bluuebunny/crossref_metadata_2025_split huggingface dataset:
4-1BB is a target for immunotherapy in patients with undifferentiated pleomorphic sarcoma
Authors: Melake MJ , Smith HG , Mansfield D , Davies E , Dillon MT , Wilkins AC , Patin EC , Pedersen M , Buus R , Miah AB , Zaidi SH , Thway K , Melcher AA , Hayes AJ , Fenton TR , Harrington KJ , McLaughlin M 
Published: July 2020

AbstractSystemic relapse, after treatment of a localised primary tumour with neo-adjuvant radiotherapy and surgery, is the major cause of disease related mortality in patients with sarcoma. As with other cancers, many sarcoma patients derive no benefit from anti-PD-1 treatment. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates and control metastatic disease. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data to explore patient stratification for immunotherapy and therapeutic targets of relevance to sarcoma. We show a group of patients with immune-hot undifferentiated pleomorphic sarcoma as one of the highest-ranking candidates for emerging 4-1BB targeting agents. A binary hot/cold classification method indicates 4-1BB-high hot sarcomas share many characteristics with immunotherapy responsive cancers of other pathologies. Hot tumours in sarcoma are however substantially less prevalent. Patient stratification, of intense interest for immunotherapies, is therefore even more important in sarcoma.
Cortical propagation as a biomarker for recovery after stroke
Authors: Cecchini Gloria , Scaglione Alessandro , Mascaro Anna Letizia Allegra , Checcucci Curzio , Conti Emilia , Adam Ihusan , Fanelli Duccio , Livi Roberto , Pavone Francesco Saverio , Kreuz Thomas 
Published: July 2020

AbstractStroke is a debilitating condition affecting millions of people worldwide. The development of improved rehabilitation therapies rests on finding biomarkers suitable for tracking functional damage and recovery. To achieve this goal, we perform a spatiotemporal analysis of cortical activity obtained by wide-field calcium images in mice before and after stroke. We compared spontaneous recovery with three different post-stroke rehabilitation paradigms, motor training alone, pharmacological contralesional inactivation and both combined. We identify three novel indicators that are able to track how movement-evoked global activation patterns are impaired by stroke and evolve during rehabilitation: the duration, the smoothness, and the angle of individual propagation events. Results show that, compared to pre-stroke conditions, propagation of cortical activity in the acute phase right after stroke is slowed down and more irregular. When comparing rehabilitation paradigms, we find that mice treated with both motor training and pharmacological intervention, the only group associated with generalized recovery, manifest new propagation patterns, that are even faster and smoother than before the stroke. In conclusion, our new spatiotemporal propagation indicators act as biomarkers that are able to uncover neural correlates not only of motor deficits caused by stroke but also of functional recovery during rehabilitation. These insights could pave the way towards more targeted post-stroke therapies.
Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS-S and MERS-S pseudotyped particles
Authors: Chen Catherine Z. , Xu Miao , Pradhan Manisha , Gorshkov Kirill , Petersen Jennifer , Straus Marco R. , Zhu Wei , Shinn Paul , Guo Hui , Shen Min , Klumpp-Thomas Carleen , Michael Samuel G. , Zimmerberg Joshua , Zheng Wei , Whittaker Gary R. 
Published: July 2020

AbstractWhile vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients.Abstract Figure
Characteristics and transmission dynamics of COVID-19 in healthcare workers at a London teaching hospital
Authors: Zheng Charlotte , Hafezi-Bakhtiari Nema , Cooper Victoria , Davidson Harriet , Habibi Maximillian , Riley Peter , Breathnach Aodhan 
Published: July 2020

