bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring the opioid epidemic via social media discussions
Authors: Smith Delaney A. , Lavertu Adam , Salecha Aadesh , Hamamsy Tymor , Humphreys Keith , Kiang Mathew V. , Altman Russ B. , Eichstaedt Johannes C.
Published: April 2021

Opioid-involved overdose deaths have risen significantly since 1999 with over 80,000 deaths annually since 2021, primarily driven by synthetic opioids, like fentanyl. Responding to the rapidly changing opioid crisis requires reliable and timely information. One possible source of such data is the social media platforms with billions of user-generated posts, a fraction of which are about drug use. We therefore assessed the utility of Reddit data for surveillance of the opioid epidemic, covering prescription, heroin, and synthetic drugs (as of September 2024, up-to-date Reddit data was still accessible on the open web). Specifically, we built a natural language processing pipeline to identify opioid-related comments and created a cohort of 1,689,039 geo-located Reddit users, each assigned to a state. We followed these users from 2010 through 2022, measured their opioid-related posting activity over time, and compared this posting activity against CDC overdose and National Forensic Laboratory Information System (NFLIS) drug report rates. To simulate the real-world prediction of synthetic drug overdose rates, we added near real-time Reddit data to a model relying on CDC mortality data with a typical 6-month reporting lag and found that Reddit data significantly improved prediction accuracy. We observed drastic, largely unpredictable changes in both Reddit and overdose patterns during the COVID-19 pandemic. Reddit discussions covered a wide variety of drug types that are currently missed by official reporting. This work suggests that social media can help identify and monitor known and emerging drug epidemics and that this data is a public health “common good” to which researchers should continue to have access.

Significance statement

The opioid epidemic persists in the United States with over 80,000 deaths annually since 2021, primarily driven by synthetic opioids like fentanyl. As the geographic and demographic patterns of the opioid epidemic are rapidly changing, accurate and timely monitoring is needed. In this paper, we used social media data from Reddit to conduct public health surveillance of the opioid epidemic, following 1.5+ million geo-located users over 10+ years. We also found that near real-time Reddit data can improve our ability to predict future overdose death rates compared to models only using CDC data with typical half-year reporting delays. Our work suggests that social media can be a useful component for public health surveillance of the opioid epidemic.
Endometrium receptivity and the dose-related effects of Acupuncture therapies in infertile women: a protocol for systematic review and meta analysis
Authors: Zheng Xiaoyan , Liu Liying , Zhou Hang , Yang Hongmei , Wang Fangge , Yang Jie
Published: April 2021

Introduction

The aim of the systematic review (SR) is to evaluate the efficacy of Acupuncture in endometrium receptivity(ER) of infertile women and find out dose-related between Acupuncture and ER improving.

Methods and analysis

We will search four English databases: PubMed, Embase, Cochrane Library, Web of Science, and five Chinese databases: SinoMed (formerly Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), Wanfang Data, and China Biomedical Literature Database (CBM), China Science Journal Database (VIP database) from inception to February 2021 in English and Chinese. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. All clinical randomized controlled trials related to Acupuncture for endometrium receptivity of infertile women will be included. Two review authors will perform all research selection, data extraction, and research quality assessment. According to suggestions, data will be synthesized in a fixed-effect model, or random effect model due to the heterogeneity test. The primary outcomes include ER (endometrial thickness and endometrial hemodynamic parameters) and clinical pregnancy rate(CPR). Secondary outcomes include a dose of the interventions(the starting time of Acupuncture, the duration, and frequency of Acupuncture sessions), and adverse events will be assessed. We will use the statistical package (RevMan5.4.0) provided by The Cochrane Collaboration to analyze data. The quality of evidence will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Ethics and dissemination

Since this article does not contain patient personal information, ethical approval is not required. The contract is distributed by a peer-review

Systematic review registration

PROSPERO, CRD42020206790

Strengths and limitations of this study

This study will be the first ever systematic review and meta-analysis in dose-related effects of Acupuncture therapies in treating endometrium receptivity.

The quality of evidence will be assessed by the Grading of Recommendations Assessment,Development, and Evaluation system.

Our research approach will only focus on the dosage of acupuncture interventions. Due to the diversity of included treatment plans, Traditional Chinese Medicine and Moxibustion will increase the heterogeneity of results.

