bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated antibody dispensing to improve high‐parameter flow cytometry throughput and analysis
Authors: Bosteels Victor , Van Duyse Julie , Ruyssinck Elien , Van der Borght Katrien , Nguyen Long , Gavel Jannes , Janssens Sophie , Van Isterdael Gert 
Published: March 2024

AbstractOver the past decade, the flow cytometry field has witnessed significant advancements in the number of fluorochromes that can be detected. This enables researchers to analyze more than 40 markers simultaneously on thousands of cells per second. However, with this increased complexity and multiplicity of markers, the manual dispensing of antibodies for flow cytometry experiments has become laborious, time‐consuming, and prone to errors. An automated antibody dispensing system could provide a potential solution by enhancing the efficiency, and by improving data quality by faithfully dispensing the fluorochrome‐conjugated antibodies and by enabling the easy addition of extra controls. In this study, a comprehensive comparison of different liquid handlers for dispensing fluorochrome‐labeled antibodies was conducted for the preparation of flow cytometry stainings. The evaluation focused on key criteria including dispensing time, dead volume, and reliability of dispensing. After benchmarking, the I.DOT, a non‐contact liquid handler, was selected and optimized in more detail. In the end, the I.DOT was able to prepare a 25‐marker panel in 20 min, including the full stain, all FMOs and all single stain controls for cells and beads. Having all these controls improved the validation of the panel, visualization, and analysis of the data. Thus, automated antibody dispensing by dispensers such as the I.DOT reduces time and errors, enhances data quality, and can be easily integrated in an automated workflow to prepare samples for flow cytometry.
Evaluating the efficacy of the selective orexin 1 receptor antagonist nivasorexant in an animal model of binge‐eating disorder
Authors: Steiner Michel Alexander , Botticelli Luca , Bergamini Giorgio , Micioni Di Bonaventura Emanuela , Gatfield John , Williams Jodi T. , Treiber Alexander , Vaillant Catherine , Cifani Carlo , Micioni Di Bonaventura Maria Vittoria 
Published: March 2024

AbstractObjectiveTest the efficacy of the selective orexin 1 receptor (OX1R) antagonist (SO1RA) nivasorexant in an animal model of binge‐eating disorder (BED) and study its dose–response relationship considering free brain concentrations and calculated OX1R occupancy. Compare nivasorexant's profile to that of other, structurally diverse SO1RAs. Gain understanding of potential changes in orexin‐A (OXA) neuropeptide and deltaFosB (ΔFosB) protein expression possibly underlying the development of the binge‐eating phenotype in the rat model used.MethodBinge‐like eating of highly palatable food (HPF) in rats was induced through priming by intermittent, repeated periods of dieting and access to HPF, followed by an additional challenge with acute stress. Effects of nivasorexant were compared to the SO1RAs ACT‐335827 and IDOR‐1104‐2408. OXA expression in neurons and neuronal fibers as well as ΔFosB and OXA‐ΔFosB co‐expression was studied in relevant brain regions using immuno‐ or immunofluorescent histochemistry.ResultsAll SO1RAs dose‐dependently reduced binge‐like eating with effect sizes comparable to the positive control topiramate, at unbound drug concentrations selectively blocking brain OX1Rs. Nivasorexant's efficacy was maintained upon chronic dosing and under conditions involving more frequent stress exposure. Priming for binge‐like eating or nivasorexant treatment resulted in only minor changes in OXA or ΔFosB expression in few brain areas.DiscussionSelective OX1R blockade reduced binge‐like eating in rats. Neither ΔFosB nor OXA expression proved to be a useful classifier for their binge‐eating phenotype. The current results formed the basis for a clinical phase II trial in BED, in which nivasorexant was unfortunately not efficacious compared with placebo.Public SignificanceNivasorexant is a new investigational drug for the treatment of binge‐eating disorder (BED). It underwent clinical testing in a phase II proof of concept trial in humans but was not efficacious compared with placebo. The current manuscript investigated the drug's efficacy in reducing binge‐like eating behavior of a highly palatable sweet and fat diet in a rat model of BED, which initially laid the foundation for the clinical trial.
Bottom‐up rather than top‐down mechanisms determine mesocarnivore interactions in Norway
Authors: Cano‐Martínez Rocío , Thorsen Neri Horntvedt , Hofmeester Tim R. , Odden John , Linnell John , Devineau Olivier , Angoh Siow Yan Jennifer , Odden Morten 
Published: March 2024

AbstractInteractions among coexisting mesocarnivores can be influenced by different factors such as the presence of large carnivores, land‐use, environmental productivity, or human disturbance. Disentangling the relative importance of bottom‐up and top‐down processes can be challenging, but it is important for biodiversity conservation and wildlife management. The aim of this study was to assess how the interactions among mesocarnivores (red fox Vulpes vulpes, badger Meles meles, and pine marten Martes martes) were affected by large carnivores (Eurasian lynx Lynx lynx and wolf Canis lupus), land cover variables (proportion of agricultural land and primary productivity), and human disturbance, as well as how these top‐down and bottom‐up mechanisms were influenced by season. We analyzed 3 years (2018–2020) of camera trapping observations from Norway and used structural equation models to assess hypothesized networks of causal relationships. Our results showed that land cover variables were more strongly associated with mesocarnivore detection rates than large carnivores in Norway. This might be caused by a combination of low density of large carnivores in an unproductive ecosystem with strong seasonality. Additionally, detection rates of all mesocarnivores showed positive associations among each other, which were stronger in winter. The prevalence of positive interactions among predators might indicate a tendency to use the same areas and resources combined with weak interference competition. Alternatively, it might indicate some kind of facilitative relationship among species. Human disturbance had contrasting effects for different species, benefiting the larger mesocarnivores (red fox and badger) probably through food subsidization, but negatively affecting apex predators (wolf and lynx) and smaller mesocarnivores (pine marten). In a human‐dominated world, this highlights the importance of including anthropogenic influences in the study of species interactions.
Species distribution modeling of northern sea otters (Enhydra lutris kenyoni) in a data‐limited ecosystem
Authors: Hasan Elizabeth L. , Gorman Kristen B. , Coletti Heather A. , Konar Brenda 
Published: March 2024

AbstractSpecies distribution models (SDMs) are used to map and predict the geographic distributions of animals based on environmental covariates. Typically, SDMs require high‐resolution habitat data and time series information on animal locations. For data‐limited regions, defined as having scarce habitat or animal survey data, modeling is more challenging, often failing to incorporate important environmental attributes. For example, for sea otters (Enhydra lutris), a federally protected keystone species with variable population trends across the species' range, predictive modeling of distributions has been successfully conducted in areas with robust sea otter population and habitat data. We used open‐access data and employed a presence‐only model, maximum entropy (MaxEnt), to investigate subtidal habitat associations (substrate and algal cover, bathymetry, and rugosity) of northern sea otters (E. lutris kenyoni) for a data‐limited ecosystem, represented by Kachemak Bay, Alaska. Habitat association results corroborated previous findings regarding the importance of bathymetry and understory kelp as predictors of sea otter presence. Novel associations were detected as filamentous algae and shell litter were positively and negatively associated with northern sea otter presence, respectively, advancing existing knowledge of sea otter benthic habitat associations useful for predicting habitat suitability. This study provides a quantitative framework for conducting species distribution modeling with limited temporal and spatial animal distribution and abundance data. Utilizing drop camera information, our novel approach allowed for a better understanding of habitat requirements for a stable northern sea otter population, including bathymetry, understory kelp, and filamentous algae as positive predictors of sea otter presence in Kachemak Bay, Alaska.
Identification of molecular signatures in epicardial adipose tissue in heart failure with preserved ejection fraction
Authors: He Shan , Zhao Lei , Zhang Jianjun , Yang Xinchun , Zhu Huagang 
Published: March 2024

AbstractAimsThe molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.MethodsRNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions.ResultsHFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P < 0.05). qRT‐PCR analysis confirmed that two lncRNAs ENST00000561775 (P = 0.0194) and ENST00000519093 (P = 0.027) and an mRNA POSTN (P = 0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling.ConclusionsWe are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT.
Current trends in medium‐chain‐length polyhydroxyalkanoates: Microbial production, purification, and characterization
Authors: Hahn Thomas , Alzate Melissa Ortega , Leonhardt Steven , Tamang Pravesh , Zibek Susanne 
Published: March 2024

AbstractPolyhydroxyalkanoates (PHAs) have gained interest recently due to their biodegradability and versatility. In particular, the chemical compositions of medium‐chain‐length (mcl)‐PHAs are highly diverse, comprising different monomers containing 6–14 carbon atoms. This review summarizes different feedstocks and fermentation strategies to enhance mcl‐PHA production and briefly discusses the downstream processing. This review also provides comprehensive details on analytical tools for determining the composition and properties of mcl‐PHA. Moreover, this study provides novel information by statistically analyzing the data collected from several reports on mcl‐PHA to determine the optimal fermentation parameters (specific growth rate, PHA productivity, and PHA yield from various structurally related and unrelated substrates), mcl‐PHA composition, molecular weight (MW), and thermal and mechanical properties, in addition to other relevant statistical values. The analysis revealed that the median PHA productivity observed in the fed‐batch feeding strategy was 0.4 g L−1 h−1, which is eight times higher than that obtained from batch feeding (0.05 g L−1 h−1). Furthermore, 3‐hydroxyoctanoate and ‐decanoate were the primary monomers incorporated into mcl‐PHA. The investigation also determined the median glass transition temperature (−43°C) and melting temperature (47°C), which indicated that mcl‐PHA is a flexible amorphous polymer at room temperature with a median MW of 104 kDa. However, information on the monomer composition or heterogeneity and the associated physical and mechanical data of mcl‐PHAs is inadequate. Based on their mechanical values, the mcl‐PHAs can be classified as semi‐crystalline polymers (median crystallinity 23%) with rubber‐like properties and a median elongation at break of 385%. However, due to the limited mechanical data available for mcl‐PHAs with known monomer composition, identifying suitable processing tools and applications to develop mcl‐PHAs further is challenging.
Genetic determinants of thermal resistance in foodborne bacterial pathogens
Authors: Soni Aswathi , Brightwell Gale 
Published: March 2024

