bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticomotor Excitability in Two Kinds of Motor Neuron Diseases: A Study on the Patients With Amyotrophic Lateral Sclerosis and Poliomyelitis Survivors
Authors: Sirin Nermin Gorkem , Erbas Bahar , Oguz-Akarsu Emel , Gula Gulsah , Kocasoy-Orhan Elif , Dede Hava Ozlem , Baslo Mehmet Baris , Idrisoglu Halil Atilla , Ketenci Aysegul , Oge Ali Emre
Published: June 2020

Purpose:

To examine upper motor neuron functions comparatively in patients with amyotrophic lateral sclerosis (ALS) and poliomyelitis survivors using transcranial magnetic stimulation (TMS) methods.

Methods:

Single- and paired-pulse TMS with conventional methods and the triple-stimulation technique were performed by recording from the abductor digiti minimi and abductor pollicis brevis muscles in 31 patients with ALS, 18 patients with poliomyelitis survivors, and 21 controls. Nine patients were diagnosed as having postpoliomyelitis syndrome after a 6-month follow-up.

Results:

Triple-stimulation technique and some of conventional TMS studies were able to distinguish ALS from both poliomyelitis survivors and controls. A reduced ipsilateral silent period in abductor pollicis brevis muscles was the only parameter to show a significant difference when comparing thenar and hypothenar muscles in ALS. No significant difference was present in any TMS parameters between the postpoliomyelitis syndrome and non-postpoliomyelitis syndrome groups.

Conclusions:

Conventional TMS and particularly triple-stimulation technique studies are helpful in disclosing upper motor neuron dysfunction in ALS. The results of this study might favor the cortical hypothesis for split hand in ALS, but they revealed no significant indication for upper motor neuron dysfunction in postpoliomyelitis syndrome.
Network-based protein structural classification
Authors: Newaz Khalique , Ghalehnovi Mahboobeh , Rahnama Arash , Antsaklis Panos J. , Milenković Tijana
Published: June 2020

Experimental determination of protein function is resource-consuming. As an alternative, computational prediction of protein function has received attention. In this context, protein structural classification (PSC) can help, by allowing for determining structural classes of currently unclassified proteins based on their features, and then relying on the fact that proteins with similar structures have similar functions. Existing PSC approaches rely on sequence-based or direct three-dimensional (3D) structure-based protein features. By contrast, we first model 3D structures of proteins as protein structure networks (PSNs). Then, we use network-based features for PSC. We propose the use of graphlets, state-of-the-art features in many research areas of network science, in the task of PSC. Moreover, because graphlets can deal only with unweighted PSNs, and because accounting for edge weights when constructing PSNs could improve PSC accuracy, we also propose a deep learning framework that automatically learns network features from weighted PSNs. When evaluated on a large set of approximately 9400 CATH and approximately 12 800 SCOP protein domains (spanning 36 PSN sets), the best of our proposed approaches are superior to existing PSC approaches in terms of accuracy, with comparable running times. Our data and code are available athttps://doi.org/10.5281/zenodo.3787922
Preferences and constraints: the value of economic games for studying human behaviour
Authors: Pisor Anne C. , Gervais Matthew M. , Purzycki Benjamin G. , Ross Cody T.
Published: June 2020

As economic games have spread from experimental economics to other social sciences, so too have critiques of their usefulness for drawing inferences about the ‘real world’. What these criticisms often miss is that games can be used to reveal individuals' private preferences in ways that observational and interview data cannot; furthermore, economic games can be designed such that they
do
provide insights into real-world behaviour. Here, we draw on our collective experience using economic games in field contexts to illustrate how researchers can strategically alter the framing or design of economic games to draw inferences about private-world or real-world preferences. A detailed case study from coastal Colombia provides an example of the subtleties of game design and how games can be combined fruitfully with self-report data. We close with a list of concrete recommendations for how to modify economic games to better match particular research questions and research contexts.
Telomere length varies substantially between blood cell types in a reptile
Authors: Olsson Mats , Geraghty Nicholas J. , Wapstra Erik , Wilson Mark
Published: June 2020

