bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pencil Beam Based X-ray Luminescence Computed Tomography Imaging of Deep Targets Three-dimensionally and Quantitatively
Authors: Fang Yile , Zhang Yibing , Li Changqing 
Published: June 2024

AbstractX-ray luminescence computed tomography (XLCT), especially pencil beam based XLCT, has been emerged for more than 15 years because it can image deep targets in tissue with high spatial resolution and high measurement sensitivity. However, its application is limited by long scanning time and the tedious efforts of finite element mesh generation for model based reconstruction. Our previous study has addressed the imaging speed issue. In this study, we propose to reconstruct XLCT with weighted filtered back projection (wFBP) which makes it possible to perform XLCT imaging three dimensionally for complex objects at a high spatial resolution. We have also proposed measurements with multiple detectors to obtain quantitative XLCT images. To evaluate the proposed methods, we have performed numerical simulations and different sets of phantom experiments including phantom experiments with a control contrast target, different concentrations, and different target sizes. We have also successfully reconstructed deep targets with a diameter of approximately 0.15 mm. For the phantom experiments with targets of different concentrations, using a 4-channel XLCT system and the wFBP, we achieved the ratio of 3.8:1.79:1, closely resembling the ground truth ratio of 4:2:1. Lastly, we have, for the first time, reconstructed different 3D targets at high spatial resolution, successfully, including a printed M target, a triangular hollow bar, and a hot background cuboid with “UCM Li Lab” slots. Our results indicate that the proposed wFBP advances the promising XLCT technology and makes it ready for in vivo studies in the future.
Transplantation of a kidney with a ureter and part of the bladder as a single block: an experimental study
Authors: Kuttymuratov Gani , Ainakulov Ardak , Ayaganov Askar , Oshakbayev Kuat , Mirmanov Arman , Zharasov Daulet , Imanberdiev Zhandos , Taszhurekov Askar , Abdimazhitov Bakhytzhan , Asanova Aruzhan , Abdurakhman Tleuzhan , Uderbayev Nurlybek , Kalieva Arnagul 
Published: June 2024

ABSTRACTObjectiveTo evaluate the effectiveness of en bloc transplantation of a donor kidney, ureters and part of the bladder to a recipient with simulated microcystis in an experimental trial.MethodsStudy Design: a 29-day, open, pilot prospective experimental trial: 14 days constituted an adaptation period, 5 days for the interventions, and 10 days constituted an observation period. The study totally included ten White Landras sibling pigs, which were divided into 12 donors and 12 recipients. The pigs were 3-4 months old and weighing 35-45 kg of both sexes from the same sow to avoid transplant rejection. The pigs lived 7-9 days after transplantation before they were euthanized, and then there were performed macrovisual and histological investigations. Descriptive, inferential statistics, and calculation of percentages were used. The Local Ethics Committee of West Kazakhstan Medical University approved the study.ResultsEleven pigs survived the operation, but one pig died 10 hours after the operation. The cause of death was pulmonary embolism according to the pathological autopsy. In the eleven animals the kidney, ureters and part of the bladder transplanted as en block visually were filled with urine, full of blood, and tissue turgor was good. Visual inspection of the kidney and ureters was satisfactory, bright red. The implanted bladder had a red-burgundy color in all eleven cases. No anastomotic leakage was observed. A histological examination of the graft tissue on the 7-9 after-surgery days showed the preservation of blood flow in the tissues of the bladder and ureters. No total tissue necrosis was detected.ConclusionsIn our experimental model, transplantation of a donor kidney, ureters and part of the bladder to a recipient with a simulated microcyst is effectively feasible. Pigs are a relevant animal model for genitourinary organ transplantation.Trial RegistrationAnimalStudyRegistry.orgDOI10.17590/asr.0000336. Registered 25 January 2024.
Urinary acetaminophen metabolites and clinical outcomes in premature infants
Authors: Guardado Miguel , Torgerson Dara , Chapin Cheryl , Atum Azuka , Hernandez Ryan D. , Ronald B , Simmons Rebecca , Parry Samuel , Ballard Philip L. 
Published: June 2024

