bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Spectral Detector Computed Tomography to Improve Liver Segmentation and Volumetry
Authors: Ng Yee Seng , Xi Yin , Qian Yuxiao , Ananthakrishnan Lakshmi , Soesbe Todd C. , Lewis Matthew , Lenkinski Robert , Fielding Julia R.
Published: March 2020

Introduction

Liver segmentation and volumetry have traditionally been performed using computed tomography (CT) attenuation to discriminate liver from other tissues. In this project, we evaluated if spectral detector CT (SDCT) can improve liver segmentation over conventional CT on 2 segmentation methods.

Materials and Methods

In this Health Insurance Portability and Accountability Act–compliant institutional review board–approved retrospective study, 30 contrast-enhanced SDCT scans with healthy livers were selected. The first segmentation method is based on Gaussian mixture models of the SDCT data. The second method is a convolutional neural network–based technique called U-Net. Both methods were compared against equivalent algorithms, which used conventional CT attenuation, with hand segmentation as the reference standard. Agreement to the reference standard was assessed using Dice similarity coefficient.

Results

Dice similarity coefficients to the reference standard are 0.93 ± 0.02 for the Gaussian mixture model method and 0.90 ± 0.04 for the CNN-based method (all 2 methods applied on SDCT). These were significantly higher compared with equivalent algorithms applied on conventional CT, with Dice coefficients of 0.90 ± 0.06 (P = 0.007) and 0.86 ± 0.06 (P < 0.001), respectively.

Conclusion

On both liver segmentation methods tested, we demonstrated higher segmentation performance when the algorithms are applied on SDCT data compared with equivalent algorithms applied on conventional CT data.
Potential of Radiation Dose Reduction by Optimizing Z-Axis Coverage in Coronary Computed Tomography Angiography on a Latest-Generation 256-Slice Scanner
Authors: von Felten Elia , Messerli Michael , Giannopoulos Andreas A. , Benz Dominik C. , Schwyzer Moritz , Benetos Georgios , Rampidis Georgios , Patriki Dimitri , Kamani Christel H. , Gräni Christoph , Fuchs Tobias A. , Pazhenkottil Aju P. , Gebhard Catherine , Kaufmann Philipp A. , Buechel Ronny R.
Published: March 2020

Objective

The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner.

Methods

A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary.

Results

The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients.

Conclusions

Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.
Liver Imaging Reporting and Data System Version 2018: What Radiologists Need to Know
Authors: Abdel Razek Ahmed Abdel Khalek , El-Serougy Lamiaa Galal , Saleh Gehad Ahmad , Shabana Walaa , Abd El-wahab Rihame
Published: March 2020

In this article, we aim to review Liver Imaging Reporting and Data System version 18 (LI-RADS v2018). Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Liver Imaging Reporting and Data System developed for standardizing interpreting, reporting, and data collection of HCC describes 5 major features for accurate HCC diagnosis and several ancillary features, some favoring HCC in particular or malignancy in general and others favoring benignity. Untreated hepatic lesions LI-RADS affords 8 unique categories based on imaging appearance on computed tomography and magnetic resonance imaging, which indicate the possibility of HCC or malignancy with or without tumor in vein. Furthermore, LI-RADS defines 4 treatment response categories for treated HCCs after different locoregional therapy. These continuous recent updates on LI-RADS improve the communication between the radiologists and the clinicians for better management and patient outcome.
Computed Tomography Manifestations of 5 Cases of the Novel Coronavirus Disease 2019 (COVID-19) Pneumonia From Patients Outside Wuhan
Authors: Lu Tao , Pu Hong
Published: March 2020

Clinical, laboratory, and computed tomography (CT) findings of 5 cases of the novel Coronavirus Disease 2019 (COVID-19) pneumonia from patients outside of Wuhan were reviewed. The human-to-human transmission of the virus may explain the infection of the disease outside of Wuhan. CT examination is important in the early detection and follow-up of the disease. With a history of exposure or travelling, symptoms of fever and cough, and the typical CT manifestation such as ground-glass opacity with a peripheral distribution, we should also think of the possibility of the COVID-19 pneumonia in patients outside of Wuhan.
Cranial Vault Remodeling in Children With Ventricular Shunts
Authors: Sinclair Nicholas , Ordenana Carlos , Lee Joan , Onwuzulike Kaine , Recinos Violette , Papay Francis , Rampazzo Antonio , Bassiri Gharb Bahar
Published: March 2020

Introduction:

Cranial vault surgery in children with ventricular shunts is more complex due to the possible interference of shunt location with surgical planning and increased risk of shunt related complications. The study evaluated the management of ventricular shunts during cranial vault remodeling (CVR) and subsequent outcomes and complications following CVR.

