bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation Of State Variables And Model Parameters For The Evolution Of COVID-19 In The City Of Rio de Janeiro
Authors: Orlande Helcio R.B. , Colaco Marcelo , Dulikravich George S. , Ferreira Luiz F.S.
Published: May 2020

Evolution model is based on that used by Hernandez et al., which considers the following groups: Susceptible, Incubating, Asymptomatic, Symptomatic, Hospitalized, Recovered and Accumulated deaths. Evolution model considers the possibility of infections from asymptomatic, symptomatic and hospitalized individuals. Evolution model considers the possibility that individuals who have recovered from the disease become symptomatic again. Observation model accounts for underreport of cases and deaths. Observation model accounts for delays in reporting cases and deaths. Model parameters were initially estimated with the Markov Chain Monte Carlo (MCMC) method, by using the data of the city of Rio de Janeiro from February 28, 2020 to April 29, 2020. These estimations were used as initial input values for the solution of the state estimation problem for the city of Rio de Janeiro. Algorithm of Liu & West for the Particle Filter was used for the solution of the state estimation problem because it allows the simultaneous estimation of state variables and model parameters. State estimation problem was solved with the data of the city of Rio de Janeiro, from February 28, 2020 to May 05, 2020. Monte Carlo simulations were run for 20 future days, considering uncertainties in the model parameters and state variables. Initial conditions were given by the state variables and corresponding distributions estimated with the particle filter on May 05, 2020. Distributions of the model parameters were also given by the estimations obtained for this date. Data of the city of Rio de Janeiro, from May 06, 2020 to May 15, 2020, were used for the validation of the solution of the state estimation problem. The present model, with the parameters obtained with the Particle Filter, accurately fits the number of reported cases and the number of reported deaths, for 10 days ahead of the period used for the solution of the state estimation problem. The Ratio of Infected Individuals per Reported Cases was around 15 on May 05, 2020. The Indexes of Under-Reported Cases and Deaths were around 12 and 2, respectively, on May 05, 2020. The Effective Reproduction Number was around 1.6 on February 28, 2020 and dropped to around 0.9 on May 05, 2020. However, uncertainties related to this parameter are large and the effective reproduction number is between 0.3 and 1.5, at the 95% credibility level. The particle filter must be used to periodically update the estimation of state variables and model parameters, so that future predictions can be made. Day 0 is February 28, 2020.
Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review
Authors: Geisler Benjamin P. , Zahabi Lara , Lang Adam E. , Eastwood Naomi , Tennant Elaine , Lukic Ljiljan , Sharon Elad , Chuang Hai-Hua , Kang Chang-Berm , Clayton-Johnson Knakita , Aljaberi Ahmed , Yu Haining , Bui Chinh , Le Mau Tuan , Li Wen-Cheng , Teodorescu Debbie , Hinske Ludwig Christian , Sun Dennis L. , Manian Farrin A. , Dunn Adam G.
Published: May 2020

Background: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19.
Methods: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence.
Discussion: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review.
Systematic review registration: PROSPERO 2020 CRD42020175648
Quantification of SARS-CoV-2 and cross-assembly phage (crAssphage) from wastewater to monitor coronavirus transmission within communities
Authors: Green Hyatt , Wilder Maxwell , Middleton Frank A. , Collins Mary , Fenty Ariana , Gentile Karen , Kmush Brittany , Zeng Teng , Larsen David Aaron
Published: May 2020

Wastewater surveillance of SARS-CoV-2 has become an attractive tool for combating the spread of COVID-19 by assessing the presence or levels of the virus shed in a population. However, the methods to quantify viral RNA and to link those quantities to the level of infection within the community vary. In this study, we sought to identify and optimize scalable methods for recovery of viral nucleic acids from wastewater and attempted to use a constitutive member of the gut virome, human-specific crAssphage, to help account for unknown levels of SARS-CoV-2 decay and dilution in the wastewater infrastructure. Results suggest that ultracentrifugation of a small volume of wastewater through a 50% sucrose cushion followed by total nucleic acid extraction yielded quantifiable virus in an area with a modest number of COVID-19 cases. Further, the ratio of log10(SARS-CoV-2):log10(crAssphage) appears to be associated with the cumulative incidence of COVID-19 in the Syracuse, NY area. In areas where ultracentrifuges are available, these methods may be used to link SARS-CoV-2 quantities in wastewater to levels of transmission within communities with sewer service.
Non-invasive estimation of intracranial pressure by diffuse optics − a proof-of-concept study
Authors: Fischer Jonas B , Ghouse Ameer , Tagliabue Susanna , Maruccia Federica , Rey-Perez Anna , Báguena Marcelino , Cano Paola , Zucca Riccardo , Weigel Udo M , Sahuquillo Juan , Poca Maria A , Durduran Turgut
Published: May 2020

