bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of published systematic reviews and meta-analyses on COVID-19
Authors: Ibrahim Nasrien E. , Ibrahim Ezzeldin M. 
Published: June 2020

AbstractPurposeThe rapid spread of the COVID-19 pandemic has prompted researchers from all over the world to share their experience. The results were numerous reports with variable quality. The latter has provided an impetus to examine all published meta-analyses and systematic reviews on COVID-19 to date to examine available evidence. Methods: Using predefined selection criteria, a literature search identified 43 eligible meta-analyses and/or systematic reviews. Results: Most (N=17) studies addressed clinical manifestations and associated comorbidity, 6 studies addressed clinical manifestations in pregnant women and younger individuals, 8 studies addressed diagnostic data, 9 studies addressed various interventions, and 9 studies addressed prevention and control. The number of studies included in the various systemic reviews and meta-analyses ranged from 2 to 89. While there were some similarities and consistency for some findings, e.g. the relation between comorbidities and disease severity, we also noted occasionally conflicting data. Conclusion: As more data are collected from patients infected with COVID-19 all over the world, more studies will undoubtedly be published and attention to scientific accuracy in the performance of trials must be exercised to inform clinical decision-making and treatment guidelines.
Trends of per-patient healthcare cost and resource utilization of opioid use disorder among privately insured individuals in the United States from 2005-2014
Authors: Jiang Bibo , Wang Li , Leslie Douglas 
Published: June 2020

AbstractBackgroundLittle are known about how per-patient healthcare cost and resource utilization of Opioid Use Disorder (OUD) have changed over time when governments continue to reduce availability and utilization barrier of OUD treatment.ObjectivesInvestigate trends of per-patient healthcare cost and utilization of outpatient, inpatient and emergency department services among privately insured individuals with OUD from 2005 to 2014.MethodsThe MarketScan® Commercial Claims and Encounters database was used to analyze healthcare cost and resource utilization of opioid used disorder from 2005 to 2014. A matched case-control design was employed to estimate the impact of OUD on healthcare cost and service utilization over this period.Main findingsExcess annual per-patient healthcare cost of OUD stayed relatively stable with an average of $14,586 between 2005 and 2014. However, excess outpatient cost increased while excess inpatient cost decreased over time. Among OUD patients, the increase of OUD related outpatient care utilization rate and average number of visits coincided with the decrease of inpatient and ED service utilization rates and average number of ED visits.ConclusionsAmong OUD patients, the increasing per-patient utilization of OUD related outpatient care, together with the decline in per-patient utilization of more urgent care including inpatient and emergency department care might indicate increased awareness and diagnosis of OUD and a better control of the disease among existing patients with private insurance.
Dominant and rare SARS-Cov2 variants responsible for the COVID-19 pandemic in Athens, Greece
Authors: Nikolaos Spanakis , Katerina Kassela , Nikolas Dovrolis , Maria Bampali , Elisavet Gatzidou , Athanasia Kafasi , Elisavet Froukala , Anastasia Stavropoulou , Konstantinos Lilakos , Stavroula Veletza , Sotirios Tsiodras , Athanasios Tsakris , Ioannis Karakasiliotis 
Published: June 2020

AbstractSARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel Coronavirus responsible for the Coronavirus Disease-2019 (COVID-19) pandemic. Since the beginning of the pandemic, the virus has spread in almost the entire world. Tracing and tracking virus international and local transmission has been an enormous challenge. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. Full-genome analysis of isolates from Athens’ Hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lock-down and passenger flight restrictions. The present work may serve as reference for resolving future lines of infection in the area and Europe especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.
Risk factors for rhinitis, allergic conjunctivitis and eczema among schoolchildren in Uganda
Authors: Mpairwe Harriet , Nkurunungi Gyaviira , Tumwesige Pius , Akurut Hellen , Namutebi Milly , Nambuya Irene , Nnaluwooza Marble , Apule Barbara , Onen Caroline , Katongole Tonny , Niwagaba Emmanuel , Mukasa Mike , Webb Emily L , Elliott Alison M , Pearce Neil 
Published: June 2020