Methods:

An IRB-approved retrospective chart review was performed including patients who underwent CVR in presence of a ventricular shunt. Measured outcomes were number of shunt revisions following CVR, 30-day complication rate, 3-month complication rate, and post-CVR Whitaker classification. Finally, a review of the literature was performed, and our results were compared to previous reports.

Results:

Eleven patients met the inclusion criteria. Ventricular shunt was not exposed in 18%; exposed and not revised in 54%; exposed and left on a bone peninsula in 18% and simultaneously exposed and revised in 18%. Two patients experienced complications within 30-days. Three additional patients experienced complications within 3-months. An average of 2.2 shunt revisions per patient were performed following CVR. Whitaker classification was I in 7 patients, II in 1 patient and III in 2 patients. Shunt revision rate for patients undergoing CVR for hydrocephalic macrocephaly was on average of 1.2 and 1.9 for shunt-induced craniosynostosis in literature.

Conclusions:

Cranial vault abnormalities in the presence of a ventricular shunt can be effectively treated with CVR. The presence of a shunt does not seem to interfere with final head shape. While leaving the shunt unexposed may appear less morbid, shunt related complications can still occur with this approach.
Application of Human Amniotic Membrane in Temporomandibular Joint Osteoarthritis
Authors: Lopez-Martos Ricardo , Martin-Lozano Guiomar , Ocete-Perez Rafael-Felix , Gonzalez-Perez Luis-Miguel , Gutierrez-Perez Jose-Luis , Infante-Cossio Pedro
Published: March 2020

Human amniotic membrane (HAM) has recently been used as an interpositional material to prevent ankylosis or primary re-ankylosis after temporomandibular joint (TMJ) arthroplasty. Here, the authors describe an unusual case of a 32-year-old woman who presented with a noninflammatory degenerative osteoarthritis of the TMJ in which a HAM was placed following a high condylar arthroplasty and discectomy and show the clinicoradiological results. The procedure resulted in total pain relief and significant improvement in jaw movements. On the long-term follow-up computed tomography, complete remodeling of the glenoid fossa with formation of new ectopic bone was observed. While the application of a HAM can be an alternative procedure to prevent ankylosis when performing a discectomy and arthroplasty, this clinical report highlights the possibility that it can induce ectopic bone formation at this location.
Opioid exposure after injury in United States trauma centers: A prospective, multicenter observational study
Authors: Harvin John A. , Truong Van Thi Thanh , Green Charles E. , Allen LaDonna , Murry Jason , Radosevich John J. , Bogert James N. , Murphy Patrick B. , Padilla-Jones Brandy B. , Zarzaur Ben L. , Taylor John R. , Sexton Kevin W. , Decker Cassandra , Schroeppel Thomas J. , Wade Charles E. , Kao Lillian S.
Published: March 2020

BACKGROUND

Efforts to reduce opioid use in trauma patients are currently hampered by an incomplete understanding of the baseline opioid exposure and variation in United States. The purpose of this project was to obtain a global estimate of opioid exposure following injury and to quantify the variability of opioid exposure between and within United States trauma centers.

STUDY DESIGN

Prospective observational study was performed to calculate opioid exposure by converting all sources of opioids to oral morphine milligram equivalents (MMEs). To estimate variation, an intraclass correlation was calculated from a multilevel generalized linear model adjusting for the a priori selected variables Injury Severity Score and prior opioid use.

RESULTS

The centers enrolled 1,731 patients. The median opioid exposure among all sites was 45 MMEs per day, equivalent to 30 mg of oxycodone or 45 mg of hydrocodone per day. Variation in opioid exposure was identified both between and within trauma centers with the vast majority of variation (93%) occurring within trauma centers. Opioid exposure increased with injury severity, in male patients, and patients suffering penetrating trauma.

CONCLUSION

The overall median opioid exposure was 45 MMEs per day. Despite significant differences in opioid exposure between trauma centers, the majority of variation was actually within centers. This suggests that efforts to minimize opioid exposure after injury should focus within trauma centers and not on high-level efforts to affect all trauma centers.

LEVEL OF EVIDENCE

Epidemiological, level III.
Laparoscopic versus open approach for adhesive small bowel obstruction, a systematic review and meta-analysis of short term outcomes
Authors: Krielen Pepijn , Di Saverio Salomone , ten Broek Richard , Renzi Claudio , Zago Mauro , Popivanov Georgi , Ruscelli Paolo , Marzaioli Rinaldo , Chiarugi Massimo , Cirocchi Roberto
Published: March 2020

BACKGROUND

Adhesive small bowel obstruction (ASBO) is one of the most frequent causes of emergency hospital admissions and surgical treatment. Current surgical treatment of ASBO consists of open adhesiolysis. With laparoscopic procedures rising, the question arises if laparoscopy for ASBO is safe and results in better patient outcomes. Although adhesiolysis was among the first surgical procedures to be approached laparoscopically, uncertainty remains about its potential advantages over open surgery. Therefore, we performed a systematic review and meta-analysis on the benefits and harms of laparoscopic surgery for ASBO.

