bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyanobacterial growth and morphology are influenced by carboxysome positioning and temperature
Authors: Rillema Rees , MacCready Joshua S. , Vecchiarelli Anthony G. 
Published: June 2020

ABSTRACTCyanobacteria are the prokaryotic group of phytoplankton responsible for a significant fraction of global CO2fixation. Like plants, cyanobacteria use the enzyme Ribulose 1,5-bisphosphate Carboxylase/Oxidase (RuBisCO) to fix CO2into organic carbon molecules via the Calvin-Benson-Bassham cycle. Unlike plants, cyanobacteria evolved a carbon concentrating organelle called the carboxysome - a proteinaceous compartment that encapsulates and concentrates RuBisCO along with its CO2substrate. In the rod-shaped cyanobacteriumSynechococcus elongatusPCC7942, we recently identified the McdAB system responsible for uniformly distributing carboxysomes along the cell length. It remains unknown what role carboxysome positioning plays with respect to cellular physiology. Here, we show for the first time that a failure to distribute carboxysomes leads to a temperature-dependent decrease in cell growth rate, cell division arrest, cell elongation, asymmetric cell division, and a significant reduction in cellular levels of RuBisCO. Unexpectedly, we also report that even wild-typeS. elongatusundergoes filamentous growth at the cool, but environmentally-relevant, growth temperature of 20°C. The findings suggest that carboxysome positioning by the McdAB system functions to maintain the carbon-fixation efficiency of RuBisCO by preventing carboxysome aggregation, which is particularly important at temperatures where rod-shaped cyanobacteria adopt a filamentous morphology.IMPORTANCEPhotosynthetic cyanobacteria are responsible for almost half of global CO2fixation. Due to eutrophication, rising temperatures, and increasing atmospheric CO2concentrations, cyanobacteria have recently gained notoriety for their ability to form massive blooms in both freshwater and marine ecosystems across the globe. Like plants, cyanobacteria use the most abundant enzyme on Earth, RuBisCO, to provide the sole source of organic carbon required for its photosynthetic growth. Unlike plants, cyanobacteria have evolved a carbon-concentrating organelle called the carboxysome that encapsulates and concentrates RuBisCO with its CO2substrate to significantly increase carbon-fixation efficiency and cell growth. We recently identified the positioning system that distributes carboxysomes in cyanobacteria. However, the physiological consequence of carboxysome mispositioning in the absence of this distribution system remains unknown. Here we find that carboxysome mispositioning triggers temperature-dependent changes in cell growth and morphology as well as a significant reduction in cellular levels of RuBisCO.
The use of negative control outcomes in Mendelian Randomisation to detect potential population stratification or selection bias
Authors: Sanderson Eleanor , Richardson Tom G , Hemani Gibran , Davey Smith George 
Published: June 2020

AbstractA key assumption of Mendelian randomisation (MR) analysis is that there is no association between the genetic variants used as instruments and the outcome other than through the exposure of interest. Two ways in which this assumption can be violated are through population stratification and selection bias which can introduce confounding of the relationship between the genetic variants and the outcome and so induce an association between them. Negative control outcomes are increasingly used to detect unobserved confounding in observational epidemiological studies. Here we consider the use of negative control outcomes in MR studies. As a negative control outcome in an MR study we propose the use of phenotypes which are determined before the exposure and outcome but which are likely to be subject to the same confounding as the exposure or outcome of interest. We illustrate our method with a two-sample MR analysis of a preselected set of exposures on self-reported tanning ability and hair colour. Our results show that, of the 33 exposures considered, GWAS studies of adiposity and education related traits are likely to be subject to population stratification and/or selection bias that is not controlled for through adjustment and so any MR study including these traits may be subject to bias that cannot be identified through standard pleiotropy robust methods.
Use of amplicon-based sequencing for testing fetal identity and monogenic traits with single circulating trophoblast (SCT) prenatal diagnosis
Authors: Zhuo Xinming , Wang Qun , Liesbeth Vossaert , Salman Roseen , Kim Adriel , Van den Veyver Ignatia , Breman Amy , Beaudet Arthur 
Published: June 2020