SummaryBackgroundHealthcare worker (HCW) associated COVID-19 is of global concern due to the potential for nosocomial spread and depletion of staff numbers. However, the literature on transmission routes and risk factors for COVID-19 in HCWs is limited.AimTo examine the characteristics and transmission dynamics of SARS-CoV-2 in HCWs in a university teaching hospital in London, UK.MethodsStaff records and virology testing results were combined to identify staff sickness and COVID-19 rates from March to April 2020. Comparisons were made with staff professional groups, department of work and ethnicity. Analysis was performed using Microsoft Excel™.FindingsCOVID-19 rates in our HCWs largely rose and declined in parallel with the number of community cases. White and non-white ethnic groups among our HCWs had similar rates of infection. Clinical staff had a higher rate of laboratory-confirmed COVID-19 than non-clinical staff, but total sickness rates were similar. Doctors had the highest rate of infection, but took the fewest sickness days. Critical Care had lower rates than the Emergency Department (ED), but rates in the ED declined once all staff were advised to use Personal Protective Equipment (PPE).ConclusionThese findings show that sustained transmission of SARS-CoV-2 among our hospital staff did not occur, beyond the community outbreak, even in the absence of strict infection control measures in non-clinical areas. The results also suggest that current PPE is effective when used appropriately. In addition, our findings emphasise the importance of testing both clinical and non-clinical staff groups during a pandemic.
A framework for making predictive models useful in practice
Authors: Jung Kenneth , Kashyap Sehj , Avati Anand , Harman Stephanie , Shaw Heather , Li Ron , Smith Margaret , Shum Kenny , Javitz Jacob , Vetteth Yohan , Seto Tina , Bagley Steven C. , Shah Nigam H. 
Published: July 2020

AbstractObjectiveTo analyze the impact of factors in healthcare delivery on the net benefit of triggering an Advanced Care Planning (ACP) workflow based on predictions of 12-month mortality.Materials and MethodsWe built a predictive model of 12-month mortality using electronic health record data and evaluated the impact of healthcare delivery factors on the net benefit of triggering an ACP workflow based on the models’ predictions. Factors included non-clinical reasons that make ACP inappropriate, limited capacity for ACP, inability to follow up due to patient discharge, and availability of an outpatient workflow to follow up on missed cases. We also quantified the relative benefits of increasing capacity for inpatient ACP versus outpatient ACP.ResultsWork capacity constraints and discharge timing can significantly reduce the net benefit of triggering the ACP workflow based on a model’s predictions. However, the reduction can be mitigated by creating an outpatient ACP workflow. Given limited resources to either add capacity for inpatient ACP versus developing outpatient ACP capability, the latter is likely to provide more benefit to patient care.DiscussionThe benefit of using a predictive model for identifying patients for interventions is highly dependent on the capacity to execute the workflow triggered by the model. We provide a framework for quantifying the impact of healthcare delivery factors and work capacity constraints on achieved benefit.ConclusionAn analysis of the sensitivity of the net benefit realized by a predictive model triggered clinical workflow to various healthcare delivery factors is necessary for making predictive models useful in practice.
White matter hyperintensities classified according to intensity and spatial location reveal specific associations with cognitive performance
Authors: Melazzini Luca , Mackay Clare E , Bordin Valentina , Suri Sana , Zsoldos Enikő , Filippini Nicola , Mahmood Abda , Sundaresan Vaanathi , Codari Marina , Duff Eugene , Singh-Manoux Archana , Kivimäki Mika , Ebmeier Klaus P , Jenkinson Mark , Sardanelli Francesco , Griffanti Ludovica 
Published: July 2020

ABSTRACTWhite matter hyperintensities (WMHs) on T2-weighted images are radiological signs of cerebral small vessel disease. As their total volume is variably associated with cognition, a new approach that integrates multiple radiological criteria is warranted. Location may matter, as periventricular WMHs have been shown to be associated with cognitive impairments. WMHs that appear as hypointense in T1-weighted images (T1w) may also indicate the most severe component of WMHs. We developed an automatic method that classifies WMHs into four categories (periventricular/deep and T1w-hypointense/nonT1w-hypointense) using MRI data from 684 community-dwelling older adults from the Whitehall II study. To test if location and intensity information can impact cognition, we derived two general linear models using either overall or subdivided volumes. Results showed that periventricular T1w-hypointense WMHs were significantly associated with poorer performance in several cognitive tests. We found no association between total WMH volume and cognition. These findings suggest that classifying WMHs according to both location and intensity in T1w adds value over and above total WMH volume.HIGHLIGHTSHeterogeneous measures of WMHs are used in research and clinical practice.Location and image intensity should be considered in the assessment of WMHs.T1-hypointense WMHs were found to be associated with poorer cognitive performance.Sub-classes of WMHs provide promising results for translation into the clinic.
No benefits of prolonged vitamin D3 supplementation for adaptations to resistance training in old adults
Authors: Mølmen KS , Hammarström D , Pedersen K , Lie AC Lian , Steile RB , Nygaard H , Khan Y , Hamarsland H , Koll L , Hanestadhaugen M , Eriksen A Lie , Grindaker E , Whist JE , Buck D , Ahmad R , Strand TA , Rønnestad BR , Ellefsen S 
Published: July 2020

AbstractBackgroundLifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those chronically diseased (e.g. chronic obstructive pulmonary disease, COPD), and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored.MethodsNinety-five male and female participants (healthy, n=71; COPD, n=24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (in average, 3333 IU.day-1), followed by 13 weeks of combined supplementation (2000 IU.day-1) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n=7), endurance performance (n=6), and muscle mass (n=3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments.ResultsOverall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%) and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, − 6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3%-points), myonuclei·fibre-1 (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. ∼336 differentially expressed genes). Vitamin D3 supplementation led to robust increases in [25(OH)D]serum (Δ49% vs placebo), but did not affect training-associated changes for any of the main outcome domains, with no interaction being evident with disease status or pre-RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue, strength gains in participants with high fat mass, and [cortisol]serum (Δ20%), all of which advocate further study.ConclusionsVitamin D3 supplementation did not affect muscular responses to resistance training in old adults with or without COPD.
Wastewater SARS-CoV-2 RNA Concentration and Loading Variability from Grab and 24-Hour Composite Samples
Authors: Curtis Kyle , Keeling David , Yetka Kathleen , Larson Allison , Gonzalez Raul 
Published: July 2020

AbstractThe ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a significant, coordinated public health response. Assessing case density and spread of infection is critical and relies largely on clinical testing data. However, clinical testing suffers from known limitations, including test availability and a bias towards enumerating only symptomatic individuals. Wastewater-based epidemiology (WBE) has gained widespread support as a potential complement to clinical testing for assessing COVID-19 infections at the community scale. The efficacy of WBE hinges on the ability to accurately characterize SARS-CoV-2 RNA concentrations in wastewater. To date, a variety of sampling schemes have been used without consensus around the appropriateness of grab or composite sampling. Here we address a key WBE knowledge gap by examining the variability of SARS-CoV-2 RNA concentrations in wastewater grab samples collected every 2 hours for 72 hours compared with three corresponding 24-hour flow-weighted composite samples collected over the same period. Results show relatively low variability (respective means for N1, N2, N3 assays = 608, 847.9, 768.4 copies 100 mL-1, standard deviations = 501.4, 500.3, 505.8 copies 100 mL-1) for grab sample concentrations, and good agreement between most grab samples and their respective composite (mean deviation from composite = 159 copies 100 mL-1). When SARS-CoV-2 RNA concentrations are used to calculate viral load (RNA concentration * total influent flow the sample day), the discrepancy between grabs (log10range for all grabs = 11.9) or a grab and its associated 24-hour composite (log10difference = 11.6) are amplified. A similar effect is seen when estimating carrier prevalence in a catchment population with median estimates based on grabs ranging 63-1885 carriers. Findings suggest that grab samples may be sufficient to characterize SARS-CoV-2 RNA concentrations, but additional calculations using these data may be sensitive to grab sample variability and warrant the use of flow-weighted composite sampling. These data inform future WBE work by helping determine the most appropriate sampling scheme and facilitate sharing of datasets between studies via consistent methodology.
A comprehensive estimation and analysis of the basic reproduction number (R0) of novel corona virus in India: A comparative study with different lockdown phase of COVID-19
Authors: Agrawal Tushant , Chhabra Mayank 
Published: July 2020