METHODS

A systematic literature review was conducted for articles published up to May 2019. Two reviewers screened all articles and did the quality assessment. Consecutively a meta-analysis was performed. To reduce selection bias, only matched studies were used in our primary analyses. All other studies were used in a sensitivity analyses. All the outcomes were measured within the 30th postoperative day. Core outcome parameters were postoperative mortality, iatrogenic bowel perforations, length of postoperative stay [days], severe postoperative complications, and early readmissions. Secondary outcomes were operative time [min], missed iatrogenic bowel perforations, time to flatus [days], and early unplanned reoperations.

RESULTS

In our meta-analysis, 14 studies (participants = 37.007) were included: 1 randomized controlled trial, 2 matched studies, and 11 unmatched studies. Results of our primary analyses show no significant differences in core outcome parameters (postoperative mortality, iatrogenic bowel perforations, length of postoperative stay, severe postoperative complications, early readmissions). In sensitivity analyses, laparoscopic surgery favored open adhesiolysis in postoperative mortality (relative risk [RR], 0.36; 95% CI, 0.29–0.45), length of postoperative hospital stay (mean difference [MD], −4.19; 95% CI, −4.43 to −3.95), operative time (MD, −18.19; 95% CI, −20.98 to −15.40), time to flatus (MD, −0.98; 95% CI, −1.28 to −0.68), severe postoperative complications (RR, 0.51; 95% CI, 0.46–0.56) and early unplanned reoperations (RR, 0.82; 95% CI, 0.70–0.96).

CONCLUSION

Results of this systematic review indicate that laparoscopic surgery for ASBO is safe and feasible. Laparoscopic surgery is not associated with better or worse postoperative outcomes compared with open adhesiolysis. Future research should focus on the correct selection of those patients who are suitable for laparoscopic approach and may benefit from this approach.

LEVEL OF EVIDENCE

Systematic Review/Meta-analysis, Level III.
Changes of physicochemical properties of Cheonggukjang prepared with various soybean cultivars and Bacillus subtilis HJ18-9
Authors: Gil Na-Young , Song Jin , Eom Jeong Seon , Park Shin-Young , Choi Hye-Sun
Published: March 2020

The purpose of this study was to investigate changes in the amino acid content and physicochemical properties of Cheonggukjang prepared by using various soybean cultivars (Daewon, Deapung, Seadanbeak, and Taekwang) and a functional microorganism (Bacillus subtilis HJ18-9). These soybeans were conventional Cheonggukjang (control) and Cheonggukjang fermented with Bacillus subtilis HJ18-9 (treated). The moisture contents of steamed, control, and treated soybean were 62.45~67.12%, 63.28~67.14%, and 64.50~66.87%; amino-type nitrogen contents were 6.53~24.25 mg%, 27.63~122.09 mg%, and 37.29~133.48 mg%; and ammonia-type nitrogen contents were 26.92~47.95 mg%, 45.45~156.36 mg%, and 28.02~121.13 mg%, respectively. The umami taste associated with several amino acids (aspartic acid　and glutamic acid) in Cheonggukjang was lower than that for steamed soybeans, while the bitter taste from amino acids (methionine, valine, isoleucine, leucine, and phenylalanine) was higher than that for steamed soybeans. The result of sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the molecular weight of steamed soybeans was less than 100 kDa, while control and treated groups showed low molecular weights below 34 kDa, confirming their protein hydrolysis to small molecular weight. These results are information for developing functional fermented soybean paste and diversification using soybean cultivars.
Physicochemical properties, bioactive composition and antioxidant activities of noni fruit juices from different regions of cultivation
Authors: Kim Ja-Min , Jo Yong Jun , Hahn Dongyup
Published: March 2020

The objectives of this study were to compare the physicochemical properties, functional components and antioxidant activities of noni fruit juices from six different regions of cultivation: Samoa, Indonesia, China (Hainan), Hawaii, Thailand and Tahiti. The pH values of noni fruit juices ranged from 3.63 to 3.83, and the soluble contents were 5.97-6.97 °Brix. In regard to color, the L, a and b values of noni juices were in the ranges of 33.41-46.51, 3.44-7.98, and 2.42-22.20, respectively. The polyphenol content of noni fruit juice from Indonesia was significantly higher than other samples. The Thailand noni fruit juice contained the highest amounts of scopoletin (8.62 mg/100 mL) and rutin (2.03 mg/100 mL). The noni fruit juice from Indonesia showed the higher antioxidant activities (DPPH and ABTS radical scavenging activity) than others. In conclusion, These results suggest that noni fruit juice may be a good source of functional food with antioxidant activity and can serve as the basis data for the use of noni fruit in the food industry.
The prevention of nosocomial SARS-CoV2 transmission in endoscopy: a systematic review of recommendations within gastroenterology to identify best practice
Authors: Ong John , Cross Gail Brenda , Dan Yock Young
Published: March 2020

