bluuebunny/crossref_metadata_2025 huggingface dataset:
Meconium androgens are correlated with ASD-related phenotypic traits in early childhood
Authors: Terloyeva Dina , Frey Alexander J. , Park Bo Y. , Kauffman Elizabeth M. , Mathew Leny , Bostwick Anna , Varner Erika L. , Lee Brian K. , Croen Lisa A. , Fallin Margaret D. , Hertz-Picciotto Irva , Newschaffer Craig J. , Lyall Kristen , Snyder Nathaniel W.
Published: March 2020

Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid and cord blood, with mixed results. To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA) and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Autism traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). 137 children (61 males, 76 females) had data on both outcomes and meconium androgen measurements. Separate robust linear regressions between each of the log-transformed androgens and log-transformed AOSI and SRS scores revealed three-way interaction between sex of the child, sex of the proband, and androgen concentration. In the adjusted analyses; t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores while u-T (P=0.004) and u-DHEA (P=0.007) were positively associated with SRS total score among females with female probands. Additionally, higher concentrations of u-T (P=0.01) and t-T (P=0.01) predicted higher SRS total score in males with male probands.

Significance

Using a prospective pregnancy cohort enriched for autism risk, we investigated prenatal androgen exposure measured from meconium as a risk factor for autism-related traits. Several meconium androgens were positively correlated with autism-related traits. In addition, we found a strong positive association between autism traits in the sub-group of individuals with an older female sibling with autism extending a previous finding based on cord blood measures in the same cohort. This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of the proband should be considered as a biological variable in relevant studies.
Which assessments are used to analyze neuromuscular control by electromyography after an anterior cruciate ligament injury to determine readiness to return to sports? A systematic review
Authors: Blasimann Angela , Koenig Irene , Baert Isabel , Baur Heiner , Vissers Dirk
Published: March 2020

Background

Adequate neuromuscular control of the knee could be one element to prevent secondary injuries after an anterior cruciate ligament (ACL) injury. To assess neuromuscular control in terms of time, amplitude and activity, electromyography (EMG) is used. However, it is unclear which assessments using EMG could be used for a safe return to sports (RTS). Therefore, we aimed to summarize EMG-related assessments for neuromuscular control of the knee in adult patients after an ACL injury to decide upon readiness for RTS.

Methods

This systematic review followed guidelines of Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane recommendations. MEDLINE/PubMed, EMBASE, CINAHL, Cochrane Library, Physiotherapy Evidence Database (PEDro), SPORTDiscus and the Web of Science were searched from inception to March 2019 and updated in November 2020. Studies identifying electromyographic assessments for neuromuscular control during dynamic tasks in adult, physically active patients with an anterior cruciate ligament injury were eligible and qualitatively synthesized. Two independent reviewers used a modified Downs and Black checklist to assess risk of bias of included studies.

Results

From initially 1388 hits, 38 mainly cross-sectional, case-controlled studies were included for qualitative analysis. Most studies provided EMG outcomes of thigh muscles during jumping, running or squatting. Outcomes measures described neuromuscular control of the knee in domains of time, amplitude or activity. Risk of bias was medium to high due to an unclear description of participants and prior interventions, confounding factors and incompletely reported results.

Conclusions

Despite a wide range of EMG outcome measures for neuromuscular control, none was used to decide upon return to sports in these patients. Additional studies are needed to define readiness towards RTS by assessing neuromuscular control in adult ACL patients with EMG. Further research should aim at finding reliable and valid, EMG-related variables to be used as diagnostic tool for neuromuscular control. Moreover, future studies should aim at more homogenous groups including adequately matched healthy subjects, evaluate gender separately and use sport-specific tasks.

Registration

The protocol for this systematic review was indexed beforehand in the International Prospective Register of Systematic Reviews (PROSPERO) and registered as CRD42019122188.
A data-driven assessment of early travel restrictions related to the spreading of the novel COVID-19 within mainland China
Authors: Aleta Alberto , Hu Qitong , Ye Jiachen , Ji Peng , Moreno Yamir
Published: March 2020

