bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary dynamics of nascent multicellular lineages
Authors: Doulcier Guilhem , Remigi Philippe , Rexin Daniel , Rainey Paul B.
Published: May 2024

The evolution of multicellular organisms involves the emergence of cellular collectives that eventually become units of selection in their own right. The process can be facilitated by ecological conditions that impose heritable variance in fitness on nascent collectives with long-term persistence depending on capacity of competing lineages to transition reliably between soma- and germ-like stages of proto-life cycles. Prior work with experimental bacterial populations showed rapid increases in collective-level fitness with capacity to switch between life cycle phases being a particular focus of selection. Here we report experiments in which the most successful lineage from the earlier study was further propagated for 10 life cycle generations under regimes that required different investment in the somalike phase. To explore the adaptive significance of switching, a control was included in which reliable transitioning between life cycle phases was abolished. The switch proved central to maintenance of fitness. Moreover, in a non-switch treatment, where solutions to producing a robust and enduring soma-phase were required, evolution ofmutL-dependent switching emergedde novo. A newly developed computational pipeline (colgen) was used to display the moment-by-moment evolutionary dynamics of lineages providing rare visual evidence of the roles of chance, history and selection.Colgen, underpinned by a Bayesian model, was further used to propagate hundreds of mutations back through temporal genealogical series, predict lineages and time points corresponding to changes of likely adaptive significance, and in one instance, via a combination of targeted sequencing, genetics and analyses of fitness consequences, adaptive significance of a single mutation was demonstrated. Overall, our results shed light on the mechanisms by which collectives adapt to new selective challenges and demonstrate the value of genealogy-centered approaches for investigating the dynamics of lineage-level selection.
Micro-CT Based Description ofDorsetichthys bechei(Actinopterygii: Teleostei): Cranial Anatomy of an Iconic Early Teleost
Authors: Atterby Jake , Friedman Matt , Giles Sam
Published: May 2024

Teleost fishes comprise more than 36,000 living vertebrate species and occupy a wide range of aquatic ecosystems. Despite their overwhelming success, extinct taxa outside of the living radiation—stem teleosts—remain poorly understood.Dorsetichthys becheiis an Early Jurassic stem teleost of historic importance. AlthoughD. becheiis well described, its proximity to the teleost crown and relationships with other stem teleosts is challenging due to previous associations with the wastebasket assemblage known as “pholidophorids”. Here we present a new, three-dimensionally preserved specimen ofDorsetichthys becheifrom the Blue Lias Formation (Sinemurian) Lyme Regis, UK. High-resolution CT scanning of this specimen plus additional material reveals previously unknown internal morphological information, including of the jaw and palate, hyoid arch, and gill skeleton. Importantly, this previously undescribed articulated specimen permits description of the external dermal skeleton and internal endoskeleton for the same individual, clarifying past accounts drawing on composite descriptions of two- and three-dimensionally preserved specimens. We confirm the presence of important teleost synapomorphies such as a mobile premaxilla and quadratojugal process. However, contrasting previous accounts, we find no evidence for dorsal and ventral hypohyals or a postarticular process of the lower jaw. We also confirm the presence of a prearticular. The presence of a mobile upper jaw, elaborate gill rakers and reduced dentition also support a possible facultative filter feeding ecology. These new anatomical data support removal ofD. becheifrom Pholidophoridae and Pholidophoriformes as currently defined but indicate that finer-scale patterns of relationships among more crownward members of the teleost stem are some way from being resolved.
Gekko geckoas a model organism for understanding aspects of laryngeal vocal evolution
Authors: Gutjahr Ruth , Kéver Loïc , Jonsson Thorin , Ontiveros Daniela Talamantes , Chagnaud Boris P , Herrel Anthony
Published: May 2024

The ability to communicate through vocalization plays a key role in the survival of animals across all vertebrate groups. While avian reptiles have received much attention relating to their stunning sound repertoire, non-avian reptiles have been wrongfully assumed to have less elaborate vocalization types and little is known about the biomechanics of sound production and their underlying neural pathways. We investigated alarm calls ofGekko geckousing audio and cineradiographic recordings of their alarm calls. Acoustic analysis revealed three distinct call types: a sinusoidal call type (type 1), a train-like call type, characterized by distinct pulse trains (type 3), and an intermediary type, which showed both sinusoidal and pulse train components (type 2). Kinematic analysis of cineradiographic recordings showed that laryngeal movements differ significantly between respiratory and vocal behavior: during respiration, animals repeatedly moved their jaws to partially open their mouths, which was accompanied by small glottal movements. During vocalization, the glottis was pulled back, contrasting with what has previously been reported.In-vitroretrograde tracing of the nerve innervating the laryngeal constrictor and dilator muscles revealed round to fusiform motoneurons in the hindbrain-spinal cord transition ipsilateral to the labeled nerve. Taken together, our observations provide insight into the alarm calls generated byG. gecko, the biomechanics of this sound generation and the underlying organization of motoneurons involved in the generation of vocalizations. Our observations suggest thatG. geckomay be an excellent non-avian reptile model organism for enhancing our understanding of the evolution of vertebrate vocalization.

Summary Statement

Investigation ofGekko geckoalarm calls revealed distinct call types, during which the larynx is being pulled back by muscles innervated by motoneurons located in the hindbrain.
Neuronal protein phosphatase 1β regulates glutamate release, cortical myelination, node of Ranvier formation, and action potential propagation in the optic nerve
Authors: McKee Cody , Foley Karl , Andersh Katherine M. , Marola Olivia J. , Wadzinski Brian , Libby Richard T. , Shrager Peter , Xia Houhui
Published: May 2024

Precise regulation of protein phosphorylation is critical for many cellular processes, and dysfunction in this process has been linked to various neurological disorders and diseases. Protein phosphatase 1 (PP1) is a ubiquitously expressed serine/threonine phosphatase with three major isoforms, (α, β, γ) and hundreds of known substrates. Previously, we reported that PP1α and PP1γ are essential for the known role of PP1 in synaptic physiology and learning/memory, while PP1β displayed a surprising opposing function.De novomutations in PP1β cause neurodevelopmental disorders in humans, but the mechanisms involved are currently unknown. A Cre-Lox system was used to delete PP1β specifically in neurons in order to study its effects on developing mice. These animals fail to survive to 3 postnatal weeks, and exhibit deficits in cortical myelination and glutamate release. There was defective compound action potential (CAP) propagation in the optic nerve of the null mice, which was traced to a deficit in the formation of nodes of Ranvier. Finally, it was found that phosphorylation of the PP1β-specific substrate, myosin light chain 2 (MLC2), is significantly enhanced in PP1β null optic nerves. Several novel importantin vivoroles of PP1β in neurons were discovered, and these data will aid future investigations in delineating the mechanisms by whichde novomutations in PP1β lead to intellectual and developmental delays in patients.
Transcription elongation is dictated by single residues in the histone core domain
Authors: Harvey Zachary H. , Stevens Kathryn M. , Warnecke Tobias , Berger Frédéric
Published: May 2024

The chromatin fiber is thought to suppress transcription in eukaryotes by acting as a structural barrier. However, once begun, transcription can readily proceed on chromatin, suggesting this model is insufficient. Here, we establish that the ultra-conserved core domain of the ancestral histone H2A.Z dictates transcription elongation via direct interaction of its loop 2 region with the RNAPII subunit Spt6, rather than biophysical changes to chromatin. Interrogating H2A.Z sequences representing more than a billion years of eukaryotic evolution in a single synthetic host, we show that Spt6 can distinguish even single-residue substitutions within their loop 2, driving either super-repressed or -activated transcriptional states. Our results place the histone core domain at the origin of eukaryotic gene expression, establishing its transformative power to shape transcription.
HIGH THROUGHPUT QUANTITATION OF HUMAN NEUTROPHIL RECRUITMENT AND FUNCTIONAL RESPONSES IN AN AIR-BLOOD BARRIER ARRAY
Authors: Viola Hannah , Chen Liang-Hsin , Jo Seongbin , Washington Kendra , Selva Cauviya , Li Andrea , Feng Daniel , Giacalone Vincent , Stephenson Susan T. , Cottrill Kirsten , Mohammed Ahmad , Williams Evelyn , Qu Xianggui , Lam Wilbur , Ng Nga Lee , Fitzpatrick Anne , Grunwell Jocelyn , Tirouvanziam Rabindra , Takayama Shuichi
Published: May 2024

Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enablesin vivo-like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry. We modeled acute respiratory distress syndrome (ARDS) with neutrophil recruitment to 20 ng/mL epithelial-side interleukin 8 (IL-8) and found a dose dependent reduction in recruitment with physiologic doses of baricitinib, a JAK1/2 inhibitor recently FDA-approved for severe COVID-19 ARDS. Additionally, neutrophil recruitment to patient-derived cystic fibrosis sputum supernatant induced disease-mimetic recruitment and activation of healthy donor neutrophils and upregulated endothelial e-selectin. Compared to 24-well assays, the L-ABBA-96 reduces required patient sample volumes by 25 times per well and quadruples throughput per plate. Compared to microfluidic assays, the L-ABBA-96 recruits two orders of magnitude more neutrophils per well, enabling downstream flow cytometry and other standard biochemical assays. This novel pairing of high-throughputin vitromodeling of organ-level lung function with parallel high-throughput leukocyte phenotyping substantially advances opportunities for pathophysiological studies, personalized medicine, and drug testing applications.
LAGOS-US LANDSAT: Remotely sensed water quality estimates for U.S. lakes over 4 ha from 1984 to 2020
Authors: Hanly Patrick J. , Webster Katherine E. , Soranno Patricia A.
Published: May 2024

Broad-scale, long-term studies of water quality (WQ) are critical to understanding global-scale pressures on inland waters, yet they are rare. This data product, LAGOS-US LANDSAT, addresses this gap by providing remote sensing-derived WQ estimates from machine learning models trained on in situ data of six essential WQ variables for 136,977 lakes in the continental US from 1984-2020. The dataset includes: (a) 45,867,023 sets of whole-lake water reflectances for six individual bands and 15 band ratios; (b) 740,627 matchups with in situ data for lake WQ data for chlorophyll, Secchi depth, true color, dissolved organic carbon, total suspended solids, and turbidity; and, (c) predictions from each reflectance set for all six WQ variables across the 37 yr period. Variance explained for the predictions ranged from 20.7% for TSS to 63.7% for Secchi. Data extraction from individual scenes was quality-controlled based on cloud-cover and pixel quality, and we tested and validated key parts of the workflow to inform future water quality studies using the Landsat platform.
Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts
Authors: Kamat Pratik , Macaluso Nico , Min Chanhong , Li Yukang , Agrawal Anshika , Winston Aaron , Pan Lauren , Starich Bartholomew , Stewart Teasia , Wu Pei-Hsun , Fan Jean , Walston Jeremy , Phillip Jude M.
Published: May 2024

Cellular senescence is an established driver of aging, exhibiting context-dependent phenotypes across multiple biological length-scales. Despite its mechanistic importance, profiling senescence within cell populations is challenging. This is in part due to the limitations of current biomarkers to robustly identify senescent cells across biological settings, and the heterogeneous, non-binary phenotypes exhibited by senescent cells. Using a panel of primary dermal fibroblasts, we combined live single-cell imaging, machine learning, multiple senescence induction conditions, and multiple protein-based senescence biomarkers to show the emergence of functional subtypes of senescence. Leveraging single-cell morphologies, we defined eleven distinct morphology clusters, with the abundance of cells in each cluster being dependent on the mode of senescence induction, the time post-induction, and the age of the donor. Of these eleven clusters, we identified threebona-fidesenescence subtypes (C7, C10, C11), with C10 showing the strongest age-dependence across a cohort of fifty aging individuals. To determine the functional significance of these senescence subtypes, we profiled their responses to senotherapies, specifically focusing on Dasatinib + Quercetin (D+Q). Results indicated subtype-dependent responses, with senescent cells in C7 being most responsive to D+Q. Altogether, we provide a robust single-cell framework to identify and classify functional senescence subtypes with applications for next-generation senotherapy screens, and the potential to explain heterogeneous senescence phenotypes across biological settings based on the presence and abundance of distinct senescence subtypes.
Retinoic acid signaling suppresses chondrocyte identity during cartilage development and regeneration
Authors: Arata Claire , Paul Sandeep , Schindler Simone , Thiruppathy Mathi , Flath Mackenzie , Giovannone Dion , Hammer Zack , Subramanie Dev , Crump J. Gage
Published: May 2024

Cartilage is a dynamic tissue during development, repair, and disease. Within developing endochondral bones, chondrocytes at growth plate edges transition to osteoblasts, adipocytes, and other connective tissue in the marrow cavity, and in diseases such as Multiple Osteochondromas (MO) chondrocytes form abnormally around growth plates and contribute to ectopic bone. On the other hand, the inability to form new chondrocytes to maintain damaged joints contributes to the high incidence of osteoarthritis. In order to assess the ability of zebrafish to regenerate cartilage, we developed a nitroreductase-based cartilage ablation model. Following ablation at larval to adult stages, we observed new chondrocytes forming around the dead cartilage matrix, with cartilage outgrowths in ablated endochondral bones resembling the exostoses of MO. By generating a perichondrium-restrictedhyal4:GFPtransgenic line, we show that new chondrocytes arise from the perichondrium surrounding the ablated cartilage. In addition, we observe enriched expression of the retinoic acid (RA) synthesis genealdh1a2in the perichondrium following ablation, and the RA degrading enzyme genecyp26b1in newly forming chondrocytes. Consistent with RA signaling suppressing chondrogenesis, treatment with the RA receptor gamma agonist palovarotene, which has been used to treat MO, prevented ablation-induced chondrogenesis. Although we find that BMP signaling is also required for ablation-induced chondrogenesis, we show a distinct role for RA signaling in suppressingsox9aexpression and chondrogenesis. Moreover, palovarotene resulted in a near complete loss of growth plates in uninjured zebrafish, which was due to the precocious dedifferentiation and exit of chondrocytes from the growth plate. Our findings suggest a common chondrocyte suppressive role of RA signaling within the developing growth plates and regenerating perichondrium, which may explain the growth plate defects observed when using RA agonists to treat MO.
aniSNA : An R package to assess bias and uncertainty in social networks obtained from animals sampled via direct observations or satellite telemetry
Authors: Kaur Prabhleen , Ciuti Simone , Reinking Adele K. , Beck Jeffrey L. , Salter-Townshend Michael
Published: May 2024

Animal social network analysis using GPS telemetry datasets provides insights into group dynamics, social structure, and interactions of the animal communities. It aids conservation by characterizing key aspects of animal sociality - including spatially explicit information on where sociality occurs (e.g., habitats, migratory corridors), contributing to informed management strategies for wildlife populations. The aniSNA package provides functions to assess and leverage data collected by sampling a subset of an animal population to perform social network analysis. The methodologies offered in this package are compatible with a variety of location and grouping data, collected through various means (e.g., direct observations, biologgers), however, they are particularly well suited to autocorrelated data streams such as data collected through GPS telemetry radio collars. The techniques assess the data’s suitability to extract reliable statistical inferences from social networks and compute uncertainty estimates around the network metrics in the scenario where a fraction of the population is monitored. The package functions are user-friendly and allow for the implementation of pre-network data permutations for auto-correlated data streams, sensitivity analysis under downsampling, bootstrapping to establish confidence intervals for global and node-level network metrics, and correlation and regression analysis to assess the robustness of node-level network metrics. Using this package, animal ecologists will be able to compute social network metrics, both at the population and individual level, assess their reliability, and use such metrics in further analyses, e.g., to study social network variation within and across populations or link individual sociality to life history. This software also has plotting features that allow for visual interpretation of the findings.
Comprehensive Usability Evaluation and Performance Overview of Pathpoint® Outcomes Software
Authors: Subramaniyan Balamurugan , Naqvi Atlas , Mohamud Muna , Mahapatra Piyush
Published: May 2024

This research evaluates the usability of Pathpoint® Outcomes Software, aligning with IEC 62366-1:2015 standards to ensure rigour and accuracy. The study involved diverse user groups like Healthcare Professionals and the General Population to provide varied perspectives. The study focused on the software’s usability, safety, and effectiveness, which are crucial to user experience, satisfaction, and performance. Any potential risks to users or patient data were identified to ensure safety standards. The software’s effectiveness was assessed, considering its accuracy, reliability, and efficiency. The study used both quantitative metrics and qualitative feedback for a balanced evaluation. It also aimed to identify and mitigate potential use errors, enhancing the software’s usability, safety, and effectiveness.
Regulatory T cell-derived enkephalin gates nociception
Authors: Midavaine Élora , Moraes Beatriz C. , Benitez Jorge , Rodriguez Sian R. , Braz Joao M. , Kochhar Nathan P. , Eckalbar Walter L. , Domingos Ana I. , Pintar John E. , Basbaum Allan I. , Kashem Sakeen W.
Published: May 2024

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. We demonstrate that mTregs are both necessary and sufficient to suppress mechanical pain sensitivity in female, but not male, mice, with this modulation reliant on sex hormones. These results uncover a fundamental sex-specific, and immunologically- derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology.

Highlights

1. Gating of allodynia by meningeal Tregs is sex hormone-dependent

3. Treg-derived enkephalin modulates mechanical pain sensitivity, not inflammation

4. Delta opioid receptor on MrgprD+sensory neuron mediates pain processing by mTregs
Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica
Authors: Gupta Meghna , Khandelwal Nitesh Kumar , Nelson Andrew , Hwang Peter , Pourmal Sergei , Bennett Jeffrey L. , Stroud Robert M.
Published: May 2024

Neuromyelitis Optica (NMO) is an autoimmune disease of the central nervous system where pathogenic autoantibodies target the human astrocyte water channel aquaporin-4 causing neurological impairment. Autoantibody binding leads to complement dependent and complement independent cytotoxicity, ultimately resulting in astrocyte death, demyelination, and neuronal loss. Aquaporin-4 assembles in astrocyte plasma membranes as symmetric tetramers or as arrays of tetramers. We report molecular structures of aquaporin-4 alone and bound to Fab fragments from patient-derived NMO autoantibodies using cryogenic electron microscopy. Each antibody binds to epitopes comprised of three extracellular loops of aquaporin-4 with contributions from multiple molecules in the assembly. The structures distinguish between antibodies that bind to the tetrameric form of aquaporin-4, and those targeting higher order orthogonal arrays of tetramers that provide more diverse bridging epitopes.

One-Sentence Summary

Pathogenic autoantibodies in Neuromyelitis Optica distinguish multiply presented epitopes on arrays of human aquaporin-4.
Effectiveness of iso-inertial resistance training on eccentric and concentric power, physical performance, and risk of falls in physically active middle-older adults: a randomised controlled trial
Authors: Cadellans-Arroniz Aida , Blanco David , Madruga-Perera Marc , Zarate-Lozano Victor , Dantony Flora , Romero-Rodriguez Daniel
Published: May 2024

Objective: To evaluate the effectiveness of iso-inertial resistance training on eccentric power compared to gravitational training in physically active middle-older adults. Methods: Parallel-group, randomised controlled trial at Espai Esport Wellness Center (Granollers, Spain). Forty-four physically active adults (>57 years of age) were randomised to iso-inertial (n=21) or gravitational (n=23) training groups (R software; 1:1 ratio). Participants had to complete a 6-week training program (2 sessions/week) consisting of three exercises (forward lunge, side lunge, forward lunge with row). Primary outcome: power in the eccentric phase of each exercise evaluated with both iso-inertial and gravitational devices. Secondary outcomes: concentric power, physical performance, risk of falls. Only outcome evaluators were blinded. We used multivariate linear regression models to analyse the effect of interventions. Results: Iso-inertial training showed better eccentric power gains than gravitational training for iso-inertial system evaluation, although the difference was only statistically significant for the side lunge. Forward lunge: between-group difference 3.99 W (95% CI: -3.99 to 11.33, p: 0.28); side lunge: difference 8.50 W (95% CI: 2.13 to 14.87; p: 0.01); forward lunge with row: difference 14.07 W (95% CI: -2.07 -to 30.20, p: 0.09). We observed no differences for the gravitational system evaluation nor for concentric power, physical performance, and risk of falls. The two groups improved remarkably from baseline for all outcomes. Conclusions: Iso-inertial resistance training might lead to better eccentric power gains than gravitational training. Both approaches seem equally effective in improving concentric power and physical performance, and reducing the risk of falls. Trial registration: ClinicalTrials.gov (NCT06160089).
Prenatal Pyrethroid Exposure, Placental Gene Network Modules, and Neonatal Neurobehavior
Authors: Wang Yewei , Holstein Jacqueline , Hermetz Karen , Burt Amber , Lesseur Corina , Panuwet Parinya , Fiedler Nancy , Prapamontol Tippawan , Suttiwan Panrapee , Nimmapirat Pimjuta , Sittiwang Supattra , Naksen Warangkana , Yakimavets Volha , Barr Dana Boyd , Hao Ke , Chen Jia , Marsit Carmen J.
Published: May 2024

Prenatal pesticide exposure may adversely affect child neurodevelopment which may partly arise from impairing the placenta’s vital role in fetal development. In a cohort of pregnant farmworkers from Thailand (N=248), we examined the links between urinary metabolites of pyrethroid pesticides during pregnancy, placental gene expression networks derived from transcriptome sequencing, and newborn neurobehavior assessed using the NICU Network Neurobehavioral Scales (NNNS) at 5 weeks of age. Focusing on the 21 gene network modules in the placenta identified by Weighted Gene Co-expression Network Analysis (WGCNA), our analysis revealed significant associations between metabolites and nine distinct modules, and between thirteen modules and NNNS, with eight modules showing overlap. Notably, stress was negatively associated with the interferon alpha response and Myc target modules, and the interferon alpha response module was correlated positively with attention, and negatively with arousal, and quality of movement. The analysis also highlighted the early and late trimesters as critical periods for the influence of exposures on placental function, with pyrethroid metabolites measured early in pregnancy significantly negatively associated with the protein secretion module, and those measured later in pregnancy negatively associated with modules related to oxidative phosphorylation (OXPHOS) and DNA repair. Additionally, the cumulative sum of 3-phenoxybenzoic acid across pregnancy was significantly negatively associated with the OXPHOS module. These findings suggest that prenatal exposure to pyrethroid pesticides may influence neonatal neurobehavior through specific placental mechanisms that impact gene expression of metabolic pathway, and these effects may be pregnancy period specific. These results offer valuable insights for future risk assessment and intervention strategies.
Cohort Profile: Health and Attainment of Pupils in a Primary Education National-Cohort (HAPPEN) – A hybrid total population cohort in Wales, UK
Authors: Locke A , Jones H , James M , Marchant E , Kennedy J , Burdett D , Bandyopadhyay A , Stratton G , Brophy S
Published: May 2024

Purpose

HAPPEN is a primary school national cohort which brings together education, health and wellbeing research in line with the Curriculum for Wales framework for health and wellbeing. Health, education and social care data of primary school children are linked and held in the Secure Anonymised Information Linkage (SAIL) Databank. In addition, school-aged children can take part in the HAPPEN Survey throughout the academic year to inform design and implementation of the Health and Wellbeing curriculum area based on their pupils’ needs. There are over 600 schools registered to take part in the HAPPEN Survey. The linkage of health and education records from the HAPPEN national cohort with the HAPPEN Survey responses gives enriched cohort depth and detail which can be used to extrapolate to other schools in Wales. We present the descriptive data available in HAPPEN, and the future expansion plans.

Participants

The HAPPEN cohort includes 37,902 primary-aged school children from 2016-July 2023. Of this number, 28,019 can be linked in SAIL with their anonymised linkage field (ALF). In addition, to date (May 2024), HAPPEN Survey data has been captured from over 45,000 children which can in turn be linked to the electronic data. The survey is completed on an ongoing basis and continues to rise by 7000-8000 responses annually.

Findings to date

The child cohort is 49% girls, 47% boys (3% prefer not to state their gender and 1% of this data is missing) and 14% are from an ethnic minority background (10% prefer not to state their ethnicity). Initial findings have explored the impact of Covid-19 on wellbeing and play opportunities. As well as a longitudinal exploration of wellbeing throughout the years.

Future plans

HAPPEN is an ongoing dynamic cohort of data collection. Access to the cohort is available through SAIL or HDRUK gateway applications. Ongoing research includes the evaluation of interventions for primary school children such as natural experiment methods, non-means tested free school meal roll-out in Wales, interventions to improve physical literacy including changes to the built environment and interventions to improve health and wellbeing of primary school children.

STRENGTHS AND LIMITATIONS OF THIS STUDY

HAPPEN is a pan-Wales primary school cohort with a specific focus on children’s self-reported health and wellbeing.

The existence of this cohort and ongoing survey data enables the evaluation of natural experiments

This cohort facilitates life course research on the health and wellbeing of the children in Wales.

Missing data or errors in routine and administrative data may be a constraint when discussing population level outcomes for children.

A potential restriction of HAPPEN is the loss of data pertaining to individuals who relocate outside of Wales during childhood.
Effects of the COVID-19 pandemic on sympathectomies in Brazil’s public health system
Authors: Sorbello Carolina Carvalho Jansen , Portela Felipe Soares Oliveira , Girardi Giulia St. Sève , da Silva Marcelo Fiorelli Alexandrino , Teivelis Marcelo Passos , Wolosker Nelson
Published: May 2024

2.

Objective

To analyze and compare the number of sympathectomies for the treatment of hyperhidrosis in the public health system (SUS - Unified Health System) before, during, and after the peak of the COVID-19 pandemic in Brazil.

Method

A retrospective cross-sectional study, in accordance with the guidelines of the Research Ethics Committee, which analyzed the number of elective surgical procedures performed in SUS-Brazil, including the number of thoracic sympathectomies for the treatment of hyperhidrosis, in the 2 years prior to the COVID-19 pandemic (2018 and 2019) as well as in the 2 years of maximum prevalence (2020-2021) and in the 2 years following the peak of cases (2022-2023). The data analyzed was obtained from the database of the Department of Informatics of the Unified Health System (DATASUS).

Results

The number of thoracic sympathectomies performed in the SUS during the years 2020 and 2021 significantly decreased, probably secondary to the allocation of resources to the care of COVID-19 patients. This was followed by a lower than expected increase in the number of sympathectomies compared to pre-pandemic data.

Conclusion

The volume of sympathectomies, and consequently the surgical treatment of hyperhidrosis patients dependent on the SUS, have been extremely affected by the COVID-19 pandemic and remain in slow recovery, with no short-term prospect of returning to previous figures.
Deep Neural Network for Direct Prediction of Analytic Signals from Neural Oscillations
Authors: Onojima Takayuki , Imai Takashi
Published: May 2024

Objective: A method for real-time prediction of analytic signals is needed for state-informed stimulation in electroencephalography (EEG) experiments. The currently available methods lack sufficient prediction accuracy or have a complicated selection process of experimental parameters. Approach: The proposed method uses a deep neural network (DNN) to predict current and future EEG phases and amplitudes from raw EEG data for real-time signal processing. Main results: The proposed method predicted EEG phases and amplitudes more accurately than the conventional method based on an autoregressive model for actual EEG data. Furthermore, the DNN incorporates a missing signal imitation layer to make the model robust against missing data due to recording failures in EEG experiments. Significance: The DNN allows the current EEG phase to be estimated directly from the raw EEG data, which reduces the number of experimental parameters required. The end-to-end prediction framework can help simplify experimental operations and facilitate the implementation of the proposed method in various applications concerning the modulation of neural dynamics.
Deep Visual Proteomics advances human colon organoid models by revealing a switch to anin vivo-like phenotype upon xenotransplantation
Authors: Post Frederik , Hausmann Annika , Kabatnik Sonja , Steigerwald Sophia , Brand Alexandra , Clement Ditte L. , Skov Jonathan , Boye Theresa L. , Sato Toshiro , Steenholdt Casper , Mund Andreas , Nielsen Ole H. , Jensen Kim B. , Mann Matthias
Published: May 2024

Abstract

Intestinal epithelial damage predisposes to chronic disorders like inflammatory bowel disease. The organoid model allows cultivation, expansion and analysis of primary intestinal epithelial cells and has been instrumental in studying epithelial behavior in homeostasis and disease. Recent advances in organoid transplantation allow studying human epithelial cell behavior within the intestinal tissue context. However, it remained unclear how organoid transplantation into the colon affects epithelial phenotypes, which is key to assessing the model’s suitability to study human epithelial cells. We employed Deep Visual Proteomics, integrating AI-guided cell classification, laser microdissection, and an improved proteomics pipeline to study the human colon. This created an in-depth cell type-resolved proteomics resource of human intestinal epithelial cells within human tissue,in vitroorganoids, and the murine colon post-xenotransplantation. Our findings reveal thatin vitroconditions induce a proliferative organoid phenotype, which was reversible upon transplantation and adjustment of organoid culturing conditions.
Deep mutational scanning of a multi-domain signaling protein reveals mechanisms of regulation and pathogenicity
Authors: Jiang Ziyuan , van Vlimmeren Anne E. , Karandur Deepti , Semmelman Alyssa , Shah Neel H.
Published: May 2024

Multi-domain signaling enzymes are often regulated through extensive inter-domain interactions, and disruption of inter-domain interfaces by mutations can lead to aberrant signaling and diseases. For example, the tyrosine phosphatase SHP2 contains two phosphotyrosine recognition domains that auto-inhibit its catalytic domain. SHP2 is canonically activated by binding of these non-catalytic domains to phosphoproteins, which destabilizes the auto-inhibited state, but numerous mutations at the main auto-inhibitory interface have been shown to hyperactivate SHP2 in cancers and developmental disorders. Hundreds of clinically observed mutations in SHP2 have not been characterized, but their locations suggest alternative modes of dysregulation. We performed deep mutational scanning on full-length SHP2 and the isolated phosphatase domain to dissect mechanisms of SHP2 dysregulation. Our analysis revealed mechanistically diverse mutational effects and identified key intra- and inter-domain interactions that contribute to SHP2 activity, dynamics, and regulation. Our datasets also provide insights into the potential pathogenicity of previously uncharacterized clinical variants.
E. coliFtsN coordinates synthesis and degradation of septal peptidoglycan by partitioning between a synthesis track and a denuded glycan track
Authors: Lyu Zhixin , Yang Xinxing , Yahashiri Atsushi , Ha Stephen , McCausland Joshua W. , Chen Xinlei , Britton Brooke M. , Weiss David S. , Xiao Jie
Published: May 2024

TheE. colicell division protein FtsN was proposed to coordinate septal peptidoglycan (sPG) synthesis and degradation to ensure robust cell wall constriction without lethal lesions. Although the precise mechanism remains unclear, previous work highlights the importance of two FtsN domains: the E domain, which interacts with and activates the sPG synthesis complex FtsWIQLB, and the SPOR domain, which binds to denuded glycan (dnG) strands, key intermediates in sPG degradation. Here, we used single-molecule tracking of FtsN and FtsW (a proxy for the sPG synthesis complex FtsWIQLB) to investigate how FtsN coordinates the two opposing processes. We observed dynamic behaviors indicating that FtsN’s SPOR domain binds to dnGs cooperatively, which both sequesters the sPG synthesis complex on dnG (termed as the dnG-track) and protects dnGs from degradation by lytic transglycosylases (LTs). The release of the SPOR domain from dnGs leads to activating the sPG synthesis complex on the sPG-track and simultaneously exposing those same dnGs to degradation. Furthermore, FtsN’s SPOR domain self-interacts and facilitates the formation of a multimeric sPG synthesis complex on both tracks. The cooperative self-interaction of the SPOR domain creates a sensitive switch to regulate the partitioning of FtsN between the dnG- and sPG-tracks, thereby controlling the balance between sequestered and active populations of the sPG synthesis complex. As such, FtsN coordinates sPG synthesis and degradation in space and time.
Nonrelativistic trace anomaly and equation of state in dense fermionic matter
Authors: Tajima Hiroyuki , Iida Kei , Liang Haozhao
Published: May 2024

We investigate theoretically a nonrelativistic trace anomaly and its impact on the low-temperature equation of state in spatially one-dimensional three-component fermionic systems with a three-body interaction, which exhibit a nontrivial three-body crossover from a bound trimer gas to dense fermionic matter with increasing density. By applying the G-matrix approach to the three-body interaction, we obtain the analytical expression for the ground-state equation of state relevant to the high-density degenerate regime and thereby address how the three-body contact or, equivalently, the trace anomaly emerges. The analytical results are compared with the recent quantum Monte Carlo data. Our study of the trace anomaly and the sound speed could have some relevance to the physics of hadron-quark crossover in compact stars.

Published by the American Physical Society
2024
New signal of atmospheric tau neutrino appearance: Sub-GeV neutral-current interactions in JUNO
Authors: Meighen-Berger Stephan A. , Beacom John F. , Bell Nicole F. , Dolan Matthew J.
Published: May 2024

We propose the first practical method to detect atmospheric tau neutrino appearance at sub-GeV energies, which would be an important test of νμ→ντ oscillations and of new-physics scenarios. In the Jiangmen Underground Neutrino Observatory (JUNO; starts in 2024), active-flavor neutrinos eject neutrons from carbon via neutral-current quasielastic scattering. This produces a two-part signal: the prompt part is caused by the scattering of the neutron in the scintillator, and the delayed part by its radiative capture. Such events have been observed in KamLAND, but only in small numbers and were treated as a background. With νμ→ντ oscillations, JUNO should measure a clean sample of 55 events/yr; with simple νμ disappearance, this would instead be 41 events/yr, where the latter is determined from Super-Kamiokande charged-current measurements at similar neutrino energies. Implementing this method will require precise laboratory measurements of neutrino-nucleus cross sections or other developments. With those, JUNO will have 5σ sensitivity to tau-neutrino appearance in five years of exposure, and likely sooner.

Published by the American Physical Society
2024
The tin content of lead inclusions in ancient tin-bronze artifacts: a time-dependent process?
Authors: Artioli Gilberto , Fontanari Alessandro , Angelini Ivana , Lucarelli Chiara , Etter Martin , Jeppesen Henrik S. , Shilstein Sana , Shalev Sariel
Published: May 2024

In antiquity, Pb was a common element added in the production of large bronze artifacts, especially large statues, to impart fluidity to the casting process. As Pb does not form a solid solution with pure Cu or with the Sn–Cu alloy phases, it is normally observed in the metal matrix as globular droplets embedded within or in interstitial positions among the crystals of Sn-bronze (normally the α phase) as the last crystallizing phase during the cooling process of the Cu–Sn–Pb ternary melt. The disequilibrium Sn content of the Pb droplets has recently been suggested as a viable parameter to detect modern materials [Shilstein, Berner, Feldman, Shalev & Rosenberg (2019). STAR Sci. Tech. Archaeol. Res.
5, 29–35]. The application assumes a time-dependent process, with a timescale of hundreds of years, estimated on the basis of the diffusion coefficient of Sn in Pb over a length of a few micrometres [Oberschmidt, Kim & Gupta (1982). J. Appl. Phys.
53, 5672–5677]. Therefore, Pb inclusions in recent Sn-bronze artifacts are actually a metastable solid solution of Pb–Sn containing ∼3% atomic Sn. In contrast, in ancient artifacts, unmixing processes and diffusion of Sn from the micro- and nano-inclusions of Pb to the matrix occur, resulting in the Pb inclusions containing a substantially lower or negligible amount of Sn. The Sn content in the Pb inclusions relies on accurate measurement of the lattice parameter of the phase in the Pb–Sn solid solution, since for low Sn values it closely follows Vegard's law. Here, several new measurements on modern and ancient samples are presented and discussed in order to verify the applicability of the method to the detection of modern artwork pretending to be ancient.
China’s space sector, firm CSR and patent quality
Authors: Li Bin , Guo Fei , Xu Lei , McIver Ron , Cao Ruiqing
Published: May 2024

Purpose

This paper examines firm-level accountability and performance implications under a state-dominated institutional environment, China, for firms engaged in the space economy. Extant studies on the rapidly evolving civil space economy predominantly focus on developed Western economies at national or sector levels, frequently ignoring alternative institutional contexts. Additionally, limited attention has been given to firm-level empirical evidence and analysis, including corporate social responsibility (CSR) practice-R&D quality relationships in the space economy. The paper addresses each of these areas.

Design/methodology/approach

This paper utilises multiple regression, propensity score matching and split sampling methods applied to a proprietary dataset of Shanghai and Shenzhen Stock Exchange-listed A-share firms. Results are robust to endogeneity issues, alternative measurement of dependent variables and sampling.

Findings

China’s space firms demonstrate superior CSR performance to their counterparts in other sectors, supporting CSR‘s role in maintaining legitimacy. Their CSR practices also positively contribute to firm patent quality. The link is more pronounced among firms facing higher economic policy uncertainty and for state-owned enterprises (SOEs). The latter is due to SOEs’ government support, advantages in financing and attracting and retaining a high-quality workforce.

Originality/value

This paper adds to discussion on major space power’s, by examining China’s state-dominated civil space sector. It also addresses a lack of empirical firm-level evidence on space firm behaviour by examining the impact of firm-level CSR practices on R&D quality outcomes, areas in which there is a limited literature.
An in-depth analysis of undergraduate students experiences in the transition from F2F learning to online learning
Authors: Saikia Sunita , Sultana Yeasmin , Law Mei Yuan
Published: May 2024

Purpose

This research aimed to capture undergraduate students' experiences in the transition from face-to-face (F2F) learning to online learning. This study explored their perceptions regarding the effectiveness of online learning in their academic lives, challenges encountered and suggestions for enhancing online learning in the post-COVID-19 era.

Design/methodology/approach

This study employed a concurrent mixed-methods research design and selected 118 undergraduate students using a multistage random sampling technique from four colleges in Assam. Standardized questionnaires and open-ended interview schedules were used.

Findings

Undergraduate students reported a positive attitude and satisfaction with online learning, valuing its adaptability to their schedules, its role as a motivating factor for self-learning, its effect on making them more technically proficient and enhancing their communication skills to articulate their thoughts. However, the challenges identified by the students have the potential to overshadow the promises of online learning. This research provided more constructive suggestions under the themes of “content delivery”, “systemic and infrastructural issues”, “pedagogy” and “capacity building” to enhance their experiences with online learning.

Practical implications

Our research findings would assist educational institutions in adopting innovative approaches for simpler and more efficient online learning experiences post-COVID-19 pandemic. Institutions should prepare themselves and design dual-mode courses for F2F and online learning.

Originality/value

The paper addressed a relevant topic in this era of online learning by examining undergraduate students’ viewpoints that added complementary information to the current body of literature on online learning in rural India. The insights gleaned from their experiences would be beneficial for the development of best practices for online learning in the coming decades.