Endoscopy generates aerosol droplets and fomites, thereby increasing the risk of SARS-CoV2 transmission to healthcare workers and uninfected patients within endoscopy departments. Despite the sharp rise in the incidence of COVID-19, authoritative recommendations to limit the spread of SARS-CoV2 within gastrointestinal endoscopy units are lacking. Therefore, with the primary aim of identifying best practice and scrutinizing its supporting evidence, we conducted a systematic review of literature for articles published between 1 January 2002 and 15 March 2020 in five databases relating to both the current SARS-CoV2 and the previous SARS-CoV outbreaks. Official websites for gastroenterology and endoscopy societies in the 15 most affected countries were also searched. Unfortunately, a paucity of high quality data and heterogeneity of recommendations between countries was observed. Interestingly, not all countries advocated the postponement of non-urgent or elective procedures. Recommendations for patient screening and personal protective equipment were commonly featured in all recommendations but specifics varied. Only 32% (9/28) of all gastroenterology and endoscopy societies issued guidance on endoscopy in the COVID-19 pandemic. In conclusion, stronger evidence to inform current practice and robust guidelines are urgently needed to prevent the transmission of SARS-CoV2 in gastrointestinal endoscopy departments worldwide.
Simple Mathematics on Covid-19 Expansion
Authors: de Abajo F. Javier García
Published: March 2020

We review the Kermack and McKendrick model of epidemics and apply it to Covid-19. Despite the simplicity of this model, solid conclusions are extracted that can assist potential decisions on the strategy to combat the outbreak, essentially configuring a scenario ranging from short-term suppression to long-term mitigation depending on the achieved reduction in the contact number.
AAEDM: Theoretical Dynamic Epidemic Diffusion Model and Covid-19 Korea Pandemic Cases
Authors: Kim Amang (Song-Kyoo)
Published: March 2020

Abstract

This paper deals with an advanced analytical epidemic diffusion model which is capable to predict the status of epidemic impacts. This newly propose model well describes an epidemic growth and it could be widely applied into various topics including pathology, epidemiology, business and data sciences. The Advanced Analytical Epidemic Diffusion Model (AAEDM) is a dynamic diffusion prediction model which is theoretically intuitive and its tractable closed formula could be easily adapted into versatile Bigdata driven analytics including the machine learning system. This dynamic model is still an analytical model but the periods of prediction are segmented for adapting the values from the dataset when the data is available. The epidemiologically vital parameters which effect on the AAEDM are also introduced in this paper. The evaluation of this theoretical model based on the Covid-19 data in Korea has been accomplished with relative fair future prediction accuracies. Although this analytical model has been designed from a basic exponential growth model, the performance of the AAEDM is competitive with other Bigdata based simulation models. Since the AAEDM is relatively simple and handy, anyone can use this model into analyzing outbreak situations in his daily life.
Can a population targeted by a CRISPR-based homing gene drive be rescued?
Authors: Rode Nicolas O. , Courtier-Orgogozo Virginie , Débarre Florence
Published: March 2020

CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations. This technique is based on the release of individuals carrying an engineered piece of DNA that can be preferentially inherited by the progeny. Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also indicates that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues.

Article summary for Issue Highlights

Homing gene drive is a new genetic control technology that aims to spread a genetically engineered DNA construct within natural populations even when it impairs fitness. In case of unanticipated damages, it has been proposed to stop homing gene drives by releasing individuals carrying a genedrive brake; however, the efficiency of such brakes has been little studied. The authors develop a model to investigate the dynamics of a population targeted by a homing drive in absence or in presence of brake. The model provides insights for the design of more efficient brakes and safer gene drives.
Heterotrophic Thaumarchaeota with ultrasmall genomes are widespread in the ocean
Authors: Aylward Frank O. , Santoro Alyson E.
Published: March 2020