Two months after it was firstly reported, the novel coronavirus disease COVID-19 has already spread worldwide. However, the vast majority of reported infections have occurred in China. To assess the effect of early travel restrictions adopted by the health authorities in China, we have implemented an epidemic metapopulation model that is fed with mobility data corresponding to 2019 and 2020. This allows to compare two radically different scenarios, one with no travel restrictions and another in which mobility is reduced by a travel ban. Our findings indicate that i) travel restrictions are an effective measure in the short term, however, ii) they are ineffective when it comes to completely eliminate the disease. The latter is due to the impossibility of removing the risk of seeding the disease to other regions. Our study also highlights the importance of developing more realistic models of behavioral changes when a disease outbreak is unfolding.
Estimating the generation interval for COVID-19 based on symptom onset data
Authors: Tapiwa Ganyani , Cécile Kremer , Dongxuan Chen , Andrea Torneri , Christel Faes , Jacco Wallinga , Niel Hens
Published: March 2020

Background

Estimating key infectious disease parameters from the COVID-19 outbreak is quintessential for modelling studies and guiding intervention strategies. Whereas different estimates for the incubation period distribution and the serial interval distribution have been reported, estimates of the generation interval for COVID-19 have not been provided.

Methods

We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates we obtained the proportions pre-symptomatic transmission and reproduction numbers.

Results

The mean generation interval was 5.20 (95%CI 3.78-6.78) days for Singapore and 3.95 (95%CI 3.01-4.91) days for Tianjin, China when relying on a previously reported incubation period with mean 5.2 and SD 2.8 days. The proportion of pre-symptomatic transmission was 48% (95%CI 32-67%) for Singapore and 62% (95%CI 50-76%) for Tianjin, China. Estimates of the reproduction number based on the generation interval distribution were slightly higher than those based on the serial interval distribution.

Conclusions

Estimating generation and serial interval distributions from outbreak data requires careful investigation of the underlying transmission network. Detailed contact tracing information is essential for correctly estimating these quantities.
3D Deep Neural Network Segmentation of Intracerebral Hemorrhage: Development and Validation for Clinical Trials
Authors: Sharrock Matthew F. , Mould W. Andrew , Ali Hasan , Hildreth Meghan , Awad Issam A. , Hanley Daniel F. , Muschelli John
Published: March 2020

Intracranial hemorrhage (ICH) occurs when a blood vessel ruptures in the brain. This leads to significant morbidity and mortality, the likelihood of which is predicated on the size of the bleeding event. X-ray computed tomography (CT) scans allow clinicians and researchers to qualitatively and quantitatively diagnose hemorrhagic stroke, guide interventions and determine inclusion criteria of patients in clinical trials. There is no currently available open source, validated tool to quickly segment hemorrhage. Using an automated pipeline and 2D and 3D deep neural networks, we show that we can quickly and accurately estimate ICH volume with high agreement with time-consuming manual segmentation. The training and validation datasets include significant heterogeneity in terms of pathology, such as the presence of intraventricular (IVH) or subdural hemorrhages (SDH) as well as variable image acquisition parameters. We show that deep neural networks trained with an appropriate anatomic context in the network receptive field, can effectively perform ICH segmentation, but those without enough context will overestimate hemorrhage along the skull and around calcifications in the ventricular system. We trained with all data from a multi-center phase II study (n = 112) achieving a best mean and median Dice coefficient of 0.914 and 0.919, a volume correlation of 0.979 and an average volume difference of 1.7ml and root mean squared error of 4.7ml in 500 out-of-sample scans from the corresponding multi-center phase III study. 3D networks with appropriate anatomic context outperformed both 2D and random forest models. Our results suggest that deep neural network models, when carefully developed can be incorporated into the workflow of an ICH clinical trial series to quickly and accurately segment ICH, estimate total hemorrhage volume and minimize segmentation failures. The model, weights and scripts for deployment are located at https://github.com/msharrock/deepbleed. This is the first publicly available neural network model for segmentation of ICH, the only model evaluated with the presence of both IVH and SDH and the only model validated in the workflow of a series of clinical trials.
A mathematical model for estimating the age-specific transmissibility of a novel coronavirus
Authors: Zhao Ze-Yu , Zhu Yuan-Zhao , Xu Jing-Wen , Hu Qing-Qing , Lei Zhao , Rui Jia , Liu Xing-Chun , Wang Yao , Yang Meng , Luo Li , Yu Shan-Shan , Li Jia , Liu Ruo-Yun , Xie Fang , Su Ying-Ying , Chiang Yi-Chen , Su Yan-Hua , Zhao Ben-Hua , Chen Tian-Mu
Published: March 2020

Background

A novel coronavirus named as “SARS-CoV-2” has spread widely in many countries since December 2019, especially in China. This study aimed to quantify the age-specific transmissibility by using a mathematical model.

