bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimizing Radiation Dose Outliers Through Systematic Analysis, Computed Tomography Technologist Education, and Standardized System Solutions
Authors: Appel Elisabeth , Boos Johannes , Fang Jieming , Zhang Da , Wilcox Carol , Camacho Andrés , Dommaraju Sujithraj , Brook Alexander , Brook Olga R.
Published: March 2020

Objectives

The aims of the study were to systematically analyze causes for radiation dose outliers in emergency department noncontrast head computed tomographies (CTs), to develop and implement standardized system solutions, and audit program success for an extended period of time.

Methods

This study was performed in a large, tertiary academic center between January 2015 and September 2017. Four phases of radiation dose data collection with and without prior interventions were performed. Outliers from 5 categories were evaluated for appropriateness in consensus by 2 radiologists and a senior CT technologist.

Results

A total of 275 ± 15 CTs per period were included. Fifty-seven inappropriate scanning parameters were found in 24 (9%) of 254 CTs during the first analysis, 27 in 21 (7%) of 290 CTs during the second, 11 in 10 (4%) of 276 during the third assessment (P = 0.006). After a year without additional intervention, the number remained stable (14 in 11/281 CTs, 4%).

Conclusions

Combining a dose reporting system, individual case analysis, staff education, and implementation of systemic solutions lead to sustained radiation exposure improvement.
Prevalence of Machine Learning in Craniofacial Surgery
Authors: Mak Martin L. , Al-Shaqsi Sultan Z. , Phillips John
Published: March 2020

Machine learning (ML) revolves around the concept of using experience to teach computer-based programs to reliably perform specific tasks. Healthcare setting is an ideal environment for adaptation of ML applications given the multiple specific tasks that could be allocated to computer programs to perform. There have been several scoping reviews published in literature looking at the general acceptance and adaptability of surgical specialities to ML applications, but very few focusing on the application towards craniofacial surgery. This study aims to present a detailed scoping review regarding the use of ML applications in craniofacial surgery.
Nasolabial Perforator Flap: A Multi-Tool for Reconstruction of Facial Units
Authors: Ercan Alp , Ercan Leman Damla , Demiroz Anil
Published: March 2020

Background:

Nasolabial flap is a work-horse flap for coverage of many facial units. However, these flaps have limited mobility and these limit their use in many instances. Facial artery with its numerous small cutaneous perforators can be a source for free-style skin flaps that can be islanded and have greater reach, one of which is nasolabial perforatory flap.

Methods:

The authors present a case series of 35 patients with central facial unit defects reconstructed by a single flap harvested from the nasolabial sulcus.

Results:

In our series, we did not encounter any significant flap loss and patient satisfaction was high both functionally and aesthetically. Main drawbacks were temporary venous congestion and hair bearing flaps in male patients.

Conclusion:

The authors think with its reliability and versatility nasolabial perforator flaps, based on the same donor area as the traditional nasolabial flap can be a valuable addition to our arsenal in reconstruction of central facial unit defects.
Variability in Current Procedural Terminology Codes for Craniomaxillofacial Trauma Reconstruction: A National Survey
Authors: Jazayeri Hossein E. , Khavanin Nima , Yu Jason W. , Wu Brendan , Payne Eric , Mundinger Gerhard S. , Patel Kamlesh B. , Peacock Zachary S. , Villa Mark T. , Dorafshar Amir H.
Published: March 2020

Background:

Current Procedural Terminology (CPT) codes are an important part of surgical documentation and billing for services provided within the United States. This limited coding language presents a challenge in the heterogenous and rapidly evolving field of craniofacial surgery. The authors aimed to survey members of the American Society of Maxillofacial Surgery (ASMS) to characterize the variability in coding practices in the surgical management of craniofacial trauma.

Methods:

A cross-sectional of 500 members of the ASMS survey was carried out. Descriptive statistics were calculated. The effect of various practice characteristics on coding practices was evaluated using Chi-squared tests and Fisher's exact tests.

Results:

In total, 79 participants responded including 77 plastic surgeons. About 75% worked in academic centers and 38% reported being in practice over 20 years. Coding practices were not significantly associated with training background or years in practice. Unilateral mandibular and unilateral nasoorbitoethmoid fractures demonstrated the greatest agreement with 99% and 88% of respondents agree upon a single coding strategy, respectively. Midface fractures, bilateral nasoorbitoethmoid fractures, and more complex mandibular demonstrated considerable variability in coding.

