bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does rainforest biodiversity stand on the shoulders of giants? Effect of disturbances by forest elephants on trees and insects on Mount Cameroon
Authors: Maicher Vincent , Delabye Sylvain , Murkwe Mercy , Doležal Jiří , Altman Jan , Kobe Ishmeal N. , Desmist Julie , Fokam Eric B. , Pyrcz Tomasz , Tropek Robert 
Published: June 2020

AbstractNatural disturbances are essential for dynamics of tropical rainforests, contributing to their tremendous biodiversity. In the Afrotropical rainforests, megaherbivores have played a key role before their recent decline. Although the influence of savanna elephants on ecosystems has been documented, their close relatives, forest elephants, remain poorly studied. Few decades ago, in the unique ‘natural enclosure experiment’ on Mount Cameroon, West/Central Africa, the rainforests were divided by lava flows which are not crossed by the local population of forest elephants. We assessed communities of trees, butterflies and two ecological guilds of moths in disturbed and undisturbed forests split by the longest lava flow at upland and montane elevations. Altogether, we surveyed 32 forest plots resulting in records of 2,025 trees of 97 species, and 7,853 butterflies and moths of 437 species. The disturbed forests differed in reduced tree density, height, and high canopy cover, and in increased DBH. Forest elephants also decreased tree species richness and altered their composition, probably by selective browsing and foraging. The elephant disturbance also increased species richness of butterflies and had various effects on species richness and composition of all studied insect groups. These changes were most probably caused by disturbance-driven alterations of (micro)habitats and species composition of trees. Moreover, the abandonment of forests by elephants led to local declines of range-restricted butterflies. Therefore, the current appalling decline of forest elephant populations across the Afrotropics most probably causes important changes in rainforest biodiversity and should be reflected by regional conservation authorities.
Viral miRNAs Confer Survival in Host Cells by Targeting Apoptosis Related Host Genes
Authors: Islam Md. Sajedul , Islam Abul BMMK 
Published: June 2020

AbstractBackgroundmiRNAs are small non-coding RNAs that regulate the expression of genes by RNA silencing method. Like eukaryotic organisms, some viruses also produce miRNAs. While contribution of host miRNA in the prevention of viral pathogenesis has been studied, it is not known very well how viral miRNA can confer its survival in the host. Here we hypothesized that viral miRNAs can bind to the host target genes to confer their pathogenicity by down-regulating specific pathways and related genes that otherwise pose threat to cell survival.Methods and ResultsUsing targets of 168 viral miRNAs from 13 different viruses overrepresentation analysis was done. Functional enrichment analysis of the genes targeted by the miRNAs indicates that viruses target specific immune system and host defense related pathways via miRNA mediated gene silencing. Integration and analysis of the publicly available experimental host gene expression data by RNA-seq provided insight that viruses target host apoptosis process by switching off related genes through miRNA induced mechanisms and thus probably ensure their survival.ConclusionsAs switching off the apoptosis of host cells would provide the viruses with selective advantages in surviving inside host, our findings therefore envisage an important function of viral miRNA which demands furtherin vivoexperiments for better understanding in this regard.
CCM signaling complex (CSC) is a master regulator governing homeostasis of progestins and their mediated signaling cascades
Authors: Abou-Fadel Johnathan , Jiang Xiaoting , Padarti Akhil , Goswami Dinesh , Smith Mark , Grajeda Brian , Walker Wendy , Zhang Jun 
Published: June 2020

AbstractWe demonstrate that a novel signaling network among the CSC and mPRS is dynamically modulated and fine-tuned with intricate feedback regulations in PR negative cells, especially endothelial cells (ECs). Depletion of any of three CCMs (1, 2, 3) genes results in the disruption of non-classic mPRs-mediated signalingin-vitroas well as defective homeostasis of PRGin-vivo. Therefore, we propose the CSC is a master regulator of homeostasis of PRG and its associated classic and non-classic signaling cascades. Assisted with omic approaches, we identified signaling pathways involved and specific biomarkers associated with hemorrhagic events during CCM pathogenesisin-vitroandin-vivo. To our knowledge, this is the first report detailing etiology to predict the occurrence of early hemorrhagic events with a set of serum biomarkers.
Transcriptional heterogeneity of stemness phenotypes in the ovarian epithelium
Authors: Carter LE. , Cook DP. , McCloskey CW. , Dang T. , Collins O. , Gamwell LF. , Dempster HA. , Vanderhyden BC. 
Published: June 2020