Methods

An age-specific susceptible – exposed – symptomatic – asymptomatic – recovered – seafood market (SEIARW) model was developed based on two suspected transmission routes (from market to person and person to person). The susceptible people from Wuhan City were divided into different age groups. We used the subscript i and j to represent age group 1 to 4 (i ≠ j; 1: ≤ 14 years; 2: 15-44 years; 3: 45-64 years; 4: ≥ 65 years) and 1 to 5 (i ≠ j; 1: ≤ 5 years; 2: 6-14 years; 3: 15-24 years; 4: 25-59 years; 4: ≥ 60 years), respectively. Data of reported COVID-19 cases were collected from one published literature from 26 November to 22 December, 2019 in Wuhan City, China. The age-specific transmissibility of the virus was estimated accordingly secondary attack rate (SAR).

Results

The age-specific SEIARW model fitted with the reported data well by dividing the population into four age groups (χ2 = 4.99 × 10−6, P > 0.999), and five age groups (χ2 = 4.85 × 10−6, P > 0.999). Based on the four-age-group SEIARW model, the highest transmissibility occurred from age group 2 to 3 (SAR23 = 17.56 per 10 million persons), followed by from age group 3 to 2 (SAR32 = 10.17 per 10 million persons). The lowest transmissibility occurred from age group 1 to 2 (SAR12 = 0.002 per 10 million persons). Based on the five-age-group SEIARW model, the highest transmissibility occurred from age group 4 to 5 (SAR45 = 12.40 per 10 million persons), followed by from age group 5 to 4 (SAR54 = 6.61 per 10 million persons). The lowest transmissibility occurred from age group 3 to 4 (SAR34 = 0.0002 per 10 million persons).

Conclusions

SARS-CoV-2 has high transmissibility among adults and elder people but low transmissibility among children and young people.
Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases
Authors: Oliveiros B , Caramelo L , Ferreira N C , Caramelo F
Published: March 2020

COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy. The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions. Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak.

In this study, an exponential model relating the number of accumulated confirmed cases and time was considered. The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed. Only China cases were considered, to control both cultural aspects and containment policies. Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China. Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression. Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen. The median value for each meteorological variable was computed, using the same time period; models with were selected. The rate of progression and doubling time were computed and used to fit a linear regression model. Models were evaluated using α = 0.05.

Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere. A 20°C increase is expected to delay the doubling time in 1.8 days. Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects.
Emotional responses and coping strategies of nurses and nursing college students during COVID-19 outbreak
Authors: Huang Long , Xu Fuming , Liu Hairong
Published: March 2020

Background

Affected by a Corona Virus Disease 2019 (COVID-19) outbreak, Since December 2019, there have been more than 76,000 cases of COVID-19 in China, causing more than 3,000 medical staff infections. Due to COVID-19 spreads quickly, is highly contagious, and can be fatal in severe cases, and there are no specific medicines, it poses a huge threat to the life and health of nurses and has a large impact on their emotional responses and coping strategies.

Methods

This study conducted an online questionnaire survey from February 1 to 9, 2020 to investigate the current state of emotional responses and coping strategies of nurses and college nursing students in Anhui Province. This study used a modified Brief COPE (Carver, 1997) and a emotional responses scale.

Results

The results found that women showed more severe anxiety and fear than men. Participants from cities showed more anxiety and fear than participants from rural, but rural participants showed more sadness than urban participants. The closer COVID-19 is to the participants, the stronger the anxiety and anger. Compared with Nursing college students, nurses have stronger emotional responses and are more willing to use Problem-focused coping. People may have a cycle of “the more fear, the more problem-focused coping”. And people may “The more angry, the more emotion-focused coping”, “the more problem-focused coping, the more anxious, the more angry, the more sadness”.

Conclusion

COVID-19 is a pressure source with great influence, both for individuals and for the social public groups. Different individuals and groups may experience different levels of psychological crisis, and those nurses at the core of the incident are affected. Hospitals should focus on providing psychological support to nurses and providing timely psychological assistance and training in coping strategies.Improving nurses’ ability to regulate emotions and effective coping strategies, providing a strong guarantee for resolutely winning the battle against epidemic prevention and control.
COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients
Authors: Song Cong-Ying , Xu Jia , He Jian-Qin , Lu Yuan-Qiang
Published: March 2020

BACKGROUND

Corona Virus Disease 2019 (COVID-19) is spreading worldwide. Effective screening for patients is important to limit the epidemic. However, some defects make the currently applied diagnosis methods are still not very ideal for early warning of patients. We aimed to develop a diagnostic model that allows for the quick screening of highly suspected patients using easy-to-get variables.