AbstractA major challenge for cell-based non-invasive prenatal testing (NIPT) is to distinguish individual presumptive fetal cells from maternal cells in female pregnancies. We have sought a rapid, robust, versatile, and low-cost next-generation sequencing method to facilitate this process. Toward this goal, single isolated cells underwent whole genome amplification prior to genotyping. Multiple highly polymorphic genomic regions (including HLA-A and HLA-B) with 10-20 very informative single nucleotide polymorphisms (SNPs) within a 200 bp interval were amplified with a modified method based on other publications. To enhance the power of cell identification, approximately 40 Human Identification SNP (Applied Biosystems) test amplicons were also utilized. This method allowed reliable differentiation of fetal and maternal cells. In fully informative cases, two haplotypes were found within the maternal reads, and fetal cells showed reads with one but not the second maternal haplotype while also showing a novel paternal haplotype absent in the mother. For SNP typing, at least 2 SNPs and 10% of informative SNPs were required to differentiate a fetal cell from a maternal cell. A paternal DNA sample is not required using this method. The assay also successfully detected point mutations causing Tay Sachs disease, cystic fibrosis, and hemoglobinopathies in single lymphoblastoid cells, and monogenic disease-causing mutations in three cell-based NIPT cases. This method could be applicable for any monogenic diagnosis.
Plasma ceramides as a sexually dimorphic biomarker of pancreatic cancer-induced cachexia
Authors: Chakedis Jeffery M. , Dillhoff Mary E. , Schmidt Carl R. , Rajasekera Priyani V. , Evans David C. , Williams Terence M. , Guttridge Denis C. , Talbert Erin E. 
Published: June 2020

AbstractBackgroundCancer patients who lose weight have low treatment tolerance and poor outcomes compared to cancer patients without weight loss, termed cachexia. Despite the clear increased risk for patients, diagnosing cachexia still primarily relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.MethodsTargeted metabolomics, including panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer. Receiver Operating Characteristic (ROC) analysis was undertaken to establish if any metabolite could effectively serve as a biomarker of cachexia.ResultsTargeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only elevated in cachectic males.ConclusionOur findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.Trial registrationNone.FundingSupport was provided through a pilot grant from U24DK100469 from the National Institute of Diabetes and Digestive and Kidney Diseases (The Mayo Clinic), National Cancer Institute P30CA016058 (The Ohio State University), National Cancer Institute R01CA180057 (DCG), American Cancer Society PF-15-156-01-CSM (EET), and a Weiss Postdoctoral Fellowship (EET).
Offset analgesia and onset hyperalgesia with different stimulus ranges
Authors: Fust Jens , Lalouni Maria , Lundqvist Viktor Vadenmark , Wärnberg Emil , Jensen Karin B. 
Published: June 2020

ABSTRACTOffset analgesia (OA), a large reduction in pain following a brief increase in intensity of an otherwise stable painful stimulus, has been established by a large body of research. But the opposite effect, onset hyperalgesia (OH), a disproportional hyperalgesic response following a briefly decreased intensity of a painful stimulus, has only been investigated in one previous study. The aim of this study was to induce OA and OH in healthy participants and explore the effects of different stimulus ranges on OA and OH. A total of 62 participants were tested in two identical experiments. OA and OH conditions included two different temperature deviations (±1°C/±2°C) from baseline and were compared to a constant temperature (control). OA was successfully elicited in three out of four conditions. A dose-response relationship was demonstrated between the increase of temperature and the resulting hypoalgesic response. OH was only elicited in one out of four conditions (OH2°Cin experiment 1). Exploratory analysis showed that OA and OH responses were only weakly correlated. The asymmetry between pain responses following a brief temperature increase and decrease could be seen as evidence for different mechanisms involved in the pain responses to increasing and decreasing temperature. This asymmetry may also be explained by high temperatures in OA condition (+1°C/+2°C above baseline) that could be seen as salient “learning signals”, which augment the response to following changes in temperature.
COVID-19: Why SOLIDARITY and DisCoVeRy trials may fail to bring informative and timely results
Authors: Toumi Mondher , Liang Shuyao , Dabbous Monique , Wang Yitong , Qiu Tingting , Han Ru 
Published: June 2020

