bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Obstacles to Education in Ireland
Authors: Doyle David M , Muldoon Marie , Thompson Stephanie , Murphy Muiread
Published: April 2021

This policy note highlights the costs of sending a child to school in Ireland and explores the extent to which these represent a significant economic barrier to schooling for low-income families. It also evaluates the efforts to reduce early school leaving and examines the increasing commodification of education in Ireland.
Species Composition, Parous Rate, and Infection Rate of Anopheles Mosquitoes (Diptera: Culicidae) in Bahir Dar City Administration, Northwest Ethiopia
Authors: Getaneh Abel , Yimer Mulat , Alemu Megbaru , Dejazmach Zelalem , Alehegn Michael , Tegegne Banchamlak
Published: April 2021

Anopheles mosquitoes are the main vectors of malaria. There is little information on the current entomological aspects of Anopheles mosquitoes in Amhara region of northwestern Ethiopia. Therefore, the aim of this study was to assess the prevailing species composition, parous rate, and infection rate of Anopheles mosquitoes in the Bahir Dar city administration. A community-based cross-sectional study was conducted from January through July 2020. For this, six Centers for Disease Control and Prevention light traps (three traps indoor and three traps outdoor) were used to collect adult female Anopheles mosquitoes. The species were morphologically identified, and the parous and infection rates were determined via dissection of ovaries and salivary gland, respectively. A total of 378 adult female Anopheles mosquitoes comprised of three species (Anopheles d’thali, Anopheles rhodesiensis, and Anopheles gambiae complex) were collected and identified at the study sites. Anopheles rhodesiensis was the predominant species accounting for 90% of all collections at the Zenzelima site, followed by An. gambiae complex (6.5%). In contrast, An. gambiae complex was the predominant species at the Tis Abay site, comprising 94% of captures. The overall parous and infection rates were 35 (62.5%) and 1 (2.9%), respectively.
A cross-sectional study of the quality of life of patients living with type 1 diabetes treated with insulin glargine and neutral protamine Hagedorn insulin and the implications
Authors: Almeida Paulo H R F , Godman Brian , de Lemos Lívia L P , Silva Thales B C , De Assis Acúrcio Francisco , Guerra‑Junior Augusto Afonso , De Araújo Vânia E , Almeida Alessandra M , Alvares-Teodoro Juliana
Published: April 2021

Objectives

The study aim was to identify key factors associated with the health-related quality of life (HRQOL) of patients with type 1 diabetes mellitus (T1DM) treated with neutral protamine Hagedorn (NPH) insulin or human insulin analog glargine (IGLA).

Methods

We conducted two cross-sectional studies in Minas Gerais State, Brazil. One with 401 patients treated with IGLA, and the other with 179 T1DM patients treated with NPH. HRQOL was measured by Euroqol (EQ-5D-3L).

Key findings

Most participants were male (51%), aged between 18 and 40 years (47%), non-black (58%) and from the highest economic strata (A1-B2) (74%). Participants perceived their health as good/very good (51%), had one to three medical consultations in the previous year (51%), were not hospitalized in the previous year (74%), did not report angina (96%), diabetic neuropathy (90%), hearing loss (94%) or kidney disease (89%). Non-severe hypoglycaemia episodes in the last 30 days were reported by 17% of participants.

Conclusions

Higher HRQOL was associated with younger age (18–40 years), good/very good health self-perception, having had up to three medical consultations in the last year, not being hospitalized in the last year, having none to three comorbidities, not reporting angina, diabetic neuropathy, hearing loss or kidney disease and having had episodes of non-severe hypoglycaemia. In addition, the findings of our study demonstrated inequalities in access to treatment, which will be the subject of future research projects.
Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics
Authors: Woods Charles R , Bradley John S , Chatterjee Archana , Copley Lawson A , Robinson Joan , Kronman Matthew P , Arrieta Antonio , Fowler Sandra L , Harrison Christopher , Carrillo-Marquez Maria A , Arnold Sandra R , Eppes Stephen C , Stadler Laura P , Allen Coburn H , Mazur Lynnette J , Creech C Buddy , Shah Samir S , Zaoutis Theoklis , Feldman David S , Lavergne Valéry
Published: April 2021

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.
Tracking Antimicrobial Resistance in Neisseria gonorrhoeae from the Molecular Level Using Endocervical Swabs
Authors: Oree G , Naicker M , Maise H C , Tinarwo P , Ramsuran V , Abbai N S
Published: April 2021

Objective

The global emergence of drug resistance in Neisseria gonorrhoeae has resulted in the use of a range of antibiotics and is now a public health concern because this pathogen may become untreatable in the future. This study aimed to detect antimicrobial-resistant determinants in N. gonorrhoeae directly from endocervical specimens.

Methods

Three hundred seven pregnant women were enrolled in this study. Endocervical swabs were collected from consenting women and used for the detection of N. gonorrhoeae. Molecular indicators associated with penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, cefixime, and ceftriaxone resistance were detected by polymerase chain reaction.

Results

Of the 307 women, 24 (7.8%) tested positive for N. gonorrhoeae. The tetM gene carried on the American-type plasmid was shown to be present in all the specimens. Approximately 87.5% of the specimens carried the penicillinase-producing African-type plasmid, and the gyrase A gene carrying the Ser-91 mutation was shown to be present in 37.5% of the specimens. Mutations associated with azithromycin, spectinomycin, cefixime, and ceftriaxone resistance were not detected in the study specimens.

Conclusion

The detection of resistance determinants without the need for culture may prove to be more feasible for future epidemiological investigations focused on tracking antimicrobial susceptibility patterns in N. gonorrhoeae.
Transcriptional control of parturition: insights from gene regulation studies in the myometrium
Authors: Khader Nawrah , Shchuka Virlana M , Shynlova Oksana , Mitchell Jennifer A
Published: April 2021

The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for foetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1, progesterone receptors, oestrogen receptors, and nuclear factor kappa B, as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour-associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.
Topologies of synthetic gene circuit for optimal fold change activation
Authors: Litovco Phyana , Barger Natalia , Li Ximing , Daniel Ramez
Published: April 2021

Computations widely exist in biological systems for functional regulations. Recently, incoherent feedforward loop and integral feedback controller have been implemented into Escherichia coli to achieve a robust adaptation. Here, we demonstrate that an indirect coherent feedforward loop and mutual inhibition designs can experimentally improve the fold change of promoters, by reducing the basal level while keeping the maximum activity high. We applied both designs to six different promoters in E. coli, starting with synthetic inducible promoters as a proof-of-principle. Then, we examined native promoters that are either functionally specific or systemically involved in complex pathways such as oxidative stress and SOS response. Both designs include a cascade having a repressor and a construct of either transcriptional interference or antisense transcription. In all six promoters, an improvement of up to ten times in the fold change activation was observed. Theoretically, our unitless models show that when regulation strength matches promoter basal level, an optimal fold change can be achieved. We expect that this methodology can be applied in various biological systems for biotechnology and therapeutic applications.
Long-term renal survival of paediatric patients with lupus nephritis
Authors: Demir Selcan , Gülhan Bora , Özen Seza , Çeleğen Kübra , Batu Ezgi Deniz , Taş Nesrin , Orhan Diclehan , Bilginer Yelda , Düzova Ali , Ozaltin Fatih , Topaloğlu Rezan
Published: April 2021

Background

Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN).

Materials and methods

This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up.

Results

The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4–15.8]. The median follow-up duration was 43.1 months (IQR 24.3–69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome.

Conclusions

Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.
Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Lee Yeonhee , Kang Min Woo , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Wook Joo Kwon , Lim Chun Soo , Kim Yon Su , Kim Dong Ki
Published: April 2021

Background

An investigation into the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted.

Methods

In this observational cohort study, first, the clinical associations of the prevalence of stages 3–5 chronic kidney disease (CKD) and the estimated glomerular filtration rate (eGFR) with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer and driving) were investigated in 329 758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567 460). The findings were replicated with the 321 024 UK White British Biobank participants in the allele-score-based one-sample MR.

Results

A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR.

Conclusion

Physical activity and television watching causally affect kidney function in the general population.
Primary caregivers’ experience with the informed consent process in the paediatric emergency department: An interview-based qualitative study
Authors: Wazir Adonis , Sandokji Ibrahim , Greaves Morten , Sawaya Rasha D
Published: April 2021

Objective

This study aims to understand primary caregivers’ (PCG) experience with the informed consent (IC) process.