METHODS

A total of 1,311 patients receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleicacid detection were included, whom with a positive result were classified into COVID-19 group. Multivariate logistic regression analyses were performed to construct the diagnostic model. Receiver operating characteristic (ROC) curve analysis were used for model validation.

RESULTS

After analysis, signs of pneumonia on CT, history of close contact, fever, neutrophil-to-lymphocyte ratio (NLR), Tmax and sex were included in the diagnostic model. Age and meaningful respiratory symptoms were enrolled into COVID-19 early warning score (COVID-19 EWS). The areas under the ROC curve (AUROC) indicated that both of the diagnostic model (training dataset 0.956 [95%CI 0.935-0.977, P < 0.001]; validation dataset 0.960 [95%CI 0.919-1.0, P < 0.001]) and COVID-19 EWS (training dataset 0.956 [95%CI 0.934-0.978, P < 0.001]; validate dataset 0.966 [95%CI 0.929-1, P < 0.001]) had good discrimination capacity. In addition, we also obtained the cut-off values of disease severity predictors, such as CT score, CD8+ T cell count, CD4+ T cell count, and so on.

CONCLUSIONS

The new developed COVID-19 EWS was a considerable tool for early and relatively accurately warning of SARS-CoV-2 infected patients.
Impact of direct-to-consumer genetic testing on Australian clinical genetics services
Authors: Millward Michael , Tiller Jane , Bogwitz Michael , Kincaid Helen , Taylor Shelby , Trainer Alison H , Lacaze Paul
Published: March 2020

Purpose

The increasing popularity of direct-to-consumer genetic testing (DTCGT) is thought to be creating a burden on clinical genetic health services worldwide. However, no studies have collected recent evidence regarding the extent of this impact in Australia.

Methods

We administered an online survey to Australian clinical genetics services, asking questions related to DTCGT-related referrals received and outcomes over the past 10 years.

Results

Eleven publicly-funded clinical genetics services completed the survey, reporting over 100 DTCGT-related referrals. Most referrals (83%) were made by general practitioners seeking interpretation of DTCGT results. More than 30% of referrals related to imputed genetic risk estimates generated from third-party web-based software tools. Services reported low validation rates for DTCGT results (<10%). Procedures for managing DTCGT referrals and granting appointments were variable between services, with most services (8/11) lacking specific procedures.

Conclusion

Our study helps quantify the impact of DTCGT on clinical genetics services, and highlights the impact of imputed genetic risk estimates generated from third-party software.
The prevalence and influencing factors for anxiety in medical workers fighting COVID-19 in China: A cross-sectional survey
Authors: Liu Chen-Yun , Yang Yun-zhi , Zhang Xiao-Ming , Xu Xinying , Dou Qing-Li , Zhang Wen-Wu
Published: March 2020

Background

The COVID-19 outbreak caused by the SARS-Cov-2 virus has been sustained in China since December 2019, and could become a pandemic if we do not contain it. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the influencing factors on medical worker anxiety in China during the COVID-19 outbreak.

Methods

We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff from 10th February 2020 to 20th February 2020 in China using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, using the criteria of normal (≤49), mild (50-59), moderate (60- 70) and severe anxiety (≥70). We used multivariable linear regression to determine the factors (e.g., having direct contact treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status.

Results

Of 512 medical staff from China, 164 healthcare workers (32.03%) had had direct contact by treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers from moderate (1.36%) and four workers from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients saw higher anxiety scores than those who had not had direct contact (βvalue=2.33, CI: 0.65 −4.00; p=0.0068). Similar things were observed in medical staff from Hubei province, compared with those from other parts of China (β value=3.67, CI: 1.44 −5.89; p=0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (βvalue=4.44, CI: 1.55 −7.33; p=0.0028).