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other side, there are other less critical conditions where ICP monitoring could still be useful, thus there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants (n=6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults (n=6) suffering from traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy less than <4 mmHg and a negligible small bias. Furthermore, we have achieved a good correlation (Pearson's correlation coefficient >0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison to standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bed-side assessment of ICP.
Time Dynamics of COVID-19
Authors: Carroll Cody , Bhattacharjee Satarupa , Chen Yaqing , Dubey Paromita , Fan Jianing , Gajardo Alvaro , Zhou Xiner , Mueller Hans-Georg , Wang Jane-Ling
Published: May 2020

We apply tools from functional data analysis to model cumulative trajectories of COVID-19 cases across countries, establishing a framework for quantifying and comparing cases and deaths across countries longitudinally. It emerges that a country's trajectory during an initial first month "priming period" largely determines how the situation unfolds subsequently. We also propose a method for forecasting case counts, which takes advantage of the common, latent information in the entire sample of curves, instead of just the history of a single country. Our framework facilitates to quantify the effects of demographic covariates and social mobility on doubling rates and case fatality rates through a time-varying regression model. Decreased workplace mobility is associated with lower doubling rates with a roughly two week delay, and case fatality rates exhibit a positive feedback pattern.
SARS-CoV-2 receptor ACE2 is expressed in human conjunctival tissue, especially in diseased conjunctival tissue
Authors: Li Shengjie , Li Danhui , Fang Jianchen , Liu Qiang , Cao Wenjun , Sun Xinghuai , Xu Gezhi
Published: May 2020

COVID-19 virus has currently caused major outbreaks worldwide. ACE2 is a major cellular-entry receptor for the COVID-19 virus. Although ACE2 is known to be expressed in many organs, whether it is expressed by the conjunctival tissue is largely unknown. Human conjunctival tissues from 68 subjects were obtained, which included 10 subjects with conjunctival nevi, 20 subjects with conjunctivitis, 9 subjects with conjunctival papilloma, 16 subjects with conjunctival cyst, 7 subjects with conjunctival polyps, and 6 ocular traumas as normal subjects. Expression of ACE2 was evaluated by immunohistochemistry, immunofluorescence, reverse transcriptase-quantitative polymerase chain reaction, and western blot assay. We observed the expression of ACE2 by conjunctival tissues, expecially in conjunctival epithelial cells. ACE2 was significantly (p<0.001) overexpressed in conjunctival cells obtained from subjects with conjunctivitis, conjunctival nevi, conjunctival papilloma, conjunctival cyst, and conjunctival polyps epithelial cells when compared to that in conjunctival epithelial cells obtained from control subjects. Collectively, clinical features of reported COVID-19 patients combined with our results indicate that COVID-19 is likely to be transmitted through the conjunctiva.
Flattening the curve and the effect of atypical events on mitigation measures in Mexico: a modeling perspective
Authors: Santana-Cibrian Mario , Acuna-Zegarra Manuel Adrian , Velasco-Hernandez Jorge X.
Published: May 2020

On 23 and 30 March 2020 the Mexican Federal government implemented social distancing measures to mitigate the COVID-19 epidemic. We use a mathematical model to explore atypical transmission events within the confinement period, triggered by the timing and strength of short time perturbations of social distancing. We show that social distancing measures were successful in achieving a significant reduction of the effective contact rate in the early weeks of the intervention. However, "flattening the curve" had an undesirable effect, since the epidemic peak was delayed too far, almost to the government preset day for lifting restrictions (01 June 2020). If the peak indeed occurs in late May or early June, then the events of children's day and mother's day may either generate a later peak (worst case scenario), a long plateau with relatively constant but high incidence (middle case scenario) or the same peak date as in the original baseline epidemic curve, but with a post-peak interval of slower decay.
Cadherin Clusters Stabilized by a Combination of Specific and Nonspecific Cis-Interactions
Authors: Thompson Connor J. , Su Zhaoqian , Vu Vinh H. , Wu Yinghao , Leckband Deborah E. , Schwartz Daniel K.
Published: May 2020

We demonstrate a combined experimental and computational approach for the quantitative characterization of lateral interactions between membrane-associated proteins. In particular, weak, lateral (cis) interactions between E-cadherin extracellular domains tethered to supported lipid bilayers, were studied using a combination of dynamic single-molecule Förster Resonance Energy Transfer (FRET) and kinetic Monte Carlo (kMC) simulations. Cadherins are intercellular adhesion proteins that assemble into clusters at cell-cell contacts through cis- and trans- (adhesive) interactions. A detailed and quantitative understanding of cis-clustering has been hindered by a lack of experimental approaches capable of detecting and quantifying lateral interactions between proteins on membranes. Here single-molecule intermolecular FRET measurements of wild-type E-cadherin and cis-interaction mutants combined with simulations demonstrate that both nonspecific and specific cis-interactions contribute to lateral clustering on lipid bilayers. Moreover, the intermolecular binding and dissociation rate constants are quantitatively and independently determined, demonstrating an approach that is generalizable for other interacting proteins.
Compromised nuclear envelope integrity drives tumor cell invasion
Authors: Nader Guilherme P.F. , Agüera-Gonzalez Sonia , Routet Fiona , Gratia Matthieu , Maurin Mathieu , Cancila Valeria , Cadart Clotilde , Gentili Matteo , Yamada Ayako , Lodillinsky Catalina , Lagoutte Emilie , Villard Catherine , Viovy Jean-Louis , Tripodo Claudio , Scita Giorgio , Manel Nicolas , Chavrier Philippe , Piel Matthieu
Published: May 2020

While mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, bothin vitroand in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to the presence of chronic DNA damage and activation of the ATM kinase. In addition, we found that depletion of the cytoplasmic exonuclease TREX1 is sufficient to abolish the DNA damage in mechanically challenged nuclei and to suppress the phenotypes associated with the loss of nuclear envelope integrity. Our results also show that TREX1-dependent DNA damage induced by physical confinement of tumor cells inside the mammary duct drives the progression ofin situbreast carcinoma to the invasive stage. We propose that DNA damage in mechanically challenged nuclei could affect the pathophysiology of crowded tissues by modulating proliferation and extracellular matrix degradation of normal and transformed cells.
Improvements on marker-free images alignment for electron tomography
Authors: Sorzano C.O.S. , de Isidro-Gómez F. , Fernández-Giménez E. , Herreros D. , Marco S. , Carazo J.M. , Messaoudi C.
Published: May 2020

Electron tomography is a technique to obtain three-dimensional structural information of samples. However, the technique is limited by shifts occurring during acquisition that need to be corrected before the reconstruction process. In 2009, we proposed an approach for post-acquisition alignment of tilt series images. This approach was marker-free, based on patch tracking and integrated in free software. Here, we present improvements to the method to make it more reliable, stable and accurate. In addition, we modified the image formation model underlying the alignment procedure to include different deformations occurring during acquisition. We propose a new way to correct these computed deformations to obtain reconstructions with reduced artifacts. The new approach has demonstrated to improve the quality of the final 3D reconstruction, giving access to better defined structures for different transmission electron tomography methods: resin embedded STEM-tomography and cryo-TEM tomography. The method is freely available in TomoJ software.
Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular signaling networks using SILAC-based phosphoproteomics
Authors: Byrne Dominic P , Clarke Christopher J , Brownridge Philip J , Kalyuzhnyy Anton , Perkins Simon , Campbell Amy , Mason David , Jones Andrew R , Eyers Patrick A , Eyers Claire E
Published: May 2020

Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication in metazoan organisms. Catalytic activity and protein turnover of PLK4 are tightly coupled in human cells, since changes in PLK4 concentration and catalysis have profound effects on centriole duplication and supernumerary centrosomes, which are associated with aneuploidy and cancer. Recently, PLK4 has been targeted with a variety of small molecule kinase inhibitors exemplified by centrinone, which rapidly induces inhibitory effects on PLK4 and leads to on-target centrosome depletion. Despite this, relatively few PLK4 substrates have been identified unequivocally in human cells, and PLK4 signaling outside centriolar networks remains poorly characterised. We report an unbiased mass spectrometry (MS)-based quantitative analysis of cellular protein phosphorylation in stable PLK4-expressing U2OS human cells exposed to centrinone. PLK4 phosphorylation was itself sensitive to brief exposure to the compound, resulting in PLK4 stabilization. Analysing asynchronous cell populations, we report hundreds of centrinone-regulated cellular phosphoproteins, including centrosomal and cell cycle proteins and a variety of likely ‘non-canonical’ substrates. Surprisingly, sequence interrogation of ~300 significantly down-regulated phosphoproteins reveals an extensive network of centrinone-sensitive [Ser/Thr]Pro phosphorylation sequence motifs, which based on our analysis might be either direct or indirect targets of PLK4. In addition, we confirm that NMYC and PTPN12 are PLK4 substrates, bothin vitroand in human cells. Our findings suggest that PLK4 catalytic output directly controls the phosphorylation of a diverse set of cellular proteins, including Pro-directed targets that are likely to be important in PLK4-mediated cell signaling.
Defective Trafficking of Annexins to the Site of Injury in ANO5-Knockout Muscle Fibers
Authors: Foltz Steven J. , Cui YuanYuan , Choo Hyojung J. , Hartzell H. Criss
Published: May 2020

Mutations inANO5(TMEM16E) cause limb-girdle muscular dystrophy R12 (limb-girdle muscular dystrophy type 2L). Recent evidence implicates defective plasma membrane repair as a likely mechanism for the disorder. Here, we probe the ANO5-dependency of the membrane repair pathway using a laser wounding assay inAno5knockout mouse muscle fibers. Wounded myofibers fromAno5knockout mice exhibit delayed membrane resealing relative to wild type fibers as revealed by an increased uptake of the membrane-impermeant FM1-43 dye and a prolonged elevation of intracellular Ca2+. The trafficking of several annexin proteins, which together form a cap at the site of injury, is altered inAno5knockout fibers. Annexin A2 accumulates at the wound to nearly twice the level observed in WT fibers, while annexin A6 accumulation is substantially inhibited in the absence of ANO5. Furthermore, trafficking of annexins A1 and A5 to the cap is decreased in theAno5knockout. These changes are correlated with an alteration in the fine structure of the annexin repair cap and the shedding of annexin-positive extracellular vesicles. Our results suggest that the meticulous coordination of the annexin repair machinery required to effectively reseal wounded sarcolemma is disrupted inAno5knockout mice. ANO5 is a putative phospholipid scramblase, responsible for exposure of intracellular phospholipids to the extracellular leaflet of the plasma membrane. However, because the membrane repair defect is rescued by overexpression of wild type ANO5 or a scramblase-defective mutant, we suggest that ANO5-mediated phospholipid scrambling is not essential for membrane repair.

Significance Statement

Mutations inANO5/TMEM16Ecause myopathies of variable severity, with some patients losing ambulation entirely. Unfortunately, relatively little is known about the function of ANO5 at the protein level, but it has been suggested that ANO5 plays a role in the repair of injured muscle plasma membranes. Here, we investigate the mechanism of ANO5-mediated repair and find that annexin proteins, which in normal muscle form a cap to seal wounds, traffic abnormally to the cap when ANO5 is not expressed. Muscle fibers lacking ANO5 reseal more slowly and thus are exposed to prolonged intracellular calcium elevation that can damage the fibers. Our findings contribute to the growing literature implicating failed repair as a probable pathogenic mechanism in patients withANO5mutations.
Intravital imaging reveals cell cycle-dependent satellite cell migration during muscle regeneration
Authors: Konagaya Yumi , Takakura Kanako , Sogabe Maina , Bisaria Anjali , Liu Chad , Meyer Tobias , Sehara-Fujisawa Atsuko , Matsuda Michiyuki , Terai Kenta
Published: May 2020

During muscle regeneration, extracellular signal-regulated kinase (ERK) promotes both proliferation and migration. However, the relationship between proliferation and migration is poorly understood in this context. To elucidate this complex relationship on a physiological level, we established an intravital imaging system for measuring ERK activity, migration speed, and cell-cycle phases in mouse muscle satellite cells. We found thatin vivo, ERK was maximally activated in satellite cells two days after injury, and this is then followed by increases in cell number and motility. With limited effects of immediate ERK activity on migration, we hypothesized that ERK increases migration speed in the later phase by promoting cell-cycle progression. Our cell-cycle analysis further revealed that in satellite cells, ERK activity is critical for the G1/S transition, and cells migrate more rapidly in the S/G2 phase three days after injury. Finally, migration speed of satellite cells was suppressed after CDK1/2, but not CDK1, inhibitor treatment, demonstrating a critical role of CDK2 in satellite cell migration. Overall, our study demonstrates that in satellite cells, the ERK-CDK2 axis not only promotes the G1/S transition, but also migration speed, which may provide a novel mechanism for efficient muscle regeneration.
Learning What a Good Structural Variant Looks Like
Authors: Chowdhury Murad , Layer Ryan M.
Published: May 2020

Structural variations (SVs) are an important class of genetic mutations, yet SV detectors still suffer from high false-positive rates. In many cases, humans can quickly determine whether a putative SV is real by merely looking at a visualization of the SV’s coverage profile. To that end, we developed Samplot-ML, a convolutional neural network (CNN) trained to genotype genomic deletions using Samplot visualizations that incorporate various forms of evidence such as genome coverage, discordant pairs, and split reads. Using Samplot-ML, we were able to reduce false positives by 47% while keeping 97% of true positives on average across several test samples.
NTR 2.0: a rationally-engineered prodrug converting enzyme with substantially enhanced efficacy for targeted cell ablation
Authors: Sharrock Abigail V. , Mulligan Timothy S. , Hall Kelsi R. , Williams Elsie M. , White David T. , Zhang Liyun , Matthews Frazer , Nimmagadda Saumya , Washington Selena , Le Katherine , Meir-Levi Danielle , Cox Olivia L. , Saxena Meera T. , Calof Anne L. , Lopez-Burks Martha E. , Lander Arthur D. , Ding Ding , Ji Hongkai , Ackerley David F. , Mumm Jeff S.
Published: May 2020

Heterologously-expressed bacterial nitroreductase (NTR) enzymes sensitize eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell ablation paradigms that have expanded studies of cell function and regeneration in vertebrate systems. However, first-generation NTRs require confoundingly toxic prodrug treatments (e.g. 10 mM MTZ) and some cell types have proven resistant. We used rational engineering and cross-species screening to develop a NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy. Toxicity tests in zebrafish showed no deleterious effects of prolonged MTZ treatments of ≤1 mM. NTR 2.0 therefore enables sustained cell loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and enable modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic resources to facilitate dissemination of NTR 2.0 to the research community.
Association of changing physical activity intensity and bout length with mortality: a study of 79,507 participants in UK Biobank
Authors: Millard Louise Amanda Claire , Tilling Kate , Gaunt Tom R , Carslake David , Lawlor Deborah A
Published: May 2020

Background
Spending more time active (and less time sedentary) is associated with many health benefits such as improved cardiovascular health and lower risk of all-cause mortality. However, it is unclear whether these associations differ depending on whether time spent sedentary or in moderate-vigorous physical activity (MVPA) is accumulated in long or short bouts. In this study we used a novel analytical approach, that accounts for substitution (i.e. more time in MVPA means spending less time sleeping, in light activity or being sedentary), to examine whether length of sedentary and MVPA bouts associates with all-cause mortality.

Methods and findings
We used data on 79,507 participants from UK Biobank. We derived the total time participants spent in activity categories - sleep, sedentary, light activity and MVPA - on average per day. We also derived the time spent in sedentary and MVPA bouts of short (1-15 minutes), medium (16-40 minutes) and long (41+ minutes) duration. We used Cox proportion hazards regression to estimate the association of spending 10 minutes more average daily time in one activity or bout length category, coupled with spending 10 minutes less time in another, with all-cause mortality. Those spending more time sedentary had higher mortality risk if this replaced time spent in light activity (hazard ratio 1.02 [95% confidence interval (CI): 1.01, 1.03]), and an even higher risk if this replaced time spent in MVPA (hazard ratio 1.08 [95% CI: 1.06, 1.10]). Those spending more time in MVPA had lower mortality risk, irrespective of whether this replaced time spent sleeping, sedentary or in light activity. We found little evidence to suggest that mortality risk differed depending on the length of sedentary or MVPA bouts. A limitation of our study is that we cannot assume that these results are causal, though we adjusted for key confounders.

Conclusions
Using our novel analytical approach, we uniquely show that time spent in MVPA is associated with reduced mortality, irrespective of whether it replaces time spent sleeping, sedentary or in light activity. This emphasizes the specific importance of MVPA. We found little evidence to suggest that the impact of MVPA differs depending on whether it is obtained from several short bouts or fewer longer bouts, supporting recent policy changes in some countries. Further studies are needed to investigate causality and explore health outcomes beyond mortality.
The effect of non-pharmaceutical interventions (NPIs) on the spread of COVID-19 pandemic in Japan: A modeling study
Authors: Sun Yingying , Sun Jikai
Published: May 2020

Non-pharmaceutical interventions (NPIs) are founded to be effective to delay epidemic spread and to reduce the number of patients. Moderate NPIs took in Japan seemed to have reduced the COVID-19 patients and to lower death rates, thus, effects of those NPIs are worthy of investigation. We used open source data and divided the data into three periods: Jan 22 to Feb 25 (Period I), Feb 26 to Apr 6 (Period II), and Apr 7 to May 14 (Period III). We developed the SIRD model and applied the Monte Carlo Simulation to estimate a combination of optimal results, including the peak of infected cases, the peak date, and R0. For Period I, the estimated peak infected cases were smaller than the observed ones, the peak date was earlier than the observed one, and the R0 was about 4.66. For the other two periods, the estimated cases were more, and the peak dates were earlier than the observed ones. The R0 was 2.50 in Period II, and 1.79 in Period III. NPIs took in Japan might have reduced more than 50% of the daily contacts per people compared to that before COVID-19. Owing to the effects of NPIs, the Japanese society had avoided collapse of medical service. Nevertheless, the capacity of daily RT-PCR may have restricted the reported confirmed cases.
Changes in premature birth rates during the Danish nationwide COVID-19 lockdown: a nationwide register-based prevalence proportion study
Authors: Hedermann Gitte , Hedley Paula L , Baekvad-Hansen Marie , Hjalgrim Henrik , Rostgaard Klaus , Poorisrisak Porntiva , Breindahl Morten , Melbye Mads , Hougaard David , Christiansen Michael , Lausten-Thomsen Ulrik
Published: May 2020

Objectives
To explore the impact of COVID-19 lockdown on premature birth rates in Denmark
Design
Nationwide register-based prevalence proportion study.
Participants
31,180 live singleton infants born in Denmark between March 12, and April 14, from 2015 to 2020
Main outcome measures
The Main outcome measure was the odds ratio of premature birth, per preterm category, during the lockdown period compared with the calendar match period in the five previous years.
Results
A total of 31 180 newborns were included in the study period, of these 58 were born extremely premature (gestational age below 28 weeks). The distribution of gestational ages was significantly different (p = 0.004) during the lockdown period compared to the previous five years. The extremely premature birth rate during the lockdown was significantly lower than the corresponding mean rate for the same dates in the previous years (odds ratio 0.09 [95 % CI 0.01 - 0.04], p < 0.001). No significant difference between the lockdown and previous years was found for other gestational age categories.
Conclusions
The birth rate of extremely premature infants decreased significantly (~90 % reduction) during the Danish nationwide lockdown from a stable rate in the preceding five years. The reasons for this decrease are unclear. Identification of possible causal mechanisms might stimulate changes in clinical practice. Ideally, some cases of extreme prematurity are preventable which may decrease infant morbidity and mortality.
Estimating Under Reporting of Leprosy in Brazil using a Bayesian Approach
Authors: Oliveira Guilherme L , Oliveira Juliane Fonseca , Andrade Roberto F S , Nery Joilda S , Pescarini Julia M , Ichihara Maria Y , Smeeth Liam , Brickley Elizabeth B , Barreto Mauricio L , Penna Gerson O , Penna Maria L F , Sanchez Mauro N
Published: May 2020

Leprosy remains an important health problem in Brazil - the country register the second largest number of new leprosy cases each year, accounting for 14% of the world's new cases in 2019. Although there was increasing advances in leprosy surveillance worldwide, the true number of leprosy cases is expected to be much larger than the reported. Leprosy underreporting impair planning effective interventions and thoughful decisions about the distribution of financial and health resources. In this study, we estimated leprosy underreporting for each Brazilian microregion in order to guide effective interventions and resouce allocation to improve leprosy detection in the country. We extracted the number of new cases of leprosy from 2007 to 2015 and population and socioeconomic information from the 2010 Census for each Brazilian municipality and grouped data in microregions. We applied a Bayesian hierarchical model to obtain the best explicative model for leprosy underreporing using Grade 2 of leprosy-related disabilities as a proxy to explain the incidence rates. Then, we estimated the number of missing leprosy cases (underreported cases) and the corrected leprosy incidence rates for each Brazilian microrregion.
Clustering method for spread pattern analysis of corona-virus (COVID-19) infection in Iran
Authors: Azarafza Mehdi , Azarafza Mohammad , Akgün Haluk
Published: May 2020

The COVID-19 is outbreak from China and infected more than 131,652 people and caused 7,300 deaths in Iran. Unfortunately, the infection numbers and deaths are still increasing rapidly which has put the world on the catastrophic abyss edge. Application of data mining to perform pattern recognition of infection is mainly used for peparing the spread mapping which considred in this work for spatiotemporal distribution assessment and spread pattern analysis of corona-virus (COVID-19) infection in Iran.
High-Throughput Human Primary Cell-Based Airway Model for Evaluating Influenza, Coronavirus, or other Respiratory Virusesin vitro
Authors: Gard A.L. , Maloney R. , Cain B.P. , Miller C.R. , Luu R.J. , Coppeta J.R. , Liu P. , Wang J.P. , Azizgolshani H. , Fezzie R.F. , Balestrini J.L. , Isenberg B.C. , Finberg R.W. , Borenstein J.T.
Published: May 2020

Influenza and other respiratory viruses represent a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as the current COVID-19 crisis. One of the greatest barriers to the development of effective therapeutic agents to treat influenza, coronaviruses, and many other infections of the respiratory tract is the absence of a robust preclinical model. Preclinical studies currently rely on high-throughput, low-fidelityin vitroscreening with cell lines and/or low-throughput animal models that often provide a poor correlation to human clinical responses. Here, we introduce a human primary airway epithelial cell-based model integrated into a high-throughput platform where tissues are cultured at an air-liquid interface (PREDICT96-ALI). We present results on the application of this platform to influenza and coronavirus infections, providing multiple readouts capable of evaluating viral infection kinetics and potentially the efficacy of therapeutic agents in anin vitrosystem. Several strains of influenza A virus are shown to successfully infect the human primary cell-based airway tissue cultured at an air-liquid interface (ALI), and as a proof-of-concept, the effect of the antiviral oseltamivir on one strain of Influenza A is evaluated. Human coronaviruses NL63 (HCoV-NL63) and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for protein priming, and we confirm expression of both in our ALI model. We also demonstrate coronavirus infection in this system with HCoV-NL63, observing sufficient viral propagation over 96 hours post-infection to indicate successful infection of the primary cell-based model. This new capability has the potential to address a gap in the rapid assessment of therapeutic efficacy of various small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses.
TuNR: Orthogonal Control of Mean and Variability of Endogenous Genes in a Human Cell Line
Authors: Bonny Alain R. , Fonseca João Pedro , Park Jesslyn E. , El-Samad Hana
Published: May 2020

