bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of subsequent and co-infections associated with SARS-CoV-2 (COVID-19) in hospitalized patients
Authors: Crotty Matthew P. , Akins Ronda , Nguyen An , Slika Rania , Rahmanzadeh Kristen , Wilson Marie H. , Dominguez Edward A. 
Published: May 2020

AbstractBackgroundSARS-CoV-2 has drastically affected healthcare globally and causes COVID-19, a disease that is associated with substantial morbidity and mortality. We aim to describe rates and pathogens involved in co-infection or subsequent infections and their impact on clinical outcomes among hospitalized patients with COVID-19.MethodsIncidence of and pathogens associated with co-infections, or subsequent infections, were analyzed in a multicenter observational cohort. Clinical outcomes were compared between patients with a bacterial respiratory co-infection (BRC) and those without. A multivariable Cox regression analysis was performed evaluating survival.ResultsA total of 289 patients were included, 48 (16.6%) had any co-infection and 25 (8.7%) had a BRC. No significant differences in comorbidities were observed between patients with co-infection and those without. Compared to those without, patients with a BRC had significantly higher white blood cell counts, lactate dehydrogenase, C-reactive protein, procalcitonin and interleukin-6 levels. ICU admission (84.0 vs 31.8%), mechanical ventilation (72.0 vs 23.9%) and in-hospital mortality (45.0 vs 9.8%) were more common in patients with BRC compared to those without a co-infection. In Cox proportional hazards regression, following adjustment for age, ICU admission, mechanical ventilation, corticosteroid administration, and pre-existing comorbidities, patients with BRC had an increased risk for in-hospital mortality (adjusted HR, 3.37; 95% CI, 1.39 to 8.16; P = 0.007). Subsequent infections were uncommon, with 21 infections occurring in 16 (5.5%) patients.ConclusionsCo-infections are uncommon among hospitalized patients with COVID-19, however, when BRC occurs it is associated with worse clinical outcomes including higher mortality.
Atorvastatin and standard treatment of Helicobacter pylori: Randomized Clinical Trial
Authors: Azar Mohammad Reza Mohammad Hoseini , Portaghali Parham , Sedokani Amin , Jafari Ali 
Published: May 2020

AbstractBackgroundConsidering the increase in drug resistance over time to Helicobacter pylori treatment relying on the anti-inflammatory and antibacterial effects of atorvastatin to increase the success rate of H. pylori eradication, we examined the effect of adding atorvastatin to standard treatment of H. pylori eradication.Materials and MethodsA total of 186 symptomatic patients who had been diagnosed with Helicobacter pylori infection and tested for H. pylori eradication were examined by a pathological response or positive urea breath test. Patients who received atorvastatin in addition to standard treatment were also identified based on a table of random numbers. Standard treatment included a 240mg bismuth subcitrate tablet, a 40mg pantoprazole tablet, a 500mg metronidazole tablet, and 2 capsules of 500mg amoxicillin, all taken BID for 14 days. After 4 weeks of treatment, all patients underwent stool testing for H. pylori fecal antigen. If the test was positive, the request was considered a failure of treatment, and if the test was negative, it was considered a successful eradication of H. pylori. The clinical trial registration code for this study is IRCT20190823044589N1.ResultsThe eradication rate of H. pylori was 80% in the control group and 80.9% in the intervention group, which did not show a statistically significant difference between the two groups (P-value=0.971).ConclusionAdding atorvastatin to 4-drug regimen of PPI, bismuth subcitrate, amoxicillin, and metronidazole as the first line of treatment for H. pylori eradication is ineffective.Significance of this Study (Summary box)What is already known about this subject?Infection of H. pylori is common worldwide and the antibiotic resistance is increasingAtorvastatin, has anti-inflammatory and antibacterial effects. But also, have D grade interaction with clarithromycin in H. pylori eradication regimen and increases the toxic and lethal risk of atorvastatin toxicity.What are the new findings?Eradication rate of H. pylori using the standard treatment of a 240mg bismuth subcitrate tablet, a 40mg pantoprazole tablet, a 500mg metronidazole tablet, and 2 capsules of 500mg amoxicillin, BID for 14 days, is at least 80%.Adding atorvastatin to 4-drug regimen of PPI, bismuth subcitrate, amoxicillin, and metronidazole as the first line of treatment for H. pylori eradication is ineffective.How might it impact on clinical practice in the foreseeable future?There should be more analysis on cost-benefice of adding atorvastatin to standard regimen of treatment for H. pylori eradication, but adding the atorvastatin to metronidazole-based H. pylori treatment is ineffective and for clarithromycin-based treatment is dangerous.
Social Distancing Interventions in the United States: An Exploratory Investigation of Determinants and Impacts
Authors: Guo Shenyang , An Ruopeng , McBride Timothy D. , Yu Danlin , Fu Linyun , Yang Yuanyuan 
Published: May 2020

