bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNAs and PFAS: A Pilot Study in Blood Collected from Firefighters
Authors: Zhang Xing , Sands Mia , La Frano Michael , Spinella Michael J. , Masoud Farzaneh , Fields Christopher , Madak-Erdogan Zeynep , Jensen Tor , Irudayaraj Joseph 
Published: April 2024

ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are chemicals with widespread industrial and consumer applications, and firefighters are known to be at risk of elevated PFAS exposure due to their occupational activities. This study aims to assess PFAS exposure and explore potential mechanistic insights through miRNA sequencing of plasma exosomes, in relation to PFAS levels in the general population. The study included 34 firefighter participants. PFAS levels in plasma were analyzed, and miRNA sequencing of plasma exosomes was conducted. The findings were compared with the general population data from the National Health and Nutrition Examination Survey (NHANES). While total PFAS levels did not significantly differ between firefighters and the general population in the cohort considered, variations in individual PFAS compounds were observed. MiRNA sequencing revealed substantial heterogeneity in miRNA expression patterns. Associations between serum PFAS levels and biochemical indicators suggested potential health implications, although further mechanistic insights need to be explored.
Interpreting single-cell and spatial omics data using deep networks training dynamics
Authors: Karin Jonathan , Mintz Reshef , Raveh Barak , Nitzan Mor 
Published: April 2024

AbstractSingle-cell and spatial genomics datasets can be organized and interpreted by annotating single cells to distinct types, states, locations, or phenotypes. However, cell annotations are inherently ambiguous, as discrete labels with subjective interpretations are assigned to heterogeneous cell populations based on noisy, sparse, and high-dimensional data. Here, we show that incongruencies between cells and their input annotations can be identified by analyzing a rich but overlooked source of information: the difficulty of training a deep neural network to assign each cell to its input annotation, or annotation trainability. Furthermore, we demonstrate that annotation trainability encodes meaningful biological signals. Based on this observation, we introduce the concept of signal-aware graph embedding, which facilitates downstream analysis of diverse biological signals in single-cell and spatial omics data, such as the identification of cellular communities corresponding to a target signal. We developed Annotatability, a publicly-available implementation of annotation-trainability analysis. We address key challenges in the interpretation of genomic data, demonstrated over seven single-cell RNA-sequencing and spatial omics datasets, including auditing and rectifying erroneous cell annotations, identifying intermediate cell states, delineating complex temporal trajectories along development, characterizing cell diversity in diseased tissue, identifying disease-related genes, assessing treatment effectiveness, and identifying rare healthy-like cell populations. These results underscore the broad applicability of annotation-trainability analysis via Annotatability for unraveling cellular diversity and interpreting collective cell behaviors in health and disease.
Nucleosome wrapping energy in CpG islands and the role of epigenetic base modifications
Authors: Giniūnaitė Rasa , Sharma Rahul , Maddocks John H. , Kriaučionis Skirmantas , Petkevičiūtė-Gerlach Daiva 
Published: April 2024

AbstractThe majority of vertebrate promoters have a distinct DNA composition, known as a CpG island. Cytosine methylation in promoter CpG islands is associated with a substantial reduction of transcription initiation. We hypothesise that both atypical sequence composition, and epigenetic base modifications may affect the mechanical properties of DNA in CpG islands, influencing the ability of proteins to bind and initiate transcription. In this work, we model two scalar measures of the sequence-dependent propensity of DNA to wrap into nucleosomes: the energy of DNA required to assume a particular nucleosomal configuration and a measure related to the probability of linear DNA spontaneously reaching the nucleosomal configuration. We find that CpG density and modification state can alter DNA mechanics by creating states more or less compatible with nucleosome formation.
Neuropeptide Bursicon and its receptor mediated the transition from summer-form to winter-form ofCacopsylla chinensis
Authors: Zhang Zhixian , Li Jianying , Wang Yilin , Li Zhen , Liu Xiaoxia , Zhang Songdou 
Published: April 2024

AbstractSeasonal polyphenism enables organisms to adapt to environmental challenges by increasing phenotypic diversity.Cacopsylla chinensisexhibits remarkable seasonal polyphenism, specifically in the form of summer-form and winter-form, which have distinct morphological phenotypes. Previous research has shown that low temperature and the temperature receptorCcTRPMregulate the transition from summer-form to winter-form inC. chinensisby impacting cuticle content and thickness. However, the underling neuroendocrine regulatory mechanism remains largely unknown. Bursicon, also known as the tanning hormone, is responsible for the hardening and darkening of the insect cuticle. In this study, we report for the first time on the novel function of Bursicon and its receptor in the transition from summer-form to winter-form inC. chinensis. Firstly, we identifiedCcBurs-α andCcBurs-β as two typical subunits of Bursicon inC. chinensis, which were regulated by low temperature (10°C) andCcTRPM. Subsequently,CcBurs-α andCcBurs-β formed a heterodimer that mediated the transition from summer-form to winter-form by influencing the cuticle chitin contents and cuticle thickness. Furthermore, we demonstrated thatCcBurs-Racts as the Bursicon receptor and plays a critical role in the up-stream signaling of the chitin biosyntheis pathway, regulating the transition from summer-form to winter-form. Finally, we discovered that miR-6012 directly targetsCcBurs-R, contributing to the regulation of Bursicon signaling in the seasonal polyphenism ofC. chinensis. In summary, these findings reveal the novel function of neuroendocrine regulatory mechanism underlying seasonal polyphenism and provide critical insights into insect Bursicon and its receptor.
Tradeoffs in ATP metabolisms via hypoxic gradient migration assays
Authors: Orabi Mohamad , Duan Kai , Zhou Mengyang , Lo Joe F. 
Published: April 2024

AbstractMigration and scratch assays are helpful tools to investigate wound healing and tissue regeneration processes, especially under disease conditions such as diabetes. However, traditional migration (injury-free) assays and scratch (with injury) assays are limited in their control over cellular environments and provide only simplified read-outs of their results. On the other hand, microfluidic-based cell assays offer a distinct advantage in their integration and scalability for multiple modalities and concentrations in a single device. Additionally,in situstimulation and detection helps to avoid variabilities between individual bioassays. To realize an enhanced, smarter migration assay, we leveraged our multilayered oxygen gradient (1-16%) to study HaCaT migrations in diabetic conditions with spatial and metabolic read-outs. An analysis of the spatial migration over time observed a new dynamic between hypoxia (at 4.16-9.14% O2) and hyperglycemia. Furthermore,in situadenosine triphosphate (ATP) and reactive oxygen species (ROS) responses suggest that this dynamic represents a switch between stationary versus motile modes of metabolism. Thus, elevated glucose and hypoxia are synergistic triggers of this switch under disease conditions. These findings illustrate the benefits of spatial microfluidics for modeling complex diseases such as hypoxia and diabetes, where multimodal measurements provide a more deterministic view of the underlying processes.
CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation
Authors: Wardell Christine M. , Fung Vivian C.W. , Chen Eleanor , Haque Manjurul , Gillies Jana , Spanier Justin A. , Mojibian Majid , Fife Brian T. , Levings Megan K. 
Published: April 2024

AbstractRegulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2+islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2.5) T cells. In mice transplanted with HLA-A2+islets, A2-CAR Tregs reduced BDC2.5 T cell engraftment, proliferation and cytokine production, and protected mice from diabetes. Tolerance to islets was systemic, including protection of the HLA-A2negativeendogenous pancreas. In tolerant mice, a significant proportion of BDC2.5 T cells gained FOXP3 expression suggesting that long-term tolerance is maintained byde novoTreg generation. Thus, A2-CAR Tregs mediate linked suppression and infectious tolerance and have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation.One Sentence SummaryAlloreactive chimeric antigen receptor-engineered regulatory T cells limit diabetogenic T cell engraftment and function to prevent type 1 diabetes.
Life Histories and Study Duration matter less than Prior Knowledge of Vital Rates to Inverse Integral Projection Models
Authors: Bernard Connor D. , Bonsall Michael B. , Salguero-Gómez Roberto 
Published: April 2024

ABSTRACTEcology has been surprisingly slow to address the uncertainty and bias that results from using short-term time series to draw long-term inference. To improve our understanding of assumptions around the temporal structure of vital rates (e.g., survival, reproduction), we need tools that are feasible and capture longer-term, state-structured population dynamics.Here, we use inverse modelling of a set of integral projection models (IPMs) to show how demographic rates can be accurately reconstructed from state-structure fluctuations in a population time-series. We use a particle-filtering optimisation algorithm to fit vital rates from time-series of varying length, parameter combinations, priors, and life histories.We show how key life history traits such as generation time have little effect on the ability of our approach to accurately identify vital rates using state structure over time. Further, contrary to our expectations, the duration of our time-series data has relatively modest impact on the estimation of vital rates compared to the critical role of prior knowledge on vital rates.ur framework to estimate IPM vital rates highlights the potential of inverse models to extend time-series for demographic models, but also demonstrates that long-term time-series are not a perfect surrogate for detailed demographic inference. We discuss the need for more work exploring the conditions when inverse modelling is an adequate tool based on species traits.
Diet and Size-at-Birth Affect Larval Rockfish Condition and Survival
Authors: Walsh Kamran A. , Thompson Andrew R. , Kwan Garfield T. , Semmens Brice X. , Fennie H. William , Swalethorp Rasmus 
Published: April 2024

ABSTRACTFeeding success and maternal effects on larval size have long been hypothesized as important contributors to interannual recruitment variability in marine fishes. This study examined the feeding ecology and influences of diet and size-at-birth on length and growth of larval rockfishes (Sebastesspp.). Prey carbon biomass and selection were calculated from gut contents, size-at-birth was estimated using otolith core size, and recent growth was derived from outer otolith increment widths. Biomass contributions of preferred prey and otolith data were integrated into Bayesian hierarchical models predicting length and growth. Larvae primarily fed on and selected for copepod nauplii and Calanoid copepodites, modulating feeding with ontogeny and in response to prey availability. Based on carbon weight, the relative contribution of Calanoid copepodites to the diet was more strongly and positively correlated with length and growth than that of nauplii. Younger larvae experienced faster growth in association with Calanoid copepodite consumption than older larvae. Positive effects of core radius suggest that initial larval size, believed to be mediated by maternal provisioning, increases the likelihood of survival, larger size and faster growth. These findings ultimately provide evidence that selective feeding and size-at-birth mediate rockfish survival in early life stages.
Exploring new nanopore sensors from the aerolysin family
Authors: Cirauqui Nuria , Bada Juarez Juan F. , Meireles Fernando Augusto T. P. , Barry Julian , Bokori-Brown Monika , Marcaida Maria J. , Cao Chan , Dal Peraro Matteo 
Published: April 2024

AbstractAerolysin-like proteins are a family of β-pore-forming toxins which are widely present in all kingdoms of life. Recently, this family of proteins is gaining attention because of their biotechnological application as nanopore sensors for sensing and sequencing of biomolecules. Here, we explore the possibilities of using the knowledge of the sequence and structure of proteins to screen and explore new potential nanopore candidates. However, in spite of the conserved structural fold, the sequence identity in this family is very low. This complicates their sequence alignment, hindering the understanding of their pore structure and properties, therefore limiting further biotechnological applications. In an attempt to further understand the properties of aerolysin-like pores, we analyzed the pore structure of three family members,Clostridium perfringensepsilon toxin (ETX),Laetiporus sulphureuslectin (LSL) andBacillus thuringiensisparasporin-2, comparing it to aerolysin. Their structure and sensing capabilities for ssDNA were first assessed byin silicomethods. Moreover, ETX was characterized experimentally in planar lipid membranes for the detection of biomolecules. We found that ETX can form three distinct pore conformations, each presenting a specific open pore current, and only one of them being able to translocate ssDNA. When the ssDNA translocate through ETX, the depth of current blockage is higher compared to aerolysin which indicates a higher sensitivity for molecular sensing. Our findings open a new venue for improving and diversifying nanopore capabilities for molecular sensing.
Gossamer: Scaling Image Processing and Reconstruction to Whole Brains
Authors: Marrett Karl , Moradi Keivan , Park Chris Sin , Yan Ming , Choi Chris , Zhu Muye , Akram Masood , Nanda Sumit , Xue Qing , Mun Hyun-Seung , Gutierrez Adriana E. , Rudd Mitchell , Zingg Brian , Magat Gabrielle , Wijaya Kathleen , Dong Hongwei , Yang X. William , Cong Jason 
Published: April 2024

AbstractNeuronal reconstruction–a process that transforms image volumes into 3D geometries and skeletons of cells– bottlenecks the study of brain function, connectomics and pathology. Domain scientists needexactandcompletesegmentations to study subtle topological differences. Existing methods are diskbound, dense-access, coupled, single-threaded, algorithmically unscalable and require manual cropping of small windows and proofreading of skeletons due to low topological accuracy. Designing a data-intensive parallel solution suited to a neurons’ shape, topology and far-ranging connectivity is particularly challenging due to I/O and load-balance, yet by abstracting these vision tasks into strategically ordered specializations of search, we progressively lower memory by 4 orders of magnitude. This enables 1 mouse brain to be fully processed in-memory on a single server, at 67× the scale with 870× less memory while having 78% higher automated yield than APP2, the previous state of the art in performant reconstruction.
Research Transparency in 59 Disciplines of Clinical Medicine: A Meta-Research Study
Authors: Sofi-Mahmudi Ahmad , Raittio Eero , Uribe Sergio E. , Khademioore Sahar , Zeraatkar Dena , Mbuagbaw Lawrence , Bouter Lex M. , Robinson Karen A. 
Published: April 2024

AbstractBackgroundTransparency in health research is crucial as it allows for the scrutiny and replication of findings, fosters confidence in scientific outcomes, and ultimately contributes to the advancement of knowledge and the betterment of society.AimWe aimed to assess five transparency practices in scientific publications (data availability, code availability, protocol registration, conflicts of interest (COI) and funding disclosures) from open-access articles published in medical journals.MethodsWe searched and exported all open-access articles from Science Citation Index Expanded (SCIE)-indexed journals through the Europe PubMed Central database published until March 16, 2024. Basic journal- and article-related information was retrieved from the database. We then assessed five transparency practices in the articles using thertransparentpackage in R.ResultsThe analysis included 2,002,955 open-access articles from SCIE-indexed medical journals (open-access percentage=59.0%). Of these, 87.5% (95% CI: 87.4%-87.5%) disclosed COI and 80.1% (95% CI: 80.0%-80.1%) disclosed funding. Protocol registration was declared in 6.6% (95% CI: 6.6%-6.6%), data sharing in 7.6% (95% CI: 7.6%-7.6%), and code sharing in 1.4% (95% CI: 1.4%-1.4%) of the articles. More than 76.0% declared at least two transparency practices, while all five practices were declared in less than 0.02%. The data showed an increasing trend in all transparency practices since the late 2000s. Articles published in journals with higher impact factors and articles receiving more citations had increased odds of COI and funding disclosures, as well as data and code sharing. There were notable differences in transparency practices across the disciplines.ConclusionWhile most articles had COI and funding disclosures, adherence to other transparency practices was grossly insufficient. To increase protocol registration, data, and code sharing, much stronger incentives and mandates are needed from all stakeholders.
GENDER NORMS AND ATTITUDE TOWARDS ABORTION AMONG VERY YOUNG ADOLESCENTS IN KENYA AND NIGERIA
Authors: Alabi Matthew Ayodele , Bello Bamidele M. , Maina Beatrice W. 
Published: April 2024

AbstractIntroductionUnsafe abortion is a major cause of death in sub-Saharan African countries with very young adolescents (VYAs) at increased risk due to their high vulnerability to unprotected sex and unplanned pregnancies. Abortion beliefs and attitudes are considered to be partly rooted in traditional views on gender and religious influences. This study is informed by the limited data on gender norm perception and its association with abortion among VYAs despite the increasing prevalence of unsafe abortion reported among this group.MaterialsData for this study was collected as part of a longitudinal survey on the gendered socialization and sexual and reproductive health of very young, in-school adolescents aged 10-14 years in Kenya and Nigeria. The study obtained quantitative data from 1,912 VYAs using a structured questionnaire. The results presented in this paper are from the quantitative baseline data collected in Kenya and NigeriaResultThe study found significant regional differentials in attitudes toward abortion and gender norm perception of the VYAs from the two regions. VYAs from Nigeria were more likely to endorse abortion practices relative to their counterparts from Kenya. Factors associated with endorsement of abortion practice were gender norms about Sexual Double Standards (SDS) and Normative Heterosexual Relation (NHR) in Nigeria and knowledge of where to get a condom, NHR, and Normative Romantic Relationship (NRR) in Kenya.ConclusionIntervention efforts seeking to promote positive gender norms and attitudes towards SRH must begin with the VYAs and must consider regional variations and address knowledge and access to SRH commodities.What is already known on this topicprevious studies have explored attitudes towards gender norms and abortion among young people and adults, with little known among very young adolescents aged 10-14 years.What this study addsthe study contributed to the limited research on gender norms and attitudes towards abortion among very young adolescents.How this study might affect research, practice, and policyThe outcome of this suggests the need to consider regional variations when developing interventions and policies addressing gender norms and attitudes towards abortion in Africa.
Evidence of aberrant anti-Epstein-Barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue
Authors: Mouat Isobel C. , Zhu Judy , Aslan Alperen , McColl Barry W. , Allan Stuart M. , Smith Craig J. , Buckwalter Marion S. , McCulloch Laura 
Published: April 2024

AbstractBACKGROUNDFatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.AIMSWe performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.METHODSIn a chronic ischemic stroke cohort (>6 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F <40) and low fatigue (FACIT-F >41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data.RESULTSWe observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar between the groups, we observed an altered antibody response against EBV antigens in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (VCA; 2.244 ± 0.926 vs 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to EBV (3.23 × 105± 4.44 × 104high fatigue versus 4.60 × 105± 9.28 × 104low fatigue; P= 0.288).CONCLUSIONSThese findings indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke and warrants further investigation.