ABSTRACTBACKGROUNDExtremely premature infants are treated with acetaminophen (APAP) for discomfort and patent ductus arteriosus. A recent study found an association between APAP metabolite levels in mothers’ breast milk and the diagnoses of both bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in their infants.METHODSUrine samples from 314 infants <29 weeks gestation in the TOLSURF and PROP studies were analyzed by untargeted UHPLC:MS/MS. We performed multivariate logistic regression and meta-analysis to examine associations between APAP metabolite levels and clinical outcomes.RESULTS4-APAP sulfate was the highest detected and most abundant metabolite of 8 detected and was present in 98% of urines. In longitudinal studies (day 6-56), periods of elevated urinary 4-APAP-sulfate occurred in 24 of 28 infants and were of longer duration (10.1 vs 4.2 days, p=0.004) and higher levels (13.3 vs 5.6, p=0.013) in infants on enteral vs total parenteral nutrition. At both day 10 and 28 there were no significant associations between levels of APAP metabolites and BPD or ROP in all infants or only those on TPN or enteral feeds.CONCLUSIONIn two cohorts of premature infants, APAP metabolites were detected uniformly and levels were not associated with increased risk for two adverse clinical outcomes.Impact StatementPremature infants are treated with acetaminophen (APAP) for analgesia and closure of patent ductus arteriosus, however an association has been reported between APAP levels in maternal milk and infant bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).In an untargeted metabolomic study of 2 cohorts of premature infants, the major urinary APAP metabolite was detected in most urine samples of all infants, and there were intervals of elevated levels.Using both longitudinal and cross-sectional analyses, we found no association between APAP levels and either BPD or ROP.Although APAP is known to have toxic effects at high doses, our findings suggest that APAP exposure, at doses experienced by infants in these cohorts, does not increase the risk for two adverse outcomes in the neonatal period.
Are rare heterozygousSYNJ1variants associated with Parkinson’s disease?
Authors: Senkevich Konstantin , Parlar Sitki Cem , Chantereault Cloe , Yu Eric , Ahmad Jamil , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Waters Cheryl , Monchi Oury , Dauvilliers Yves , Dupré Nicolas , Miliukhina Irina , Timofeeva Alla , Emelyanov Anton , Pchelina Sofya , Greenbaum Lior , Hassin-Baer Sharon , Alcalay Roy N. , Gan-Or Ziv 
Published: June 2024

AbstractPrevious studies have suggested that rare biallelicSYNJ1mutations may cause autosomal recessive parkinsonism and Parkinson’s disease (PD). Our study explored the impact of rareSYNJ1variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (Pfdr=0.040). Additionally, a meta-analysis focusing on patients with EOPD demonstrated an association between all rareSYNJ1variants and PD (Pfdr=0.029). RareSYNJ1variants may be associated with sporadic PD, and more specifically with EOPD.
Scalable Differentiable Folding for mRNA Design
Authors: Krueger Ryan , Ward Max 
Published: June 2024

AbstractmRNA is an emerging therapeutic platform with applications ranging from vaccines to genome editing. However, there are an exponential number of mRNA sequences to deliver a given payload and the choice in nucleotide sequence largely determines stability and translation efficiency. There exist several computational approaches for optimizing mRNA sequences but these algorithms are limited in performance or the choice of optimization metric. In this work we describe a new mRNA design algorithm that overcomes both of these limitations and is based on differentiable folding, a recently developed paradigm for RNA design in which a probabilistic sequence representation is optimized via gradient-based methods. First, we present major improvements to the original differentiable folding algorithm that drastically reduce the memory overhead of the gradient calculation. Second, we formulate the mRNA design problem in the context of continuous sequences, requiring the generalization of existing metrics and careful treatment of constraints. Given this scaled algorithm and our mRNA design formalism, we then developed a generative deep learning approach that treats our differentiable folding algorithm as a module in a larger optimization pipeline to learn a network that samples optimized sequences. As a demonstration of our method, we optimize mRNA sequences via complex, therapeutically relevant objective functions.
Genes of the fatty acid oxidation pathway are upregulated in female as compared to male cardiomyocytes
Authors: Talukdar Maya , Chmátal Lukáš , Mao Linyong , Reichart Daniel , Murashige Danielle , Skaletsky Yelena , DeLaughter Daniel M. , Arany Zoltan , Seidman Jonathan G. , Seidman Christine , Page David C. 
Published: June 2024

AbstractHuman females and males differ in cardiac physiology and pathology, even after controlling for sex differences in anthropometrics, lifestyle, and environment. For example, females and males differ in cardiac stroke volume and ventricular thickness, and they exhibit different rates and symptoms of cardiovascular disease. Less is understood about molecular differences in female and male hearts, such as sex differences in gene expression. Here we present an integrative framework utilizing bulk and single-nucleus RNA-sequencing data to study sex differences in the cardiac transcriptome. We show that genes of the fatty acid oxidation (FAO) pathway, the primary source of energy in the heart, are expressed more highly in healthy female than in healthy male hearts. We demonstrate that this sex difference is due to cardiomyocyte-specific, female-biased expression of FAO genes and cannot be explained by sex differences in cardiac cellular composition or number of mitochondria, where FAO takes place. Finally, we observe increased cardiac flux and energetic utilization of free fatty acids in female compared to male hearts. Overall, our results demonstrate that male and female human hearts exhibit fundamental differences in metabolism that likely contribute to sex differences in cardiac physiology and pathology.
Drug-Induced p53 Activation Limits Pancreatic Cancer Initiation
Authors: Twardowski Jennifer J , Heist Thomas I , Soares Zamira Guerra , Berry Emily S , Ruffolo Luis I , Pröschel Christoph , Mello Stephano S 
Published: June 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, initiated predominantly by mutations inKras, which induce acinar-to-ductal metaplasia (ADM) and subsequent formation of precursor lesions, such as pancreatic intraepithelial neoplasia (PanIN). Progression to PDAC is frequently associated with mutations in the tumor suppressorTP53, presumably via disrupting p53-mediated cellular senescence of PanINs. WhetherTP53also has tumor-suppressive activity in earlier phases of PDAC initiation has been less clear. In this study, we investigate the impact of pharmacological stabilization of the wild-type p53 protein on the formation of ADM in aKrasG12D-driven mouse model of PDAC. Our findings demonstrate that p53 stabilization via Nutlin-3a significantly reduces both ADM and PanIN formation by promoting the differentiation of ADM into acinar cells. This differentiation coincides with p53-dependent upregulation of the transcription factor Mist1 (Bhlha15), a critical inducer of acinar cell identity. Our results reveal a role for p53 in tissue repair and maintenance of homeostasis in tumor suppression and suggest pharmacological engagement of p53 as an intervention strategy to prevent PDAC initiation.
Bioinformatics analysis of the potential biomarkers of Multiple Sclerosis and Guillain-Barré syndrome
Authors: Kwok Tyler , Huerta-White Tajah , Briegel Karl , Singh Aaisha , Yeguvapalli Suneetha , Chitrala Kumaraswamy Naidu 
Published: June 2024

AbstractRecent research emphasizes the intricate interplay of genetics and epigenetics in neurological disorders, notably Multiple Sclerosis (MS) and Guillain-Barre Syndrome (GBS), both of which exhibit cardiovascular dysregulation, with GBS often featuring serious bradyarrhythmias requiring prompt recognition and treatment. While cardiovascular autonomic dysfunction in MS is typically less severe, orthostatic intolerance affects around half of MS patients. Their distinction lies in their autoimmune responses, MS is an autoimmune disease affecting the central nervous system, causes demyelination and axon damage, leading to cognitive, ocular, and musculoskeletal dysfunction. In contrast, GBS primarily affects the peripheral nervous system, resulting in paralysis and respiratory complications. Despite their differences, both diseases share environmental risk factors such as viral infections and Vitamin D deficiency. This study aims to explore shared gene expression pathways, functional annotations, and molecular pathways between MS and GBS to enhance diagnostics, pathogenesis understanding, and treatment strategies through molecular analysis techniques. Through the gene expression analysis, five significant genes were found UTS2, TNFSF10, GBP1, VCAN, FOS. Results shows that Common DEGs are linked to apoptosis, bacterial infections, and atherosclerosis. Molecular docking analysis suggests Aflatoxin B1 as a potential therapeutic compound due to its high binding affinity with common differentially expressed proteins.
Real-time Biomechanical Characterisation of Cytoskeletal Remodelling
Authors: Zhang Kaiwen , Reeves Chayla , Berry Joseph D. , Fox Kate , Elbourne Aaron , Gelmi Amy 
Published: June 2024

AbstractAs progenitors for tissue, human mesenchymal stem cells (hMSCs) with ability of self-proliferation and differentiation into various cell types such as osteocytes and adipocytes show great potential applications for tissue engineering. Stem cell fate regulation is highly affected by the cytoskeleton structure and mechanical properties. In this paper, quantitative Atomic Force Microscopy (Q-AFM) was used to continuously characterise topography and biomechanical properties while applying cytoskeleton disruptors to hMSCs. The cell stiffness (quantified by Young’s modulus), primarily governed by the cytoskeleton network, had quantifiable changes associated with cytoskeleton polymerisation and depolymerisation when treatments were applied. Furthermore, with Q-AFM measurements, these changes were tracked in real time over a period of minutes to hours, and the biomechanical properties of the cells were tracked through the applied treatment and subsequent recovery post treatment. Here we present the capability of Q-AFM to perform real time biomechanical characterisation of living cells, directly correlated to intracellular structure and cytoskeletal remodelling.
Phylogeny and species delimitation of ciliates in the genusSpirostomum(Class, Heterotrichea) using single-cell transcriptomes
Authors: Shazib Shahed Uddin Ahmed , Cote-L’Heureux Auden , Ahsan Ragib , Muñoz-Gómez Sergio A. , Lee JunMo , Katz Laura A. , Shin Mann Kyoon 
Published: June 2024

AbstractCiliates are single-celled microbial eukaryotes that diverged from other eukaryotic lineages over a billion years ago. The extensive evolutionary timespan of ciliate has led to enormous genetic and phenotypic changes, contributing significantly to their high level of diversity. Recent analyses based on molecular data have revealed numerous cases of cryptic species complexes in different ciliate lineages, demonstrating the need for a robust approach to delimit species boundaries and elucidate phylogenetic relationships. Heterotrich ciliate species of the genusSpirostomumare abundant in freshwater and brackish environments and are commonly used as biological indicators for assessing water quality. However, someSpirostomumspecies are difficult to identify due to a lack of distinguishable morphological characteristics, and the existence of cryptic species in this genus remains largely unexplored. Previous phylogenetic studies have focused on only a few loci, namely the ribosomal RNA genes, alpha-tubulin, and mitochondrial CO1. In this study, we obtained single-cell transcriptome of 25Spirostomumspecies populations (representing six morphospecies) sampled from South Korea and the USA, and used concatenation- and coalescent-based methods for species tree inference and delimitation. Phylogenomic analysis of 37Spirostomumpopulations and 265 protein-coding genes provided a robustious insight into the evolutionary relationships amongSpirostomumspecies and confirmed that species with moniliform and compact macronucleus each form a distinct monophyletic lineage. Furthermore, the multispecies coalescent (MSC) model suggests that there are at least nine cryptic species in theSpirostomumgenus, three inS. minus, two inS. ambiguum, S. subtilis, andS. tereseach. Overall, our fine sampling of closely relatedSpirostomumpopulations and wide scRNA-seq allowed us to demonstrate the hidden crypticity of species within the genusSpirostomum, and to resolve and provide much stronger support than hitherto to the phylogeny of this important ciliate genus.
Housing temperature dictates the systemic and tissue-specific molecular responses to cancer in mice
Authors: Irazoki Andrea , Frank Emma , Phung Pham Tang Cam , Braun Jessica L , Ehrlich Amy M. , Haid Mark , Riols Fabien , Friis Hansen Camilla Hartmann , Rydal Jørgensen Anne-Sofie , Andersen Nicoline Resen , Hidalgo-Corbacho Laura , Meneses-Valdes Roberto , Ali Mona Sadek , Raun Steffen Henning , Modvig Johanne Louise , Gallero Samantha , Larsen Steen , Gerhart-Hines Zach , Jensen Thomas Elbenhardt , Rohm Maria , Treebak Jonas T. , Fajardo Val Andrew , Sylow Lykke 
Published: June 2024

SummaryCancer cachexia is a metabolic condition affecting up to 80% of patients with cancer. Cachexia is mediated by reduced muscle and fat mass and impaired function, and it lowers survival for patients. With no approved drugs to treat cachexia, preclinical efforts focus on understanding the molecular mechanisms underlying this condition to reveal treatment targets. Housing laboratory mice at ambient temperature imposes cold stress, leading to induced thermogenic activity and consequent whole-body metabolic adaptations. Yet, the impact of housing temperature inin vivopreclinical cachexia remains unknown. We found that thermoneutral (TN) housing in C26 carcinoma-bearing (C26) mice affected lean and fat mass, but not muscle weight or force. TN housing improved glucose tolerance in C26 mice, while enhancing circulating abundance of FGF21 and IL-6. Thermogenic tissues, especially brown adipose tissue, exhibited housing temperature-dependent molecular responses to cancer in oxygen consumption, ATP levels and SERCA ATPase activity, which are all crucial for cancer-induced whole-body metabolic adaptations. We conclude that molecular and systemic adaptations to cancer in mice critically depend on housing temperature, which should be considered in the design and interpretation of preclinical cancer studies.
Painting the diversity of a world’s favourite fruit: A next generation catalogue of cultivated bananas
Authors: Sardos Julie , Cenci Alberto , Martin Guillaume , Breton Catherine , Guignon Valentin , Van den Houwe Ines , Mendez Yaleidis , Sachter-Smith Gabriel L. , Chase Rachel , Ruas Max , Rivallan Ronan , Paofa Janet , Wigmore William , Hunter David Tilafono , D’Hont Angélique , Yahiaoui Nabila , Jenny Christophe , Perrier Xavier , Roux Nicolas , Rouard Mathieu 
Published: June 2024

AbstractSocietal impact statementBananas are nutritious fruits of major importance in the tropics and subtropics. Characterizing their diversity is essential to ensure their conservation and use. A catalogue showcasing cultivated bananas genomic diversity was compiled and is to be used as a tool to support the classification of banana cultivars. This research revealed that cultivated banana groups are not all made of identical clones. Materials from recent collecting missions indicated that more banana diversity is expected to be found as the exploration of the banana gene pool continues. These discoveries will drive dynamic conservation strategies for banana genetic resources and will increase their use.SummaryBanana is an important food crop cultivated in many tropical and subtropical regions around the world. Due to their low fertility, banana landraces are clonally propagated. However, different factors, such as synonymy and the effects of environment, make their assignment to described sets of clones, or cultivar groups, difficult. Consequently, passport data of accessions in genebanks is often uncomplete and sometimes inaccurate.With the recent advances in genomics, a new powerful tool was developed enabling the fine-scale characterization of banana’s ancestry along chromosomes, i.e.in silicochromosome painting. We applied this method to a high-throughput genotyping data set obtained from 317 banana accessions spanning most of the known cultivar groups. This set included both genebank and new uncharacterized materials.By comparing curated morphological assignation to the genomic patterns resulting fromin silicochromosome painting, we were able to compile a catalogue referencing the chromosome painting patterns of most of the described cultivar groups.Examining the genomic patterns obtained, we discovered intra-cultivar group variability. In some cultivar groups, mitotic recombination or deletions were clonally accumulated in cultivars. In addition, we identified at least 4 cultivar groups in which cultivars likely resulting from distinct sexual events co-existed, notably Pisang Awak in which 5 distinct genomic patterns of two ploidy levels were identified. New patterns were also discovered in the newest materials of the set, showing that a wider diversity of clones still existon farm.