bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-CasΦ from huge phages is a hypercompact genome editor
Authors: Pausch Patrick , Al-Shayeb Basem , Bisom-Rapp Ezra , Tsuchida Connor A. , Li Zheng , Cress Brady F. , Knott Gavin J. , Jacobsen Steven E. , Banfield Jillian F. , Doudna Jennifer A.
Published: April 2021

Compact defense system in bacteriophages

The CRISPR-Cas system, naturally found in many prokaryotes, is widely used for genome editing. CRISPR arrays in the bacterial genome, derived from the genome of invading viruses, are used to generate a CRISPR RNA that guides the Cas enzyme to destroy repeat viral invaders. Recently, an unexpectedly compact CRISPR-Cas system was identified in huge bacteriophages. Pausch
et al
. show that even though this system lacks commonly found accessory proteins, it is functional. In addition to a CRISPR array, the only component of the system is an enzyme called CasF, which uses the same active site to process transcripts of the CRISPR arrays into CRISPR RNA and to destroy foreign nucleic acids. This system, which is active in human and plant cells, provides a hypercompact addition to the genome-editing toolbox.

Science
this issue p.
333
Boron-enabled geometric isomerization of alkenes via selective energy-transfer catalysis
Authors: Molloy John J. , Schäfer Michael , Wienhold Max , Morack Tobias , Daniliuc Constantin G. , Gilmour Ryan
Published: April 2021

An E-Z boron swivel

Compounds with carbon-carbon double bonds can form two distinct isomers, depending on whether the heaviest substituents on both carbons lie on the same side (labeled Z) or diagonally across from each other (labeled E). Molloy
et al.
present a convenient method to reorient double bonds that bear boron and carbonyl substituents. When they are diagonally opposed, both substituents stay in plane, and the double bond is easily swiveled by photosensitization. However, once on the same side as the carbonyl, the boron rotates out of plane and further sensitization is inhibited.

Science
this issue p.
302
Science has always been political
Authors: Thorp H. Holden
Published: April 2021

This month marks the 75th anniversary of Vannevar Bush's paper, “Science—The Endless Frontier.” The report set out the rationale and structure of a system to fund science in the United States; it is the Magna Carta of American science.
Science
published a summary of Bush's paper on the same day it was submitted to President Harry Truman, and Bush's close relationship with the magazine is evident by the number of times he wrote and was quoted in
Science
during the 1940s.
Extinction at the end-Cretaceous and the origin of modern Neotropical rainforests
Authors: Carvalho Mónica R. , Jaramillo Carlos , de la Parra Felipe , Caballero-Rodríguez Dayenari , Herrera Fabiany , Wing Scott , Turner Benjamin L. , D’Apolito Carlos , Romero-Báez Millerlandy , Narváez Paula , Martínez Camila , Gutierrez Mauricio , Labandeira Conrad , Bayona German , Rueda Milton , Paez-Reyes Manuel , Cárdenas Dairon , Duque Álvaro , Crowley James L. , Santos Carlos , Silvestro Daniele
Published: April 2021

The birth of modern rainforests

The origin of modern rainforests can be traced to the aftermath of the bolide impact at the end of the Cretaceous. Carvalho
et al.
used fossilized pollen and leaves to characterize the changes that took place in northern South American forests at this time (see the Perspective by Jacobs and Currano). They not only found changes in species composition but were also able to infer changes in forest structure. Extinctions were widespread, especially among gymnosperms. Angiosperm taxa came to dominate the forests over the 6 million years of recovery, when the flora began to resemble that of modern lowland neotropical forest. The leaf data also imply that the forest canopy evolved from relatively open to closed and layered, leading to increased vertical stratification and a greater diversity of plant growth forms.

Science
, this issue p.
63
; see also p.
28
Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies
Authors: Fernández-Ruiz Antonio , Oliva Azahara , Soula Marisol , Rocha-Almeida Florbela , Nagy Gergo A. , Martin-Vazquez Gonzalo , Buzsáki György
Published: April 2021

Brain region coordination in learning

Gamma-frequency oscillations have been hypothesized as a physiological mechanism of interregional communication in the brain. However, until now, all supporting data have been correlational and thus indirect. Fernández-Ruiz
et al.
examined gamma-frequency activity and spike coupling between the entorhinal cortex and hippocampal dentate gyrus during learning and after selective perturbation of gamma-frequency spike timing. They observed an integrated neuron, gamma-band, and task-specific organization of the entorhinal cortex–hippocampal circuits. These data demonstrate that specific, projected gamma-frequency oscillation patterns dynamically engage functionally related cell assemblies across brain regions in a task-specific manner.

Science
, this issue p.
eabf3119
Striatal dopamine mediates hallucination-like perception in mice
Authors: Schmack K. , Bosc M. , Ott T. , Sturgill J. F. , Kepecs A.
Published: April 2021

How to model hallucinations in mice

There has not been enough progress in our understanding of the basic mechanisms underlying psychosis. Studying psychotic disorders in animal models is difficult because the diagnosis relies on self-reported symptoms that can only be assessed in humans. Schmack
et al.
developed a paradigm to probe and rigorously measure experimentally controlled hallucinations in rodents (see the Perspective by Matamales). Using dopamine-sensor measurements and circuit and pharmacological manipulations, they demonstrated a brain circuit link between excessive dopamine and hallucination-like experience. This could potentially be useful as a translational model of common psychotic symptoms described in various psychiatric disorders. It may also help in the development of new therapeutic approaches based on anatomically selective modulation of dopamine function.

Science
, this issue p.
eabf4740
; see also p.
33
Reversal of exhaustion in engineered T cells
Authors: Mamonkin Maksim , Brenner Malcolm K.
Published: April 2021

Antitumor activity of exhausted engineered T cells is improved with pulsatile signaling
Hydrated crust stores Mars' missing water
Authors: Kurokawa Hiroyuki
Published: April 2021

Mars' liquid water might not have been lost to space as thought
Intracellular Passage Triggers a Molecular Response in Brucella abortus That Increases Its Infectiousness
Authors: Altamirano-Silva Pamela , Cordero-Serrano Marlen , Méndez-Montoya Joselyn , Chacón-Díaz Carlos , Guzmán-Verri Caterina , Moreno Edgardo , Chaves-Olarte Esteban
Published: April 2021

Brucella abortus
is a facultatively extracellular-intracellular pathogen that encounters a diversity of environments within the host cell. We report that bacteria extracted from infected cells at late stages (48 h postinfection) of the intracellular life cycle significantly increase their ability to multiply in new target cells.
The RD2 Pathogenicity Island Modifies the Disease Potential of the Group A
Streptococcus
Authors: Roshika Roshika , Jain Ira , Medicielo Josette , Wächter Jasmin , Danger Jessica L. , Sumby Paul
Published: April 2021

Serotype M28 isolates of the group A
Streptococcus
(GAS;
Streptococcus pyogenes
) are nonrandomly associated with cases of puerperal sepsis, a potentially life-threatening infection that can occur in women following childbirth. Previously, we discovered that the 36.3-kb RD2 pathogenicity island, which is present in serotype M28 isolates but lacking from most other isolates, promotes the ability of M28 GAS to colonize the female reproductive tract.
Supplemental Material: Early and middle Miocene ice sheet dynamics in the Ross Sea: Results from integrated core-log-seismic interpretation
Authors: Pérez L F
Published: April 2021

Additional information regarding methods (Reflection seismic processing, Drill-site measurements, Core-log-seismic correlations, Spatial Velocity calculations, and Reflection Tomography model) and regional stratigraphy descriptions, as well as detailed considerations regarding the opal distribution and depth.
Nasal-type extranodal NK/T-cell lymphoma presenting as recurrent periorbital cellulitis
Authors: Hussein Mansoor Ali , Boyle Seamus , Abdulrahman Shawkat , Fennessy Brendan
Published: April 2021

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) is a rare disease with a poor prognosis. It has features similar to other granulomatous and infectious diseases of the nose and paranasal sinuses, which can make diagnosis challenging and delayed. We present a case of 38-year-old man who was admitted to the hospital on three occasions over a 3-month period for right periorbital erythema, nasal congestion and discharge. Following two separate surgical debridement and biopsies, ENKTCL was diagnosed and the patient was commenced on chemoradiotherapy. The case highlights the atypical nature of his presentation and the high degree of suspicion for a pathological process that must be maintained to formulate the diagnosis.
Relapse of treated anti-GBM disease following hair dye use
Authors: Povey James , Rutherford Elaine , Levy Jeremy , Muniraju Thalakunte
Published: April 2021

An 18-year-old woman was treated for acute kidney injury (AKI) secondary to antiglomerular basement membrane (GBM) disease with prednisolone, cyclophosphamide and plasma exchange. She also had epistaxis at initial presentation with no other organ involvement and achieved good recovery of her kidney function. Two weeks after completing induction treatment, she re-presented with further AKI and pulmonary haemorrhage. She was recommenced on plasma exchange and steroids and was given rituximab. She recovered from her illness with significant improvement to her kidney function. The cause of her relapse was thought to be possibly due to the use of hair dye. This case highlights the importance of acknowledging potential environmental exposures to prevent relapses of disease. We were also able to demonstrate a case of successful treatment of anti-GBM disease with rituximab.
Treatment-resistant priapism associated with long-term low-molecular-weight heparin
Authors: Bouchier-Hayes David , Nolan Philip , Pate Gordon
Published: April 2021

This case report summarises the case of a 56-year-old man with low-flow, ischaemic priapism requiring urgent insertion of a penile prosthesis following prophylactic anticoagulation with tinzaparin. Low-molecular-weight heparin (LMWH) has been proposed as a cause of ischaemic priapism, although reported cases of this are rare. This particular side effect of tinzaparin has been reported once in a case report in 2018, and there are scant other reports of LMWH-induced priapism. This case was refractory to the full treatment algorithm, including multiple aspirations, phenylephrine injection, cavernosal shunt and required transfer for implantation of a penile prosthesis. Only one other case of such a severe case of priapism has been documented, involving LMWH and warfarin. Documented evidence of possible causes of priapism are vital, given the rarity of this condition, the frequency of LMWH and the potentially devastating complications.
Government management capacities and the containment of COVID-19: a repeated cross-sectional study across Chinese cities
Authors: Li Wenchao , Li Jing , Yi Junjian
Published: April 2021

Objectives

Better understanding of the dynamics of the COVID-19 (2019 novel coronavirus disease) pandemic to curb its spread is now a global imperative. While travel restrictions and control measures have been shown to limit the spread of the disease, the effectiveness of the enforcement of those measures should depend on the strength of the government. Whether, and how, the government plays a role in fighting the disease, however, has not been investigated. Here, we show that government management capacities are critical to the containment of the disease.

Setting

We conducted a statistical analysis based on cross-city comparisons within China. China has undergone almost the entire cycle of the anticoronavirus campaign, which allows us to trace the full dynamics of the outbreak, with homogeneity in standards for statistics recording.

Primary and secondary outcome measures

Outcome measures include city-specific COVID-19 case incidence and recoveries in China.

Results

The containment of COVID-19 depends on the effectiveness of the enforcement of control measures, which in turn depends on the local government’s management capacities. Specifically, government efficiency, capacity for law enforcement, and the transparency of laws and policies significantly reduce COVID-19 prevalence and increase the likelihood of recoveries. The organisation size of the government, which is not closely related to its capacity for management, has a limited role.
Cross-sectional online survey to determine the prevalence, knowledge, attitude and practice of tobacco cessation among governmental healthcare workers in Qatar
Authors: AlMulla Ahmad , Kouyoumjian Silva , ElNakib Nour
Published: April 2021

Objectives

One effective approach of tobacco control is to encourage the role and the participation of healthcare workers in the prevention efforts against tobacco use. This study aimed to determine the prevalence of tobacco use among governmental healthcare workers in Qatar, to assess healthcare workers’ knowledge, attitude and practice of tobacco cessation and to predict factors associated with above average tobacco cessation practice scores.

Design

A cross-sectional survey study was conducted among healthcare workers working in Hamad Medical Corporation and Primary Healthcare Centres in Qatar using a self-administered online questionnaire in 2019.

Setting

Hamad Medical Corporation and Primary Healthcare Centres in Qatar.

Participants

Governmental healthcare workers aged 18 years and above (n=7214).

Results

The response rate of our online survey was 20.6% (7214/35 000). Of the 7214 healthcare workers, 16.3% (n=1178) were current tobacco users. In particular, the prevalence of tobacco use among physicians was 11.0%. Fifty-two per cent of healthcare workers (n=2338) attained an average knowledge score (12–17), 71.8% (n=3094) attained positive attitude scores (8–12) and 57.1% (n=3052) attained above average practice scores (12–26). Among the different professions, physicians were having the highest mean knowledge (15.3±4.7), attitude (9.4±1.9) and practice (13.7±6.1) scores. Multivariate analysis showed that having good knowledge (adjusted OR (AOR)=2.8; p<0.0001) and training (AOR=2.4; p<0.0001) were the strongest factors associated positively with above average tobacco cessation practice scores.

Conclusions

Healthcare workers in Qatar have a relatively similar prevalence of tobacco use than earlier studies with no significant increase. Investing more in training programmes for healthcare workers are needed to root out this negative behaviour and to increase their skills to assist users to quit.
Diet quality indices, genetic risk and risk of cardiovascular disease and mortality: a longitudinal analysis of 77 004 UK Biobank participants
Authors: Livingstone Katherine M , Abbott Gavin , Bowe Steven J , Ward Joey , Milte Catherine , McNaughton Sarah A
Published: April 2021

Objectives

To examine associations of three diet quality indices and a polygenic risk score with incidence of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke.

Design

Prospective cohort study.

Setting

UK Biobank, UK.

Participants

77 004 men and women (40–70 years) recruited between 2006 and 2010.

Main outcome measures

A polygenic risk score was created from 300 single nucleotide polymorphisms associated with CVD. Cox proportional HRs were used to estimate independent effects of diet quality and genetic risk on all-cause mortality, CVD mortality, MI and stroke risk. Dietary intake (Oxford WebQ) was used to calculate Recommended Food Score (RFS), Healthy Diet Indicator (HDI) and Mediterranean Diet Score (MDS).

Results

New all-cause (n=2409) and CVD (n=364) deaths and MI (n=1141) and stroke (n=748) events were identified during mean follow-ups of 7.9 and 7.8 years, respectively. The adjusted HR associated with one-point higher RFS for all-cause mortality was 0.96 (95% CI: 0.94 to 0.98), CVD mortality was 0.94 (95% CI: 0.90 to 0.98), MI was 0.97 (95% CI: 0.95 to 1.00) and stroke was 0.94 (95% CI: 0.91 to 0.98). The adjusted HR for all-cause mortality associated with one-point higher HDI and MDS was 0.97 (95% CI: 0.93 to 0.99) and 0.95 (95% CI: 0.91 to 0.98), respectively. The adjusted HR associated with one-point higher MDS for stroke was 0.93 (95% CI: 0.87 to 1.00). There was little evidence of associations between HDI and risk of CVD mortality, MI or stroke. There was evidence of an interaction between diet quality and genetic risk score for MI.

Conclusion

Higher diet quality predicted lower risk of all-cause mortality, independent of genetic risk. Higher RFS was also associated with lower risk of CVD mortality and MI. These findings demonstrate the benefit of following a healthy diet, regardless of genetic risk.
Prediction of treatment dosage and duration from free-text prescriptions: an application to ADHD medications in the Swedish prescribed drug register
Authors: Zhang Le , Lagerberg Tyra , Chen Qi , Ghirardi Laura , D'Onofrio Brian M , Larsson Henrik , Viktorin Alexander , Chang Zheng
Published: April 2021

Background

Accurate estimation of daily dosage and duration of medication use is essential to pharmacoepidemiological studies using electronic healthcare databases. However, such information is not directly available in many prescription databases, including the Swedish Prescribed Drug Register.

Objective

To develop and validate an algorithm for predicting prescribed daily dosage and treatment duration from free-text prescriptions, and apply the algorithm to ADHD medication prescriptions.

Methods

We developed an algorithm to predict daily dosage from free-text prescriptions using 8000 ADHD medication prescriptions as the training sample, and estimated treatment periods while taking into account several features including titration, stockpiling and non-perfect adherence. The algorithm was implemented to all ADHD medication prescriptions from the Swedish Prescribed Drug Register in 2013. A validation sample of 1000 ADHD medication prescriptions, independent of the training sample, was used to assess the accuracy for predicted daily dosage.

Findings

In the validation sample, the overall accuracy for predicting daily dosage was 96.8%. Specifically, the natural language processing model (NLP1 and NLP2) have an accuracy of 99.2% and 96.3%, respectively. In an application to ADHD medication prescriptions in 2013, young adult ADHD medication users had the highest probability of discontinuing treatments as compared with other age groups. The daily dose of methylphenidate use increased with age substantially.

Conclusions

The algorithm provides a flexible approach to estimate prescribed daily dosage and treatment duration from free-text prescriptions using register data. The algorithm showed a good performance for predicting daily dosage in external validation.

Clinical implications

The structured output of the algorithm could serve as basis for future pharmacoepidemiological studies evaluating utilization, effectiveness, and safety of medication use, which would facilitate evidence-based treatment decision-making.
Racial, ethnic and socioeconomic disparities in patients undergoing left atrial appendage closure
Authors: Sparrow Robbie , Sanjoy Shubrandu , Choi Yun-Hee , Elgendy Islam Y , Jneid Hani , Villablanca Pedro A , Holmes David R , Pershad Ashish , Alraies Chadi , Sposato Luciano A , Mamas Mamas A , Bagur Rodrigo
Published: April 2021

Objective

This manuscript aims to explore the impact of race/ethnicity and socioeconomic status on in-hospital complication rates after left atrial appendage closure (LAAC).

Methods

The US National Inpatient Sample was used to identify hospitalisations for LAAC between 1 October 2015 to 31 December 2018. These patients were stratified by race/ethnicity and quartiles of median neighbourhood income. The primary outcome was the occurrence of in-hospital major adverse events, defined as a composite of postprocedural bleeding, cardiac and vascular complications, acute kidney injury and ischaemic stroke.

Results

Of 6478 unweighted hospitalisations for LAAC, 58% were male and patients of black, Hispanic and ‘other’ race/ethnicity each comprised approximately 5% of the cohort. Adjusted by the older Americans population, the estimated number of LAAC procedures was 69.2/100 000 for white individuals, as compared with 29.5/100 000 for blacks, 47.2/100 000 for Hispanics and 40.7/100 000 for individuals of ‘other’ race/ethnicity. Black patients were ~5 years younger but had a higher comorbidity burden. The primary outcome occurred in 5% of patients and differed significantly between racial/ethnic groups (p<0.001) but not across neighbourhood income quartiles (p=0.88). After multilevel modelling, the overall rate of in-hospital major adverse events was higher in black patients as compared with whites (OR: 1.60, 95% CI 1.22 to 2.10, p<0.001); however, the incidence of acute kidney injury was higher in Hispanics (OR: 2.19, 95% CI 1.52 to 3.17, p<0.001). No significant differences were found in adjusted overall in-hospital complication rates between income quartiles.

Conclusion

In this study assessing racial/ethnic disparities in patients undergoing LAAC, minorities are under-represented, specifically patients of black race/ethnicity. Compared with whites, black patients had higher comorbidity burden and higher rates of in-hospital complications. Lower socioeconomic status was not associated with complication rates.
New generation of DNA-based immunotherapy induces a potent immune response and increases the survival in different tumor models
Authors: Lopes Alessandra , Bastiancich Chiara , Bausart Mathilde , Ligot Sophie , Lambricht Laure , Vanvarenberg Kevin , Ucakar Bernard , Gallez Bernard , Préat Véronique , Vandermeulen Gaëlle
Published: April 2021

Background

Strategies to increase nucleic acid vaccine immunogenicity are needed to move towards clinical applications in oncology. In this study, we designed a new generation of DNA vaccines, encoding an engineered vesicular stomatitis virus glycoprotein as a carrier of foreign T cell tumor epitopes (plasmid to deliver T cell epitopes, pTOP). We hypothesized that pTOP could activate a more potent response compared with the traditional DNA-based immunotherapies, due to both the innate immune properties of the viral protein and the specific induction of CD4 and CD8 T cells targeting tumor antigens. This could improve the outcome in different tumor models, especially when the DNA-based immunotherapy is combined with a rational therapeutic strategy.

Methods

The ability of pTOP DNA vaccine to activate a specific CD4 and CD8 response and the antitumor efficacy were tested in a B16F10-OVA melanoma (subcutaneous model) and GL261 glioblastoma (subcutaneous and orthotopic models).

Results

In B16F10-OVA melanoma, pTOP promoted immune recognition by adequate processing of both MHC-I and MHC-II epitopes and had a higher antigen-specific cytotoxic T cell (CTL) killing activity. In a GL261 orthotopic glioblastoma, pTOP immunization prior to tumor debulking resulted in 78% durable remission and long-term survival and induced a decrease of the number of immunosuppressive cells and an increase of immunologically active CTLs in the brain. The combination of pTOP with immune checkpoint blockade or with tumor resection improved the survival of mice bearing, a subcutaneous melanoma or an orthotopic glioblastoma, respectively.

Conclusions

In this work, we showed that pTOP plasmids encoding an engineered vesicular stomatitis virus glycoprotein, and containing various foreign T cell tumor epitopes, successfully triggered innate immunity and effectively promoted immune recognition by adequate processing of both MHC-I and MHC-II epitopes. These results highlight the potential of DNA-based immunotherapies coding for viral proteins to induce potent and specific antitumor responses.
Microwave ablation induces Th1-type immune response with activation of ICOS pathway in early-stage breast cancer
Authors: Zhou Wenbin , Yu Muxin , Pan Hong , Qiu Wen , Wang Hui , Qian Mengjia , Che Nan , Zhang Kai , Mao Xinrui , Li Li , Wang Ruoxi , Xie Hui , Ling Lijun , Zhao Yi , Liu Xiaoan , Wang Cong , Ding Qiang , Wang Shui
Published: April 2021

Background

Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported.

Methods

The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed.

Results

Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor.

Conclusions

MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.
Impact of RapidAI mobile application on treatment times in patients with large vessel occlusion
Authors: Al-Kawaz Mais , Primiani Christopher , Urrutia Victor , Hui Ferdinand
Published: April 2021

Background

Current efforts to reduce door to groin puncture time (DGPT) aim to optimize clinical outcomes in stroke patients with large vessel occlusions (LVOs). The RapidAI mobile application (Rapid Mobile App) provides quick access to perfusion and vessel imaging in patients with LVOs. We hypothesize that utilization of RapidAI mobile application can significantly reduce treatment times in stroke care by accelerating the process of mobilizing stroke clinicians and interventionalists.

Methods

We analyzed patients presenting with LVOs between June 2019 and October 2020. Thirty-one patients were treated between June 2019 and March 2020 (pre-app group). Thirty-three patients presented between March 2020 and October 2020 (post-app group). Mann–Whitney U test and Kruskal–Wallis tests were used to examine variables that are not normally distributed. In a secondary analysis we analyzed interhospital time metrics between primary stroke centers and our comprehensive stroke center.

Results

Baseline demographic and vascular risk factors were similar in both groups. Use of Rapid Mobile App resulted in 33 min reduction in DGPT (P=0.02), 35 min reduction in door to first pass time (P=0.02), and 37 min reduction in door to recanalization time (P=0.02) in univariate analyses when compared with patients treated pre-app. In a multiple linear regression model, utilization of Rapid Mobile App significantly predicted shorter DGPT (P=0.002). In an adjusted model, National Institutes of Health Stroke Scale (NIHSS) 24 hours after procedure and at discharge were significantly lower in the post-app group (P=0.03). Time of transfer between primary and comprehensive stroke center was comparable in both groups (P=0.26).

Conclusion

In patients with LVOs, the implementation of the RapidAI mobile application was independently associated with reductions in intrahospital treatment times.
Site-specific responses of fungal and bacterial abundances to experimental warming in litter and soil across Arctic and alpine tundra
Authors: Jeanbille Mathilde , Clemmensen Karina , Juhanson Jaanis , Michelsen Anders , Cooper Elisabeth J. , Henry Greg H.R. , Hofgaard Annika , Hollister Robert D. , Jónsdóttir Ingibjörg S. , Klanderud Kari , Tolvanen Anne , Hallin Sara
Published: April 2021

Vegetation change of the Arctic tundra due to global warming is a well-known process, but the implication for the belowground microbial communities, key in nutrient cycling and decomposition, is poorly understood. We characterized the fungal and bacterial abundances in litter and soil layers across 16 warming experimental sites at 12 circumpolar locations. We investigated the relationship between microbial abundances and nitrogen (N) and carbon (C) isotopic signatures, indicating shifts in microbial processes with warming. Microbial abundances were 2–3 orders of magnitude larger in litter than in soil. Local, site-dependent responses of microbial abundances were variable, and no general effect of warming was detected. The only generalizable trend across sites was a dependence between the warming response ratios and C:N ratio in controls, highlighting a legacy of the vegetation on the microbial response to warming. We detected a positive effect of warming on the litter mass and δ15N, which was linked to bacterial abundance under warmed conditions. This effect was stronger in experimental sites dominated by deciduous shrubs, suggesting an altered bacterial N-cycling with increased temperatures, mediated by the vegetation, and with possible consequences on ecosystem feedbacks to climate change.
Multi-scale and multi-system perspectives of zooplankton structure and function in Canadian freshwaters
Authors: Pinel-Alloul Bernadette , Patoine Alain , Marty Jérôme
Published: April 2021

This review provides a Canadian perspective on freshwater zooplankton diversity and ecology across scales and systems. It aims at describing how zooplankton are diverse in forms and functions, and constitute a key component of plankton food webs, a model for ecological theories and a sentinel for monitoring ecological integrity and function in lakes facing environmental changes and anthropogenic stressors. These objectives are addressed across a continuum of scales (continental, regional and local) and systems (reservoirs, lakes and ponds). This perspective shows that the environmental control of zooplankton biodiversity, community structure and function in Canada is complex and variable. Zooplankton communities demonstrated a wide range of responses to anthropogenic disturbances across scales and systems due to interactions with watershed biogeochemistry and climate. This review supports the Multiple Forces hypothesis where forcing by abiotic factors (climate, nutrients, morphometry and chemistry) has a fundamental role at continental scale over Canadian ecoregions, and at regional scale in the Boreal ecozones. In contrast, forcing by biotic factors (algal resources and predators) is relatively more influential at local scale, in resort and urban regions. The challenge for future research will be to combine all new concepts and approaches in a global perspective to better understand the responses of freshwater zooplankton to multiple environmental changes and anthropogenic stressors in Canada.
Atmospheric aerosols elevated ecosystem productivity of a poplar plantation in Beijing, China
Authors: Gao Yuan , Zhang Zhiqiang , Chen Jiquan , McNulty Steven , Xu Hang , Chen Lixin , Chen Zuosinan , Jin Zhihua
Published: April 2021

Atmospheric aerosols can influence energy allocation, environmental factors, and thus, canopy photosynthesis. However, the regulations of aerosols on ecosystem productivity are not well understood. Here, we applied the optical properties of aerosols to quantify the effects of aerosol type and concentration on the environmental factors and associated gross primary productivity (GPP) of a poplar (Populus euramericana) plantation during the months of June to August from 2014 to 2016 in Beijing, China. As aerosol optical depth (AOD) increased from 0 to 2.5, total photosynthetically active radiation (PAR) decreased by 29%, while the diffuse PAR increased by 39%. Although there was no significant impact of aerosols on air temperature (p > 0.05), aerosols decreased vapor pressure deficit by more than 40%. We found that the plantation GPP changed exponentially with AOD, indicating that aerosols elevated GPP by about 37% under severe aerosol pollution (AOD ≥ 1) compared with background aerosol (AOD < 0.4). Aerosols type also had a significant effect on GPP. We concluded that aerosols could increase the GPP of the poplar plantation, and the promotion effect of aerosols on poplar plantation would not be significantly reduced until AOD was <1 under the projected decrease in aerosol loading in the future.
Preliminary assessments of shoot cold tolerance for American elm bred for enhanced tolerance to Dutch elm disease
Authors: Schaberg Paul G. , Murakami Paula F. , Hansen Christopher F. , Hawley Gary J. , Marks Christian O. , Slavicek James M.
Published: April 2021

Although Dutch elm disease (DED) is the primary threat to American elm (Ulmus americana L.), we hypothesized that shoot freezing injury may also limit tree productivity and survival in the north. We assessed shoot cold tolerance and field winter injury of American elm bred for DED tolerance planted in Lemington, Vermont. We tested for differences in cold tolerance associated with date, maternal DED tolerance sources, paternal sources from plant hardiness zones 5a, 6a, and 6b (determined using data from 1996 to 2005), and the interactions of these. Cold tolerance was greatest in the winter, followed by fall and then spring. For all dates, cold tolerance never differed between maternal DED tolerance sources. However, in mid-winter, paternal sources from zone 5a (coldest zone) were significantly more cold tolerant than sources from zone 6b (warmest zone), and sources from zone 6a were intermediate. Field freezing injury confirmed that shoots were only marginally cold tolerant relative to ambient temperature lows.
Ten considerations for conservation policy makers for the post-COVID-19 transition
Authors: Cooke S.J. , Soroye P. , Brooks J.L. , Clarke J. , Jeanson A.L. , Berberi A. , Piczak M.L. , Reid C.H. , Desforges J.E. , Guay J.D. , Drake A.K. , Jardine A.M. , Ethier J.P. , Keefe H.E. , Medd A.M. , Edwards B.P.M. , Reeve C. , Perkovic A. , Frempong-Manso A. , LaRochelle L. , Patterson S. , Roach-Krajewski M. , Howarth A. , Bard B. , Harmsen E.J. , Robichaud J. , Serré S. , Bihun C.J. , Buxton R.T. , Nguyen V.M. , Woodall L.C. , Sutherland W.J. , Bennett J.R.
Published: April 2021

Public health and safety concerns around the SARS-CoV-2 novel coronavirus and the COVID-19 pandemic have greatly changed human behaviour. Such shifts in behaviours, including travel patterns, consumerism, and energy use, are variously impacting biodiversity during the human-dominated geological epoch known as the Anthropocene. Indeed, the dramatic reduction in human mobility and activity has been termed the “Anthropause”. COVID-19 has highlighted the current environmental and biodiversity crisis and has provided an opportunity to redefine our relationship with nature. Here we share 10 considerations for conservation policy makers to support and rethink the development of impactful and effective policies in light of the COVID-19 pandemic. There are opportunities to leverage societal changes as a result of COVID-19, focus on the need for collaboration and engagement, and address lessons learned through the development of policies (including those related to public health) during the pandemic. The pandemic has had devastating impacts on humanity that should not be understated, but it is also a warning that we need to redefine our relationship with nature and restore biodiversity. The considerations presented here will support the development of robust, evidence-based, and transformative policies for biodiversity conservation in a post-COVID-19 world.
Internal migration and mobile communication patterns among pairs with strong ties
Authors: Fudolig Mikaela Irene D. , Monsivais Daniel , Bhattacharya Kunal , Jo Hang-Hyun , Kaski Kimmo
Published: April 2021

Using large-scale call detail records of anonymised mobile phone service subscribers with demographic and location information, we investigate how a long-distance residential move within the country affects the mobile communication patterns between an ego who moved and a frequently called alter who did not move. By using clustering methods in analysing the call frequency time series, we find that such ego-alter pairs are grouped into two clusters, those with the call frequency increasing and those with the call frequency decreasing after the move of the ego. This indicates that such residential moves are correlated with a change in the communication pattern soon after moving. We find that the pre-move calling behaviour is a relevant predictor for the post-move calling behaviour. While demographic and location information can help in predicting whether the call frequency will rise or decay, they are not relevant in predicting the actual call frequency volume. We also note that at four months after the move, most of these close pairs maintain contact, even if the call frequency is decreased.
A note on the Kervaire semi-characteristic
Authors: Zhang Weiping
Published: April 2021

We present a potential generalization of the Kervarie semi-characteristic (with real coefficient) to the case of non-orientable manifolds.
Phase Drift in Networks of Coupled Colpitts Oscillators
Authors: Coria Lourdes , Lopez Horacio , Palacios Antonio , In Visarath , Longhini Patrick
Published: April 2021

In modern times, satellite-based global positioning and navigation systems, such as the GPS, include precise time-keeping devices, e.g. atomic clocks, which are crucial for navigation and for a wide range of economic and industrial applications. However, precise timing might not be available when the environment renders satellite equipment inoperable. In response to this critical need, we have been carrying out, over the past three years, theory and preliminary experiments [Buono et al., 2018a; Buono et al., 2018b; Palacios et al., 2020], towards developing a novel and inexpensive precision timing device that can function independently of GPS availability. The fundamental idea is to exploit collective behavior generated by networks of coupled nonlinear oscillators. Common sense may suggest that synchronized oscillations may lead to higher accuracy. Previous works show, however, that it is not synchronization but rather, traveling wave patterns, in which consecutive oscillators are out of phase by a constant amount, that can better reduce the negative effects of noise and material imperfections which cause phase drift. In this work we advance the state-of-art in the network-based concept by studying, mainly computationally, collective behavior in networks of Colpitts oscillators. These type of oscillators are chosen because they offer a wide range of advantages (such as the ability to tune up the oscillations over a broad frequency range). The results highlight the regions of parameter space, including coupling strength, where traveling wave patterns have the largest basins of attraction and the ability to reduce phase drift by a [Formula: see text] scaling law, where [Formula: see text] is the number of oscillators in the network. The results should also provide guidelines for follow-up design and fabrication tasks of a network-based technology for precision timing.
Coexisting Hidden and Self-Excited Attractors in an Economic Model of Integer or Fractional Order
Authors: Danca Marius-F.
Published: April 2021

In this paper, the dynamics of an economic system with foreign financing, of integer or fractional order, are analyzed. The symmetry of the system determines the existence of two pairs of coexisting attractors. The integer-order version of the system proves to have several combinations of coexisting hidden attractors with self-excited attractors. Because one of the system variables represents the foreign capital inflow, the presence of hidden attractors could be of real interest in economic models. The fractional-order variant presents another interesting coexistence of attractors in the fractional-order space.
Information-based Analysis of the Coupling between Dynamic Visual Stimuli, Eye Movements, and Brain Signals
Authors: Namazi Hamidreza , Menon Avinash , Krejcar Ondrej
Published: April 2021

Our eyes are always in search of exploring our surrounding environment. The brain controls our eyes’ activities through the nervous system. Hence, analyzing the correlation between the activities of the eyes and brain is an important area of research in vision science. This paper evaluates the coupling between the reactions of the eyes and the brain in response to different moving visual stimuli. Since both eye movements and EEG signals (as the indicator of brain activity) contain information, we employed Shannon entropy to decode the coupling between them. Ten subjects looked at four moving objects (dynamic visual stimuli) with different information contents while we recorded their EEG signals and eye movements. The results demonstrated that the changes in the information contents of eye movements and EEG signals are strongly correlated ([Formula: see text]), which indicates a strong correlation between brain and eye activities. This analysis could be extended to evaluate the correlation between the activities of other organs versus the brain.
Information-Based Analysis of the Coupling Between the Alterations of Heart and Brain Activities in Response to Auditory Stimuli
Authors: Namazi Hamidreza , Kumarasinghe Tisara , Krejcar Ondrej
Published: April 2021

In this work, we investigated the coupling among the activities of the brain and heart versus the changes in auditory stimuli using information-based analysis. Three music were selected based on the difference in their complexity. We applied these auditory stimuli on 11 subjects, and accordingly, computed and compared the Shannon entropy of electroencephalography (EEG) signals and heart rate variability (R–R time series). The results demonstrated a correlation among the alterations of the information contents of EEG signals and R–R time series. This finding shows the coupling between the activities of the brain and heart. This analysis could be expanded to analyze the activities of other organs versus the brain’s reaction in various conditions.
Investigation of Droplet Impinging on a Heated Porous Surface Under Various Working Conditions; A Mathematical Modeling
Authors: Azadeh Mohammad , Khakrah Hamidreza
Published: April 2021

This study numerically investigated the behavior of a Newtonian droplet impacting a heated porous surface. In this regard, a two-phase finite volume code was used for laminar flow. The time adaptive method was applied to enhance the accuracy of results and better convergence of the solving process. Also, the dynamic grid adaptation technique was adopted to predict the liquid-air interface precisely. The results were first validated against experimental data at different Weber numbers. Then the effect of variations in the droplet temperature was investigated on the spreading factor. The obtained results revealed that the rise in droplet temperature led to an increase in the maximum spreading diameter due to the reduction in the effects of viscosity, density, and surface tension. In the next step, the effects of droplet impact on the hydrophilic and superhydrophobic surfaces with the porosities of 20–80% were evaluated. The obtained results revealed that the increase in the surface porosity caused a decrease in the droplet diameter during the impact time. Also, at high surface porosity values, the decline in the contact angle influence on the droplet dynamic behavior was observed.
Molecular Modeling Studies on 2,4-Disubstituted Imidazopyridines as Anti-Malarials: Atom-Based 3D-QSAR, Molecular Docking, Virtual Screening, In-Silico ADMET and Theoretical Analysis
Authors: Mali Suraj N. , Pandey Anima
Published: April 2021

Malarial parasites have been reported for moderate-high resistance towards classical antimalarial agents and henceforth development of newer novel chemical entities targeting multiple targets rather than targeting single target will be a highly promising strategy in antimalarial drug discovery. Herein, we carried out molecular modeling studies on 2,4-disubstituted imidazopyridines as anti-hemozoin formation inhibitors by using Schrödinger’s molecular modeling package (2020_4). We have developed statistically robust atom-based 3D-QSAR model (training set, [Formula: see text]; test set, [Formula: see text]; [Formula: see text] [Formula: see text]; root-mean-square error, [Formula: see text]; standard deviation, [Formula: see text]). Our molecular docking, in-silico ADMET analysis showed that dataset molecule 37, has highly promising results. Our ligand-based virtual screening resulted in top five ZINC hits, among them ZINC73737443 hit was observed with lesser energy gap, i.e. 7.85[Formula: see text]eV, higher softness value (0.127[Formula: see text]eV), and comparatively good docking score of [Formula: see text]10.2[Formula: see text]kcal/mol. Our in-silico analysis for a proposed hit, ZINC73737443 showed that this molecule has good ADMET, in-silico nonames toxic as well as noncarcinogenic profile. We believe that further experimental as well as the in-vitro investigation will throw more lights on the identification of ZINC73737443 as a potential antimalarial agent.
Carboniferous tetrapod footprint biostratigraphy, biochronology and evolutionary events
Authors: Lucas Spencer G. , Stimson Matthew R. , King Olivia A. , Calder John H. , Mansky Chris F. , Hebert Brian L. , Hunt Adrian P.
Published: April 2021

The Carboniferous record of tetrapod footprints is mostly of Euramerican origin and provides the basis for a footprint biostratigraphy and biochronology of Carboniferous time that identifies four tetrapod footprint biochrons: (1) stem-tetrapod biochron of Middle Devonian–early Tournaisian age; (2)
Hylopus
biochron of middle Tournaisian–early Bashkirian age; (3)
Notalacerta–Dromopus
interval biochron of early Bashkirian–Kasimovian age; and (4)
Dromopus
biochron of Kasimovian–early Permian age. Particularly significant is the Carboniferous tetrapod footprint record of the Maritimes basin of eastern Canada (New Brunswick, Nova Scotia and Prince Edward Island), which encompasses well-dated and stratigraphically superposed footprint assemblages of Early Mississippian–early Permian age. The Carboniferous tetrapod footprint record provides these important biostratigraphic datums: (1) oldest temnospondyls (middle Tournaisian); (2) oldest reptiliomorphs, likely anthracosaurs (middle Tournaisian); (3) oldest amniotes (early Bashkirian); and (4) oldest high-fibre herbivores (Bashkirian). Carboniferous tetrapod footprints thus provide significant insight into some major events of the Carboniferous evolution of tetrapods.