Conclusion

Our results highlight that government authorities should make early detection of the high risk of anxiety among medical staff a priority, and implement appropriate psychological intervention programs, to prevent medical staff from developing psychological disorders that could potentially exert an adverse effect on combating the COVID-19 epidemic.
Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19
Authors: Moore Shona C. , Penrice-Randal Rebekah , Alruwaili Muhannad , Dong Xiaofeng , Pullan Steven T. , Carter Daniel P. , Bewley Kevin , Zhao Qin , Sun Yani , Hartley Catherine , Zhou En-min , Solomon Tom , Beadsworth Michael B. J. , Cruise James , Bogaert Debby , Crook Derrick W. , Matthews David A. , Davidson Andrew D. , Mahmood Zana , Aljabr Waleed , Druce Julian , Vipond Richard T. , Ng Lisa F. P. , Renia Laurent , Openshaw Peter J. M. , Baillie J. Kenneth , Carroll Miles W. , Semple Malcolm G. , Turtle Lance , Hiscox Julian A.
Published: March 2020

COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality. Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium.
Direct RNA sequencing and early evolution of SARS-CoV-2
Authors: Taiaroa George , Rawlinson Daniel , Featherstone Leo , Pitt Miranda , Caly Leon , Druce Julian , Purcell Damian , Harty Leigh , Tran Thomas , Roberts Jason , Scott Nichollas , Catton Mike , Williamson Deborah , Coin Lachlan , Duchene Sebastian
Published: March 2020

Fundamental aspects of SARS-CoV-2 biology remain to be described, having the potential to provide insight to the response effort for this high-priority pathogen. Here we describe the first native RNA sequence of SARS-CoV-2, detailing the coronaviral transcriptome and epitranscriptome, and share these data publicly. A data-driven inference of viral genetic features and evolutionary rate is also made. The rapid sharing of sequence information throughout the SARS-CoV-2 pandemic represents an inflection point for public health and genomic epidemiology, providing early insights into the biology and evolution of this emerging pathogen.
A simplified calculation of the correlations between relatives
Authors: Smith Reginald D.
Published: March 2020

The correlations between relatives is one of the fundamental ideas and earliest success of quantitative genetics. Whether using genomic data to infer relationships between individuals or estimating heritability from correlations of phenotypes amongst relatives, understanding the theoretical genetic correlations is a common task. Calculating the correlations between arbitrary relatives in an outbred population, however, can be a careful and somewhat complex task for increasingly distant relatives. This paper introduces an equation based method that consolidates the results of path analysis and uses easily obtainable data from non-inbred pedigrees to allow the rapid calculation of additive or dominance correlations between relatives even in more complicated situations such as cousins sharing more than two grandparents and inbreeding.
LY6E impairs coronavirus fusion and confers immune control of viral disease
Authors: Pfaender Stephanie , Mar Katrina B. , Michailidis Eleftherios , Kratzel Annika , Hirt Dagny , V’kovski Philip , Fan Wenchun , Ebert Nadine , Stalder Hanspeter , Kleine-Weber Hannah , Hoffmann Markus , Hoffmann H. Heinrich , Saeed Mohsan , Dijkman Ronald , Steinmann Eike , Wight-Carter Mary , Hanners Natasha W. , Pöhlmann Stefan , Gallagher Tom , Todt Daniel , Zimmer Gert , Rice Charles M. , Schoggins John W. , Thiel Volker
Published: March 2020

Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized2. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoVin vitroandin vivo, knowledge that could help inform strategies to combat infection by emerging CoV.
Intra-molecular Electro-potential Circuit & ElectroNegatrode: Hypothesis, Algorithm & Implementation for universal indicative rule towards activity of biomolecules
Authors: Prakash Om
Published: March 2020

No universal indicative rule has been defined till now for activity & selectivity of biomolecules. This lacks very early perception about any molecule (specifically small molecule) in the biological system, beyond doing any experiment. The present study is all about hypothesizing, algorithm development and implementation of theoretical processing of 3D structure of biomolecules in the search of ground for developing perception about biomolecules individually or in combination of other biomolecules. The developed algorithm has been evaluated with small molecules and was found to be implementable as universal indicative rule towards activity & selectivity of biomolecules.
Estimating the scale of COVID-19 Epidemic in the United States: Simulations Based on Air Traffic Directly from Wuhan, China
Authors: Li Dalin , Lv Jun , Bowtin Gregory , Braun Jonathan , Cao Weihua , Li Liming , McGovern Dermot P.B.
Published: March 2020

Introduction

Coronavirus Disease 2019 (COVID-19) infection has been characterized by rapid spread and unusually large case clusters. It is important to have an estimate of the current state of COVID-19 epidemic in the U.S. to help develop informed public health strategies.