Telomeres are repeat sequences of non-coding DNA-protein molecules that cap or intersperse metazoan chromosomes. Interest in telomeres has increased exponentially in recent years, to now include their ongoing dynamics and evolution within natural populations where individuals vary in telomere attributes. Phylogenetic analyses show profound differences in telomere length across non-model taxa. However, telomeres may also differ in length within individuals and between tissues. The latter becomes a potential source of error when researchers use different tissues for extracting DNA for telomere analysis and scientific inference. A commonly used tissue type for assessing telomere length is blood, a tissue that itself varies in terms of nuclear content among taxa, in particular to what degree their thrombocytes and red blood cells (RBCs) contain nuclei or not. Specifically, when RBCs lack nuclei, leucocytes become the main source of telomeric DNA. RBCs and leucocytes differ in lifespan and how long they have been exposed to ‘senescence' and erosion effects. We report on a study in which cells in whole blood from individual Australian painted dragon lizards (
Ctenophorus pictus
) were identified using flow cytometry and their telomere length simultaneously measured. Lymphocyte telomeres were on average 270% longer than RBC telomeres, and in azurophils (a reptilian monocyte), telomeres were more than 388% longer than those in RBCs. If this variation in telomere length among different blood cell types is a widespread phenomenon, and DNA for comparative telomere analyses are sourced from whole blood, evolutionary inference of telomere traits among taxa may be seriously complicated by the blood cell type comprising the main source of DNA.
Dietary palaeoecology of an Early Cretaceous armoured dinosaur (Ornithischia; Nodosauridae) based on floral analysis of stomach contents
Authors: Brown Caleb M. , Greenwood David R. , Kalyniuk Jessica E. , Braman Dennis R. , Henderson Donald M. , Greenwood Cathy L. , Basinger James F.
Published: June 2020

The exceptionally well-preserved holotype of the armoured dinosaurBorealopelta markmitchelli(Ornithischia; Nodosauridae) from the Early Cretaceous (Clearwater Formation) of northern Alberta preserves a distinct mass within the abdominal cavity. Fourteen independent criteria (including: co-allochthony, anatomical position, gastroliths) support the interpretation of this mass as ingested stomach contents—a cololite. Palynomorphs in the cololite are a subset of the more diverse external sample. Analysis of the cololite documents well-preserved plant material dominated by leaf tissue (88%), including intact sporangia, leaf cross-sections and cuticle, but also including stems, wood and charcoal. The leaf fraction is dominated (85%) by leptosporangiate ferns (subclass Polypodiidae), with low cycad–cycadophyte (3%) and trace conifer foliage. These data represent the most well-supported and detailed direct evidence of diet in an herbivorous dinosaur. Details of the dietary palaeoecology of this nodosaur are revealed, including: selective feeding on ferns; preferential ingestion of leptosporangiate ferns to the exclusion of Osmundaceae and eusporangiate ferns such as Marattiaceae; and incidental consumption of cycad–cycadophyte and conifer leaves. The presence of significant (6%) charcoal may represent the dietary use of recently burned conifer forest undergoing fern succession, early evidence of a fire succession ecology, as is associated with many modern large herbivores.
Turing and Benjamin–Feir instability mechanisms in non-autonomous systems
Authors: Van Gorder Robert A.
Published: June 2020

The Turing and Benjamin–Feir instabilities are two of the primary instability mechanisms useful for studying the transition from homogeneous states to heterogeneous spatial or spatio-temporal states in reaction–diffusion systems. We consider the case when the underlying reaction–diffusion system is non-autonomous or has a base state which varies in time, as in this case standard approaches, which rely on temporal eigenvalues, break down. We are able to establish respective criteria for the onset of each instability using comparison principles, obtaining inequalities which involve the in general time-dependent model parameters and their time derivatives. In the autonomous limit where the base state is constant in time, our results exactly recover the respective Turing and Benjamin–Feir conditions known in the literature. Our results make the Turing and Benjamin–Feir analysis amenable for a wide collection of applications, and allow one to better understand instabilities emergent due to a variety of non-autonomous mechanisms, including time-varying diffusion coefficients, time-varying reaction rates, time-dependent transitions between reaction kinetics and base states which change in time (such as heteroclinic connections between unique steady states, or limit cycles), to name a few examples.
Perturbation drives changing metapopulation dynamics in a top marine predator
Authors: Carroll Emma L. , Hall Ailsa , Olsen Morten Tange , Onoufriou Aubrie B. , Gaggiotti Oscar E. , Russell Debbie JF
Published: June 2020

Metapopulation theory assumes a balance between local decays/extinctions and local growth/new colonisations. Here we investigate whether recent population declines across part of the UK harbour seal range represent normal metapopulation dynamics or are indicative of perturbations potentially threatening the metapopulation viability, using 20 years of population trends, location tracking data (n= 380), and UK-wide, multi-generational population genetic data (n= 269). First, we use microsatellite data to show that two genetic groups previously identified are distinct metapopulations: northern and southern. Then, we characterize the northern metapopulation dynamics in two different periods, before and after the start of regional declines (pre-/peri-perturbation). We identify source–sink dynamics across the northern metapopulation, with two putative source populations apparently supporting three likely sink populations, and a recent metapopulation-wide disruption of migration coincident with the perturbation. The northern metapopulation appears to be in decay, highlighting that changes in local populations can lead to radical alterations in the overall metapopulation's persistence and dynamics.
Phylogenomics indicates Amazonia as the major source of Neotropical swarm-founding social wasp diversity
Authors: Menezes Rodolpho S. T. , Lloyd Michael W. , Brady Seán G.
Published: June 2020

