bluuebunny/crossref_metadata_2025 huggingface dataset:
Partnerships to Take on Climate Change: Adaptation Forestry and Conifer Strongholds Projects in the Northwoods, Minnesota, USA
Authors: White Mark A , Cornett Meredith W , Frerker Katie , Etterson Julie R
Published: March 2020

Northeastern Minnesota forests are vulnerable to declines in boreal tree species at their southern range limits. Temperate tree species may have a competitive advantage in this region as the climate warms. Enhancing the adaptive capacity of northern forests requires a multifaceted approach, one that involves cooperative relations given the region’s complex ownership patterns. In this context, a nongovernment conservation organization and public land-management agencies are partnering to test climate-informed forest management approaches, including: (1) Resilience, targeting northern conifer planting at “climate-resilient sites” with suitable microclimates to sustain boreal species over time; (2) Transition, catalyzing the shift to a temperate forest matrix using within-range plantings of native, climate-adapted tree species. Deployed together, Resilience and Transition strategies can help the Northwoods shift towards future forest conditions. Results from this work will help land managers make informed decisions about forest management and enhance landscape resilience in a changing climate.
Scrotal abscess after a perforated appendicitis
Authors: Keyes Jonathan , Casas-Melley Adela T , Liu Cherry , Epelman Monica S , Ellsworth Pamela I
Published: March 2020

Although perforated appendicitis in pediatric patients can result in a diverse array of complications, scrotal abscess is a rarely documented phenomenon. We present a case of acute scrotum after laparoscopic appendectomy. A retrospective review of prior literature on scrotal abscess secondary to perforated appendicitis was performed via PubMed to review the clinical presentation, etiology, type of treatment and outcome of pediatric patients. Patients without a patent processus vaginalis still require vigilant follow-up postoperatively to ensure timely intervention if scrotal pain develops during recovery.
Transcriptomics in Erigeron canadensis reveals rapid photosynthetic and hormonal responses to auxin herbicide application
Authors: McCauley Cara L , McAdam Scott A M , Bhide Ketaki , Thimmapuram Jyothi , Banks Jo Ann , Young Bryan G
Published: March 2020

The perception pathway for endogenous auxin has been well described, yet the mode of action of synthetic auxin herbicides, used for >70 years, remains uncharacterized. We utilized transcriptomics and targeted physiological studies to investigate the unknown rapid response to synthetic auxin herbicides in the globally problematic weed species Erigeron canadensis. Synthetic auxin herbicide application consistently and rapidly down-regulated the photosynthetic machinery. At the same time, there was considerable perturbation to the expression of many genes related to phytohormone metabolism and perception. In particular, auxin herbicide application enhanced the expression of the key abscisic acid biosynthetic gene, 9-cis-epoxycarotenoid deoxygenase (NCED). The increase in NCED expression following auxin herbicide application led to a rapid biosynthesis of abscisic acid (ABA). This increase in ABA levels was independent of a loss of cell turgor or an increase in ethylene levels, both proposed triggers for rapid ABA biosynthesis. The levels of ABA in the leaf after auxin herbicide application continued to increase as plants approached death, up to >3-fold higher than in the leaves of plants that were drought stressed. We propose a new model in which synthetic auxin herbicides trigger plant death by the whole-scale, rapid, down-regulation of photosynthetic processes and an increase in ABA levels through up-regulation of NCED expression, independent of ethylene levels or a loss of cell turgor.
Traceability mining between unit test and source code based on textual analysis applied to software systems
Authors: Arshia Amir Hossein , Rasekh Amir Hossein , Moosavi Mohammad Reza , Fakhrahmad Seyed Mostafa , Sadreddini Mohammad Hadi
Published: March 2020

Correctness of the designed system is one of the most important issues in the software development process. Therefore, various tests have been defined and designed to help software teams develop software with little or no problem. Finding a proper link between test class and the class under the test is an important but difficult task. Finding this relation helps the developers to conduct regression tests more efficiently. In this paper, we seek to propose a model for recovering traceable links between test classes and the classes under the test. The proposed method encompasses three parts: (1) method for extracting keywords and the measure of similarity of a specific part of code, (2) backward chain method based on a rule-based system, (3) using hybrid model to find traceable links between test classes and the code under test. This study uses three open-source and one industrial source projects to conduct experiments. The results are satisfactory compared to previous studies.
Making top-heavy IMFs from canonical IMFs near the Galactic Centre
Authors: Park So-Myoung , Goodwin Simon P , Kim Sungsoo S
Published: March 2020