Conclusion:

There is a wide variability among members of the ASMS in CPT coding practices for the operative management of craniofacial trauma. To more accurately convey the complexity of craniofacial trauma reconstruction to billers and insurance companies, the authors must develop a more descriptive coding language that captures the heterogeneity of patient presentation and surgical procedures.
Peer Role-Play for Training Communication Skills in Medical Students
Authors: Gelis Anthony , Cervello Sophie , Rey Romain , Llorca Guy , Lambert Philippe , Franck Nicolas , Dupeyron Arnaud , Delpont Marion , Rolland Benjamin
Published: March 2020

Summary Statement

Peer role-play (PRP) is a simulation-based training method (SBTM) in which medical students alternately play the patient's and clinician's role. This review aimed to assess the effectiveness of PRP for improving the communication skills of medical students. A systematic search was conducted in the MedLine, PsycInfo, and ERIC databases. Studies were qualitatively analyzed according to the Kirkpatrick evaluation level (Kirkpatrick level) and the Medical Education Research Study Quality Instrument.

Twenty-two studies were included. Studies assessing the “reaction” of students (Kirkpatrick level 1, n = 15) found that PRP was appreciated, whereas those assessing the effect of PRP on “learning” (Kirkpatrick level 2, n = 12) found that PRP improves communication skills but no more than other SBTMs. No study assessed real-life “attitudes” or “clinical outcomes” (Kirkpatrick levels 3 and 4), whereas 2 studies found that using PRP had a better cost-efficacy ratio than the use of simulated patients. Compared with other SBTMs, PRP improved communication skills similarly in medical students and seemed less expensive.
Developing a Profile of Procedural Expertise
Authors: Kerrey Benjamin T. , Boyd Stephanie D. , Geis Gary L. , MacPherson Ryan P. , Cooper Edward , Kiefer Adam W.
Published: March 2020

Background

Improving the assessment and training of tracheal intubation is hindered by the lack of a sufficiently validated profile of expertise. Although several studies have examined biomechanics of tracheal intubation, there are significant gaps in the literature. We used 3-dimensional motion capture to study pediatric providers performing simulated tracheal intubation to identify candidate kinematic variables for inclusion in an expert movement profile.

Methods

Pediatric anesthesiologists (experienced) and pediatric residents (novices) were recruited from a pediatric institution to perform tracheal intubation on airway mannequins in a motion capture laboratory. Subjects performed 21 trials of tracheal intubation, 3 each of 7 combinations of laryngoscopic visualization (direct or indirect), blade type (straight or curved), and mannequin size (adult or pediatric). We used repeated measures analysis of variance to determine whether various kinematic variables (3-trial average for each participant) were associated with experience.

Results

Eleven experienced and 15 novice providers performed 567 successful tracheal intubation attempts (9 attempts unsuccessful). For laryngoscopy, experienced providers exhibited shorter path length (total distance traveled by laryngoscope handle; 77.6 ± 26.0 cm versus 113.9 ± 53.7 cm; P = 0.013) and greater angular variability at the left wrist (7.4 degrees versus 5.5 degrees, P = 0.013) and the left elbow (10.1 degrees versus 7.6 degrees, P = 0.03). For intubation, experienced providers exhibited shorter path length of the right hand (mean = 61.1 cm versus 99.9 cm, P < 0.001), lower maximum acceleration of the right hand (0.19 versus 0.14 m/s2, P = 0.033), and smaller angular, variability at the right elbow (9.7 degrees versus 7.9 degrees, P = 0.03).

Conclusions

Our study and the available literature suggest specific kinematic variables for inclusion in an expert profile for tracheal intubation. Future studies should include a larger sample of practitioners, actual patients, and measures of the cognitive and affective components of expertise.
Bone Mineral Density and Aortic Calcification: Evidence for a Bone-vascular Axis After Kidney Transplantation
Authors: Sotomayor Camilo G. , Benjamens Stan , Gomes-Neto António W. , Pol Robert A. , Groothof Dion , te Velde-Keyzer Charlotte A. , Chong Guillermo , Glaudemans Andor W.J.M. , Berger Stefan P. , Bakker Stephan J.L. , Slart Riemer H.J.A.
Published: March 2020

Background.

Chronic kidney disease mineral and bone disorders (CKD-MBD) and vascular calcification are often seen in kidney transplantation recipients (KTR). This study focused on the bone–vascular axis hypothesis, the pathophysiological mechanisms driving both bone loss and vascular calcification, supported by an association between lower bone mineral density (BMD) and higher risk of vascular calcification.

Methods.

