bluuebunny/crossref_metadata_2025 huggingface dataset:
The observed velocity distribution of young pulsars – II. Analysis of complete PSRπ
Authors: Igoshev Andrei P
Published: April 2020

Understanding the natal kicks, or birth velocities, of neutron stars is essential for understanding the evolution of massive binaries and double neutron star formation. We use maximum likelihood methods as published in Verbunt et al. to analyse a new large data set of parallaxes and proper motions measured by Deller et al. This sample is roughly three times larger than number of measurements available before. For both the complete sample and its younger part (spin-down ages τ < 3 Myr), we find that a bimodal Maxwellian distribution describes the measured parallaxes and proper motions better than a single Maxwellian with probability of 99.3 and 95.0 per cent, respectively. The bimodal Maxwellian distribution has three parameters: fraction of low-velocity pulsars and distribution parameters σ1 and σ2 for low- and high-velocity modes. For a complete sample, these parameters are as follows: $42_{-15}^{+17}$ per cent, $\sigma _1=128_{-18}^{+22}$ km s−1, and σ2 = 298 ± 28 km s−1. For younger pulsars, which are assumed to represent the natal kick, these parameters are as follows: $20_{-10}^{+11}$ per cent, $\sigma _1=56_{-15}^{+25}$ km s−1, and σ2 = 336 ± 45 km s−1. In the young population, 5 ± 3 per cent of pulsars have velocities less than 60 km s−1. We perform multiple Monte Carlo tests for the method taking into account realistic observational selection. We find that the method reliably estimates all parameters of the natal kick distribution. Results of the velocity analysis are weakly sensitive to the exact values of scale lengths of the Galactic pulsar distribution.
Efficient solution of the anisotropic spherically aligned axisymmetric Jeans equations of stellar hydrodynamics for galactic dynamics
Authors: Cappellari Michele
Published: April 2020

I present a flexible solution for the axisymmetric Jeans equations of stellar hydrodynamics under the assumption of an anisotropic (three-integral) velocity ellipsoid aligned with the spherical polar coordinate system. I describe and test a robust and efficient algorithm for its numerical computation. I outline the evaluation of the intrinsic velocity moments and the projection of all first and second velocity moments, including both the line-of-sight velocities and the proper motions. This spherically aligned Jeans anisotropic modelling (JAMsph) method can describe in detail the photometry and kinematics of real galaxies. It allows for a spatially varying anisotropy, or stellar mass-to-light ratio gradients, as well as for the inclusion of general dark matter distributions and supermassive black holes. The JAMsph method complements my previously derived cylindrically aligned JAMcyl and spherical Jeans solutions, which I also summarize in this paper. Comparisons between results obtained with either JAMsph or JAMcyl can be used to assess the robustness of inferred dynamical quantities. As an illustration, I modelled the ATLAS3D sample of 260 early-type galaxies with high-quality integral-field spectroscopy, using both methods. I found that they provide statistically indistinguishable total density logarithmic slopes. This may explain the previously reported success of the JAM method in recovering density profiles of real or simulated galaxies. A reference software implementation of JAMsph is included in the publicly available jam software package.
Inverted duplicate DNA sequences increase translocation rates through sequencing nanopores resulting in reduced base calling accuracy
Authors: Spealman Pieter , Burrell Jaden , Gresham David
Published: April 2020

Inverted duplicated DNA sequences are a common feature of structural variants (SVs) and copy number variants (CNVs). Analysis of CNVs containing inverted duplicated DNA sequences using nanopore sequencing identified recurrent aberrant behavior characterized by low confidence, incorrect and missed base calls. Inverted duplicate DNA sequences in both yeast and human samples were observed to have systematic elevation in the electrical current detected at the nanopore, increased translocation rates and decreased sampling rates. The coincidence of inverted duplicated DNA sequences with dramatically reduced sequencing accuracy and an increased translocation rate suggests that secondary DNA structures may interfere with the dynamics of transit of the DNA through the nanopore.
Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials
Authors: Genovese Mark C , Mysler Eduardo , Tomita Tetsuya , Papp Kim A , Salvarani Carlo , Schwartzman Sergio , Gallo Gaia , Patel Himanshu , Lisse Jeffrey R , Kronbergs Andris , Leage Soyi Liu , Adams David H , Xu Wen , Marzo-Ortega Helena , Lebwohl Mark G
Published: April 2020

Objectives

The aim of this integrated analysis is to evaluate the long-term safety and tolerability of ixekizumab in adults with psoriasis, PsA and axial SpA.

Methods

Integrated safety data from 21 clinical trials are presented by indication in patients who received at least one dose of ixekizumab. Adverse events (AEs) and treatment-emergent adverse events (TEAEs) adjusted incidence rates (IRs) per 100 patient-years (PY) up to 5 years’ exposure are reported.

Results

A total of 8228 patients with an ixekizumab exposure of 20 895.9 PY were included in this analysis. The most common TEAEs were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Across populations, IRs were low for AEs leading to discontinuation (IRs ≤5.1 per 100 PY), serious AEs (IRs ≤6.0 per 100 PY) and death (IRs ≤0.3 per 100 PY). The most reported TEAEs of special interest were infections (IRs ≤35.8 per 100 PY). Patients rarely reported malignancies (IR ≤0.8), IBD including ulcerative colitis and Crohn’s disease (IR ≤0.8) and major adverse cardiovascular events (IR ≤0.5). TEAEs were most commonly reported the first 2 years of exposure with ixekizumab and IR decreased over the years (infections, injection-site reactions and depression) or remained constant over the entire treatment period (serious infections, major adverse cardiovascular events, malignancies and IBD).

Conclusion

This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals. The safety profile and tolerability reported in this integrated analysis remained consistent with the known safety profile for ixekizumab.
EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies
Authors: Pregnolato Francesca , Gerosa Maria , Raimondo Maria Gabriella , Comerio Chiara , Bartoli Francesca , Lonati Paola A , Borghi Maria Orietta , Acaia Barbara , Ossola Manuela Wally , Ferrazzi Enrico , Trespidi Laura , Meroni Pier Luigi , Chighizola Cecilia B
Published: April 2020

Objectives

aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria (‘criteria aPL’) and at titres lower than thresholds considered by classification criteria (‘low-titre aPL’) on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM).

Methods

Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations.

Results

EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly.

Conclusion

EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.
Transport losses in market weight pigs: II. U.S. incidence and economic impact
Authors: Ritter Matthew J , Yoder Chad L , Jones Corey L , Carr Scott N , Calvo-Lorenzo Michelle S
Published: April 2020

An industry survey representing approximately 310 million (M) market weight pigs was conducted with 20 U.S. slaughter facilities over the calendars years of 2012 to 2015 to determine the incidence, seasonal patterns, and estimated economic impact of dead and non-ambulatory pigs. Each plant entered daily totals in a secure online database for the following variables: 1) pigs slaughtered, 2) dead on arrival (DOA; dead on the truck), 3) euthanized on arrival (EOA; non-ambulatory pig with an injury that required euthanasia), 4) dead in pen (DIP; died after unloading), and 5) non-ambulatory (pig unable to move or keep up with the rest of the group from unloading to stunning). Total dead pigs were calculated as DOA + EOA + DIP, and total losses were calculated as non-ambulatory + total dead. The economic impact was estimated based on the 4-yr weighted averages from USDA annual reports for market swine slaughtered (108,470,550 pigs), live market weight (126.9 kg), and live market price ($1.44/kg). The 4-yr weighted averages for total dead, non-ambulatory, and total losses were 0.26%, 0.63%, and 0.88%, respectively. Total dead consisted of 0.15% DOA, 0.05% EOA, and 0.05% DIP. The months with the highest rates of total dead were July (0.29%), August (0.32%), and September (0.30%), while the lowest incidence rates occurred in February (0.22%), March (0.22%), and April (0.22%). The months with the highest rates of non-ambulatory pigs were observed during the months of October (0.70%), November (0.71%), and December (0.70%), whereas the lowest rates of non-ambulatory pigs were observed during the months of April (0.57%), May (0.53%), and June (0.54%). The following assumptions were used in the economic analysis: 1) dead pigs received no value and 2) non-ambulatory pigs were discounted 30%. Based on these assumptions, the annual cost to the industry for dead and non-ambulatory pigs was estimated to be $52 M ($0.48 per pig marketed) and $37 M ($0.35 per pig marketed), respectively. Therefore, total losses represent approximately $89 M in economic losses or $0.83 per pig marketed. This is the first industry-wide survey on the incidence of transport losses in market weight pigs at U.S. slaughter facilities, and this information is important for establishing an industry baseline and benchmark for transport losses that can be used for measuring industry improvements.
Society of Behavioral Medicine Call to Action: Include obesity/overweight management education in health professional curricula and provide coverage for behavior-based treatments of obesity/overweight most commonly provided by psychologists, dieticians, counselors, and other health care professionals and include such providers on all multidisciplinary teams treating patients who have overweight or obesity
Authors: Ockene Judith K , Ashe Karen , Peterson Kenneth S , Fitzgibbon Marian , Buscemi Joanna , Dulin Akilah
Published: April 2020

Obesity is a serious chronic disease whose prevalence has grown to epidemic proportions over the past five decades and is a major contributor to the global burden of most common cancers, heart disease, Type 2 diabetes, liver disease, and sleep apnea. Primary care clinicians, including physicians, nurse practitioners, and physician assistants, are often the first health care professionals to identify obesity or overweight during routine long-term care and have the opportunity to intervene to prevent and treat disease. However, they often lack the training and skills needed to deliver scientifically validated, behavior-based treatments. These gaps must be addressed in order to treat the obesity epidemic.

The Society of Behavioral Medicine strongly urges health professional educators and accrediting agencies to include obesity and overweight management education for primary care clinicians. Additionally, we support promoting referrals and reimbursement for psychologists, dieticians, and other health care professionals as critical members of the care team and improving reimbursement levels for behavioral obesity and overweight management treatment.
Tanyrhinichthys mcallisteri, a long-rostrumed Pennsylvanian ray-finned fish (Actinopterygii) and the simultaneous appearance of novel ecomorphologies in Late Palaeozoic fishes
Authors: Stack Jack , Hodnett John-Paul , Lucas Spencer G , Sallan Lauren
Published: April 2020

The Carboniferous radiation of fishes was marked by the convergent appearance of then-novel but now common ecomorphologies resulting from changes in the relative proportions of traits, including elongation of the front of the skull (rostrum). The earliest ray-finned fishes (Actinopterygii) with elongate rostra are poorly known, obscuring the earliest appearances of a now widespread feature in actinopterygians. We redescribe Tanyrhinichthys mcallisteri, a long-rostrumed actinopterygian from the Upper Pennsylvanian (Missourian) of the Kinney Brick Quarry, New Mexico. Tanyrhinichthys has a lengthened rostrum bearing a sensory canal, ventrally inserted paired fins, posteriorly placed median fins unequal in size and shape, and a heterocercal caudal fin. Tanyrhinichthys shares these features with sturgeons, but lacks chondrostean synapomorphies, indicating convergence on a bottom-feeding lifestyle. Elongate rostra evolved independently in two lineages of bottom-dwelling, freshwater actinopterygians in the Late Pennsylvanian of Euramerica, as well as in at least one North American chondrichthyan (Bandringa rayi). The near-simultaneous appearance of novel ecomorphologies among multiple, distantly related lineages of actinopterygians and chondrichthyans was common during the Carboniferous radiation of fishes. This may reflect global shifts in marine and freshwater ecosystems and environments during the Carboniferous favouring such ecomorphologies, or it may have been contingent on the plasticity of early actinopterygians and chondrichthyans.
LPS stimulation during HCV infection induces MMP/TIMP1 imbalance in macrophages
Authors: Fan Chao , Zhang Xiaoxiao , Zhang Peixin , Zhao Jieru , Shen Huanjun , Zhang Ying , Wu Xingan , Jia Zhansheng , Wang Yili
Published: April 2020

Introduction. During chronic hepatitis C virus (HCV) infections, HCV antigens establish cross-tolerance of endotoxins, but additional lipopolysaccharide (LPS) stimulation effects in this condition are poorly understood.

Aim. This study aims to investigate the effects of the upregulated LPS on MMP and TIMP expression during chronic hepatitis C infection.

Methodology. In the present study, we analysed the effect of HCV antigens and LPS stimulation on peripheral blood mononuclear cells (PBMCs) both in vivo and in vitro. Macrophages from HCV patients were isolated and their association with endotoxin tolerance was examined. MMP/TIMP1 expression and the related signalling pathways in macrophages were analysed. The macrophage and Huh7.5 cell co-culture model was used to analyse the effects of the cross-tolerance on collagen I deposition.

Results. LPS levels were found to be significantly higher in HCV patients, particularly in those with HCV-induced liver fibrosis. In addition, although LPS serum level was occasionally upregulated in the patients, it did not induce intense immune response in PBMCs due to endotoxin cross-tolerance, and this was measured according to the changes in IL-6 and TNF-α levels. However, TIMP1 expression increased significantly during stimulation, exhibiting a tolerance/resistance phenotype, which was associated with TGF-β/Erk activation in macrophages. However, MMP levels did not increase due to endotoxin tolerance, which ultimately led to MMP/TIMP imbalance and influenced the deposition of collagen I.

Conclusion. Increased LPS stimulation of macrophage during HCV antigen-induced endotoxin cross-tolerance contributes to MMP/TIMP1 imbalance and collagen I deposition.
Interactions between the visual and motor systems during optokinetic stimulation and simultaneous dynamic handgrip exercise: an EEG study
Authors: Cross-Villasana Fernando , Dowsett James , Mastropasqua Angela , Dieterich Marianne , Taylor Paul C.J.
Published: April 2020

Inhibitory interactions between the visual and motor systems are robustly found during the transient stimulation of either system. However, it is unknown how such interactions operate if both systems are continuously and simultaneously activated. To test this, we engaged the visual-oculomotor system in 14 right-handers with a large moving striped pattern that elicits characteristic eye movement responses, the optokinetic nystagmus (OKN). We also engaged the motor system with dynamic handgrip exercise simultaneous to OKN. We hypothesised that central versus occipital EEG upper-alpha (10-12 Hz) synchronisation would reflect systems-level inhibition between visual and motor processes. Optokinetic responses were recorded with eye tracking, and gripping force measured with dynamometry. First, when exploring whether continuous visual activation inhibits motor activity, we found that OKN increased alpha synchronisation over central electrodes, in line with classic findings of motor downregulation to transient visual stimuli. We found further evidence for the visual inhibition of motor-cortical activity, by comparing between visual conditions: increasing visual input, from closed eyes, to eye opening, to visual stimulation, produced progressively greater motor synchronisation into the inhibitory upper-alpha band. Second, we tested for the opposite interaction, that is, effects of motor engagement over ongoing visual and oculomotor processes. Behaviourally, left hand-grip exercise accelerated the ongoing OKN, increasing slow phase velocity. Electrophysiologically, performing this repetitive motor task with either hand interfered the occipital alpha desynchronization that OKN normally induces on EEG. These results support that mutual visual and motor inhibitory interactions persist during their simultaneous engagement, and show their effects on eye movements.

Key points

Increasing levels of visual activation produced increasingly stronger signs of cortical inhibition.

Hand motor activation interfered with visual cortical activation during visual stimulation.

Hand motor activation altered oculomotor responses.

Ongoing visual-motor interactions were reflected by the EEG alpha band.

EEG can be reliably assessed during nystagmus.
The protein expression profile of ACE2 in human tissues
Authors: Hikmet Feria , Méar Loren , Edvinsson Åsa , Micke Patrick , Uhlén Mathias , Lindskog Cecilia
Published: April 2020

The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across >150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitutes an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.
Spacing spheroids, curl-up and coiled neuritic plexus of the sacral spinal cord of aged dog: Hypothesis based on continued NADPH diaphorase histological observations
Authors: Jia Yunge , Li Yinhua , Hou Wei , Tan Huibing
Published: April 2020

NADPH diaphorase (N-d) neurons distribute in spinal cord and function for visceral sensation and autonomic regulation. N-d positive neurons innervate pelvic organs. In previous investigation, we report that aging-related N-d body (ANB) in the lumbosacral spinal cord in aged rat and megaloneurite in the sacral spinal cord in aged dog. This article was a continued data report of aging-related N-d alterations in aged dog. N-d positivity in aged spinal cord has revealed a certain of morphological profiles in the spinal cord of several species. However, we still found some denoted N-d neurodegenerative changes that we failed to notice in our previous studies when re-examination of the sacral spinal cord of aged dog. In the horizontal section, spacing spheroids in the superficial laminae of the dorsal horn, curl-up and coiled neurites in the intermediate zone were detected in the sacral spinal cord. The ANB and vacuolar neurite were also detected. Vacuolar degeneration also occurred in the dorsal ganglia at the sacral segment. The curl-up and coiled neurites did not occur in the lumbothoracic segment, but the ANB and vacuolar neurite were scatteringly detected in in the lumbothoracic segment of aged dog. The results suggested that the N-d sensory inputs interrupted and disconnected with integration of autonomic centers and output circuits of regulating urogenital organs during the aging. These specialized profiles were speculated that the N-d neurite deterioration of visceral sensory circuit implicated dysfunction of pelvic organs in the aging. Megaloneurite and fiber dilation may make backward reasoning to N-d fiber architecture under normal condition.
Risperidone-induced changes in DNA methylation from peripheral blood in first-episode schizophrenia parallel neuroimaging and cognitive phenotype
Authors: Hu Maolin , Xia Yan , Zong Xiaofen , Sweeney John A. , Bishop Jeffrey R , Liao Yanhui , Giase Gina , Li Bingshan , Rubin Leah H. , Wang Yunpeng , Li Zongchang , He Ying , Chen Xiaogang , Liu Chunyu , Chen Chao , Tang Jinsong
Published: April 2020

Today, second generation anti-psychotics such as clozapine and risperidone are the favored treatment for schizophrenia. Yet, the absence of relevant biomarkers that can decode their neurobiological effect shackles our ability to accurately predict and track response to treatment. While researchers have investigated DNA methylation as a biomarker for schizophrenia risk, none have performed a systematic analysis of the effect of antipsychotics upon DNA methylation. We hypothesize that disease-related methylation changes occur before treatment, and that acute antipsychotic treatment may affect DNA methylation. We designed a longitudinal DNA methylation study to estimate risperidone’s effect on DNA methylation and how changes in DNA methylation might influence risperidone’s therapeutic effect on behavioral and neuroimaging phenotypes. Thirty-eight patients with first-episode drug-naïve schizophrenia (FES) and 38 demographically-matched individuals (healthy controls) participated. We identified brain related pathways enriched in 8,204 FES-associated methylation sites. Risperidone administration altered methylation in 6,143 CpG DNA sites. Post-treatment FES associated with methylation in 6760 CpG sites. Majority of the DNA methylation changes were treatment effect in the overall CpG sites, the FES associated CpG sites, and risperidone associated CpG sites, except for the post-treatment FES associated CpG sites. There were 590 DNA methylation cites normalized by risperidone treatment. The methylation changes of these 590 CpG sites were related to alterations in symptom severity, spontaneous neurophysiological activity, and cognitive function. To our knowledge, this is the first longitudinal methylation study of drug treatment effect and side effect in psychiatric disorders to include parallel studies of neuroimaging and cognitive phenotypes. We identified FES-associated CpG sites not confounded by drug treatment as potential SCZ biomarkers. The normalization effect of risperidone monotherapy suggests that DNA methylation changes may serve as a predictive biomarker for treatment effect. The constructed methylation-phenotype network revealed a relationship between methylation and a wide range of biological and psychological variables.
From an invariant sensory code to a perceptual categorical code in second somatosensory cortex
Authors: Rossi-Pool Román , Zainos Antonio , Alvarez Manuel , Romo Ranulfo
Published: April 2020

A crucial role of cortical networks is the conversion of sensory inputs into perception. In the cortical somatosensory network, neurons of the primary somatosensory cortex (S1) show invariant sensory responses, while frontal lobe neuron responses correlate with the animal’s perceptual behavior. But, where in the cortical somatosensory network are the sensory inputs transformed into perceptual behavior? Here, we report that in the secondary somatosensory cortex (S2), neurons with invariant sensory responses coexist with neurons whose responses correlate with the animal’s perceptual behavior. These distinct neural responses exhibit analogous timescales of intrinsic fluctuations, suggesting that they belong to the same hierarchical processing stage. Furthermore, during a non-demanding control task, the sensory responses remained unaltered while perceptual responses vanished. Conclusively, the S2 population responses exhibit intermediate dynamics between S1 and frontal lobe neurons. These results suggest that the conversion of touch into perception crucially depends on S2.
Adolescent rats show estrous cycle-mediated sex-differences in extinction of conditioned fear
Authors: Perry Christina J , Ganella Despina E , Nguyen Ly Dao , Du Xin , Drummond Katherine D , Whittle Sarah , Pang Terence Y , Kim Jee Hyun
Published: April 2020

Anxiety disorders are more prevalent in females than males, and frequently emerge during adolescence. Despite this, preclinical research commonly focuses on adult males. Here we use Pavlovian fear conditioning and extinction in adolescent male and female rats to understand sex- and age-dependent processes relevant to anxiety disorders. In experiment 1, 35-day-old male and female rats were exposed to 6 pairings of a conditioned stimulus (CS, a tone) with an aversive unconditioned stimulus (US, a footshock). The next day they were extinguished in a contextually distinct chamber, via 60 presentations of the CS without the US. Extinction recall was tested 24 hours later in the extinction context. Estrous phase was monitored by cytology on vaginal smears taken 1 hour after each behavioral session. In experiment 2, male and female rats were given sham surgery or gonadectomy at 21 days of age. They were then trained and tested as for experiment 1. We observed that females in proestrus or met/diestrus during extinction showed delayed extinction and impaired extinction recall the next day compared to males. Ovariectomy enhanced extinction for female rats, but orchidectomy delayed extinction for males. Plasma analyses showed that met/di/proestrus phases were associated with high estradiol levels. These findings suggest that high plasma estradiol levels impair extinction for adolescent females. While these results contradict what is observed in adult animals, they are consistent with the prevalence of anxiety disorders observed in females. Our findings have important implications for understanding and treating anxiety in adolescents, particularly where treatment involves extinction-based therapies.
Japanese citizens’ behavioral changes and preparedness against COVID-19: How effective is Japan’s approach of self-restraint ?
Authors: Muto Kaori , Yamamoto Isamu , Nagasu Miwako , Tanaka Mikihito , Wada Koji
Published: April 2020

The Japanese government instituted countermeasures against COVID-19, a pneumonia caused by the new coronavirus, in January 2020. Seeking “people’s behavioral changes,” in which the government called on the public to take precautionary measures or exercise self-restraint, was one of the important strategies. The purpose of this study is to investigate how and from when Japanese citizens have changed their precautionary behavior under these circumstances, where the government has only requested their cooperation. This study uses micro data from a cross-sectional survey conducted on an online platform of an online research company, based on quota sampling that is representative of the Japanese population. By the end of March 2020, we had recruited a total of 11,342 respondents, aged from 20 to 64 years. About 85% reported practising the social distancing recommended by the government. More females than males and more older than younger participants are supportive of practicing social distancing. Frequent handwashing is conducted by 86 percent of all, 92 percent of female and 87.9 percent of over-40 participants. The most important event influencing these precautionary actions was the infection aboard the Diamond Princess cruise ship, which occurred in early February 2020 (23%). Information from the central and local governments, received by 60% of the participants, was deemed trustworthy by 50%. However, the results also showed that about 20% of the participants were reluctant to implement proper prevention measures. The statistical analysis indicated that the typical characteristics of those people were male, younger (under 30 years old), unmarried, from lower-income households, with a drinking or smoking habit and a higher extraversion score. To prevent the spread of infection in Japan, it is imperative to address these individuals and encourage their behavioral changes using various means to reach and influence them.
Harmonizing heterogeneous endpoints in COVID-19 trials without loss of information –an essential step to facilitate decision making
Authors: von Cube Maja , Grodd Marlon , Wolkewitz Martin , Hazard Derek , Lambert Jerome
Published: April 2020

Background

Many trials are now underway to inform decision-makers on potential effects of treatments for COVID-19. To provide sufficient information for all involved decision-makers (clinicians, public health authorities, drug regulatory agencies) a multiplicity of endpoints must be considered. It is a challenge to generate detailed high quality evidence from data while ensuring fast availability and evaluation of the results.

Methods

We reviewed all interventional COVID-19 trials on Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine registered in the National Library of Medicine (NLM) at the National Institutes of Health (NIH) and summarized the endpoints used to assess treatment effects. We propose a multistate model that harmonizes heterogeneous endpoints and differing lengths of follow-up within and between trials.

Results

There are currently, March 27, 2020, 23 registered interventional trials investigating the potential benefits of Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine. The endpoints are highly heterogeneous. Follow-up for the primary endpoints ranges from four to 168 days.

A detailed precisely defined endpoint has been proposed by the global network REMAP-CAP, which is specialized on community-acquired pneumonia. Their seven-category endpoint accounts for major clinical events informative for all decision-makers. Moreover, the Core Outcome Measures in Effectiveness Trials (COMET) Initiative is currently working on a core outcome set. We propose a multistate model that accommodates analysis of these recommended endpoints. The model allows for a detailed investigation of treatment effects for various endpoints over the course of time thereby harmonizing differing endpoints and lengths of follow-up.

Conclusion

Multistate model analysis is a powerful tool to study clinically heterogeneous endpoints (mortality, discharge) as well as endpoints influencing hospital capacities (duration of hospitalization and ventilation) simultaneously over time. Our proposed model extracts all information available in the data and is - by harmonizing endpoints within and between trials - a step towards faster decision making. All ongoing clinical trials, especially those with severe cases, should accommodate primary analysis with a stacked probability plot of the major events mechanical ventilation, discharge alive and death.
Globalized low-income countries may experience higher COVID-19 mortality rates
Authors: Jaffé Rodolfo , Ortiz Mabel , Jaffé Klaus
Published: April 2020

Understanding the factors underpinning COVID-19 infection and mortality rates is essential in order to implement actions that help mitigate the current pandemic. Here we evaluate how a suit of 15 climatic and socio-economic variables influence COVID-19 exponential growth-phase infection and mortality rates across 36 countries. We found that imports of goods and services, international tourism and the number of published scientific papers are good predictors of COVID-19 infection rates, indicating that more globalized countries may have experienced multiple and recurrent introductions of the virus. However, high-income countries showed lower mortality rates, suggesting that the consequences of the current pandemic will be worse for globalized low-income countries. International aid agencies could use this information to help mitigate the consequences of the current pandemic in the most vulnerable countries.
Modelling the COVID-19 epidemics in Brasil: Parametric identification and public health measures influence
Authors: Cotta R.M. , Naveira-Cotta C.P. , Magal P.
Published: April 2020

A SIRU-type epidemic model is proposed for the prediction of COVID-19 spreading within Brasil, and analyse the influence of public health measures on simulating the control of this infectious disease. Since the reported cases are typically only a fraction of the total number of the symptomatic infectious individuals, the model accounts for both reported and unreported cases. Also, the model allows for the time variation of both the transmission rate and the fraction of asymptomatic infectious that become reported symptomatic individuals, so as to reflect public health interventions, towards its control, along the course of the epidemic evolution. An analytical exponential behaviour for the accumulated reported cases evolution is assumed at the onset of the epidemy, for explicitly estimating initial conditions, while a Bayesian inference approach is adopted for parametric estimations employing the present direct problem model with the data from the known portion of the epidemics evolution, represented by the time series for the reported cases of infected individuals. The direct-inverse problem analysis is then employed with the actual data from China, with the first half been employed for the parametric estimation and the second half for validation of the predictive capability of the proposed approach. The full dataset for China is then employed in another parameter identification, aimed at refining the values for the average times that asymptomatic infectious individuals and that symptomatic individuals remain infectious. Following this validation, the available data on reported cases in Brasil from February 15thtill March 29th, 2020, is used for estimating parameters and then predict the epidemy evolution under these conditions. Finally, public health interventions are simulated, aimed at diminishing the effects of the disease spreading, by acting on both the transmission rate and the fraction of the total number of the symptomatic infectious individuals, considering time variable exponential behaviours for these two parameters, usually assumed constant in epidemic evolutions without intervention. It is demonstrated that a combination of actions to affect both parameters can have a much faster and effective result in the control of the epidemy dynamics.
A flexible method for optimising sharing of healthcare resources and demand in the context of the COVID-19 pandemic
Authors: Lacasa Lucas , Challen Robert , Brooks-Pollock Ellen , Danon Leon
Published: April 2020

Abstract

As the number of cases of COVID-19 continues to grow, local health services are at risk of being overwhelmed with patients requiring intensive care. We develop and implement an algorithm to provide optimal re-routing strategies to either transfer patients requiring Intensive Care Units (ICU) or ventilators, constrained by feasibility of transfer. We validate our approach with realistic data from the United Kingdom and Spain. In the UK, we consider the National Health Service at the level of trusts and define a 4-regular geometric graph which indicates the four nearest neighbours of any given trust. In Spain we coarse-grain the healthcare system at the level of autonomous communities, and extract similar contact networks. Through random search optimisation we identify the best load sharing strategy, where the cost function to minimise is based on the total number of ICU units above capacity. Our framework is general and flexible allowing for additional criteria, alternative cost functions, and can be extended to other resources beyond ICU units or ventilators. Assuming a uniform ICU demand, we show that it is possible to enable access to ICU for up to 1000 additional cases in the UK in a single step of the algorithm. Under a more realistic and heterogeneous demand, our method is able to balance about 600 beds per step in the Spanish system only using local sharing, and over 1300 using countrywide sharing, potentially saving a large percentage of these lives that would otherwise not have access to ICU.
COVID-19 infection during pregnancy: a systematic review to summarize possible symptoms, treatments, and pregnancy outcomes
Authors: Ali Khan Md. Mostaured , Khan Md. Nuruzzaman , Mustagir Md. Golam , Rana Juwel , Haque Md. Rajwanul , Rahman Md. Mosfequr
Published: April 2020

Background

With the exponential increase in coronavirus disease 2019 (COVID-19) worldwide, an increasing proportion of pregnant women are now infected during their pregnancy. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during their pregnancy.

Methods

Four databases (Medline, Web of Science, Scopus, and CINAHL) were searched on March 25, 2020, using the following keywords: “COVID-19”, “nCoV-2019”, and “coronavirus.” Articles included if they reported either the symptoms, treatments for the women who had been infected with the COVID-19 during their pregnancy or pregnancy outcomes. The selected articles’ results were summarized employing a narrative synthesis approach.

Results

A total of nine studies were selected for this study, comprising 101 infected pregnant women. Other than the infected general population, infected pregnant women reported different symptoms; however, fever (66.7%), cough (39.4%), fatigue (15.2%), and breathing difficulties (14.1%) were common. Infected pregnant women were given different treatments than the general infected population. The C-section was a common (83.9%) mode of delivery among infected pregnant women, and a higher proportion of births were preterm births (30.4%) and low birth weight (17.9%).

Conclusions

Pregnant infected women had different symptoms, and they were given dissimilar treatments than the general infected population. Healthcare providers may have appropriately informed about these symptoms and treatments. They, therefore, would be able to handle infection during pregnancy effectively, which would reduce common adverse consequences among infected pregnant women.
Projected ICU and Mortuary load due to COVID-19 in Sydney
Authors: Francis Andrew , Guo Yi , Hurley Paul , Obst Oliver , Park Laurence , Tanaka Mark , Thomson Russell , Wang X. Rosalind
Published: April 2020

The spread of COVID-19 is expected to put a large strain on many hospital resources, including ICU bed space, and mortuary capacity. In this report we study the possible demands on ICU and mortuary capacity in Sydney, Australia, using an adapted SEIR epidemiological model.
Simple model for Covid-19 epidemics – back-casting in China and forecasting in the US
Authors: Hermanowicz Slav W.
Published: April 2020

Abstract and Findings

In our previous work, we analyze, in near-real time, evolution of Covid-19 epidemic in China for the first 22 days of reliable data (up to February 6, 2020). In this work, we used the data for the whole 87 days (up to March 13, 2020) in China and the US data available till March 31 (day 70) for systematic evaluation of the logistic model to predict epidemic growth. We sequentially estimated sets of model parameters (maximum number of casesK, growth rater, and half-timet0) and the epidemic “end time”t95(defined as the time when the number of cases, predicted or actual, reached 95% of the maximum). The estimates of these parameters were done for sequences of reported cases growing daily (back-casting for China and forecasting for the US). In both countries, the estimates ofKgrew very much in time during the exponential and nearly exponential phases making longer term forecasting not reliable. For the US, the current estimate of the maximum number of casesKis about 265,000 but it is very likely that it will grow in the future. However, running estimates of the “end time”t95were in a much smaller interval for China (60 – 70 daysvs. the actual value of 67). For the US, the values estimated from the data sequences going back two weeks from now range from 70 to 80 days. If the behavior of the US epidemic is similar to the previous Chinese development, thenumber of reported casescould reach amaximum around April 10 to 14.
Versatile workflow for cell type resolved transcriptional and epigenetic profiles from cryopreserved human lung
Authors: Llamazares Prada M , Espinet E , Mijosek V , Schwartz U , Waszak SM , Lutsik P , Tamas R , Richter M , Behrendt A , Pohl S , Benz N , Muley T , Warth A , Heußel CP , Winter H , Herth F , Mertens T , Karmouty-Quintana H , Koch I , Benes V , Korbel JO , Trumpp A , Wyatt D , Stahl H , Plass C , Jurkowska RZ
Published: April 2020

The complexity of the lung microenvironment together with changes in cellular composition during disease progression make it exceptionally hard to understand the molecular mechanisms leading to the development of chronic lung diseases. Although recent advances in cell type resolved and single-cell sequencing approaches hold great promise for studying complex diseases, their implementation greatly relies on local access to fresh tissue, as traditional methods to process and store tissue do not allow viable cell isolation. To overcome these hurdles, we developed a novel, versatile workflow that allows long-term storage of human lung tissue with high cell viability, permits thorough sample quality check before cell isolation, and is compatible with next generation sequencing-based profiling, including single-cell approaches. We demonstrate that cryopreservation is suitable for isolation of multiple cell types from different lung locations and is applicable to both healthy and diseased tissue, including COPD and tumor samples. Basal cells isolated from cryopreserved airways retain the ability to differentiate, indicating that cellular identity is not altered by cryopreservation. Importantly, using RNA sequencing (RNA-seq) and Illumina EPIC Array, we show that genome-wide gene expression and DNA methylation signatures are preserved upon cryopreservation, emphasizing the suitability of our workflow for -omics profiling of human lung cells. In addition, we obtained high-quality single-cell RNA sequencing data of cells isolated from cryopreserved human lung, demonstrating that cryopreservation empowers single-cell approaches. Overall, thanks to its simplicity, our cryopreservation workflow is well-suited for prospective tissue collection by academic collaborators and biobanks, opening worldwide access to human tissue.
Computational target fishing by mining transcriptional data using a novel Siamese spectral-based graph convolutional network
Authors: Zhong Feisheng , Wu Xiaolong , Li Xutong , Wang Dingyan , Fu Zunyun , Liu Xiaohong , Wan XiaoZhe , Yang Tianbiao , Luo Xiaomin , Chen Kaixian , Jiang Hualiang , Zheng Mingyue
Published: April 2020

Computational target fishing aims to investigate the mechanism of action or the side effects of bioactive small molecules. Unfortunately, conventional ligand-based computational methods only explore a confined chemical space, and structure-based methods are limited by the availability of crystal structures. Moreover, these methods cannot describe cellular context-dependent effects and are thus not useful for exploring the targets of drugs in specific cells. To address these challenges, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. Using a benchmark set, the model achieved impressive target inference results compared with previous methods such as Connectivity Map and ProTINA. More importantly, the powerful generalization ability of the model observed with the external LINCS phase II dataset suggests that the model is an efficient target fishing or repositioning tool for bioactive compounds.
Changes in the abundance of Danish orchids over the past 30 years
Authors: Damgaard Christian , Moeslund Jesper Erenskjold , Wind Peter
Published: April 2020

Orchid abundance data collected over the past 30 years (1987-2016) from 440 sites within the National Orchid Monitoring Program were analysed to quantify the population trends of orchids in Denmark, and the underlying reasons for the observed population trends were analysed and discussed. Twenty of the 45 monitored Danish orchids showed a significant decrease in abundance over the past 30 years (16, if only orchids with at least 50 observations each were selected), thus corroborating the previous observations of declining orchid abundances at European scale. Generally, there was a significant negative effect of overgrowing with tall-growing herbs and shrubs on the abundance of Danish orchids mainly caused by change of farming practises, as extensive management, such as grazing or mowing of light-open grassland areas, has decreased.