The Neotropical realm harbours unparalleled species richness and hence has challenged biologists to explain the cause of its high biotic diversity. Empirical studies to shed light on the processes underlying biological diversification in the Neotropics are focused mainly on vertebrates and plants, with little attention to the hyperdiverse insect fauna. Here, we use phylogenomic data from ultraconserved element (UCE) loci to reconstruct for the first time the evolutionary history of Neotropical swarm-founding social wasps (Hymenoptera, Vespidae, Epiponini). Using maximum likelihood, Bayesian, and species tree approaches we recovered a highly resolved phylogeny for epiponine wasps. Additionally, we estimated divergence dates, diversification rates, and the biogeographic history for these insects in order to test whether the group followed a ‘museum’ (speciation events occurred gradually over many millions of years) or ‘cradle’ (lineages evolved rapidly over a short time period) model of diversification. The origin of many genera and all sampled extant Epiponini species occurred during the Miocene and Plio-Pleistocene. Moreover, we detected no major shifts in the estimated diversification rate during the evolutionary history of Epiponini, suggesting a relatively gradual accumulation of lineages with low extinction rates. Several lines of evidence suggest that the Amazonian region played a major role in the evolution of Epiponini wasps. This spatio-temporal diversification pattern, most likely concurrent with climatic and landscape changes in the Neotropics during the Miocene and Pliocene, establishes the Amazonian region as the major source of Neotropical swarm-founding social wasp diversity.
Improving the recovery and detection of bloodstream pathogens from blood culture
Authors: Falconer Kerry , Hammond Robert , Gillespie Stephen H.
Published: June 2020

Introduction. Bloodstream infections (BSI) are growing in incidence and present a serious health threat. Most patients wait up to 48 h before microbiological cultures can confirm a diagnosis. Low numbers of circulating bacteria in patients with BSI mean we need to develop new methods and optimize current methods to facilitate efficient recovery of bacteria from the bloodstream. This will allow detection of positive blood cultures in a more clinically useful timeframe. Many bacterial blood recovery methods are available and usually include a combination of techniques such as centrifugation, filtration, serum separation or lysis treatment. Here, we evaluate nine different bacteria recovery methods performed directly from blood culture.

Aim. We sought to identify a bacterial recovery method that would allow for a cost-effective and efficient recovery of common BSI pathogens directly from blood culture.

Methods. Simulated

E. coli

ATCC 25922 blood culture was used as a model system to evaluate nine different bacteria recovery methods. Each method was assessed on recovery yield, cost, hands-on time, risk of contamination and ease of use. The highest scoring recovery method was further evaluated using simulated blood cultures spiked with seven of the most frequently occurring bloodstream pathogens. The recovery yield was calculated based on c.f.u. count before and after each recovery method. Independent t-tests were performed to determine if the recovery methods evaluated were significantly different based on c.f.u. ml−1 log recovery.

Results. All nine methods evaluated successfully recovered

E. coli

ATCC 25922 from simulated blood cultures although the bacterial yield differed significantly. The MALDI-TOF intact cell method offered the poorest recovery with a mean loss of 2.94±0.37 log c.f.u. ml−1. In contrast, a method developed by Bio-Rad achieved the greatest bacterial yield with a mean bacteria loss of 0.27±0.013 log c.f.u. ml−1. Overall, a low-speed serum-separation method was demonstrated to be the most efficient method in terms of time, cost and recovery efficiency and successfully recovered seven of the most frequent BSI pathogens with a mean bacteria loss of 0.717±0.18 log c.f.u. ml−1.

Conclusion. The efficiency of bacterial recovery can vary significantly between different methods and thereby can have a critical impact on downstream analysis. The low-speed serum-separation method offered a simple and effective means of recovering common BSI pathogens from blood culture and will be further investigated for use in the rapid detection of bacteraemia and susceptibility testing in clinical practice.
Modulation of binocular rivalry with rapid monocular visual stimulation
Authors: Abuleil Dania , McCulloch Daphne , Patterson Heidi , Thompson Benjamin
Published: June 2020

