bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Alu exonization in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge
Authors: Bhattacharya Aniket , Jha Vineet , Singhal Khushboo , Fatima Mahar , Singh Dayanidhi , Chaturvedi Gaura , Dholakia Dhwani , Kutum Rintu , Pandey Rajesh , Bakken Trygve E , Seth Pankaj , Pillai Beena , Mukerji Mitali 
Published: November 2020

Abstract
Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Our study highlights how exonized Alus could nucleate large-scale mRNA-miRNA interactions. Using a functional genomics approach, we characterize a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that has exonization of 23 Alus in its 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9 kb 3’UTR) and widely expressed. Using publically available datasets, we demonstrate its expression in higher primates and presence in single nucleus RNA-seq of 15928 human cortical neurons. miRanda predicts ∼4700 miRNA recognition elements (MREs) for ∼1000 miRNAs, primarily originated within these 3’UTR-Alus. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbors ≥10 MREs for 140 miRNAs and has cytosolic localization. We further tested whether expression of CYP20A1_Alu-LT correlates with mRNAs harboring similar MRE targets. RNA-seq with conjoint miRNA-seq analysis was done in primary human neurons where we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. 380 genes were positively correlated with its expression (significantly downregulated in heat shock and upregulated in Tat) and they harbored MREs for nine expressed miRNAs which were also enriched in CYP20A1_Alu-LT. MREs were significantly enriched in these 380 genes compared to random sets of differentially expressed genes (p = 8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways thus proposing a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.
Positive Cones and Gauges on Algebras With Involution
Authors: Astier Vincent , Unger Thomas 
Published: November 2020

AbstractWe extend the classical links between valuations and orderings on fields to Tignol–Wadsworth gauges and positive cones on finite-dimensional simple algebras with involution. We also study the compatibility of gauges and positive cones and prove lifting results in the style of the Baer–Krull theorem for fields.
Predicting load on ground anchor using a metaheuristic optimized least squares support vector regression model: a Taiwan case study
Authors: Cheng Min-Yuan , Cao Minh-Tu , Tsai Po-Kun 
Published: November 2020

Abstract
Failure of ground anchor is a major cause of landslides and severe natural hazards, especially in the highly developed mountainous areas such as New Taipei City. Accurately estimating load on ground anchors is thus essential for evaluating the stability status of slope to prevent landslide from happening. This study first employed correlation analyses to identify possible influential factors of load on ground anchors. Second, various artificial intelligence models were used to map the relationship of the found influencing factors with the current load on ground anchors. The results indicated that the symbiotic organisms search-optimized least squares support vector regression (SOS-LSSVR) model had the optimal accuracy by earning the smallest value of mean absolute percentage error (9.10%) and the most outstanding value of correlation coefficient (R = 0.988). The study applied the established inference model for the real case of estimating load on un-monitoring ground anchors. The analyzed results strongly advised administrators to conduct site surveying and patrolling more frequently to take early proper actions. In summary, the obtained results have demonstrated SOS-LSSVR as an effective alternative for the conventional subjective evaluation methods, which is able to rapidly provide accurate values of load on un-monitoring ground anchors.
An Analysis of Sectional Title Dispute Resolution in South Africa
Authors: Baboolal-Frank Rashri 
Published: November 2020

ABSTRACT
This article aims to explore alternative dispute resolution mechanisms, which are relevant to sectional titles schemes disputes. The alternative dispute resolution mechanisms will be discussed as an innovative trend to resolve disputes, especially in foreign jurisdictions. In South Africa there are challenges that confront South Africa because litigation is in many instances the cause of the break-down of relationships and may cause a rift and hinder development within a particular scheme. This article aims to address, on the one hand, particular pitfalls in sectional title scheme litigation, and on the other hand to address possible solutions through alternative dispute resolution mechanisms.
Testing the Independent and Joint Contribution of Exposure to Neurodevelopmental Adversity and Childhood Trauma to Risk of Psychotic Experiences in Adulthood
Authors: Liu Yiwen , Mendonça Marina , Cannon Mary , Jones Peter B , Lewis Glyn , Thompson Andrew , Zammit Stanley , Wolke Dieter 
Published: November 2020

Abstract
Exposure to neurodevelopmental adversity and childhood trauma are both independently associated with psychosis. However, there is little research on the mechanism underlying their relationship with each other. The current study investigated both the independent and joint effects of neurodevelopmental adversity and childhood trauma to better understand the etiology of psychosis. A large population-based cohort (N = 3514) followed from birth was assessed on psychotic experiences (PE) at 24 years. Neurodevelopmental adversity included obstetric complications (birth weight, gestational age, in-utero influenza exposure, resuscitation) and developmental impairment (cognitive and motor impairments). Trauma exposure included caregiver and peer inflicted trauma up to 17 years. Multiple regression models tested their independent and interactive effect on PE, and path analysis estimated the indirect effect of neurodevelopmental adversity on PE via trauma. Neurodevelopmental adversity (OR = 1.32, 95%CI: 1.08–1.62) and trauma (OR = 1.97, 95%CI: 1.65–2.36) independently increased the odds of PE. There was also an indirect relationship between neurodevelopmental adversity and PE via increased exposure to childhood trauma (β = 0.01, 95%CI: 0.004–0.024). In particular, peer bullying mediated the association between developmental impairment to PE (β = 0.02, 95%CI: 0.01–0.03). In conclusion, children with neurodevelopmental adversity, in particular those with developmental impairment, are more likely to be exposed to trauma. This new etiological understanding of psychosis suggests that PE may be partially modifiable through reducing exposure to peer bullying, especially in children with developmental impairment.
Mandibular advancement splint response is associated with the pterygomandibular raphe
Authors: Brown Elizabeth C , Jugé Lauriane , Knapman Fiona L , Burke Peter G R , Ngiam Joachim , Sutherland Kate , Butler Jane E , Eckert Danny J , Cistulli Peter A , Bilston Lynne E 
Published: November 2020

Abstract

Study Objectives
To investigate whether the presence of tendinous PMR could predict treatment outcome and how it affects lateral wall mechanical properties. Mandibular advancement increases the lateral dimensions of the nasopharyngeal airway via a direct connection from the airway to the ramus of the mandible. The anatomical structure in this region is the pterygomandibular raphe (PMR), but a tendinous component is not always present. Whether tendon presence influences treatment outcome is unknown.

Methods
In total, 105 participants with obstructive sleep apnea completed detailed anatomical magnetic resonance imaging with and without mandibular advancement. The study design was case–control. Variables were compared between participants with and without the tendon present.

Results
The amount of maximum mandibular advancement decreased when pterygomandibular tendon was present (4.0 ± 1.2 mm present versus 4.6 ± 1.4 mm absent, p = 0.04). PMR tendon-absent participants had a lower posttreatment apnea hypopnea index (16 ± 12 events/hour tendon present versus 9 ± 9 events/hour absent, p = 0.007) and were more likely to have complete response (63% versus 36%, p = 0.02). However, tendon-absent participants were more likely to not complete the study (χ 2 (3) = 10.578, p = 0.014). Tendon-absent participants had a greater increase in midline anteroposterior airway diameter (1.6 ± 1.7 mm versus 0.6 ± 2.3 mm, p = 0.04).

Conclusion
When PMR tendon is absent, treatment response and amount of maximum advancement improve, possibly at the expense of reduced splint tolerability. Tendon presence may help predict a group less likely to respond to mandibular advancement splint therapy.
UNEXPLAINED VISUAL LOSS AFTER GAS TAMPONADE FOR MACULA-ON RETINAL DETACHMENT
Authors: Iuliano Lorenzo , Corbelli Eleonora , Ramoni Andrea , Bandello Francesco , Codenotti Marco 
Published: November 2020

Purpose:
To identify the incidence rate and the clinical characteristics of unexplained visual loss after gas tamponade for primary macula-sparing rhegmatogenous retinal detachment.

Methods:
Retrospective longitudinal analysis of all subjects undergoing vitrectomy with gas for primary macula-on rhegmatogenous retinal detachment from 2010 to 2019. Outcome was the unexplained visual loss evaluated after gas absorption, defined as a loss of vision to less than 20/200 without evident causes. The diagnostic workup was reviewed.

Results:
Nine eyes with unexplained visual loss of 357 surgeries were found. The incidence proportion was 2.52 new cases every 1,000 eyes affected by macula-on rhegmatogenous retinal detachment treated with gas per year. All subjects had an absolute central scotoma, with a median postoperative visual acuity of 20/1,600 (counting fingers). Structural findings were consistent with an axonal damage; all eyes had microcystoid macular edema and reduced thickness of both macular ganglion cell and retinal nerve fiber layers. No photoreceptor structural damages were noted.

Conclusion:
The incidence of unexplained visual loss after gas tamponade for primary macula-on rhegmatogenous retinal detachment is 2.52 new cases every 1,000 eyes per year. This rare complication, which findings are suggestive of an axonal damage within retinal ganglion cells, remains a serious and unexplained concern for vitreoretinal surgeons.
Screening Adolescent Trauma Patients for Substance Use at 10 Pediatric Trauma Centers
Authors: Mello Michael J. , Becker Sara J. , Spirito Anthony , Bromberg Julie R. , Wills Hale , Barczyk Amanda , Lee Lois , Pruitt Charles , Ebel Beth E. , Zonfrillo Mark R. , Nimaja Evelyn , Scott Kelli , Kiragu Andrew , Nasr Isam W. , Aidlen Jeremy T. , Maxson R. Todd , Baird Janette 
Published: November 2020

Background:The American College of Surgeons Committee on Trauma recommends universal alcohol screening be part of the evaluation of admitted trauma patients. Yet, suboptimal screening rates have been reported for admitted adult and adolescent trauma patients. This lack of screening, in turn, has limited the ability of trauma services to provide patients with brief interventions during their hospital admission and subsequent referrals to treatment after discharge. The primary aim of this study was to examine current rates of alcohol and other drug screening with admitted injured adolescents across a national cohort of 10 pediatric trauma centers.Methods:This retrospective observational study was nested within a larger adolescent screening, brief intervention, and referral to treatment implementation study (Clinicaltrials.gov NCT03297060). Ten pediatric trauma centers participated in a retrospective chart review of a random sample of adolescent trauma patients presenting for care between March 1, 2018, and November 30, 2018.Results:Three hundred charts were abstracted across the 10 participating trauma centers (n= 30 per site). Screening rates varied substantially across centers from five (16.7%) to 28 (93.3%) of the 30 extracted charts. The most frequent screening type documented was blood alcohol concentration (BAC) (N= 80, 35.2% of all screens), followed by the CRAFFT (N= 79, 26.3%), and then the urine drug screen (UDS) (N= 77, 25.6%). The BAC test identified 11 patients as positive for recent alcohol use. The CRAFFT identified 11 positive patients.Conclusions:Alcohol and drug screening is underutilized for adolescents admitted to pediatric trauma centers. More research is warranted on how best to utilize the teachable moment of the pediatric trauma visit to ensure comprehensive screening of adolescent alcohol or other drug (AOD) use.
Innate immunity plays a key role in controlling viral load in COVID-19: mechanistic insights from a whole-body infection dynamics model
Authors: Dogra Prashant , Ruiz-Ramírez Javier , Sinha Kavya , Butner Joseph D. , Peláez Maria J , Rawat Manmeet , Yellepeddi Venkata K. , Pasqualini Renata , Arap Wadih , Sostman H. Dirk , Cristini Vittorio , Wang Zhihui 
Published: November 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogen of immense public health concern. Efforts to control the disease have only proven mildly successful, and the disease will likely continue to cause excessive fatalities until effective preventative measures (such as a vaccine) are developed. To develop disease management strategies, a better understanding of SARS-CoV-2 pathogenesis and population susceptibility to infection are needed. To this end, physiologically-relevant mathematical modeling can provide a robust in silico tool to understand COVID-19 pathophysiology and the in vivo dynamics of SARS-CoV-2. Guided by ACE2-tropism (ACE2 receptor dependency for infection) of the virus, and by incorporating cellular-scale viral dynamics and innate and adaptive immune responses, we have developed a multiscale mechanistic model for simulating the time-dependent evolution of viral load distribution in susceptible organs of the body (respiratory tract, gut, liver, spleen, heart, kidneys, and brain). Following calibration with in vivo and clinical data, we used the model to simulate viral load progression in a virtual patient with varying degrees of compromised immune status. Further, we conducted global sensitivity analysis of model parameters and ranked them for their significance in governing clearance of viral load to understand the effects of physiological factors and underlying conditions on viral load dynamics. Antiviral drug therapy, interferon therapy, and their combination was simulated to study the effects on viral load kinetics of SARS-CoV-2. The model revealed the dominant role of innate immunity (specifically interferons and resident macrophages) in controlling viral load, and the impotance of timing when initiating therapy following infection.Graphical Abstract
Trends in known and undiagnosed diabetes, HbA1c levels, cardio-metabolic risk factors and diabetes treatment target achievement in repeated cross-sectional surveys – The Tromsø Study 1994-2016
Authors: Langholz Petja Lyn , Wilsgaard Tom , Njølstad Inger , Jorde Rolf , Hopstock Laila Arnesdatter 
Published: November 2020

AbstractObjectivesThe aim of this study was to investigate time trends in known and undiagnosed diabetes, HbA1c levels, and other cardio-metabolic risk factors in the general population as well as treatment target achievement among those with diabetes.Design and settingRepeated cross-sectional surveys in the population-based Tromsø Study.MethodsWe used age-adjusted generalized estimating equation models to study trends in self-reported and undiagnosed (HbA1c ≥6.5%) diabetes, cardio-metabolic risk factors and the metabolic syndrome in 27281 women and men aged 40-84 years examined in up to four surveys of the Tromsø Study between 1994 and 2016. Further, we analyzed trends in diabetes treatment target achievement.ResultsDuring 1994-2016 diabetes prevalence increased in women (2.3% to 3.9%) and men (2.4% to 5.3%) and in all age-groups, while the proportion of undiagnosed diabetes in women (33% to 20%) and men (37% to 27%) decreased. Blood pressure and total cholesterol decreased, while waist circumference increased in participants with and without diabetes, leading to a relatively stable prevalence of the metabolic syndrome throughout the study period. There was a marginal increase in HbA1c levels among participants without diabetes. Only half of those with diabetes achieved the treatment target of HbA1c ≤7.0%.ConclusionIn the last two decades diabetes prevalence increased, while the proportion of undiagnosed diabetes declined. The prevalence of the metabolic syndrome remained stable throughout, driven by opposing trends with an increase in obesity and a decrease in other cardio-metabolic risk factors. HbA1c treatment target achievement did not improve.
Epigenome-wide association studies of three social determinants of health and implications for lung functions among survivors of childhood cancer
Authors: Song Nan , Sim Jin-ah , Dong Qian , Zheng Yinan , Hou Lifang , Li Zhenghong , Hsu Chia-Wei , Pan Haitao , Mulder Heather , Easton John , Walker Emily , Neale Geoffrey , Wilson Carmen L. , Ness Kirsten K. , Krull Kevin R. , Srivastava Deo Kumar , Yasui Yutaka , Zhang Jinghui , Hudson Melissa M. , Robison Leslie L. , Huang I-Chan , Wang Zhaoming 
Published: November 2020

AbstractBackgroundEmerging evidence suggests that social determinants of health (SDOH) may influence health and wellness through an epigenetic mechanism in the general population. However, the social epigenomic approach has not yet been applied to survivors of childhood cancer, a vulnerable population with elevated risk for chronic health conditions (CHCs).MethodsStudy participants were drawn from the St Jude Lifetime Cohort, a hospital-based retrospective cohort with prospective follow up. DNA methylation (DNAm) profiling was generated based on blood derived DNA collected during follow-up visit. SDOH included educational attainment, personal income, and area deprivation index (ADI) based on baseline or follow-up questionnaires and geocoding. CHCs were clinically assessed with severity grade.ResultsWe included 258 childhood cancer survivors of African ancestry (AA) (median time from diagnosis=25.2 years, interquartile range [IQR]=19.9-32.1 years) and 1,618 survivors of European ancestry (EA) (median time from diagnosis=27.3, IQR=21.1-33.7 years). Through epigenome-wide association studies, we identified 130 SDOH-CpG associations including educational attainment (N=88), personal income (N=23), and ADI (N=19) at epigenome-wide significance level (P<9×10−8). There were 13 CpGs, commonly associated with all three SDOH factors, with attenuated remaining effect sizes (36.8-48.3%) after additionally adjusting body mass index and smoking, mapped to smoking-related genes including GPR55, CLDND1, CPOX, GPR15, AHRR, PRRC2B, and ELMSAN1. Among 130 SDOH-related CpGs, three independent CpGs (cg04180924, cg1120500, and cg27470486) had a significant combined mediation effect for educational attainment (%mediation=48.9%), and a single mediator cg08064403 was found with significant mediation effect for personal income (25.9%) and ADI (24.1%) on pulmonary diffusion deficit, which showed higher incidence in AA than in EA survivors implying racial disparity which is possibly due to more disadvantageous SDOH factors in AA than in EA.ConclusionsWe demonstrated striking DNAm signatures associated with multiple SDOH factors (educational attainment, personal income, and ADI) and many epigenome-wide significant CpG sites resembling the effect of smoking exposure. We also identified an exemplified racial health disparity in pulmonary diffusion deficit between AA and EA survivors and illuminated DNAm as potential mechanistic mediators for SDOH factors using a social epigenomic approach.
ROLE OF LUNG ULTRASOUND FOR THE ETIOLOGICAL DIAGNOSIS OF COMMUNITY- ACQUIRED PNEUMONIA IN CHILDREN: A PROSPECTIVE STUDY
Authors: Buonsenso Danilo , Musolino Annamaria , Ferro Valentina , De Rose Cristina , Morello Rosa , Ventola Chiara , Liotti Flora Marzia , Chiaretti Antonio , Biasucci Daniele Guerino , Spanu Teresa , Sanguinetti Maurizio , Valentini Piero 
Published: November 2020

ABSTRACTObjective and designOur prospective study is one of the largest prospective study assessing the role of detailed lung ultrasound features to discriminate the etiological diagnosis of Community acquired pneumonia (CAP) in children.MethodologyWe prospectively analysed patients aged from 1 month to 17 years admitted between March 2018 and April 2020 who were hospitalized for CAP. For all patients included in the study, history, clinical parameters, microbiological data, and lung ultrasound data were collected.Patients were stratified into three main groups (“bacterial”, “viral”, “atypical”) according to the presumed microbial aetiology and lung ultrasound findings evaluated according to the aetiological group.ResultsWe found that some ultrasound findings as size, number and distribution of consolidations, the position and motion of air bronchograms, pleural effusions and distribution of vertical artifacts significantly differ (p < 0.05) in children with bacterial, viral and atypical CAP. Conversely, clinical parameters and laboratory were not able to significantly distinguish between these groups. Chest x-ray, despite being still widely used, was the less useful tool in this discrimination.ConclusionOur study provides a detailed analysis of LUS features able to predict the etiology CAP in children. These findings may help the physicians to better manage a child with CAP and to offer personalized approach, from diagnosis to treatment and follow-up.
Size matters: large copy number losses reveal novel Hirschsprung disease genes
Authors: Kuil Laura , MacKenzie Katherine C. , Tang Clara S , Windster Jonathan D. , Le Thuy Linh , Karim Anwarul , de Graaf Bianca M. , van der Helm Robert , van Bever Yolande , Sloots Cornelius E.J. , Meeussen Conny , Tibboel Dick , de Klein Annelies , Wijnen René M. H. , Amiel Jeanne , Lyonnet Stanislas , Garcia-Barcelo Maria-Mercè , Tam Paul K.H. , Alves Maria M. , Brooks Alice , Hofstra Robert M.W. , Brosens Erwin 
Published: November 2020

AbstractBackgroundHirschsprung disease (HSCR) is characterized by absence of ganglia in the intestine. Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). HSCR is a complex genetic disease in which the loss of enteric ganglia stems from a combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Pinpointing the responsible culprits within a large CNV is challenging as often many genes are affected. We investigated if we could find deleterious CNVs and if we could identify the genes responsible for the aganglionosis.ResultsDeleterious CNVs were detected in three groups of patients: HSCR-AAM, HSCR patients with a confirmed causal genetic variant and HSCR-isolated patients without a known causal variant and controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients withoutRETcoding variants. CNV profiling proved that HSCR-AAM patients had larger copy number losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes in Copy Number Losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution ofUFD1L, TBX2, SLC8A1andMAPK8to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expressionin vivo.ConclusionRare large Copy Number losses - oftende novo- contribute to the disease in HSCR-AAM patients specifically. We proved the involvement of five genes in enteric nervous system development and Hirschsprung disease.