AbstractBackgroundTo combat the Covid-19 pandemic in the United States, many states and Washington DC enacted Stay-at-Home order and nonpharmaceutical mitigation interventions. This study examined the determinants of the timing to implement an intervention. Through an impact analysis, the study explored the effects of the interventions and the potential risks of removing them under the context of reopening the economy.MethodA content analysis identified nine types of mitigation interventions and the timing at which states enacted these strategies. A proportional hazard model, a multiple-event survival model, and a random-effect spatial error panel model in conjunction with a robust method analyzing zero-inflated and skewed outcomes were employed in the data analysis.FindingsTo our knowledge, we provided in this article the first explicit analysis of the timing, determinants, and impacts of mitigation interventions for all states and Washington DC in the United States during the first five weeks of the pandemic. Unlike other studies that evaluate the Stay-at-Home order by using simulated data, the current study employed the real data of various case counts of Covid-19. The study obtained two meritorious findings: (1) states with a higher prevalence of Covid-19 cases per 10,000 population reacted more slowly to the outbreak, suggesting that some states may have missed the optimal timing to prevent the wide spread of the Covid-19 disease; and (2) of nine mitigation measures, three (non-essential business closure, large-gathering bans, and restaurant/bar limitations) showed positive impacts on reducing cumulative cases, new cases, and death rates across states.InterpretationThe opposite direction of the prevalence rate on the timing of issuing the mitigation interventions partially explains why the Covid-19 caseload in the U.S. remains high. A swift implementation of social distancing is crucial— the key is not whether such measures should be taken but when. Because there is no preventive vaccine and because there are few potentially effective treatments, recent reductions in new cases and deaths must be due, in large part, to the social interventions delivered by states. The study suggests that the policy of reopening economy needs to be implemented carefully.
Trend analysis, modelling and impact assessment of COVID-19 in Nepal
Authors: Bhandary Shital , Shrestha Srijan Lal , Khatiwada Ram Prasad , Shah Deep Narayan , Munankarmi Nabin Narayan , Banjara Megha Raj , Thapa-Parajuli Resham , Manandhar Krishna Das , Adhikari Rameshwar , Tuladhar Reshma 
Published: May 2020

AbstractWith continued global expansion of COVID-19 transmission and mounting threat of the the timely analysis of its trend in Nepal and forecasting the potential situation in the country has been deemed necessary. We analyzed the trend, modelling and impact assessment of COVID-19 disease, cases of Nepal from 23rdJanuary 2020 to 30thApril 2020 to portray the scenario of COVID-19 after the first phase of lockdown. Exponential smoothing state-space and autoregressive integrated moving average (ARIMA) models were constructed to forecast the cases. Susceptible-infectious-recovered (SIR) model was fit to estimate the basic reproduction number (Ro) of COVID-19 in Nepal. There has been increase in the number of cases but the overall growth in COVID-19 was not high. Statistical modelling has shown that COVID-19 cases may continue to increase exponentially in Nepal. The basic reproduction number in Nepal being maintained at low level of 1.08 for the period of 23rdJanuary to 30thApril 2020 is an indication of effectiveness of lockdown in containing the COVID-19 spread. The models further suggest that COVID-19 might persist until December 2020 with peak cases in August 2020. On the other hand, basic reproduction number of 1.25 was computed for total cases reported for the 22ndMarch to 30thApril 2020 period implying that COVID-19 may remain for at least for a year in the country. Thus, maintaining social distance and stay home policy with an implementation of strict lockdown in COVID-19 affected district is highly recommended.
CUE: CpG impUtation Ensemble for DNA Methylation Levels Across the Human Methylation450 (HM450) and EPIC (HM850) BeadChip Platforms
Authors: Li Gang , Raffield Laura , Logue Mark , Miller Mark W , Santos Hudson P. , O’Shea T.Michael , Fry Rebecca C. , Li Yun 
Published: May 2020

