bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of convalescent plasma versus standard of care for the treatment of COVID-19 in hospitalized patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial
Authors: Diago-Sempere Elena , Bueno José Luis , Sancho-López Aránzazu , Rubio Elena Múñez , Torres Ferrán , de Molina Rosa Malo , Fernández-Cruz Ana , de Diego Isabel Salcedo , Velasco-Iglesias Ana , Payares-Herrera Concepción , Flecha Inmaculada Casas , Avendaño-Solà Cristina , Palomino Rafael Duarte , Ramos-Martínez Antonio , Ruiz-Antorán Belén 
Published: January 2021

Abstract
Background
COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions.
It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia.

Methods/design
The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment.

Discussion
This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease.

Trial registration
ClinicalTrials.gov NCT04345523. Registered on 30 March, 2020. First posted date: April 14, 2020.
The complexities of the diet-microbiome relationship: advances and perspectives
Authors: Leeming Emily R. , Louca Panayiotis , Gibson Rachel , Menni Cristina , Spector Tim D. , Le Roy Caroline I. 
Published: January 2021

AbstractPersonalised dietary modulation of the gut microbiota may be key to disease management. Current investigations provide a broad understanding of the impact of diet on the composition and activity of the gut microbiota, yet detailed knowledge in applying diet as an actionable tool remains limited. Further to the relative novelty of the field, approaches are yet to be standardised and extremely heterogeneous research outcomes have ensued. This may be related to confounders associated with complexities in capturing an accurate representation of both diet and the gut microbiota. This review discusses the intricacies and current methodologies of diet-microbial relations, the implications and limitations of these investigative approaches, and future considerations that may assist in accelerating applications. New investigations should consider improved collection of dietary data, further characterisation of mechanistic interactions, and an increased focus on -omic technologies such as metabolomics to describe the bacterial and metabolic activity of food degradation, together with its crosstalk with the host. Furthermore, clinical evidence with health outcomes is required before therapeutic dietary strategies for microbial amelioration can be made. The potential to reach detailed understanding of diet-microbiota relations may depend on re-evaluation, progression, and unification of research methodologies, which consider the complexities of these interactions.
Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals
Authors: Arredondo-Alonso Sergio , Top Janetta , Corander Jukka , Willems Rob J. L. , Schürch Anita C. 
Published: January 2021

Abstract
Background
Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations.

Methods
We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination.

Results
On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination.

Conclusions
In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.
Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice
Authors: Kapadia Minesh , Mian M. Firoz , Ma Donglai , Hutton Craig P. , Azam Amber , Narkaj Klotilda , Cao Chuanhai , Brown Breanna , Michalski Bernadeta , Morgan David , Forsythe Paul , Zovkic Iva B. , Fahnestock Margaret , Sakic Boris 
Published: January 2021

Abstract
Background
Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer’s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model.

Methods
Young 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration.

Results
Chronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors.

Conclusion
The results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.
Exponential stability for delayed complex-valued neural networks with reaction-diffusion terms
Authors: Xu Xiaohui , Yang Jibin , Xu Quan , Xu Yanhai , Sun Shulei 
Published: January 2021

AbstractIn this study, we investigate reaction-diffusion complex-valued neural networks with mixed delays. The mixed delays include both time-varying and infinite distributed delays. Criteria are derived to ensure the existence, uniqueness, and exponential stability of the equilibrium state of the addressed system on the basis of the M-matrix properties and homeomorphism mapping theories as well as the vector Lyapunov function method. The results demonstrate the positive effect of reaction-diffusion on the stability, which further improves the existing conditions. Finally, the analysis of several examples is compared to the present results to verify the correctness and reduced conservatism of the primary results.
Modeling and forecasting the spread of COVID-19 with stochastic and deterministic approaches: Africa and Europe
Authors: Atangana Abdon , İğret Araz Seda 
Published: January 2021