We show that dynamical evolution in a strong (Galactic Centre-like) tidal field can create clusters that would appear to have very top-heavy initial mass functions (IMFs). The tidal disruption of single star-forming events can leave several bound ‘clusters’ spread along 20 pc of the orbit within 1–2 Myr. These surviving (sub)clusters tend to contain an overabundance of massive stars, with low-mass stars tending to be spread along the whole ‘tidal arm’. Therefore, observing a cluster in a strong tidal field with a top-heavy IMF might well not mean the stars were formed with a top-heavy IMF.
Uncovering the orbital dynamics of stars hidden inside their powerful winds: application to η Carinae and RMC 140
Authors: Grant David , Blundell Katherine , Matthews James
Published: March 2020

Determining accurate orbits of binary stars with powerful winds is challenging. The dense outflows increase the effective photospheric radius, precluding direct observation of the Keplerian motion; instead, the observables are broad lines emitted over large radii in the stellar wind. Our analysis reveals strong, systematic discrepancies between the radial velocities extracted from different spectral lines: the more extended a line’s emission region, the greater the departure from the true orbital motion. To overcome these challenges, we formulate a novel semi-analytical model that encapsulates both the star’s orbital motion and the propagation of the wind. The model encodes the integrated velocity field of the out-flowing gas in terms of a convolution of past motion due to the finite flow speed of the wind. We test this model on two binary systems. (1) For the extreme case η Carinae, in which the effects are most prominent, we are able to fit the model to 10 Balmer lines from H α to H κ concurrently with a single set of orbital parameters: time of periastron T0 = 2454848 (JD), eccentricity e = 0.91, semi-amplitude $k=69 \, \rm {\, km \, s^{-1}}$, and longitude of periastron ω = 241°. (2) For a more typical case, the Wolf–Rayet star in RMC 140, we demonstrate that for commonly used lines, such as He ii and N iii/iv/v, we expect deviations between the Keplerian orbit and the predicted radial velocities. Our study indicates that corrective modelling, such as presented here, is necessary in order to identify a consistent set of orbital parameters, independent of the emission line used, especially for future high accuracy work.
Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes
Authors: Crespo Marion , Damont Annelaure , Blanco Melina , Lastrucci Emmanuelle , Kennani Sara El , Ialy-Radio Côme , Khattabi Laila El , Terrier Samuel , Louwagie Mathilde , Kieffer-Jaquinod Sylvie , Hesse Anne-Marie , Bruley Christophe , Chantalat Sophie , Govin Jérôme , Fenaille François , Battail Christophe , Cocquet Julie , Pflieger Delphine
Published: March 2020

Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.
Phosphoinositide 3-kinase γ deficiency attenuates kidney injury and fibrosis in angiotensin II–induced hypertension
Authors: An Changlong , Wen Jia , Hu Zhaoyong , Mitch William E , Wang Yanlin
Published: March 2020

Background

We have shown that the CXCL16/CXCR6 axis plays a critical role in recruiting inflammatory cells and bone marrow-derived fibroblasts into the kidney leading to renal injury and fibrosis. However, the underlying signaling mechanisms are not known.

Methods

In the present study, we examined the role of phosphoinositide-3 kinase γ (PI3Kγ) signaling in the recruitment of inflammatory cells and bone marrow-derived fibroblasts into the kidney and development of renal injury and fibrosis in an experimental model of hypertension induced by angiotensin II.

Results

Blood pressure was comparable between wild-type (WT) and PI3Kγ knockout (KO) mice at baseline. Angiotensin II treatment led to an increase in blood pressure that was similar between WT and PI3Kγ KO mice. Compared with WT mice, PI3Kγ KO mice were protected from angiotensin II-induced renal dysfunction and injury and developed less proteinuria. PI3Kγ deficiency suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidney and inhibited total collagen deposition and extracellular matrix protein production in the kidney in response to angiotensin II. PI3Kγ deficiency inhibited the infiltration of F4/80+ macrophages and CD3+ T cells into the kidney and reduced gene expression levels of pro-inflammatory cytokines in the kidney following angiotensin II treatment. Finally, inhibition of PI3Kγ suppressed CXCL16-induced monocyte migration in vitro.