AbstractThe ovarian surface epithelium (OSE) is a monolayer of epithelial cells covering the surface of the ovary. During ovulation, the OSE is ruptured to allow release of the oocyte. This wound is quickly repaired, but mechanisms of this repair are poorly understood. The contribution of tissue-resident stem cells in the homeostasis of several epithelial tissues is widely accepted, such as the intestinal epithelium, airway epithelium, and skin, but their involvement in OSE maintenance is unclear. While putative stem cell populations in the OSE have been described, how they are regulated is poorly defined. We show that traits associated with stem cells (stemness) can be increased in OSE following exposure to the cytokine TGFB1, overexpression of the transcription factorSnai1, or deletion ofBrca1. By assessing the gene expression profiles of these populations, we show that stemness is often linked to mesenchymal-associated gene expression and higher activation of ERK signalling, but it is not consistently dependent on their activation. Expression profiles of these populations are extremely context specific, suggesting that stemness may not correspond to a single, distinct population, but rather is a heterogenous state that can possibly emerge from diverse environmental cues. Together, these findings support that the OSE may not require distinct stem cell populations for long-term maintenance, and may achieve this through transient dedifferentiation into a stem-like state.
Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2
Authors: Rosenke Kyle , Jarvis Michael A. , Feldmann Friederike , Schwarz Benjamin , Okumura Atsushi , Lovaglio Jamie , Saturday Greg , Hanley Patrick W. , Meade-White Kimberly , Williamson Brandi N. , Hansen Frederick , Perez-Perez Lizette , Leventhal Shanna , Tang-Huau Tsing-Lee , Nason Martha , Callison Julie , Haddock Elaine , Scott Dana , Sewell Graham , Bosio Catharine M. , Hawman David , de Wit Emmie , Feldmann Heinz 
Published: June 2020

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.One Sentence SummaryHydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease models.
Ultrasonic Texture Analysis Identifies Cardiac Microstructural Alterations in Immune-Inflammatory Disease
Authors: Kwan Alan C. , Nguyen Trevor , Kim Elizabeth H. , Demosthenes Emmanuella , Salto Gerran , Luong Eric , Hiremath Pranoti , Li Debiao , Berman Daniel S. , Patel Jignesh , Cheng Susan 
Published: June 2020

ABSTRACTBackgroundEchocardiographic texture analysis using the signal intensity coefficient (SIC) can identify fibrosis-associated microstructural changes. This approach has not been tested in immune-inflammatory disease states such as myocarditis or transplant rejection.MethodsRetrospective pilot analysis using the SIC was performed in populations including myocarditis (n=5), acute left anterior descending coronary artery STEMI (n=6), severe aortic stenosis with normal ejection fraction (n=7), ATTR amyloidosis (n=6), and cardiac transplant patients undergoing biopsy including patients with active rejection on histopathology (n=22), patients with history of rejection but no current rejection (n=15), and patients without history of or current rejection (n=5), and a healthy control group (n=28).ResultsDecreased SIC was noted in the myocarditis and transplant rejection populations, with decreasing SIC by presence and history of rejection. Consistent with prior literature, the SIC was elevated in cardiac conditions associated with fibrosis.ConclusionsThe SIC may be able to capture microstructural changes associated with immune-inflammatory processes such as cardiac transplant rejection and myocarditis.
Resource requirements for reintroducing elective surgery in England during the COVID-19 pandemic: a modelling study
Authors: Fowler A. J. , Dobbs T. D. , Wan Y. I. , Laloo R. , Hui S. , Nepogodiev D. , Bhangu A. , Whitaker I. S. , Pearse R. M. , Abbott T. E. F. 
Published: June 2020

AbstractBackgroundThe response to COVID-19 has required cancellation of all but the most urgent surgeries, including many cancer operations. We estimated the number of cancelled surgical procedures in the National Health Service (NHS) in England due to COVID-19 and how this deficit would change over time once elective surgery was reintroduced.MethodsModelling study using Hospital Episode Statistics (HES) data from 2014 to 2019. Using NHS England definitions, surgical procedures were grouped into four classes of urgency. We calculated time-weighted average numbers of surgical procedures from 1stMarch 2020 and extrapolated to 28thFebruary 2021 informed by activity in previous years. We estimated the procedure deficit using multiple conservative assumptions and then modelled the reintroduction of elective surgery between 1stJune 2020 and 28thFebruary 2021, estimating the resources required to achieve this. Costs of surgery were calculated using NHS reference costs. Estimates are reported with 95% confidence intervals.Findings4,547,534 (3,318,195 - 6,250,771) patients with pooled mean age of 53.5 years were expected to undergo surgery in the NHS in England between 1stMarch 2020 and 28thFebruary 2021. Due to COVID-19, 749,248 (513,565 - 1,077,448) surgical procedures were cancelled by 31stMay 2020. As current guidelines require a gradual reintroduction of elective surgery, this deficit will increase further and 2,270,178 (1,453,057 - 3,363,472) patients will be awaiting surgery by 28th February 2021. The cost of these delayed procedures is £4,688,318,443 (£2,726,364,240 - £7,070,166,056). However, the safe delivery of surgery during the pandemic will require substantial extra resources including personal protective equipment and universal preoperative screening, leading to additional costs of £606,252,901 (£521,159,931 - £730,720,808).InterpretationReintroduction of elective surgery during the pandemic response in NHS England will be associated with substantial treatment delays for many patients, and a large increase in treatment costs.FundingNIHR (DRF-2018-11-ST2-062) to AJF.
Priority Setting of Ventilators in the COVID-19 Pandemic from the public’s perspective
Authors: Asghari Fariba , Parsapour Alireza , Gooshki Ehsan Shamsi 
Published: June 2020

AbstractBackgroundVentilator allocation plan for public health crisis should be developed through recognizing the values of society and engaging the general public. This study was conducted to assess the Iranian citizens’ attitude about a number of principles and criteria for allocation of ventilators in current COVID-19 epidemic.Materials and MethodsAn electronic self-administered questionnaire was publicly distributed through social networks of Telegram and WhatsApp to perform this cross-sectional study. The questionnaire consisted of 11 statements about the selection and prioritization of patients for the use of a ventilator.Results1262 persons, including 767 citizens and 495 health care providers participated in this study. More than 95% of participants agreed upon the necessity to avoid discrimination and avoid prioritization according to patients’ gender, economic and political status. While 40.9% of citizens and 49.6% of healthcare workers believed that a ventilator can be disconnected from a patient with a poor prognosis to help a patient who has a better prognosis (P-value=0.13), 34.3% of people and 29.6% of healthcare workers believed that the earlier admitted patients have the right to receive the device even if the likeliness of his/her survival is less than the next patient (P-value=0.009).ConclusionsThis study showed that people accept maximizing health benefits as a measure of ventilator allocation in the pandemic of COVID-19. At the same time, periodic evaluation of patients and disconnecting the device from a patient that no longer benefits from ICU services requires its scientific and ethical basis to be brought in public discourse.
Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?
Authors: Gittins Adam , Talbott Nick , Gilani Ahmed A , Packer Greg , Browne Richard , Mullhi Randeep , Khan Zaheed , Whitehouse T , Belli Antonio , Mehta Rajnikant L , Gao-Smith Fang , Veenith Tonny 
Published: June 2020

ABSTRACTBackground/ObjectivePatients with poor-grade subarachnoid bleed (pSAH, World Federation of Neurosurgeons grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 hours (IM) and delayed management after 24 hours (DM) in patients following pSAH.MethodsThis was a retrospective population-based study, including patients with pSAH who received definitive management between 1st January 2011 and 31st December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio (OR) of favourable outcome (Glasgow Outcome Scale (GOS) 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale (GOS). The secondary outcomes included adjusted OR of a favourable outcome at discharge, three months and six months following discharge and survival rate at 28 days, three months, six months and 12 months following haemorrhage.Results111 patients were included in this study: 53 (48%) received immediate management (IM) and 58 (41%) received delayed management (DM). The mean time delay from referral to intervention was 14.9±5.8 hours in IM patients, compared to 79.6±106.1 hours in DM patients. At 12 months following discharge, the adjusted OR for favourable outcome in IM versus DM patients was 0.96 (CI 0.17, 5.39; p=0.961). At hospital discharge, three months and six months, the adjusted OR for favourable outcome was 3.85 (CI 1.38, 10.73; p=0.010), 1.04 (CI 0.22, 5.00; p=0.956) and 0.98 (CI 0.21, 4.58; p=0.982), respectively. There were no differences in survival rate between the groups at 28 days, three months, six months and 12 months (71.7% in IM group vs 82.8% in DM group at 12 months, p=0.163).ConclusionsIM and DM after pSAH are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.
Association of genetic liability to smoking initiation with e-cigarette use in young adults
Authors: Khouja Jasmine N , Wootton Robyn E , Taylor Amy E , Smith George Davey , Munafò Marcus R 
Published: June 2020

AbstractBackgroundSmoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.Methods and FindingsPRS of smoking initiation were calculated for young adults (aged 23 to 26 years) of European ancestry in the Avon Longitudinal Study of Parents and Children using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5×10−8 to 0.5 were used to calculate five PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and both self-reported smoking initiation and self-reported e-cigarette use, as well as a number of negative control outcomes (socioeconomic position at birth, externalising disorders in childhood and risk-taking in young adulthood). We observed positive associations of similar magnitude between smoking initiation PRS and both smoking initiation (OR = 1.29, 95% CI 1.19 to 1.39) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34) by the age of 24 years. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth).ConclusionsOur results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. Taken together, this indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.
The origin and early spread of SARS-CoV-2 in Europe
Authors: Nadeau Sarah A. , Vaughan Timothy G. , Sciré Jérémie , Huisman Jana S. , Stadler Tanja 
Published: June 2020

AbstractThe investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.Significance StatementWe estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures based on viral genome sequences using a phylodynamic model with geographic structure. We confirm that the predominant European outbreak most likely started in Italy and spread from there. This outbreak was probably seeded by a transmission event in either Hubei or Germany. In particular, we find that before the first border closures in Europe, the rate of new cases occurring from within-country transmission was within the estimated bounds on the rate of new migration cases.
At-home self-collection of saliva, oropharyngeal swabs and dried blood spots for SARS-CoV-2 diagnosis and serology: post-collection acceptability of specimen collection process and patient confidence in specimens
Authors: Valentine-Graves Mariah , Hall Eric , Guest Jodie , Adam Elizabeth , Valencia Rachel , Hardee Isabel , Shinn Katlin , Sanchez Travis , Siegler Aaron J , Sullivan Patrick 
Published: June 2020

AbstractBackgroundOptions to increase the ease of testing for SARS-CoV-2 infection and immune response are needed. Self-collection of diagnostic specimens at home offers an avenue to allow people to test for SARS-CoV-2 infection or immune response without traveling to a clinic or laboratory. Before this study, survey respondents indicated willingness to self-collect specimens for COVID-related tests, but hypothetical willingness can differ from post-collection acceptability after participants collect specimens.Methods153 US adults were enrolled in a study of the willingness and feasibility of patients to self-collect three diagnostic specimens (saliva, oropharyngeal swab (OPS) and dried blood spot (DBS) card) while observed by a clinician through a telehealth session. After the specimens were collected, 148 participants participated in a survey about the acceptability of the collection, packing and shipping process, and their confidence in the samples collected for COVID-related laboratory testing.ResultsA large majority of participants (>84%) reported that collecting, packing and shipping of saliva, OPS, and DBS specimens were acceptable. Nearly nine in 10 (87%) reported being confident or very confident that the specimens they collected were sufficient for laboratory analysis. There were no differences in acceptability for any specimen type, packing and shipping, or confidence in samples by gender, age, race/ethnicity, or educational level.ConclusionsSelf-collection of specimens for SARS-CoV-2 testing and preparing and shipping specimens for analysis were acceptable in a diverse group of US adults. Further refinement of materials and instructions to support self-collection of saliva, OPS and DBS specimens for COVID-related testing is needed.Trial registrationNo intervention was tested in this study