bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study
Authors: Cann Alexandra , Clarke Candice , Brown Jonathan , Thomson Tina , Prendecki Maria , Moshe Maya , Badhan Anjna , Elliott Paul , Darzi Ara , Riley Steven , Ashby Deborah , Willicombe Michelle , Kelleher Peter , Randell Paul , Ward Helen , Barclay Wendy S , Cooke Graham 
Published: July 2021

AbstractBackgroundLateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine.MethodsThis is a prospective diagnostic accuracy study.SettingSampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities.ParticipantsTwo cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected.InterventionsDuring the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.Main outcome measuresThe accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay.ResultsUsing the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard.ConclusionsFortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.
SARS-CoV-2 variants of concern, Gamma (P.1) and Delta (B.1.617), sensitive detection and quantification in wastewater employing direct RT-qPCR
Authors: Yaniv Karin , Ozer Eden , Kushmaro Ariel 
Published: July 2021

AbstractSARS-CoV-2 variants of concern present a worldwide threat. Demonstrating higher infection rate and durability to antibodies when compared to the original SARS-CoV-2 virus, the variants of concern are responsible for continuing global outbreaks. Prompt identification of the infecting SARS-CoV-2 variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive, time-consuming next generation sequencing. Rapid identification methodology for variants of concern is of great need and various variant-specific assays are being developed. Amongst the variants of concern that have recently appeared, the Gamma variant (P.1, Brazilian) and Delta variant (B.1.617, Indian) are the most prominent. Here we describe the development of a sensitive RT-qPCR assay for the quick direct detection of the Gamma and Delta variants as part of a methodical characterization and detection in municipal wastewater.
London Ramadan Fasting Study (LORANS): Rationale, design, and methods
Authors: Al-Jafar Rami , Elliott Paul , Tsilidis Konstantinos K. , Dehghan Abbas 
Published: July 2021

AbstractBackgroundHundreds of millions of Muslims fast during the month of Ramadan. The London Ramadan Fasting Study (LORANS) aims to assess the lifestyle changes during this month and investigate the effect of Ramadan fasting on health.MethodsLORANS is an observational study of participants that follow religious fasting in Ramadan. We advertised, recruited, and visited participants in five mosques in London, United Kingdom. In total, 146 individuals were recruited before Ramadan in May 2019 of which 85 participated in the follow up visit after Ramadan. The study protocol was approved by the ethics committee affiliated to Imperial College London. A written informed consent was signed by all the participants. Every participant completed a questionnaire, a physical examination, and gave blood samples at each visit. Moreover, they completed a 3-day food diary before Ramadan and once again during Ramadan to record dietary changes during the month of fasting.ResultsThe mean age of participants was 45.6± 15.9 years. 47.1% of the participants were females, 25.5% were obese, 4.7% were smokers, 14% were diabetic, 24% were hypertensive, and 5.2% had cardiovascular diseases. Data collection covered demographics, lifestyle, food intake, blood pressure, anthropometric measurements, body composition, and metabolic biomarker profiling.ConclusionBy engaging with mosques, proper introduction of the study aims and convenient recruitment in the mosque, we were able to recruit a balanced population regarding age and sex and collected valuable data on Ramadan fasting using high-quality techniques.
Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults
Authors: Sumazin Pavel , Peters Tricia L. , Sarabia Stephen F. , Kim Hyunjae R. , Urbicain Martin , Hollingsworth Emporia Faith , Alvarez Karla R. , Perez Cintia R. , Pozza Alice , Panah Mohammad Javad Najaf , Elswood Jessica L. , Scorsone Kathy , Katzenstein Howard , O’Neal Allison , Meyers Rebecka , Tiao Greg , Geller Jim , Ranganathan Sarangarajan , Rangaswami Arun A. , Woodfield Sarah E. , Goss John A. , Vasudevan Sanjeev A. , Heczey Andras , Roy Angshumoy , Fisher Kevin E. , Alaggio Rita , Patel Kalyani R. , Finegold Milton J. , López-Terrada Dolores H. 
Published: July 2021

ABSTRACTMalignant hepatocellular cancers are the most common primary liver malignancies in children, and hepatoblastomas (HBs) account for more than two-thirds of these cases. While most HBs respond to chemotherapy and have favorable outcomes, the 3-year overall survival rate for high-risk HBs is below 50% and guidelines for their classification and treatment are still evolving. HB risk-stratification efforts using clinical, histological, and molecular parameters have been reported to help identify patients that require more or less aggressive therapies in retrospective studies, and are being validated in clinical trials. However, risk assessment is particularly challenging for cancers with certain histologies, including tumors in the recently proposed provisionalhepatocellular neoplasm not otherwise specified(HCN NOS) category. HCN NOSs exhibit either intermediate or combined HB and hepatocellular carcinoma (HCC) histological features, and while neoplasms with such features were observed over a decade ago, only a handful have been characterized and little is known about their biology and clinical features. Here, we molecularly characterized a series of clinically annotated HCN NOSs that demonstrated either intermediate HB/HCC histology or distinct coexisting areas with HB and HCC histological features. In addition, molecular profiling of HBs demonstrating focal pleomorphism or anaplasia (HB FPA) revealed underlying biological features previously observed in HCCs. Our study suggested that HCN NOSs and HB FPAs are aggressive tumors, irrespective of patient age or resectability. Consequently, we designated them collectively asHBs with carcinoma features(HBCs) and outlined histological and molecular characteristics for their diagnosis and treatment. In our single-institution study, transplanted HBC patients were significantly and more than twice as likely to have good outcomes, highlighting the importance of molecular testing and aggressive early intervention.
Unravelling the puzzle of anthranoids metabolism in living plant cells using spectral imaging coupled to mass spectrometry
Authors: Chevalier Quentin , Gallé Jean-Baptiste , Wasser Nicolas , Mazan Valérie , Villette Claire , Mutterer Jérôme , Elustondo Maria M. , Girard Nicolas , Elhabiri Mourad , Schaller Hubert , Hemmerlin Andréa , Vonthron-Sénécheau Catherine 
Published: July 2021

AbstractVismione H (VH) is a fluorescent prenylated anthranoid produced by plants from the Hypericaceae family, with antiprotozoal activities against malaria and leishmaniosis. Little is known about its biosynthesis and metabolism in plants or its mode of action against parasites. When VH is isolated from Psorospermum glaberrimum, it is rapidly converted into madagascine anthrone and anthraquinone, which are characterized by markedly different fluorescent properties. To locate the fluorescence of VH in living plant cells and discriminate it from that of the other metabolites, an original strategy combining spectral imaging (SImaging), confocal microscopy and non-targeted metabolomics using mass spectrometry, was developed. Besides VH, structurally related molecules including madagascine, emodin, quinizarin as well as lapachol and fraxetin were analyzed. This strategy readily allowed a spatiotemporal characterization and discrimination of spectral fingerprints from anthranoids-derived metabolites and related complexes with cations and proteins. In addition, our study validates the capability of plant cells to metabolize VH into madagascine anthrone, anthraquinones and unexpected metabolites, leading to new hypotheses on the metabolism of anthranoids in plants.
Visualizing Amino Acid Substitutions in a Physicochemical Vector Space
Authors: Nemzer Louis R. 
Published: July 2021