KTR referred for a dual-energy X-ray absorptiometry procedure within 6 mo after transplantation were included in a cross-sectional study (2004–2014). Areal BMD was measured at the proximal femur, and abdominal aortic calcification (AAC) was quantified (8-points score) from lateral single-energy images of the lumbar spine. Patients were divided into 3 AAC categories (negative-AAC: AAC 0; low-AAC: AAC 1–3; and high-AAC: AAC 4–8). Multivariable-adjusted multinomial logistic regression models were performed to study the association between BMD and AAC.

Results.

We included 678 KTR (51 ± 13 y old, 58% males), 366 (54%) had BMD disorders, and 266 (39%) had detectable calcification. High-AAC was observed in 9%, 11%, and 25% of KTR with normal BMD, osteopenia, and osteoporosis, respectively (P < 0.001). Higher BMD (T-score, continuous) was associated with a lower risk of high-AAC (odds ratio 0.61, 95% confidence interval 0.42-0.88; P = 0.008), independent of age, sex, body mass index, estimated glomerular filtration rate, and immunosuppressive therapy. KTR with normal BMD were less likely to have high-AAC (odds ratio 0.24, 95% confidence interval 0.08-0.72; P = 0.01).

Conclusions.

BMD disorders are highly prevalent in KTR. The independent inverse association between BMD and AAC may provide evidence to point toward the existence, while highlighting the clinical and epidemiological relevance, of a bone–vascular axis after kidney transplantation.
Hippocampal complement C3 might contribute to cognitive impairment induced by anesthesia and surgery
Authors: Ji Mu-huo , Qiu Li-li , Mao Ming-Jie , Zhang Lin , Yang Jian-jun
Published: March 2020

Postoperative cognitive dysfunction is a well-recognized complication after major surgery in the elderly, but its pathophysiological mechanism is not fully understood. In the present study, we used liquid chromatography-tandem mass spectrometry combined with tandem mass tags to identify differentially expressed proteins and perform further functional studies on protein of interest. Here, we showed that hippocampal complement C3 was significantly upregulated after surgery, which was accompanied by marked decreases in synaptic related proteins and density. In aged patients undergoing gastrointestinal surgery, we also found significantly increased plasma level of C3b postoperatively and were negatively associated with cognitive performance. Notably, selective inhibition of complement C3 by compstatin was able to rescue synaptic and cognitive impairments induced by surgery in aged mice. Collectively, our study confirms that surgery can induce cognitive impairments, and the possible mechanisms might be related to abnormal complement signaling and synaptic disruption.
The onjisaponin B metabolite tenuifolin ameliorates dopaminergic neurodegeneration in a mouse model of Parkinson’s disease
Authors: Peng Fang , Lu Linyu , Wei Fei , Wu Die , Wang Kai , Tang Juanjuan
Published: March 2020

Onjisaponin B (OB) is the main active ingredient of the traditional Chinese medicinal herb polygala, which is effective against neurodegenerative disorders. However, the target of OB is currently unknown. Neuroinflammation and oxidative stress are both risk factors for the pathogenesis and progression of Parkinson’s disease (PD). Here, we used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute mouse model of PD to explore the efficacy and neuroprotective mechanism of OB in PD. Immunohistochemistry was used to mark dopaminergic (DA) neurons and microglia in the substantia nigra pars compact. Administration of OB (20 and 40 mg/kg) prevented the degeneration of DA neurons and improved motor impairment in the rotarod test. Furthermore, OB attenuated microglia over-activation and reduced the secretion of inflammatory factors including tumor necrosis factor-alpha, interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), as determined by ELISA. Meanwhile, the activities of superoxide dismutase and malondialdehyde were used to measure the level of oxidative stress in brain homogenates and suppression of excessive lipid epoxidation and increased antioxidant enzyme activity were found in OB-treated PD mice. Finally, OB inhibits the expression of the p65 subunit of NF-κB in the nucleus and attenuated expression of the RhoA and ROCK2 proteins in PD mice. Consequently, our results show that OB ameliorates DA neurodegeneration in a MPTP-induced mouse model of PD through anti-oxidant and anti-inflammatory activities mediated via the RhoA/ROCK2 signaling pathway. This finding demonstrates that OB may be a promising drug for DA neuron degeneration, which may provide a new therapeutic agent for future discovery of drugs for PD.

See video abstract: http://links.lww.com/WNR/A580
Molecular epidemiology of human rhinovirus from one-year surveillance within a school setting in rural coastal Kenya
Authors: Luka Martha M. , Kamau Everlyn , Adema Irene , Munywoki Patrick K. , Otieno Grieven P. , Gicheru Elijah , Gichuki Alex , Kibinge Nelson , Agoti Charles N. , Nokes D. James
Published: March 2020

Background

Human rhinovirus (HRV) is the most common cause of the common cold but may also lead to more severe respiratory illness in vulnerable populations. The epidemiology and genetic diversity of HRV within a school setting have not been described.