Rapid visual stimulation can increase synaptic efficacy by repeated synaptic activation. This long-term potentiation-like (LTP-like) effect can induce increase human visual cortex excitability. To examine the effect of rapid visual stimulation on perception, we tested the hypothesis that rapid monocular visual stimulation would increase the dominance of the stimulated eye in a binocular rivalry task. Participants (n = 25) viewed orthogonal 0.5 cpd gratings presented in a dichoptic anaglyph to induce binocular rivalry. Rivalry dynamics (alternation rate, dominance, and piecemeal durations) were recorded before and after 2 min of rapid monocular stimulation (9Hz flicker of one grating) or a binocular control condition (9Hz alternation of the orthogonal gratings viewed binocularly). Rapid monocular stimulation did not affect alternation rates or piecemeal percept duration. However, unexpectedly, rivalry dominance of the stimulated eye was significantly reduced. A control experiment revealed that this effect could not be explained by monocular adaptation. Together, the results suggest that rapid monocular stimulation boosts dominance in the non-stimulated eye, possibly by activating homeostatic interocular gain control mechanisms.
Incidence and risk factors of kidney impairment on patients with COVID-19: a systematic review and meta-analysis
Authors: Yang Qixin , Yang Xiyao
Published: June 2020

Background

The novel coronavirus is pandemic around the world. Several researchers have given the evidence of impacts of COVID-19 on the respiratory, cardiovascular and gastrointestinal system. Studies still have debated on kidney injury of COVID-19 patients. The purpose of the meta-analysis was to evaluate the association of kidney impairment with the development of COVID-19.

Methods

The PubMed, Embase and MedRxiv databases were searched until April 1, 2020. We extracted data from eligible studies to summarize the clinical manifestations and laboratory indexes of kidney injury on COVID-19 infection patients and further compared the prevalence of acute kidney injury (AKI) and the mean differences of three biomarkers between in ICU/severe and non-ICU/non-severe cases. Heterogeneity was evaluated using the I2method.

Results

In the sum of 19 studies with 4375 patients were included in this analysis. The pooled prevalence of AKI, increased serum creatinine (Scr), increased blood urea nitrogen (BUN), increased D-dimer, proteinuria and hematuria in patients with COVID-19 were 7.7%, 6.6%,6.2%, 49.8%, 42% and 30.3% respectively. Moreover, the means of Scr, BUN and D-dimer were shown 6-folds, 1.8-folds and 0.68-folds, respectively, higher in ICU/severe cases than in corresponding non-ICU/non-severe patients. The prevalence of AKI was about 17 folds higher in ICU/severe patients compared with the non-ICU/non-severe cases.

Conclusions

Overall, we assessed the incidences of the clinic and laboratory features of kidney injury in COVID-19 patients. And kidney dysfunction may be a risk factor for COVID-19 patients developing into the severe condition. In reverse, COVID-19 can also cause damage to the kidney.
Detection of lung hypoperfusion in Covid-19 patients during recovery by digital imaging quantification
Authors: Patelli Gianluigi , Paganoni Silvia , Besana Francesca , Codazzi Fabiana , Ronzoni Mattia , Manini Simone , Remuzzi Andrea
Published: June 2020

Purpose

A large number of patients affected by the SARS-Cov-2 virus worldwide undergo recovery of symptoms in about one month. Among these patients, the healing process is still under observation, with some patients in need of careful clinical monitoring. While the radiological findings have been shown to regress almost completely, little knowledge is available at the moment about other complications in the lung and in other organs. We then investigated the lung perfusion conditions in patients affected by COVID-19 during recovery.

Method

We retrospectively studied 20 patients, from 14 to 60 days after resolution of the COVID-19 symptoms, using chest CT. In a subgroup of 5 patients contrasted CT was used. Beside normal radiological evaluation of lung tissue, perfusion conditions were evaluated by digital image processing in the lung volume automatically segmented.

Results

Pulmonary lung evaluation showed that COVID-19 pneumonia almost completely regressed, with mild focal areas affected by fibrous stripes. In patients that reported dyspnea, lung CT showed complete resolution of interstitial changes. Quantification of lung perfusion condition by contrasted CT, showed that dyspnea in 3 patients was associated with areas of hypoperfusion, while in 2 patients not reporting dyspnea perfusion conditions were comparable to normal controls.

Conclusions

Although we obtained preliminary data, this is the first report on quantitative evaluation of hypoperfused lung tissue detected in recovering COVID-19 patients. These results suggest the need to further investigate these patients and to redefine the role of CT evaluation for diagnostic purposes as well as for evaluation of potential treatments.

Funding

This was an academic study that received no direct funding.
Tocilizumab for treatment of mechanically ventilated patients with COVID-19
Authors: Somers Emily C , Eschenauer Gregory A , Troost Jonathan P , Golob Jonathan L , Gandhi Tejal N , Wang Lu , Zhou Nina , Petty Lindsay A , Baang Ji Hoon , Dillman Nicholas O , Frame David , Gregg Kevin S , Kaul Dan R , Nagel Jerod , Patel Twisha S , Zhou Shiwei , Lauring Adam S , Hanauer David A , Martin Emily , Sharma Pratima , Fung Christopher M , Pogue Jason M
Published: June 2020

Background

Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment.

Methods

We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW).

Findings

154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42].

