bluuebunny/crossref_metadata_2025 huggingface dataset:
Bar Atmospherics and Smoking: A Qualitative Analysis of New Zealand Young Adult Smokers
Authors: Brillinger Julia , Marsh Louise , Hoek Janet
Published: November 2020

Introduction

Smoking among young adults is often associated with social contexts and alcohol use. Although many countries, including New Zealand, have prohibited smoking inside licensed premises, outdoor areas have enabled smoking and alcohol co-use to persist. We examined whether and how outdoor bar areas facilitate and normalize young adult smoking and explored potential policy implications.

Methods

We conducted in-depth interviews with 22 young adults who had recently smoked in a New Zealand bar or nightclub and investigated how physical design attributes (atmospherics) influenced experiences of smoking in outside bar settings. We used qualitative description to identify recurring accounts of the outdoor bar environment and thematic analysis to explore how participants experienced the bar in relation to smoking.

Results

Participants valued outdoor smoking areas that were comfortable and relaxing, and saw attributes such as seating, tables, heating, protection from inclement weather, and minimal crowding, as important. We identified four themes; these explained how participants used smoking to gain respite and make social connections, showed how bar settings enabled them to manage smoking’s stigma, and identified potential policy measures that would decouple smoking and alcohol co-use.

Conclusions

Evidence bar environments facilitate and normalize smoking among young adults questions whether smokefree policies should be expanded to include all bar areas. Introducing more comprehensive smokefree outdoor policies could reduce the influence of design attributes that foster smoking while also reframing smoking as outside normal social practice.

Implications

Bar environments contain many stimuli that cue and reinforce smoking and integrate smoking into social experiences. Expanding smokefree bar settings to include outdoor areas would reduce exposure to these stimuli, decrease opportunities for casual smoking, help maintain young people’s smokefree status, and support longer-term goals of sustained reductions in smoking prevalence.
Early-onset neonatal sepsis: Organism patterns between 2009 and 2014
Authors: Sgro Michael , Campbell Douglas M , Mellor Kaitlyn L , Hollamby Kathleen , Bodani Jaya , Shah Prakesh S
Published: November 2020

Objective

To evaluate trends in organisms causing early-onset neonatal sepsis (EONS). Congruent with recent reports, we hypothesized there would be an increase in EONS caused by Escherichia coli.

Study Design

National data on infants admitted to neonatal intensive care units from 2009 to 2014 were compared to previously reported data from 2003 to 2008. We report 430 cases of EONS from 2009 to 2014. Bivariate analyses were used to analyze the distribution of causative organisms over time and differences by gestational age. Linear regression was used to estimate trends in causative organisms.

Results

Since 2003, there has been a trend of increasing numbers of cases caused by E coli (P<0.01). The predominant organism was E coli in preterm infants and Group B Streptococcus in term infants.

Conclusions

With the majority of EONS cases now caused by E coli, our findings emphasize the importance of continued surveillance of causative organism patterns and developing approaches to reduce cases caused by E coli.
Health trajectories of children with severe obesity attending a weight management program
Authors: Buchholz Annick , Howard Andrea L , Baldwin Katherine , Hammond Nicole G , Mohipp Charmaine , Rutherford Jane , Kazoun Fatima , Clark Laurie , Adamo Kristi , Goldfield Gary , Hadjiyannakis Stasia
Published: November 2020

Purpose

The objective of the present study is to examine physical and mental health trajectories of change in youth with severe obesity attending a tertiary care weight management program. It was predicted that younger children would show favourable changes in body mass index (BMI), markers of cardiovascular health, quality of life, and mental health.

Methods

This 2-year longitudinal study examined health trajectories of children referred to a weight management program at a Canadian paediatric tertiary care centre from November 2010 to December 2013. Participants were 209 of 217 consecutive referred paediatric patients (families) aged 3 to 17 years who met criteria for severe obesity and consented to participate. To maximize generalizability of results, there were no exclusion criteria. Primary outcomes were children’s quality of life and BMI. Secondary outcomes included anxiety, depression, and non–high-density lipoprotein cholesterol levels.

Results

The findings suggest an improvement in mental health, quality of life, and cardiometabolic health of children and adolescents of all ages over the 2 years of programming. These positive findings were consistent across gender, age, and distance to the program. BMI trajectory changes varied across age cohorts such that younger children showed more favourable outcomes. The retention rate over the 2 years was high at 82.9%.

Conclusions

This is the first study to show improvements in both physical and mental health outcomes beyond 1 year in a tertiary care setting with a high-risk population of children and youth with severe obesity. Findings highlight the need to examine both mental and physical health outcomes beyond 1 year.
Molecular and Alkaloid Characterization of Claviceps purpurea Sensu Lato From Grass Seed Production Areas of the U.S. Pacific Northwest
Authors: Dung Jeremiah K. S. , Duringer Jennifer M. , Kaur Navneet , Scott Jeness C. , Frost Kenneth E. , Walenta Darrin L. , Alderman Stephen C. , Craig A. Morrie , Hamm Philip B.
Published: November 2020

Ergot, caused by Claviceps purpurea sensu lato, is an economically important seed replacement disease of Kentucky bluegrass (Poa pratensis) and perennial ryegrass (Lolium perenne) seed crops. C. purpurea sensu stricto is considered the primary Claviceps species responsible, but genetic diversity and cryptic species within C. purpurea sensu lato have previously been reported. Fifty-six C. purpurea sensu lato isolates collected from P. pratensis (n = 21) and L. perenne (n = 35) in Oregon and Washington between 2010 and 2014 were characterized via random amplified polymorphic DNA (RAPD), partial internal transcribed spacer (ITS), β-tubulin and elongation factor-1α (EF-1α) sequences, conidial size, and ergot alkaloid chemotype. Based on RAPD analysis, seven isolates from P. pratensis and 33 isolates from L. perenne collected in Oregon corresponded to C. purpurea sensu stricto, and 13 isolates collected from P. pratensis in Washington and Oregon were identified as C. humidiphila. Partial ITS, β-tubulin, and EF-1α sequences identified 10 isolates from P. pratensis as C. humidiphila, and seven isolates from P. pratensis and 33 isolates from L. perenne were identified as C. purpurea sensu stricto. Several isolates generated ambiguous RAPD bands or sequences that prevented identification. Ergot alkaloid chemotype profiling found that ergocornine and its epimer were predominant in sclerotia from P. pratensis, whereas ergotamine and its epimer were most abundant in sclerotia from L. perenne. This study confirms the presence of the C. purpurea sensu lato species complex in the U.S. Pacific Northwest and suggests that more research is needed to characterize and mitigate Claviceps spp. infection of grass seed crops in North America.
A Method for the Examination of SDHI Fungicide Resistance Mechanisms in Phytopathogenic Fungi Using a Heterologous Expression System in Sclerotinia sclerotiorum
Authors: Peng Jingyu , Sang Hyunkyu , Proffer Tyre J. , Gleason Jacqueline , Outwater Cory A. , Jung Geunhwa , Sundin George W.
Published: November 2020

Succinate dehydrogenase inhibitors (SDHIs) are a class of broad-spectrum fungicides used for management of diseases caused by phytopathogenic fungi. In many cases, reduced sensitivity to SDHI fungicides has been correlated with point mutations in the SdhB and SdhC target genes that encode components of the succinate dehydrogenase complex. However, the genetic basis of SDHI fungicide resistance mechanisms has been functionally characterized in very few fungi. Sclerotinia sclerotiorum is a fast-growing and SDHI fungicide–sensitive phytopathogenic fungus that can be conveniently transformed. Given the high amino acid sequence similarity and putative structural similarity of SDHI protein target sites between S. sclerotiorum and other common phytopathogenic ascomycete fungi, we developed an in vitro heterologous expression system that used S. sclerotiorum as a reporter strain. With this system, we were able to demonstrate the function of mutant SdhB or SdhC alleles from several ascomycete fungi in conferring resistance to multiple SDHI fungicides. In total, we successfully validated the function of Sdh alleles that had been previously identified in field isolates of Botrytis cinerea, Blumeriella jaapii, and Clarireedia jacksonii (formerly S. homoeocarpa) in conferring resistance to boscalid, fluopyram, or fluxapyroxad and used site-directed mutagenesis to construct and phenotype a mutant allele that is not yet known to exist in Monilinia fructicola populations. We also examined the functions of these alleles in conferring cross-resistance to more recently introduced SDHIs including inpyrfluxam, pydiflumetofen, and pyraziflumid. The approach developed in this study can be widely applied to interrogate SDHI fungicide resistance mechanisms in other phytopathogenic ascomycetes.
Massive subcutaneous hematoma of the anterior abdominal wall at the heparin injection site following anterior lumbar interbody fusion: a case report and review of literature
Authors: Ouyang Hanqiang , Jiang Liang , Lam Khai Sing
Published: November 2020

Introduction:

Various vascular complications of anterior lumbar interbody fusion (ALIF) have been reported in the orthopedic literature. However, a subcutaneous hematoma is an unexpected complication, especially following minimally invasive ALIF.

Patient Concerns:

We report a very rare case of a heparin-induced subcutaneous hematoma in a 25-year-old man who underwent a revision L5/S1 ALIF followed by a computer-assisted posterior pedicle screw fixation.

Diagnosis:

Massive subcutaneous hematoma of the anterior abdominal wall was diagnosed.

Interventions:

The patient presented with a massive, tense and severely painful lump at the subcutaneous heparin injection site affecting the left anterior abdominal wall on the fifth postoperative day. An urgent computer tomography angiography scan revealed a massive abdominal wall hematoma arising from one of the left deep inferior epigastric artery perforators. The patient was taken back to the operating theater for an evacuation of the hematoma and subsequently recovered without any further complications.

Outcomes:

The patient was discharged without complication on the postoperative sixth day.

Conclusion:

This is the first documented case of a massive subcutaneous hematoma of the abdominal wall following a minimally invasive ALIF procedure. This report adds to the body of evidence on the risk of postoperative bleeding in patients following ALIF surgery. Also, spine surgeons need to be aware that subcutaneous injury to the abdominal wall deep inferior epigastric artery perforators at the site of the heparin injection can rarely occur. Therefore heparin injection sites remote from the anterior abdominal wall must be considered especially following ALIF surgery.
Detection of hypofibrinogenemia during cardiac surgery: a comparison of resonance-based thrombelastography with the traditional Clauss method
Authors: Magunia Harry , Azizy Emily , Krautter Lisa , Rosenberger Peter , Straub Andreas
Published: November 2020

Bleeding after cardiac surgery is associated with significant morbidity and mortality. Hypofibrinogenemia is a crucial factor for bleeding in this setting and may be rapidly detected using point-of-care viscoelastic tests (POC-VET). However, the correlation of POC-VET with conventional coagulation assays is still unclear. The current study aimed to correlate resonance-based POC-VET assays (Haemonetics TEG 6s) with the traditional nonrapid Clauss method. Another aim was to identify a cut-off value for the detection of hypofibrinogenemia (fibrinogen plasma level below 150 mg/dl) focusing on the maximum amplitude of the TEG 6s citrated functional fibrinogen (CFF) assay. Adult patients undergoing cardiac surgery were screened for inclusion in this single-centre retrospective cohort study. Inclusion criteria were the availability of a TEG assay and timely corresponding laboratory results. Calculation of a CFF-maximum amplitude (CFF-MA) cut-off value was performed using receiver operating curve analysis in the baseline cohort and validated in the control cohort. The best correlation with the Clauss method was observed for the CFF-MA (r = 0.77; P < 0.0001) compared with the citrate kaolin maximum amplitude assay (r = 0.57; P < 0.0001) and the citrate kaolin heparinase maximum amplitude assay (r = 0.67; P < 0.0001). A cut-off value of 19.9 mm for the CFF-MA was calculated [area under the curve 0.87 (95% confidence interval: 0.82–0.92; P < 0.0001)]. This cut-off value had a sensitivity of 81.8% and a specificity of 71.1% for identification of hypofibrinogenemia in the control cohort. The resonance-based thrombelastography analyser can identify hypofibrinogenemia. Future clinical studies should investigate whether cut-off value guided coagulation therapy with POC-VET may improve patient outcomes in patients who suffer from bleeding complications.
An infectious diseases perspective on the microbiome and allogeneic stem cell transplant
Authors: Smibert Olivia C. , Trubiano Jason A. , Slavin Monica A. , Kwong Jason C.
Published: November 2020

Purpose of review

The gut microbiome presents a novel source of diagnostic and therapeutic potential to modify post allogeneic stem cell transplant complications. There is an explosion of interest in microbiome research, mostly in the form of single-centre prospective time-series cohorts utilizing a variety of sampling frequencies and metagenomic technologies to sequence the microbiome. The purpose of this review is to summarize important recent publications and contextualize them within what has already been described in this rapidly growing field.

Recent finding

Results from observational human cohort and animal transplant models add to the growing body of evidence that the microbiome modulates the immunopathogenesis of posttransplant complications. This is particularly the case for recipients of grafts replete with T cells where the evidence that acute graft-versus-host disease is mediated by anaerobic commensal-associated short-chain fatty acids, which interact with mucosa-associated (CD4+FOXP3+) T-regulatory cells.

Future human research into the role of the microbiome in allogeneic stem transplant should incorporate rigorous and considered experimental design in addition to next-generation sequencing technology to better portray microbiome functional potential and active gene expression. In combination with host immune phenotyping, which would facilitate a robust understanding of the host--microbiome interaction that is required before meaningful translation into clinical diagnostics and therapeutics can be expected.
Association of Mass Gatherings and COVID-19 Hospitalization
Authors: Miron Oren , Yu Kun-Hsing , Wilf-Miron Rachel , Davidovitch Nadav
Published: November 2020

We examined COVID-19 hospitalizations following mass gatherings in Wisconsin and Minnesota, United States (September 17-18, 2020). We found that the hospitalization rate increased 15-fold in the Minnesota gathering county, and 12.7-fold in the Wisconsin gathering county. On the state level, it increased 2-fold in Minnesota, and 2.3-fold in Wisconsin, while not increasing significantly in states without gatherings. Our findings suggest that mass gatherings are followed by increased COVID-19 hospitalizations, and that precautions should be taken.
SARS-CoV-2 detection by nasal strips: a superior tool for surveillance of pediatric populations
Authors: Chan Renee WY , Chan Kate C , Chan Kathy YY , Lui Grace CY , Tsun Joseph GS , Wong Rity YK , Yu Michelle WL , Wang Maggie HT , Chan Paul KS , Lam Hugh Simon , Li Albert M
Published: November 2020

Background

Deep throat saliva (DTS) and pooled nasopharyngeal swab and throat swab (NPSTS) are utilized for viral detection. DTS is challenging for children. Swabbing the respiratory mucosa requires trained personnel and may trigger sneezing and coughing, which generate droplets. A reliable, simple and safe sampling method applicable to a wide age range is required for community-based surveillance.

Methods

We introduced nasal strip as an easy and low-risk collection method. Asymptomatic and symptomatic SARS-CoV-2 infected patients (n = 38) were recruited. Nasal epithelial lining fluid (NELF) (n = 43) strip paired with nasal swab (n = 13) were collected by a healthcare worker to compare with NPSTS (n = 21) or DTS (n =22) collected within 24 hours as reference. All samples were subjected to viral RNA quantitation by real-time PCR targeting the nucleoprotein gene.

Results

Comparable Ct values were observed between paired nasal strip and nasal swab samples. The agreement between nasal strip samples and NPSTS was 94.44% and 100% for NPSTS positive and negative samples. Higher viral RNA concentration was detected in nasal strips than DTS samples. False-negative results were recorded in six DTS specimens, of which four were from children. Storage at room temperature up to 72 (n = 3) hours did not affect diagnostic yield of nasal strips.

Conclusions

Nasal strip is a reliable and non-invasive sampling method for SARS-CoV-2 detection, and viral detection remains stable for at least 72 hours. It can be used as an alternative tool for community-based surveillance.
Causal contribution of malignancy to anomalous baroreflex functionality in patients with cancer: An overlooked aspect of cardio-oncology
Authors: Fang Chi , Tsai Ching-Yi , Chien Chih-Yen , Chan Samuel H.H.
Published: November 2020

The current trend in cardio-oncology places major emphasis on circulatory toxicity induced by cancer therapy. Whether malignancy itself is a direct contributing factor to cardiovascular dysfunctions and baroreflex dysregulation in patients with cancer, however, has rarely appeared in literature. The present study addressed this largely overlooked aspect of cardio-oncology by evaluating blood pressure, heart rate and baroreflex functionality before and after curative surgery in patients with oral cavity squamous cell carcinoma (OSCC). We found that these patients exhibited reduced baroreflex-mediated sympathetic vasomotor tone and augmented cardiac vagal baroreflex, and such inherent anomalies were readily reversed to levels of healthy controls after surgical removal of the primary tumor. It is concluded that by being more prone to hypotension and bradycardia, anomalous baroreflex functionality causally induced by malignancy predisposes patients with cancer to detrimental cardiovascular abnormalities that may be further exacerbated by cancer therapy.
Predicting the Effect of Malaria Control Strategies Using Mathematical Modeling Approach
Authors: Eguda Felix Yakubu , Abah Samuel Eneojo , Andrawus James , Atuba Sunday , Abba Aliyu
Published: November 2020

Malaria is a life-threatening disease which has caused enormous public health challenge. A mathematical model describing the dynamics of malaria between the human and vector population is formulated to understand the important parameters in the transmission and develop effective prevention and control strategies. We analysed the model and found that the model has a disease-free equilibrium (DFE) which is locally and globally asymptotically stable if the effective reproduction number can be brought below unity. Our model shows that the infectivity of mildly infected children and adults amplifies the disease burden in a population. It was shown that the model does not undergo the phenomenon of backward bifurcation so long as the recovered children and adults do not lose their acquired immunity and if the infection of mildly infected adult is not high enough to infect susceptible mosquitoes. However, control strategies involving mosquito reduction through high rate of application of insecticide will serve as an effective malaria control strategy. It is further shown that whenever the effective reproduction number is greater than unity the model has a unique endemic equilibrium which is globally stable for the case when there is loss of acquired immunity in children and adults. Numerical simulations show that the presence of all the control strategies is more effective in preventing mild malaria cases in adult and children as compared to severe malaria cases in adult and children.
Sample pooling, a population screening strategy for SARS-CoV2 to prevent future outbreak and mitigate the “second-wave” of infection of the virus
Authors: Sawarkar S. , Victor A. , Viotti M. , Haran S. , Verma S. , Griffin D. , Sams J.
Published: November 2020

Problem

How do we manage treatment and stabilization in clinical settings and static population communities like assisted living facility settings of their patient or resident populations during and post the SARS-CoV-2 pandemic?

Scope

This proposal explores the possible and predicted changes to standard operating procedures to the facility management and associated landscape and focuses on series of deployments, during and post peak SARS-CoV-2 activity, and will outline possible models for the current medical facility model that we operate with. This article primarily focuses on non-emergency facility management.

Assumptions and understanding of the field

With a reduction in the numbers nationally, patients are highly motivated and likely to seek non-emergency and planned medical procedural treatment as early as possible as social distancing measures are eased and restrictions on non-urgent procedures are lifted.

Conclusions and next steps

An initial pan-national shutdown and suspension of services was necessary in an effort to ensure that essential medical services and resources were not strained. The authors feel that a strategic resumption of regular non-emergency treatments around the United States and continued provision of services at care facilities is possible with innovative testing strategies like pooled screening of large populations at a manageable price point. Moreover, pooling as a strategy when used widely, would be extremely effective at predicting outbreaks of the virus and as an effect help in mitigating the spread of the virus in its “second-wave”. We have developed one such innovative pooling strategy that can be easily deployed across laboratories and reduce the cost of population wide COVID-19 testing significantly
Clinical validation of Whole Genome Sequencing for cancer diagnostics
Authors: Roepman Paul , Bruijn Ewart de , Lieshout Stef van , Schoenmaker Lieke , Boelens Mirjam C , Dubbink Hendrikus J , Geurts-Giele Willemina RR , Groenendijk Floris H , Huibers Manon MH , EG Kranendonk Mariëtte , Roemer Margaretha GM , Samsom Kris G , Steehouwer Marloes , Leng Wendy WJ de , Hoischen Alexander , Ylstra Bauke , Monkhorst Kim , van der Hoeven Jacobus JM , Cuppen Edwin
Published: November 2020

Whole genome sequencing (WGS) using fresh frozen tissue and matched blood samples from cancer patients is becoming in reach as the most complete genetic tumor test. With a trend towards the availability of small biopsies and the need to screen an increasing number of (complex) biomarkers, the use of a single all-inclusive test is preferred over multiple consecutive assays. To meet high-quality diagnostics standards, we optimized and clinically validated WGS sample and data processing procedures resulting in a technical success rate of 95.6% for fresh-frozen samples with sufficient (≥20%) tumor content.

Independent validation of identified biomarkers against commonly used diagnostic assays showed a high sensitivity (recall) (98.5%) and precision (positive predictive value) (97.8%) for detection of somatic SNV and indels (across 22 genes), and high concordance for detection of gene amplification (97.0%, EGRF and MET) as well as somatic complete loss (100%, CDKN2A/p16). Gene fusion analysis showed a concordance of 91.3% between DNA-based WGS and an orthogonal RNA-based gene fusion assay. Microsatellite (in)stability assessment showed a sensitivity of 100% with a precision of 94%, and virus detection (HPV) an accuracy of 100% compared to standard testing.

In conclusion, whole genome sequencing has a >95% sensitivity and precision compared to routinely used DNA techniques in diagnostics and all relevant mutation types can be detected reliably in a single assay.
Service user experiences of community services for Complex Emotional Needs: A qualitative thematic synthesis
Authors: Rains Luke Sheridan , Echave Athena , Rees Jessica , Scott Hannah Rachel , Lever-Taylor Billie , Broeckelmann Eva , Steare Thomas , Barnett Phoebe , Cooper Chris , Jeynes Tamar , Russell Jessica , Oram Sian , Rowe Sarah , Johnson Sonia
Published: November 2020

Background

There is a recognised need to develop clear service models and pathways to provide high quality care in the community for people with complex emotional needs, who may have been given a “personality disorder” diagnosis. Services should be informed by the views of people with these experiences.

Aims

To systematically review and synthesise qualitative studies on service user experiences of community mental health care for Complex Emotional Needs.

Methods

We searched six bibliographic databases for papers published since 2003. We included peer reviewed studies reporting data on service user experiences and views about good care from community-based mental health services for adults with CEN, including generic mental health services and specialist “personality disorder” services. Studies using any qualitative method were included and thematic synthesis used to identify over-arching themes.

Results

Forty-seven papers were included. Main themes were: 1) The need for a long-term perspective on treatment journeys; 2) The need for individualised and holistic care; 3) Large variations in accessibility and quality of mental health services; 4) The centrality of therapeutic relationships; 5) Impacts of ‘personality disorder’ diagnosis. Themes tended to recur across studies from different countries and years.

Discussion

Recurrent major themes included wanting support that is individualised and holistic, provides continuity over long journeys towards recovery, and that is delivered by empathetic and well-informed clinicians who are hopeful but realistic about the prospects of treatment. Care that met these simple and clearly stated priorities tended to be restricted to often limited periods of treatment by specialist “personality disorder” services: generic and primary care services were often reported as far from adequate. There is an urgent need to co-design and test strategies for improving long-term support and treatment care for people with “personality disorders” throughout the mental health care system.
OmicPioneer-sc: an integrated, interactive visualization environment for single-cell sequencing data
Authors: Weinstein John N. , Rohrdanz Mary A. , Stucky Mark , Melott James , Ma Jun , Mohanty Vakul , Manyam Ganiraju , Wakefield Christopher , Chen Ken , Navin Nicholas E. , Ryan Michael C. , Akbani Rehan , Broom Bradley M.
Published: November 2020

OmicPioneer-sc is an open-source data visualization/analysis package that integrates dimensionality-reduction plots (DRPs) such as t-SNE and UMAP with Next-Generation Clustered Heat Maps (NGCHMs) and Pathway Visualization Modules (PVMs) in a seamless, highly interactive exploratory environment. It includes fluent zooming and navigation, a statistical toolkit, dozens of link-outs to external public bioinformatic resources, high-resolution graphics that meet the requirements of all major journals, and the ability to store all metadata needed to reproduce the visualizations at a later time. A user-friendly, multi-panel graphical interface enables non-informaticians to interact with the system without programming, asking and answering questions that require navigation among the three types of modules or extension from them to the Gene Ontology or information on therapies. The visual integration can be useful for detective work to identify and annotate cell-types for color-coding of the DRPs, and multiple NGCHMs can be layered on top of each other (with toggling among them) as an aid to multi-omic analysis. The tools are available in containerized form with APIs to facilitate incorporation as a plug-in to other bioinformatic environments. The capabilities of OmicPioneer-sc are illustrated here through application to a single-cell RNA-seq airway dataset pertinent to the biology of both cancer and COVID-19.

[Supplemental material is available for this article.]
Canopy micrometeorology monitoring in diverse climates innovatively improves the evaluation heat-induced sterility of rice under climate change
Authors: Yoshimoto Mayumi , Fukuoka Minehiko , Tsujimoto Yasuhiro , Matsui Tsutomu , Kobayasi Kazuhiro , Saito Kazuki , van Oort Pepijn A.J. , Inusah Baba I.Y , Vijayalakshmi Chenniappan , Vijayalakshmi Dhashnamurthi , Weerakoon W.M.W. , Chandradasa Silva , Daw Tin Tin Myint , Daw Zar Chi Phyo , Tian Xiaohai , Lur Huu-Sheng , Yang Chwen-Ming , Tarpley Lee , Manigbas Norvie L. , Hasegawa Toshihiro
Published: November 2020

This study is the first and unique of open-field studies to assess the determination process of heat-induced spikelet sterility (HISS) of rice by using the same variety and the same monitoring system, MINCER (Micrometeorological Instrument for Near Canopy Environment of Rice), covering the major-rice growing regions from Sub-Saharan Africa, South, Southeast, and East Asia, and USA. Applying the observation data from the monitoring network, MINCERnet, to the canopy heat balance model, IM2PACT, it was quantitatively corroborated in open-field conditions worldwide that the canopy and panicle transpiration and their evaporative cooling effect played a great role on the micrometeorological gap between the ambient air temperature and the panicle temperature, and that the sterility rate due to HISS in open-fields can be evaluated accurately in diverse climates by the mean panicle temperature at flowering hours in the flowering period. The heat balance structure suggested that the risk of HISS should be higher in high humidity climates rather than in dry climates also in the future, which lead to the importance of the humidity accuracy as well as of the air temperature in climate scenarios and their spatial downscaling for future prediction of rice heat stress and production. Applying the heat-tolerant variety was suggested to be able to keep the sterility due to HISS low in all climates. It is needed of the approach using the panicle temperature as indicator of HISS by intervening sub-model and/or monitoring of micrometeorology inside the canopy to reduce uncertainties in future rice yield prediction under various adaptation measures.
Trade-offs between risks of predation and starvation in larvae make the shelf break an optimal spawning location for Atlantic Bluefin tuna
Authors: Shropshire Taylor A. , Morey Steven L. , Chassignet Eric P. , Coles Victoria J. , Karnauskas Mandy , Malca Estrella , Laiz-Carrión Raúl , Fiksen Øyvind , Reglero Patricia , Shiroza Akihiro , Quintanilla Hervas José M. , Gerard Trika , Lamkin John T. , Stukel Michael R.
Published: November 2020

Atlantic Bluefin tuna (ABT) (Thunnus thynnus) travel long distances to spawn in oligotrophic regions of the Gulf of Mexico. To estimate regional larval ABT mortality, we developed a spatially-explicit, Lagrangian, individual-based model that simulates dispersal, growth, and mortality within realistic predator and prey fields during the spawning periods from 1993-2012. Modelled larval ABT experience high mortality in the first week of feeding with an average mortality rate of 0.53 ± 0.26 d−1prior to postflexion. Survival ranged from 0.12%–0.32% suggesting that recruitment may vary by a factor of 2.7 due to early life stage mortality alone. Starvation is the dominant source of mortality driven by the early critical period; however, survival is ultimately limited by predation on older individuals. As a result, first-feeding larvae survive better in the more food-rich areas on the shelf, while larger larvae survive better in the open ocean with fewer predators, making the shelf break an optimal spawning area. Our findings support the hypothesis that ABT spawn in oligotrophic regions to minimize predation on their larvae. Ocean modeling tools presented in this study may help facilitate an ecosystem-based management approach to improve future stock assessment models by better resolving the stock-recruitment relationship.
Structural basis for repurpose and design of nucleoside drugs for treating COVID-19
Authors: Yin Wanchao , Luan Xiaodong , Li Zhihai , Xie Yuanchao , Zhou Ziwei , Liu Jia , Gao Minqi , Wang Xiaoxi , Zhou Fulai , Wang Qingxia , Wang Qingxing , Shen Dandan , Zhang Yan , Tian Guanghui , Aisa Haji A. , Hu Tianwen , Wei Daibao , Jiang Yi , Xiao Gengfu , Jiang Hualiang , Zhang Leike , Yu Xuekui , Shen Jingshan , Zhang Shuyang , Xu H. Eric
Published: November 2020

SARS-CoV-2 has caused a global pandemic of COVID-19 that urgently needs an effective treatment. Nucleoside analog drugs including favipiravir have been repurposed for COVID-19 despite of unclear mechanism of their inhibition of the viral RNA polymerase (RdRp). Here we report the cryo-EM structures of the viral RdRp in complex with favipiravir and two other nucleoside inhibitor drugs ribavirin and penciclovir. Ribavirin and the ribosylated form of favipiravir share a similar ribose scaffold that is distinct from penciclovir. However, the structures reveal that all three inhibitors are covalently linked to the primer strand in a monophosphate form despite the different chemical scaffolds between favipiravir and penciclovir. Surprisingly, the base moieties of these inhibitors can form mismatched pairs with the template strand. Moreover, in view of the clinical disadvantages of remdesivir mainly associated with its prodrug form, we designed several orally-available remdesivir parent nucleoside derivatives, including VV16 that showed 5-fold more potent than remdesivir in inhibition of viral replication. Together, these results demonstrate an unexpected promiscuity of the viral RNA polymerase and provide a basis for repurpose and design of nucleotide analog drugs for COVID-19.

One Sentence Summary

Cryo-EM structures of the RNA polymerase of SARS-CoV-2 reveals the basis for repurposing of old nucleotide drugs to treat COVID-19.
Beyond linearity in neuroimaging: Capturing nonlinear relationships with application to longitudinal studies
Authors: Chen Gang , Nash Tiffany A. , Reding Katherine M. , Kohn Philip D. , Wei Shau-Ming , Gregory Michael D. , Eisenberg Daniel P. , Cox Robert W. , Berman Karen F. , Kippenhan J. Shane
Published: November 2020

The ubiquitous adoption of linearity for quantitative explanatory variables in statistical modeling is likely attributable to its advantages of straightforward interpretation and computational feasibility. The linearity assumption may be a reasonable approximation especially when the variable is confined within a narrow range, but it can be problematic when the variable’s effect is non-monotonic or complex. Furthermore, visualization and model assessment of a linear fit are usually omitted because of challenges at the whole brain level in neuroimaging. By adopting a principle of learning from the data in the presence of uncertainty to resolve the problematic aspects of conventional polynomial fitting, we introduce a flexible and adaptive approach of multilevel smoothing splines (MSS) to capture any nonlinearity of a quantitative explanatory variable for population-level neuroimaging data analysis. With no prior knowledge regarding the underlying relationship other than a parsimonious assumption about the extent of smoothness (e.g., no sharp corners), we express the unknown relationship with a sufficient number of smoothing splines and use the data to adaptively determine the specifics of the nonlinearity. In addition to introducing the theoretical framework of MSS as an efficient approach with a counterbalance between flexibility and stability, we strive to (a) lay out the specific schemes for population-level nonlinear analyses that may involve task (e.g., contrasting conditions) and subject-grouping (e.g., patients vs controls) factors; (b) provide modeling accommodations to adaptively reveal, estimate and compare any nonlinear effects of an explanatory variable across the brain, or to more accurately account for the effects (including nonlinear effects) of a quantitative confound; (c) offer the associated program 3dMSS to the neuroimaging community for whole-brain voxel-wise analysis as part of the AFNI suite; and (d) demonstrate the modeling approach and visualization processes with a longitudinal dataset of structural MRI scans.
Chemical signatures of human odour generate a unique neural code in the brain ofAedes aegyptimosquitoes
Authors: Zhao Zhilei , Zung Jessica L. , Kriete Alexis L. , Iqbal Azwad , Younger Meg A. , Matthews Benjamin J. , Merhof Dorit , Thiberge Stephan , Strauch Martin , McBride Carolyn S.
Published: November 2020

A globally invasive form of the mosquitoAedes aegyptispecializes in biting humans, making it an efficient vector of dengue, yellow fever, Zika, and chikungunya viruses. Host-seeking females strongly prefer human odour over the odour of non-human animals, but exactly how they distinguish the two is not known. Vertebrate odours are complex blends of volatile chemicals with many shared components, making discrimination an interesting sensory coding challenge. Here we show that human and animal odour blends evoke activity in unique combinations of olfactory glomeruli within theAedes aegyptiantennal lobe. Human blends consistently activate a ‘universal’ glomerulus, which is equally responsive to diverse animal and nectar-related blends, and a more selective ‘human-sensitive’ glomerulus. This dual signal robustly distinguishes humans from animals across concentrations, individual humans, and diverse animal species. Remarkably, the human-sensitive glomerulus is narrowly tuned to the long-chain aldehydes decanal and undecanal, which we show are consistently enriched in (though not specific to) human odour and which likely originate from unique human skin lipids. We propose a model of host-odour coding wherein normalization of activity in the human-sensitive glomerulus by that in the broadly-tuned universal glomerulus generates a robust discriminatory signal of the relative concentration of long-chain aldehydes in a host odour blend. Our work demonstrates how animal brains may distil complex odour stimuli of innate biological relevance into simple neural codes and reveals novel targets for the design of next-generation mosquito-control strategies.
A molecular calcium integrator reveals a striatal cell-type driving aversion
Authors: Kim Christina K. , Sanchez Mateo I. , Hoerbelt Paul , Fenno Lief E. , Malenka Robert C. , Deisseroth Karl , Ting Alice Y.
Published: November 2020

The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell-type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE’s modular design, we expressed an optogenetic channel selectively in this cell-type, and showed that direct recruitment of this otherwise genetically-inaccessible population elicits behavioral aversion. The specificity and minute-resolution of FLiCRE enables molecularly-informed characterization, manipulation, and reprogramming of activated cellular ensembles.
Designing safe and potent herbicides with the cropCSM online resource
Authors: Pires Douglas E. V. , Stubbs Keith A. , Mylne Joshua S. , Ascher David B.
Published: November 2020

Herbicides have revolutionised weed management, increased crop yields and improved profitability allowing for an increase in worldwide food security. Their widespread use, however, has also led to not only a rise in resistance but also concerns about their environmental impact. To help identify new, potent, non-toxic and environmentally safe herbicides we have employed interpretable predictive models to develop the online tool cropCSM (http://biosig.unimelb.edu.au/crop_csm).
Defective Autophagy inSf1Neurons Perturbs the Metabolic Response to Fasting and Causes Mitochondrial Dysfunction
Authors: Coupé Bérengère , Leloup Corinne , Maillard Julien , Pénicaud Luc , Horvath Tamas L. , Bouret Sebastien G.
Published: November 2020

Objective

The ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive. Autophagy is an evolutionarily conserved mechanism that maintains cellular homeostasis by turning over cellular components and providing nutrients to the cells during starvation. Here we investigated the importance of the autophagy-related geneAtg7inSf1-expressing neurons of the VMH in control and fasted conditions.

Methods

We generatedSf1-Cre;Atg7loxP/loxPmice and examined their metabolic and cellular response to fasting.

Results

Fasting induces autophagy in the VMH, and mice lackingAtg7inSf1-expressing neurons display altered regulation in glucose and leptin homeostasis and impaired energy expenditure regulation in response to fasting. Moreover, loss ofAtg7inSf1neurons causes alterations in the central response to fasting. Furthermore, alterations in mitochondria morphology and activity are observed in mutant mice.

Conclusion

Together, these data show that autophagy is nutritionally regulated in VMH neurons and that VMH autophagy participates in the control of energy homeostasis during fasting.
Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning
Authors: Brierley Liam , Fowler Anna
Published: November 2020

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 225 and 187 viruses belonging to the familyCoronaviridae, respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached ∼73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases.
Ivermectin reduces coronavirus infectionin vivo: a mouse experimental model
Authors: Arévalo AP , Pagotto R , Pórfido J , Daghero H , Segovia M , Yamasaki K , Varela B , Hill M , Verdes JM , Duhalde Vega M , Bollati-Fogolín M , Crispo M
Published: November 2020

SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.
High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
Authors: Pierce Sarah E. , Granja Jeffrey M. , Greenleaf William J.
Published: November 2020

Spear-ATAC is a modified droplet-based single-cell ATAC-seq (scATAC-seq) protocol that enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at a time. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations revealed the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles, demonstrating a high-throughput method for perturbing and evaluating dynamic single-cell epigenetic states.