AbstractDNA methylation at CpG dinucleotides is one of the most extensively studied epigenetic marks. With technological advancements, geneticists can profile DNA methylation with multiple reliable approaches. However, profiling platforms can differ substantially in the CpGs they assess, consequently hindering integrated analysis across platforms. Here, we present CpG impUtation Ensemble (CUE), which leverages multiple classical statistical and modern machine learning methods, to impute from the Illumina HumanMethylation450 (HM450) BeadChip to the Illumina HumanMethylationEPIC (HM850) BeadChip. Data were analyzed from two population cohorts with methylation measured both by HM450 and HM850: the Extremely Low Gestational Age Newborns (ELGAN) study (n=127, placenta) and the VA Boston Posttraumatic Stress Disorder (PTSD) genetics repository (n=144, whole blood). Cross-validation results show that CUE achieves the lowest predicted root mean square error (RMSE) (0.026 in PTSD) and the highest accuracy (99.97% in PTSD) compared with five individual methods tested, including k-nearest-neighbors, logistic regression, penalized functional regression, random forest and XGBoost. Finally, among all 339,033 HM850-only CpG sites shared between ELGAN and PTSD, CUE successfully imputed 289,604 (85.4%) sites, where success was defined as RMSE < 0.05 and accuracy >95% in PTSD. In summary, CUE is a valuable tool for imputing CpG methylation from the HM450 to HM850 platform.
Accurate prediction of genetic circuit behavior requires multidimensional characterization of parts
Authors: Dods Galen , Gómez-Schiavon Mariana , El-Samad Hana , Ng Andrew H. 
Published: May 2020

AbstractMathematical models can aid the design of genetic circuits, but may yield inaccurate results if individual parts are not modeled at the appropriate resolution. To illustrate the importance of this concept, we study transcriptional cascades consisting of two inducible synthetic transcription factors connected in series. Despite the simplicity of this design, we find that accurate prediction of circuit behavior requires mapping the dose responses of each circuit component along the dimensions of both its expression level and its inducer concentration. With such multidimensional characterizations, we were able to computationally explore the behavior of 16 different circuit designs. We experimentally verified a subset of these predictions and found substantial agreement. This method of biological part characterization enables the use of models to identify (un)desired circuit behaviors prior to experimental implementation, thus shortening the design-build-test cycle for more complex circuits.
Epigenome dysregulation resulting from NSD1 mutation in head and neck squamous cell carcinoma
Authors: Farhangdoost Nargess , Horth Cynthia , Hu Bo , Bareke Eric , Chen Xiao , Li Yinglu , Coradin Mariel , Garcia Benjamin A. , Lu Chao , Majewski Jacek 
Published: May 2020

ABSTRACTEpigenetic dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the epigenetic and transcriptomic consequences of mutations in epigenetic modifier genes. Recently, mutations in the histone methyltransferase gene NSD1 have been identified in a subset of head and neck squamous cell carcinomas (HNSCCs) – one of the most common and deadly cancers. Here, we use whole (epi)genome approaches and genome editing to dissect the downstream effects of loss of NSD1 in HNSCC. We demonstrate that NSD1 mutations are directly responsible for loss of intergenic H3K36me2 domains, followed by loss of DNA methylation, and gain of H3K27me3 in the affected genomic regions. We further show that those regions are enriched in cis-regulatory elements and that subsequent loss of H3K27ac correlates with reduced expression of their target genes. Our analysis identifies genes and pathways affected by the loss of NSD1 and paves the way to further understanding the interplay among chromatin modifications in cancer.
Quantifying Structural Diversity of CNG Trinucleotide Repeats Using Diagrammatic Algorithms
Authors: Phan Ethan N. H. , Mak Chi H. 
Published: May 2020