AbstractUsing the existing collected data from European and African countries, we present a statistical analysis of forecast of the future number of daily deaths and infections up to 10 September 2020. We presented numerous statistical analyses of collected data from both continents using numerous existing statistical theories. Our predictions show the possibility of the second wave of spread in Europe in the worse scenario and an exponential growth in the number of infections in Africa. The projection of statistical analysis leads us to introducing an extended version of the well-blancmange function to further capture the spread with fractal properties. A mathematical model depicting the spread with nine sub-classes is considered, first converted to a stochastic system, where the existence and uniqueness are presented. Then the model is extended to the concept of nonlocal operators; due to nonlinearity, a modified numerical scheme is suggested and used to present numerical simulations. The suggested mathematical model is able to predict two to three waves of the spread in the near future.
Current plastics pollution threats due to COVID-19 and its possible mitigation techniques: a waste-to-energy conversion via Pyrolysis
Authors: Aragaw Tadele Assefa , Mekonnen Bassazin Ayalew 
Published: January 2021

Abstract
Background
The extensive use and production of PPE, and disposal in the COVID-19 pandemic increases the plastic wastes arise environmental threats. Roughly, 129 billion face masks and 65 billion plastic gloves every month are used and disposed of on the globe. The study aims to identify the polymer type of face masks and gloves and sustainable plastic waste management options.

Results
The identification of polymers, which can help for fuel conversion alternatives, was confirmed by FTIR and TGA/DTA analysis and confirms that the polymeric categories fit for the intended purpose. Moreover, the handling technique for upcycling and the environmental impacts of the medical face mask and glove were discussed. The FTIR result revealed that face masks and gloves are polypropylene and PVC thermoplastic polymer, respectively and they can be easily transformed to fuel energy via pyrolysis. The endothermic peaks around 431 ℃ for medical glove and 175 ℃ for surgical is observed tells that the melting point of the PVC and polypropylene of plastic polymers, respectively. The pyrolysis of the face mask and glove was carried out in a closed reactor at 400 ℃ for 1 h. Conferring to lab-scale processes, liquid, and wax fuel rate of 75%, char of 10%, and the rest non-condensable gases were estimated at the end.

Conclusions
It can be concluded that the medical plastics can be recycled into oil due to their thermoplastics nature having high oil content and the waste to energy conversion can potentially reduce the volume of PPE plastic wastes.
Understanding the host-microbe interactions using metabolic modeling
Authors: Jansma Jack , El Aidy Sahar 
Published: January 2021

AbstractThe human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health.
Improved effect of a mitochondria-targeted antioxidant on hydrogen peroxide-induced oxidative stress in human retinal pigment epithelium cells
Authors: Kim Myung Hee , Kim Do-Hun , Yang Su Geun , Kim Dae Yu 
Published: January 2021

Abstract
Background
Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells.

Methods
The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR).

Results
TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).

Conclusion
We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.
Winter fidelity, movements, and energy expenditure of Midcontinent Greater White-fronted Geese
Authors: VonBank Jay A. , Weegman Mitch D. , Link Paul T. , Cunningham Stephanie A. , Kraai Kevin J. , Collins Daniel P. , Ballard Bart M. 
Published: January 2021