The Thaumarchaeota comprise a diverse archaeal phylum including numerous lineages that play key roles in global biogeochemical cycling, particularly in the ocean. To date, all genomically-characterized marine Thaumarchaeota are reported to be chemolithoautotrophic ammonia-oxidizers. In this study, we report a group of heterotrophic marine Thaumarchaeota (HMT) with ultrasmall genome sizes that is globally abundant in deep ocean waters, apparently lacking the ability to oxidize ammonia. We assemble five HMT genomes from metagenomic data derived from both the Atlantic and Pacific Oceans, including two that are >95% complete, and show that they form a deeply-branching lineage sister to the ammonia-oxidizing archaea (AOA). Metagenomic read mapping demonstrates the presence of this group in mesopelagic samples from all major ocean basins, with abundances reaching up to 6% that of AOA. Surprisingly, the predicted sizes of complete HMT genomes are only 837-908 Kbp, and our ancestral state reconstruction indicates this lineage has undergone substantial genome reduction compared to other related archaea. The genomic repertoire of HMT indicates a highly reduced metabolism for aerobic heterotrophy that, although lacking the carbon fixation pathway typical of AOA, includes a divergent form III-a RuBisCO that potentially functions in a nucleotide scavenging pathway. Despite the small genome size of this group, we identify 13 encoded pyrroloquinoline quinone (PQQ)-dependent dehydrogenases that are predicted to shuttle reducing equivalents to the electron transport chain, suggesting these enzymes play an important role in the physiology of this group. Our results suggest that heterotrophic Thaumarchaeota are widespread in the ocean and potentially play key roles in global chemical transformations.

Importance

It has been known for many years that marine Thaumarchaeota are abundant constituents of dark ocean microbial communities, where their ability to couple ammonia oxidation and carbon fixation plays a critical role in nutrient dynamics. In this study we describe an abundant group of heterotrophic marine Thaumarchaeota (HMT) in the ocean with physiology distinct from their ammonia-oxidizing relatives. HMT lack the ability to oxidize ammonia and fix carbon via the 3-hydroxypropionate/4-hydroxybutyrate pathway, but instead encode a form III-a RuBisCO and diverse PQQ-dependent dehydrogenases that are likely used to generate energy in the dark ocean. Our work expands the scope of known diversity of Thaumarchaeota in the ocean and provides important insight into a widespread marine lineage.
A Model Describing COVID-19 Community Transmission Taking into Account Asymptomatic Carriers and Risk Mitigation
Authors: Aguilar Jacob B. , Faust Jeremy Samuel , Westafer Lauren M. , Gutierrez Juan B.
Published: March 2020

Coronavirus disease 2019 (COVID-19) is a novel human respiratory disease caused by the SARS-CoV-2 virus. Asymptomatic carriers of the COVID-19 virus display no clinical symptoms but are known to be contagious. Recent evidence reveals that this subpopulation, as well as persons with mild disease, are a major contributor in the propagation of the disease. The rapid spread of COVID-19 forced governments around the world to establish and enforce generalized risk mitigation strategies, from lockdowns to guidelines for social distancing, in an effort to minimize community transmission. This created an unprecedented epidemiological situation not properly characterized by existing mathematical models of isolation and quarantine. In this manuscript, we present a mathematical model for community transmission of COVID-19 taking into account asymptomatic carriers and varying degrees of risk mitigation. The main results consist of an exact calculation of the effective reproduction number , and a modeling framework that enables the quantification of the effect of risk mitigation and asymptomatism on community transmission. A computation of is provided using mean parameters. The point estimate of the basic reproduction number is .
Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase
Authors: Park James Yeongjun
Published: March 2020

Background

Coronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC).

Method

Using the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020.

Results

Using spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters.

Conclusion

Compared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.
TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats
Authors: Gawrys-Kopczynska Marta , Konop Marek , Maksymiuk Klaudia , Kraszewska Katarzyna , Derzsi Ladislav , Sozański Krzysztof , Holyst Robert , Pilz Marta , Samborowska Emilia , Dobrowolski Leszek , Jaworska Kinga , Mogilnicka Izabella , Ufnal Marcin
Published: March 2020

Background

There is an ongoing debate whether trimethylamine-oxide (TMAO), a molecule present in seafood and a derivate of microbiota metabolism, is beneficial or harmful for the circulatory system. Interestingly, deep-water animals accumulate TMAO that protects proteins such as lactate dehydrogenase (LDH) against high hydrostatic pressure. We hypothesized that TMAO may benefit the circulatory system by protecting cardiac LDH exposed to hydrostatic stress (HS) produced by contracting heart.

Methods and Results

Male, 6-week-old, Sprague-Dawley (SD, n=40) and Spontaneously-Hypertensive-Heart-Failure (SHHF n=18) rats were divided into either Water or TMAO oral treatment. After 56 weeks, half of Water and TMAO SD rats were given isoprenaline (ISO) to produce catecholamine stress. In vitro, LDH with or without TMAO was exposed to HS (changes in pressure 0-250mmHg x 280min−1) and was evaluated using fluorescence correlation spectroscopy. After 58 weeks of the treatment survival was 100% in SD-Water, SD-TMAO, ISO-TMAO and 90% in ISO-Water. In SHHF-Water survival was 66% vs 100% in SHHF-TMAO. In general, TMAO-treated rats showed higher diuresis and natriuresis. In comparison to SHHF-Water, SHHF-TMAO showed significantly lower diastolic arterial blood pressure, plasma NT-proBNP and expression of angiotensinogen and AT1 receptors in the heart. In separate experiments, intravenous TMAO but not vehicle or urea significantly increased diuresis in SD. In vitro, exposure of LDH to HS with or without TMAO did not affect the protein structure.