AbstractBackgroundThe prevalence of allergy-related diseases (ARDs), including rhinitis, allergic conjunctivitis and eczema, is on the increase in Africa and globally. The causes of this increase are not well established.ObjectivesTo investigate the risk factors for ARDs among schoolchildren in Uganda.MethodsWe conducted a secondary data analysis of a large asthma case-control study involving 1,700 schoolchildren, 5-17 years, in urban Uganda. ARDs were defined according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Skin prick testing (SPT) was conducted using standard procedures and allergen-specific IgE (asIgE) using ImmunoCAP®. We used inverse probability weighting to account for the differences in the sampling fractions in all our analyses.ResultsThe lifetime prevalence of reported rhinitis, allergic conjunctivitis and eczema was 43.3%, 39.5%, and 13.5%, respectively. There was overlap of ARDs, with 66.3% of 1,193 schoolchildren who reported having ever an ARDs (including asthma) reporting two or more. The important risk factors for ‘rhinitis ever’ were city residence at birth [adjusted odds ratio (95% confidence interval) 1.97 (1.26-3.10) compared to rural]; father’s [2.08 (1.57-2.75)] and mother’s history of allergic disease [2.29 (1.81-2.91)]; frequent de-worming in the last 12 months [1.80 (1.32-2.45), ≥2 versus none]; current high frequency of ‘trucks passing on the street near home’ [1.90 (1.19-3.03), ‘almost all the time’ versus rarely] and positive SPT [1.56 (1.24-1.96)] but not asIgE [1.33 (0.81-2.18)]. The same pattern of risk factors was observed for allergic conjunctivitis and eczema.ConclusionWe found extensive multi-morbidity of, and overlap in the risk factors for, rhinitis, conjunctivitis, and eczema - similar to asthma risk factors - among schoolchildren in urban Uganda. This suggests a similar underlying cause for all ARDs, associated with exposure to urban lifestyles and environment in Uganda. Thus, epidemiological research should investigate causes of all ARDs as one disease entity.
Modelling daily infections with Covid-19 in Germany, France, and Sweden with a trend line based on day-to-day reproduction rates
Authors: Mergel Dieter 
Published: June 2020

AbstractThe number of persons daily infected with Covid-19 as a function of time is fitted with a trend line based on an iterative power law (n = ¼) with a day-to-day reproduction rate modelled with a polyline. From the trend line, an effective reproduction rate Reff of Covid-19 is calculated. In all three states, Reff decreases in the initial phase to one indicating that there is no exponential growth. In Sweden, a steady state with Reff around 1 and a high daily infection rates. In Germany, Reff = 1 is reached before public and private life is restricted. With these restrictions, Reff is reduced further to 0.87 (CI95 [0.83.; 0.91]) after 40 days so that, speculatively estimated, 9500 premature fatalities within two months may have been avoided. In France, it seems that only strongly restricting private life sends Reff down to 1 and further down to about 0.7 (CI95 [0.3; 1.1]) after 45 days. With Reff permanently below 1, an exponential decline of the number of daily infections is observed in Germany and France.
Exploring the Feasibility of Using Real-World Data from a Large Clinical Data Research Network to Simulate Clinical Trials of Alzheimer’s Disease
Authors: Chen Zhaoyi , Zhang Hansi , Guo Yi , George Thomas J , Prosperi Mattia , Hogan William R , He Zhe , Shenkman Elizabeth A , Wang Fei , Bian Jiang 
Published: June 2020