AbstractA three-dimensional representation of the twenty proteinogenic amino acids in a physicochemical space is presented. Vectors corresponding to amino acid substitutions are classified based on whether they are accessible via a single-nucleotide mutation. It is shown that the standard genetic code establishes a “choice architecture” that permits nearly independent tuning of the properties related with size and those related with hydrophobicity. This work sheds light on the non-arbitrary benefits of evolvability that may have shaped the development standard genetic code to increase the probability that adaptive point mutations will be generated. Illustrations of the usefulness of visualizing amino acid substitutions in a 3D physicochemical space are shown using recent datasets collected regarding the SARS-CoV-2 receptor binding domain. First, the substitutions most responsible for antibody escape are almost always inaccessible via single nucleotide mutation, and change multiple properties concurrently. Second, it is shown that assays of ACE2 binding by sarbecovirus variants, including the viruses responsible for SARS and COVID-19, are more easily understood when plotted with this method. The results of this research can extend our understanding of certain hereditary disorders caused by point mutations, as well as guide the development of rational protein and vaccine design.
Ultraviolet screening by slug tissue and tight packing of plastids protect photosynthetic sea slugs from photoinhibition
Authors: Havurinne Vesa , Aitokari Riina , Mattila Heta , Käpylä Ville , Tyystjärvi Esa 
Published: July 2021

SummaryOne of the main unsolved questions regarding photosynthetic sea slugs is how the slug plastids handle photoinhibition of Photosystem II. Photoinhibition has not been studied in detail in these animals although resilience against photoinhibition might obviously explain the longevity of plastids inside animal cytosol.Light response and action spectrum of photoinhibition were measured from the slug Elysia timida and its prey alga Acetabularia acetabulum. Plastid packing in the slugs and algae was compared with spectroscopic and microscopic methods. The importance of plastid concentration was also estimated by measuring photoinhibition from starved slugs.Compared to A. acetabulum, E. timida is highly resistant against photoinhibition. The resilience of the slugs is even more pronounced in the UV-region, as the slug tissue screens UV radiation. The plastids in the slug tissue are tightly packed, and the outer plastids protect the inner ones from photoinhibition.The sea slug E. timida protects its plastids from photoinhibition by screening UV radiation and packing the plastids tightly in its tissues. Both mechanisms enhance the longevity of the plastids in slug cytosol and ameliorate the need for repair of photoinhibited Photosystem II.
Cellular translational enhancer elements that recruit eukaryotic initiation factor 3
Authors: Koubek Jiří , Niederer Rachel O. , Stanciu Andrei , Aitken Colin Echeverría , Gilbert Wendy V. 
Published: July 2021

AbstractTranslation initiation is a highly regulated process which broadly affects eukaryotic gene expression. Eukaryotic initiation factor 3 (eIF3) is a central player in canonical and alternative pathways for ribosome recruitment. Here we have investigated how direct binding of eIF3 contributes to the large and regulated differences in protein output conferred by different 5′-untranslated regions (5′-UTRs) of cellular mRNAs. Using an unbiased high-throughput approach to determine the affinity of budding yeast eIF3 for native 5′-UTRs from 4,252 genes, we demonstrate that eIF3 binds specifically to a subset of 5′-UTRs that contain a short unstructured binding motif, AMAYAA. eIF3 binding mRNAs have higher ribosome density in growing cells and are preferentially translated under certain stress conditions, supporting the functional relevance of this interaction. Our results reveal a new class of translational enhancer and suggest a mechanism by which changes in core initiation factor activity enact mRNA-specific translation programs.
Structural basis for protein glutamylation by the Legionella pseudokinase SidJ
Authors: Adams Michael , Sharma Rahul , Colby Thomas , Weis Felix , Matic Ivan , Bhogaraju Sagar 
Published: July 2021

ABSTRACTLegionella pneumophila (LP) avoids phagocytosis by secreting nearly 300 effector proteins into the host cytosol. SidE family of effectors (SdeA, SdeB, SdeC and SidE) employ phosphoribosyl serine ubiquitination to target an array of host Rab GTPases and innate immune factors. To suppress the deleterious toxicity of SidE enzymes in a timely manner, LP employs a metaeffector named SidJ. Upon activation by host Calmodulin (CaM), SidJ executes an ATP-dependent glutamylation to modify the catalytic residue Glu860 in the mono-ADP-ribosyl transferase (mART) domain of SdeA. SidJ is a unique glutamylase that adopts a kinase-like fold but contains two nucleotide-binding pockets. There is a lack of consensus about the substrate recognition and catalytic mechanism of SidJ. Here, we determined the cryo-EM structure of SidJ in complex with its substrate SdeA in two different states of catalysis. Our structures reveal that both phosphodiesterase (PDE) and mART domains of SdeA make extensive contacts with SidJ. In the pre-glutamylation state structure of the SidJ-SdeA complex, adenylylated E860 of SdeA is inserted into the non-canonical (migrated) nucleotide-binding pocket of SidJ. Structure-based mutational analysis indicates that SidJ employs its migrated pocket for the glutamylation of SdeA. Finally, using mass spectrometry, we identified several transient autoAMPylation sites close to both the catalytic pockets of SidJ. Our data provide unique insights into the substrate recognition and the mechanism of protein glutamylation by the pseudokinase SidJ.
Accurate Direct PCR with Arabidopsis and rice
Authors: Lynagh Peter , Osuna-Kleist Paul , Wang Bohai , Malagon Edgar , Anleu Gil Maria Ximena , Comai Luca 
Published: July 2021

AbstractPlant sampling methods for PCR that avoid costly and time-consuming plant DNA purification can be accurate but have not been widely adopted, partly because the efficacy of the methods is unclear. Here, we introduce new sampling methods for Direct PCR in Arabidopsis and rice and compare them to previously published methods. CutTip, stabbing a pipette tip into a plant and depositing the tip of the pipette tip into the reaction buffer, yielded high accuracy for genotyping Arabidopsis and rice. This did not require visible tissue fragments in the reactions. We found that using short thin segments of fishing line, called Line-PCR, to be even more practical and highly accurate. Compared to traditional and other Direct PCR preparation methods, Line-PCR is faster, inexpensive, easier, uses less plastic and chemicals, and causes the least tissue damage. CutTip and Line-PCR require no modified PCR reagents. Line-PCR particularly lacks any complicated steps. Probably, the most difficult step in Line-PCR is a wipe of the tweezer between samples. These methods can help address the challenge of genotyping at different scales with high accuracy. CutTip and Line-PCR also simplify the application of PCR in the field.
A single de novo substitution in SARS-CoV-2 spike informs enhanced adherence to human ACE2
Authors: Erausquin Elena , López-Sagaseta Jacinto 
Published: July 2021

AbstractSARS-CoV-2 initiates colonization of host cells by binding to cell membrane ACE2 receptor. This binding is mediated by the viral spike receptor binding domain (RBD). The COVID-19 pandemic has brought devastating consequences at a clinical, social and economical levels. Therefore, anticipation of potential novel SARS-causing species or SARS-CoV-2 variants with enhanced binding to ACE2 is key in the prevention of future threats to come. We have characterized a de novo single substitution, Q498Y, in SARS-CoV-2 RBD that confers stronger adherence to ACE2. While the SARS-CoV-2 β variant, which includes three simultaneous amino acid replacements, induces a 4-fold stronger affinity, a single Q498Y substitution results in 2.5-fold tighter binding, compared to the Wuhan-Hu-1 SARS-CoV-2 2019 strain. Additionally, we crystallized RBDQ498Y complexed with ACE2 and provide here the structural basis for this enhanced affinity. These studies inform a rationale for prevention of potential SARS-causing viruses to come.
Obsessive Compulsive Disorder and Response Inhibition: Meta-analysis of the Stop-Signal Task
Authors: Mar Kendall , Townes Parker , Pechlivanoglou Petros , Arnold Paul , Schachar Russell 
Published: July 2021