Conclusions

TMAO reduces mortality in SHHF rats that is associated with diuretic, natriuretic and hypotensive effects. HS produced by the contracting heart is neutral for cardiac LDH structure.
Pseudomonas putidachromosomal toxin-antitoxin systems carry neither clear fitness benefits nor big costs
Authors: Rosendahl Sirli , Tamman Hedvig , Brauer Age , Remm Maido , Hõrak Rita
Published: March 2020

Chromosomal toxin-antitoxin (TA) systems are widespread genetic elements among bacteria, yet, despite extensive studies in the last decade, their biological importance remains ambivalent. The ability of TA-encoded toxins to affect stress tolerance supports the hypothesis of TA systems being associated with stress adaptation. However, the deletion of TA genes has usually no fitness consequences, supporting the selfish elements hypothesis. Here, we aimed to evaluate the cost and benefits of chromosomal TA systems toPseudomonas putida. We show that multiple TA systems do not confer fitness benefits to this bacterium as deletion of 13 TA loci does not influence stress tolerance, persistence and biofilm formation. Our results instead show that TA loci are costly and decrease the competitive fitness ofP. putida. Still, the cost of multiple TA systems is low and detectable in certain conditions only. Construction of antitoxin deletion strains showed that only five TA systems code for toxic proteins, while other TA loci have evolved towards reduced toxicity and encode non-toxic or moderately potent proteins. Analysis ofP. putidaTA systems’ homologs among fully sequencedPseudomonadssuggests that the TA loci have been subjected to purifying selection and that TA systems spread among bacteria by horizontal gene transfer.
CRISPR/Cas9-based genome editing in the silverleaf whitefly (Bemisia tabaci)
Authors: Heu Chan C. , McCullough Francine M. , Luan Junbo , Rasgon Jason L.
Published: March 2020

Bemisia tabacicryptic species Middle East-Asia Minor I (MEAM1) is a serious agricultural polyphagous insect pest, and vector of numerous plant viruses, causing major worldwide economic losses.B. tabacicontrol is limited by lack of robust gene editing tools. Gene editing is difficult inB. tabacidue to small embryos that are technically challenging to inject, and which have high mortality post-injection. We developed a CRISPR/Cas9 gene editing protocol based on injection of vitellogenic adult females rather than embryos (“ReMOT Control”). We identified an ovary-targeting peptide ligand (“BtKV”) that, when fused to Cas9 and injected into adult females, transduced the ribonucleoprotein complex to the germline, resulting in efficient, heritable editing of the offspring genome. In contrast to embryo injection, adult injection is easy and does not require specialized equipment. Development of easy-to-use gene editing protocols forB. tabaciwill allow researchers to apply the power of reverse genetic approaches to this species and will lead to novel control methods for this devastating pest insect.
Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs
Authors: Ono T. , Kamada K. , Hayashi R. , Piacenti A. R. , Gabbutt C. , Sriwilaijaroen N. , Hiramatsu H. , Kanai Y. , Inoue K. , Nakakita S. , Kawahara T. , Ie Y. , Watanabe Y. , Suzuki Y. , Contera S. , Matsumoto K.
Published: March 2020

Small solid-state devices are candidates for accelerating biomedical assays/drug discovery, however their potential remains unfulfilled. Here, we demonstrate that graphene-field effect transistors (FET) can be used to successfully detect the key molecular events underlying viral infections and the effect of antiviral drugs. Our device success is achieved by bio-mimicking the host-cell surface during an influenza infection at the graphene channel. In-situ AFM confirms the biological interactions at the sialic acid-functionalized graphene: viral hemagglutinin (HA) binds to sialic acid, and neuraminidase (NA) reacts with the sialic acid-HA complex. The graphene-FET detects HA binding to sialic acid, and NA cleavage of sialic acid. The inhibitory effect of the drug “zanamivir” on NA-sialic acid interactions is monitored in real-time; the reaction rate constant of NA-sialic acid reaction was successfully determined. We demonstrate that graphene-FETs are powerful platforms for measurement of biomolecular interactions and contribute to future deployment of solid-state devices in drug discovery/biosensing.
Ancient RNA virus epidemics through the lens of recent adaptation in human genomes
Authors: Enard David , Petrov Dmitri A.
Published: March 2020

Over the course of the last several million years of evolution, humans likely have been plagued by hundreds or perhaps thousands of epidemics. Little is known about such ancient epidemics and a deep evolutionary perspective on current pathogenic threats is lacking. The study of past epidemics has typically been limited in temporal scope to recorded history, and in physical scope to pathogens that left sufficient DNA behind, such asYersinia pestisduring the Great Plague.