We will only retrieve data from Chinese and English databases which could limit available data or result in language bias.
Modelling, Simulations and Analysis of the First and Second COVID-19 Epidemics in Beijing
Authors: Min Lequan
Published: April 2021

To date, over 130 million people on infected with COVID-19. It causes more 2.8 millions deaths. This paper introduces a symptomatic-asymptomatic-recoverer-dead differential equation model (SARDDE). It gives the conditions of the asymptotical stability on the disease-free equilibrium of SARDDE. It proposes the necessary conditions of disease spreading for the SARDDE. Based on the reported data of the first and the second COVID-19 epidemics in Beijing and simulations, it determines the parameters of SARDDE, respectively. Numerical simulations of SARDDE describe well the outcomes of current symptomatic and asymptomatic individuals, recovered symptomatic and asymptomatic individuals, and died individuals, respectively. The numerical simulations suggest that both symptomatic and asymptomatic individuals cause lesser asymptomatic spread than symptomatic spread; blocking rate of about 90% cannot prevent the spread of the COVID19 epidemic in Beijing; the strict prevention and control strategies implemented by Beijing government is not only very effective but also completely necessary. The numerical simulations suggest also that using the data from the beginning to the day after about two weeks at the turning point can estimate well or approximately the following outcomes of the two COVID-19 academics, respectively. It is expected that the research can provide better understanding, explaining, and dominating for epidemic spreads, prevention and control measures.
A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India
Authors: Kaur Upinder , Ojha Bisweswar , Pathak Bhairav Kumar , Singh Anup , Giri Kiran R , Singh Amit , Das Agniva , Misra Anamika , Yadav Ashish Kumar , Chakrabarti Sankha Shubhra , Kansal Sangeeta
Published: April 2021

Vaccines are an important public health measure for tiding over the COVID-19 pandemic. Several vaccines have been approved in different countries for emergency use. In India, two vaccines have been currently approved-COVISHIELD (Serum Institute of India (SII)) which is a recombinant simian adenovirus-based vaccine and COVAXIN (Bharat Biotech) which is an inactivated SARS-CoV-2 vaccine. Our current study provides the first post approval safety data on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers in northern India (n=804). Around one half of vaccine recipients developed adverse events at any time post vaccination with majority of reactions being mild to moderate in severity. AEFIs were seen in 40% participants after first dose and around 16% participants after second dose. This observed reactogenicity is much less compared to 60-88% reactogenicity rate observed with Oxford-AstraZeneca’s ChAdOx1 vaccine in the UK based population. Individually, fever, injection site pain and headache were the commonly observed AEFIs. Overall, the frequency of systemic events of severity grade 3 was only 0.5% and is much less than the reported rates for other recombinant adenoviral vaccines. The rate of serious AEFIs in our study was only 0.1% (n=1). There was a possibility of this AEFI being an immunization stress related response. No deaths were reported in the vaccine recipients in our study during the study period. Reactogenicity rate was observed to decrease with age and was higher in females. On the basis of interim findings of this safety study, it may be interpreted that the ChAdOx1 nCoV-19 corona virus vaccine (recombinant) (COVISHIELD, Serum Institute of India) carries a good safety profile overall.
Evidence for a moderating effect of drinking severity but not HIV status on brain age in heavy episodic drinkers
Authors: Ipser Jonathan , Joska John , Sevenoaks Tatum , Gouse Hetta , Freeman Carla , Kaufmann Tobias , Andreassen Ole A. , Shoptaw Steve , Stein Dan J.
Published: April 2021

Background

Chronic HIV infection and alcohol use have been associated with brain changes and neurocognitive impairment. However, their combined effects are less well studied. We correlated measures of “brain age gap” (BAG) and neurocognitive impairment in participants with and without HIV/AIDS and heavy episodic drinking (HED). We predicted that BAG will be greater in PWH who engage in HED and that these effects will be particularly pronounced in frontoparietal and subcortical regions.

Method

69 participants were recruited from a community health centre in Cape Town: HIV-/HED-(N = 17), HIV+/HED- (N = 14), HIV-/HED+ (N = 21), and HIV+/HED+ (N = 17). Brain age gap (BAG) was derived from thickness, area and volumetric measurements from the whole brain or one of six brain regions. Linear regression models were employed to identify differences in BAG between patient groups and controls. Associations between BAG and clinical indicators of HIV and HED status were also tested using bivariate statistical methods.

Results

Compared to controls, greater whole brain BAG was observed in HIV-/HED+ (Cohen’s d = 1.61, p < 0.001), and HIV+/HED+ (d = 1.52, p = 0.005) participants. Differences in BAG between patients and controls were observed subcortically, as for the cingulate and the parietal cortex. An exploratory analysis revealed that higher relative brain ageing in HED participants with the highest drinking scores (W = 66, p = 0.036) but did not vary as a function of nadir CD4 count or current HIV viral load.