Objective

To characterise HRV molecular epidemiology among children attending primary school in a rural location of Kenya.

Methods

Between May 2017 to April 2018, over three school terms, we collected 1859 nasopharyngeal swabs (NPS) from pupils and teachers with symptoms of acute respiratory infection in a public primary school in Kilifi County, coastal Kenya. The samples were tested for HRV using real-time RT-PCR. HRV positive samples were sequenced in the VP4/VP2 coding region for species and genotype classification.

Results

A total of 307 NPS (16.4%) from 164 individuals were HRV positive, and 253 (82.4%) were successfully sequenced. The proportion of HRV in the lower primary classes was higher (19.8%) than upper primary classes (12.2%),p-value <0.001. HRV-A was the most common species (134/253, 53.0%), followed by HRV-C (73/253, 28.9%) and HRV-B (46/253, 18.2%). Phylogenetic analysis identified 47 HRV genotypes. The most common genotypes were A2 and B70. Numerous (up to 22 in one school term) genotypes circulated simultaneously, there was no individual re-infection with the same genotype, and no genotype was detected in all three school terms.

Conclusion

HRV was frequently detected among school-going children with mild ARI symptoms, and particularly in the younger age groups (<5-year-olds). Multiple HRV introductions were observed characterised by the considerable genotype diversity.

Summary points

We describe the molecular epidemiology of human rhinovirus (HRV) within a school setting over one-year in rural coastal Kenya. A high diversity of HRV infections was observed across all classes with evidence of introduction and transmission of 47 different genotypes.
The effect of control strategies that reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China
Authors: Prem Kiesha , Liu Yang , Russell Timothy W , Kucharski Adam J , Eggo Rosalind M , Davies Nicholas ,   Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Jit Mark , Klepac Petra
Published: March 2020

BACKGROUND

In December 2019, a novel strain of SARS-CoV-2 emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures and efforts in response to the outbreak.

METHODS

We quantified the effects of control measures on population contact patterns in Wuhan, China, to assess their effects on the progression of the outbreak. We included the latest estimates of epidemic parameters from a transmission model fitted to data on local and internationally exported cases from Wuhan in the age-structured epidemic framework. Further, we looked at the age-distribution of cases. Lastly, we simulated lifting of the control measures by allowing people to return to work in a phased-in way, and looked at the effects of returning to work at different stages of the underlying outbreak.

FINDINGS

Changes in mixing patterns may have contributed to reducing the number of infections in mid-2020 by 92% (interquartile range: 66–97%). There are benefits to sustaining these measures until April in terms of reducing the height of the peak, overall epidemic size in mid-2020 and probability that a second peak may occur after return to work. However, the modelled effects of social distancing measures vary by the duration of infectiousness and the role school children play in the epidemic.

INTERPRETATION

Restrictions on activities in Wuhan, if maintained until April, would likely contribute to the reduction and delay the epidemic size and peak, respectively. However, there are some limitations to the analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.

FUNDING

Bill and Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.
Clinical features of imported cases of coronavirus disease 2019 in Tibetan patients in the Plateau area
Authors: Lei Yu , Huang Xiaobo , SiLang Bamu , Lan YunPing , Lu Jianli , Zeng Fan
Published: March 2020

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread throughout China, but the clinical characteristics of Tibetan patients living in the Qinghai-Tibetan plateau are unknown. We aimed to investigate the epidemiological, clinical, laboratory and radiological characteristics of these patients. We included 67 Tibetan patients with confirmed SARS-CoV-2 infection. The patients were divided into two groups based on the presence of clinical symptoms at admission, with 31 and 36 patients in the symptomatic and asymptomatic groups, respectively. The epidemiological, clinical, laboratory and radiological characteristics were extracted and analysed. No patient had a history of exposure to COVID-19 patients from Wuhan or had travelled to Wuhan. The mean age of Tibetan patients was 39.3 years and 59% of the patients were male. Seven patients presented with fever on admission and lymphocytopenia was present in 20 patients. 47 patients had abnormal chest CTs at admission instead of stating that 20 were unchanged. Lactate dehydrogenase levels were increased in 31 patients. Seven patients progressed to severe COVID-19; however, after treatment, their condition was stable. No patients died. Of the 36 asymptomatic patients, the mean age was younger than the symptomatic group (34.4±17.3vs 44.9±18.1 years, P=0.02). Lymphocyte count and prealbumin levels were higher in the asymptomatic group than the group with clinical symptoms (1.6±0.5 vs 1.3±0.6 and 241.8±68.2 vs 191.9±60.3, respectively; P<0.05). Imported cases of COVID-19 in Tibetan patients were generally mild in this high-altitude area. Absence of fever or radiologic abnormalities on initial presentation were common.
Estimates of the severity of COVID-19 disease
Authors: Verity Robert , Okell Lucy C , Dorigatti Ilaria , Winskill Peter , Whittaker Charles , Imai Natsuko , Cuomo-Dannenburg Gina , Thompson Hayley , Walker Patrick GT , Fu Han , Dighe Amy , Griffin Jamie T , Baguelin Marc , Bhatia Sangeeta , Boonyasiri Adhiratha , Cori Anne , Cucunubá Zulma , FitzJohn Rich , Gaythorpe Katy , Green Will , Hamlet Arran , Hinsley Wes , Laydon Daniel , Nedjati-Gilani Gemma , Riley Steven , van Elsland Sabine , Volz Erik , Wang Haowei , Wang Yuanrong , Xi Xiaoyue , Donnelly Christl A , Ghani Azra C , Ferguson Neil M
Published: March 2020