Host genomes however offer an indirect way to detect ancient epidemics beyond the current temporal and physical limits. Arms races with pathogens have shaped the genomes of the hosts by driving a large number of adaptations at many genes, and these signals can be used to detect and further characterize ancient epidemics.

Here, we detect the genomic footprints left by ancient viral epidemics that took place in the past ~50,000 years in the 26 human populations represented in the 1,000 Genomes Project. By using the enrichment in signals of adaptation at ~4,500 host loci that interact with specific types of viruses, we provide evidence that RNA viruses have driven a particularly large number of adaptive events across diverse human populations. These results suggest that different types of viruses may have exerted different selective pressures during human evolution. Knowledge of these past selective pressures will provide a deeper evolutionary perspective on current pathogenic threats.
Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis
Authors: Su Tingting , Yang Yilin , Lai Sanchuan , Jeong Jain , Jung Yirang , McConnell Matthew , Utsumi Teruo , Iwakiri Yasuko
Published: March 2020

Dysfunction of liver endothelial cells (ECs), particularly sinusoidal endothelial cells (LSECs), is permissive for the progression of liver fibrosis/cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal versus cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using single-cell RNA sequencing technology. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. To add finer detail, we mapped the 3 clusters of LSECs to Zones 1 to 3. We found that heterogeneous liver EC identities are conserved even in liver cirrhosis and that Zone 3 LSECs are most susceptible to damage associated with liver cirrhosis, demonstrating increased capillarization and decreased ability to regulate endocytosis. Altogether, this study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most highly dysfunctional liver ECs.
Fear, Access, and the Real-Time Estimation of Etiological Parameters for Outbreaks of Novel Pathogens
Authors: Fefferman Nina H. , Lofgren Eric T. , Li Nianpeng , Blue Pieter , Weber David J. , Yakubu Abdul-Aziz
Published: March 2020

Early analysis of outbreaks of novel pathogens to evaluate their likely public health impact depends on fitting predictive models to data gathered and updated in real-time. Both transmission rates and the criticalR0threshold (i.e. the pathogen’s ‘reproductive number’) are inferred by finding the values that provide the best model fit to reported case incidence. These models and inferred results are then the basic tools used for public health planning: how many people expected to be infected, at what scales of time and space, and whether potential intervention strategies impact disease transmission and spread. An underlying assumption, however, is that the ability to observe new cases is either constant, or at least constant relative to diagnostic test availability.

We present a demonstration, discussion, and mathematical analysis of how this assumption of predictable observability in disease incidence can drastically impact model accuracy. We also demonstrate how to tailor estimations of these parameters to a few examples of different types of shifting influences acting on detection, depending on the likely sensitivity of surveillance systems to errors from sources such as clinical testing rates and differences in healthcare-seeking behavior from the public over time. Finally, we discuss the implications of these corrections for both historical and current outbreaks.
Age profile of susceptibility, mixing, and social distancing shape the dynamics of the novel coronavirus disease 2019 outbreak in China
Authors: Zhang Juanjuan , Litvinova Maria , Liang Yuxia , Wang Yan , Wang Wei , Zhao Shanlu , Wu Qianhui , Merler Stefano , Viboud Cecile , Vespignani Alessandro , Ajelli Marco , Yu Hongjie
Published: March 2020

Strict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.
Chromosomal resolution reveals symbiotic virus colonization of parasitic wasp genomes
Authors: Gauthier Jérémy , Boulain Hélène , van Vugt Joke J.F.A. , Baudry Lyam , Persyn Emma , Aury Jean-Marc , Noel Benjamin , Bretaudeau Anthony , Legeai Fabrice , Warris Sven , Chebbi Mohamed Amine , Dubreuil Géraldine , Duvic Bernard , Kremer Natacha , Gayral Philippe , Musset Karine , Josse Thibaut , Bigot Diane , Bressac Christophe , Moreau Sébastien , Periquet Georges , Harry Myriam , Montagné Nicolas , Boulogne Isabelle , Sabeti-Azad Mahnaz , Maïbèche Martine , Chertemps Thomas , Hilliou Frédérique , Siaussat David , Amselem Joëlle , Luyten Isabelle , Capdevielle-Dulac Claire , Labadie Karine , Merlin Bruna Laís , Barbe Valérie , de Boer Jetske G. , Marbouty Martial , Cônsoli Fernando Luis , Dupas Stéphane , Hua Van Aurélie , Le Goff Gaëlle , Bézier Annie , Jacquin-Joly Emmanuelle , Whitfield James B. , Vet Louise E.M. , Smid Hans M. , Kaiser-Arnault Laure , Koszul Romain , Huguet Elisabeth , Herniou Elisabeth A. , Drezen Jean-Michel
Published: March 2020