Interpretation

In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.

KEY POINTS

Question

Can therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation?

Findings

In this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings.

Meaning

Tocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials.
Spreading of COVID-19 in Brazil: Impacts and uncertainties in social distancing strategies
Authors: Volpatto Diego T. , Resende Anna Claudia M. , dos Anjos Lucas , Silva João V. O. , Dias Claudia M. , Almeida Regina C. , Malta Sandra M. C.
Published: June 2020

Brazil’s continental dimension poses a challenge to the control of the spread of COVID-19. Due to the country specific scenario of high social and demographic heterogeneity, combined with limited testing capacity, lack of reliable data, under-reporting of cases, and restricted testing policy, the focus of this study is twofold: (i) to develop a generalized SEIRD model that implicitly takes into account the quarantine measures, and (ii) to estimate the response of the COVID-19 spread dynamics to perturbations/uncertainties. By investigating the projections of cumulative numbers of confirmed and death cases, as well as the effective reproduction number, we show that the model parameter related to social distancing measures is one of the most influential along all stages of the disease spread and the most influential after the infection peak. Due to such importance in the outcomes, different relaxation strategies of social distancing measures are investigated in order to determine which strategies are viable and less hazardous to the population. The results highlight the need of keeping social distancing policies to control the disease spread. Specifically, the considered scenario of abrupt social distancing relaxation implemented after the occurrence of the peak of positively diagnosed cases can prolong the epidemic, with a significant increase of the projected numbers of confirmed and death cases. An even worse scenario could occur if the quarantine relaxation policy is implemented before evidence of the epidemiological control, indicating the importance of the proper choice of when to start relaxing social distancing measures.
Kalman Filter Based Short Term Prediction Model for COVID-19 Spread
Authors: Kumar Suraj , Singh Koushlendra Kumar , Dixit Prachi , Kumar Bajpai Manish
Published: June 2020

COVID-19 has emerged as global medical emergency in recentdecades. The spread scenario of this pandemic has shown many variations. Keeping all this in mind, this article is written after various studies and analysis on the latest data on COVID-19 spread, which also includes the demographic and environmental factors. After gathering data from various resources, all data are integrated and passed into different Machine Learning Models to check the fit. Ensemble Learning Technique,Random Forest, gives a good evaluation score on the test data. Through this technique, various important factors are recognised and their contribution to the spread is analysed. Also, linear relationship between various features is plotted through heatmap of Pearson Correlation matrix. Finally, Kalman Filter is used to estimate future spread of COVID19, which shows good result on test data. The inferences from Random Forest feature importance and Pearson Correlation gives many similarities and some dissimilarities, and these techniques successfully identify the different contributing factors. The Kalman Filter gives a satisfying result for short term estimation, but not so good performance for long term forecasting. Overall, the analysis, plots, inferences and forecast are satisfying and can help a lot in fighting the spread of the virus.
Evaluating the adequacy of Prima Covid-19 IgG/IgM Rapid Test for the assessment of exposure to SARS-CoV-2 virus
Authors: Di Lorenzo Giulia , Toniolo Paolo , Lurani Caterina , Foresti Luca , Carrisi Chiara
Published: June 2020

1.

The outbreak of the SARS-CoV-2 in early 2020 found health authorities worldwide unprepared to control the pandemic. The adoption of accurate, rapid and inexpensive methods to identify infected subjects in the general population is of paramount relevance for the control of the disease. We evaluated one of the available serological tests, thePrima LabCovid-19 IgG/IgM Rapid Tests, on 739 volunteers. We first assessed the test’s reproducibility by administering it twice on the same day on 104 subjects obtaining and overall score of 93 percent. Since the intensity of the color in the test line regions varies depending on the concentration of Covid-19 antibodies in each sample and that the determination of the positivity depends strictly on the subjective assessment by the reader, after excluding the subjects whose color intensity was too tenuous to be deemed unquestionably positive by the reader the reproducibility increased to 96%. The test would not perform properly for 6 subjects for a very limited overall technical failure of 0.83%. For 138 subjects information was available regarding a previous Real Time PCR nasopharyngeal swab test performed elsewhere. The correspondence of positive results between the two tests was 90.58% (125/138). In spite of some limitation owing especially to the choice of a self selected population sample, we conclude thatPrima LabCovid-19 IgG/IgM Rapid Test represents a low-cost, easily applicable and reproducible tool in detecting SARS-Cov-2 diffusion in the general population.
Missing clinical trial data: the evidence gap in the safety of potential COVID-19 drugs
Authors: Rodgers Florence , Pepperrell Toby , Keestra Sarai , Pilkington Victoria
Published: June 2020

Background

Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19 by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications.

Methods

ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance.

Results

Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. 1172 (31.2%) completed trials had tabular results on ClinicalTrials.gov. A further 1066 (28.4%) completed trials had results from the literature search, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%).

Conclusions

There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause a large burden of additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.
Minimising exposure to droplet and aerosolised pathogens: a computational fluid dynamics study
Authors: Perella Paolo , Tabarra Mohammad , Hataysal Ertan , Pournasr Amir , Renfrew Ian
Published: June 2020

Background

Hazardous pathogens are spread in either droplets or aerosols produced during aerosol generating procedures (AGP). Adjuncts minimising exposure of healthcare workers to hazardous pathogens released during AGP may be beneficial. We used state-of-the-art Computational Fluid Dynamics modelling to optimise the performance of a custom-designed shield.

Methods

We modelled airflow patterns and trajectories of particles (size range 1–500µm) emitted during a typical cough using Computational Fluid Dynamics (ANSYS Fluent software), in the presence and absence of a protective shield enclosing the head of a patient. We modelled the effect of different shield designs, suction tube position, and suction flow rate on particle escape from the shield.

Results

Use of the shield prevented escape of 99.1–100% of particles, which were either trapped on the shield walls (16–21%) or extracted via suction (79–82%). At most, 0.9% particles remained floating inside the shield. Suction flow rates (40–160L min−1) had no effect on the final location of particles in a closed system. Particle removal from within the shield was optimal when a suction catheter was placed vertically next to the head of the patient. Addition of multiple openings in the shield reduced the purging performance from 99% at 160 L min−1 to 67% at 40 L min−1.

Conclusion

Computational fluid dynamics modelling provides information to guide optimisation of the efficient removal of hazardous pathogens released during AGP from a custom-designed shield. These data are essential to establish before clinical use and/or pragmatic clinical trials.
Suggestibility in functional neurological disorder: A meta-analysis
Authors: Wieder Lillian , Brown Richard J. , Thompson Trevor , Terhune Devin B.
Published: June 2020

Objective

Responsiveness to direct verbal suggestions (suggestibility) has long been hypothesized to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether FND patients display elevated suggestibility relative to controls via meta-analysis.

Methods

Four electronic databases were searched in November 2019, with the search updated in April 2020, for original studies assessing suggestibility using standardized behavioural scales or suggestive symptom induction protocols in FND patients and controls. The meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data extraction and study quality coding were performed by two independent reviewers. Standardized suggestibility scores and responsiveness to symptom induction protocols were used to calculate standardized mean differences (SMDs) between groups.

Results

Of 26,643 search results, 19 articles presenting 11 standardized suggestibility datasets (FND: n = 316; control: n = 360) and 11 symptom suggestibility datasets (FND: n = 1285; control: n = 1409) were included in random-effects meta-analyses. Meta-analyses revealed that FND patients displayed greater suggestibility than controls on standardized behavioural scales (SMD, 0.48 [95% CI, 0.15, 0.81]) and greater responsiveness to suggestive symptom induction (SMD, 1.39 [95% CI, 0.92, 1.86]). Moderation analyses presented mixed evidence regarding the extent to which effect sizes covaried with methodological differences across studies. No evidence of publication bias was found.

Conclusions

These results corroborate the hypothesis that FND is characterized by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.
COVID-19 apparent reproductive number dropped during Spain’s nationwide dropdown, then spiked at lower-incidence regions
Authors: Santamaría L. , Hortal J.
Published: June 2020

COVID-19 pandemic has rapidly spread worldwide. Spain has suffered one of the largest nationwide bursts, particularly in the highly populated areas of Madrid and Barcelona (two of the five largest conurbations in Europe). We used segmented regression analyses to identify shifts in the evolution of the apparent reproductive number (Rt) reported for 16 Spanish administrative regions. We associate these breaking points with a timeline of key containment measures taken by national and regional governments, applying time lags for the time from contagion to case detection, with their associated errors. Results show an early decrease of Rt that preceded the nationwide lockdown; a generalized, sharp decrease in Rt associated with such lockdown; a low impact of the strengthened lockdown, with a flattening of Rt evolution in high-incidence regions regions – but increases in Rt at low-incidence regions; and an increase in Rt, associated to the relaxation of the lockdown measures, in ten regions. These results evidence the importance of generalized lockdown measures to contain COVID-19 spread; and the limited effect of the subsequent application of a stricter lockdown (restrictions to all non-essential economic activities). Most importantly, they highlight the importance of maintaining strong social distancing measures and strengthening public health control during lockdown de-escalation.
A Statistical Model for Quantifying the Needed Duration of Social Distancing for the COVID-19 Pandemic
Authors: Rakocz Nadav , Fu Boyang , Halperin Eran , Sankararaman Sriram
Published: June 2020

Understanding the effectiveness of strategies such as social distancing is a central question in attempts to control the COVID-19 pandemic. A key unknown in social distancing strategies is the duration of time for which such strategies are needed. Answering this question requires an accurate model of the transmission trajectory. A challenge in fitting such a model is the limited COVID-19 case data available from a given location. To overcome this challenge, we propose fitting a model of SARS-CoV-2 transmission jointly across multiple locations. We apply the model to COVID-19 case data from Spain, UK, Germany, France, Denmark, and New York to estimate the distribution for the time needed for social distancing to end to range from May 2020 to July 2021 (95% credible interval), where the median date is October, 2020. Our method is not specific to COVID-19, and it can also be applied to future pandemics.
Statistical Methods for Estimating Cure Fraction of COVID-19 Patients In India
Authors: Sreedevi E. P. , Sankaran P. G.
Published: June 2020

Abstract

The human race is under the COVID-19 pandemic menace since beginning of the year 2020. Even though the disease is easily transmissible, a massive fraction of the affected people are recovering. Most of the recovered patients will not experience death due to COVID-19, even if they observed for a long period. They can be treated as long term survivors (cured population) in the context of lifetime data analysis. In this article, we present some statistical methods to estimate the cure fraction of the COVID-19 patients in India. Proportional hazards mixture cure model is used to estimate the cure fraction and the effect of covariates gender and age on lifetime. The data available on website ‘https://api.cvoid19india.org’ is used in this study. We can see that, the cure fraction of the COVID-19 patients in India is more than 90%, which is indeed an optimistic information.
COVID-SGIS: A smart tool for dynamic monitoring and temporal forecasting of Covid-19
Authors: de Lima Clarisse Lins , da Silva Cecilia Cordeiro , da Silva Ana Clara Gomes , Silva Eduardo Luiz , Marques Gabriel Souza , de Araújo Lucas Job Brito , Júnior Luiz Antônio Albuquerque , de Souza Samuel Barbosa Jatobá , de Santana Maíra Araújo , Gomes Juliana Carneiro , de Freitas Barbosa Valter Augusto , Musah Anwar , Kostkova Patty , dos Santos Wellington Pinheiro , da Silva Filho Abel Guilhermino
Published: June 2020

Objective

The new kind of coronavirus SARS-Cov2 spread to countries in all continents in the World. The coronavirus disease 2019 (Covid-19) causes fever, cough, sore throat, and in severe cases shortness of breath and death. To evaluate strategies, it is necessary to forecast the number of cases and deaths, in order to aid the stakeholders in the process of making decisions against the disease. We propose a system for real-time forecast of the cumulative cases of Covid-19 in Brazil.

Study Design

Monitoring of all Brazilian cities using oficial information from the National Notification System, from March to May 2020, concentrated on Brazil.io databases. Training and evaluation of ARIMA and other machine learning algorithms for temporal forecasting using correlation indexes (Pearson’s, Spearman’s, and Kendall’s) and RMSE(%). Validation from the relative errors of the following six days.

Methods

Our developed software, COVID-SGIS, captures information from the 26 states and the Distrito Federal at the Brazil.io database. From these data, ARIMA models are created for the accumulation of confirmed cases and death cases by Covid-19. Finally, six-day forecasts graphs are available for Brazil and for each of its federative units, separately, with a 95% CI. In addition to these predictions, the worst and best scenarios are also presented.

Results

ARIMA models were generated for Brazil and its 27 federative units. The states of Bahia, Maranhão, Piauí, Rio Grande do Norte and Amapá, Rondônia every day of the predictions were in the projection interval. The same happened to the states of Espírito Santo, Minas Gerais, Paraná and Santa Catarina. In Brazil, the percentage error between the predicted values and the actual values varied between 2.56% and 6.50%. For the days when the forecasts outside the prediction interval, the percentage errors in relation to the worst case scenario were below 5%. The states of Bahia, Maranhão, Piauí, Rio Grande do Norte, Amapá, and Rondônia every day of the predictions were in the projection interval. The same happened to the states of Espírito Santo, Minas Gerais, Paraná and Santa Catarina.

Conclusion

The proposed method for dynamic forecasting may be used to guide social policies and plan direct interventions in a robust, flexible and fast way. Since it is based on information from multiple databases, it can be adapted to the different realities, becoming an important tool to guide the course of politics and action against Covid-19 pandemic worldwide.
A Mendelian randomization study of telomere length and blood-cell traits
Authors: Adams Charleen D. , Boutwell Brian B.
Published: June 2020

Whether telomere attrition reducing proliferative reserve in blood-cell progenitors is causal has important public-health implications. Mendelian randomization (MR) is an analytic technique using germline genetic variants as instrumental variables. If certain assumptions are met, estimates from MR should be free from most environmental sources of confounding and reverse causation. Here, two-sample MR is performed to test whether longer telomeres cause changes to hematological traits. Summary statistics for genetic variants strongly associated with telomere length were extracted from a genome-wide association (GWA) study for telomere length in individuals of European ancestry (n=9190) and from GWA studies of blood-cell traits, also in those of European ancestry (n∼173,000 participants). A standard deviation increase in genetically influenced telomere length increased red blood cell (RBC) and white blood cell (WBC) counts, decreased mean corpuscular hemoglobin (MCH) and mean cell volume (MCV), and had no observable impact on mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), hematocrit, or hemoglobin. Sensitivity tests for pleiotropic distortion were mostly inconsistent with glaring violations to the MR assumptions. Similar to how germline mutations in TERT can lead to bone-marrow failure, these data provide evidence that genetically influenced common variation in telomere length impacts hematologic traits in the population.
A Systematic Review of Mutations Associated with Isoniazid Resistance Points to Lower Diagnostic Sensitivity for Common Mutations and Increased Incidence of Uncommon Mutations in Clinical Strains of Mycobacterium tuberculosis
Authors: Valafar Siavash J.
Published: June 2020

Molecular testing is rapidly becoming integral to the global tuberculosis (TB) control effort. Uncommon mechanisms of resistance can escape detection by these platforms and lead to the development of Multi-Drug Resistant (MDR) strains. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September-2013 and December-2019. The aims were to catalogue mutations associated with INH resistance, estimate their global prevalence and co-occurrence, and their utility in molecular diagnostics. The genes commonly associated with INH resistance, katG, inhA, fabG1, and the intergenic region oxyR’-ahpC were considered in this review. In total, 52 articles were included describing 5,632 INHR clinical isolates from 31 countries. The three most frequently mutated loci continue to be katG315 (4,100), inhA-15 (786), and inhA-8 (105). However, the diagnostic value of inhA-8 is far lower than previously thought, only appearing in 25 (0.4%) INHR isolates that lacked a mutation at the first two loci. Importantly, of the four katG loci recommended by the previous systematic review for diagnostics, only katG315 was observed in our INHR isolates. This indicates continued evolution and regional differences in INH resistance. We have identified 58 loci (common to both systematic reviews) in three genomic regions as a reliable basis for molecular diagnostics. We also catalogue mutations at 49 new loci associated with INH resistance. Including all observed mutations provides a cumulative sensitivity of 85.1%. The most disconcerting is the remaining 14.9% of isolates that harbor an unknown mechanism of resistance, will escape molecular detection, and likely convert to MDR-TB, further complicating treatment. Integrating the information cataloged in this and other similar studies into current diagnostic tools is essential for combating the emergence of MDR-TB. Exclusion of this information will lead to an “unnatural” selection which will result in eradication of the common but propagation of the uncommon mechanisms of resistance, leading to ineffective global published articles that reported isoniazid (INH) resistance-conferring mutations between describing 5,632 INHR clinical isolates from 31 countries. The three most frequently mutated treatment policy and a need for region-specific regiments. Finally, the observance of many low-frequency resistance-conferring mutations point to an advantage of platforms that consider regions rather than specific loci for detection of resistance.
The Chest CT Features of Coronavirus Disease 2019 (COVID-19) in China: A Meta-analysis of 19 Trials
Authors: Yang Haitao , Lan Yuzhu , Yao Xiujuan , Lin Sheng , Xie Baosong
Published: June 2020

Objective

This study aimed to summarize the characteristics of chest CT imaging in Chinese patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine.

Methods

PubMed, Embase and Web of Science databases were thoroughly searched to identified relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R software version i386 4.0.0. Random-effects models were employed to calculate pooled mean differences.

Results

19 trials incorporating 1332 cases were included in the study. The results demonstrated that the incidence of ground-glass opacities (GGO) was 0.79, consolidation was 0.34; mixed GGO and consolidation was 0.46; air bronchogram sign was 0.41; crazy paving pattern was 0.32; interlobular septal thickening was 0.55; reticulation was 0.30; bronchial wall thickening was 0.24; vascular enlargement was 0.74. subpleural linear opacity was 0.28; intrathoracic lymph node enlargement was 0.03; pleural effusions was 0.03. The distribution in lung: the incidence of central was 0.05; peripheral was 0.74; peripheral involving central was 0.38; diffuse was 0.19; unifocal involvement was 0.09; multifocal involvement was 0.57; unilateral was 0.16; bilateral was 0.83; The incidence of lobes involved (>2) was 0.70; lobes involved (≦2) was 0.35.

Conclusion

GGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19. Peripheral, bilateral, involved lobes >2 might be the features of COVID-19 in the distribution aspect. Therefore, based on the aboved features of COVID-19 in chest CT imaging, it might be a promising means for identifying COVID-19.