AbstractBackgroundWorld Health organization declared Covid-19 as an outbreak, hence preventive measure like lockdown should be taken to control the spread of infection. This study offers an exhaustive analysis of the reproductive number (R0) in India with major intervention for COVID-19 outbreaks and analysed the lockdown effects on the Covid-19.MethodologyCovid-19 data extracted from Ministry of Health and Family Welfare, Government of India. Then, a novel method implemented in the incidence and Optimum function in desolve package to the data of cumulative daily new confirmed cases for robustly estimating the reproduction number in the R software.ResultAnalysis has been seen that the lockdown was really quite as effective, India has already shown a major steady decline. The growth rate has fluctuated about 20 percent with trend line projections in various lockdown. A comparative analysis gives an idea of decline in value of R0 from 1.73 to 1.08. Annotation plot showing the predicted R0 values based on previous lockdown in month of June and July.ConclusionWithout lockdown, the growth might not have been contained in India and may have gone into the exponential zone. We show that, the lockdown in India was fairly successful. The effect partial lifting of the lockdown (unlock) is also seen in the results, in terms of increment in R0 values. Hence this study provides a platform for policy makers and government authorities for implementing the strategies to prevent the spread of infection.
What effect might border screening have on preventing importation of COVID-19 compared with other infections? A modelling study
Authors: Bays Declan , Bennett Emma , Finnie Thomas 
Published: July 2020

AbstractThe effectiveness of screening travellers during times of international disease outbreak is contentious, especially as the reduction in the risk of disease importation can be very small. Border screening typically consists of travellers being thermally scanned for signs of fever and/or completing a survey declaring any possible symptoms prior to admission to their destination country; while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we describe a simple Monte Carlo based model that incorporates the epidemiology of COVID-19 to investigate the potential benefit of requiring all travellers to undergo thorough screening upon arrival. This is a purely theoretical study to investigate whether a single test at point of entry might ever prove to be a way of significantly decreasing risk of importation. We therefore assume ideal conditions such as 100% compliance among travellers and the use of a “perfect” test. In addition to COVID-19, we also apply the presented model to simulated outbreaks of Influenza, SARS and Ebola for comparison. Our model only considers screening implemented at airports, being the predominant method of international travel. Primary results showed that in the best-case scenario, screening may expect to detect 8.8% of travellers infected with COVID-19, compared to 34.8.%, 9.7% and 3.0% for travellers infected with influenza, SARS and Ebola respectively. While results appear to indicate that screening is more effective at preventing disease ingress when the disease in question has a shorter average incubation period, our results indicate that screening alone does not represent a sufficient method to adequately protect a nation from the importation of COVID-19 cases.Data availabilityAll results described in the work, in addition to technical descriptions of methods used, are made available in the supplementary material. The Python package used to implement these methods and obtain our results has been made accessible online[1].
Subsequent waves of viral pandemics, a hint for the future course of the SARS-CoV-2 pandemic
Authors: Standl Fabian , Jöckel Karl-Heinz , Kowall Bernd , Schmidt Börge , Stang Andreas 
Published: July 2020

AbstractBackgroundIt is unknown if the SARS-CoV-2 pandemic will have a second wave. We analysed published data of five influenza pandemics (such as the Spanish Flu and the Swine Flu) and the SARS-CoV-1 pandemic to describe whether there were subsequent waves and how they differed.MethodsWe reanalysed literature and WHO reports on SARS-CoV-1 and literature on five influenza pandemics. We report frequencies of second and third waves, wave heights, wavelengths and time between subsequent waves. From this, we estimated peak-to-peak ratios to compare the wave heights, and wave-length-to-wave-length ratios to compare the wavelengths differences in days. Furthermore, we analysed the seasonality of the wave peaks and the time between the peak values of two waves.ResultsSecond waves, the Spanish Flu excluded, were usually about the same height and length as first waves and were observed in 93% of the 57 described epidemic events of influenza pandemics and in 42% of the 19 epidemic events of the SARS-CoV-1 pandemic. Third waves occurred in 54% of the 28 influenza and in 11% of the 19 SARS-CoV-1 epidemic events. Third waves, the Spanish Flu excluded, usually peaked higher than second waves with a peak-to-peak ratio of 0.5.ConclusionWhile influenza epidemics are usually accompanied by 2nd waves, this is only the case in the minority of SARS-Cov1 epidemics.