bluuebunny/crossref_metadata_2025_split huggingface dataset:
LimbNET: collaborative platform for simulating spatial patterns of gene networks in limb development
Authors: Matyjaszkiewicz Antoni , Sharpe James 
Published: August 2024

AbstractSuccessful computational modelling of complex biological phenomena will depend on the seamless sharing of models and hypotheses among researchers of all backgrounds - experimental and theoretical. LimbNET, a new online tool for modelling, simulating and visualising spatiotemporal patterning in limb development, aims to facilitate this process within the limb development community. LimbNET enables remote users to define and simulate arbitrary gene regulatory network (GRN) models of 2D spatiotemporal developmental patterning processes. Researchers can test and compare each others’ hypotheses - GRNs and predicted spatiotemporal patterns - within a common framework. A database of previously created models empowers users to simulate, explore, and extend each others’ work. Spatiotemporally-varying gene expression intensities, derived from image-based data, are mapped into a standardised computational description of limb growth, integrated within our modelling framework. This enables direct comparison not only between datasets but between data and simulation outputs, closing the feedback loop between experiments and simulation via parameter optimisation. All functionality is accessible through a web browser, requiring no special software, and opening the field of image-driven modelling to the full scientific community.
Microfluidic creep experiment for measuring linear viscoelastic mechanical properties of microparticles in a cross-slot extensional flow device
Authors: Mamaghani Sara Ghanbarpour , Dahl Joanna B. 
Published: August 2024

ABSTRACTThe micromechanical measurement field has struggled to establish repeatable techniques, likely because the deforming stresses can be complicated and difficult to model. Here we demonstrate experimentally the ability of cross-slot microfluidic device to create a quasi-steady deformation state in agarose hydrogel microparticles to replicate a traditional uniaxial creep test at the microscale and at relatively high throughput. A recent numerical study by Lu et al. [Lu, Guo, Yu, Sui.J. Fluid Mech., 2023, 962, A26] showed that viscoelastic capsules flowing through a cross-slot can achieve a quasi-steady strain near the extensional flow stagnation point that is equal to the equilibrium static strain, thereby implying that continuous operation of a cross-slot can accurately capture capsule elastic mechanical behavior in addition to transient behavior. However, no microfluidic cross-slot studies have reported quasi-steady strains for suspended cells or particles, to our knowledge. By using large dimension cross-slots relative to the microparticle diameter, our cross-slot implementation created an extensional flow region that was large enough for agarose hydrogel microparticles to achieve a strain plateau while dwelling near the stagnation point. This strain plateau will be key for accurately and precisely measuring linear viscoelastic properties of small microscale biological objects. The mechanical test was performed in the linear regime, so an analytical mechanical model derived using the elastic-viscoelastic correspondence principle was proposed to extract linear viscoelastic mechanical properties from observed particle strain histories. Particle image velocimetry measurements of the unperturbed velocity field were used to determine where in the device particles experienced extensional flow and the mechanical model should be applied. The measurement throughput in this work was 1 – 2 particles achieving a quasi-steady strain plateau per second, though measurement yield and throughput can be increased with particle-centering upstream device design features. Finally, we provide recommendations for applying the cross-slot microscale creep experiment to other biomaterials and criteria to identify particles that likely achieved a quasi-steady strain state.
A Versatile Antibody Capture System that Drives PreciseIn Vivo Delivery of mRNA loaded Lipid Nanoparticles and Enhances Gene Expression
Authors: Chen Moore Z. , Yuen Daniel , McLeod Victoria M. , Yong Ken W. , Smyth Cameron H. , Herling Bruna Rossi , Payne Thomas. J. , Fabb Stewart A. , Belousoff Matthew J. , Algarni Azizah , Sexton Patrick M. , Porter Christopher J. H. , Pouton Colin W. , Johnston Angus P. R. 
Published: August 2024

ABSTRACTEfficient and precise delivery of mRNA is critical to advance mRNA therapies beyond their current use as vaccines. Lipid nanoparticles (LNP) efficiently encapsulate and protect mRNA, but non-specific cellular uptake may lead to off-target delivery and minimal delivery to target cells. Functionalizing LNPs with antibodies enables targeted mRNA delivery, but traditional modification techniques require complex conjugation and purification, which often reduces antibody affinity. Here, we present a simple method for capturing antibodies in their optimal orientation on LNPs, without antibody modification or complex purification. This strategy uses an optimally oriented anti-Fc nanobody on the LNP surface to capture antibodies, resulting in protein expression levels >1000 times higher than non-targeted LNPs and >8 times higher than conventional antibody functionalization techniques. These precisely targeted LNPs showed highly efficientin vivotargeting to T cells, with minimal delivery to other immune cells. This approach enables the rapid development of targeted LNPs and has the potential to broaden the use of mRNA therapies.
Global distribution and diversity of haloarchaeal pL6-family plasmids
Authors: Dyall-Smith Mike , Pfeiffer Friedhelm 
Published: August 2024

AbstractAustralian isolates ofHaloquadratum walsbyi, a square-shaped haloarchaeon, often harbor small cryptic plasmids of the pL6-family, approximately 6 kb in size. These plasmids exhibit a highly conserved gene arrangement and encode a replicase similar to those of betapleolipoviruses. To assess their global distribution and recover more examples for analysis, fifteen additional plasmids were reconstructed from the metagenomes of seven hypersaline sites across four countries: Argentina, Australia, Puerto Rico, and Spain. Including the five previously described plasmids, the average plasmid size is 6,002 bp, with an average G+C content of 52.5%. The tetramers GGCC and CTAG are either absent or significantly under-represented, except in the two plasmids with the highest %G+C. All plasmids share a similar arrange-ment of genes organized as outwardly facing replication and ATPase modules, but variations were observed in some core genes, such as F2, and some plasmids had acquired accessory genes. Two plasmids, pCOLO-c1 and pISLA-c6 shared 92.7% nt identity despite originating from Argentina and Spain, respectively. Numerous metagenomic CRISPR spacers matched sequences in the fifteen reconstructed plasmids, indicating frequent invasion of haloarchaea. Spacers could be assigned to haloarchaeal genera by mapping their associated direct repeats (DR), with half of these matching toHaloquadratum. Finally, strand-specific metatranscriptome (RNA-seq) data could be used to demonstrate the active transcription of two pL6-family plasmids, including antisense transcripts.
Integrated germline and somatic molecular profiling to detect cancer predisposition has a high clinical impact in poor-prognosis paediatric cancer
Authors: Fuentes-Bolanos Noemi A , Courtney Eliza , Mayoh Chelsea , Warby Meera , Lau Loretta M S , Wong-Erasmus Marie , Khuong-Quang Dong-Anh , Barahona Paulette , Padhye Bhavna , El-Kamand Sam , Nunag Sheena , Ajuyah Pamela , Sherstyuk Alexandra , Altekoester Ann-Kristin , Sullivan Ashleigh , Poplawski Nicola , Kiraly-Borri Catherine , O’Sullivan Sarah , Marfan Helen , Alli Rozanna , Curnow Lisette , Bhatia Kanika , Anazodo Antoinette , Trahair Toby N , Mateos Marion , Hansford Jordan R. , Dholaria Hetal , Josephi-Taylor Sarah , Moore Andrew S , Nicholls Wayne , Gottardo Nicholas G , Downie Peter , Khaw Seong-Lin , Tapp Heather , McCowage Geoffrey , Dalla-Pozza Luciano , Alvaro Frank , Wood Paul J , Tyrrell Vanessa , Haber Michelle , Cowley Mark J , Ekert Paul G , Marshall Glenn M , Kirk Judy , Tucker Katherine , Pinese Mark , Ziegler David S 
Published: August 2024

AbstractGermline predisposition has a significant role in paediatric cancer. However, the optimal approach to identifying cancer-causing germline pathogenic variants (GPV) in children, and even the prevalence of GPV among children with cancer, remain unclear. Here we report our findings from a comprehensive survey of GPV in 496 children with poor-prognosis cancer. By integrating tumour and germline molecular profiling we identified GPV in 15.5% of patients, 48.1% of whom had not met clinical genetic testing criteria. Although the cancer type was outside the recognised phenotypic spectrum for 43.7% of reported GPV, 63.2% of these were clinically actionable for cancer risk. Integrated germline-tumour analysis increased the GPV detection rate by 8.5%, and informed germline interpretation in 14.3% of patients with GPV, highlighting the value of integrated analyses. Our findings establish the benefit of broad integrated tumour-germline screening, over phenotype-guided testing, to detect GPV in children with poor prognosis cancers.
Advancing oncology with federated learning: transcending boundaries in breast, lung, and prostate cancer. A systematic review
Authors: Ankolekar Anshu , Boie Sebastian , Abdollahyan Maryam , Gadaleta Emanuela , Hasheminasab Seyed Alireza , Yang Guang , Beauville Charles , Dikaios Nikolaos , Kastis George Anthony , Bussmann Michael , Khalid Sara , Kruger Hagen , Lambin Philippe , Papanastasiou Giorgos 
Published: August 2024

AbstractFederated Learning (FL) has emerged as a promising solution to address the limitations of centralised machine learning (ML) in oncology, particularly in overcoming privacy concerns and harnessing the power of diverse, multi-center data. This systematic review synthesises current knowledge on the state-of-the-art FL in oncology, focusing on breast, lung, and prostate cancer. Distinct from previous surveys, our comprehensive review critically evaluates the real-world implementation and impact of FL on cancer care, demonstrating its effectiveness in enhancing ML generalisability, performance and data privacy in clinical settings and data. We evaluated state-of-the-art advances in FL, demonstrating its growing adoption amid tightening data privacy regulations. FL outperformed centralised ML in 15 out of the 25 studies reviewed, spanning diverse ML models and clinical applications, and facilitating integration of multi-modal information for precision medicine. Despite the current challenges identified in reproducibility, standardisation and methodology across studies, the demonstrable benefits of FL in harnessing real-world data and addressing clinical needs highlight its significant potential for advancing cancer research. We propose that future research should focus on addressing these limitations and investigating further advanced FL methods, to fully harness data diversity and realise the transformative power of cutting-edge FL in cancer care.
15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN
Authors: Daniels Alisha J. , McDade Eric , Llibre-Guerra Jorge J. , Xiong Chengjie , Perrin Richard J. , Ibanez Laura , Supnet-Bell Charlene , Cruchaga Carlos , Goate Alison , Renton Alan E. , Benzinger Tammie L.S. , Gordon Brian A. , Hassenstab Jason , Karch Celeste , Popp Brent , Levey Allan , Morris John , Buckles Virginia , Allegri Ricardo F. , Chrem Patricio , Berman Sarah B. , Chhatwal Jasmeer P. , Farlow Martin R. , Fox Nick C. , Day Gregory S. , Ikeuchi Takeshi , Jucker Mathias , Lee Jae-Hong , Levin Johannes , Lopera Francisco , Takada Leonel , Sosa Ana Luisa , Martins Ralph , Mori Hiroshi , Noble James M. , Salloway Stephen , Huey Edward , Rosa-Neto Pedro , Sánchez-Valle Raquel , Schofield Peter R. , Roh Jee Hoon , Bateman Randall J. ,   the Dominantly Inherited Alzheimer Network
Published: August 2024

AbstractThis manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer’s disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.
“Safety and Efficacy of Exercise-based cardiac rehabilitation in patients with refractory angina: a randomized, controlled trial”
Authors: Dourado Luciana Oliveira Cascaes , Jordão Camila Paixão , Vieira Marcelo Luiz Campos , Gowdak Luis Henrique Wolff , Negrão Carlos Eduardo , de Matos Luciana Diniz Nagem Janot 
Published: August 2024

ABSTRACTAimEvidence is scarce regarding safety and anti-ischemic effects of exercise-based cardiac rehabilitation (ECR) in patients with refractory angina (RA).MethodsThis was a prospective, single-center, randomized controlled study that assessed a 12-week ECR program in patients with RA. Death and cardiovascular events, anginal symptoms, exercise stress echocardiogram (ESE) and cardiopulmonary exercise test (CPET) parameters were evaluated. When significant differences were detected, Bonferroni post hoc comparisons were conducted.ResultsNo difference regarding clinical events and anginal symptoms was found between groups. In ESE, rehab group (RG) increased in peak load (RGpostto RGpre,P= 0.001; interaction,P< 0.001), angina quantification (RGpostto RGpre,P= 0.004; control group (CG)prethan CGpost,P= 0.006; RGpostthan CGpre,P= 0.0019; interaction,P= 0.001), exercise duration (RGpostto RGpre,P= 0.009; interaction,P= 0.006), ischemic threshold (RGpostto RGpre,P= 0.001; CGprethan CGpost,P= 0.03; RGpostthan CGpre,P= 0.008; interaction,P= 0.005) and angina threshold (RGpostto RGpre,P= 0.04; RGpostthan CGpost,P= 0.04; interaction,P= 0.002). In CPET, RG had increased exercise duration and covered distance in RGpost(RGprethan RGpost,P= 0.001; interaction,P= 0.014, RGprethan RGpost,P< 0.001; interaction,P< 0.01; respectively).ConclusionA 12-week ECR was safe and promoted positive clinical effects regarding exercise duration, intensity of angina, and angina and ischemic thresholds in RA patients.The trial registry: Cardiac Rehabilitation in Patients with Refractory Angina (NCT03218891)
Astrocyte Regulation of Synaptic Plasticity Balances Robustness and Flexibility of Cell Assemblies
Authors: Koshkin Roman , Fukai Tomoki 
Published: August 2024

AbstractCell assemblies are believed to represent the substrate of memory. Although long-term plasticity likely enables the formation of cell assemblies, how other factors, such as astrocytes and short-term plasticity (STP), affect their properties is poorly understood. To close this gap, we investigated cell assembly dynamics in a recurrent network model mimicking the hippocampal area CA3. As shown in experiment, recurrent connections in our model obey a symmetric spike-timing-dependent plasticity (STDP), in which weight change may or may not depend on the releasable amount of neurotransmitter. The former case involves an interplay between STDP and STP. In addition, we implicitly modeled the effect of astrocyte NMDA receptors by manipulating the breadth of the distribution of neurotransmitter release probability in STP. Both STP-dependent and STP-independent STDP enabled spontaneous cell assembly formation. Under the former, however, cell assemblies tend to be smaller and more responsive to external stimulation, improving the network’s memory capacity and enabling flexible network restructuring. Furthermore, astrocyte regulation of the STP-dependent STDP facilitates stimulus-driven reorganization of neural networks without destroying existing assembly structure, thus balancing cell assemblies’ flexibility and robustness. Our findings elucidate the computational advantages of interaction between STP and STDP and highlight astrocytes’ possible regulatory role in memory formation.
Plasmid-chromosome transcriptional crosstalk in multidrug resistant clinical enterobacteria
Authors: Toribio-Celestino Laura , Calvo-Villamañán Alicia , Herencias Cristina , Valle Aida Alonso-del , Sastre-Dominguez Jorge , Quesada Susana , Mazel Didier , Rocha Eduardo PC , Fernández-Calvet Ariadna , San Millan Alvaro 
Published: August 2024

AbstractConjugative plasmids promote the dissemination and evolution of antimicrobial resistance in bacterial pathogens. However, plasmid acquisition can produce physiological alterations in the bacterial host, leading to potential fitness costs that determine the clinical success of bacteria-plasmid associations. In this study, we used a transcriptomic approach to characterize the interactions between a globally disseminated carbapenem resistance plasmid, pOXA-48, and a diverse collection of multidrug resistant clinical enterobacteria. Although pOXA-48 produced mostly strain-specific transcriptional alterations, it also led to the common overexpression of a small chromosomal operon present inKlebsiellaspp. andCitrobacter freundiistrains. This operon included two genes coding for a pirin and an isochorismatase family proteins (pfpandifp), and showed evidence of horizontal mobilization across Proteobacteria species. Combining genetic engineering, transcriptomics, and CRISPRi gene silencing, we showed that a pOXA-48-encoded LysR regulator is responsible for the plasmid-chromosome crosstalk. Crucially, the operon overexpression produced a fitness benefit in a pOXA-48-carryingK. pneumoniaeclinical strain, suggesting that this crosstalk promotes the dissemination of carbapenem resistance in clinical settings.
Pyruvate from bone marrow mesenchymal stem cells supports myeloma redox homeostasis and anabolism
Authors: Vera-Sigüenza Elías , Escribano-Gonzalez Cristina , Serrano-Gonzalo Irene , Eskla Kattri-Liis , Speakman Charlotte , Huerta-Uribe Alejandro , Vettore Lisa , Rana Himani , Boufersaoui Adam , Vellama Hans , Nashebi Ramin , Cloete Ielyaas , Roberts Jennie , Basu Supratik , Drayson Mark , Bunce Christopher , Pratt Guy , Spill Fabian , Maddocks Oliver D.K. , Tennant Daniel A. 
Published: August 2024

AbstractMultiple myeloma is an incurable cancer of plasma cells that depends on the bone marrow for its survival. Despite its prevalence, the molecular mechanisms underlying this malignancy remain poorly understood. In this study, we aim to bridge this knowledge gap by elucidating the metabolic interplay between myeloma cells and bone marrow mesenchymal stem cells (BMMSCs). BMMSCs are crucial in supporting myeloma cell metabolism, contributing to their proliferation, survival, and resistance to chemotherapy. Through a combination of mathematical modelling and experimental co-cultures, we demonstrate that pyruvate – the end product of glycolysis – plays a key role in myeloma cell metabolism. Our findings reveal that myeloma cells predominantly rely on the uptake of pyruvate produced by neighbouring BMM-SCs via the plasma membrane proton-linked monocarboxylate transporters MCT-1 and MCT-2 encoded by the Slc16a1 and a2 genes, respectively. Furthermore, we show that pharmacological inhibition of the MCT-1/2, with AZD3965, triggers a cascade of compensatory metabolic responses, disrupting redox balance and significantly reducing the proliferation capacity of co-cultured myeloma cells.
DeepKin: Predicting relatedness from low-coverage genomes and paleogenomes with convolutional neural networks
Authors: Güler Merve N. , Yılmaz Ardan , Katırcıoğlu Büşra , Kantar Sarp , Ünver Tara Ekin , Vural Kıvılcım Başak , Altınışık N. Ezgi , Akbaş Emre , Somel Mehmet 
Published: August 2024

AbstractDeepKinis a novel tool designed to predict relatedness from genomic data using convolutional neural networks (CNNs). Traditional methods for estimating relatedness often struggle when genomic data is limited, as with paleogenomes and degraded forensic samples.DeepKinaddresses this challenge by leveraging two CNN models trained on simulated genomic data to classify relatedness up to the third-degree and to identify parent-offspring and sibling pairs. Our benchmarking showsDeepKinperforms comparably or better than the widely used toolREADv2.We validatedDeepKinon empirical paleogenomes from two paleological sites, demonstrating its robustness and adaptability across different genetic backgrounds, with accuracy >90% above 10K shared SNPs. By capturing information across genomic segments,DeepKinoffers a new methodological path for relatedness estimation in settings with highly degraded samples, with applications in ancient DNA, as well as forensic and conservation genetics.
Development of an immunoassay for the detection and diagnosis of microbially-influenced corrosion caused by methanogenic Archaea
Authors: Lahme Sven , Mantilla Aguas Jorge 
Published: August 2024

AbstractMicrobially-influenced corrosion (MIC) is a costly problem across several industries. The steadily rising use of advanced molecular biological methods to investigate MIC allowed ever deeper insights in the underlying microbial community structure and function. However, currently available technologies do not allow accurate detection and diagnosis of MIC in the field. Recent discovery of a special hydrogenase in certain corrosive methanogenic Archaea allowed for the development of a first ever MIC biomarker termed heremicH. ThemicHgene encodes the large subunit of a special [NiFe] hydrogenase involved in MIC. Here we describe the development of a recombinant antibody that enable the specific and sensitive detection of the MicH protein in western blot immunoassays. Using a recombinant MicH protein we determined the lower limit of detection per assay to be around 0.3 fg MicH. The immunoassay was able to detect a strong signal for the MicH protein inmicH-positive pure cultures ofMethanobacterium-like. strain IM1 that was cultivated on iron granules, and the signal was over 500 times lower in amicH-negativeMethanococcus maripaludisS2 culture. To further evaluate the ability to differentiate corrosive from non-corrosive microbial communities, we tested ten oil field enrichment cultures that showed a wide range of corrosion rates (0.02 – 0.48 mm/yr). We detected the MicH protein in planktonic (36.5 – 1473.5 pg/mL) and carbon steel biofilm samples (41.0 – 7971.3 pg/cm2) from corrosive methanogenic enrichments (0.17 – 0.48 mm/yr) but did not detect MicH in any of the non-corrosive tests (<0.08 mm/yr) despite methanogenic activity. The results indicate that corrosion was likely caused by methanogenic Archaea expressing a corrosive [NiFe] hydrogenase and that the newly developed MicH-specific immunoassay can detect and monitor their activity. The development of a specific and sensitive immunoassays to detect a MIC biomarker allow corrosion scientists and field practitioners to detect and monitor the activity of corrosive methanogenic Archaea.