bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity ofStaphylococcus epidermidisin prosthetic joint infections: Time to reevaluate microbiological criteria?
Authors: Widerström Micael , Stegger Marc , Johansson Anders , Gurram Bharat Kumar , Larsen Anders Rhod , Wallinder Lars , Edebro Helen , Monsen Tor 
Published: April 2021

ABSTRACTProsthetic joint infection (PJI) is a feared complication after arthroplasty withStaphylococcus epidermidisas a major pathogen. One diagnostic criteria for PJI diagnosis is the finding of phenotypically identical organisms based on common laboratory tests in two or more periprosthetic microbial cultures. Because of phenotypical variation within a genetic clone, and clonal variation within a phenotype, the criteria may be ambiguous. Here, we investigate the extent of diversity among coagulase-negative staphylococci in PJI and characterize in detailS. epidermidisisolates from these infections.We performed a retrospective cohort study of 62 consecutive patients with PJI caused by coagulase-negative staphylococci (CoNS) from two hospitals in Northern Sweden. From 16 of the patients, two to nineS. epidermidisisolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones ofS. epidermidiswere identified in 40/62 (65%) of the PJIs using a combination of analysis by pulsed-field gel electrophoresis and multiple-locus sequence typing. Whole genome sequencing showed presence of multiple sequence types (STs) in seven (7/16, 44%) PJIs. Among isolates of the same ST, within-patient phenotypical variation in antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%).These results highlight the ambiguity of using phenotypical characterization ofS. epidermidisas diagnostic criteria in PJI. The results call for larger systematic studies to determine the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and for the therapeutic outcome in patients.
Which traits predict elevated distress during the Covid-19 pandemic? Results from a large, longitudinal cohort study with psychiatric patients and healthy controls
Authors: Brosch Katharina , Meller Tina , Pfarr Julia-Katharina , Stein Frederike , Schmitt Simon , Ringwald Kai G. , Waltemate Lena , Lemke Hannah , Thiel Katharina , Schrammen Elisabeth , Hülsmann Carina , Meinert Susanne , Dohm Katharina , Leehr Elisabeth J. , Opel Nils , Krug Axel , Dannlowski Udo , Nenadić Igor , Kircher Tilo 
Published: April 2021

AbstractBackgroundThe Covid-19 pandemic resulted in repeated, prolonged restrictions in daily life. Social distancing policies as well as health anxiety are thought to lead to mental health impairment. However, there is lack of longitudinal data identifying at-risk populations particularly vulnerable for elevated Covid-19-related distress.MethodsWe collected data of N=1268 participants (n=622 healthy controls (HC), and n=646 patients with major depression, bipolar disorder, schizophrenia or schizoaffective disorder) at baseline (2014-2018) and during the first lockdown in Germany (April-May 2020). We obtained information on Covid-19 restrictions (number and subjective impact of Covid-19 events), and Covid-19-related distress (i.e., subjective fear and isolation). Using multiple linear regression models including trait variables and individual Covid-19 impact, we sought to predict Covid-19-related distress.ResultsHC and patients reported similar numbers of Covid-19-related events, and similar subjective impact rating. They did not differ in Covid-19-related subjective fear. Patients reported significantly higher subjective isolation. 30.5% of patients reported worsened self-rated symptoms since the pandemic. Subjective fear in all participants was predicted by four variables: trait anxiety (STAI-T), conscientiousness (NEO-FFI), Covid-19 impact, and sex. Subjective isolation in HC was predicted by social support (FSozu), Covid-19 impact, age, and sex; in patients, it was predicted by social support and Covid-19 impact.ConclusionOur data shed light on differential effects of the pandemic in psychiatric patients and HC. They identify relevant, easy-to-obtain variables for risk profiles related to interindividual differences in Covid-19-related distress for direct translation into clinical practice.
Clinical implementation of RNA sequencing for Mendelian disease diagnostics
Authors: Yépez Vicente A. , Gusic Mirjana , Kopajtich Robert , Mertes Christian , Smith Nicholas H. , Alston Charlotte L. , Ban Rui , Beblo Skadi , Berutti Riccardo , Blessing Holger , Ciara Elżbieta , Distelmaier Felix , Freisinger Peter , Häberle Johannes , Hayflick Susan J. , Hempel Maja , Itkis Yulia S. , Kishita Yoshihito , Klopstock Thomas , Krylova Tatiana D. , Lamperti Costanza , Lenz Dominic , Makowski Christine C. , Mosegaard Signe , Müller Michaela F. , Muñoz-Pujol Gerard , Nadel Agnieszka , Ohtake Akira , Okazaki Yasushi , Procopio Elena , Schwarzmayr Thomas , Smet Joél , Staufner Christian , Stenton Sarah L. , Strom Tim M. , Terrile Caterina , Tort Frederic , Van Coster Rudy , Vanlander Arnaud , Wagner Matias , Xu Manting , Fang Fang , Ghezzi Daniele , Mayr Johannes A. , Piekutowska-Abramczuk Dorota , Ribes Antonia , Rötig Agnès , Taylor Robert W. , Wortmann Saskia B. , Murayama Kei , Meitinger Thomas , Gagneur Julien , Prokisch Holger 
Published: April 2021

AbstractBackgroundLack of functional evidence hampers variant interpretation, leaving a large proportion of cases with a suspected Mendelian disorder without genetic diagnosis after genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. However, collection of additional biopsies, and establishment of lab workflows, analytical pipelines, and defined concepts in clinical interpretation of aberrant gene expression are still needed for adopting RNA-sequencing (RNA-seq) in routine diagnostics.MethodsWe implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial disease which previously underwent WES.ResultsWe detected on average 12,500 genes per sample including around 60% disease genes - a coverage substantially higher than with whole blood, supporting the use of skin biopsies. We prioritized genes demonstrating aberrant expression, aberrant splicing, or mono-allelic expression. The pipeline required less than one week from sample preparation to result reporting and provided a median of eight disease-associated genes per patient for inspection. A genetic diagnosis was established for 16% of the 205 WES-inconclusive cases. Detection of aberrant expression was a major contributor to diagnosis including instances of 50% reduction, which, together with mono-allelic expression, allowed for the diagnosis of dominant disorders caused by haploinsufficiency. Moreover, calling aberrant splicing and variants from RNA-seq data enabled detecting and validating splice-disrupting variants, of which the majority fell outside WES-covered regions.ConclusionTogether, these results show that streamlined experimental and computational processes can accelerate the implementation of RNA-seq in routine diagnostics.One sentence summaryImplementation of RNA-seq as a complementary tool in standard diagnostics achieves a 16% in diagnosis rate over whole exome sequencing.
Chemotherapy-induced collagen IV drives cancer cell invasion through activation of Src/FAK signaling
Authors: Fatherree Jackson P. , Guarin Justinne R. , McGinn Rachel A. , Naber Stephen P. , Oudin Madeleine J. 
Published: April 2021

AbstractTriple-negative breast cancer (TNBC) is the most aggressive and deadly subtype of breast cancer, accounting for 30,000 cases annually in the US. While there are several clinical trials ongoing to identify new agents to treat TNBC, the majority of TNBC patients are treated with anthracycline- or taxane-based chemotherapies in the neoadjuvant setting, followed by surgical resection and adjuvant chemotherapy. While many patients respond well to this approach, as many as 25% will suffer local or metastatic recurrence within five years. Understanding the mechanisms that drive recurrence after chemotherapy treatment is critical to improving survival for patients with TNBC. It is well-established that the extracellular matrix, which provides structure and support to tissues, is a major driver of tumor growth, local invasion and dissemination of cancer cells to distant metastatic sites. In the present study, we show that decellularized extracellular matrix (dECM) obtained from chemotherapy-treated mice increases invasion of treatment-naïve breast cancer cells compared to vehicle-treated dECM. Using tandem-mass-tag proteomics, we further demonstrate that anthracycline- and taxane-based chemotherapies induce drug-specific changes in tumor ECM composition. We identify the basement membrane protein collagen IV as significantly upregulated in the ECM of chemotherapy-treated mice and patients treated with neoadjuvant chemotherapy. We show that collagen IV drives invasion via Src/FAK signaling and that inhibiting collagen IV-driven signaling decreases invasion in chemotherapy-treated dECM. These studies provide a novel mechanism by which chemotherapy may induce metastasis via effects on ECM composition.One Sentence SummaryChemotherapy alters the extracellular matrix of breast tumors leading to increased invasion of residual cancer cells.
Physiological function of Flo11p domains and the particular role of amyloid core sequences of this adhesin inSaccharomyces cerevisiae
Authors: Bouyx Clara , Schiavone Marion , Teste Marie-Ange , Dague Etienne , Sieczkowski Nathalie , Julien Anne , Francois Jean Marie 
Published: April 2021

ABSTRACTFlocculins are a family of glycosylated proteins that provide yeast cells with several properties such as biofilm formation, flocculation, invasive growth or formation of velum. These proteins are similarly organised with a N-terminal (adhesion) domain, a stalk-like central B-domain with several repeats and a C-terminal sequence carrying a cell wall anchor site. They also contain amyloid β-aggregation-prone sequences whose functional role is still unclear. In this work, we show that Flo11p differs from other flocculins by the presence of unique amyloid-forming sequences, whose the number is critical in the formation of adhesion nanodomains under a physical shear force. Using a genome editing approach to identify the function of domains in Flo11p phenotypes, we show that the formation of cellular aggregates whose density increases with the number of amyloid sequences cannot be attributed to a specific domain of Flo11p. The same is true for plastic adhesion and surface hydrophobicity the intensity of which depends mainly on the abundance of Flo11p on the cell surface. In contrast, the N and C domains of Flo11p are essential for invasive growth in agar, whereas a reduction in the number of repeats of the B domain weakens this phenotype. However, expression ofFLO11alone is not sufficient to trigger this invasion phenotype. Finally, we show that this flocculin contributes to the integrity of the cell wall.
MICOS and F1FO-ATP synthase crosstalk is a fundamental property of mitochondrial cristae
Authors: Cadena Lawrence Rudy , Gahura Ondřej , Panicucci Brian , Zíková Alena , Hashimi Hassan 
Published: April 2021

AbstractMitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the Mitochondrial Contact Site and Cristae Organization System (MICOS) and the FOF1-ATP synthase are vital for sculpting cristae by opposing membrane bending forces. While MICOS promotes negative curvature at cristae junctions, dimeric FOF1- ATP synthase is crucial for positive curvature at cristae rims. Crosstalk between these two complexes has been observed in baker’s yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved inTrypanosoma brucei, a member of the Discoba supergroup that separated from Opisthokonta ∼2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO- ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged trypanosome homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers, interacts with Mic10 and its silencing results in severe defects to cristae and disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting cristae shape throughout eukaryotes.ImportanceMitochondria have undergone profound diversification in separate lineages that have radiated since the last common ancestor of eukaryotes some eons ago. Most eukaryotes are unicellular protists, including etiological agents of infectious diseases likeTrypanosoma brucei. Thus, the study of a broad range of protists can reveal fundamental features shared by all eukaryotes and lineage-specific innovations. Here we report that two different protein complexes, MICOS and F1FO-ATP synthase, known to affect mitochondrial architecture, undergo crosstalk inT. brucei, just as in baker’s yeast. This is remarkable considering that these complexes have otherwise undergone many changes during their almost two billion years of independent evolution. Thus, this crosstalk is a fundamental property needed to maintain proper mitochondrial structure even if the constituent players considerably diverged.
Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients
Authors: David Goncalves , Mehdi Mezidi , Paul Bastard , Magali Perret , Kahina Saker , Nicole Fabien , Rémi Pescarmona , Christine Lombard , Thierry Walzer , Jean-Laurent Casanova , Alexandre Belot , Jean-Christophe Richard , Sophie Trouillet-Assant 
Published: April 2021

AbstractObjectivesImpairment of type I interferon (IFN-I) immunity has been reported in critically-ill COVID-19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto-Abs) against IFN-I. We set out to improve the detection and the quantification of IFN-I auto-Abs in a cohort of critically-ill COVID-19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease.MethodsThe concentration of anti-IFN-α2 Abs was determined in the serum of 84 critically-ill COVID-19 patients who were admitted to ICU in Hospices Civils de Lyon, France using a commercially available kit (Thermo-Fisher, Catalog #BMS217).ResultsA total of 21/84 (25%) critically-ill COVID-19 patients had circulating anti-IFN-α2 Abs above cut-off (>34 ng.mL-1). Among them, 15/21 had Abs with neutralizing activity against IFN-α2, i.e. 15/84 (18%) of critically-ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralizing anti-IFN-α2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralizing anti-IFN-α2 auto-Abs. We detected anti-IFN-α2 auto-Abs in COVID-19 patients’ sera throughout their ICU stay. Finally, we also found auto-Abs against multiple subtypes of IFN-I including IFN-ω.ConclusionsWe reported that 18% of critically-ill COVID-19 patients were positive for IFN-I auto-Abs, confirming that the presence of these antibodies is associated with higher risk of developing a criticall COVID-19 form.
Signatures of COVID-19 severity and immune response in the respiratory tract microbiome
Authors: Merenstein Carter , Liang Guanxiang , Whiteside Samantha A. , Cobián-Güemes Ana G. , Merlino Madeline S. , Taylor Louis J. , Glascock Abigail , Bittinger Kyle , Tanes Ceylan , Graham-Wooten Jevon , Khatib Layla A. , Fitzgerald Ayannah S. , Reddy Shantan , Baxter Amy E. , Giles Josephine R. , Oldridge Derek A. , Meyer Nuala J. , Wherry E. John , McGinniss John E. , Bushman Frederic D. , Collman Ronald G. 
Published: April 2021

AbstractRationaleViral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease.ObjectiveTo define the respiratory tract microbiome in COVID-19 and relationship disease severity, systemic immunologic features, and outcomes.Methods and MeasurementsWe examined 507 oropharyngeal, nasopharyngeal and endotracheal samples from 83 hospitalized COVID-19 patients, along with non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR, and immune features were characterized by lymphocyte/neutrophil (L/N) ratios and deep immune profiling of peripheral blood mononuclear cells (PBMC).Main ResultsCOVID-19 patients had upper respiratory microbiome dysbiosis, and greater change over time than critically ill patients without COVID-19. Diversity at the first time point correlated inversely with disease severity during hospitalization, and microbiome composition was associated with L/N ratios and PBMC profiles in blood. Intubated patients showed patient-specific and dynamic lung microbiome communities, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity.ConclusionsThe respiratory tract microbiome and commensal virome are disturbed in COVID-19, correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, possible use as biomarkers, and role of bacterial and viral taxa identified here in COVID-19 pathogenesis.
Diagnostic Utility of Antigen Detection Rapid Diagnostic Tests for Covid- 19: A Systematic Review and Meta-Analysis
Authors: Ebrahimi Mina , Harmooshi Narges Nazari , Rahim Fakher 
Published: April 2021

AbstractBackgroundEarly detection of coronavirus disease (COVID-19) infection to improve disease management, becomes the greatest challenge. Despite high sensitivity of RT-PCR, not only it was reported that 20-67% of infected patients have false negative results. Rapid diagnostic tests (RDTs) are widely used as a point-of-care test for SARS-CoV-2 detection in both pharyngeal and blood specimens. To be less time-consuming, not seem so costly, and requiring no special training make it more favorable, but the low sensitivity is the main limitation. Several reports indicated rapid test of blood and pharyngeal samples has the same sensitivity as the RT-PCR, but some reports have lower sensitivity especial in asymptomatic patients.MethodsIn the present survey, we investigate the eligible studies for sensitivity and specificity of rapid tests and explore the factors that influence the result to help better diagnose COVID-19 infection. 20 studies met the inclusion criteria, which impose 33 different tests.ResultsOur findings showed, type of sample, type of assay, time of sampling, and load of virus influence on sensitivity of RDTs.ConclusionThis research extends our knowledge of how to improve the sensitivity of RDTs to better diagnose of infected patients to address the controlling COVID-19 pandemic.
EgGLUT1 is crucial for the viability of larvae ofEchinococcus granulosus sensus latoby involving its glucose uptake
Authors: Amahong Kuerbannisha , Yan Mingzhi , Li Jintian , Yang Ning , Liu Hui , Bi Xiaojuan , Vuitton Dominique A. , Lin Renyong , Lü Guodong 
Published: April 2021

ABSTRACTCystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae ofEchinococcus granulosus sensu lato(s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, presence and role of GLUT1 inE. granulosus s.l.(EgGLTU1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) fromE. granulosus sensu stricto(s.s.) and found EgGLUT1-ss was crucial for glucose uptake of the protoscoleces ofE. granulosus s.s..WZB117, a GLUT1 inhibitor, inhibited glucose uptake ofE. granulosus s.s.and the viability of the metacestodein vitro.In addition, WZB117 showed potent therapeutic activity inE. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts as well as the reference drug, albendazole. Our data have defined EgGLUT1 as a keyE. granulosus s.l.vulnerability target, involved in its glucose uptake from the host; this opens a new avenue to identify drugs with an ideal activity profile for the treatment of CE.