Background

A range of case fatality ratio (CFR) estimates for COVID-19 have been produced that differ substantially in magnitude.

Methods

We used individual-case data from mainland China and cases detected outside mainland China to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the CFR by relating the aggregate distribution of cases by dates of onset to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for the demography of the population, and age- and location-based under-ascertainment. We additionally estimated the CFR from individual line-list data on 1,334 cases identified outside mainland China. We used data on the PCR prevalence in international residents repatriated from China at the end of January 2020 to obtain age-stratified estimates of the infection fatality ratio (IFR). Using data on age-stratified severity in a subset of 3,665 cases from China, we estimated the proportion of infections that will likely require hospitalisation.

Findings

We estimate the mean duration from onset-of-symptoms to death to be 17.8 days (95% credible interval, crI 16.9–19.2 days) and from onset-of-symptoms to hospital discharge to be 22.6 days (95% crI 21.1-24.4 days). We estimate a crude CFR of 3.67% (95% crI 3.56%-3.80%) in cases from mainland China. Adjusting for demography and under-ascertainment of milder cases in Wuhan relative to the rest of China, we obtain a best estimate of the CFR in China of 1.38% (95% crI 1.23%-1.53%) with substantially higher values in older ages. Our estimate of the CFR from international cases stratified by age (under 60 / 60 and above) are consistent with these estimates from China. We obtain an overall IFR estimate for China of 0.66% (0.39%-1.33%), again with an increasing profile with age.

Interpretation

These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.
Trends in CD4 and viral load testing 2005 to 2018: Multi-cohort study of people living with HIV in Southern Africa
Authors: Zaniewski Elizabeth , Dao Ostinelli Cam Ha , Chammartin Frédérique , Maxwell Nicola , Davies Mary-Ann , Euvrard Jonathan , van Dijk Janneke , Bosomprah Samuel , Phiri Sam , Tanser Frank , Sipambo Nosisa , Muhairwe Josephine , Fatti Geoffrey , Prozesky Hans , Wood Robin , Ford Nathan , Fox Matthew P , Egger Matthias
Published: March 2020

Introduction

WHO recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.

Methods

We analysed data from 14 HIV treatment programs with over 300 clinics in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in years 2005-2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3) or failing to suppress viral replication (>1000 HIV-RNA copies/ml) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex.

Results

Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017. The percentage starting with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018. VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested but fewer than 2% were tested in the other four countries. The probability of having a CD4 cell count at ART start declined by 14% each year (odds ratio [OR] 0.86; 95% CI 0.86-0.86); the probability of advanced HIV disease declined by 20% per year (OR 0.80; 95% CI 0.80-0.81). The increase in VL testing after ART start was only modest (OR 1.06; 95% CI 1.05-1.06) and there was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99-1.01).

Conclusions

CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.
Modelling the situation of COVID-19 and effects of different containment strategies in China with dynamic differential equations and parameters estimation
Authors: Liu Xiuli , Hewings Geoffrey , Wang Shouyang , Qin Minghui , Xiang Xin , Zheng Shan , Li Xuefeng
Published: March 2020

This paper proposed a quarantine-susceptible-exposed-infectious-resistant (QSEIR) model which considers the unprecedented strict quarantine measures in almost the whole of China to resist the epidemic. We estimated model parameters from published information with the statistical method and stochastic simulation, we found the parameters that achieved the best simulation test result. The next stage involved quantitative predictions of future epidemic developments based on different containment strategies with the QSEIR model, focused on the sensitivity of the outcomes to different parameter choices in mainland China. The main results are as follows. If the strict quarantine measures are being retained, the peak value of confirmed cases would be in the range of [52438, 64090] and the peak date would be expected in the range February 7 to February 19, 2020. During March18-30, 2020, the epidemic would be controlled. The end date would be in the period from August 20 to September 1, 2020. With 80% probability, our prediction on the peak date was 4 days ahead of the real date, the prediction error of the peak value is 0.43%, both estimates are much closer to the observed values compared with published studies. The sensitive analysis indicated that the quarantine measures (or with vaccination) are the most effective containment strategy to control the epidemic, followed by measures to increase the cured rate (like finding special medicine). The long-term simulation result and sensitive analysis in mainland China showed that the QSEIR model is stable and can be empirically validated. It is suggested that the QSEIR model can be applied to predict the development trend of the epidemic in other regions or countries in the world. In mainland China, the quarantine measures can’t be relaxed before the end of March 2020. China can fully resume production with appropriate anti-epidemic measures beginning in early April 2020. The results of this study also implied that other countries now facing the epidemic outbreaks should act more decisively and take in time quarantine measures though it may have negative short-term public and economic consequences.
The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak
Authors: Park Sang Woo , Cornforth Daniel M. , Dushoff Jonathan , Weitz Joshua S.
Published: March 2020

The role of asymptomatic carriers in transmission poses challenges for control of the COVID-19 pandemic. Study of asymptomatic transmission and implications for surveillance and disease burden are ongoing, but there has been little study of the implications of asymp- tomatic transmission on dynamics of disease. We use a mathematical framework to evaluate expected effects of asymptomatic transmission on the basic reproduction numberℛ0(i.e., the expected number of secondary cases generated by an average primary case in a fully sus- ceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases,ℛ0will be over-estimated, and if they have a longer generation interval,ℛ0will be under-estimated. Estimates of the realized proportion of asymptomatic transmission during the exponential phase also depend on asymptomatic generation intervals. Our analysis shows that understanding the temporal course of asymptomatic transmission can be important for assessing the importance of this route of transmission, and for disease dynamics. This provides an additional motivation for investigating both the importance and relative duration of asymptomatic transmission.
Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
Authors: Sharp Gemma C , Alfano Rossella , Ghantous Akram , Urquiza Jose , Rifas-Shiman Sheryl L , Page Christian M , Jin Jianping , Fernández-Barrés Silvia , Santorelli Gillian , Tindula Gwen , Yousefi Paul , Kupers Leanne , Ruiz-Arenas Carlos , Jaddoe Vincent WV , DeMeo Dawn , Fossati Serena , Wright John , Huen Karen , Popovic Maja , Nohr Ellen A , Smith George Davey , Lepeule Johanna , Baccarelli Andrea , Magnus Maria C , Nystad Wenche , Casas Maribel , Oken Emily , Håberg Siri E , Vafeiadi Marina , Roumeliotaki Theano , Vrijheid Martine , Munthe-Kaas Monica C , Eskenazi Brenda , Ronfani Luca , Holland Nina , Chatzi Leda , Meltzer Helle Margrete , Herceg Zdenko , Plusquin Michelle , Bustamante Mariona , Hivert Marie-France , Lawlor Deborah A , Sørensen Thorkild IA , London Stephanie J , Felix Janine F , Relton Caroline L
Published: March 2020

Background

Accumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.

Methods and findings

In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.

Conclusion

Our findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.

Author Summary

Previous small, mostly candidate gene studies have shown associations between paternal pre-pregnancy BMI and offspring blood DNA methylation. However, in our large meta-analysis of co-ordinated EWAS results from a total of 19 datasets across two timepoints, we found little evidence to support these findings, even at imprinted regions. This does not rule out the possibility of a paternal epigenetic effect in different tissues, at regions not covered by the 450k array, via different mechanisms, or in populations with greater extremes of paternal BMI. More research is warranted to help understand the size and nature of contributions of paternal adiposity to offspring epigenetics and health outcomes.
Factors associated with participation over time in the Avon Longitudinal Study of Parents and Children: a study using linked education and primary care data
Authors: Cornish RP , Macleod J , Boyd A , Tilling K
Published: March 2020

Background

Dropout from studies can lead to biased exposure-outcome estimates if the outcome is associated with continued participation, but this cannot be investigated using incomplete data. Linkage to external datasets provides a means of obtaining outcome – or proxy outcome - data on non-responders.