Stochastic fluctuations at the transcriptional level contribute to isogenic cell-to-cell heterogeneity in mammalian cell populations. However, we still have no clear understanding of the repercussions of this heterogeneity, given the lack of tools to independently control mean expression and variability of a gene. Here, we engineered a synthetic circuit to independently modulate mean expression and heterogeneity of transgenes and endogenous human genes. The circuit, a Tunable Noise Rheostat (TuNR), consists of a transcriptional cascade of two inducible transcriptional activators, where the output mean and variance can be modulated by two orthogonal small molecule inputs. In this fashion, different combinations of the inputs can achieve the same mean but with different population variability. With TuNR, we achieve low basal expression, over 1000-fold expression of a transgene product, and up to 7-fold induction of the endogenous geneNGFR. Importantly, for the same mean expression level, we are able to establish varying degrees of heterogeneity in expression within an isogenic population, thereby decoupling gene expression noise from its mean. TuNR is therefore a modular tool that can be used in mammalian cells to enable direct interrogation of the implications of cell-to-cell variability.
Teachers talk about inclusion… but can they implement it in their classroom? Exploring teachers’ views on inclusion in a Scottish secondary school
Authors: Ferriday Gillian , Cantali Dianne
Published: May 2020

Although there is much research regarding the inclusion of pupils with additional support needs (ASN) in mainstream secondary education, there is little research specifically exploring the perspectives of staff who support and teach this population. This small‐scale exploratory study in a Scottish secondary school investigated staff perspectives, aiming to provide unique insights and personal accounts of issues pertaining to inclusion. The findings suggest that there is a need to increase the skills of staff in order for them to be suitably equipped, competent and confident to meet all pupils’ needs.
“The Galigir Room”: a resourced provision for young people with social, emotional and mental health difficulties (SEMH) in their first years at secondary school
Authors: Greer Julie
Published: May 2020

This paper examines the values, vision and practice originally outlined in a proposal for a secondary phase resourced provision for young people with social, emotional and mental health (SEMH) challenges. The provision was based on a well‐established model (the ‘Jarjums Room’) which had been implemented in Cherbourg Primary School in Eastleigh, England. The article offers a first‐hand narrative account of the way that this initiative, the ‘Galigir Room’, was conceptualised, successfully embraced and implemented, thanks to the commitment of a senior leadership team, a group of staff and governors and the foresight and support of the local secondary school.
Action research to improve confidence in meeting diverse need and the quality of inclusive practice through lesson observations
Authors: Connett Helen
Published: May 2020

This paper reports an action research study undertaken towards the National Award for Special Educational Needs Coordination (NASENCO) on a university‐based course. It follows an earlier evaluative study that identified a tension between teachers’ self‐rated high levels of confidence in meeting diverse need and values which did not appear to support inclusive practice. The ‘action’ which was subsequently taken was the collection of further data through lesson observations to assess whether such confidence was reflected in inclusive classroom practice. Planning reviews were also undertaken. Several recognised features of inclusive practice that are known to benefit pupils with special educational needs (SEN) were not observed in all classrooms. The action research study findings identified very specific training needs relating to inclusive classroom practice, the design of individual education plans and the development of a shared school ethos and understanding of inclusive pedagogy.
Early years practitioners’ knowledge of early signs of autism in England
Authors: MacLeod Jessica , Perepa Prithvi
Published: May 2020

This research explores early years practitioners’ knowledge and ability to recognise the signs of autism and provide appropriate support. It was carried out using semi‐structured interviews with six UK‐based early years practitioners who have worked with children with autism. The findings highlighted that early years practitioners are aware of autism but have a limited understanding of the early signs of the condition. Furthermore, there are inconsistencies in training and collaboration in early years settings. All these factors influence whether the practitioners are able to recognise the early signs of autism and provide appropriate support. This study highlights the need to address the issue of training provided to early years practitioners.
Families of children on the autism spectrum: experience of daily life and impact of parent education
Authors: Stošić Jasmina , Frey Škrinjar Jasmina , Preece David
Published: May 2020

Information and support for families of children on the autism spectrum is limited in south‐east Europe. A three‐year project, Equity and Social Inclusion Through Positive Parenting (ESIPP), was established to develop and provide parent education (PE) in autism for families in Croatia, Cyprus and North Macedonia. This paper presents findings from Croatia regarding family life and the impact of PE. Data were collected via pre‐ and post‐PE questionnaires and semi‐structured interviews. Participants discussed the impact of autism on family life, the difficulty of obtaining a diagnosis, the importance of family support (and varying experience of formal support), common experiences of stigma and social exclusion and concerns for the future. The value and benefit of PE is identified, and recognition of its impact within Croatia has ensured its ongoing provision.
Editorial: increasing burden of nonalcoholic fatty liver disease—a call to action
Authors: Chuah Kee‐Huat , Chan Wah‐Kheong
Published: May 2020

LINKED CONTENT

This article is linked to Estes et al papers. To view these articles, visit https://doi.org/10.1111/apt.15673 and https://doi.org/10.1111/apt.15718.
Letter: how can we reduce mortality in elderly patients with acute severe ulcerative colitis?
Authors: Li Wai Suen Christopher F.D. , Choy Matthew C. , De Cruz Peter
Published: May 2020

