bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a unified classification for human respiratory syncytial virus genotypes
Authors: Ramaekers Kaat , Rector Annabel , Cuypers Lize , Lemey Philippe , Keyaerts Els , Van Ranst Marc 
Published: July 2020

Abstract
Since the first human respiratory syncytial virus (HRSV) genotype classification in 1998, inconsistent conclusions have been drawn regarding the criteria that define HRSV genotypes and their nomenclature, challenging data comparisons between research groups. In this study, we aim to unify the field of HRSV genotype classification by reviewing the different methods that have been used in the past to define HRSV genotypes and by proposing a new classification procedure, based on well-established phylogenetic methods. All available complete HRSV genomes (&gt;12,000 bp) were downloaded from GenBank and divided into the two subgroups: HRSV-A and HRSV-B. From whole-genome alignments, the regions that correspond to the open reading frame of the glycoprotein G and the second hypervariable region (HVR2) of the ectodomain were extracted. In the resulting partial alignments, the phylogenetic signal within each fragment was assessed. Maximum likelihood phylogenetic trees were reconstructed using the complete genome alignments. Patristic distances were calculated between all pairs of tips in the phylogenetic tree and summarized as a density plot in order to determine a cutoff value at the lowest point following the major distance peak. Our data show that neither the HVR2 fragment nor the G gene contains sufficient phylogenetic signal to perform reliable phylogenetic reconstruction. Therefore, whole-genome alignments were used to determine HRSV genotypes. We define a genotype using the following criteria: a bootstrap support of ≥70 per cent for the respective clade and a maximum patristic distance between all members of the clade of ≤0.018 substitutions per site for HRSV-A or ≤0.026 substitutions per site for HRSV-B. By applying this definition, we distinguish twenty-three genotypes within subtype HRSV-A and six genotypes within subtype HRSV-B. Applying the genotype criteria on subsampled data sets confirmed the robustness of the method.
Origin, extinction and ancient DNA of a new fossil insular viper: molecular clues of overseas immigration
Authors: Torres-Roig Enric , Mitchell Kieren J , Alcover Josep Antoni , Martínez-Freiría Fernando , Bailón Salvador , Heiniger Holly , Williams Matthew , Cooper Alan , Pons Joan , Bover Pere 
Published: July 2020

AbstractViperinae is a subfamily of viperid snakes whose fossil record in the Mediterranean islands is, until now, restricted to 12 palaeontological deposits on seven islands. Revision of the material excavated 30 years ago from the Middle/Late Pleistocene–Holocene deposit of Es Pouàs [Eivissa (= Ibiza), Balearic Islands, western Mediterranean] revealed about 6000 bones of a small-sized viper across different stratigraphic levels. Its morphological characteristics are different enough to known species of Vipera to warrant the description of a new species, but the nearly complete mitochondrial genome obtained from this snake based on a sample dated to 16 130 ± 45 bp, suggested it belonged to a new insular population of Lataste’s viper (Vipera latastei), Vipera latastei ebusitana subsp. nov. Phylogenetic analysis indicates that the dispersal of the ancestors of V. l. ebusitana to Eivissa, most probably from a north-east Iberian population, occurred via overwater colonization &lt; 1.5 Mya, well after the Messinian Salinity Crisis (5.97–5.32 Mya) when land bridges allowed terrestrial colonization of the Balearic Islands by mainland faunas. The morphological differences between V. l. ebusitana and the Iberian populations suggest that it is a new dwarf taxon resulting from insular evolutionary processes, becoming extinct shortly after the first human arrival to this island about 4000 years ago.
A Novel Tool for Teaching Cardiac Point-of-Care Ultrasound: An Exploratory Application of the Design-Based Research Approach*
Authors: Brown Kyle A. , Riley Alan F. , Alade Kiyetta H. , Kyle William Buck , Castro Danny , Tcharmtchi Mohammad Hossein , Thammasitboon Satid 
Published: July 2020

Objectives:
To develop a competency-based educational tool for cardiac point-of-care ultrasound image interpretation using the design-based research approach.

Design:
In accordance with design-based research, multiple methods were used to determine that learners would benefit from achieving competency in cardiac point-of-care ultrasound image interpretation before they attempted it at the bedside. A competency-based educational tool was designed and underwent a rapid prototyping process with experts. Evaluative data was used to redesign and reevaluate the educational tool with a new group of learners to improve its effectiveness.

Setting:
Large, university-based children’s hospital.

Subjects:
Pediatric critical care attending physicians, fellow physicians and advanced practice providers, and pediatric resident physicians.

Interventions:
Integrating mastery learning and deliberate practice as theoretical frameworks, the authors designed an online “Image Library” composed of 90 questions of cardiac point-of-care ultrasound image clips with varying degrees of pathology that were organized into three levels of difficulty. Learners answered a set of 10 questions, learned from feedback, and repeated an additional set in the same difficulty until achieving a predefined level of mastery.

Measurements and Main Results:
Two learning cycles were implemented with a total of 41 learners. Forty learners (98%) were able to demonstrate mastery on the Image Library and required a range of 30 to 210 questions to do so. On a 10-question final assessment, learners scored an average of 72%, while experts and novices scored 83% and 17%, respectively. On a 5-point scale, learners rated the quality of the Image Library for facilitation of learning (median 5), enjoyment of learning (5), and useful knowledge and skills to improve clinical practice (5).

Conclusions:
An effective and innovative tool for teaching cardiac point-of-care ultrasound image interpretation was developed using the design-based research approach. Our results demonstrate the importance of individualized learning timelines for ultrasound image interpretation.
Kinetics and Isotype Assessment of Antibodies Targeting the Spike Protein Receptor Binding Domain of SARS-CoV-2 In COVID-19 Patients as a function of Age and Biological Sex
Authors: Graham Nancy R. , Whitaker Annalis N. , Strother Camilla A. , Miles Ashley K. , Grier Dore , McElvany Benjamin D. , Bruce Emily A. , Poynter Matthew E. , Pierce Kristen K. , Kirkpatrick Beth D. , Stapleton Renee D. , An Gary , Botten Jason W. , Crothers Jessica W. , Diehl Sean A. 
Published: July 2020

AbstractSARS-CoV-2 is the newly emerged virus responsible for the global COVID-19 pandemic. There is an incomplete understanding of the host humoral immune response to SARS-CoV-2 during acute infection. Host factors such as age and sex as well the kinetics and functionality of antibody responses are important factors to consider as vaccine development proceeds. The receptor-binding domain of the CoV spike (RBD-S) protein is important in host cell recognition and infection and antibodies targeting this domain are often neutralizing. In a cross-sectional study of anti-RBD-S antibodies in COVID-19 patients we found equivalent levels in male and female patients and no age-related deficiencies even out to 93 years of age. The anti-RBD-S response was evident as little as 6 days after onset of symptoms and for at least 5 weeks after symptom onset. Anti-RBD-S IgG, IgM, and IgA responses were simultaneously induced within 10 days after onset, but isotype-specific kinetics differed such that anti-RBD-S IgG was most sustained over a 5-week period. The kinetics and magnitude of neutralizing antibody formation strongly correlated with that seen for anti-RBD-S antibodies. Our results suggest age- and sex-related disparities in COVID-19 fatalities are not explained by anti-RBD-S responses. The multi-isotype anti-RBD-S response induced by live virus infection could serve as a potential marker by which to monitor vaccine-induced responses.
A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
Authors: Farhoudian Ali , Radfar Seyed Ramin , Ardabili Hossein Mohaddes , Rafei Parnian , Ebrahimi Mohsen , Zonoozi Arash Khojasteh , De Jong Cornelis A J , Vahidi Mehrnoosh , Yunesian Masud , Kouimtsidis Christos , Arunogiri Shalini , Hansen Helena , Brady Kathleen T , Potenza Marc N ,   ISAM-PPIG Global Survey Consortium, Baldacchino Alexander Mario , Ekhtiari Hamed 
Published: July 2020

AbstractBackground and aimsCOVID-19 has infected more than 13 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing and ‘lockdown’ measures have affected drug and alcohol supply chains and subsequently their availability, price and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic.DesignCross-sectional survey.SettingWorldwide.ParticipantsStarting on April 4th, 2020 during a 5-week period, the survey received 185 responses from 77 countries.MeasurementsTo assess addiction medicine professionals’ perceived changes in drug and alcohol supply, price, use pattern and related complications during the COVID-19 pandemic.FindingsParticipants reported (among who answered “decreased” or “increased”, percentage of those who were in majority is reported in the parenthesis) a decrease in drug supply (69.0%), and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported while the use of amphetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall.ConclusionsThe global report on changes in the availability, use patterns and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to SUDs.Competing interestAuthors claimed no competing interest
Evidence for the Placenta-Brain Axis: Multi-Omic Kernel Aggregation Predicts Intellectual and Social Impairment in Children Born Extremely Preterm
Authors: Santos Hudson P , Bhattacharya Arjun , Joseph Robert M , Smeester Lisa , Kuban Karl CK , Marsit Carmen J , O’Shea T. Michael , Fry Rebecca C 
Published: July 2020

AbstractBackgroundChildren born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may explain origins of neurodevelopmental outcomes.MethodsWe examined associations between placental genomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II (DAS-II) and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayed with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850K array, respectively. We conducted genome-wide differential mRNA/miRNA and epigenome-wide placenta analyses. These molecular features were integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the genomically-predicted component of IQ and SRS.ResultsGenes with important roles in placenta angiogenesis and neural function were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of the variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status.LimitationsThe ELGAN is a cohort of children born pre-term, andgeneralization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size of the out-sample dataset (N= 49) and the scope of the available placental datasets are limited. Further validation of the models is merited.ConclusionsAggregating information from biomarkers within and between molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits influenced by the placenta-brain axis may be omnigenic.
Conflict Processing in Schizophrenia: Dissociable Neural Mechanisms Revealed by the N2 and Frontal Midline Theta
Authors: Hong Xiangfei , Yang Fuzhong , Wang Jijun , Li Chunbo , Ding Mingzhou , Sheng Jianhua 
Published: July 2020

AbstractDeficits in executive control have long been regarded as one of the hallmark cognitive characteristics in people with schizophrenia (SZ), and current neurocognitive models of SZ generally regard the dysfunctional anterior cingulate cortex (ACC) as the possible neural mechanism. This however, contrasts with recent studies showing that conflict processing, a key component of executive functions that relies on ACC, remains relatively intact in SZ. The current study aimed to investigate this issue through two well-known electrophysiological signatures of conflict processing that have been suggested to origin from ACC, i.e., the N2 component of event-related potentials (ERPs) and frontal midline theta (FMθ) oscillations. We recorded 64-channel scalp electroencephalography from 29 SZ (17 women; mean age: 30.4 years) and 31 healthy control subjects (HC; 17 women; mean age: 29.1 years) performing a modified flanker task. Behavioral data revealed no significant differences in flanker conflict effects (lower accuracy and longer reaction time in incongruent trials than in congruent trials) between HC and SZ. Trial-averaged ERP and spectral analysis suggested that both N2 and FMθ were significantly impaired in SZ relative to HC. Furthermore, by sorting incongruent trials according to their reaction times within individual subjects, we found that the trial-by-trial modulation of N2 (larger amplitude and longer latency in slower trials) which was observed and localized in ACC in HC was totally absent in SZ. By contrast, the trial-by-trial modulation of FMθ (larger power in slower trials) was observed and localized in ACC in both groups, despite a relatively smaller magnitude in SZ. Notably, such trial-by-trial FMθ modulation was only present in incongruent trials that demanded conflict processing. Taken together, our results not only support the idea that FMθ, not N2, serves as the neural substrate of conflict processing in SZ, but also provide novel insights into the functional roles of ACC during executive control, enriching the current neurocognitive models of SZ.
Family and provider perceptions of quality of care in the management of sick young infants in primary health care settings in four counties of Kenya
Authors: Mbugua Samuel Mungai , Gitaka Jesse , Gitau Tabither , Odwe George , Mwaura Peter , Liambila Wilson , Ndwiga Charity , K’Oduol Kezia , Warren Charlotte E. , Abuya Timothy 
Published: July 2020

ABSTRACTBackgroundUnderstanding the perceptions of quality of care given to sick young infants in primary health care settings is key for developing strategies for effective uptake and utilization of PSBI guidelines. The purpose of this study is to assess families’ and providers’ perceptions of care given to sick young infants at primary healthcare facilities in four diverse counties in Kenya.MethodsA cross-sectional qualitative design involving in-depth interviews (23) and focus group discussions (25) with very young (15-18 years), young (19-24 years) and older (25-45 years) caregivers of young infants 0-59 days; and key informant interviews with community- and facility-based frontline health providers (14) in primary health care facilities. Qualitative data were captured using audio tapes and field notes, transcribed, translated, and exported into QSR NVivo 12 for analysis. A thematic framework approach was adopted to classify and analyze data.ResultsPerceived care given to SYIs was described around six domains of WHO’s framework for the quality of maternal and newborn health care: evidence-based practices for routine and emergency care; functional referral systems; effective communication; respect and preservation of dignity; availability of competent, motivated human resources; and availability of physical resources. Views of caregivers and providers regarding SYIs care at PHCs were similar across the four sites. Main hindrance to SYI care includes stockout of essential drugs, limited infrastructure, lack of functional referral system, inadequate providers which led to delays in receiving treatment, inadequate provider skills and poor provider attitudes. Despite these challenges, motivation and teamwork of health providers were key tenets in care provision.ConclusionThe findings underscore the need to prioritize improving quality of SYIs services at PHCs by building capacity of providers through training, ensuring continuous supply of essential medicines and equipment, improving infrastructure including referral.
A Recurrent Neural Network and Differential Equation Based Spatiotemporal Infectious Disease Model with Application to COVID-19
Authors: Li Zhijian , Zheng Yunling , Xin Jack , Zhou Guofa 
Published: July 2020

AbstractThe outbreaks of Coronavirus Disease 2019 (COVID-19) have impacted the world significantly. Modeling the trend of infection and realtime forecasting of cases can help decision making and control of the disease spread. However, data-driven methods such as recurrent neural networks (RNN) can perform poorly due to limited daily samples in time. In this work, we develop an integrated spatiotemporal model based on the epidemic differential equations (SIR) and RNN. The former after simplification and discretization is a compact model of temporal infection trend of a region while the latter models the effect of nearest neighboring regions. The latter captures latent spatial information. We trained and tested our model on COVID-19 data in Italy, and show that it out-performs existing temporal models (fully connected NN, SIR, ARIMA) in 1-day, 3-day, and 1-week ahead forecasting especially in the regime of limited training data.
Lenticular nucleus volume predicts performance in real-time strategy game - cross-sectional and training approach using voxel-based morphometry
Authors: Kowalczyk N. , Skorko M. , Dobrowolski P. , Kossowski B. , Myśliwiec M. , Hryniewicz N. , Gaca M , Marchewka A. , Kossut M. , Brzezicka A. 
Published: July 2020

AbstractIt is unclear why some people learn faster than others. We performed two independent studies in which we investigated the neural basis of real-time strategy (RTS) gaming and neural predictors of RTS games skill-acquisition. In the first (cross-sectional) study we found that experts in the RTS game StarCraft II (SC2) had a larger lenticular nucleus volume than non-RTS players. We followed a cross validation procedure where we used the volume of regions identified in the first study to predict the quality of learning a new, complex skill (SC2) in a sample of individuals who were naïve to RTS games (second training study). Our findings provide new insights into how the volume of lenticular nucleus, which is associated with motor as well as cognitive functions, can be utilized to predict successful skill-learning, and be applied to a much broader context than just video games, e.g. contributing to optimizing cognitive training interventions.
INTS13Mutations Causing a Developmental Ciliopathy Disrupt Integrator Complex Assembly
Authors: Mascibroda Lauren G. , Shboul Mohammad , Elrod Nathan D. , Colleaux Laurence , Hamamy Hanan , Huang Kai-Lieh , Peart Natoya , Singh Moirangthem Kiran , Lee Hane , Merriman Barry , Jodoin Jeanne N. , Lee Laura A. , Fathalla Raja , Al-Rawashdeh Baeth , Ababneh Osama , El-Khateeb Mohammad , Escande-Beillard Nathalie , Nelson Stanley F. , Wu Yixuan , Tong Liang , Kenney Linda J. , Russell William K. , Amiel Jeanne , Reversade Bruno , Wagner Eric J. 
Published: July 2020

ABSTRACTOral-facial-digital syndromes (OFD) are a heterogeneous group of congenital disorders characterized by malformations of the face and oral cavity, and digit anomalies. To date, mutations in 12 ciliary-related genes have been identified that cause several types of OFD, suggesting that OFDs constitute a subgroup of developmental ciliopathies. Through homozygosity mapping and exome sequencing of two families with variable OFD type 2, we identified distinct germline mutations inINTS13, a subunit of the Integrator complex. This 14-component complex associates with RNAPII and can cleave nascent RNA to modulate gene expression. We determined that INTS13 utilizes a discrete domain within its C-terminus to bind the Integrator cleavage module, which is disrupted by the identified germlineINTS13mutations. Depletion ofINTS13disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Accordingly, its knockdown inXenopusembryos lead to motile cilia anomalies. Altogether, we show that mutations inINTS13cause an autosomal recessive ciliopathy, which reveals key interactions within Integrator components.
Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types
Authors: Saez-Atienzar Sara , Bandres-Ciga Sara , Langston Rebekah G. , Kim Jonggeol J. , Choi Shing Wan , Reynolds Regina H. ,   the International ALS Genomics Consortium; ITALSGEN, Abramzon Yevgeniya , Dewan Ramita , Ahmed Sarah , Landers John E. , Chia Ruth , Ryten Mina , Cookson Mark R. , Nalls Michael A. , Chiò Adriano , Traynor Bryan J. 
Published: July 2020

ABSTRACTDespite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namelyneuron projection morphogenesis, membrane trafficking, andsignal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic cortical interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated five differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, PLXNB2, andSCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.