Methods

We examined the association between baseline socio-demographic factors and participation in the Avon Longitudinal Study of Parents and Children. We investigated whether child and adolescent outcomes measured in linked education and primary care data were associated with participation after accounting for baseline factors. To demonstrate the potential for bias, we examined whether the association between maternal smoking and these outcomes differed in the subsample who completed the 19-year questionnaire.

Results

Lower levels of school attainment, lower GP consultation and prescription rates, higher BMI, special educational needs (SEN) status, not having an asthma diagnosis, depression and being a smoker were all associated with lower participation after adjustment for baseline factors. For example, adjusted odds ratio (OR) for participation comparing ever smokers (by 18 years) to non-smokers: 0.65, 95% CI (0.56, 0.75). The association of maternal smoking differed between the subsample of participants at 19 years and the entire sample, although differences were small and confidence intervals overlapped. For example: for SEN status OR=1.19 (1.06, 1.33) (all participants); OR=1.03 (0.79, 1.45) (subsample).

Conclusions

Linkage to routine data provides a unique opportunity to compare continuing participators to those who drop out, and the impact this self-selection can have on results. Cohort studies should use linkage to routine data to explore participation and conduct sensitivity analyses.

Key messages

Educational and health-related characteristics are strongly associated with ongoing participation in the Avon Longitudinal Study of Parents and Children after adjustment for detailed socio-demographic factors.

This could bias analyses using the dataset, with bias dependent on the variables used in the analysis and their impact on participation.

Linkage to routine data provides a means of assessing whether factors measured across the life course are associated with ongoing participation in observational studies and the potential impact of this in terms of bias.

Researchers can use linkage to external sources of data to make informed decisions about the likely impact of selective participation and to guide their analyses.
Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure
Authors: Wells Stephen A.
Published: March 2020

The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19.
Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase
Authors: Xing Yuhan , Ni Wei , Wu Qin , Li Wenjie , Li Guoju , Tong Jianning , Song Xiufeng , Xing Quansheng
Published: March 2020

Background

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Presence of SARS-CoV-2 has been constantly reported in stools of patients with coronavirus disease 2019 (COVID-19). However, there is a paucity of data concerning fecal shedding of the virus in pediatric patients.

Objective

To investigate dynamic changes of SARS-CoV-2 in respiratory and fecal specimens in children with COVID-19.

Methods

From January 17, 2020 to February 23, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Patients were followed up to March 10, 2020, the final date of follow-up, and dynamic profiles of RT-PCR results were closely monitored.

Results

All the three pediatric cases were household contacts of adults whose symptoms developed earlier. Severity of disease was mild to moderate and fever was the most consistent and predominant symptom at onset of illness of these children (two cases had body temperature higher than 38.5°C). All children showed increased lymphocytes (>4.4×109 /L) with normal white blood cell counts on admission. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained positive in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 turned negative 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.

Interpretation

SARS-CoV-2 may exist in gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.
Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning
Authors: Banerjee Abhishek , Parente Giuseppe , Teutsch Jasper , Lewis Christopher , Voigt Fabian F. , Helmchen Fritjof
Published: March 2020

Flexible decision-making is crucial for adaptive behaviour. Such behaviour in mammals largely relies on the frontal cortex, and specifically, the orbitofrontal cortex (OFC). How OFC neurons encode decision variables and instruct sensory areas to guide adaptive behaviour is a key open question. Here we developed a reversal learning task for head-fixed mice together with two-photon calcium imaging to monitor the activity of lateral OFC neuronal populations and investigated their dynamic interaction with primary somatosensory cortex (S1). Mice trained on this task learned to discriminate go/no-go tactile stimuli and adapt their behaviour upon changes in stimulus–reward contingencies (‘rule-switch’). Longitudinal imaging at cellular resolution across weeks during all behavioural phases revealed a distinct engagement of S1 and lateral OFC neurons: S1 neural activity reflected task learning-related responses, while neurons in the lateral OFC saliently and transiently responded to the rule-switch. A subset of OFC neurons conveyed a value prediction error signal via feedback projections to S1, as direct anatomical long-range projections were revealed by retrograde tracing combined with whole-brain light-sheet microscopy. Top-down signals implemented an update of sensory representations and functionally reconfigured a small subpopulation of S1 neurons that were differentially modulated by reward-history. Functional remapping of these neurons crucially depended on top-down inputs, as chemogenetic silencing of lateral OFC neurons disrupted reversal learning and impaired plastic changes in these outcome-sensitive S1 neurons. Our results reveal the presence of long-range cortical interactions between cellular ensembles in higher and lower-order brain areas specifically recruited during context-dependent learning and task-switching. Such interactions crucially implement history-dependent reward-value computations and error heuristics, which, in turn, help guide adaptive behaviour.
A device for exploring the full angular excitation space - Can more angular projections improve determination of a molecules 3D-orientation in the presence of noise?
Authors: Pfennig Dominik , Albrecht Andreas , Nowak Julia , Walla Peter Jomo
Published: March 2020