Conclusion

These results indicate that PI3Kγ mediates the influx of macrophages, T cells and bone marrow-derived fibroblasts into the kidney resulting in kidney injury and fibrosis.
Heterogeneous Taxes and Limited Risk Sharing: Evidence from Municipal Bonds
Authors: Babina Tania , Jotikasthira Chotibhak , Lundblad Christian , Ramadorai Tarun
Published: March 2020

We evaluate the impacts of tax policy on asset returns using the U.S. municipal bond market. In theory, tax-induced ownership segmentation limits risk sharing, creating downward-sloping regions of the aggregate demand curve for the asset. In the data, cross-state variation in tax privilege policies predicts differences in in-state ownership of local municipal bonds; the policies create incentives for concentrated local ownership. High tax privilege states have muni bond yields that are more sensitive to variations in supply and local idiosyncratic risk. The effects are stronger when local investors face correlated background risk and/or diminishing marginal nonpecuniary benefits from holding local assets.
Facet joint ankylosis in r-axSpA: detection and 2-year progression on whole spine low-dose CT and comparison with syndesmophyte progression
Authors: Stal Rosalinde , van Gaalen Floris , Sepriano Alexandre , Braun Juergen , Reijnierse Monique , van den Berg Rosaline , van der Heijde Désirée , Baraliakos Xenofon
Published: March 2020

Objectives

To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (ldCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression of facet joint ankylosis and syndesmophytes.

Methods

Patients with r-axSpA from the Sensitive Imaging in Ankylosing Spondylitis (SIAS) cohort underwent ldCT at baseline (n = 60) and 2 years (n = 53). Facet joints (right and left, levels C2-S1) were scored as ankylosed, not ankylosed or unable to assess. Joints that were frequently poorly visible (>15% missing), were excluded. Inter-reader reliability on the patient level was assessed with intraclass correlation coefficients (ICCs) and smallest detectable change (SDC). Ankylosis was assessed at joint level and patient level for both timepoints. Syndesmophytes were assessed with CT syndesmophyte score.

Results

Levels C5-T2 were difficult to assess and excluded from all further analyses. Facet joint ICCs were good to excellent for status scores (0.72–0.93) and poor to excellent for progression scores (0.10–0.91). Facet joint ankylosis was detected at every level but most frequently in the thoracic joints. In total, 48% of patients showed 2-year progression. Most progression occurred in the thoracic segment. Using SDCs as cutoff, 18% of patients had progression of facet joint ankylosis only, whereas 20% of patients had progression of syndesmophytes only.

Conclusion

This is the first study evaluating facet joints in the whole spine by ldCT in r-axSpA. Facet joint ankylosis was detected most often in the thoracic spine. Assessing facet joints in addition to syndesmophytes detected substantially more patients with damage progression over two years.
CONSTRUCTION AND VALIDATION OF IN VITRO DOSE–RESPONSE CALIBRATION CURVE USING DICENTRIC CHROMOSOME ABERRATION
Authors: Mirrezaei Ehsan , Setayeshi Saeed , Zakeri Farideh , Baradaran Samaneh
Published: March 2020

Cytogenetic biodosimetry is a well-known method for quantifying the absorbed dose based on measuring biological radiation effects. To correlate the induced chromosomal abberrations with the absorbed dose of the individuals, a reliable dose–response calibration curve should be established. This study aimed to use frequencies and distributions of radiation-induced dicentric chromosome aberrations to develop a standard dose–response calibration curve. Peripheral blood samples taken from six male donors irradiated by an X-ray generator up to 4 Gy were studied. Three different blood samples were irradiated by known doses, then scored blindly for verification of the proposed calibration curve. Dose estimation was also carried out for three real overexposed cases. The results showed good accordance with the other published curves. The constructed dose–response curve provides a reliable tool for biological dosimetry in accidental or occupational radiation exposures.
Functional heterogeneity of perceived control in feedback processing
Authors: Zheng Ya , Wang Mengyao , Zhou Shiyu , Xu Jing
Published: March 2020

Perceived control is a fundamental psychological function that can either boost positive affect or buffer negative affect. The current study addressed the electrophysiological correlates underlying perceived control, as exercised by choice, in the processing of feedback valence. Thirty-six participants performed an EEG choice task during which they received positive or negative feedback following choices made either by themselves or by a computer. Perceived control resulted in an enhanced reward positivity for positive feedback but increased theta power for negative feedback. Further, perceived control led to greater feedback P3 amplitude and delta power, regardless of feedback valence. These results suggest functional heterogeneity of perceived control in feedback processing as diverse as magnifying the reward signal, enhancing the need for control and increasing the motivational salience of outcome irrespective of valence.
The Global Politics of Medical Reform in Britain and Jamaica in the Early Nineteenth Century
Authors: Graham Aaron
Published: March 2020