Methods

We estimated the potential scale of the COVID-19 epidemic (as of 03/01/2020) in the U.S. from cases ‘imported’ directly from Wuhan area. We used simulations based on transmission dynamics parameters estimated from previous studies and air traffic data from Wuhan to the U.S and deliberately built our model based on conservative assumptions. Detection and quarantine of individual COVID-19 cases in the U.S before 03/01/2020 were also taken into account. A SEIR model was used to simulate the growth of the number of infected individuals in Wuhan area and in the U.S.

Results

With the most likely model, we estimated that there would be 9,484 infected cases (90%CI 2,054-24,241) as of 03/01/2020 if no successful intervention procedure had been taken to reduce the transmissibility in unidentified cases. Assuming current preventive procedures have reduced 25% of the transmissibility in unidentified cases, the number of infected cases would be 1,043 (90%CI 107-2,474).

Conclusion

Our research indicates that, as of 03/01/2020., it is likely that there are already thousands of individuals in the US infected with SARS-CoV-2. Our model is dynamic and is available to the research community to further evaluate as the situation becomes clearer.
Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole
Authors: Xia Wei , Liao Jiaqiang , Li Chunhui , Li Yuanyuan , Qian Xi , Sun Xiaojie , Xu Hongbo , Mahai Gaga , Zhao Xin , Shi Lisha , Liu Juan , Yu Ling , Wang Meng , Wang Qianqian , Namat Asmagvl , Li Ying , Qu Jingyu , Liu Qi , Lin Xiaofang , Cao Shuting , Huan Shu , Xiao Jiying , Ruan Fengyu , Wang Hanjin , Xu Qing , Ding Xingjuan , Fang Xingjie , Qiu Feng , Ma Jiaolong , Zhang Yu , Wang Aizhen , Xing Yuling , Xu Shunqing
Published: March 2020

Background

The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others.

Methods

We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset.

Results

The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1±3.3 days, with the 2.5th and 97.5th percentiles at −1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period.

Conclusions

The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk.
Coronavirus in pregnancy and delivery: rapid review and expert consensus
Authors: Mullins E , Evans D , Viner RM , O’Brien P , Morris E
Published: March 2020

BACKGROUND

Person to person spread of COIVD-19 in the UK has now been confirmed. There are limited case series reporting the impact on women affected by coronaviruses (CoV) during pregnancy. In women affected by SARS and MERS, the case fatality rate appeared higher in women affected in pregnancy compared with non-pregnant women. We conducted a rapid, review to guide management of women affected by COVID -19 during pregnancy and developed interim practice guidance with the RCOG and RCPCH to inform maternity and neonatal service planning

METHODS

Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies or randomised-controlled trial describing women affected by coronavirus in pregnancy and on neonates. Data was extracted from relevant papers and the review was drafted with representatives of the RCPCH and RCOG who also provided expert consensus on areas where data were lacking

RESULTS

From 9964 results on PubMed and 600 on MedRxiv, 18 relevant studies (case reports and case series) were identified. There was inconsistent reporting of maternal, perinatal and neonatal outcomes across case reports and series concerning COVID-19, SARS, MERS and other coronaviruses. From reports of 19 women to date affected by COVID-19 in pregnancy, delivering 20 babies, 3 (16%) were asymptomatic, 1 (5%) was admitted to ICU and no maternal deaths have been reported. Deliveries were 17 by caesarean section, 2 by vaginal delivery, 8 (42%) delivered pre-term. There was one neonatal death, in 15 babies who were tested there was no evidence of vertical transmission.

CONCLUSIONS

Morbidity and mortality from COVID-19 appears less marked than for SARS and MERS, acknowledging the limited number of cases reported to date. Pre-term delivery affected 42% of women hospitalised with COVID-19, which may put considerable pressure on neonatal services if the UK reasonable worse-case scenario of 80% of the population affected is realised. There has been no evidence of vertical transmission to date. The RCOG and RCPCH have provided interim guidance to help maternity and neonatal services plan their response to COVID-19.
Evaluation of the secondary transmission pattern and epidemic prediction of COVID-19 in the four metropolitan areas of China
Authors: Su Longxiang , Hong Na , Zhou Xiang , He Jie , Ma Yingying , Jiang Huizhen , Han Lin , Chang Fengxiang , Shan Guangliang , Zhu Weiguo , Long Yun
Published: March 2020