ABSTRACTIn this study, we explored the feasibility of using real-world data (RWD) from a large clinical research network to simulate real-world clinical trials of Alzheimer’s disease (AD). The target trial (i.e.,NCT00478205) is a Phase III double-blind, parallel-group trial that compared the 23 mg donepezil sustained release with the 10 mg donepezil immediate release formulation in patients with moderate to severe AD. We followed the target trial’s study protocol to identify the study population, treatment regimen assignments, and outcome assessments, and to set up a number of different simulation scenarios and parameters. We considered two main scenarios: (1) a one-arm simulation: simulating a standard-of-care arm that can serve as an external control arm; and (2) a two-arm simulation: simulating both intervention and control arms with proper patient matching algorithms for comparative effectiveness analysis. In the two-arm simulation scenario, we used propensity score matching controlling for baseline characteristics to simulate the randomization process. In the two-arm simulation, higher SAE rates were observed in the simulated trials than the rates reported in original trial, and a higher SAE rate was observed in the 23mg arm than the 10 mg standard-of-care arm. In the one-arm simulation scenario, similar estimates of SAE rates were observed when proportional sampling was used to control demographic variables. In conclusion, trial simulation using RWD is feasible in this example of AD trial in terms of safety evaluation. Trial simulation using RWD could be a valuable tool for post-market comparative effectiveness studies and for informing future trials’ design. Nevertheless, such approach may be limited, for example, by the availability of RWD that matches the target trials of interest, and further investigations are warranted.
Disparities in COVID-19 related knowledge, attitudes, beliefs and behaviours by health literacy
Authors: McCaffery KJ , Dodd RH , Cvejic E , Ayre J , Batcup C , Isautier JMJ , Copp T , Bonner C , Pickles K , Nickel B , Dakin T , Cornell S , Wolf MS 
Published: June 2020

ABSTRACTObjectivesTo explore the variation in understanding, attitudes and uptake of COVID-19 health advice during the 2020 pandemic lockdown by health literacy.Study designNational cross sectional community survey.SettingAustralian general public.ParticipantsAdults aged over 18 years (n = 4362).Main outcome measuresKnowledge, attitudes and behaviours related to COVID-19; health literacy and socio-demographic factors.ResultsPeople with inadequate health literacy had poorer understanding of COVID-19 symptoms (49% vs 68%; p<0.001), were less able to identify behaviours to prevent infection (59% vs 72%; p<0.001), and experienced more difficulty finding information and understanding government messaging about COVID-19 than people with adequate health literacy. They were less likely to rate social distancing as important (6.1 vs 6.5, p<0.001) and reported more difficulty remembering/accessing medication since lockdown (3.6 vs 2.7, p<0.001). Importantly there was higher endorsement of misinformation beliefs related to COVID-19 and vaccination in people with lower health literacy. Similar results were observed among people who primarily speak a language other than English at home.ConclusionOur findings show important disparities by health literacy and language in COVID-19 related knowledge, attitudes and behaviours that have the potential to undermine efforts to reduce viral transmission and may lead to social inequalities in health outcomes in Australia. Those with the greatest burden of chronic disease are most disadvantaged, and most likely to experience severe disease and die from COVID-19. Addressing the health literacy needs of the community in public health messaging about COVID-19 must now be a priority in Australia.
Diverse viruses in deep-sea hydrothermal vent fluids have restricted dispersal across ocean basins
Authors: Thomas Elaina , Anderson Rika , Li Viola , Rogan Jenni , Huber Julie A. 
Published: June 2020