LINKED CONTENT

This article is linked to Dong et al papers. To view these articles, visit https://doi.org/10.1111/apt.15592 and https://doi.org/10.1111/apt.15776.
Editorial: increasing burden of nonalcoholic fatty liver disease—a call to action. Authors' reply
Authors: Estes Chris , Chan Henry L. Y. , Chien Rong N. , Chuang Wan‐Long , Fung James , Goh George Boon‐Bee , Hu Tsung H. , Huang Jee‐Fu , Jang Byoung K. , Jun Dae W. , Kao Jia H. , Lee Jin‐Woo , Lin Han‐Chieh , Razavi‐Shearer Kathryn , Seto Wai‐Kay , Wong Grace L.‐H. , Wong Vincent W.‐S. , Razavi Homie
Published: May 2020

LINKED CONTENT

This article is linked to Estes et al and Chuah and Chan papers. To view these articles, visit https://doi.org/10.1111/apt.15673 and https://doi.org/10.1111/apt.15700.
Editorial: hepatitis C and porphyria cutanea tarda in 2020
Authors: Rudnick Sean , Bonkovsky Herbert L.
Published: May 2020

LINKED CONTENT

This article is linked to Sastre et al paper. To view this article, visit https://doi.org/10.1111/apt.15703.
Letter: are microbes other than Helicobacter pylori associated with gastric cancer? Authors' reply
Authors: Gantuya Boldbaatar , El‐Serag Hashem B. , Yamaoka Yoshio
Published: May 2020

LINKED CONTENT

This article is linked to Gantuya et al and He et al papers. To view these articles, visit https://doi.org/10.1111/apt.15675 and https://doi.org/10.1111/apt.15757.
Letter: how can we reduce mortality in elderly patients with acute severe ulcerative colitis? Authors' reply
Authors: Dong Catherine , Metzger Marie , Holsbø Einar E. , Perduca Vittorio , Carbonnel Franck
Published: May 2020

LINKED CONTENT

This article is linked to Dong et al and Li et al papers. To view these articles, visit https://doi.org/10.1111/apt.15592 and https://doi.org/10.1111/apt.15702.
Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome
Authors: Ostojic Sergej M.
Published: May 2020

LINKED CONTENT

This article is linked to Ianiro et al paper. To view this article, visit https://doi.org/10.1111/apt.14201.
Editorial: hepatitis B DNA thresholds and risk of hepatocellular carcinoma: different number patterns in HBeAg‐positive versus HBeAg‐negative patients
Authors: Dusheiko Geoffrey
Published: May 2020

LINKED CONTENT

This article is linked to Kim et al and Kim and Lim papers. To view these articles, visit https://doi.org/10.1111/apt.15725 and https://doi.org/10.1111/apt.15794.
Editorial: hepatitis B DNA thresholds and risk of hepatocellular carcinoma: different number patterns in HBeAg‐positive versus HBeAg‐negative patients. Authors' reply
Authors: Kim Gi‐Ae , Lim Young‐Suk
Published: May 2020

LINKED CONTENT

This article is linked to Kim et al and Dusheiko papers. To view these articles, visit https://doi.org/10.1111/apt.15725 and https://doi.org/10.1111/apt.15783.
Letter: Helicobacter pylori eradication treatment and the risk of oesophageal adenocarcinoma
Authors: Sun Yulan
Published: May 2020

LINKED CONTENT

This article is linked to Kumar et al paper. To view this article, visit https://doi.org/10.1111/apt.15677.
The ‘biomineralization toolkit’ and the origin of animal skeletons
Authors: Murdock Duncan J. E.
Published: May 2020

Biomineralized skeletons are widespread in animals, and their origins can be traced to the latest Ediacaran or early Cambrian fossil record, in virtually all animal groups. The origin of animal skeletons is inextricably linked with the diversification of animal body plans and the dramatic changes in ecology and geosphere–biosphere interactions across the Ediacaran–Cambrian transition. This apparent independent acquisition of skeletons across diverse animal clades has been proposed to have been driven by co‐option of a conserved ancestral genetic toolkit in different lineages at the same time. This ‘biomineralization toolkit’ hypothesis makes predictions of the early evolution of the skeleton, predictions tested herein through a critical review of the evidence from both the fossil record and development of skeletons in extant organisms. Furthermore, the distribution of skeletons is here plotted against a time‐calibrated animal phylogeny, and the nature of the deep ancestors of biomineralizing animals interpolated using ancestral state reconstruction. All these lines of evidence point towards multiple instances of the evolution of biomineralization through the co‐option of an inherited organic skeleton and genetic toolkit followed by the stepwise acquisition of more complex skeletal tissues under tighter biological control. This not only supports the ‘biomineralization toolkit’ hypothesis but also provides a model for describing the evolution of complex biological systems across the Ediacaran–Cambrian transition.