bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: A rapid scoping review
Authors: Mc Evoy David , McAloon Conor G. , Collins Áine B. , Hunt Kevin , Butler Francis , Byrne Andrew W. , Casey Miriam , Barber Ann , Griffin John , Lane Elizabeth Ann , Wall Patrick , More Simon J. 
Published: August 2020

ABSTRACTObjectivesThe aim of this study was to conduct a scoping review of estimates of the relative infectiousness of asymptomatic persons infected with SARS-CoV-2 compared with symptomatic individuals.DesignRapid scoping review of literature available until 8thApril 2020.SettingInternational studies on the infectiousness of individuals infected with SARS-CoV-2ParticipantsStudies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from pre-symptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics.Primary outcome measuresThe relative number of secondary cases produced by an average primary case, the relative probability of transmitting infection upon contact, and the degree of viral shedding.ResultsVery few studies reported estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. Significant differences exist in the definition of infectiousness. Viral shedding studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals but are likely to be impacted by insufficient statistical power. Two contact tracing studies provided estimates of 0.7 and 1.0, but differences in approach and definition preclude comparison across the two studies. Finally, two modelling studies suggest a relative infectiousness of around 0.5 but one of these was more reflective of the infectiousness of undocumented rather than asymptomatic cases. Importantly, one contact tracing study showing a very low level of infectiousness of asymptomatic was not included in the analysis at this point due difficulties interpreting the reported findings.ConclusionsThe present study highlights the need for additional studies in this area as a matter of urgency. For the purpose of epidemiological modelling, we cautiously suggest that at present, asymptomatics could be considered to have a degree of infectiousness which is about 0.40-0.70 that of symptomatics. However, it must be stressed that this suggestion comes from a very low evidence base and that estimates exist that are close to zero and close to 1.ARTICLE SUMMARYStrengths and limitations of this study-Differences in the definition of infectiousness and a low number of studies estimating this parameter negate the potential to provide a pooled quantitative estimate or relative infectiousness.-The present study highlights the need for additional studies in this area as a matter of urgency.-Several of the studies reviewed are in pre-print stage and are not peer-reviewed.
Clinical manifestations of patients with Coronavirus Disease 2019 (COVID-19) attending at hospitals in Bangladesh
Authors: Morshed Md. Shahed , Mosabbir Abdullah Al , Chowdhury Prodipta , Ashadullah Sheikh Mohammad , Hossain Mohammad Sorowar 
Published: August 2020

AbstractBangladesh is in the rising phase of the ongoing pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The scientific literature on clinical manifestations of COVID-19 patients from Bangladesh is scarce. This study aimed to report the sociodemographic and clinical characteristics of patients with COVID-19 in Bangladesh. We conducted a cross-sectional study at three dedicated COVID-19 hospitals. The severity of the COVID-19 cases was assessed based on the WHO interim guidance. Data were collected only from non-critical COVID-19 patients as critical patients required immediate intensive care admission making them unable to respond to the questions. A total of 103 RT-PCR confirmed non-critical COVID-19 patients were enrolled. Most of the patients (71.8%) were male. Mild, moderate and severe illness were assessed in 74.76%, 9.71% and 15.53% of patients respectively. Nearly 52.4% of patients had a co-morbidity, with hypertension being the most common (34%), followed by diabetes mellitus (21.4%) and ischemic heart disease (9.7%). Fever (78.6%), weakness (68%) and cough (44.7%) were the most common clinical manifestations. Other common symptoms included loss of appetite (37.9%), difficulty in breathing (37.9%), altered sensation of taste or smell (35.0%), headache (32%) and body ache (32%). The median time from onset of symptom to attending hospitals was 7 days (IQR 4-10). This study will help both the clinicians and epidemiologists to understand the magnitude and clinical spectrum of COVID-19 patients in Bangladesh.
Effects of COVID-19 lockdown on heart rate variability
Authors: Bourdillon Nicolas , Yazdani Sasan , Schmitt Laurent , P.Millet Grégoire 
Published: August 2020

ABSTRACTIntroductionStrict lockdown rules were imposed to the French population from 17 March to 11 May 2020, which may result in limited possibilities of physical activity, modified psychological and health states. This report is focused on HRV parameters kinetics before, during and after this lockdown period.Methods95 participants were included in this study, who underwent regular orthostatic tests (a 5-minute supine followed by a 5-minute standing recording of heart rate (HR)) on a regular basis before, during and after the lockdown (BSL, CFN and RCV, respectively). HR, power in low- and high-frequency bands (LF, HF, respectively) and root mean square of the successive differences (RMSSD) were computed for each orthostatic test, and for each positions. Subjective well-being was assessed on a 0-10 visual analogic scale (VAS).ResultsOut of the 95 participants, 19 (WB+) reported an improved well-being (i.e., increase >2 in VAS score) during CFN, contradictory to the 76 other participants (WB-). There was an increase in HR and a decrease in RMSSD when measured supine in CFN and RCV, compared to BSL in WB-, whilst opposite results were found in WB+ (i.e. decrease in HR and increase in RMSSD in CFN and RCV; increase in LF and HF in RCV). There was a moderate significant correlation between VAS and HR, RMSSD, HF, respectively, in the supine position; the higher the VAS score (i.e., subjective well-being), the higher the RMSSD and HF and the lower the HR. In standing position, HRV parameters were not modified during CFN.ConclusionThe strict COVID-19 lockdown likely had opposite effects on French population as 20% of participants improved parasympathetic activation (RMSSD, HF) and rated positively this period, whilst 80% showed altered responses and deteriorated well-being. The changes in HRV parameters during and after the lockdown period were in line with subjective well-being responses. These results confirmed the usefulness of HRV as a non-invasive means for monitoring well-being and health in the general population.
Development and Evaluation of MADDIE: Method to Acquire Delivery Date Information from Electronic Health Records
Authors: Canelón Silvia P. , Burris Heather H. , Levine Lisa D. , Boland Mary Regina 
Published: August 2020

AbstractObjectiveTo develop an algorithm that infers patient delivery dates (PDDs) and delivery-specific details from Electronic Health Records (EHRs) with high accuracy.Materials and MethodsWe obtained EHR data from 1,060,100 female patients treated at Penn Medicine hospitals or outpatient clinics between 2010-2017. We developed an algorithm called MADDIE: Method to Acquire Delivery Date Information from Electronic Health Records that infers a PDD for distinct deliveries based on EHR encounter dates assigned a delivery code, the frequency of code usage, and the time differential between code assignments. We validated MADDIE’s PDDs against a birth log independently maintained by the Department of Obstetrics and Gynecology.ResultsMADDIE identified 50,560 patients having 63,334 distinct deliveries. MADDIE was 98.6% accurate (F1-score 92.1%) when compared to the birth log. The PDD was on average 0.68 days earlier than the true delivery date for patients with only one delivery (± 1.43 days) and 0.52 days earlier for patients with more than one delivery episode (± 1.11 days).DiscussionMADDIE is the first algorithm to successfully infer PDD information using only structured delivery codes and identify multiple deliveries per patient. MADDIE is also the first to validate the accuracy of the PDD using an external gold standard of known delivery dates as opposed to manual chart review of a sample.ConclusionMADDIE infers delivery dates and delivery-specific details from the EHR with high accuracy and relies only on structured EHR elements while harnessing temporal information and the frequency of code usage to identify accurate PDDs.
Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety between 2015 and 2020
Authors: Creese Byron , Khan Zunera , Henley William , O’Dwyer Siobhan , Corbett Anne , Da Silva Miguel Vasconcelos , Mills Kathryn , Wright Natalie , Testad Ingelin , Aarsland Dag , Ballard Clive 
Published: August 2020

BackgroundLoneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies and are potentially modifiable.MethodWe analysed mental health data collected during COVID-19 from adults aged 50 and over alongside comparable annual data collected between 2015 and 2019 from the same sample. Trajectories of depression (PHQ-9) and anxiety (GAD-7) were analysed with respect to loneliness, physical activity levels and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression.Results3,281 people completed the COVID-19 mental health questionnaire, all had at least one data point prior to 2020. In 2020, the adjusted PHQ-9 score for loneliness was 3.2. (95% CI: 3.0-3.4), an increase of one point on previous years and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.2, 95% CI: 1.1-1.3). PHQ-9 was 2.6 (95% CI: 2.4-2.8) in people with decreased physical activity, an increase of 0.5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.7 (95% CI: 1.6-1.8), similar to previous years. A similar relationship was observed for GAD-7 though the differences were smaller and the absolute burden of symptoms lower.ConclusionsAfter accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors.
Microbial contamination of powered air purifying respirators (PAPR) used during the COVID-19 pandemic: an in situ microbiological study
Authors: Chakladar Abhijoy , Jones Claire G , Siu Jimmy , Hassan-Ibrahim Mohammed Osman , Khan Mansoor 
Published: August 2020

ABSTRACTOBJECTIVETo determine whether internal components of powered air purifying respirators (PAPR) used during the Corona virus 2019 disease (COVID-19) pandemic are contaminated with bacteria, fungi and/or any viral material.DESIGN & SETTINGIn situ microbiological study. Single NHS Trust, UK.OUTCOME MEASURESGrowth of any bacteria or fungi, or positive polymerase chain reaction results for common respiratory viruses and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)RESULTS25 PAPR hoods were swabbed; ten (40%) returned positive results. Bacterial growth was detected on six hoods (bacillus simplex, kocuria rhizophilia, bacillus weihenstephensis, microcccus luteus and staphylococcus epidermidis); five of the hoods were positive for fungal growth (non-sporulating environmental mould, NSEM); all sampled hoods tested negative for both SARS-CoV-2 and an expanded panel of respiratory viruses. There was wide variation in the storage of cleaned hoods.CONCLUSIONDespite following recommended cleaning procedures, bacteria and fungi can remain on the internal components of PAPR hoods, at levels significant enough to be swabbed and cultured. PAPR hoods have the potential to cross-infect wearers and patients and are used primarily by clinicians who fail to fit disposable FFP3 respirators; the female sex and non-Caucasian people are less likely to fit FFP3 respirators. The hoods tested cannot be adequately cleaned for use in high risk healthcare environments, PAPR hoods and tubes can act as fomites, and there are evident shortcomings in their provision.SUMMARYWHAT IS ALREADY KNOWN ON THIS TOPICPrior to this study there had been no similar investigations looking at the microbiological contamination of PAPR hoods in situ in the real work place hospital environment.SARS-CoV-2 is able to persist in an infective state on surfaces for up to 72 hours.The possibility of internal contamination of PAPR had never been addressed by manufacturers as the hoods were not designed for shared usage.WHAT THIS PAPER ADDSPAPR hoods in their current form risk transmitting infection between users, and do not protect patients from infected healthcare workersIt is possible to detect biological agents within the PAPR hoods despite cleaning as per guidelinesAn infected asymptomatic carrier is at risk of infecting those around them due to contaminated exhalation
NAD modulates DNA methylation and cell differentiation
Authors: Ummarino Simone , Bassal Mahmoud A. , Zhang Yanzhou , Seelam Andy Joe , Kobayashi Ikei S. , Borchiellini Marta , Ebralidze Alexander K. , Trinh Bon Q. , Kobayashi Susumu S. , Di Ruscio Annalisa 
Published: August 2020

AbstractNutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Herein, we present a novel epigenetic effect of the essential nutrient, NAD. We demonstrate that impairment of DNMT1 enzymatic activity by NAD-promoted ADP-ribosylation, leads to demethylation and transcriptional activation ofCEBPAgene, suggesting the existence of an unknown NAD-controlled region within the locus. In addition to the molecular events, NAD treated cells exhibit significant morphological and phenotypical changes that correspond to myeloid differentiation.Collectively, these results delineate a novel role for NAD in cell differentiation and indicate novel nutri-epigenetic strategy to regulate and control gene expression in human cells.
Engineered ACE2 receptor traps potently neutralize SARS-CoV-2
Authors: Glasgow Anum , Glasgow Jeff , Limonta Daniel , Solomon Paige , Lui Irene , Zhang Yang , Nix Matthew A. , Rettko Nicholas J. , Lim Shion A. , Zha Shoshana , Yamin Rachel , Kao Kevin , Rosenberg Oren S. , Ravetch Jeffrey V. , Wiita Arun P. , Leung Kevin K. , Zhou Xin X. , Hobman Tom C. , Kortemme Tanja , Wells James A. 
Published: August 2020

AbstractAn essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the 10-100 ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be pre-designed for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated or generated from convalescent patients.
The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities
Authors: Valle Aida Alonso-del , León-Sampedro Ricardo , Rodríguez-Beltrán Jerónimo , DelaFuente Javier , Hernández-García Marta , Ruiz-Garbajosa Patricia , Cantón Rafael , Peña-Miller Rafael , Millán Álvaro San 
Published: August 2020

Introductory paragraphPlasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.
Circular RNA expression profiles in pediatric ependymomas
Authors: Ahmadov Ulvi , Bendikas Meile M. , Ebbesen Karoline K. , Sehested Astrid M. , Kjems Jørgen , Broholm Helle , Kristensen Lasse S. 
Published: August 2020

AbstractPediatric brain tumors frequently develop in the cerebellum, where ependymoma, medulloblastoma and pilocytic astrocytoma are the most prevalent subtypes. These tumors are currently treated using non-specific therapies, in part because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) have recently emerged as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but so far they have not been described in pediatric brain tumors. To advance our understanding of these tumors, we performed high-throughput sequencing of ribosomal RNA-depleted total RNA from 10 primary ependymoma and 3 control samples. CircRNA expression patterns were determined using two independent bioinformatics algorithms, and correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, we performed NanoString nCounter experiments using a custom-designed panel including 66 selected circRNA targets and analyzed formalin-fixed paraffin-embedded (FFPE) samples from a larger cohort of ependymoma patients as well as patients diagnosed with medulloblastoma or pilocytic astrocytoma. These experiments were used to validate our findings and, in addition, indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRMST and a circRNA derived from the LRBA gene were specifically upregulated in ependymomas. In conclusion, circRNAs have profoundly different expression profiles in ependymomas relative to controls and other pediatric brain tumor subtypes.
Validation of multiplex steroid hormone measurements in prostate cancer using plasma for multimodality biomarker studies
Authors: Snaterse Gido , van Dessel Lisanne F , Taylor Angela E , Visser Jenny A , Arlt Wiebke , Lolkema Martijn P , Hofland Johannes 
Published: August 2020

ABSTRACTBackgroundSteroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias caused by matrix effects, thus assessing potential matrix effects is an important step in combining circulating tumour DNA analysis with hormone status.MethodsWe investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain circulating tumour DNA (ctDNA), compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in samples obtained from ten healthy controls and ten castration-resistant prostate cancer (CRPC) patients.ResultsSteroid measurements were comparable between MSP and serum. A small but consistent decrease of 8 – 21% compared to serum was observed when using CS plasma, which was considered to be within the acceptable margin. The minimal residual testosterone levels of CRPC patients could be sensitively quantified in both MSP and CS samples.ConclusionsWe validated the use of MSP and CS samples for multi-steroid profiling by LC-MS/MS. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients.