bluuebunny/crossref_metadata_2025_split huggingface dataset:
School Distress in UK school children: A story dominated by neurodivergence and unmet needs
Authors: Connolly Sophie E. , Constable Hannah , Mullally Sinéad L. 
Published: September 2022

AbstractBackgroundThe Covid-19 pandemic has brought into sharp focus a school attendance crisis in many countries, although this likely pre-dates the pandemic. Children and young people (CYP) with school attendance problems (SAPs) often display extreme emotional distress when required to attend school. We term this School Distress (SD). Here we sought to elucidate the characteristics of the CYP struggling to attend school in the UK.MethodsUsing a case-control, concurrent embedded mixed-method research design, 947 parents of CYP with experience of SD completed a bespoke online questionnaire (February/March 2022), alongside an aged-matched control group (n=149) and a smaller group of parents who electively home-educate (n=25).ResultsIn 94.3% of cases, SAPs were underpinned by significant emotional distress, with often harrowing accounts of this distress provided by parents. Whilst the mean age of the CYP in this sample was 11.6 years (StDev 3.1 years), their SD was evident to parents from a much younger age (7.9 years). Notably, 92.1% of CYP currently experiencing SD were described as neurodivergent (ND) and 83.4% as autistic. The Odds Ratio of autistic CYP experiencing SD was 46.61 (95% CI [24.67, 88.07]). Autistic CYP displayed SD at a significantly earlier age, and it was significantly more enduring. Multi-modal sensory processing difficulties and ADHD (amongst other ND conditions) were also commonly associated with SD; with SD CYP having an average of 3.62 NDs (StDev 2.68). In addition, clinically significant anxiety symptomology (92.5%; ASC-ASD-P) and elevated demand avoidance (EDA-8) were also pervasive. Mental health difficulties in the absence of a ND profile were, however, relatively rare (6.17%). Concerningly, despite the striking levels of emotional distress and disability reported by parents, parents also reported a dearth of meaningful support for their CYP at school.ConclusionWhilst not a story of exclusivity relating solely to autism, SD is a story dominated by complex neurodivergence and a seemingly systemic failure to meet the needs of these CYP in UK schools. Given the disproportionate number of disabled CYP impacted, we ask whether the UK is upholding its’ responsibility to ensure the “right to an education” for all CYP (Human Rights Act 1998).
Cardiorespiratory signature of neonatal sepsis: Development and validation of prediction models in 3 NICUs
Authors: Kausch Sherry L. , Brandberg Jackson G. , Qiu Jiaxing J. , Panda Aneesha , Binai Alexandra , Isler Joseph , Sahni Rakesh , Vesoulis Zachary A. , Moorman J. Randall , Fairchild Karen D. , Lake Douglas E. , Sullivan Brynne A. 
Published: September 2022

AbstractBackgroundHeart rate characteristics aid early detection of late-onset sepsis (LOS), but respiratory data contain additional signatures of illness due to infection. Predictive models using cardiorespiratory data may improve early sepsis detection. We hypothesized that heart rate (HR) and oxygenation (SpO2) data contain signatures that improve sepsis risk prediction over HR or demographics alone.MethodsWe analyzed cardiorespiratory data from very low birth weight (VLBW, <1500g) infants admitted to three NICUs. We developed and externally validated four machine learning models to predict LOS using features calculated every 10m: mean, standard deviation, skewness, kurtosis of HR and SpO2, and cross-correlation. We compared feature importance, discrimination, calibration, and dynamic prediction across models and cohorts. We built models of demographics and HR or SpO2 features alone for comparison with HR-SpO2 models.ResultsPerformance, feature importance, and calibration were similar among modeling methods. All models had favorable external validation performance. The HR-SpO2 model performed better than models using either HR or SpO2 alone. Demographics improved the discrimination of all physiologic data models but dampened dynamic performance.ConclusionsCardiorespiratory signatures detect LOS in VLBW infants at 3 NICUs. Demographics risk-stratify, but predictive modeling with both HR and SpO2 features provides the best dynamic risk prediction.
Comparative IgG responses to SARS-CoV-2 after natural infection or vaccination
Authors: Olds Kaylan M. , Humphreys Devon P. , Gavin Kathleen M. , Wyllie Anne L. , Bauer Timothy A. 
Published: September 2022

AbstractBackgroundWhether vaccination or natural infection provides greater benefit regarding the development of sustained immunity against SARS-CoV-2 remains unknown. Therefore, the aim of this study was to provide a direct comparison of IgG durability in vaccinated and unvaccinated adults.MethodsThis was a prospective, cross-sectional study of antibody durability in 1087 individuals with a median (IQR) age of 42 (35, 52) years who were unvaccinated and previously infected with SARS-CoV-2 (Arm 1, n=351) or vaccinated against the virus (Arm 2, n=737). Participants self-reported vaccination and infection history and provided self-collected serology samples using mailed collection kits.ResultsAnti-S1 IgG seroprevalence was 15.6% higher in vaccinated versus unvaccinated, previously-infected individuals across intervals ranging from 1 to 12 months and antibody survival was sustained near 100% through 12 months in the vaccinated group.ConclusionsThese findings suggest that vaccination as opposed to natural infection alone provides significant advantages in terms of sustained and effective immunity against prior variants of SARS-CoV-2. Future efforts to characterize SARS-CoV-2 immune responses should address hybrid immunity, booster status and formulation, and protection against (sub)variants of Omicron and future lineages, as well as weigh the potential impact of other immune system mechanisms.
Sudden cardiac death in the young: A qualitative study of experiences of family members with cardiogenetic evaluation
Authors: van den Heuvel Lieke , Do Judy , Yeates Laura , Burns Charlotte , Semsarian Chris , Ingles Jodie 
Published: September 2022

ABSTRACTIntroductionSudden cardiac death (SCD) is a devastating event for the family and the community, especially when it occurs in a young person (<45 years). Genetic heart diseases, including cardiomyopathies and primary arrhythmia syndromes, are an important cause of SCD in the young. Although cardiogenetic evaluation, i.e., clinical evaluation, genetic testing and psychological support, is increasingly performed after SCD, it is unknown how suddenly bereaved family members experience the process. We aimed to explore the experiences of family members with cardiogenetic evaluation after SCD, and their perception of the process and care received.MethodsIn-depth interviews were conducted with eighteen family members of young people (<45 years old) who died suddenly, including parents, siblings and partners. The interviews were thematically analysed by two researchers independently.ResultsIn total, 18 interviews were conducted from 17 families. The following themes were identified: (1) Experiences with postmortem genetic testing including managing expectations and psychological impact, (2) appreciation of care such as access to genetic counselling and relief following cardiac evaluation of relatives, and (3) need for support including unmet psychological support needs and better coordination of care immediately after the death.ConclusionAlthough participants appreciated the opportunity for cardiogenetic evaluation, they also experienced a lack of coordination of cardiogenetic and psychological care. Our findings stress the importance of access to expert multidisciplinary teams, including psychological care, to adequately support these families after a SCD in a young family member.
eIF4E phosphorylation recruits β-catenin to mRNA cap and selectively promotes Wnt pathway translation in dentate gyrus LTP maintenance in vivo
Authors: Patil Sudarshan , Chalkiadaki Kleanthi , Mergiya Tadiwos Feyissa , Simbriger Konstanze , Amorim Inês S. , Akerkar Shreeram , Gkogkas Christos G. , Bramham Clive R. 
Published: September 2022

SUMMARYThe mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, while basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in in vivo LTP. Surprisingly, the canonical Wnt effector, β-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a critical role for activity-evoked eIF4E phosphorylation in dentate gyrus LTP maintenance, bidirectional remodeling of the mRNA cap-binding complex, and mRNA-specific translational control linked to Wnt pathway.Key highlightsSynaptic activity-induced eIF4E phosphorylation controls DG-LTP maintenance in vivoeIF4E phosphorylation triggers release of translational repressors from cap complexeIF4E phosphorylation recruits β-catenin to cap complexeIF4E phosphorylation selectively enhances translation of Wnt pathway
Bacteriophages targeting protective commensals impair resistance againstSalmonellaTyphimurium infection in gnotobiotic mice
Authors: von Strempel Alexandra , Weiss Anna S. , Wittmann Johannes , Salvado Silva Marta , Ring Diana , Wortmann Esther , Clavel Thomas , Debarbieux Laurent , Kleigrewe Karin , Stecher Bärbel 
Published: September 2022

AbstractGut microbial communities protect the host against a variety of major human gastrointestinal pathogens. Bacteriophages (phages) are ubiquitous in nature and frequently ingested via food and drinking water. Moreover, they are an attractive tool for microbiome engineering due to the lack of known serious adverse effects on the host. However, the functional role of phages within the gastrointestinal microbiome remain poorly understood. Here, we investigated the effects of microbiota-directed phages on infection with the human enteric pathogenSalmonella entericaserovar Typhimurium (S. Tm), using a gnotobiotic mouse model (OMM12) for colonization resistance (CR). We show that phage cocktails targetingEscherichia coliandEnterococcus faecalisacted in a strain-specific manner. They transiently reduced the population density of their respective target before establishing coexistence for up to 9 days. Infection susceptibility toS. Tm was markedly increased at an early time point after phage challenge. Surprisingly, OMM12mice were more susceptible 7 days after a single phage inoculation, when the targeted bacterial populations were back to pre-phage administration density. The presence of phages that dynamically modulates the density of protective members of the gut microbiota provides opportunities for invasion of bacterial pathogens.
svep1 and tie1 genetically interact and affect aspects of facial lymphatic development in a Vegfc-independent manner
Authors: Hußmann Melina , Weischer Sarah , Carlantoni Claudia , Stainier Didier Y. R. , Zobel Thomas , Schulte-Merker Stefan 
Published: September 2022

AbstractMultiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vegfc signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds. Additionally, we find that multiple specific and newly uncovered phenotypic hallmarks of svep1 mutants are also present in tie1, but not in tie2 or vegfc mutants. These phenotypes are observed in the lymphatic vasculature of both head and trunk, as well as in the development of the dorsal longitudinal anastomotic vessel (DLAV) under reduced flow conditions. Furthermore, we show genetic interaction between svep1 and tie1 during the migration of parachordal lymphangioblasts (PLs). Therefore, our study demonstrates an important function for Tie1 signalling during lymphangiogenesis as well as blood vessel development in zebrafish and provides the first in vivo evidence for zebrafish Svep1 and Tie1 interaction. Since compound heterozygous mutations for SVEP1 and TIE2 have recently been reported in human glaucoma patients, our data have clinical relevance in demonstrating a role for Svep1 in Tie signalling in an in vivo setting.
A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Authors: Fernanda dos Reis Thaila , Alves de Castro Patrícia , Bastos Rafael Wesley , Pinzan Camila Figueiredo , Souza Pedro F. N. , Ackloo Suzanne , Hossain Mohammad Anwar , Drewry David Harold , Alkhazraji Sondus , Ibrahim Ashraf S. , Jo Hyunil , deGrado William F. , Goldman Gustavo H. 
Published: September 2022

AbstractA. fumigatus is the main etiological agent of a group of heterogeneous diseases called aspergillosis of which the most lethal form is the invasive pulmonary aspergillosis (IPA). Fungicidal azoles and amphotericin B are the first line defense against A. fumigatus, but fungistatic echinocandins, such as caspofungin (CAS), can be used as salvage therapy for IPA. Here, we screened repurposing libraries and identified several compounds that potentiate CAS activity against A. fumigatus, including the host defense peptide mimetic, brilacidin (BRI). BRI converts CAS into a fungicidal drug and potentiates voriconazole (VOR) against A. fumigatus. BRI increases the ability of both CAS and VOR to control A. fumigatus biofilm growth. BRI depolarizes the A. fumigatus cell membrane leading to disruption of membrane potential. By using a combination of protein kinase inhibitors and screening of a catalytic subunit null mutant library, we identified the mitogen activated protein kinase (MAPK) MpkA and the phosphatase calcineurin as mediators of the synergistic action of BRI. These results suggest the most likely BRI mechanism of action for CAS potentiation is the inhibition of A. fumigatus cell wall integrity (CWI) pathway. BRI potentiates CAS activity against C. albicans, C. auris, and C. neoformans. Interestingly, BRI overcomes the CAS-acquired resistance in both A. fumigatus and C. albicans and the CAS-intrinsic resistance in C. neoformans. BRI also has an additive effect on the activity of posaconazole (POSA) against several Mucorales fungi. Cell toxicity assays and fungal burden studies in an immunosuppressed murine model of IPA showed that BRI combined with CAS is not toxic to the cells and significantly clears A. fumigatus lung infection, respectively. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of IPA and other fungal infections.
The generation of the first chromosome-level de-novo genome assembly and the development and validation of a 50K SNP array for North American Atlantic salmon
Authors: Gao Guangtu , Waldbieser Geoffrey C. , Youngblood Ramey C. , Zhao Dongyan , Pietrak Michael R. , Allen Melissa S. , Stannard Jason A. , Buchanan John T. , Long Roseanna L. , Milligan Melissa , Burr Gary , Mejía-Guerra Katherine , Sheehan Moira J. , Scheffler Brian E. , Rexroad Caird E. , Peterson Brian C. , Palti Yniv 
Published: September 2022

AbstractGiven the genetic and genomic differences between Atlantic salmon of European origin and North American (N.A.) origin, it is crucial to develop unique genomic resources for each lineage. Here we describe the resources that we recently developed for genomic and genetic research in N.A. Atlantic salmon. Firstly, a new single nucleotide polymorphism (SNP) database for N.A. Atlantic salmon consisting of 3.1 million putative SNPs was generated using data from whole genome resequencing of 80 N.A. Atlantic salmon individuals; Secondly, a high density 50K SNP array enriched for the genic regions of the genome and containing three sex determination and 61 continent of origin markers was developed and validated; Thirdly, a genetic map composed of 27 linkage groups with 36K SNP markers, was generated from 2,512 individuals in 141 full-sib families; Finally, a chromosome level de-novo assembly of a male N.A. Atlantic salmon genome was generated using PacBio long-reads. Information from Hi-C proximity ligation sequences and Bionano optical mapping was used to concatenate the contigs into scaffolds. The assembly contains 1,755 scaffolds and only 1,253 gaps, with a total length of 2.83 Gb and N50 of 17.2 Mb. A BUSCO analysis detected 96.2% of conserved Actinopterygii genes in the assembly and the genetic linkage information was used to guide the formation of 27 chromosome sequences. In contrast, the karyotype of the European Atlantic salmon lineage is composed of 29 chromosomes. Comparative analysis with the reference genome assembly of the European Atlantic salmon confirmed that the karyotype differences between the two linages are caused by a fission in chromosome Ssa01 and three chromosome fusions including the p arm of chromosome Ssa01 with Ssa23, Ssa08 with Ssa29 and Ssa26 with Ssa28. The genomic resources we have generated for Atlantic salmon provide a crucial boost for genetic research and for management of farmed and wild populations in this highly valued species.
Synthetic carbon fixation via the autocatalytic serine threonine cycle
Authors: Wenk Sebastian , Rainaldi Vittorio , He Hai , Schann Karin , Bouzon Madeleine , Döring Volker , Lindner Steffen N. , Bar-Even Arren 
Published: September 2022

AbstractAtmospheric CO2 poses a major threat to life on Earth by causing global warming and climate change. On the other hand, it is the only carbon source that is scalable enough to establish a circular carbon economy. Accordingly, technologies to capture and convert CO2 to reduced one-carbon (C1) molecules (e.g. formate) using renewable energy are improving fast. Driven by the idea of creating sustainable bioproduction platforms, natural and synthetic C1-utilization pathways are engineered into industrially relevant microbes. The realization of synthetic C1-assimilation cycles in living organisms is a promising but challenging endeavour. Here, we engineer the autocatalytic serine threonine cycle, a synthetic C1-assimilation route in Escherichia coli. Our stepwise engineering approach in tailored selection strains combined with adaptive laboratory evolution experiments enabled the organism to grow on formate. The synthetic strain uses formate as the sole carbon and energy source and is capable of growing at ambient CO2 concentrations, demonstrating the feasibility of establishing synthetic C1-assimilation cycles over laboratory timescales.
Meta-analysis refinement of plasma extracellular vesicle composition identifies proplatelet basic protein as a signaling messenger in type 1 diabetes
Authors: Vallejo Milene C. , Sarkar Soumyadeep , Elliott Emily C. , Henry Hayden R. , Huang Fei , Payne Samuel H. , Ramanadham Sasanka , Sims Emily K. , Metz Thomas O. , Mirmira Raghavendra G. , Nakayasu Ernesto S. 
Published: September 2022

AbstractExtracellular vesicles (EVs) play important roles in cell-to-cell communication and are potential biomarkers as they carry markers of their derived tissues and disease signatures. However, obtaining pure EV preparations from biofluids is challenging due to contaminants with similar physicochemical properties. Here, we performed a meta-analysis of plasma EV proteomics data deposited in public repositories to refine the protein composition of EVs and investigate potential roles in type 1 diabetes development. With the concept that each purification method yields different proportions of distinct contaminants, we grouped proteins into clusters based on their abundance profiles. This allowed us to separate clusters with classical EV markers, such as CD9, CD40, C63 and CD81, from clusters of well-known contaminants, such as serum albumin, apolipoproteins and components of the complement and coagulation pathways. Two clusters containing a total of 1720 proteins combined were enriched with EV markers and depleted in common contaminants; therefore, they were considered to containbona fideEV components. As possible origins of plasma EVs, these clusters had markers of tissues such as spleen, liver, brain, lungs, pancreas, and blood/immune cells. These clusters were also enriched in cell surface markers CD antigens, and proteins from cell-to-cell communication and signaling pathways, such as chemokine signaling and antigen presentation. We also show that the EV component and type 1 diabetes biomarker, platelet basic protein (PPBP/CXCL7) regulates apoptosis in both beta and macrophage cell lines. Overall, our meta-analysis refined the composition of plasma EVs, reinforcing a primary function as messengers for cell-to-cell communication and signaling. Furthermore, this analysis identifies optimal avenues to target EVs for development of disease biomarkers.
Identification and management of thyroid dysfunction using at-home sample collection and telehealth services
Authors: Gavin Kathleen M. , Kreitzberg Daniel , Gaudreau Yvette , Cruz Marisa , Bauer Timothy A. 
Published: September 2022

AbstractIntroductionPrograms aimed at modernizing thyroid care by pairing at-home sample collection methods with telehealth options may serve an important and emerging role in thyroid care. The primary objective of this analysis was to evaluate telehealth utilization, demographics, and clinical characteristics of a cohort of consumer initiated at-home lab thyroid test users who were also offered the option of follow-up telehealth consultations.MethodsThis was a retrospective analysis of real-world data from a de-identified consumer database of home-collected, mail-in Thyroid Tests utilized from March to May 2021 (n=8,152). The mean age was 38.6 (range 18-85) years and 86.6% of individuals identified as female.ResultsSeven percent of test takers fell into a thyroid dysfunction category (0.9% overthypothyroidism, 2.9% subclinical hypothyroidism, 0.1% overt-hypothyroidism, and 3.3% subclinical-hyperthyroidism). Twelve percent of the overall sample opted into a telehealth consultation, with 91.8% receiving a non-treatment telehealth consultation and 8.2% receiving a treatment telemedicine consultation. Sixteen percent of individuals with overt or subclinical thyroid dysfunction engaged in telehealth consultations. Of those opting into a treatment consultation, 59.3% reported a history of thyroid issues, 55.6% indicated wanting to discuss their current thyroid medication, and 48% received a prescription medication.DiscussionThe combination of at-home sample collection and telehealth is an innovative model for screening for thyroid disorders, monitoring thyroid function, and increasing access to care that can be implemented at a large scale and across a wide range of age groups.