Conclusion

The association between heavy episodic drinking and BAG, independent of HIV status, points to the importance of screening for and targeting alcohol use disorders in primary care. Our findings also point to the utility of assessing the contribution of brain regions to the BAG.
Evolving SARS-CoV-2 variants and mutational cascades
Authors: Halley John M. , Vokou Despoina , Pappas Georgios , Sainis Ioannis
Published: April 2021

The emergence of novel SARS-CoV-2 variants of concern (VOC), in late 2020, with selective transmission advantage and partial immunity escape potential, threatens a pandemic resurgence. The timing of mutational evolution and its limits are thus of paramount importance in preparedness planning. Here, we present a model predicting the pattern of epidemic growth including the emergence of variants through mutation. It is based on the SEIR (Susceptible, Exposed, Infected, Removed) model, but its equations are modifiable according to the transmission parameters of novel variants. Since more transmissible strains will drive a further increase in the number of cases, they will also lead to further novel mutations. As one cannot predict whether there is a viral mutational evolutionary limit, we model a cascade that could lead to hyper-exponential growth involving the emergence of even more transmissible mutants that could overwhelm systemic response. Our results are consistent with the timing, since the beginning of the pandemic, of the concurrent and independent emergence of the VOCs. We examine conditions that favor the expected appearance of similar variants, thus enabling better preparedness and relevant research.
Comparing between survived and deceased patients with Diabetes Mellitus and COVID-19 in Bangladesh: A cross sectional study from a COVID-19 dedicated hospital
Authors: Morshed Md. Shahed , Al Mosabbir Abdullah , Hossain Mohammad Sorowar
Published: April 2021

The current coronavirus disease 2019 (COVID-19) outbreak was reported to cause significantly higher mortality and morbidity among patients with diabetes mellitus (DM). Although Bangladesh is amongst the top 10 countries with diabetic people, data on these patients with COVID-19 is scarce from this region. This study aimed to illustrate the clinical features and outcomes of hospitalized patients with COVID-19 and DM in Bangladesh while comparing survivors and deceased.

This retrospective cross-sectional study was conducted among RT-PCR confirmed COVID-19 patients with pre-existing Diabetes Mellitus in a specialized COVID-19 hospital in Bangladesh. Data from hospital records were analyzed.

Among 921 RT-PCR confirmed COVID-19 admitted during the study period, 231 (∼25%) patients with pre-existing DM (median age 60 years) were included in the analysis. The death rate among all hospitalized patients (with and without DM) was 2.8% compared to 11.3% among diabetic patients. The median hospital stay was 13 days (IQR 10.5, 17.0) for survivors and five days (IQR 2.0-8.3) for the deceased. The clinical features were not significantly different between survivors and the deceased. However, deceased patients had significantly lower blood oxygen level (85% vs 93%, p <0.001), and higher neutrophil-lymphocyte ratio (7.9 vs 4.5, p 0.003) and serum ferritin (946.0 vs 425.0 ng/ml, p 0.03). Glycemic status was poor in both groups.

This study would help identify a subgroup of diabetic patients with COVID-19 who are at higher risk of in-hospital death and improve clinical decision making.
A study of clinical outcomes and prognostic factors associated with invasive mechanical ventilation of patients in non-ICU settings: A systematic review and meta-analysis
Authors: Agarwal Shubham , Ray Animesh , Anand Abhishek , Chopra Neha , Narayan Ananthu , Keri Vishakh , Rastogi Neha , Roy Debarchan , Jadon Ranveer Singh , Vikram Naval K
Published: April 2021

There is paucity of evidence related to mechanical ventilation in the general ward setting. We aimed to study the clinico-etiological profile, outcomes and prognostic factors of patients receiving invasive mechanical ventilation in non-ICU (ward) setting, and compare these parameters with that of patients in the ICU, wherever it was reported. A systematic review and meta-analysis was done on articles published till June 2020. Two authors independently extracted the data. The study population included patients who received mechanical ventilation in ward setting. Fourteen studies reporting on 20833 patients were included (20252 exclusively ventilated in ward), with most of the studies being from Israel, USA, Japan and Taiwan. Risk of bias was estimated using the Newcastle-Ottawa Scale for observational studies, and was found to be low. Most common reason for intubation was respiratory illness. Most common variables predicting mortality were prognostic scores like APACHE-II and Acute Physiology Score (APS). Pooled mortality rate in ward across 6 studies was 0.72 (95% CI 0.69-0.74) with no heterogeneity among these 6 studies (I2=0.0). Mortality rate varied significantly with study population characteristics, and was lower among patients being weaned in ward. A major limitation of our study was the paucity of studies and significant heterogeneity among existing studies, with respect to outcomes like duration of ventilation, hospital stay, rates of complications, and prognostic factors. This systematic review and meta-analysis found that mortality among patients receiving invasive mechanical ventilation in ward settings remains high. Data regarding other outcomes and prognostic factors predicting mortality was very heterogeneous highlighting the need for future studies concentrating specifically on these aspects.