AbstractIn the ocean, viruses impact microbial mortality, regulate biogeochemical cycling, and alter the metabolic potential of microbial lineages. At deep-sea hydrothermal vents, abundant viruses infect a wide range of hosts among the archaea and bacteria that inhabit these dynamic habitats. However, little is known about viral diversity, host range, and biogeography across different vent ecosystems, which has important implications for how viruses manipulate microbial function and evolution. Here, we examined viral diversity, viral and host distribution, and viral-host interactions in microbial metagenomes generated from venting fluids from several vent sites within three different geochemically and geographically distinct hydrothermal systems: Piccard and Von Damm vent fields at the Mid-Cayman Rise in the Caribbean Sea, and at several vent sites within Axial Seamount in the Pacific Ocean. Analysis of viral sequences and Clustered Regularly InterSpaced Palindromic Repeats (CRISPR) spacers revealed highly diverse viral assemblages and evidence of active infection. Network analysis revealed that viral host range was relatively narrow, with very few viruses infecting multiple microbial lineages. Viruses were largely endemic to individual vent sites, indicating restricted dispersal, and in some cases viral assemblages persisted over time. Thus, we show that hydrothermal vent fluids are home to novel, diverse viral assemblages that are highly localized to specific regions and taxa.ImportanceViruses play important roles in manipulating microbial communities and their evolution in the ocean, yet not much is known about viruses in deep-sea hydrothermal vents. However, viral ecology and evolution are of particular interest in hydrothermal vent habitats because of their unique nature: previous studies have indicated that most viruses in hydrothermal vents are temperate rather than lytic, and it has been established that rates of horizontal gene transfer (HGT) are particularly high among thermophilic vent microbes, and viruses are common vectors for HGT. If viruses have broad host range or are widespread across vent sites, they have increased potential to act as gene-sharing “highways” between vent sites. By examining viral diversity, distribution, and infection networks across disparate vent sites, this study provides the opportunity to better characterize and constrain the viral impact on hydrothermal vent microbial communities. We show that viruses in hydrothermal vents are diverse and apparently active, but most have restricted host range and are not widely distributed among vent sites. Thus, the impacts of viral infection are likely to be highly localized and constrained to specific taxa in these habitats.
MYBL2 regulates ATM to control replication initiation and prevent replication stress in pluripotent stem cells
Authors: Blakemore Daniel , Vilaplana Nuria , Almaghrabi Ruba , Gonzalez Elena , Moya Miriam , Ward Carl , Murphy George , Gambus Agnieszka , Petermann Eva , Stewart Grant S. , García Paloma 
Published: June 2020

SummaryReplication stress, a major cause of genome instability in cycling cells, is mainly prevented by the ATR-dependent replication stress response pathway in somatic cells. However, the replication stress response pathway in embryonic stem cells (ESCs) may be substantially different due to alterations in cell cycle phase length. The transcription factor MYBL2, which is implicated in cell cycle regulation, is expressed between hundred to thousand-fold more highly in ESCs compared to somatic cells. Here we show that MYBL2 functions to activate ATM and suppress replication stress in ESCs. Consequently, loss of MYBL2 or inhibition of ATM or Mre11 in ESCs, results in replication fork slowing, increased fork stalling and elevated origin firing. Additionally, we demonstrate that inhibition of CDC7 activity rescues replication stress induced by MYBL2 loss and ATM inhibition, suggesting that uncontrolled new origin firing may underlie the replication stress phenotype resulting from loss/inhibition of MYBL2 and ATM. Overall, this study proposes that in addition to ATR, a MYBL2-MRN-ATM replication stress response pathway functions in ESCs to control DNA replication initiation and prevent genome instability.
Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype
Authors: Beevi Syed Sultan , Verma Vinod Kumar , Panigrahi Manas Kumar , Bhale Aishwarya , Madigubba Sailaja , Chowdary Radhika , Korabathina Radhika , Reddy Sukrutha Gopal 
Published: June 2020

AbstractBackgroundClinical management of glioma is crucial irrespective of tumor grade. Despite newer treatment modalities, the prognosis of glioma is abysmal and, survival statistics are not remarkable.In vitroglioma culture is emerging as a standard model to get insight into phenotypic transformation, drug response, and tumor relapse. In this viewpoint, this study established comprehensive patient-specific short-term cultures comprising low-grade, and high-grade glioma, and evaluated their pertinence in the potential disease management.Methods50 patients with MRI diagnosed glioma were recruited for this study. Primary glioma cultures established from fresh surgical tumor tissues, which were then evaluated for their intrinsic growth kinetics, response to temozolomide, and expression profile of Glial-Mesenchymal Transition (GMT) markers along with an oncogenic marker, cMyc.ResultsShort-term glioma culture was successfully established in 40 clinical samples. Glioma culture, irrespective of tumor grade, displayed two distinct patterns of growth kinetics – one with shorter doubling time (high-proliferating) and another group with longer doubling time (low-proliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, the expression pattern of GMT markers and their association with 1p/19q co-deletion and p53 expression.ConclusionOur findings effectively demonstrated the practicality of the development of short-term glioma culture toward a functional approach for personalized medicine. Our study revealed the presence of a highly proliferative, drug-resistant phenotype irrespective of tumor grade. Hence, short-term culture could be an important prognostic tool for predicting patient clinical responses and cue about imminent tumor relapse.
Bacteriocin production inStreptococcus gallolyticusis controlled by a complex 4-component regulatory system with activator and anti-activator activities
Authors: Proutière Alexis , Périchon Bruno , du Merle Laurence , Varet Hugo , Trieu-Cuot Patrick , Dramsi Shaynoor 
Published: June 2020