Understanding the transmission dynamics of COVID-19 is crucial for evaluating its spread pattern, especially in metropolitan areas of China, as its spread can lead to secondary outbreaks outside Wuhan, the center of the new coronavirus disease outbreak. In addition, the experiences gained and lessons learned from China have the potential to provide evidence to support other metropolitan areas and large cities outside China with emerging cases. We used data reported from January 24, 2020, to February 23, 2020, to fit a model of infection, estimate the likely number of infections in four high-risk metropolitan areas based on the number of cases reported, and increase the understanding of the COVID-19 spread pattern. Considering the effect of the official quarantine regulations and travel restrictions for China, which began January 23∼24, 2020, we used the daily travel intensity index from the Baidu Maps app to roughly simulate the level of restrictions and estimate the proportion of the quarantined population. A group of SEIR model statistical parameters were estimated using Markov chain Monte Carlo (MCMC) methods and fitting on the basis of reported data. As a result, we estimated that the basic reproductive number, R0, was 2.91 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen based on the data from January 24, 2020, to February 23, 2020. In addition, we inferred the prediction results and compared the results of different levels of parameters. For example, in Beijing, the predicted peak number of cases was approximately 466 with a peak time of February 29, 2020; however, if the city were to implement different levels (strict, mild, or weak) of travel restrictions or regulation measures, the estimation results showed that the transmission dynamics would change and that the peak number of cases would differ by between 56% and ∼159%. We concluded that public health interventions would reduce the risk of the spread of COVID-19 and that more rigorous control and prevention measures would effectively contain its further spread but that the risk will increase when businesses and social activities return to normal before the end of the epidemic. Besides, the experiences gained and lessons learned from China are potential to provide evidences supporting for other metropolitan areas and big cities with emerging cases outside China.
Associations between adolescent mental health and health-related behaviours in 2005 and 2015: A population cross-cohort study
Authors: Gage Suzanne H. , Patalay Praveetha
Published: March 2020

Background

Adolescent mental ill-health is a growing concern. There is little understanding of changes over time in the associations between mental health and health-related behaviours and outcomes such as substance use, anti-social behaviour and obesity. We investigate whether the associations between different health-related outcomes in adolescence are changing over time in two recent cohorts of adolescents born ten years apart.

Methods

Data from two UK birth cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC, born 1991-92, N=5627, 50.7% female) and Millennium Cohort Study (MCS, born 2000-2, N=11318, 50.6% female) at age 14 sweeps are used. The health outcomes of focus are depressive symptom score, substance use (alcohol, smoking, cannabis and other drugs), antisocial behaviours (assault, graffiti, vandalism, shoplifting and rowdy behaviour), weight (BMI), weight perception (perceive self as overweight) and sexual activity (had sexual intercourse). Regression analyses are conducted to examine associations between these variables with cohort as a moderator to examine cohort differences.

Results

The directions of associations between mental-health and health-related behaviours (eg smoking) are similar over time, however, their strength across the distribution has changed. While smoking and alcohol use behaviours are decreasing in adolescents, those that endorse these behaviours in 2015 are more likely to have co-occurring mental-health than those born in 2005. Similarly, higher BMI is more strongly associated with depressive symptoms in 2015 compared to 2005.

Conclusions

Adverse health-related outcomes such as greater substance use, mental health difficulties and higher BMI appear to be more likely to cluster together in the more recent cohort, with implications for public health planning, service provision and lifelong disease burden.

Implications and Contribution

Adverse health outcomes like internalising mental ill-health, substance use and high BMI were more likely to co-occur in 2015 than 2005, albeit decreases in prevalence of substance use and antisocial behaviours and increases in internalising mental ill-health and BMI over this decade. This has implications for their causal associations and appropriate public-health action.
A Systematic Review of effect of Non-Invasive Brain Stimulation on Cognition Impairment after a Stroke and Traumatic Brain Injury
Authors: Hara Takatoshi , Shanmugalingam Aturan , McIntyre Amanda , Burhan Amer M.
Published: March 2020

Background

In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for stroke and traumatic brain injury (TBI) populations.

Methods

All English articles from the following sources were searched from inception up to December 31, 2018: PubMed, Scopus, CINAHL, Embase, PsycINFO and CENTRAL. Randomized and prospective controlled trials, including cross-over studies, were included for analysis. Studies with at least five individuals post stroke or TBI, whereby at least five sessions of NIBS were provided and used standardized neuropsychological measurement of cognition, were included.

Results

A total of 17 studies met eligibility criteria which included 546 patients receiving either repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS). Sample sizes ranged 5-25 subjects per group. Seven studies used rTMS and ten studies used tDCS. Target symptoms included global cognition (n=8), memory (n=1), attention (n=1), and unilateral spatial neglect (USN) (n=7). Nine studies combined rehabilitation or additional therapy with NIBS. Six of ten studies showed significant improvement in attention, memory, working memory, and executive function. In the USN study, five of the seven studies had a significant improvement in the intervention group.

Conclusions

The effect of NIBS on executive functions including attention and memory post stroke or TBI yielded mixed results with variable stimulation parameters. A significant, consistent improvement was observed for USN post stroke or TBI. Future studies using advanced neurophysiological and neuroimaging tools to allow network-based approach to NIBS for cognitive symptoms post stroke or TBI are warranted.
Role of Specialized Composition of SWI/SNF Complexes in Prostate Cancer Lineage Plasticity
Authors: Cyrta Joanna , Augspach Anke , de Filippo Maria Rosaria , Prandi Davide , Thienger Phillip , Benelli Matteo , Cooley Victoria , Bareja Rohan , Wilkes David , Chae Sung-Suk , Cavaliere Paola , Dephoure Noah , Uldry Anne-Christine , Lagache Sophie Braga , Cohen Sandra , Jaquet Muriel , Brandt Laura P. , Alshalalfa Mohammed , Sboner Andrea , Feng Felix , Wang Shangqian , Beltran Himisha , Lotan Tamara , Spahn Martin , Julio Marianna Kruithof-de , Chen Yu , Ballman Karla V. , Demichelis Francesca , Piscuoglio Salvatore , Rubin Mark A.
Published: March 2020

Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in ∼10% of these patients is through lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data suggest a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may be relevant for other solid tumors.
Network structure of the mouse brain connectome with voxel resolution
Authors: Coletta Ludovico , Pagani Marco , Whitesell Jennifer D. , Harris Julie A. , Bernhardt Boris , Gozzi Alessandro
Published: March 2020

Fine-grained descriptions of brain connectivity are fundamental for understanding how neural information is processed and relayed across spatial scales. Prior investigations of the mouse brain connectome have employed discrete anatomical parcellations, limiting spatial resolution and potentially concealing network attributes critical to the organization of the mammalian connectome. Here we provide a voxel-level description of the network and hierarchical structure of the directed mouse connectome, unconstrained by regional partitioning. We show that integrativehubregions can be directionally segregated into neural sinks and sources, defining a hierarchical axis. We describe a set of structural communities that spatially reconstitute previously described fMRI networks of the mouse brain, and document that neuromodulatory nuclei are strategically wired as critical orchestrators of inter-modular and network communicability. Notably, like in primates, the directed mouse connectome is organized along two superimposed cortical gradients reflecting unimodal-transmodal functional processing and a modality-specific sensorimotor axis. These structural features can be related to patterns of intralaminar connectivity and to the spatial topography of dynamic fMRI brain states, respectively. Together, our results reveal a high-resolution structural scaffold linking mesoscale connectome topography to its macroscale functional organization, and create opportunities for identifying targets of interventions to modulate brain function in a physiologically-accessible species.
Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin(az)oline inhibitors
Authors: Asquith Christopher R. M. , Tizzard Graham J. , Bennett James M. , Wells Carrow I. , Elkins Jonathan M. , Willson Timothy M. , Poso Antti , Laitinen Tuomo
Published: March 2020

Water networks within kinase inhibitor design and more widely within drug discovery are generally poorly understood. The successful targeting of these networks prospectively has great promise for all facets of inhibitor design, including potency and selectivity on target. Here we describe the design and testing of a targeted library of 4-anilinoquinolines for use as inhibitors of cyclin G associated kinase (GAK). The GAK cellular target engagement assays, ATP binding site modelling and extensive water mapping provide a clear route to access potent inhibitors for GAK and beyond.
Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
Authors: Kang Sisi , Yang Mei , Hong Zhongsi , Zhang Liping , Huang Zhaoxia , Chen Xiaoxue , He Suhua , Zhou Ziliang , Zhou Zhechong , Chen Qiuyue , Yan Yan , Zhang Changsheng , Shan Hong , Chen Shoudeng
Published: March 2020

The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented byin vitrobinding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.