AbstractObjectiveThe SOLIDARITY and DisCoVeRy trials were launched to facilitate the rapid worldwide comparison of the efficacy and safety of treatments against COVID-19. This study aimed to review the trial designs of SOLIDARITY and DisCoVeRy and their feasibility to generate high-quality evidence.MethodA systematic search of the European Clinical trial registry, the U.S. National Library of Medicine ClinicalTrials.gov, and the World Health Organization’s (WHO) International Clinical Trials Registry Platform (ICTRP) was conducted on May 10th, 2020 to identify the study details of the SOLIDARITY and DisCoVeRy trials. A supplementary search of PubMed, WHO’s website, French authorities’ websites, and Google search engine was conducted. A critical review was performed on the findings.ResultsThe DisCoVeRy trial design was detailed consistently in both the European and the US clinical rial registries. SOLIDARITY was registered on ICTRP, with country-specific information reported on country-level registry platforms. The DisCoVeRy trial’s design appears to be ideal from the methodological perspective. Both trials appear difficult to implement, impractical, and disconnected from the pandemic reality. This is consistent with the apparent failure of the trials to deliver conclusions before the end of the pandemic.ConclusionBoth trials constitute an interesting initiative yet may lack the resources to support a high-quality implementation. The authors call for a pandemic task force, with various experts on the front-line of COVID-19, to inform policy-makers to make effective decisions that may not be based on traditional, methodological state-of-the-art evidence, but rather pragmatic and revisable decisions reflecting emerging evidence for the benefit of patients and society.
Quantitative assessment of the risk of airborne transmission of SARS-CoV-2 infection: prospective and retrospective applications
Authors: Buonanno G. , Morawska L. , Stabile L. 
Published: June 2020

AbstractAirborne transmission is a recognized pathway of contagion; however, it is rarely quantitatively evaluated. This study presents a novel approach for quantitative assessment of the individual infection risk of susceptible subjects exposed in indoor microenvironments in the presence of an asymptomatic infected SARS-CoV-2 subject. The approach allowed the maximum risk for an exposed healthy subject to be evaluated or, starting from an acceptable risk, the maximum exposure time. We applied the proposed approach to four distinct scenarios for a prospective assessment, highlighting that, in order to guarantee an acceptable individual risk of 10−3for exposed subjects in naturally ventilated indoor environments, the exposure time should be shorter than 20 min. The proposed approach was used for retrospective assessment of documented outbreaks in a restaurant in Guangzhou (China) and at a choir rehearsal in Mount Vernon (USA), showing that, in both cases, the high attack rate values can be justified only assuming the airborne transmission as the main route of contagion. Moreover, we shown that such outbreaks are not caused by the rare presence of a superspreader, but can be likely explained by the co-existence of conditions, including emission and exposure parameters, leading to a highly probable event, which can be defined as a “superspreading event”.
A data driven epidemic model to analyse the lockdown effect and predict the course of COVID-19 progress in India
Authors: Sahoo B.K. , Sapra B.K. 
Published: June 2020

AbstractWe propose a data driven epidemic model using the real data on the infection, recovery and death cases for the analysis of COVID-19 progression in India. The model assumes continuation of existing control measures such as lockdown and quarantines, the suspected and confirmed cases and does not consider the scenario of 2nd surge of the epidemic due to any reason. The model is arrived after least square fitting of epidemic behaviour model based on theoretical formulation to the real data of cumulative infection cases reported between 24 March 2020 and 15 May 2020. The predictive capability of the model has been validated with real data of infection cases reported during May 15–30, 2020. A detailed analysis of model predictions in terms of future trend of COVID-19 progress individually in 18 states of India and India as a whole has been attempted. Infection rate in India as a whole is continuously decreasing with time and has reached 3 times lower than the initial infection rate after 6 weeks of lock down suggesting the effectiveness of the lockdown in containing the epidemic. Results suggest that India as a whole could see the peak and end of the epidemic in the month of July 2020 and January 2021. As per the current trend in the data, active infected cases in India may reach 2 lakhs at the peak time and total infected cases may reach around 14 lakhs. State-wise results have been discussed in the manuscript. However, the prediction may deviate particularly for longer dates, as assumptions of model cannot be met always in a real scenario. In view of this, a real time application (COV-IND Predictor) has been developed which automatically syncs the latest data from COVID19 dash board on daily basis and update the model input parameters and predictions of relevant results on daily basis. This application can serve as a practical tool for epidemic management decisions
Performance of suspected influenza case definition before and during the COVID-19 pandemic
Authors: Murillo-Zamora Efrén , Hernandez-Suarez Carlos 
Published: June 2020