ABSTRACTTrinucleotide repeat expansion disorders (TREDs) exhibit complex mechanisms of pathogenesis, some of which have been attributed to RNA transcripts of overexpanded CNG repeats, resulting in possibly a gain-of-function. In this paper, we aim to probe the structures of these expanded transcript by analyzing the structural diversity of their conformational ensembles. We used graphs to catalog the structures of an NG-(CNG)16-CN and NG-(CNG)50-CN oligomer and grouped them into sub-ensembles based on their characters and calculated the structural diversity and thermodynamic stability for these ensembles using a previously described graph factorization scheme. Our findings show that the generally assumed structure for CNG repeats—a series of canonical helices connected by two-way junctions and capped with a hairpin loop—may not be the most thermodynamically favorable, and the ensembles are characterized by largely open and less structured conformations. Furthermore, a length-dependence is observed for the behavior of the ensembles’ diversity as higher-order diagrams are included, suggesting that further studies of CNG repeats are needed at the length scale of TREDs onset to properly understand their structural diversity and how this might relate to their functions.STATEMENT OF SIGNIFICANCETrinucleotide repeats are DNA satellites that are prone to mutations in the human genome. A family of diverse disorders are associated with an overexpansion of CNG repeats occurring in noncoding regions, and the RNA transcripts of the expanded regions have been implicated as the origin of toxicity. Our understanding of the structures of these expanded RNA transcripts is based on sequences that have limited lengths compared to the scale of the expanded transcripts found in patients. In this paper, we introduce a theoretical method aimed at analyzing the structure and conformational diversity of CNG repeats, which has the potential of overcoming the current length limitations in the studies of trinucleotide repeat sequences.
Intra-tumor heterogeneity of Diffuse Large B-cell Lymphoma involves the induction of diversified stroma-tumor interfaces
Authors: Sangaletti Sabina , Iannelli Fabio , Zanardi Federica , Cancila Valeria , Portararo Paola , Botti Laura , Vacca Davide , Chiodoni Claudia , Di Napoli Arianna , Valenti Cesare , Vegliante Maria Carmela , Pisati Federica , Gulino Alessandro , Ponzoni Maurilio , Colombo Mario Paolo , Tripodo Claudio 
Published: May 2020

ABSTRACTIntra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-intrinsic mesenchymal determinants impact on the diversification of aggressive lymphomas is still unknown. In this study we adopted the established A20 line-based model of Diffuse Large B-cell Lymphoma (DLBCL), to investigate the intra-tumor heterogeneity associated with the infiltration of different tissue microenvironments and the specific mesenchymal modifications that characterize stromal adaptation to lymphoma seeding. Combiningin situquantitative immunophenotypical analyses and RNA sequencing, we found that the tissue microenvironment casts a relevant influence over A20 transcriptional landscape also impacting on Myc and DNA damage response programs. Extending the investigation to mice deficient for the matricellular protein Sparc, a stromal determinant endowed with a strong prognostic significance in human DLBCL, we demonstrated a different immune imprint on A20 cells related to stromalSparcproficiency. The study provides the first evidence of human DLBCL intra-lesional heterogeneity arising from diversified mesenchymal contextures and impacting on MYC expression, advancing the challenge for resolving intra-tumor heterogeneity probing stromal/immune interfaces.KEY POINTSDiversified stromal adaptations of infiltrated tissues shape DLBCL intra-tumor heterogeneity regulating transcriptional/phenotypic featuresStromal Sparc, which endorses prognostic significance in DLBCL, tunes the immune pressure exerted on lymphoma cells by the microenvironment
On the Ontological Foundations of Cellular Development
Authors: Burek Patryk , Scherf Nico , Herre Heinrich 
Published: May 2020

AbstractTime-lapse microscopy is a principal tool to unravel the mystery of how cells form and maintain organisms. The complexity of the domain of cellular dynamics demands a conceptual architecture as a solid theoretical foundation that supports the integration of knowledge obtained across experiments and theories. In this work, we outline the ontological foundation of cellular genealogies, a key concept for describing and representing of cellular development. We build the conceptual framework following the onto-axiomatic method: We first analyse the domain within the context of a top-level ontology (GFO). The resulting domain-specification provides the basis for a conceptualisation where we introduce concepts and relations. From these conceptualisations, we then construct model-structures adhering to the principles of model-theory. We finally elaborate axioms based on these model-structures. The developed framework provides the fundamental concepts underlying a Cell Tracking Ontology (CTO) that supports extraction and integration of biological knowledge from systems-level experiments across different types of observations at the single-cell level.
Structure and lipid dynamics in theA. baumanniimaintenance of lipid asymmetry (MLA) inner membrane complex
Authors: Mann Daniel , Fan Junping , Farrell Daniel P. , Somboon Kamolrat , Muenks Andrew , Tzokov Svetomir B. , Khalid Syma , Dimaio Frank , Miller Samuel I. , Bergeron Julien R. C. 
Published: May 2020