AbstractBacteriocins are natural antimicrobial peptides produced by bacteria to kill closely related competitors. The opportunistic pathogenStreptococcus gallolyticus(Sgg) was recently shown to outcompete commensal enterococci of the murine microbiota in tumoral conditions thanks to the production of a two-peptide bacteriocin named gallocin. We here identified 4 genes involved in the regulatory control of gallocin inSggUCN34, respectively encoding a histidine kinase/response regulator two-component system (BlpH/BlpR), a secreted peptide (GSP), and a putative regulator of unknown function (BlpS). While BlpR is a typical 243-aa response regulator possessing a phospho-receiver domain and a LytTR DNA-binding domain, BlpS is a 108-aa protein containing only a LytTR domain. Our results showed that the secreted peptide GSP activates the dedicated two-component system BlpH/BlpR to induce gallocin transcription. A genome-wide transcriptome analysis indicates that this regulatory system (GSP-BlpH/BlpR) is highly specific for bacteriocin production. Importantly, as opposed to BlpR, BlpS was shown to repress gallocin gene transcription. A conserved operator DNA sequence of 30-bp was found in all promoter regions regulated by BlpR and BlpS. EMSA assays showed direct and specific binding of the two gallocin regulators to various regulated promoter regions in a dose dependent manner. Gallocin expression appears tightly controlled inSggby quorum sensing and antagonistic activity of 2 LytTR-containing proteins.SignificanceStreptococcus gallolyticus(Sgg), formely known asS. bovisbiotype I, is an opportunistic pathogen causing septicemia and endocarditis in the elderly often associated with asymptomatic colonic neoplasia. We previously showed thatSggproduces a bacteriocin, termed gallocin, enabling colonization of the colon in tumoral conditions by outcompeting commensal members of the gut. Here we characterized a 4-component regulatory system that regulates gallocin transcription, which is activated by the response regulator BlpR. BlpR itself is activated by a quorum sensing peptide GSP and a dedicated histidine kinase BlpH. Interestingly, BlpS, a small DNA-binding protein co-transcribed with BlpR was found to repress gallocin genes transcription, likely by antagonizing BlpR. Understanding gallocin regulation is crucial to preventSggcolon colonization in tumoral conditions.
HDAC4 controls senescence and aging by safeguarding the epigenetic identity and ensuring the genomic integrity
Authors: Di Giorgio Eros , Paluvai Harikrishnareddy , Dalla Emiliano , Ranzino Liliana , Renzini Alessandra , Moresi Viviana , Cutano Valentina , Picco Raffaella , Brancolini Claudio 
Published: June 2020

ABSTRACTThe epigenome of senescent cells is characterized by a deep redistribution of H3K27 acetylation. H3K27 is target of class IIa Histone Deacetylases (HDAC4, 5, 7, 9) as part of large repressive complexes. We report here that, among class IIa HDACs, HDAC4 is post-transcriptionally downregulated during senescence and aging. HDAC4 knock-out (KO) triggers premature senescence as a result of two waves of biological events: the accumulation of replication stress (RS) and the expression of inflammatory genes. The latter is achieved directly, through the activation of enhancers (TEs) and super-enhancers (SEs) that are normally monitored by HDAC4, and indirectly, through the de-repression of repetitive elements of retroviral origin (ERVs). The accumulation of DNA damage and the activation of the inflammatory signature influence each other and integrate into a synergistic response required for senescence onset. Our work discloses the key role played by HDAC4 in maintaining epigenome identity and genome integrity.