Most endogenous viruses, an important proportion of eukaryote genomes, are doomed to slowly decay. Little is known, however, on how they evolve when they confer a benefit to their host. Bracoviruses are essential for the parasitism success of parasitoid wasps, whose genomes they integrated ~103 million years ago. Here we show, from the assembly of a parasitoid wasp genome, for the first time at a chromosomal scale, that symbiotic bracovirus genes spread to and colonized all the chromosomes. Moreover, large viral clusters are stably maintained suggesting strong evolutionary constraints. Genomic comparison with another wasps revealed that this organization was already established ~53 mya. Transcriptomic analyses highlight temporal synchronization of viral gene expression, leading to particle production. Immune genes are not induced, however, indicating the virus is not perceived as foreign by the wasp. This recognition suggests that no conflicts remain between symbiotic partners when benefits to them converge.
Social interaction and network structure in groups ofDrosophilamales are shaped by prior social experience and group composition
Authors: Bentzur Assa , Ben-Shaanan Shir , Benishou Jennifer , Costi Eliezer , Ilany Amiyaal , Shohat-Ophir Galit
Published: March 2020

Living in a group creates a complex and dynamic environment in which the behavior of the individual is influenced by and affects the behavior of others. Although social interactions and group living are fundamental adaptations exhibited by many organisms, relatively little is known about how prior social experience, internal states and group composition shape behavior in a group, and the neuronal and molecular mechanisms that mediate it. Here we present a practical framework for studying the interplay between social experience and group interaction inDrosophila melanogasterand show that the structure of social networks and group interactions are sensitive to group composition and individuals’ social experience. We simplified the complexity of interactions in a group using a series of experiments in which we controlled the social experience and motivational states of individuals to dissect patterns that represent distinct structures and behavioral responses of groups under different social conditions. Using high-resolution data capture, machine learning and graph theory, we analyzed 60 distinct behavioral and social network features, generating a comprehensive representation (“group signature”) for each condition. We show that social enrichment promotes the formation of a distinct group structure that is characterized by high network modularity, high inter-individual and inter-group variance, high inter-individual coordination, and stable social clusters. Using environmental and genetic manipulations, we show that this structure requires visual and pheromonal cues, and that cVA sensing neurons are necessary for the expression of different aspects of social interaction in a group. Finally, we explored the formation of group behavior and structure in heterogenous groups composed of flies with distinct internal states, and discovered evidence suggesting that group structure and dynamics reflect a level of complexity that cannot be explained as a simple average of the individuals that constitute it. Our results demonstrate that fruit flies exhibit complex and dynamic social structures that are modulated by the experience and composition of different individuals within the group. This paves the path for using simple model organisms to dissect the neurobiology of behavior in complex social environments.
Click-ExM enables expansion microscopy for all biomolecules
Authors: Sun De-en , Fan Xinqi , Zhang Hao , Huang Zhimin , Tang Qi , Li Wei , Bai Jinyi , Lei Xiaoguang , Chen Xing
Published: March 2020

Expansion microscopy (ExM) allows super-resolution imaging on conventional fluorescence microscopes, but has been limited to proteins and nucleic acids. Here we develop click-ExM, which integrates click-labeling into ExM to enable a “one-stop-shop” method for nanoscale imaging of various types of biomolecules. Using 18 clickable labels for click-ExM imaging of DNA, RNA, proteins, lipids, glycans and small molecules, we demonstrate its universality, compatibility with signal-amplification techniques, and broad applications in cellular imaging.
Convergent evolution of the Hedgehog/Intein fold in protein splicing
Authors: Beyer Hannes M. , Virtanen Salla I. , Aranko A. Sesilja , Mikula Kornelia M. , Lountos George T. , Wlodawer Alexander , Ollila O. H. Samuli , Iwaï Hideo
Published: March 2020

The widely used molecular evolutionary clock assumes the divergent evolution of proteins. Convergent evolution has been proposed only for small protein elements but not for an entire protein fold. We investigated the structural basis of the protein splicing mechanism by class 3 inteins, which is distinct from class 1 and 2 inteins. We gathered structural and mechanistic evidence supporting the notion that the Hedgehog/INTein (HINT) superfamily fold, commonly found in protein splicing and related phenomena, could be an example of convergent evolution of an entire protein fold. We propose that the HINT fold is a structural and biochemical solution fortrans-peptidyl andtrans-esterification reactions.