Between 1826 and 1843, the medical practitioners of Jamaica engaged in a long and fraught campaign to create a College of Physicians and Surgeons. This campaign linked the island with global processes of medical and political reform, especially in Britain, and numerous studies have revealed the political barriers that faced efforts to reshape medical practices in this period. Yet, the metropole was also in a continuous dialogue with its colonial periphery. Existing work has looked at what this dialogue meant for the circulation of medical theories and practices, but equally important was the transmission of medical institutions, which provided structures for their development and application. The campaign in Jamaica offers an important case study of the complex process by which medical institutions spread in this period and reveals both the imperial aspects of medical and social reform in Jamaica and the colonial aspects of medical reform in Britain.
Gender Equality Prior to and Following Separation: Nordic and Liberal Policy Inconsistencies
Authors: Hakovirta Mia , Cook Kay , Sinclair Sarah
Published: March 2020

We compare family policy in Australia and Finland, focusing on child support as interrogating how gender equality ideals and realities play out when families diverge from the dual-parent model. Despite Finland’s de-gendered leave and employment policy, a gender wage gap continues to position mothers as primary carers. In Australia, pre-separation policies are gendered in that leave benefits position mothers as primary carers. In both countries, child support policy took the opposite approach. Finland’s child support policy provides less incentive for the father to take care of children post-separation.
Future directions for implementation science at the National Cancer Institute: Implementation Science Centers in Cancer Control
Authors: Oh April , Vinson Cynthia A , Chambers David A
Published: March 2020

The National Cancer Institute (NCI) Cancer Moonshot initiative seeks to accelerate cancer research for the USA. One of the scientific priorities identified by the Moonshot’s Blue Ribbon Panel (BRP) of scientific experts was the implementation of evidence-based approaches. In September 2019, the NCI launched the Implementation Science Centers in Cancer Control (ISC3 or “Centers”) initiative to advance this Moonshot priority. The vision of the ISC3 is to promote the development of research centers to build capacity and research in high-priority areas of cancer control implementation science (e.g., scale-up and spread, sustainability and adaptation, and precision implementation), build implementation laboratories within community and clinical settings, improve the state of measurement and methods, and improve the adoption, implementation, and sustainment of evidence-based cancer control interventions. This paper highlights the research agenda, vision, and strategic direction for these Centers and encourages transdisciplinary scientists to learn more about opportunities to collaborate with these Centers.
Sensitivity of Puccinia graminis f. sp. tritici Isolates From China to Triadimefon and Cross-Resistance Against Diverse Fungicides
Authors: Wu Xianxin , Bian Qiang , Lin Qiujun , Sun Qian , Ni Xinyu , Xu Xiaofeng , Qiu Yongchun , Xuan Yuanhu , Cao Yuanyin , Li Tianya
Published: March 2020

Wheat stem rust caused by Puccinia graminis f. sp. tritici is an important wheat disease with sudden and devastating characteristics. The appearance and spread of new P. graminis f. sp. tritici races (Ug99, TKTTF, and TTTTF) have once again renewed the interest in the prevention and control of wheat stem rust. Fungicides can effectively control the epidemics of this disease in a short period of time. However, the fungal pathogen is prone to developing resistance. Therefore, we collected 89 isolates of P. graminis f. sp. tritici from four provinces in China and used the spore germination method to test the sensitivity of the isolates to fungicide triadimefon. Seven relatively triadimefon-sensitive isolates and six relatively triadimefon-resistant isolates were further tested for sensitivity to fungicides carbendazim, mancozeb, thiophanate-methyl, and kresoxim-methyl. The results showed that the mean concentration for 50% of maximal effect of the isolates to triadimefon was 16.14 mg·liter−1, and the mean resistance factor was 4.48. Only 29 isolates were resistant to triadimefon in which 27 isolates had low levels of resistance and 2 isolates had moderate levels of resistance. However, most of the 89 isolates had no resistance to triadimefon. There was a positive correlation between resistance to triadimefon and carbendazim, but there was no cross-resistance between triadimefon resistance with thiophanate-methyl or kresoxim-methyl resistance. This study provides valuable information for managing fungicide resistant isolates of P. graminis f. sp. tritici.
Bioactivity of the Novel Fungicide SYP-14288 Against Plant Pathogens and the Study of its Mode of Action Based on Untargeted Metabolomics
Authors: Wang Zhiwen , Dai Tan , Peng Qin , Gao Xiang , Zhong Shan , Gao Huige , Liu Pengfei , Liu Xili
Published: March 2020