AbstractBackgroundThe influenza-related burden remains high and the COVID-19 pandemic may difficult its accurate surveillance. This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20, 511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analyzed.ResultsA high sensitivity and modest specificity was documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the Area Under the Receiver Operating Characteristics among the analyzed periods.ConclusionsThe evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak.
High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay
Authors: McDade Thomas W. , McNally Elizabeth M. , Zelikovich Aaron S. , D’Aquila Richard , Mustanski Brian , Miller Aaron , Vaught Lauren A. , Reiser Nina L. , Bogdanovic Elena , Fallon Katherine S. , Demonbreun Alexis R. 
Published: June 2020

AbstractObjectiveSerological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS).MethodsAn ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members.ResultsAmong 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain.ConclusionDBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARSCoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection.
Association between NSAIDs use and adverse clinical outcomes among adults hospitalised with COVID-19 in South Korea: A nationwide study
Authors: Jeong Han Eol , Lee Hyesung , Shin Hyun Joon , Choe Young June , Filion Kristian B. , Shin Ju-Young 
Published: June 2020

SUMMARYBACKGROUNDNon-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate COVID-19 and worsen associated outcomes by upregulating the enzyme that SARS-CoV-2 binds to enter cells. However, to our knowledge, no study has examined the association between NSAID use and the risk of COVID-19-related outcomes among hospitalised patients.METHODSWe conducted a population-based cohort study using South Korea’s nationwide healthcare database, which contains data of all subjects who received a test for COVID-19 (n=69,793) as of April 8, 2020. We identified a cohort of adults hospitalised with COVID-19, where cohort entry was the date of hospitalisation. NSAIDs users were those prescribed NSAIDs in the 7 days before and including the date of cohort entry and non-users were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcome was cardiovascular or renal complications. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CI) using inverse probability of treatment weighting to minimize potential confounding.FINDINGSOf 1,824 adults hospitalised with COVID-19 (mean age 490 years, standard deviation 19 0 years; female 59%), 354 were NSAIDs users and 1,470 were non-users. Compared with non-use, NSAIDs use was associated with increased risks of the primary composite outcome (OR 1 65, 95% CI 1-21-2-24) and of cardiovascular or renal complications (OR 187, 95% CI 1-25-2-80). Our main findings remained consistent when we extended the exposure ascertainment window to include the first three days of hospitalisation (OR 187, 95% CI 1 06-3 29).INTERPRETATIONUse of NSAIDs, compared with non-use, is associated with worse outcomes among hospitalised COVID-19 patients. While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution among patients with COVID-19 as the harms associated with their use may outweigh their benefits in this population.FUNDINGGovernment-wide R&D Fund for Infectious Disease Research (HG18C0068).
The SARS-CoV-2 pandemic course in Saudi Arabia: A dynamic epidemiological model
Authors: Murhaf Al-Khani Abdullah , Abdelghafour Khalifa Mohamed , AlMazrou Abdulrahman , Saquib Nazmus 
Published: June 2020

AbstractObjectiveSaudi Arabia ranks second in the number of coronavirus disease 2019 (COVID-19) cases in the Eastern Mediterranean region. It houses the two most sacred religious places for Muslims: Mecca and Medina. It is important to know what the trend in case numbers will be in the next 4–6 months, especially during the Hajj pilgrimage season.MethodsEpidemiological data on COVID-19 were obtained from the Saudi Arabian Ministry of Health, the World Health Organization, and the Humanitarian Data Exchange. A susceptible-exposed-infectious-recovered (SEIR) prediction model was constructed to predict the trend in COVID-19 in Saudi Arabia in the next 6 months.FindingsThe model predicts that the number of active cases will peak by 20 May 2020. The cumulative infected cases are predicted to reach 59,663 at that time. The total number of infected individuals is estimated reach to 102,647 by the end of the pandemic.ConclusionOur estimates show that by the time the Hajj season commences in Saudi Arabia, the pandemic will be in the midst of its deceleration phase (phase 3). This information will likely be useful to policymakers in their management of the outbreak.