Systematic review registration: PROSPERO 2020 (CRD42020166775)
Outcomes of COVID-19 Vaccination Efforts in Florida from December 14, 2020 to March 15, 2021 on Older Individuals
Authors: Rivkees Scott. A. , Roberson Shamarial , Blackmore Carina
Published: April 2021

Per-capita, Florida ranks second in those 65 years of age and older (20.5%) with more than 4,500,000 individuals in this category. COVID-19 vaccine was allocated in a phased roll-out beginning December 14, 2020. Phase 1A included health care personnel with direct patient contact, and residents and staff of nursing homes (NHs) and assisted living facilities (ALFs). Following this initial phase, individuals 65 years of age and older became eligible for vaccination, along with individuals determined by hospital providers to be extremely medically vulnerable to COVID-19. This strategy was based on the desire to most immediately reduce morbidity and mortality, as COVID-19 morbidity and mortality is age-related. Through March 15, 2021, 4,338,099 individuals received COVID-19 vaccine, including 2,431,540 individuals who completed their vaccination series. Of all those vaccinated, 70% were 65 years of age and older, and 63% of those 65 years of age and older. Beginning February 1, 2021, the decline in the number of new cases per week became greater in those 65 years of age and older than those younger. By March 15, 2021, the number of new cases, hospitalizations, and deaths per day for those 65 years of age and older relative to mid-January, were 82%, 80%, and 92% lower respectively. In comparison, the number of new cases, hospitalizations, and deaths per day for those younger than 65 years of age were 70%, 60%, and 87% lower respectively. Reductions in rates in those 65 year of age and older, were thus greater than in those who were younger (p <0.01; Wilcoxon test). These data show that vaccination efforts directed at those 65 years of age and older results in accelerated rates of overall declines in COVID-19 hospitalizations and mortality.
Distinct patterns of cognitive outcome in young children with autism spectrum disorder receiving the Early Start Denver Model
Authors: Michel Godel , François Robain , Nada Kojovic , Martina Franchini , Hilary Wood de Wilde , Marie Schaer
Published: April 2021

Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child’s developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15 – 42). Our aim was to identify early predictors of response to treatment. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of treatment. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of treatment (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to treatment. The majority significantly improved developmental scores over the course of treatment (Optimal Responders: OptR) whereas a minority of children showed little to no improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal two-year treatment outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR).
Impact of COVID-19 on Pediatric Emergency Department Visits: A Retrospective Cohort Study
Authors: Fontaine Pierre , Osmanlliu Esli , Gravel Jocelyn , Boutin Ariane , D. Trottier Evelyne , Gaucher Nathalie Orr , D’Angelo Antonio , Drouin Olivier
Published: April 2021

Background & Objective

COVID-19 has caused significant shifts in healthcare utilization, including pediatric emergency departments (EDs). We describe variations in visits made to two large pediatric EDs during the first three months of the COVID-19 pandemic, compared to a historical control period.

Methods

We performed a retrospective cohort study of children presenting to two academic pediatric EDs in Quebec, Canada. We compared the number of ED visits during the first wave of COVID-19 pandemic (March-May 2020) to historical controls (March-May 2015-2019), using Poisson regression, adjusting for site and the underlying baseline trend. Secondary analyses examined variations in ED visits by acuity, disposition, and disease categories.

Results

From 2015 to 2019, the two EDs had a median of 1,632 visits per week [interquartile range (IQR) 1,548; 1,703]; in 2020, this number decreased to 536 visits per week [IQR 446; 744]. In multivariable analyses, this represent a 53.3% (95%CI: 52.1, 54.4) reduction in the number of ED visits. The reduction was larger among visits triage categories 4 and 5 (lower acuity) than categories 1, 2 and 3 (higher acuity): -54.2% vs. -42.0% (p<0.001). A greater proportion of children presenting to these sites were hospitalized during the COVID period than in pre-COVID period: 11.8% vs. 5.5% (p<0.001).

Conclusions

During the early stages of the COVID-19 pandemic, there was a large decrease in visits to pediatric EDs. Patients presented with higher acuity at triage and the proportion of patients requiring hospitalization increased.
Does the occurrence of a severe asthma exacerbation change the rate of subsequent events?
Authors: Lee Tae Yoon , Petkau John , Sadatsafavi Mohsen
Published: April 2021

Background

Severe exacerbations requiring hospitalization are an important component of the natural history of asthma and a major source of its burden. Whether the occurrence of a severe exacerbation affects the rate of subsequent events has far-reaching implications in asthma management.

Methods

Using the centralized administrative health databases of British Columbia, Canada (1997/01/01 –2016/03/31), we created an incidence cohort of patients with at least one severe asthma exacerbation, defined as an episode of hospitalization with asthma as the primary diagnosis. We used an accelerated failure time joint frailty model for the time intervals between severe asthma exacerbations. Analyses were conducted separately for pediatric (< 14 years old) and adult (≥14 years old) patients.

Results

There were 3,039 patients (mean age at baseline 6.4, 35% female) in the pediatric group and 5,459 patients (mean age at baseline 50.8, 68% female) in the adult group, with 16% and 15%, respectively, experiencing at least one severe asthma exacerbation during follow-up. The first follow-up severe asthma exacerbation was associated with an increase of 79% (95% CI: 15% – 186%) in the rate of the subsequent events for the pediatric group. The corresponding value was 186% (95% CI: 85% – 355%) for the adult group. For both groups, the effects of subsequent severe exacerbations were not statistically significant.

Conclusion

Our findings suggest that among patients who have experienced their first severe asthma exacerbation, preventing the next event can drastically change the course of the disease and reduce the burden of future exacerbations.
Levels of produced antibodies after vaccination with mRNA vaccine; effect of previous infection with SARS-CoV-2
Authors: Konstantinidis Theocharis , Zisaki Stavroula , Mitroulis Ioannis , Konstantinidou Eleni , Kontekaki Eftychia G. , Romanidoui Gioulia , Karvelas Alexandros , Nanousi Ioanna , Lazidis Leonidas , Cassimos Dimitrios , Tsigalou Christina , Martinis George , Panopoulou Maria
Published: April 2021

The aim of this study was to estimate the immunogenic effect of mRNA vaccine against SARS-CoV-2. This study included 510 participants who received mRNA vaccine. The measurement of anti-Covid-19 antibodies was performed using the Abbott SARS-CoV-2 IgG quantitative assay (Abbott). Overall, mean title of anti-Spike antibodies was 19319.2±1787.5 AU/ml. Vaccination induced a robust immunogenic response in previous infected with SARS-CoV-2 compared. Additionally, individuals that were asymptomatic after vaccination produced lower levels of antibodies compared to feverish individuals. In conclusion, remarkable high level of anti-Spike Covid-19 antibodies was found after vaccination.
Co-circulation of SARS-CoV-2 variants B.1.1.7 and P.1
Authors: Stefanelli Paola , Trentini Filippo , Guzzetta Giorgio , Marziano Valentina , Mammone Alessia , Poletti Piero , Grané Carla Molina , Manica Mattia , del Manso Martina , Andrianou Xanthi , Pezzotti Patrizio , Ajelli Marco , Rezza Giovanni , Brusaferro Silvio , Merler Stefano ,   COVID-19 National Microbiology Surveillance Study Group
Published: April 2021

SARS-CoV-2 variants of concern (B.1.1.7, P.1 and B.1.351) have emerged in different continents of the world. To date, little information is available on their ecological interactions. Based on two genomic surveillance surveys conducted on February 18 and March 18, 2021 across the whole Italian territory and covering over 3,000 clinical samples, we found significant co-circulation of B.1.1.7 and P.1. We showed that B.1.1.7 was already dominant on February 18 in a majority of regions/autonomous provinces (national prevalence 54%) and almost completely replaced historical lineages by March 18 (dominant in all regions/autonomous provinces, national prevalence 86%). At the same time, we found a substantial proportion of cases of the P.1 lineage on February 18, almost exclusively in Central Italy (with an overall prevalence in the macro-area of 18%), which remained at similar values on March 18, suggesting the inability by this lineage to outcompete B.1.1.7. Only 9 cases from variant B.1.351 were identified in the two surveys. At the national level, we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). The relative transmissibility of P.1 estimated at the national level varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. These observations may have important consequences on the assessment of future pandemic scenarios.
The Fatty Acid Methyl Ester (FAME) profile ofPhytophthora agathidicidaand its potential use as diagnostic tool
Authors: Lacey Randy F. , Sullivan-Hill Blake A. , Deslippe Julie R. , Keyzers Robert A. , Gerth Monica L.
Published: April 2021

Phytophthoradiseases cause devastation to crops and native ecosystems worldwide. In New Zealand,Phytophthora agathidicidais threatening the survival of kauri, an endemic, culturally and ecologically important tree species. The current method for detectingP. agathidicidais a soil bating assay that is time-consuming and requires high levels of expertise to assess, thus limiting the analytical sample throughput. Here, we characterized the fatty acid methyl ester (FAME) profile ofP. agathidicida. We also compared it with the FAME profile ofP. cinnamomiand assessed the efficacy of FAME analysis as a diagnostic tool for detecting the pathogen in soil samples. In FAME analysis, the total fatty acid content is isolated from a sample and converted to FAMEs for analysis, a process that takes less than a day. Unique fatty acid acyl chains can serve as biomarkers for specific organisms. We detected 12 fatty acids inP. agathidicida, two of which (20:4ω6 and 20:5ω3) show promise as potentialPhytophthoraspecific biomarkers. Collectively, these findings advance our fundamental understanding ofP. agathidicidabiology and provide a promising technique to increase the rate of sample processing and the speed of pathogen detection forP. agathidicidain soil.
A novel approach to partitioning evapotranspiration into evaporation and transpiration in flooded ecosystems
Authors: Eichelmann Elke , Mantoani Mauricio C. , Chamberlain Samuel D. , Hemes Kyle S. , Oikawa Patricia Y. , Szutu Daphne , Valach Alex , Verfaillie Joseph , Baldocchi Dennis D.
Published: April 2021

Reliable partitioning of micrometeorologically measured evapotranspiration (ET) into evaporation (E) and transpiration (T) would greatly enhance our understanding of the water cycle and its response to climate change. While some methods on ET partitioning have been developed, their underlying assumptions make them difficult to apply more generally, especially in sites with large contributions of E. Here, we report a novel ET partitioning method using Artificial Neural Networks (ANN) in combination with a range of environmental input variables to predict daytime E from nighttime ET measurements. The study uses eddy covariance data from four restored wetlands in the Sacramento-San Joaquin Delta, California, USA, as well as leaf-level T data for validation. The four wetlands vary in structure from some with large areas of open water and little vegetation to very densely vegetated wetlands, representing a range of ET conditions. The ANNs were built with increasing complexity by adding the input variable that resulted in the next highest average value of model testing R2across all sites. The order of variable inclusion (and importance) was: vapor pressure deficit (VPD) > gap-filled sensible heat flux (H_gf) > air temperature (Tair) > friction velocity (u∗) > other variables. Overall, 36 ANNs were analyzed. The model using VPD, H_gf, Tair, and u∗(F11), showed an average testing R2value across all sites of 0.853. In comparison with the model that included all 10 variables (F36), F11 generally performed better during validation with independent data. In comparison to other methods described in the literature, the ANN method generated more consistent T/ET partitioning results especially for more complex sites with large E contributions. Our method improves the understanding of T/ET partitioning. While it may be particularly suited to flooded ecosystems, it can also improve T/ET partitioning in other systems, increasing our knowledge of the global water cycle.
Tubular ERGIC (t-ERGIC): a SURF4-mediated expressway for ER-to-Golgi transport
Authors: Yan Rui , Chen Kun , Xu Ke
Published: April 2021

The endoplasmic reticulum (ER)-to-Golgi transport is critical to protein secretion and intracellular sorting. Cargo carriers mediating the ER-to-Golgi transport are morphologically diverse, but it remains unclear whether this diversity arises from different cargo receptors, or whether it could lead to differential transport kinetics. Here we report a tubular ER-Golgi intermediate compartment (t-ERGIC) that is induced by the cargo receptor SURF4 and selectively expedites the ER-to-Golgi transport of SURF4 cargoes. Lacking the canonical ERGIC marker ERGIC-53 yet positive for the small GTPase Rab1, the t-ERGIC is further distinct from the stereotypical vesiculo-tubular cluster (VTC) ERGIC by its extremely elongated shape (~10 μm long with <30 nm diameter). With its exceptional surface-to-volume ratio anden bloccargo packaging, high (~2 μm/s) intracellular traveling speeds, and ER-Golgi recycling capability, the t-ERGIC provides an efficient means for trafficking SURF4-bound cargoes. The biogenesis and cargo selectivity of t-ERGIC both depend on SURF4, which recognizes the N-terminus of soluble cargoes and co-clusters with the selected cargoes to expand the ER exit site. At the steady state, the t-ERGIC-mediated fast ER-to-Golgi transport is antagonized by retrograde transport based on the cargo C-terminal ER retrieval signal: we thus demonstrate the fine-tuning of protein trafficking and localization via its primary structure. Together, our results argue that specific cargo-receptor interactions give rise to distinct transport carriers, which in turn regulate the ER-to-Golgi trafficking kinetics.
Shared and Unique Evolutionary Trajectories to Ciprofloxacin Resistance in Gram-negative Bacterial Pathogens
Authors: Zlamal Jaime E. , Leyn Semen A. , Iyer Mallika , Elane Marinela L. , Wong Nicholas A. , Wamsley James W. , Vercruysse Maarten , Garcia-Alcalde Fernando , Osterman Andrei L.
Published: April 2021

The resistance to broad-spectrum antibiotic ciprofloxacin is detected in high rates for a wide range of bacterial pathogens. To investigate dynamics of ciprofloxacin resistance development we proposed a comparative resistomics workflow for three clinically relevant species of Gram-negative bacteria:Escherichia coli,Acinetobacter baumannii, andPseudomonas aeruginosa. We combined experimental evolution in a morbidostat with deep sequencing of evolving bacterial populations in time series that reveals both shared and unique aspects of evolutionary trajectories patterns. Representative clone characterization by sequencing and MIC measurements enabled direct assessment of mutations impact on the extent of acquired drug resistance. In all three species we observed a two-stage evolution: (1) early ciprofloxacin resistance reaching 4-16-fold of wildtype MIC commonly as a result of single mutations in DNA gyrase target genes (gyrAorgyrB) and (2) additional genetic alterations affecting transcriptional control of drug efflux machinery or secondary target genes (DNA topoisomeraseparCorparE).