Plant disease is a major threat to crop production, and fungicide application is one of the most effective methods to control plant disease. With emerging issues related to toxic residues and pathogen resistance, new fungicides with novel modes of action are urgently needed. SYP-14288 is a novel fungicide that could efficiently promote respiration and inhibit ATP biosynthesis in target organisms, but its bioactivity against various plant pathogens and exact mode of action are still unknown. In this study, we found that SYP-14288 is highly effective against 31 important plant pathogens belonging to a range of taxonomic groups. In addition, SYP-14288 has demonstrated excellent activity against all life stages of the important fungal plant pathogen Magnaporthe oryzae and is especially effective during the pathogen’s high energy consumption stages. SYP-14288 showed good preventative control efficacy against pepper blight and rice blast in the greenhouse and field, respectively. In an untargeted metabolomics assay designed to determine the exact mode of action of SYP-14288, significant changes occurred in 25 metabolites, with the accumulation of seven fatty acid metabolites and a decrease in 18 starch and sugar metabolites (e.g., from the tricarboxylic acid cycle). This suggests that SYP-14288 is an uncoupling agent similar to 2,4-dinitrophenol, which can allow for accumulation of various fatty acids after destroying oxidative phosphorylation coupling, thereby inhibiting the growth of the phytopathogen. These results indicate that the novel uncoupler SYP-14288 is a promising agrochemical in plant disease management.
ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens
Authors: Suo Tao , Liu Xinjin , Feng Jiangpeng , Guo Ming , Hu Wenjia , Guo Dong , Ullah Hafiz , Yang Yang , Zhang Qiuhan , Wang Xin , Sajid Muhanmmad , Huang Zhixiang , Deng Liping , Chen Tielong , Liu Fang , Ke Xu , Liu Yuan , Zhang Qi , Liu Yingle , Xiong Yong , Chen Guozhong , Lan Ke , Chen Yu
Published: March 2020

Real time fluorescent quantitative PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load in patient throats and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, early treat, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 nucleic acid from 77 clinical throat swab samples, including 63 suspected outpatients with fever and 14 supposed convalescents who were about to discharge after treatment, and compared with RT-PCR in terms of the diagnostic accuracy. In this double-blind study, we tested, surveyed subsequently and statistically analyzed 77 clinical samples. According to our study, 26 samples from COVID-19 patients with RT-PCR negative were detected as positive by ddPCR. No FPRs of RT-PCR and ddPCR were observed. The sensitivity, specificity, PPV, NPV, NLR and accuracy were improved from 40% (95% CI: 27–55%), 100% (95% CI: 54–100%), 100%, 16% (95% CI: 13–19%), 0.6 (95% CI: 0.48–0.75) and 47% (95% CI: 33–60%) for RT-PCR to 94% (95% CI: 83–99%), 100% (95% CI: 48–100%), 100%, 63% (95% CI: 36–83%), 0.06 (95% CI: 0.02–0.18) and 95% (95% CI: 84–99%) for ddPCR, respectively. Moreover, 14 (42.9 %) convalescents still carry detectable SARS-CoV-2 after discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the current standard RT-PCR. It also suggests that the current clinical practice that the convalescent after discharge continues to be quarantined for at least 2 weeks is completely necessary which can prevent potential viral transmission.
68 Consecutive patients assessed for COVID-19 infection; experience from a UK regional infectious disease unit
Authors: Easom Nicholas , Moss Peter , Barlow Gavin , Samson Anda , Taynton Thomas , Adams Kate , Ivan Monica , Burns Phillipa , Gajee Kavitha , Eastick Kirstine , Lillie Patrick J
Published: March 2020

Clinical assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for the outbreak of COVID-19 respiratory illness, has been a major activity of infectious diseases services in the UK and elsewhere since the first report of cases in December 2019. We report our case series of 68 patients, reviewed by Infectious Diseases Consultants at a Regional Infectious Diseases Unit in the UK. We prospectively evaluated our service between the 29th Jan 2020 and 24th Feb 2020.