AbstractThis systematic review and meta-analysis updates evidence pertaining to deficient response inhibition in obsessive-compulsive disorder (OCD) as measured by the stop-signal task (SST). We conducted a meta-analysis of the literature to compare response inhibition in patients with OCD and healthy controls, meta-regressions to determine relative influences of age and sex on response inhibition impairment, and a risk of bias assessment for included studies using the Newcastle-Ottawa Scale (NOS). Stop-signal reaction time (SSRT), which estimates the latency of the stopping process deficit, was significantly longer in OCD samples than in controls, reflecting inferior inhibitory control (Raw mean difference = 23.43ms; p = <0.001; 95% CI = [17.42, 29.45]). We did not observe differences in mean reaction time (MRT) in OCD compared to controls (Raw mean difference = 2.51ms; p = 0.755; 95% CI = [−13.27, 18.30]). Age impacted effect size of SSRT, indicating a greater deficit in older patients than younger ones. We did not observe a significant effect of sex on SSRT or MRT scores.General Scientific SummaryDifficulty inhibiting responses is an hypothesized deficit in Obsessive-Compulsive Disorder (OCD). The results of this systematic review and meta-analysis of studies using the Stop Signal Task support the notion of deficient response inhibition in OCD and indicate that older individuals with OCD show greater impairments than younger ones.
Efficient Estimation of Indirect Effects in Case-Control Studies Using a Unified Likelihood Framework
Authors: Satten Glen A. , Curtis Sarah W. , Solis-Lemus Claudia , Leslie Elizabeth J. , Epstein Michael P. 
Published: July 2021

ABSTRACTMediation models are a set of statistical techniques that investigate the mechanisms that produce an observed relationship between an exposure variable and an outcome variable in order to deduce the extent to which the relationship is influenced by intermediate mediator variables. For a case-control study, the most common mediation analysis strategy employs a counterfactual framework that permits estimation of indirect and direct effects on the odds ratio scale for dichotomous outcomes, assuming either binary or continuous mediators. While this framework has become an important tool for mediation analysis, we demonstrate that we can embed this approach in a unified likelihood framework for mediation analysis in case-control studies that leverages more features of the data (in particular, the relationship between exposure and mediator) to improve efficiency of indirect effect estimates. One important feature of our likelihood approach is that it naturally incorporates cases within the exposure-mediator model to improve efficiency. Our approach does not require knowledge of disease prevalence and can model confounders and exposure-mediator interactions, and is straightforward to implement in standard statistical software. We illustrate our approach using both simulated data and real data from a case-control genetic study of lung cancer.
Transcriptomic analysis of mdx mouse muscles reveals a signature of early human Duchenne muscular dystrophy
Authors: Ralston Evelyn , Gutierrez-Cruz Gustavo , Kenea Aster , Brooks Stephen R. 
Published: July 2021

ABSTRACTThe mdx mouse (C57BL/10ScSn-DMDmdx/J) is the oldest model of Duchenne muscular dystrophy (DMD). Mdx remains popular and has not been replaced by newer mouse models, despite criticisms that mdx has a nearly normal lifespan and mild pathology while DMD remains a severe, fatal disease. At some point we noticed that the absence of mdx RNA-seq data limited our ability to assess the results of physiological work on the mouse model and to compare these results to human genetic data [1]. We carried out RNA-seq analysis of wild-type and mdx mice of 2 and 5 months of age, using three hindlimb muscles per mouse: the flexor digitorum brevis (FDB), the extensor digitorum longus (EDL) and the soleus (SOL), with a total of 55 samples. We then mined the data and found that each of the three muscles is a valid experimental model for DMD-related mouse work, even the FDB, despite a delayed pathology development. We also show that the mdx mouse muscles are enriched in metabolic, developmental, regenerational and structural pathways that have been found to be the “disease signature” of DMD in young and presymptomatic subjects [38, 39]. Additionally, we show that healthy human muscle fiber microtubules present the grid-like organization found in control rodents but perturbed in the mdx mouse. We conclude that the mdx mouse appropriately mimics the early stages of DMD, with its microtubule defects signaling fiber regeneration [35]. We hope that these results may contribute to a better understanding of the failure of regeneration as DMD progresses.