Importance

The challenge of spreading antibiotic resistance calls for systematic efforts to develop more “irresistible” drugs based on deeper understanding of dynamics and mechanisms of antibiotic resistance acquisition. To address this challenge, we have established a comparative resistomics approach which combines experimental evolution in a continuous culturing device, the morbidostat, with ultradeep sequencing of evolving microbial populations to identify evolutionary trajectories (mutations and genome rearrangements) leading to antibiotic resistance over a range of target pathogens. Here we report the comparative resistomics study of three Gram-negative bacteria (Escherichia coli,Acinetobacter baumannii, andPseudomonas aeruginosa),which revealed shared and species-specific aspects of the evolutionary landscape leading to robust resistance against the clinically important antibiotic ciprofloxacin. In addition to specific findings, the impact of this study is in highlighting the anticipated utility of a morbidostat-based comparative genomic approach to guide rational optimization of treatment regimens for current antibiotics and development of novel antibiotics with minimized resistance propensities.
The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signalling
Authors: Russo Lillian Cristina , Tomasin Rebeka , Araújo Matos Isaac , Manucci Antonio Carlos , Sowa Sven T. , Dale Katie , Caldecott Keith W. , Lehtiö Lari , Schechtman Deborah , Meotti Flavia Carla , Bruni-Cardoso Alexandre , Hoch Nicolas Carlos
Published: April 2021

SARS-CoV-2 non-structural protein 3 (Nsp3) contains a macrodomain that is essential for virus replication and is thus an attractive target for drug development. This macrodomain is thought to counteract the host interferon (IFN) response, an important antiviral signalling cascade, via the removal of ADP-ribose modifications catalysed by host poly(ADP-ribose) polymerases (PARPs). Here, we show that activation of the IFN response induces ADP-ribosylation of host proteins and that ectopic expression of the SARS-CoV-2 Nsp3 macrodomain reverses this modification in human cells. We further demonstrate that this can be used to screen for cell-active macrodomain inhibitors without the requirement for BSL-3 facilities. This IFN-induced ADP-ribosylation is dependent on the PARP9/DTX3L heterodimer, but surprisingly the expression of Nsp3 macrodomain or PARP9/DTX3L deletion do not impair STAT1 phosphorylation or the induction of IFN-responsive genes. Our results suggest that PARP9/DTX3L-dependent ADP-ribosylation is a downstream effector of the host IFN response and that the cellular function of the SARS-CoV-2 Nsp3 macrodomain is to hydrolyse this end product of IFN signalling, and not to suppress the IFN response itself.
Antibody Activities in Hyperimmune Plasma Against theRhodococcus equiVirulence-Associated Protein A or Poly-N-Acetyl Glucosamine are Associated with Protection of Foals Against Rhodococcal Pneumonia
Authors: Kahn Susanne K. , Cywes-Bentley Colette , Blodgett Glenn P. , Canaday Nathan M. , Turner-Garcia Carly E. , Vinacur Mariana , Cortez-Ramirez Sophia C. , Sutter Patrick J. , Meyer Sarah C. , Bordin Angela I. , Vlock Daniel R. , Pier Gerald B. , Cohen Noah D.
Published: April 2021

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused byRhodococcus equiremains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either withR. equi(RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C’1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n=119) or subclinical pneumonia at Farm B (n=114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C’1q deposition, respectively. Results indicated that levels of activity of antibodies againstR. equiantigens are correlates of protection against both subclinical and clinicalR. equipneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C’1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection againstR. equipneumonia in foals.
Effects of potassium fertilizer on dry matter accumulation and potassium absorption characteristics of maize (Zea mays L.) inbred lines with different yield types
Authors: Fan Ya-fang , Gao Ju-lin , Sun Ji-ying , Liu Jian , Su Zhi-jun , Hu Shu-ping , Wang Zhi-gang , Yu Xiao-fang
Published: April 2021