Demographic, clinical, epidemiological and laboratory data were collected. We have compared clinical features and subsequent diagnosis between well patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment.

Final microbiological diagnoses included SARS-CoV-2 (COVID-19), Mycoplasma pneumonia, influenza A, RSV, non SARS/MERS coronaviruses, rhinovirus/enterovirus. 9/68 were treated with antimicrobials, 15/68 were admitted to a negative pressure room of whom 5/68 were admitted solely due to an inability to isolate at home. Patients requiring either admission on clinical grounds or antimicrobials (14/68) were similar to those not requiring admission or antimicrobials, with modestly more fever and shortness of breath in the clinically admitted / antimicrobial group. The most commonly prescribed antimicrobials were doxycycline, moxifloxacin and oseltamivir.

The majority of patients had mild illness which did not require a clinical intervention to manage. This finding supports a community testing approach supported by clinicians to review the proportion of more unwell patients.
Risk estimation and prediction by modeling the transmission of the novel coronavirus (COVID-19) in mainland China excluding Hubei province
Authors: Wan Hui , Cui Jing-an , Yang Guo-jing
Published: March 2020

Background

In December 2019, an outbreak of coronavirus disease (COVID-19) was identified in Wuhan, China and, later on, detected in other parts of China. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in mainland China excluding Hubei province based on the published data and a novel mathematical model.

Methods

A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. COVID-19 daily data of mainland China excluding Hubei province, including the cumulative confirmed cases, the cumulative deaths, newly confirmed cases and the cumulative recovered cases for the period January 20th-March 3rd, 2020, were archived from the National Health Commission of China (NHCC). We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number Rc, as well as the effective daily reproduction ratio Re(t), of the disease transmission in mainland China excluding Hubei province.

Results

The estimation outcomes indicate that Rc is 3.36 (95% CI 3.20-3.64) and Re(t) has dropped below 1 since January 31st, 2020, which implies that the containment strategies implemented by the Chinese government in mainland China excluding Hubei province are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to the spread of disease for a longer time and more people would be infected, and may even cause epidemic or outbreak again. By calculating the effective reproduction ratio, we prove that the contact rate should be kept at least less than 30% of the normal level by April, 2020.

Conclusions

To ensure the epidemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in mainland China apart from Hubei province.
Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach
Authors: Aleta Alberto , Moreno Yamir
Published: March 2020

Our society is currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China - where the outbreak started - seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays being detected in multiple countries. Much is currently unknown about the natural history of the disease, such as a possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. Nonetheless, authorities have to take action and implement contention measures, even if not everything is known. To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work specifically refers to the situation in Spain as of February 28th, 2020, where a few dozens of cases have been detected. We implemented an SEIR-metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which although not efficacious for disease eradication, would produce as a second order effect a delay of several days in the raise of the number of infected cases.
Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence
Authors: Lussier Alexandre A. , Hawrilenko Matt , Wang Min-Jung , Choi Karmel W. , Cerutti Janine , Zhu Yiwen ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Dunn Erin C.
Published: March 2020

Background

Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13 years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depression trajectories assessed from childhood to adolescence.

Methods

Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample=7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms trajectories spanning 4 to 16.5 years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andme, Inc. We used MAGMA to identify gene-level associations with these measures.

Results

Youth were classified into 6 classes of depressive symptom trajectories: high/renitent (26.5% of youth), high/reversing (5.8%), childhood decrease (6.1%), late childhood peak (3%), adolescent spike (2.5%), and minimal symptoms (56.1%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level.

Conclusions

This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.
The effect of human mobility and control measures on the COVID-19 epidemic in China
Authors: Kraemer Moritz U.G. , Yang Chia-Hung , Gutierrez Bernardo , Wu Chieh-Hsi , Klein Brennan , Pigott David M. ,   open COVID-19 data working group, Plessis Louis du , Faria Nuno R. , Li Ruoran , Hanage William P. , Brownstein John S. , Layan Maylis , Vespignani Alessandro , Tian Huaiyu , Dye Christopher , Cauchemez Simon , Pybus Oliver G. , Scarpino Samuel V.
Published: March 2020

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.
Maximising information on smell, quantitative motor impairment and probable REM-sleep behaviour disorder in the prediction of Parkinson’s disease
Authors: Bestwick Jonathan P. , Auger Stephen D. , Schrag Anette E. , Grosset Donald G , Kanavou Sofia , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Noyce Alastair J.
Published: March 2020

Background

Hyposmia, motor impairment and probable REM-sleep behaviour disorder (RBD) are markers for Parkinson’s disease (PD). Proposed PD risk prediction models have dichotomised test results and applied likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance prediction models.

Methods

Smell and probable RBD data for PD patients were taken from the Tracking Parkinson’s study (n=1046). For motor impairment previously published data were supplemented (n=87). PREDICT-PD pilot study participants were the controls. Smell, motor impairment and RBD were assessed using the University of Pennsylvania Smell Identification Test (UPSIT), the Bradykinesia-Akinesia Incoordination (BRAIN) test and the REM sleep behaviour disorder Screening Questionnaire (RBDSQ). UPSIT and RBDSQ data were analysed using logistic regression to determine which items were predictive of PD, or using total scores. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or from score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated.

Results

Logistic regression modelling yielded a greater range of LRs. 16 odours were associated with PD; LRs ranged from 0.005-5511. 6 RBDSQ questions were associated with PD; LRs ranged from from 0.34-69. BRAIN test LRs ranged from 0.16-1311. For a 70% DR the FPR for the 16 odours was 2.4%, for 50% DRs, the BRAIN test FPR was 6.6% and 12.2% for the RBDSQ.

Conclusions

Maximising information on PD markers can potentially improve the ability of algorithms to detect PD by generating LRs with a larger range of values than using dichotomised results.
Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China
Authors: Qiu Chengfeng , Xiao Qian , Liao Xin , Deng Ziwei , Liu Huiwen , Shu Yuanlu , Zhou Dinghui , Deng Ye , Wang Hongqiang , Zhao Xiang , Zhou Jianliang , Wang Jin , Shi Zhihua , Long Da
Published: March 2020

Background

Cases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness.

Methods

Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test.

Results

Of the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 “generations” was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy.

Conclusions

Family but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.
Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses
Authors: Wang Ming , Fu Aisi , Hu Ben , Tong Yongqing , Liu Ran , Gu Jiashuang , Liu Jianghao , Jiang Wen , Shen Gaigai , Zhao Wanxu , Men Dong , Deng Zixin , Yu Lilei , Li Yan , Liu Tiangang
Published: March 2020

The ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS- CoV-2 and other respiratory viruses simultaneously within 6–10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.
Pinna-Imitating Microphone Directionality Improves Sound Localization and Discrimination in Bilateral Cochlear Implant Users
Authors: Fischer Tim , Schmid Christoph , Kompis Martin , Mantokoudis Georgios , Caversaccio Marco , Wimmer Wilhelm
Published: March 2020

Abstract

Objectives

To compare the sound-source localization, discrimination and tracking performance of bilateral cochlear implant users with omnidirectional (OMNI) and pinna-imitating (PI) microphone directionality modes.

Design

Twelve experienced bilateral cochlear implant users participated in the study. Their audio processors were fitted with two different programs featuring either the OMNI or PI mode. Each subject performed static and dynamic sound field spatial hearing tests in the horizontal plane. The static tests consisted of an absolute sound localization test and a minimum audible angle (MAA) test, which was measured at 8 azimuth directions. Dynamic sound tracking ability was evaluated by the subject correctly indicating the direction of a moving stimulus along two circular paths around the subject.

Results

PI mode led to statistically significant sound localization and discrimination improvements. For static sound localization, the greatest benefit was a reduction in the number of front-back confusions. The front-back confusion rate was reduced from 47% with OMNI mode to 35% with PI mode (p = 0.03). The ability to discriminate sound sources at the sides was only possible with PI mode. The MAA value for the sides decreased from a 75.5 to a 37.7-degree angle when PI mode was used (p < 0.001). Furthermore, a non-significant trend towards an improvement in the ability to track sound sources was observed for both trajectories tested (p = 0.34 and p = 0.27).

Conclusions

Our results demonstrate that PI mode can lead to improved spatial hearing performance in bilateral cochlear implant users, mainly as a consequence of improved front-back discrimination with PI mode.
AI boosted molecular MRI for apoptosis detection in oncolytic virotherapy
Authors: Perlman Or , Ito Hirotaka , Herz Kai , Shono Naoyuki , Nakashima Hiroshi , Zaiss Moritz , Chiocca E. Antonio , Cohen Ouri , Rosen Matthew S. , Farrar Christian T.
Published: March 2020

Oncolytic virotherapy is a promising treatment for high mortality cancers1. Non-invasive imaging of the underlying molecular processes is an essential tool for therapy optimization and assessment of viral spread, innate immunity, and therapeutic response2, 3. However, previous methods for imaging oncolytic viruses did not correlate with late viral activity4or had poor sensitivity and specificity5. Similarly, methods developed to image treatment response, such as apoptosis, proved to be slow, nonspecific, or require the use of radioactive or metal-based contrast agents6–8. To date, no method has been widely adopted for clinical use. We describe here a new method for fast magnetic resonance molecular imaging with quantitative proton chemical-exchange specificity to monitor oncolytic virotherapy treatment response. A deep neural network enabled the computation of quantitative biomarker maps of protein and lipid/macromolecule concentrations as well as intracellular pH in a glioblastoma multiforme mouse brain tumor model. Early detection of apoptotic response to oncolytic virotherapy, characterized by decreased cytosolic pH and protein synthesis, was observed in agreement with histology. Clinical translation was demonstrated in a normal human subject, yielding molecular parameters in good agreement with literature values9. The developed method is directly applicable to a wide range of pathologies, including stroke10, cancer11–13, and neurological disorders14, 15.
Optimization of psoriasis – like mouse models: A comparative study
Authors: Karamani Christina , Antoniadou Ivi Theodosia , Dimou Aikaterini , Andreou Evgenia , Kostakis Georgios , Sideri Asimina , Vitsos Andreas , Gkavanozi Athina , Sfiniadakis Ioannis , Skaltsa Helen , Papaioannou Georgios Theodoros , Maibach Howard , Rallis Michael
Published: March 2020

Psoriasis, a common chronic, autoimmune, inflammatory, relapsing disease should benefit from reliable and human relevant animal models in order to pre-clinically test drugs and approach their mechanism of action. Due to ease of use, convenience and low cost, imiquimod (IMQ) induced psoriasis-like model is widely utilized; however, are all mouse strains equivalent, is the hairless mouse utilizable and can the imiquimod model be further optimized? Under similar experimental conditions, common mouse strains (BALB/c, C57BL/6J, ApoE) and a new hairless strain (ApoE/SKH-hr2) as well as several inducers (IMQ, IMQ + Acetic Acid (AcOH) topical and IMQ +AcOH systemic) were compared by clinical, histopathological, biophysical and locomotor activity assessment. Results showed that BALB/c mice yielded optimal psoriasis-like phenotype with IMQ+AcOH topical treatment, C57BL/6J moderate, ApoE mild, while the ApoE/SKH-hr2 mice due to Munro abscess absence in histopathology analysis left doubts about the psoriasis-like acquisition. The locomotor activity of BALB/c mice treated with IMQ, IMQ+AcOH topically and IMQ+AcOH systemically, showed with all treatments, a decreased covered distance and rearing and an increased immobility. In conclusion, BALB/c appears an optimal psoriasis-like model when utilizing IMQ+AcOH topical application.
An Endocytic Capture Model for Skeletal Muscle T-tubule Formation
Authors: Hall Thomas E , Martel Nick , Ariotti Nicholas , Xiong Zherui , Lo Harriet P , Ferguson Charles , Rae James , Lim Ye-Wheen , Parton Robert G
Published: March 2020

The skeletal muscle T-tubule is a specialized membrane domain essential for coordinated muscle contraction that shows dysmorphology in a number of genetically inherited muscle diseases. However, in the absence of genetically tractable systems the mechanisms involved in T-tubule formation are unknown. Here, we have used the optically transparent and genetically tractable zebrafish system to probe T-tubule developmentin vivo. By combining live imaging with three-dimensional electron microscopy we derived a four-dimensional quantitative model for T-tubule formation. To elucidate the mechanisms involved in T-tubule formationin vivowe developed a quantitative screen for proteins that associate with and modulate early T-tubule formation including an overexpression screen of the entire zebrafish Rab protein family. We propose a new endocytic capture model involving i) formation of dynamic endocytic tubules at transient nucleation sites on the sarcolemma ii) stabilization by myofibrils/sarcoplasmic reticulum and iii) delivery of membrane from the recycling endosome and Golgi complex.