In the past, different methods have been presented to determine the 3D orientation of single molecules in a microscopic set-up by excitation polarization modulation. Using linearly polarized illumination from different directions and thereby measuring different 2D projections enables reconstructing the full 3D orientation. Theoretically, two projections suffice for a full 3D orientation determination if the intensities are properly calibrated. If they are not, a third projection will enable unambiguous orientation measurements. The question arises if three projections already contain the maximum information on the 3D orientation when also considering the limited number of available photons and shot noise in an experiment, or if detecting more projections or even continuously changing the projection direction during a measurement provides more information with an identical number of available photons. To answer this principle question, we constructed a simple device allowing for exploring any projection direction available with a particular microscope objective and tested several different excitation modulation schemes using simulated as well as experimental single molecule data. We found that three different projections in fact already do provide the maximum information also for noisy data. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement.

In fluorescence microscopy polarized illumination from different directions enables the determination of the 3D orientation of single molecules by combining the 2D information of different projection directions. Ambiguities that emerge when using only two projections can be eliminated using a third projection. In a systematic study we show that – also considering the limited number of available photons and shot noise in an experiment – three projection directions already contain the maximum information on the 3D orientation. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement.
Altered kinetics of circulating progenitor cells in cardiopulmonary bypass (CPB) associated vasoplegic patients: A pilot study
Authors: Nandi Sanhita , Potunuru Uma Rani , Kumari Chandrani , Nathan Abel Arul , Gopal Jayashree , Menon Gautam I , Siddharthan Rahul , Dixit Madhulika , Thangaraj Paul Ramesh
Published: March 2020

Vasoplegia observed post cardiopulmonary bypass (CPB) is associated with substantial morbidity, multiple organ failure and mortality. Circulating counts of hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPC) are potential markers of neo-vascularization and vascular repair. However, the significance of changes in the circulating levels of these progenitors in perioperative CPB, and their association with post-CPB vasoplegia, are currently unexplored. We enumerated HSC and EPC counts, via flow cytometry, at different time-points during CPB in 19 individuals who underwent elective cardiac surgery. These 19 individuals were categorized into two groups based on severity of post-operative vasoplegia, a clinically insignificant vasoplegic Group 1 (G1) and a clinically significant vasoplegic Group 2 (G2). Differential changes in progenitor cell counts during different stages of surgery were compared across these two groups. Machine-learning classifiers (logistic regression and gradient boosting) were employed to determine if differential changes in progenitor counts could aid the classification of individuals into these groups. Enumerating progenitor cells revealed an early and significant increase in the circulating counts of CD34+and CD34+CD133+hematopoietic stem cells (HSC) in G1 individuals, while these counts were attenuated in G2 individuals. Additionally, EPCs (CD34+VEGFR2+) were lower in G2 individuals compared to G1. Gradient boosting outperformed logistic regression in assessing the vasoplegia grouping based on the fold change in circulating CD 34+levels. Our findings indicate that a lack of early response of CD34+cells and CD34+CD133+HSCs might serve as an early marker for development of clinically significant vasoplegia after CPB.
Patterns of gene-body-methylation conservation and its divergent association with gene expression in Pigeonpea and Soybean
Authors: Junaid Alim , Singh N.K. , Gaikwad Kishor
Published: March 2020

Pigeonpea and Soybean are closely related agronomically important legumes that diverged ∼23 million years ago followed by a whole genome duplication event in Soybean. However, the impact of divergence on their epigenomes is not known. Comparative epigenomics is a powerful tool to understand shaping of epigenomes and its functional consequences during evolution. In this study, we investigated the conservation and divergence of Gene body methylation (GbM) and gene-expression patterns between the two species. We compared their genome-wide DNA methylation landscape at single-base resolution and studied the influence of GbM on duplicate gene retention. Our results indicate that during the divergence of Pigeonpea and Soybean, the effects of methylation on gene expression evolved in a heterogeneous manner. GbM features-slow evolution rate and increased length remained conserved in Pigeonpea and Soybean. We also found that contrary to high CG-methylation conservation, non-CG methylated genes remained diverged during evolution due to transposons insertion in adjacent sequences. The methylation differences in paralogs were associated with expression divergence. Notably, we found that variably methylated marks are less likely to target evolutionary conserved sequences. Finally, our findings identify conservation of nitrogen-related genes during evolution, which are promising candidates for epi-alleles for crop improvement.