Methods

We conducted in-depth interviews with PCGs of paediatric patients who underwent a procedure requiring IC in the paediatric emergency department (PED) of a tertiary care paediatric centre in the USA, between January and March 2013 and between September 2013 and January 2014. We triangulated the qualitative findings from the PCG interviews with Likert-scale responses from the PCGs and with results from surveyed physicians.

Results

We included 14 PCG–physician dyads. Our results show that PCGs understand the importance of the IC process. They appreciated the calm demeanor of providers, and the clarity of their wording. PCGs felt that IC can add to the stress, and that it could be made simpler and timelier. PCGs also had varying extents of retention of the information provided.

Conclusion

This exploratory study suggests an overall positive IC experience of the PCGs while highlighting areas for improvement including a more thorough discussion of alternatives, a better assessment of knowledge transmission and retention by the PCG, and recognition of the PCG’s discomfort during decision making in a stressful environment.
A dopamine-based biosynthetic pathway produces decarboxylated betalains in Chenopodium quinoa
Authors: Henarejos-Escudero Paula , Contreras-Llano Luis Eduardo , Lozada-Ramírez José Daniel , Gómez-Pando Luz Rayda , García-Carmona Francisco , Gandía-Herrero Fernando
Published: April 2021

Betalains are the nitrogenous pigments that replace anthocyanins in the plant order Caryophyllales. Here, we describe unconventional decarboxylated betalains in quinoa (Chenopodium quinoa) grains. Decarboxylated betalains are derived from a previously unconsidered activity of the 4,5-DOPA-extradiol-dioxygenase enzyme (DODA), which has been identified as the key enzymatic step in the established biosynthetic pathway of betalains. Here, dopamine is fully characterized as an alternative substrate of the DODA enzyme able to yield an intermediate and structural unit of plant pigments: 6-decarboxy-betalamic acid, which is proposed and described. To characterize this activity, quinoa grains of different colors were analyzed in depth by chromatography, time-of-flight mass spectrometry, and reactions were performed in enzymatic assays and bioreactors. The enzymatic-chemical scheme proposed leads to an uncharacterized family of 6-decarboxylated betalains produced by a hitherto unknown enzymatic activity. All intermediate compounds as well as the final products of the dopamine-based biosynthetic pathway of pigments have been unambiguously determined and the reactions have been characterized from the enzymatic and functional perspectives. Results evidence a palette of molecules in quinoa grains of physiological relevance and which explain minor betalains described in plants of the Caryophyllales order. An entire family of betalains is anticipated.
Malaria elimination in India requires additional surveillance mechanisms
Authors: Rahi Manju , Das Payal , Sharma Amit
Published: April 2021

Malaria surveillance is weak in high malaria burden countries. Surveillance is considered as one of the core interventions for malaria elimination. Impressive reductions in malaria-associated morbidity and mortality have been achieved across the globe, but sustained efforts need to be bolstered up to achieve malaria elimination in endemic countries like India. Poor surveillance data become a hindrance in assessing the progress achieved towards malaria elimination and in channelizing focused interventions to the hotspots. A major obstacle in strengthening India’s reporting systems is that the surveillance data are captured in a fragmented manner by multiple players, in silos, and is distributed across geographic regions. In addition, the data are not reported in near real-time. Furthermore, multiplicity of malaria data resources limits interoperability between them. Here, we deliberate on the acute need of updating India’s surveillance systems from the use of aggregated data to near real-time case-based surveillance. This will help in identifying the drivers of malaria transmission in any locale and therefore will facilitate formulation of appropriate interventional responses rapidly.
Evaluating blockchain technology and related policies in China and the USA
Authors: Jiang Nan , Liu Xing , Xu Ming
Published: April 2021

Blockchain has been regarded as an emerging global technological phenomenon. This study uses the patent analysis method to compare the development of blockchain technology in China and the USA. An overview of blockchain policies in China and the USA is presented. Our analyses suggest that policies related to the blockchain stimulate the number of blockchain patent applications and create regional innovation in China. The innovation capability of Chinese enterprises has been more affected by these policies than that of the USA, which is reflected in the fact that Chinese enterprises have become key players in China and actively carry out patent layout in the USA. Although the developmental trend of blockchain technology in China and the USA is almost identical, the USA attaches more importance to safety technology, whereas China pays more attention to the application technology based on the differences in policies.
Effect of drying and/or warming piglets at birth under warm farrowing room temperatures on piglet rectal temperature over the first 24 h after birth
Authors: Vande Pol Katherine D , Tolosa Andres F , Shull Caleb M , Brown Catherine B , Alencar Stephan A S , Lents Clay A , Ellis Michael
Published: April 2021

Piglets experience a decline in body temperature immediately after birth, and both drying and warming piglets at birth reduce this. However, these interventions may be less effective at higher farrowing room temperatures. This study was carried out at a commercial facility to compare the effect of drying and/or warming piglets at birth on postnatal rectal temperature (RT) under relatively warm farrowing room temperatures (26.6 ± 2.09 °C). Forty-five sows/litters were used in a completely randomized design to compare three Intervention Treatments (applied at birth): Control (no treatment); Warming (piglets placed in a plastic box under a heat lamp for 30 min); and Drying+Warming (piglets dried with desiccant and warmed as above). Temperatures in the warming boxes over the study period averaged 37.7 ± 2.75 °C. At birth, piglets were weighed; RT temperature was measured at 0, 10, 20, 30, 45, 60, 120, and 1,440 min after birth. Blood samples were collected at 24 h after birth from a subsample of one piglet from each birth weight quartile within each litter to measure plasma immunocrit concentration. Data were analyzed using PROC MIXED of SAS with litter as the experimental unit, and piglet as a subsample of litter. The model for analysis of piglet rectal temperature included fixed effects of Intervention Treatment, measurement time (repeated measure), the interaction, and the random effect of sow. Compared with the Control, piglet RT were higher (P ≤ 0.05) for the Warming treatment between 10 and 60 min, and higher (P ≤ 0.05) for the Drying+Warming treatment between 10 and 120 min after birth. Rectal temperatures were higher (P ≤ 0.05) for the Drying+Warming than the Warming treatment between 20 and 120 min. Responses to drying and/or warming were greater for low-birth-weight piglets (<1.0 kg) than heavier littermates, but were generally less than observed in previous experiments with similar treatments carried out under cooler temperatures. Piglet immunocrit values were lower (P ≤ 0.05) for the Drying+Warming treatment compared to the other Intervention Treatments, which were similar (P > 0.05). Immunocrit values tended (P = 0.10) to be lower for light (<1.0 kg) compared with heavier birth weight piglets. In conclusion, drying and warming piglets at birth was more effective for reducing piglet RT decline after birth than warming alone, though the effect was less than observed in previous studies carried out under cooler farrowing room temperatures.
The threshold between life and death in Cistus albidus L. seedlings: mechanisms underlying drought tolerance and resilience
Authors: Pérez-Llorca Marina , Caselles Vicent , Müller Maren , Munné-Bosch Sergi
Published: April 2021

Drought can lead to important shifts in population dynamics if it occurs during seedling establishment. With the aim of elucidating the underlying mechanisms of drought tolerance and resilience, here we monitored the survival of seedlings of the Mediterranean shrub Cistus albidus L. throughout a year growing in the natural Park of the Montserrat Mountains (Spain) and, additionally, we studied the response to severe drought and subsequent recovery after rewatering of seedlings grown in growth chambers. To find possible mechanisms explaining how seedlings respond to drought, growth and survival together with physiological-related parameters such as chlorophyll contents, vitamin E and stress-related phytohormones were measured. We found that survival decreased by 30% at the end of summer and that the main proxy of seedling survival was total chlorophyll. This proxy was further confirmed in the growth chambers, where we found that seedlings that recovered from drought had higher levels of total chlorophyll compared with the seedlings that did not recover. Furthermore, modulation of vitamin E and jasmonates contents appeared to be crucial in the drought response of C. albidus seedlings. We propose a prediction model of survival that includes total chlorophyll height, leaf mass area and maximum photosystem II efficiency with chlorophyll contents being a good long-term predictor of C. albidus seedling survival under severe stress, which, in turn, could help to better foresee population fluctuations in the field.
Free-floating bike-sharing green relocation problem considering greenhouse gas emissions
Authors: Chen Dawei
Published: April 2021

This paper introduces the problem of green bike relocation considering greenhouse gas emissions in free-floating bike-sharing systems (FFBSSs) and establishes a mathematical model of the problem. This model minimizes the total imbalance degree of bikes in the FFBSS and the greenhouse gas emissions generated by relocation in the FFBSS. Before the relocation phase, the FFBSS is divided into multiple relocation areas using a two-layer clustering method to reduce the scale of the relocation problem. In the relocation phase, the relocation route problem is converted into a pickup and delivery vehicle-routing problem. Then, an adaptive variable neighbourhood tabu search algorithm with a three-dimensional tabu list is proposed, which can simultaneously solve the relocation problem and the routing problem. A computational study based on the actual FFBSS used in Shanghai shows that this method can effectively solve the green relocation problem of FFBSSs.
A Novel Sulfone Derivative ControlsLasiodiplodia theobromaein Tea Leaf Spot by Reducing the Ergosterol Content
Authors: Bao Xingtao , Yang Rui , Jiang Shilong , Zhao Jinping , Wang Delu , Li Dongxue , Wu Xian , Song Baoan , Chen Zhuo
Published: April 2021

Diseases caused by fungi can affect the quality and yield of the leaves of tea [Camellia sinensis (L.) Kuntze]. At present, the availability of highly effective and safe fungicides for controlling tea plants remains limited. The objectives of this study were to identify novel compounds with antifungal activities and to determine their molecular mechanisms. A series of sulfone compounds containing 1,3,4-oxadiazole were evaluated in China for their antifungal activities against several pathogens causing foliar diseases and high production losses. Transcriptomics and bioinformatics were used to analyze the differentially expressed genes of Lasiodiplodia theobromae treated with a representative compound, jiahuangxianjunzuo (JHXJZ). Moreover, the effects of JHXJZ on ergosterol content, membrane permeability, cell structure, and seven key genes involved in the ergosterol biosynthetic pathway were investigated. JHXJZ had a strong antifungal activity against L. theobromae in vitro, with an effective concentration giving 50% inhibition of 3.54 ± 0.55 μg/ml, and its curative efficacies on detached tea leaves reached 41.78% at 100 μg/ml. JHXJZ upregulated 899 genes (P < 0.05) and downregulated 1,185 genes (P < 0.05) in L. theobromae. These genes were found to be associated with carbohydrate metabolic processes, which are closely related to steroid biosynthesis in the Kyoto Encyclopedia of Genes and Genomes pathways. Because JHXJZ regulates the key genes of sterol biosynthesis, it decreased the ergosterol content, increased cell-membrane permeability, changed the cellular structure, enhanced the roughness of the surface of the hyphae, and resulted in degradation of the hyphal nuclei and necrosis of the hyphal cytoplasm. Our study demonstrates that JHXJZ is a fungicide with a novel mechanism of action that differs from that of triazole fungicides. JHXJZ has potential for applications in controlling tea plant diseases.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
High SARS-CoV-2 attack rates following exposure during five singing events in the Netherlands, September-October 2020
Authors: Shah Anita A. , Dusseldorp Florien , Veldhuijzen Irene K. , te Wierik Margreet J.M. , Bartels Alvin , Schijven Jack , Vermeulen Lucie C. , Knol Mirjam J.
Published: April 2021

Background

Previous reports suggest SARS-CoV-2 transmission risk increases during singing events. From September-October 2020, several clusters of COVID-19 cases among singing events were reported across the Netherlands. Our aim was to investigate whether singing increased SARS-CoV-2 transmission risk during these events.

Methods

Data from 5 events were retrospectively collected from spokespersons and singing group members via questionnaires. Information was consolidated with the National Notifiable Diseases Surveillance System. Specimens were requested for sequencing for point source and cluster assessment. We described outbreaks in terms of person, place and time and depicted potential SARS-CoV-2 transmission routes. A previously published model (AirCoV2) was used to estimate mean illness risk of 1 person through airborne transmission under various scenarios.

Results

Events included 9-21 persons (mean: 16), aged 20-89 years (median: 62). Response rates ranged 58-100%. Attack rates were 53-74%. Limited sequencing data was obtained from 2 events. Events lasted 60-150 minutes (singing: 20-120). Rooms ranged 320-3000m3. SARS-CoV-2 transmission likely occurred during all events; with a possible index case identified in 4 events. AirCoV2 showed 86% (54-100%) mean illness risk for 120 minutes of singing, smaller room (300m3), 1 air exchange/hour (ACH), and supershedder presence.

Conclusions

Droplet transmission and indirect contact probably caused some cases, but unlikely explain the high attack rates. AirCoV2 indicated that airborne transmission due to singing is possible in case of supershedder presence. Airflow expelling respiratory droplets >1.5m possibly influenced transmission. It is possible that singing itself increased SARS-CoV-2 transmission risk through airborne transmission.

This outbreak investigation among five singing events with high SARS-CoV-2 attack rates (53-74%) suggested that airflow expelling respiratory droplets >1.5m possibly influenced transmission and it is possible that singing itself increased SARS-CoV-2 transmission risk through airborne transmission.
Spatiotemporal Correlations of Mesoscale Neocortical Activities in Patients with Focal Epilepsy
Authors: Lee Somin , Deshpande Sarita S. , Merricks Edward M. , van Putten Michel J.A.M. , Schevon Catherine A. , van Drongelen Wim
Published: April 2021

Brain function is reflected in both the action potentials of individual neurons and interactions through e.g. synaptic currents reflected in widespread, slow fluctuations of the local field potential (LFP). We analyzed microelectrode array data to determine state-dependent correlations between action potential and LFP during seizure events as well as interictally in patients with focal epilepsy. We also examined activity in two different cortical network territories: the seizure core and surrounding penumbra (Schevon et al., 2012).

The cross-correlation of spiking activity in the core showed an association of the ictal action potentials with the global oscillatory aspect of the seizure activity and indicated local failure of inhibitory restraint surrounding the ictal spike. These patterns were not observed in the penumbra.

Our analyses from clinical recordings and a model of a single ictal spike in the core revealed that both the temporal and spatial components of the network’s cross-correlation can be approximated by a sine cardinal (sinc) function. The biological interpretation of these findings is that important functional differences across the neocortical network exist, with a critical role of the millimeter-range excitatory connections within the grey matter. Therefore, localized intervention that prevents escape of hyperactivity from the seizure core may be considered as a therapeutic strategy.

Significance Statement

Analysis and modeling of spatiotemporal cross-correlation between multi-unit spike activity and the local field potential of human seizure activity demonstrates a difference of network functionality between the seizure core and its surrounding penumbral network. In this study, we show that millimeter-range excitatory connections, known to exist within the gray matter of neocortex, play a critical role in propagating the effects of ictal hyperexcitation. These findings contribute to our understanding of ictal mechanisms and hold promise for further development of strategies to detect the ictal core territory and prevent seizure propagation.
COVIDOUTCOME – Estimating COVID Severity Based on Mutation Signatures in the SARS-CoV-2 Genome
Authors: Nagy Ádám , Ligeti Balázs , Szebeni János , Pongor Sándor , Győrffy Balázs
Published: April 2021

Introduction

Numerous studies demonstrate frequent mutations in the genome of SARS-CoV-2. Our goal was to statistically link mutations to severe disease outcome.

Methods

We used an automated machine learning approach where 1,594 viral genomes with available clinical follow-up data were used as the training set (797 “severe” and 797 “mild”). The best algorithm, based on random forest classification combined with the LASSO feature selection algorithm was employed to the training set to link mutation signatures and outcome. The performance of the final model was estimated by repeated, stratified, 10-fold cross validation (CV), then adjusted for multiple testing with Bootstrap Bias Corrected CV.

Results

We identified 26 protein and UTR mutations significantly linked to severe outcome. The best classification algorithm uses a mutation signature of 22 mutations as well as the patient’s age as the input and shows high classification efficiency with an AUC of 0.94 (CI: [0.912, 0.962]) and a prediction accuracy of 87% (CI: [0.830, 0.903]). Finally, we established an online platform (https://covidoutcome.com/) which is capable to use a viral sequence and the patient’s age as the input and provides a percentage estimation of disease severity.

Discussion

We demonstrate a statistical association between mutation signatures of SARS-CoV-2 and severe outcome of COVID-19. The established analysis platform enables a real-time analysis of new viral genomes.

KEY MESSAGES

A statistical link between SARS-Cov-2 mutation status and severe COVID outcome was established using automated machine learning techniques based on random forest and logistic regression combined with feature selection algorithms.

A mutation signature based on 3,779 protein coding and 36 UTR mutations capable to identify severe outcome cases was established.

The trained model showed high classification performance (AUC=0.94 (CI: [0.912, 0.962]), accuracy=0.87 (CI: [0.830, 0.903])).

A registration-free web-server for automated classification of new samples was set up and is accessible athttp://www.covidoutcome.com.

The established pipeline provides a quick assessment of future patients warranting a prospective clinical validation.
Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms
Authors: Kanen Jonathan W. , Luo Qiang , Yellowlees Robyn , Arntz Fréderique E. , Christmas David M. , Sahakian Barbara J. , Apergis-Schoute Annemieke M. , Cardinal Rudolf N. , Robbins Trevor W.
Published: April 2021

The authors have withdrawn their manuscript as the results and interpretation have changed substantially following further analyses. Please do not cite this manuscript in its current form. If you have any questions, please contact the corresponding author.
A new SARS-CoV-2 lineage that shares mutations with known Variants of Concern is rejected by automated sequence repository quality control
Authors: Thornlow Bryan , Hinrichs Angie S. , Jain Miten , Dhillon Namrita , La Scott , Kapp Joshua D. , Anigbogu Ikenna , Cassatt-Johnstone Molly , McBroome Jakob , Haeussler Maximilian , Turakhia Yatish , Chang Terren , Olsen Hugh E , Sanford Jeremy , Stone Michael , Vaske Olena , Bjork Isabel , Akeson Mark , Shapiro Beth , Haussler David , Kilpatrick A. Marm , Corbett-Detig Russell
Published: April 2021

We report a SARS-CoV-2 lineage that shares N501Y, P681H, and other mutations with known variants of concern, such as B.1.1.7. This lineage, which we refer to as B.1.x (COG-UK sometimes references similar samples as B.1.324.1), is present in at least 20 states across the USA and in at least six countries. However, a large deletion causes the sequence to be automatically rejected from repositories, suggesting that the frequency of this new lineage is underestimated using public data. Recent dynamics based on 339 samples obtained in Santa Cruz County, CA, USA suggest that B.1.x may be increasing in frequency at a rate similar to that of B.1.1.7 in Southern California. At present the functional differences between this variant B.1.x and other circulating SARS-CoV-2 variants are unknown, and further studies on secondary attack rates, viral loads, immune evasion and/or disease severity are needed to determine if it poses a public health concern. Nonetheless, given what is known from well-studied circulating variants of concern, it seems unlikely that the lineage could pose larger concerns for human health than many already globally distributed lineages. Our work highlights a need for rapid turnaround time from sequence generation to submission and improved sequence quality control that removes submission bias. We identify promising paths toward this goal.
Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance
Authors: Yousefi Soheil , Deng Ruizhi , Lanko Kristina , Salsench Eva Medico , Nikoncuk Anita , van der Linde Herma C. , Perenthaler Elena , van Ham Tjakko , Mulugeta Eskeatnaf , Barakat Tahsin Stefan
Published: April 2021

Background

Non-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is complex and can be affected by numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognised genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging.

Results

Here we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain. Our in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, these regions are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism.

Conclusion

Our compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of the human brain and will be relevant to uncover missing heritability in human genetic brain disorders.
DeepTrio: Variant Calling in Families Using Deep Learning
Authors: Kolesnikov Alexey , Goel Sidharth , Nattestad Maria , Yun Taedong , Baid Gunjan , Yang Howard , McLean Cory Y , Chang Pi-Chuan , Carroll Andrew
Published: April 2021

Every human inherits one copy of the genome from their mother and another from their father. Parental inheritance helps us understand the transmission of traits and genetic diseases, which often involve de novo variants and rare recessive alleles. Here we present DeepTrio, which learns to analyze child-mother-father trios from the joint sequence information, without explicit encoding of inheritance priors. DeepTrio learns how to weigh sequencing error, mapping error, and de novo rates and genome context directly from the sequence data. DeepTrio has higher accuracy on both Illumina and PacBio HiFi data when compared to DeepVariant. Improvements are especially pronounced at lower coverages (with 20x DeepTrio roughly equivalent to 30x DeepVariant). As DeepTrio learns directly from data, we also demonstrate extensions to exome calling solely by changing the training data. DeepTrio includes pre-trained models for Illumina WGS, Illumina exome, and PacBio HiFi.
East-African savanna dynamics: from a knowledge-based model to the possible futures of a social-ecological system
Authors: Cosme Maximilien , Hély Christelle , Pommereau Franck , Pasquariello Paolo , Tiberi Christel , Treydte Anna , Gaucherel Cédric
Published: April 2021

