejandro , Sousa Jeremy , Fonseca Kaori L. , Wang Qian , Vashakidze Sergo , Rodríguez-Martínez Paula , Vilaplana Cristina , Saraiva Margarida , Papayannopoulos Venizelos , O’Garra Anne 
Published: November 2020

AbstractTuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outcome of M. tuberculosis infection.