AbstractMulti-resistant bacteria are a major threat in modern medicine. The gram-negative coccobacillusAcinetobacter baumanniicurrently leads the WHO list of pathogens in critical need for new therapeutic development. The maintenance of lipid asymmetry (MLA) protein complex is one of the core machineries that transport lipids from/to the outer membrane in gram-negative bacteria. It also contributes to broad-range antibiotic resistance in several pathogens, most prominently inA. baumannii. Nonetheless, the molecular details of its role in lipid transport has remained largely elusive.Here, we report the cryo-EM structures of the core MLA complex, MlaBDEF, from the pathogenA. baumannii, in the apo-, ATP- and ADB-bound states. These structures reveal multiple lipid binding sites, in the cytosolic and periplasmic side of the complex. Molecular dynamics simulations suggest their potential trajectory across the membrane. Collectively with the recently-reported structures of theE.coliorthologue, these data also allows us to propose a molecular mechanism of lipid transport by the MLA system.
Electrical properties, accuracy, and multi-day performance of gelatine phantoms for electrophysiology
Authors: Owda Amani Yousef , Casson Alexander J. 
Published: May 2020

AbstractGelatine based phantoms for electrophysiology are becoming widely used as they allow the controlled validation of new electrode and new instrumentation designs. The phantoms mimic the electrical properties of the human body and allow a pre-recorded electrophysiology signal to beplayed-out, giving a known signal for the novel electrode or instrumentation to collect. Such controlled testing is not possible with on-person experiments where the signal to be recorded is intrinsically unknown. However, despite the rising interest in gelatine based phantoms there is relatively little public information about their electrical properties and accuracy, how these vary with phantom formulation, and across both time and frequency. This paper investigates ten different phantom configurations, characterising the impedance path through the phantom and comparing this impedance path to both previously reported electrical models of Ag/AgCl electrodes placed on skin and to a model made from ex vivo porcine skin. This article shows how the electrical properties of the phantoms can be tuned using different concentrations of gelatine and of sodium chloride (NaCl) added to the mixture, and how these properties vary over the course of seven days for a.c. frequencies in the range 20–1000 Hz. The results demonstrate that gelatine phantoms can accurately mimic the frequency response properties of the body–electrode system to allow for the controlled testing of new electrode and instrumentation designs.
Protein enhanced NIR-IIb emission of indocyanine green for functional bioimaging
Authors: He Mubin , Wu Di , Zhang Yuhuang , Fan Xiaoxiao , Lin Hui , Qian Jun 
Published: May 2020

AbstractFluorescence imaging performed in the 1500-1700 nm spectral range (labeled as near-infrared IIb, NIR-IIb) promises high imaging contrast and spatial resolution for its little photon scattering effect and minimum auto-fluorescence. Though inorganic and organic probes have been developed for NIR-IIb bioimaging, most are in preclinical stage, hampering further clinical application. Herein, we showed that indocyanine green (ICG), an US Food and Drug Administration (FDA)-approved agent, exhibited remarkable amount of NIR-IIb emission when dissolved into different protein solutions, including human serum albumin, rat bile, and fetal bovine serum. We performed fluorescence imaging in NIR-IIb window to visualize structures of lymph system, extrahepatic biliary tract and cerebrovascular. Results demonstrated that proteins promoted NIR-IIb emission of ICGin vivoand that NIR-IIb imaging with ICG preserved higher signal-to-background ratio (SBR) and spatial resolution compared with the conventional near-infrared II (NIR-II) fluorescence imaging. Our findings confirm that NIR-IIb fluorescence imaging can be successfully performed using the clinically approved agent ICG. Further clinical application in NIR-IIb region would hopefully be carried out with appropriate ICG-protein solutions.