Sub-Saharan savanna ecosystems are undergoing transitions such as bush encroachment, desertification or agricultural expansion. Such shifts and persistence of land cover are increasingly well understood, especially bush encroachment which is of major concern in pastoral systems. Although dominant factors can explain such transformations, they often result from intertwined causes in which human activities play a significant role. Therefore, in this latter case, these issues may require integrated solutions, involving many interacting components. Ecosystem modelling has proved appropriate to support decision-makers in such complex situations. However, ecosystem models often require lots of quantitative information for estimating parameters and the precise functional form of interactions is often unknown. Alternatively, in rangeland management, States-and-Transitions Models (STMs) have been developed to organize knowledge about system transitions and to help decision-makers. However, these conceptual diagrams often lack mathematical analyzing tools, which strongly constrains their complexity. In this paper, we introduce the Ecological Discrete-Event Network (EDEN) modelling approach for representing the qualitative dynamics of an East-African savanna as a set of discrete states and transitions generated from empirical rules. These rules are derived from local knowledge, field observations and scientific literature. In contrast with STMs, EDEN generates automatically every possible states and transitions, thus enabling the prediction of novel ecosystem structures. Our results show that the savanna is potentially resilient to the disturbances considered. Moreover, the model highlights all transitions between vegetation types and socio-economic profiles under various climatic scenarios. The model also suggests that wildlife diversity may increase socio-economic resistance to seasonal drought. Tree-grass coexistence and agropastoralism have the widest ranges of conditions of existence of all vegetation types and socio-economic profiles, respectively. As this is a preliminary use of EDEN for applied purpose, analysis tools should be improved to enable finer investigation of desirable trajectories. By translating local knowledge into ecosystem dynamics, the EDEN approach seems promising to build a new bridge between managers and modellers.
Overturning the paradigm that IL6 signaling drives liver regrowth while shining light on a new therapeutic target for regenerative medicine
Authors: Dong Jinrui , Viswanathan Sivakumar , Adami Eleonora , Schafer Sebastian , Kuthubudeen Fathima F. , Widjaja Anissa A. , Cook Stuart A.
Published: April 2021

It is accepted that IL6 signaling in hepatocytes, mediated via glycoprotein 130 (gp130), is beneficial and that HyperIL6 promotes liver regeneration by activating STAT3. Recently, autocrine IL11 activity, which also signals via gp130 and ERK, was found to be hepatotoxic. Here we examined whether the beneficial effects of HyperIL6 could reflect unappreciated competitive inhibition of IL11 signaling. In hepatocytes, HyperIL6 inhibited N-acetyl-p-aminophenol (APAP)-induced cell death that mimicked inhibition of IL11 signaling and was unrelated to STAT3 phosphorylation. In mice, expression of HyperIL6 reduced liver damage due to IL11 dosing or APAP and promoted hepatic regeneration in a STAT3-independent manner. Following APAP, mice deleted forIl11were protected from liver failure and exhibited spontaneous regeneration. Despite robustly activating STAT3, HyperIL6 had no beneficial effect inIl11null mice. These data overturn the premise that IL6 promotes liver regeneration, show STAT3 activation to be redundant and suggest IL11 as a focus for regenerative medicine.
Ultrafast, alignment-free detection of repeat expansions in next-generation DNA and RNA sequencing data
Authors: Fearnley L.G. , Bennett M.F. , Bahlo M.
Published: April 2021

Short tandem repeat expansions are an established cause of diseases such as Huntington’s disease. Bioinformatic methods for detecting repeat expansions in short-read sequencing have revealed new repeat expansions in humans. Current bioinformatic methods to detect repeat expansions require alignment information to identify repetitive motif enrichment at genomic locations. We present superSTR, an ultrafast method that does not require alignment. We demonstrate superSTR’s ability to efficiently process both whole-genome and whole-exome sequencing data. Using superSTR we perform the first analysis of the UK Biobank to efficiently screen the exomes of 49,953 biobank participants for repeat expansions. We identify known mutations, as well as diseases not previously associated with REs. We further demonstrate the first bioinformatic screening of RNA sequencing data to detect repeat expansions in patients with spinocerebellar ataxia and Fuchs’ endothelial corneal dystrophy, and mouse models of myotonic dystrophy. superSTR is a highly computationally-efficient repeat expansion tool screening and detection tool for genomewide novel repeat expansion analysis, significantly outperforming existing methods. superSTR is available fromhttps://github.com/bahlolab/superSTR.