bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotiana benthamiana Argonaute10 plays a pro‐viral role in Bamboo mosaic virus infection
Authors: Huang Ying Wen , Hu Chung Chi , Tsai Ching Hsiu , Lin Na Sheng , Hsu Yau Heiu
Published: July 2019

RNA silencing is a major defense mechanism against invading viruses in plants. Argonaute proteins (AGOs) are the key players in RNA silencing. The number of AGO family members involved varies depending on the plant species and they play distinct or sometimes redundant roles in antiviral defense.

By using a virus‐induced gene silencing technique, it was found that Nicotiana benthamiana AGO1 restricted Bamboo mosaic virus (BaMV) accumulation, but NbAGO10, the closest paralog of NbAGO1, positively regulated BaMV accumulation.

Immunoprecipitation assay revealed BaMV virus‐derived small interfering RNAs (vsiRNAs) in NbAGO10 complexes. Transient overexpression of NbAGO10 increased BaMV RNA accumulation, but with co‐expression of NbAGO1, BaMV RNA accumulation was reduced, which suggests that NbAGO10 may have competed with NbAGO1 for sequestering BaMV vsiRNA and prevented the formation of RNA‐induced silencing complexes. In addition, overexpression of NbAGO10 decreased BaMV vsiRNA accumulation. A host enzyme, small RNA degrading nuclease 1 (SDN1), also was found to interact with NbAGO10 on in vivo pull‐down assay. Silencing of SDN1 elevated BaMV vsiRNA level and decreased BaMV RNA accumulation in N. benthamiana, indicating that NbAGO10 might recruit SDN1 for BaMV vsiRNA degradation.

The results herein suggested that NbAGO10 plays a pro‐viral role by BaMV vsiRNA sequestration and degradation.
MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome
Authors: Al‐Rawaf Hadeel A. , Alghadir Ahmad H. , Gabr Sami A.
Published: July 2019

Background

Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain‐related comorbidities in adolescents with CFS and healthy controls (HCs).

Methods

A total of 150 adolescents, 12 to 18 years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n = 100) and HCs (n = 50). Reverse‐transcription polymerase chain reaction was used to evaluate the expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and cyclooxygenase‐2 (COX‐2).

Results

Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL‐6, TNF‐α, and COX‐2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain–related markers IL‐6, TNF‐α, and COX‐2 compared with the levels of boys with CFS.

Conclusions

The intensity and consequences of pain were influenced by differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143, which was directly associated with higher expression of the immune inflammatory‐related genes TNFα, IL‐6, and COX‐2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.
IsomiRs and tRNA‐derived fragments are associated with metastasis and patient survival in uveal melanoma
Authors: Londin Eric , Magee Rogan , Shields Carol L. , Lally Sara E. , Sato Takami , Rigoutsos Isidore
Published: July 2019

Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with patient prognosis, including the copy number of chromosome 3, genetic alterations in the BAP1, EIF1AX and SF3B1 genes, and other transcriptional features. Here, we expand upon previous reports by comprehensively characterizing the short RNA‐ome in 80 primary UVM tumor samples. In particular, we describe a previously unseen complex network involving numerous regulatory molecules that comprise microRNA (miRNAs), novel UVM‐specific miRNA loci, miRNA isoforms (isomiRs), and tRNA‐derived fragments (tRFs). Importantly, we show that the abundance profiles of isomiRs and tRFs associate with various molecular phenotypes, metastatic disease, and patient survival. Our findings suggest deep involvement of isomiRs and tRFs in the disease etiology of UVM. We posit that further study and characterization of these novel molecules will improve understanding of the mechanisms underlying UVM, and lead to the development of new diagnostic and therapeutic approaches.
Novel ERCC2 mutation in two siblings with trichothiodystrophy
Authors: Lund Emily B. , Stein Sarah L.
Published: July 2019

Trichothiodystrophy describes a group of recessively inherited multisystem neuroectodermal disorders that takes its name from the characteristic feature of brittle, sulfur‐deficient hair. We describe two siblings with trichothiodystrophy due to a novel genotype. The maternal mutation (p.Arg722Trp) is a previously described pathogenic mutation in ERCC2 that has been shown to result in a severe phenotype, while the paternal mutation (c.1480‐1G > C) has not been previously reported. Our cases confirm the severe phenotype associated with the p.Arg722Trp mutation and expand the known genetic mutations associated with trichothiodystrophy by demonstrating a novel pathogenic mutation in ERCC2.
Microwave treatment of breast milk for prevention of cytomegalovirus infection
Authors: Mikawa Takeshi , Mizuno Katsumi , Tanaka Kazuo , Kohda Chikara , Ishii Youko , Yamamoto Kazuya , Kobayashi Shunjiro
Published: July 2019

Background

Breast milk (BM) is the best nutrition for very preterm infants (VPI), except when provided by human cytomegalovirus (HCMV)‐seropositive mothers. Given that VPI are at high risk of developing a sepsis‐like syndrome or cholestasis, methods for prevention of HCMV infection via BM have been investigated. Although Holder pasteurization (HP) is the gold standard, HP needs special instruments. Microwave (MW) is available anywhere, therefore, we performed this study to determine whether MW can be used for HCMV prevention.

Methods

Human cytomegalovirus Towne strain was added to formula, followed by heating procedure using HP or MW (at 500 W for 20, 30, 40, or 60 s). HFL‐III cells were seeded in culture dishes. Aliquots of HCMV‐milk samples after heating were inoculated onto susceptible cell monolayers. The number of plaques was counted to determine the viral titer. The determination of HCMV‐DNA copies was also performed.

Results

Addition of HCMV for a viral load of 5.0 × 103 plaque‐forming units (p.f.u.)/mL achieved 772 p.f.u./mL at baseline, with a decrease to 257 p.f.u./mL after MW radiation for 20 s. No plaque was detected after HP or MW for 30, 40, and 60 s. The temperature of the breast milk reached 60°C after MW radiation for 40 s. The number of HCMV‐DNA copies did not change with MW.

Conclusions

Microwave at 500 W for 40 s can be used as a prevention strategy for HCMV transmission. Further research including the loss of bioactive properties in BM is required prior to clinical application.
What Gets Measured, Gets Done: Understanding and Addressing Middle‐Class Challenges
Authors: Ely Todd L. , Propheter Geoffrey , Jones Rich , Wasserman Scott
Published: July 2019

Middle‐class families face a range of challenges, including uneven income growth, imposing child care costs, and affordability gaps for higher education. The ideal policies by which policy makers and public administrators can aid the middle class are far from obvious. Policy solutions are likely to mirror our government and population, meaning that they will be decentralized and varied. Achieving a “growing and thriving middle class” requires understanding the composition of the middle class across the country. Benchmarking and measuring the middle‐class condition at the state and substate levels is critical to crafting and adopting effective policy solutions. This Viewpoint essay highlights the Colorado context to demonstrate the measurement of the middle class and tracking of its lived experiences.
Case-Only Trees and Random Forests for Exploring Genotype-Specific Treatment Effects in Randomized Clinical Trials with Dichotomous End Points
Authors: Dai James Y. , LeBlanc Michael
Published: July 2019

Discovering gene–treatment interactions in clinical trials is of rising interest in the era of precision medicine. Non-parametric statistical learning methods such as trees and random forests are useful tools for building prediction rules. We introduce trees and random forests to the recently proposed case-only approach for discovering gene–treatment interactions and estimating marker-specific treatment effects for a dichotomous trial's end points. The motivational example is a case–control genetic association study in the prostate cancer prevention trial, which tested the hypothesis whether finasteride can prevent prostate cancer. We compare this novel approach with the interaction tree method previously proposed. Because of the modelling simplicity—directly targeting at interaction—and the statistical efficiency of the case-only approach, case-only trees and random forests yield more accurate prediction of heterogeneous treatment effects and a better measure of variable importance, relative to the interaction tree method which uses data from both cases and controls. Application of the proposed case-only trees and random forests to the prostate cancer prevention trial study yielded a discovery of genotypes that may influence the prevention effect of finasteride.
Appetite for Destruction? China, Ecologically Unequal Exchange, and Forest Loss
Authors: Shandra John M. , Restivo Michael , Sommer Jamie M.
Published: July 2019

We test the hypothesis from the theory of ecologically unequal exchange that agricultural exports to China are related to increased forest loss in low‐ and middle‐income nations exporting to it. We do so by analyzing data for 75 low‐ and middle‐income nations using ordinary least squares regression. We find support for our hypothesis that flows of agricultural exports from low‐ and middle‐income nations to China are related to increased forest loss in exporting nations. We also find that a country's total agricultural exports, proximity of forest to infrastructure, and protected areas tend to increase forest loss.
Neighborhood Norms, Disadvantage, and Intimate Partner Violence Perpetration
Authors: Copp Jennifer E. , Giordano Peggy C. , Manning Wendy D. , Longmore Monica A.
Published: July 2019

Most theoretical treatments of intimate partner violence (IPV) focus on individual‐level processes. More recently, scholars have begun to examine the role of macrolevel factors. Results of that research indicate that social ties facilitate the diffusion of cultural norms—including tolerance of deviance/violence—across neighborhoods. Yet the influence of the neighborhood normative climate extends beyond norms regarding the use of violence, shaping cultural understanding about dating and the opposite sex. Using data from the Toledo Adolescent Relationships Study (TARS), the current investigation examines the multilevel association between dating norms and IPV perpetration among a large, diverse sample of adolescents and young adults. Results indicate that individuals’ liberal dating attitudes are associated with IPV perpetration. Furthermore, this effect varies across levels of neighborhood disadvantage.
Melanated Millennials and the Politics of Black Hair
Authors: Orey Byron D'Andra , Zhang Yu
Published: July 2019

Objective

This research employs the phenotypic prototypicality framework to makes a connection between African‐American voters' perceptions of African‐American women candidates' appearances and candidate evaluations in contests with limited information. The primary focus is on the candidates' skin tone and hair texture.

Methods

The data consist of a convenience sample of 672 African‐American students from a Historically Black University in the Deep South. An experimental research design was employed to test whether African‐American candidates who possessed phenotypes that mirrored the prototypical African American were perceived differently when compared to those with more Eurocentric features. Each subject was randomly exposed to a stimulus that consisted of a brief campaign platform and an image of a light or dark woman donning either straight hair, twist outs or dreadlocks. Those subjects in the control group were exposed to an image of a dark male with short hair.

Results

African‐American students found the dark candidates to be more attractive when compared to their lighter counterparts, regardless of hairstyles. Candidates who possessed the prototypical Afrocentric appearance (i.e., dark skin and/or textured hair) were found to be more supportive of Historically Black Colleges and Universities, progressive policies and were perceived to be more hardworking, when compared to their lighter counterparts. Light‐skinned women, regardless of hairstyles, were perceived to be less supportive of Black Nationalist views.

Conclusion

The findings here run counter to the conventional wisdom associated with colorism, whereby African Americans have been deemed to possess self‐hatred by possessing a more positive bias toward women with a lighter hue and straight hair. In recent years, due to such events as police shootings of unarmed African‐Americans and the Black Lives Matter movement, Black Millennials have become more aware of the oppression and discrimination faced by many African Americans. This heightened level of consciousness, in tandem with the fact that they were born during an era when natural hairstyles were being popularized, has led them to embrace the aesthetic revolution that includes appreciating their melanated skin and kinky hair.
A contemporary description of patients’ estimated blood losses from diagnostic phlebotomy in a census of hospital episodes from a Canadian tertiary care center
Authors: Quinn Jason G. , Levy Adrian R. , Cheng Calvino K. , Doucette Steve , Theriault Chris , Doiron Don , Kiberd Bryce A. , Tennankore Karthik K.
Published: July 2019

BACKGROUND

Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital‐wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations.

STUDY DESIGN AND METHODS

Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients.

RESULTS

Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p < 0.001). Phlebotomy volumes were highest on the first day of admission and declined thereafter (p < 0.001). For nontransfused individuals in the first week of admission, Hb levels decreased by the highest percentage in the ICU. The rate of RBC unit transfusion was highest in the ICU (232.4 units/1000 patient‐days; 95% confidence interval, 225.8‐239.2; p < 0.0001 compared with all other locations).

CONCLUSION

Considerable variation was observed in estimated blood loss due to diagnostic phlebotomy across different services within one teaching hospital. Thi information is foundational for planning interventions to minimize estimated blood loss from phlebotomy.
Emerging roles of adjunct therapies in acquired thrombotic thrombocytopenia purpura
Authors: Racine‐Brzostek Sabrina E. , Shi Patricia A.
Published: July 2019

KEY IDEAS

Acquired thrombotic thrombocytopenia purpura (aTTP) is caused by autoantibody‐mediated severe deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), with subsequent accumulation of ultra‐large vWF‐multimers that spontaneously form platelet‐VWF complexes and microthrombi within the microcirculation.

Therapeutic plasma exchange (TPE), by removing autoantibodies and excess ultra‐large vWF multimers and replenishing ADAMTS13 activity, remains the urgent primary initial treatment. Although heterogeneity in treatment exists, most centers add upfront immunosuppression with steroids, and many also add upfront rituximab. Refractoriness, exacerbation and relapse are commonly treated with adjunct rituximab.

Despite adjunct steroids and rituximab, TTP refractoriness, exacerbation, relapse, morbidity, and mortality remain problematic. Newer adjunct therapies include suppression of ADAMTS13 autoantibody production via plasma cell depletion, inhibition of vWF‐platelet interaction, and replenishment of ADAMTS13 function with recombinant ADAMTS13 protein.
Recent Advances in Shock Vibration Isolation: An Overview and Future Possibilities
Authors: Ledezma-Ramírez Diego Francisco , Tapia-González Pablo Ernesto , Ferguson Neil , Brennan Michael , Tang Bin
Published: July 2019

Mechanical shock is a common problem that is present in many situations, such as ground motion, blast, explosions, crash, and impact. The development of passive, active, or adaptive control and isolation strategies for shock-induced vibration has experienced recent interest, typically due to the increasing demand in improved isolation requirements for sensitive equipment subjected to harsh environments. This paper presents a review of some of the significant recent works developed in the field, focusing on novel developments that contribute to the shock isolation. The article explores several isolation approaches considering passive, active, and nonlinear systems discussing both theoretical and experimental results. In addition, important outcomes of the work are reviewed. The paper concludes with suggestions for potential developments, applications, and recommendations for future research.
Acoustic radiation of subsonic jets in the vicinity of an inclined flat plate
Authors: Nogueira Petrônio A. S. , Sirotto José R. L. N. , Miotto Renato F. , Cavalieri André V. G. , Cordioli Julio A. , Wolf William R.
Published: July 2019

Acoustic measurements of turbulent jets in the vicinity of a flat plate, mimicking a neighbouring wing, were compared to results from two wavepacket-based source models previously studied in the literature: the Tailored Green's Function method, which considers the radiation of the turbulent structure in the vicinity of a semi-infinite flat plate, and the Boundary Element Method, which can represent the full geometry of the plate used in the experiments. Particular interest is given to analysing how the angle of attack of the plate (α) affects the sound radiated by an installed jet with trailing edge 6 diameters away from the nozzle and 1 diameter away from the centerline for 0° ≤ α ≤ 45°. The results herein confirm the behaviour identified by the models: the scattered acoustic field follows the rotation of the plate, shifting a silence region with negligible scattered sound, and creating regions with lower noise levels in positions that correspond to the ground for an aircraft with engines under its wings. This is further explored by means of a Mach number analysis for M = 0.5, 0.7, and 0.9, showing that this trend is present whenever trailing-edge scattering of jet disturbances is dominant in the acoustic field.
Optical DNA Mapping Combined with Cas9-Targeted Resistance Gene Identification for Rapid Tracking of Resistance Plasmids in a Neonatal Intensive Care Unit Outbreak
Authors: Bikkarolla Santosh K. , Nordberg Viveka , Rajer Fredrika , Müller Vilhelm , Kabir Muhammad Humaun , KK Sriram , Dvirnas Albertas , Ambjörnsson Tobias , Giske Christian G. , Navér Lars , Sandegren Linus , Westerlund Fredrik
Published: July 2019

This study presents how a novel method, based on visualizing single plasmids using sequence-specific fluorescent labeling, could be used to analyze the genetic dynamics of an outbreak of resistant bacteria in a neonatal intensive care unit at a Swedish hospital. Plasmids are a central reason for the rapid global spread of bacterial resistance to antibiotics. In a single experimental procedure, this method replaces many traditional plasmid analysis techniques that together provide limited details and are slow to perform. The method is much faster than long-read whole-genome sequencing and offers direct genetic comparison of patient samples. We could conclude that no transfer of resistance plasmids had occurred between different bacteria during the outbreak and that secondary cases of ESBL-producing
Enterobacteriaceae
carriage were instead likely due to influx of new strains. We believe that the method offers potential in improving surveillance and infection control of resistant bacteria in hospitals.
Metabolic Model of thePhytophthora infestans-Tomato Interaction Reveals Metabolic Switches during Host Colonization
Authors: Rodenburg Sander Y. A. , Seidl Michael F. , Judelson Howard S. , Vu Andrea L. , Govers Francine , de Ridder Dick
Published: July 2019

Late blight disease caused by the oomycete pathogenPhytophthora infestansleads to extensive yield losses in tomato and potato cultivation worldwide. To effectively control this pathogen, a thorough understanding of the mechanisms shaping the interaction with its hosts is paramount. While considerable work has focused on exploring host defense mechanisms and identifyingP. infestansproteins contributing to virulence and pathogenicity, the nutritional strategies of the pathogen are mostly unresolved. Genome-scale metabolic models (GEMs) can be used to simulate metabolic fluxes and help in unravelling the complex nature of metabolism. We integrated a GEM of tomato with a GEM ofP. infestansto simulate the metabolic fluxes that occur during infection. This yields insights into the nutrients thatP. infestansobtains during different phases of the infection cycle and helps in generating hypotheses about nutritionin planta.
Expression and Immunostaining Analyses Suggest that
Pneumocystis
Primary Homothallism Involves Trophic Cells Displaying Both Plus and Minus Pheromone Receptors
Authors: Luraschi A. , Richard S. , Almeida J. M. G. C. F. , Pagni M. , Cushion M. T. , Hauser P. M.
Published: July 2019

The fungi belonging to the genus
Pneumocystis
may cause severe pneumonia in immunocompromised humans, a disease that can be fatal if not treated. This disease is nowadays one of the most frequent invasive fungal infections worldwide. Whole-genome sequencing revealed that the sexuality of these fungi involves a single partner that can self-fertilize. Here, we report that two receptors recognizing specifically excreted pheromones are involved in this self-fertility within infected human lungs. Using fluorescent antibodies binding specifically to these receptors, we observed that most often, the fungal cells display both receptors at their surface. These pheromone-receptor systems might play a role in mate recognition and/or postfertilization events. They constitute an integral part of the
Pneumocystis
obligate sexuality within human lungs, a cycle that is necessary for the dissemination of the fungus to new individuals.
The Extracellular Domain of the β
2
Integrin β Subunit (CD18) Is Sufficient for Escherichia coli Hemolysin and Aggregatibacter actinomycetemcomitans Leukotoxin Cytotoxic Activity
Authors: Ristow Laura C. , Tran Vy , Schwartz Kevin J. , Pankratz Lillie , Mehle Andrew , Sauer John-Demian , Welch Rodney A.
Published: July 2019

Urinary tract infections are one of the most common bacterial infections worldwide. Uropathogenic
Escherichia coli
strains are responsible for more than 80% of community-acquired urinary tract infections. Although we have known for nearly a century that severe infections stemming from urinary tract infections, including kidney or bloodstream infections are associated with expression of a toxin, hemolysin, from uropathogenic
Escherichia coli
, how hemolysin functions to enhance virulence is unknown. Our research defines the interaction of hemolysin with the β
2
integrin, a human white cell adhesion molecule, as a potential therapeutic target during urinary tract infections. The
E. coli
hemolysin is the prototype for a toxin family (RTX family) produced by a wide array of human and animal pathogens. Our work extends to the identification and characterization of the receptor for an additional member of the RTX family, suggesting that this interaction may be broadly conserved throughout the RTX toxin family.
Implantation of Scharioth macula lens in patients with age-related macular degeneration: results of a prospective European multicentre clinical trial
Authors: Srinivasan Sathish , Scharioth Gabor , Riehl Anneliese , Tanev Ivan V , Rozsival Pavel , Acker Emmanuel Van , Nagy Zoltan Z , Balta Florian , Nekolova Jana
Published: July 2019

Objective

To report the visual and refractive outcomes following monocular implantation of a supplementary (piggyback) Scharioth macula lens (SML) in previously pseudophakic eyes with age-related macular degeneration (AMD).

Methods and analysis

Prospective European multicentre clinical trial. 50 eyes of 50 pseudophakic patients with either dry or previously treated and stable neovascular AMD for at least 6 months were included. The inclusion criteria were age over 55, corrected distance visual acuity (CDVA) of 0.4–0.1 (decimal), improvement of at least three lines of corrected near visual acuity (CNVA) when tested with a +6.0 dioptre (D) reading addition at 15 cm, compared with a +2.5 D reading addition at 40 cm using a standardised, self-illuminated Early Treatment Diabetic Retinopathy Study near vision chart. The SML intraocular lens (IOL) was implanted as an add-on/piggyback IOL in the ciliary sulcus, monocularly in the better seeing eye of each subject meeting the inclusion criteria.

Results

There were no intraoperative complications. One subject had the SML explanted in the postoperative period due to postoperative glare/halos. The mean CNVA improved from 0.23±0.12 (decimal) preoperatively to 0.57±0.33 at 1 year. The mean CDVA remained unchanged measuring 0.19±0.13 preoperatively and 0.19±0.09 at 1 year postoperatively.

Conclusion

The SML appears to be safe and effective in improving the CNVA in patients with AMD. Data suggest that the CDVA remains unaffected following implantation. Further data are needed to assess the long-term safety and efficacy.
Time of day and endovascular treatment decision in acute stroke with relative endovascular treatment indication: insights from UNMASK EVT international survey
Authors: Ospel Johanna Maria , Kashani Nima , Goyal Mayank , Menon Bijoy K , Campbell Bruce C V , Fischer Urs , Turjman Francis , Mitchell Peter , Yoshimura Shinichi , Podlasek Anna , Rabinstein Alejandro A , Wilson Alexis T , Kim Byung Moon , Baxter Blaise W , Cherian Mathew P , Heo Ji Hoe , Foss Mona , Demchuk Andrew M , Sylaja Pillai N , Hill Michael D , Saposnik Gustavo , Almekhlafi Mohammed A
Published: July 2019

Background and purpose

The decision to proceed with endovascular thrombectomy should ideally be made independent of inconvenience factors, such as daytime. We assessed the influence of patient presentation time on endovascular therapy decision making under current local resources and assumed ideal conditions in acute ischemic stroke with level 2B evidence for endovascular treatment.

Methods and materials

In an international cross sectional survey, 607 stroke physicians from 38 countries were asked to give their treatment decisions to 10 out of 22 randomly assigned case scenarios. Eleven scenarios had level 2B evidence for endovascular treatment: 7 daytime scenarios (7:00 am–5:00 pm) and four night time cases (5:01 pm– 6:59 am). Participants provided their treatment approach assuming (A) there were no practice constraints and (B) under their current local resources. Endovascular treatment decisions in the 11 scenarios were analyzed according to presentation time with adjustment for patient and physician characteristics.

Results

Participants selected endovascular therapy in 74.2% under assumed ideal conditions, and 70.7% under their current local resources of night time scenarios, and in 67.2% and 63.8% of daytime scenarios. Night time presentation did not increase the probability of a treatment decision against endovascular therapy under current local resources or assumed ideal conditions.

Conclusion

Presentation time did not influence endovascular treatment decision making in stroke patients in this international survey.
Early versus delayed stenting for intracranial atherosclerotic artery stenosis with ischemic stroke
Authors: Zhang Yong , Sun Yujie , Li Xin , Liu Tonghui , Liu Peng , Wang Hongxia , Ding Jian , Miao Zhong-Rong , Li Guangwen
Published: July 2019

Objective

To evaluate the clinical outcomes of early stenting (≤14 days) or late stenting (>14 days) in patients who underwent intracranial stent placement.

Methods

Patients with ischemic stroke caused by 70–99% intracranial atherosclerotic stenosis combined with poor collaterals were enrolled. The early stenting group, who underwent stenting within 14 days of last ischemic symptoms, were compared with the late stenting group who underwent stenting >14 days from last ischemic symptom. The patients were treated either with a balloon-mounted stent or a self-expanding stent as determined by the operators following a guideline. The baseline characteristics and clinical outcomes were evaluated and compared.

Results

One hundred and fifteen stroke patients were recruited into the study. Four patients (4/41) in the early stenting group and two patients (2/74) in the late stenting group were diagnosed with a cerebral vascular event associated with stenting within 3 days (p=0.184). In the long-term follow-up, eight patients in the early stenting group had restenosis ≥50%, which was higher than patients in the late stenting group (8/41 vs 4/74, p=0.018). The total rates of any ischemic stroke, transient ischemic attack, hemorrhagic stroke, and death in the early stenting group were higher than in the late stenting group (9/41 vs 6/74, p=0.035). The recurrence rate of ischemic stroke in the early stenting group was higher than in the late stenting group (5/41 vs 2/74, p=0.041).

Conclusions

Stent placement in the setting of ischemic stroke caused by intracranial artery stenosis within 14 days may confer a higher risk of long-time cerebral vascular events and lead to a higher risk of restenosis.

Clinical trial registration

NCT01968122.
The impact of ectoparasitism on thermoregulation in Yarrow’s Spiny Lizards (Sceloporus jarrovii)
Authors: Johnson N. , Lymburner A.H. , Blouin-Demers G.
Published: July 2019

Parasites are ubiquitous and can have large impacts on the fitness of their hosts. The effects of ectoparasites on physiology, behaviour, and immune function suggest that they could be part of the factors which impact thermoregulation. We tested the hypothesis that ectoparasites impact thermoregulation in Yarrow’s Spiny Lizards (Sceloporus jarrovii Cope in Yarrow, 1875) living along an elevational gradient. We predicted a positive association between ectoparasite load and body temperature (Tb), and a negative association between ectoparasite load and effectiveness of thermoregulation (de – db index). We also predicted that the impacts of ectoparasites would be greatest at high elevation where thermal quality of the environment is low because the costs of thermoregulation increase with elevation and these costs can impact thermal immune responses. We found a significant association between the number of chiggers (Trombiculoidea) harboured by lizards and Tb that depended on elevation, but no association between ectoparasite load and de – db index. The mean chigger infection rate was associated with a ΔTb of +0.18 °C at low elevation (consistent with fever) and of –1.07 °C at high elevation (consistent with hypothermia). These findings suggest that parasitism by chiggers impacts lizard Tb in a way that depends on environmental thermal quality.
Highlighting the potential of peer-led workshops in training early-career researchers for conducting research with Indigenous communities
Authors: MacMillan Gwyneth A. , Falardeau Marianne , Girard Catherine , Dufour-Beauséjour Sophie , Lacombe-Bergeron Justine , Menzies Allyson K. , Henri Dominique A.
Published: July 2019

For decades, Indigenous voices have called for more collaborative and inclusive research practices. Interest in community-collaborative research is consequently growing among university-based researchers in Canada. However, many researchers receive little formal training on how to collaboratively conduct research with Indigenous communities. This is particularly problematic for early-career researchers (ECRs) whose fieldwork often involves interacting with communities. To address this lack of training, two peer-led workshops for Canadian ECRs were organized in 2016 and 2017 with the following objectives: ( i) to cultivate awareness about Indigenous cultures, histories, and languages; ( ii) to promote sharing of Indigenous and non-Indigenous ways of knowing; and ( iii) to foster approaches and explore tools for conducting community-collaborative research. Here we present these peer-led Intercultural Indigenous Workshops and discuss workshop outcomes according to five themes: scope and interdisciplinarity, Indigenous representation, workshop environment, skillful moderation, and workshop outcomes. Although workshops cannot replace the invaluable experience gained through working directly with Indigenous communities, we show that peer-led workshops can be an effective way for ECRs to develop key skills for conducting meaningful collaborative research. Peer-led workshops are therefore an important but insufficient step toward more inclusive research paradigms in Canada.
Somatic Mutation and Evolution in Plants
Authors: Schoen Daniel J. , Schultz Stewart T.
Published: July 2019

Somatic mutations are common in plants, and they may accumulate and be passed on to gametes. The determinants of somatic mutation accumulation include the intraorganismal selective effect of mutations, the number of cell divisions that separate the zygote from the formation of gametes, and shoot apical meristem structure and branching. Somatic mutations can promote the evolution of diploidy, polyploidy, sexual recombination, outcrossing, clonality, and separate sexes, and they may contribute genetic variability in many other traits. The amplification of beneficial mutations via intraorganismal selection may relax selection to reduce the genomic mutation rate or to protect the germline in plants. The total rate of somatic mutation, the distribution of selective effects and fates in the plant body, and the degree to which the germline is sheltered from somatic mutations are still poorly understood. Our knowledge can be improved through empirical estimates of mutation rates and effects on cell lineages and whole organisms, such as estimates of the reduction in fitness of progeny produced by within- versus between-flower crosses on the same plant, mutation coalescent studies within the canopy, and incorporation of somatic mutation into theoretical models of plant evolutionary genetics.
Paleomicrobiology: Diagnosis and Evolution of Ancient Pathogens
Authors: Bos Kirsten I. , Kühnert Denise , Herbig Alexander , Esquivel-Gomez Luis Roger , Andrades Valtueña Aida , Barquera Rodrigo , Giffin Karen , Kumar Lankapalli Aditya , Nelson Elizabeth A. , Sabin Susanna , Spyrou Maria A. , Krause Johannes
Published: July 2019

The last century has witnessed progress in the study of ancient infectious disease from purely medical descriptions of past ailments to dynamic interpretations of past population health that draw upon multiple perspectives. The recent adoption of high-throughput DNA sequencing has led to an expanded understanding of pathogen presence, evolution, and ecology across the globe. This genomic revolution has led to the identification of disease-causing microbes in both expected and unexpected contexts, while also providing for the genomic characterization of ancient pathogens previously believed to be unattainable by available methods. In this review we explore the development of DNA-based ancient pathogen research, the specialized methods and tools that have emerged to authenticate and explore infectious disease of the past, and the unique challenges that persist in molecular paleopathology. We offer guidelines to mitigate the impact of these challenges, which will allow for more reliable interpretations of data in this rapidly evolving field of investigation.
The Evolution, Ecology, and Mechanisms of Infection by Gram-Positive, Plant-Associated Bacteria
Authors: Thapa Shree P. , Davis Edward W. , Lyu Qingyang , Weisberg Alexandra J. , Stevens Danielle M. , Clarke Christopher R. , Coaker Gitta , Chang Jeff H.
Published: July 2019

Gram-positive bacteria are prominent members of plant-associated microbial communities. Although many are hypothesized to be beneficial, some are causative agents of economically important diseases of crop plants. Because the features of Gram-positive bacteria are fundamentally different relative to those of Gram-negative bacteria, the evolution and ecology as well as the mechanisms used to colonize and infect plants also differ. Here, we discuss recent advances in our understanding of Gram-positive, plant-associated bacteria and provide a framework for future research directions on these important plant symbionts.
Retrieval of Emotional Events from Memory
Authors: Kensinger Elizabeth A. , Ford Jaclyn H.
Published: July 2019

The enhancing effects of emotion on memory have been well documented; emotional events are often more frequently and more vividly remembered than their neutral counterparts. Much of the prior research has emphasized the effects of emotion on encoding processes and the downstream effects of these changes at the time of retrieval. In the current review, we focus specifically on how emotional valence influences retrieval processes, examining how emotion influences the experience of remembering an event at the time of retrieval (retrieval as an end point) as well as how emotion alters the way in which remembering the event affects the underlying memory representation and subsequent retrievals (retrieval as a starting point). We suggest ways in which emotion may augment or interfere with the selective enhancement of particular memory details, using both online and offline processes, and discuss how these effects of emotion may contribute to memory distortions in affective disorders.
Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?
Authors: Keeler Allison M. , Flotte Terence R.
Published: July 2019

The recent market approvals of recombinant adeno-associated virus (rAAV) gene therapies in Europe and the United States are landmark achievements in the history of modern science. These approvals are also anticipated to herald the emergence of a new class of therapies for monogenic disorders, which had hitherto been considered untreatable. These events can be viewed as stemming from the convergence of several important historical trends: the study of basic virology, the development of genomic technologies, the imperative for translational impact of National Institutes of Health–funded research, and the development of economic models for commercialization of rare disease therapies. In this review, these historical trends are described and the key developments that have enabled clinical rAAV gene therapies are discussed, along with an overview of the current state of the field and future directions.
Regulation of Viral Infection by the RNA Modification N6-Methyladenosine
Authors: Williams Graham D. , Gokhale Nandan S. , Horner Stacy M.
Published: July 2019

In recent years, the RNA modification N6-methyladenosine (m6A) has been found to play a role in the life cycles of numerous viruses and also in the cellular response to viral infection. m6A has emerged as a regulator of many fundamental aspects of RNA biology. Here, we highlight recent advances in techniques for the study of m6A, as well as advances in our understanding of the cellular machinery that controls the addition, removal, recognition, and functions of m6A. We then summarize the many newly discovered roles of m6A during viral infection, including how it regulates innate and adaptive immune responses to infection. Overall, the goals of this review are to summarize the roles of m6A on both cellular and viral RNAs and to describe future directions for uncovering new functions of m6A during infection.
Interferon-Stimulated Genes: What Do They All Do?
Authors: Schoggins John W.
Published: July 2019

In the absence of an intact interferon (IFN) response, mammals may be susceptible to lethal viral infection. IFNs are secreted cytokines that activate a signal transduction cascade leading to the induction of hundreds of interferon-stimulated genes (ISGs). Remarkably, approximately 10% of the genes in the human genome have the potential to be regulated by IFNs. What do all of these genes do? It is a complex question without a simple answer. From decades of research, we know that many of the protein products encoded by these ISGs work alone or in concert to achieve one or more cellular outcomes, including antiviral defense, antiproliferative activities, and stimulation of adaptive immunity. The focus of this review is the antiviral activities of the IFN/ISG system. This includes general paradigms of ISG function, supported by specific examples in the literature, as well as methodologies to identify and characterize ISG function.
Host Determinants of Influenza RNA Synthesis
Authors: Peacock Thomas P. , Sheppard Carol M. , Staller Ecco , Barclay Wendy S.
Published: July 2019

Influenza viruses are a leading cause of seasonal and pandemic respiratory illness. Influenza is a negative-sense single-stranded RNA virus that encodes its own RNA-dependent RNA polymerase (RdRp) for nucleic acid synthesis. The RdRp catalyzes mRNA synthesis, as well as replication of the virus genome (viral RNA) through a complementary RNA intermediate. Virus propagation requires the generation of these RNA species in a controlled manner while competing heavily with the host cell for resources. Influenza virus appropriates host factors to enhance and regulate RdRp activity at every step of RNA synthesis. This review describes such host factors and summarizes our current understanding of the roles they play in viral synthesis of RNA.
In Vivo Imaging-Driven Approaches to Study Virus Dissemination and Pathogenesis
Authors: Uchil Pradeep D. , Haugh Kelsey A. , Pi Ruoxi , Mothes Walther
Published: July 2019

Viruses are causative agents for many diseases and infect all living organisms on the planet. Development of effective therapies has relied on our ability to isolate and culture viruses in vitro, allowing mechanistic studies and strategic interventions. While this reductionist approach is necessary, testing the relevance of in vitro findings often takes a very long time. New developments in imaging technologies are transforming our experimental approach where viral pathogenesis can be studied in vivo at multiple spatial and temporal resolutions. Here, we outline a vision of a top-down approach using noninvasive whole-body imaging as a guide for in-depth characterization of key tissues, physiologically relevant cell types, and pathways of spread to elucidate mechanisms of virus spread and pathogenesis. Tool development toward imaging of infectious diseases is expected to transform clinical diagnosis and treatment.
Coding Principles in Adaptation
Authors: Weber Alison I. , Krishnamurthy Kamesh , Fairhall Adrienne L.
Published: July 2019

Adaptation is a common principle that recurs throughout the nervous system at all stages of processing. This principle manifests in a variety of phenomena, from spike frequency adaptation, to apparent changes in receptive fields with changes in stimulus statistics, to enhanced responses to unexpected stimuli. The ubiquity of adaptation leads naturally to the question: What purpose do these different types of adaptation serve? A diverse set of theories, often highly overlapping, has been proposed to explain the functional role of adaptive phenomena. In this review, we discuss several of these theoretical frameworks, highlighting relationships among them and clarifying distinctions. We summarize observations of the varied manifestations of adaptation, particularly as they relate to these theoretical frameworks, focusing throughout on the visual system and making connections to other sensory systems.
The Science Behind Virtual Reality Displays
Authors: Scarfe Peter , Glennerster Andrew
Published: July 2019

Virtual reality (VR) is becoming an increasingly important way to investigate sensory processing. The converse is also true: in order to build good VR technologies, one needs an intimate understanding of how our brain processes sensory information. One of the key advantages of studying perception with VR is that it allows an experimenter to probe perceptual processing in a more naturalistic way than has been possible previously. In VR, one is able to actively explore and interact with the environment, just as one would do in real life. In this article, we review the history of VR displays, including the philosophical origins of VR, before discussing some key challenges involved in generating good VR and how a sense of presence in a virtual environment can be measured. We discuss the importance of multisensory VR and evaluate the experimental tension that exists between artifice and realism when investigating sensory processing.