AbstractBackgroundAnimal movement patterns are the result of both environmental and physiological effects, and the rates of movement and energy expenditure of given movement strategies are influenced by the physical environment an animal inhabits. Greater white-fronted geese in North America winter in ecologically distinct regions and have undergone a large-scale shift in wintering distribution over the past 20 years. White-fronts continue to winter in historical wintering areas in addition to contemporary areas, but the rates of movement among regions, and energetic consequences of those decisions, are unknown. Additionally, linkages between wintering and breeding regions are generally unknown, and may influence within-winter movement rates.MethodsWe used Global Positioning System and acceleration data from 97 white-fronts during two winters to elucidate movement characteristics, model regional transition probabilities using a multistate model in a Bayesian framework, estimate regional energy expenditure, and determine behavior time-allocation influences on energy expenditure using overall dynamic body acceleration and linear mixed-effects models. We assess the linkages between wintering and breeding regions by evaluating the winter distributions for each breeding region.ResultsWhite-fronts exhibited greater daily movement early in the winter period, and decreased movements as winter progressed. Transition probabilities were greatest towards contemporary winter regions and away from historical wintering regions. Energy expenditure was up to 55% greater, and white-fronts spent more time feeding and flying, in contemporary wintering regions compared to historical regions. White-fronts subsequently summered across their entire previously known breeding distribution, indicating substantial mixing of individuals of varying breeding provenance during winter.ConclusionsWhite-fronts revealed extreme plasticity in their wintering strategy, including high immigration probability to contemporary wintering regions, high emigration from historical wintering regions, and high regional fidelity to western regions, but frequent movements among eastern regions. Given that movements of white-fronts trended toward contemporary wintering regions, we anticipate that a wintering distribution shift eastward will continue. Unexpectedly, greater energy expenditure in contemporary wintering regions revealed variable energetic consequences of choice in wintering region and shifting distribution. Because geese spent more time feeding in contemporary regions than historical regions, increased energy expenditure is likely balanced by increased energy acquisition in contemporary wintering areas.
Drug supply situation in Rwanda during COVID-19: issues, efforts and challenges
Authors: Uwizeyimana Theogene , Hashim Hashim Talib , Kabakambira Jean Damascene , Mujyarugamba Jean Claude , Dushime Jackson , Ntacyabukura Blaise , Ndayizeye Remy , Adebisi Yusuff Adebayo , Lucero-Prisno Don Eliseo 
Published: January 2021

AbstractCOVID-19 is a threat to health systems around the world and Rwanda is not an exception. The impact of the pandemic is far-reaching and access to health commodities is not spared. Proper drug supply is critical for a robust healthcare system. It determines the extent at which the population are likely to have access to essential medicines and treatments. In Rwanda, the pharmaceutical sector heavily relies on imports. With the emergence of COVID-19 pandemic, the drug supply system was interrupted leaving many stores from small local pharmacies to the big medical stores running out of stock. The reasons were limited importation of goods from abroad, and the panic buying practice among the customers and some institutions when responding to the pandemic. Drug and medicines accessibility, availability and affordability should be the core of any drug management policy. It is with no doubt that, Rwanda has made a tremendous work to mitigate the effect of COVID-19 on the country’s drug supply; however, efforts are still needed to invest in local pharmaceutical production as a way to minimize import expenses in the country. Good policy on drug importation, production and distribution should be enforced to avoid any drug shortage that may be encountered in the Rwandan drug market.
Advanced echocardiographic phenotyping of critically ill patients with coronavirus-19 sepsis: a prospective cohort study
Authors: Bagate François , Masi Paul , d’Humières Thomas , Al-Assaad Lara , Chakra Laure Abou , Razazi Keyvan , de Prost Nicolas , Carteaux Guillaume , Derumeaux Genevieve , Mekontso Dessap Armand 
Published: January 2021

Abstract
Background
Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis.

Methods
Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference.

Results
Sixty-seven patients were assessed (55 males), with a median age of 61 [50–70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers’ concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices.

Conclusions
In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.
COVID-19 associated acute demyelination masquerading as stroke: a case report
Authors: Khandelwal Krati , Puranik Monika , Gupta Vivek , Khandelwal Gaurav , Dave Pranav Kumar , Hirve Makarand 
Published: January 2021

AbstractBackgroundDuring the recent outbreak of COVID-19, various atypical extrapulmonary manifestations are being seen, including neurological ones. Reported cases mainly include encephalopathy, myelitis, and cranial nerve involvement. This case describes uncommon neuroradiological finding in the context of COVID-19.Case presentationWe report an atypical case of COVID-19 presenting with stroke-like episode, with MRI brain showing isolated bilateral posterior internal capsule involvement. This has rarely been reported in literature.ConclusionAs the numbers of COVID-19 cases are increasing, such atypical presentations should be kept in mind.