In this experiment, 20 different maize inbred lines were used as basic materials, which were divided into high-yield type, middle-yield type and low-yield type by yield cluster analysis. A 3-year long-term positioning field experiment (2016–2018) was carried out to assess the effects of potassium fertilizer on dry matter, potassium absorption and potassium absorption efficiency of maize inbred lines with different yield types. The results showed that the dry matter, potassium absorption and potassium absorption efficiency of leaf, stem, bract, rachis and grain of maize inbred lines have been significantly increased with potassium application in comparison with no potassium application. Potassium fertilizer could improve the dry matter accumulation capacity and potassium absorption characteristics of maize, promote the potassium absorption by maize plants, influence the growth and development of maize, and then improve the maize yield. The decrease of dry matter, potassium absorption and potassium absorption efficiency of high-yield maize inbred lines was smaller under low potassium stress. The high-yield maize inbred lines had stronger ability to maintain higher dry matter accumulation and potassium absorption characteristics under low potassium stress. The study provided a theoretical basis for the breeding of potassium-efficient maize materials.
Linkage disequilibrium and population structure in a core collection ofBrassica napus(L.)
Authors: Rahman Mukhlesur , Hoque Ahasanul , Roy Jayanta
Published: April 2021

Estimation of genetic diversity in rapeseed/canola is important for sustainable breeding program to provide an option for the development of new breeding lines. The objective of this study was to elucidate the patterns of genetic diversity within and among different structural groups, and measure the extent of linkage disequilibrium (LD) of 383 globally distributed rapeseed/canola germplasm using 8,502 single nucleotide polymorphism (SNP) markers. The germplasm accessions were divided into five subpopulations (P1 to P5) with obvious geographic and growth habit-related patterns. All subpopulations showed moderate genetic diversity (averageH= 0.22 andI= 0.34). The pairwiseFstcomparison revealed a great degree of divergence (Fst> 0.24) between most of the combinations. The rutabaga type showed highest divergence with spring and winter types. Higher divergence was also found between winter and spring types. Overall, mean linkage disequilibrium was 0.03 and it decayed to its half maximum within < 45 kb distance for whole genome. The LD decay was slower in C genome (< 93 kb), relative to the A genome (< 21 kb) which was confirmed by availability of larger haplotype blocks in C genome than A genome. To maximize genetic gain, hybridization between rutabaga and other types are potentially the best option. Hybridization between spring and winter, semi-winter type is also helpful to maximize the diversity in subsequent populations. Low genetic differentiation between both spring type subpopulations (P4 and P3) will accelerate favorable allele accumulation for specific traits in elite lines. The Neighbor-Joining tree and kinship matrix will assist to identify distantly related genotypes from subpopulations to utilize in hybridization. The low levels of LD and population structure make the core collection an important resource for association mapping efforts to identify genes useful in crop improvement as well as for selection of parents for hybrid breeding.
A Toolbox and Crowdsourcing Platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE)
Authors: Soghoyan Gurgen , Ledovsky Alexander , Nekrashevich Maxim , Martynova Olga , Polikanova Irina , Portnova Galina , Rebreikina Anna , Sysoeva Olga , Sharaev Maxim
Published: April 2021

Independent Component Analysis (ICA) is a conventional approach to exclude non-brain signals such as eye-movements and muscle artifacts from electroencephalography (EEG). Due to other possible EEG contaminations, a rejection of independent components (ICs) is usually performed in semiautomatic mode and requires experts’ involvement. Noteworthy, as also revealed by our study, experts’ opinion about the nature of a component often disagrees highlighting the need to develop a robust and sustainable automatic system for EEG ICs classification. The current article presents a toolbox and crowdsourcing platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE) available via linkhttp://alice.adase.org/. The ALICE toolbox aims to build a sustainable algorithm not only to remove artifacts but also to find specific patterns in EEG signals using ICA decomposition based on accumulated experts’ knowledge.

The difference from previous toolboxes is that the ALICE project will accumulate different benchmarks based on crowdsourced visual labeling of ICs collected from publicly available and in-house EEG recordings. The choice of labeling is based on estimation of IC time-series, IC amplitude topography and spectral power distribution. The platform allows supervised ML model training and re-training on available data subsamples for better performance in specific tasks (i.e. movement artifact detection in healthy or autistic children). Also, current research implements the novel strategy for consentient labeling of ICs by several experts. The provided baseline model shows that it can be used not only for detection of noisy IC but also for automatic identifications of components related to the functional brain oscillations such as alpha and mu-rhythm.

The ALICE project implies the creation and constant replenishment of the IC database, which will be used for continuous improvement of ML algorithms for automatic labeling and extraction of non-brain signals from EEG. The toolbox and current dataset are open-source and freely available to the researcher community.
Host factors drive the within-host competition between highly and low pathogenic H5N8 avian influenza viruses
Authors: Bessière Pierre , Figueroa Thomas , Coggon Amelia , Foret-Lucas Charlotte , Houffschmitt Alexandre , Fusade-Boyer Maxime , Dupré Gabriel , Guérin Jean-Luc , Delverdier Maxence , Volmer Romain
Published: April 2021

Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LPincreased H5N8HPreplication and pathogenesis. By contrast, the H5N8LPantagonized H5N8HPreplication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HPinhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution.