bluuebunny/crossref_metadata_2025_split huggingface dataset:
High fidelity genetic markers for sexingCannabis sativaseedlings
Authors: Prentout Djivan , El Aoudati Salma , Mathis Fabienne , Marais Gabriel AB , Henri Hélène 
Published: September 2024

AbstractThe uses ofCannabis sativa, a dioecious species with an XY sex chromosome system, are varying from fiber and oil to cannabinoids, among others. In most cases, males are undesirable and the sexual dimorphism at immature plants is too subtle for reliable phenotypic sexing, making genetic approaches promising. In this technical note, we present a multiplex PCR-mix, that includes two markers of Y-specific coding regions and one autosomal control marker. This PCR-mix, tested across 12 hemp-type cultivars, encompassing approximately 200 individuals, achieved a 99.5% success rate in identifying the sex ofC. sativaseedlings.
Pushing the limits of single molecule transcript sequencing to uncover the largest disease-associated transcript isoforms in the human neural retina
Authors: Stemerdink Merel , Riepe Tabea , Zomer Nick , Salz Renee , Kwint Michael , Timmermans Raoul , Ferrari Barbara , Ferrari Stefano , Dueñas Rey Alfredo , Delanote Emma , de Bruijn Suzanne E. , Kremer Hannie , Roosing Susanne , Coppieters Frauke , Hoischen Alexander , Cremers Frans P. M. , ’t Hoen Peter A.C. , van Wijk Erwin , de Vrieze Erik 
Published: September 2024

ABSTRACTSequencing technologies have long limited the comprehensive investigation of large transcripts associated with inherited retinal diseases (IRDs) like Usher syndrome, which involves 11 associated genes with transcripts up to 19.6 kb. To address this, we used PacBio long-read mRNA isoform sequencing (Iso-Seq) following standard library preparation and an optimized workflow to enrich for long transcripts in the human neural retina. While our workflow achieved sequencing of transcripts up to 15 kb, this was insufficient for Usher syndrome-associated genesUSH2AandADGRV1, with transcripts of 18.9 kb and 19.6 kb, respectively. To overcome this, we employed the Samplix Xdrop System for indirect target enrichment of cDNA, a technique typically used for genomic DNA capture. This method facilitated the successful capture and sequencing ofADGRV1transcripts as well as the full-length 18.9 kbUSH2Atranscripts. By combining algorithmic analysis with detailed manual curation of sequenced reads, we identified novel isoforms and alternative splicing events across the 11 Usher syndrome-associated genes, with implications for diagnostics and therapy development. Our findings demonstrate the Xdrop system’s adaptability for cDNA capture and the advantages of integrating computational and manual transcript analyses. The full neural retina sequencing dataset is available via EGA under identifier EGAD50000000720.
Validity of a New Stress Induction Protocol using Speech Improvisation (IMPRO)
Authors: Saskovets Marina , Lohachov Mykhailo , Liang Zilu , Piumarta Ian 
Published: September 2024

AbstractThis paper proposes a novel stress induction protocol utilizing speech improvisation — Interactive Multitask Performance Response Observation (IMPRO) — in front of an audience. This approach aims to induce stress through a combination of public speaking, cognitive effort, and challenge to maintain a spontaneous narrative. We investigate the validity of this novel approach by examining physiological responses of 35 healthy participants aged 18 to 38. Saliva cortisol was measured as the ground truth for mental stress assessment. In addition, electrodermal activity (EDA) was used as a non-invasive measure of sympathetic activation, offering real-time data with high resolution. Functional near-infrared spectroscopy (fNIRS) measurement was performed to assess the cortical hemodynamic responses induced by the IMPRO protocol. We focused on hemodynamics in the prefrontal cortex (PFC), a region associated with stress processing. We found that cortisol levels and EDA significantly increased in response to the stress task compared to the baseline. We also observed a significant change in PFC hemodynamic levels in a set of channels compared to the baseline, with a higher overall increase in the right frontopolar area compared to the left. In conclusion, our findings validated IMPRO as an effective and easy to perform method for mental stress induction.
SCAMPI: A scalable statistical framework for genome-wide interaction testing harnessing cross-trait correlations
Authors: Bian Shijia , Bass Andrew J. , Liu Yue , Wingo Aliza P. , Wingo Thomas , Cutler David J. , Epstein Michael P. 
Published: September 2024

AbstractFamily-based heritability estimates of complex traits are often considerably larger than their single-nucleotide polymorphism (SNP) heritability estimates. This discrepancy may be due to non-additive effects of genetic variation, including variation that interacts with other genes or environmental factors to influence the trait. Variance-based procedures provide a computationally efficient strategy to screen for SNPs with potential interaction effects without requiring the specification of the interacting variable. While valuable, such variance-based tests consider only a single trait and ignore likely pleiotropy among related traits that, if present, could improve power to detect such interaction effects. To fill this gap, we propose SCAMPI (Scalable Cauchy Aggregate test using Multiple Phenotypes to test Interactions), which screens for variants with interaction effects across multiple traits. SCAMPI is motivated by the observation that SNPs with pleiotropic interaction effects induce genotypic differences in the patterns of correlation among traits. By studying such patterns across genotype categories among multiple traits, we show that SCAMPI has improved performance over traditional univariate variance-based methods. Like those traditional variance-based tests, SCAMPI permits the screening of interaction effects without requiring the specification of the interaction variable and is further computationally scalable to biobank data. We employed SCAMPI to screen for interacting SNPs associated with four lipid-related traits in the UK Biobank and identified multiple gene regions missed by existing univariate variance-based tests. SCAMPI is implemented in software for public use.
Subcellular Level Spatial Transcriptomics with PHOTON
Authors: Rajachandran Shreya , Xu Qianlan , Cao Qiqi , Zhang Xin , Chen Fei , Mangiameli Sarah M. , Chen Haiqi 
Published: September 2024

AbstractThe subcellular localization of RNA is closely linked to its function. Many RNA species are partitioned into organelles and other subcellular compartments for storage, processing, translation, or degradation. Thus, capturing the subcellular spatial distribution of RNA would directly contribute to the understanding of RNA functions and regulation. Here, we present PHOTON (Photoselection of Transcriptome over Nanoscale), a method which combines high resolution imaging with high throughput sequencing to achieve spatial transcriptome profiling at subcellular resolution. We demonstrate PHOTON as a versatile tool to accurately capture the transcriptome of target cell typesin situat the tissue level such as granulosa cells in the ovary, as well as RNA content within subcellular compartments such as the nucleolus and the stress granule. Using PHOTON, we also reveal the functional role of m6A modification on mRNA partitioning into stress granules. These results collectively demonstrate that PHOTON is a flexible and generalizable platform for understanding subcellular molecular dynamics through the transcriptomic lens.
On the design and stability of cancer adaptive therapy cycles: deterministic and stochastic models
Authors: Vilela Yuri G. , Fassoni Artur C. , Neves Armando G. M. 
Published: September 2024

AbstractAdaptive therapy is a promising paradigm for treating cancers, that exploits competitive interactions between drug-sensitive and drug-resistant cells, thereby avoiding or delaying treatment failure due to evolution of drug resistance within the tumor. Previous studies have shown the mathematical possibility of building cyclic schemes of drug administration which restore tumor composition to its exact initial value in deterministic models. However, algorithms for cycle design, the conditions on which such algorithms are certain to work, as well as conditions for cycle stability remain elusive. Here, we state biologically motivated hypotheses that guarantee existence of such cycles in two deterministic classes of mathematical models already considered in the literature: Lotka-Volterra and adjusted replicator dynamics. We stress that not only existence of cyclic schemes, but also stability of such cycles is a relevant feature for applications in real clinical scenarios. We also analyze stochastic versions of the above deterministic models, a necessary step if we want to take into account that real tumors are composed by a finite population of cells subject to randomness, a relevant feature in the context of low tumor burden. We argue that the stability of the deterministic cycles is also relevant for the stochastic version of the models. In fact, Dua, Ma and Newton [Cancers (2021)] and Park and Newton [Phys. Rev. E (2023)] observed breakdown of deterministic cycles in a stochastic model (Moran process) for a tumor. Our findings indicate that the breakdown phenomenon is not due to stochasticity itself, but to the deterministic instability inherent in the cycles of the referenced papers. We then illustrate how stable deterministic cycles avoid for very large times the breakdown of cyclic treatments in stochastic tumor models.
Randomly oriented microgrooved hydrogel guides cellular motility, modulates speed, and governs directionality of cellular spread
Authors: Ghosh Biswajoy , Agarwal Krishna 
Published: September 2024

ABSTRACTCell migration is a fundamental biological process, yet the mechanisms underlying how cells sense and navigate complex environments remain poorly understood. In this study, we developed a system of randomly oriented microgrooves, designed at cellular length scales, to explore motility intelligence in response to varied topographies. These microgrooves allowed cells to freely choose their migratory paths, revealing key insights into how cells sense and adapt to topological cues. Using fibroblast cells migrating over these grooved substrates, we examined cellular processes such as actin cytoskeleton remodeling, cell adhesion dynamics, and the impact of groove alignment on migration speed and directionality. Our results demonstrate that cells align their cytoskeletal structures to groove geometries, forming actin-rich anchors that enhance migration in groove-aligned environments. Cells migrating in grooves aligned with their intrinsic polarity exhibited faster, more directed migration compared to those in misaligned or control conditions. This work advances our understanding of cell-topology interaction and provides new perspectives for tissue engineering applications in cancer therapy and wound healing.
Distinct Stromal Cell Populations Define the B-cell Acute Lymphoblastic Leukemia Microenvironment
Authors: Blanco Mauricio N. Ferrao , Kazybay Bexultan , Belderbos Mirjam , Heidenreich Olaf , Vormoor Hermann Josef 
Published: September 2024

AbstractThe bone marrow microenvironment is critical for B-cell acute lymphoblastic leukemia (B-ALL) but its cellular heterogeneity remains poorly defined. Here, we employed single-cell RNA sequencing to comprehensively characterize the stromal and hematopoietic niches in pediatric B-ALL. Our analysis revealed two distinct mesenchymal stromal cell (MSC) populations as primary leukemia-supportive niches: early mesenchymal progenitors and adipogenic progenitors. Single-cell transcriptomic analysis infers that ALL blasts use distinct cell-cell interactions to communicate with the different stromal populations. Purified adipogenic progenitors from the bone of children with ALL support survival of the leukemic blastsex vivoand their signature is enriched in relapse samples. Our data establish adipogenic progenitors as a distinct and novel component of the ALL niche.
In silicostudy of selected alkaloids as dual inhibitors of β and γ-Secretases for Alzheimer’s disease
Authors: Onifade Isreal Ayobami , Umar Haruna Isiyaku , Aborode Abdullahi Tunde , Awaji Aeshah A. , Jegede Ifeoluwapo Deborah , Adeleye Bunmi Helen , Fatoba Dorcas Oladayo 
Published: September 2024

AbstractAlzheimer’s disease (AD) has become ubiquitous as the number of elderly individuals increases and has been conceived as a socioeconomic problem lately. To date, no success is recorded for disease-modifying therapies for AD but only drugs for symptomatic relief exist. Research has been centered on the role of β-amyloid on the pathogenesis of AD, which has led to the development of drugs that target Aβ (β and γ-Secretase inhibitors) to reduce the amount of Aβ formed. However, the existing β and γ-Secretase inhibitors were associated with harmful side effects, low efficacy, and inability to cross the blood-brain barrier. Thus, in this current study, 54 alkaloids from the PhytoHub server (phytohub.eu), and two approved drugs were docked against β-Secretases. Additionally, galantamine and 5 alkaloids with the utmost binding potential with β-secretase were subjected to pharmacokinetics evaluation and docked against γ-secretase. . From our result, 5 compounds displayed for both docking periods, with demissidine, solasodine, tomatidine, and solanidine having better BE than the control drugs. Based on the Pharmacokinetics evaluation, 4 compounds possessed good pharmacokinetic evaluation and biological activities than galantamine. This study suggests that demissidine, solasodine, tomatidine, and solanidine are promising dual inhibitors against β and γ-Secretase proteinsin silico. However, there is an urgent need to carry out in vitro and in vivo experiments on these new leads to validate the findings of this study.
Islet amyloid disrupts MHC Class II antigen presentation and protects NOD mice from autoimmune diabetes
Authors: Denroche Heather C , Ng Tori , Velghe Jane , Suen Imelda , Stanley Liam , Nackiewicz Dominika , Komba Mitsu , Chen Sam , Soukhatcheva Galina , Dai Lei , Verchere C. Bruce 
Published: September 2024

AbstractIslet amyloid contributes to beta cell failure in type 2 diabetes through several mechanisms, one being the potent induction of local islet inflammation through activating inflammatory pathways in islet macrophages. We performed an unbiased phenotypic investigation of islet macrophages in the early stage of islet amyloid formation using single cell RNA sequencing of resident islet macrophages in mice with and without the amyloidogenic form of human islet amyloid polypeptide (hIAPP). This revealed that MHC Class II antigen presentation genes were strongly down-regulated in islet macrophages during islet amyloid formation. As islet amyloid has recently been reported in pancreases of people with type 1 diabetes, we sought to investigate the impact of islet amyloid in the NOD mouse model of type 1 diabetes. Both overexpression and physiological expression of hIAPP delayed diabetes in NOD mice relative to littermate controls, corresponding with decreased markers of antigen presentation and activation, as well as decreased immune cell infiltration in islets. Adoptive transfer studies showed that systemic autoimmune function remained intact and beta cells from hIAPP transgenic mice did not evade immune recognition by diabetogenic T cells, collectively indicating the protection from diabetes was mediated by localized disruption of antigen presentation in the pancreas. Consistent with this, incubation of dendritic cells with IAPP aggregates decreased MHC Class II surface expression and diminished antigen-specific T cell activation in vitro, through a phagocytosis-dependent mechanism.Collectively our data show that despite the well-established pro-inflammatory response of macrophages to IAPP aggregates, the uptake of IAPP aggregates during early amyloid formation also disrupts MHC Class II antigen presentation and slows beta cell autoimmunity.
Protocol for the Work And Vocational advicE (WAVE) randomised controlled trial testing the addition of vocational advice to usual primary care (Clinical Trials: NCT04543097)
Authors: Wynne-Jones G , Lewis M , Sowden G , Madan I , Walker-Bone K , Chew-Graham CA , Bromley K , Jowett S , Parsons V , Mansell G , Cooke K , Lawton SA , Saunders B , Pemberton J , Cooper C , Foster NE 
Published: September 2024

AbstractObjectivesTo investigate the effectiveness of adding a brief vocational advice intervention to usual care in reducing the number of days absent from work over a period of 6 months in adults given a fit note by their general practice.DesignMulticentre, pragmatic, two parallel-arm, randomised controlled trial with health economic analyses and nested qualitative study. A computer-generated stratified block randomisation (ratio 1:1) was used to allocate arms.SettingParticipants will be recruited from general practices in the UK.Participants720 adults consulting in general practice, for any health condition, and receiving a fit note who have been absent from work for more than two-weeks but less than six months.InterventionsParticipants in the intervention arm will be offered usual care and vocational advice delivered by a Vocational Support Worker (VSW) remotely via phone or videoconferencing. Participants in the control arm will be offered usual care.Main outcome measureNumber of days off work over 6 months. Follow-up data collection is via questionnaires at 6 weeks and 6 months.ConclusionsThis paper presents the rationale, design and methods of the Work And Vocational advicE (WAVE) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for patients with work absence.Trial registration:Clinical Trials:NCT04543097Protocol number: Version 5.1
Assessing the Impact of COVID-19 on Multimorbidity: Insights from Structural Equation Modeling in Colombia
Authors: Porras-Ramírez A , Rico-Mendoza A , Campos-Maya A , Cardenas-Sanchez J , Penagos-Lopez D , Gomez-Puentes A , Delgado-Quiroz N , Guarin-Muñoz L , Ortiz-Elejalde J 
Published: September 2024

AbstractBackgroundMultimorbidity, the coexistence of multiple chronic diseases, poses significant challenges for healthcare systems worldwide. This study aims to assess the situation of multimorbidity in Colombia using structural equation models and to characterize multimorbidity by sex, age group, region, and health insurance regime between 2019 and 2023.MethodsWe conducted a cross-sectional analytical study utilizing data from the Individual Health Service Provision Registry (RIPS) and other national databases, including the Unit of Payment by Capitation (UPC) Sufficiency Study Database. Structural equation models were employed to identify and analyze multimorbidity clusters among patients with two or more chronic diseases.ResultsThe study revealed a multimorbidity prevalence of 61.5% in the general population. Hypertension emerged as the most prevalent chronic condition, frequently associated with diabetes and chronic kidney disease. Multimorbidity was more common in women and individuals affiliated with the contributory insurance regime. The study also identified significant variations in multimorbidity prevalence across different regions and age groups.ConclusionsMultimorbidity is a prevalent issue in Colombia, with substantial variations by sex, age, and insurance regime. These findings underscore the need for tailored healthcare strategies to address the diverse needs of multimorbid patients. The results provide critical insights for health service planning and management, emphasizing the importance of continued research and policy development to mitigate the burden of chronic diseases and multimorbidity in Colombia.
The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity
Authors: Guha Abhishek , Si Ying , Smith Reed , Kazamel Mohamed , Jiang Nan , Smith Katherine A. , Thalacker-Mercer Anna , Singh Brijesh K. , Ho Ritchie , Andrabi Shaida A , Silva Pereira Joao D Tavares Da , Salgado Juliana S. , Agrawal Manasi , Velic Emina Horvat , King Peter H. 
Published: September 2024

AbstractAmyotrophic lateral sclerosis (ALS) is an age-related and fatal neurodegenerative disease characterized by progressive muscle weakness. There is marked heterogeneity in clinical presentation, progression, and pathophysiology with only modest treatments to slow disease progression. Molecular markers that provide insight into this heterogeneity are crucial for clinical management and identification of new therapeutic targets. In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21. We analyzed human ALS muscle biopsy samples and found a large increase in FGF21 expression with localization to atrophic myofibers and surrounding endomysium. A concomitant increase in FGF21 was detected in ALS spinal cords which correlated with muscle levels. FGF21 was increased in the SOD1G93Amouse beginning in presymptomatic stages. In parallel, there was dysregulation of the co-receptor, β-Klotho. Plasma FGF21 levels were increased and high levels correlated with slower disease progression, prolonged survival, and increased body mass index. In NSC-34 motor neurons and C2C12 muscle cells expressing SOD1G93Aor exposed to oxidative stress, ectopic FGF21 mitigated loss of cell viability. In summary, FGF21 is a novel biomarker in ALS that correlates with slower disease progression and exerts trophic effects under conditions of cellular stress.
Assessing the risk of highly pathogenic avian influenza H5 viruses spread within French broiler and layer production networks
Authors: Hautefeuille Claire , Muñoz Facundo , Dauphin Gwenaëlle , Paul Mathilde , Peyre Marisa , Goutard Flavie 
Published: September 2024

AbstractSince 2015, French poultry production is threatened almost every year by a reintroduction of highly pathogenic avian influenza H5 viruses. The duck sector was the most concerned by this crisis but other sectors such as broiler, layer and turkey were also affected by outbreaks. The objective of this work was to assess the risk of highly pathogenic avian influenza H5 virus transmission from one farm to another within the French broiler and layer production network.This study used the WOAH risk assessment framework. After drawing up a scenario tree of virus transmission from one farm to another, data were collected through a literature review or through experts’ elicitation. Three questionnaires were developed according to the experts’ field of expertise: avian influenza, broiler and layer sectors. The experts’ estimates were combined using a beta distribution weighted by their confidence level. A Monte Carlo iteration process was used to combine the different probabilities of the scenario tree and to assess the transmission risk.In the broiler sector, the highest transmission probabilities were observed if the exposed farm was an indoor broiler farm and the source a broiler farm (indoor or free-range). The high transmission probability between broiler farm integrated within the same company highlighted the role of integration in this probability. In the layer sector, the highest transmission probabilities were observed if the source farm was a free-range farm and the exposed farm a production farm (indoor or free-range). The sensitivity analysis showed that the exposed farm’s biosecurity had a significant impact on the transmission probability.Our results provide an insight on the role of each type of farms in the virus spread within the French broiler and layer production network and will be useful for the implementation of control measures such as movement restriction or vaccination.