AbstractThermal food processing stands as the conventional and prevalent intervention utilized by food industries to uphold food safety standards. Some bacteria are known to withstand thermal treatments up to definite extents. This ability primarily stems from genetically determined traits that can be influenced by environmental conditions. This review focuses on the genetic determinants of thermal resistance in foodborne pathogens including the locus of heat resistance (LHR). Genes contributing to the expression of proteins that might indirectly contribute to thermal resistance have also been covered. The emergence of thermal tolerance in these pathogens raises significant food safety concerns, given global worries about bacterial resistance. The review consolidates existing research on genetic components and loci of heat resistance and highlights potential areas of gaps that warrant further research. Furthermore, acquired cross‐protection leading to resistance across multiple interventions has also been highlighted as an emerging concern. Acquiring insights into the environmental conditions that promote the selection of the LHR will empower the adoption of more efficient strategies to obstruct the pathways by which these pathogens persist within processing chains.
The Surprising Diversity of UV‐Induced Mutations
Authors: Laughery Marian F. , Wilson Hannah E. , Sewell Allysa , Stevison Scott , Wyrick John J. 
Published: March 2024

AbstractUltraviolet (UV) light is the most pervasive environmental mutagen and the primary cause of skin cancer. Genome sequencing of melanomas and other skin cancers has revealed that the vast majority of somatic mutations in these tumors are cytosine‐to‐thymine (C>T) substitutions in dipyrimidine sequences, which, together with tandem CC>TT substitutions, comprise the canonical UV mutation “signature”. These mutation classes are caused by DNA damage directly induced by UV absorption, namely cyclobutane pyrimidine dimers (CPDs) or 6‐4 pyrimidine‐pyrimidone photoproducts (6‐4PP), which form between neighboring pyrimidine bases. However, many of the key driver mutations in melanoma do not fit this mutation signature, but instead are caused by T>A, T>C, C>A, or AC>TT substitutions, frequently occurring in non‐dipyrimidine sequence contexts. This article describes recent studies indicating that UV light causes a more diverse spectrum of mutations than previously appreciated, including many of the mutation classes observed in melanoma driver mutations. Potential mechanisms for these diverse mutation signatures are discussed, including UV‐induced pyrimidine‐purine photoproducts and indirect DNA damage induced by UVA light. Finally, the article reviews recent findings indicating that human DNA polymerase eta normally suppresses these non‐canonical UV mutation classes, which can potentially explain why canonical C>T substitutions predominate in human skin cancers.
Management strategies to improve the nitrogen use efficiency in grasslands and the protein quality in grass silages: Lessons from a practical study on dairy farms in Flanders
Authors: Van den Bossche Tine , De Boever Johan L. , Haesaert Geert , Cougnon Mathias , Debevere Sandra , Vandaele Leen , Goossens Karen 
Published: March 2024

AbstractBackgroundGrasslands are the primary source of forage for ruminants. Legal restrictions on nitrogen fertilization force farmers to optimize nitrogen use efficiency (NUE) of grassland and protein quality in grass silage.MethodsThe present study included grassland data from 10 dairy farms in Flanders. For each grassland field, the presence of clover was determined based on the seed mixture composition. Soil and manure were sampled before the first application and analyzed to determine plant available N content. The annual NUE was calculated for each field possible (n = 28). Prewilted grass samples were taken just before ensiling (n = 65) and grass silage samples (n = 41) were collected from the same fields.ResultsClover fields demonstrated improved NUE due to a lower nitrogen input from fertilizers compared to pure grassland fields (75 vs. 265 kg ha−1). The protein quality of the grass silage was positively correlated with the organic matter digestibility, sugar content, and dry matter content of the prewilted grass. Conversely, crude ash content had a negative effect.ConclusionsThese findings underscore the importance and potential of clover and the practical feasibility of optimizing grassland management to improve both NUE in grasslands and protein quality of the silage.
The tumor microenvironment of benign and malignant salivary gland tumors
Authors: Wai Katherine C. , Okholm Trine Line H. , Ha Patrick K. , Marquez Diana M. , Tenvooren Iliana , Jones Kyle B. , Spitzer Matthew H. 
Published: March 2024

AbstractBackgroundTreatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs.MethodsEleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time‐of‐flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high‐grade and low‐grade malignancies, corrected for multiple hypothesis testing.ResultsThere were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High‐grade malignancies exhibited trends towards higher frequencies of CD8+ PD‐1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF‐1+ CD127− Tregs, and CD69+ CD25− CD4+ T cells compared to low‐grade malignancies.ConclusionSGTs exhibit significant immunologic diversity. High‐grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.
Dietary composition of adult eosinophilic esophagitis patients is related to disease severity
Authors: Eussen Simone R. B. M. , Wielders Sanne , de Rooij Willemijn E. , Van Ampting Marleen T. J. , Van Esch Betty C. A. M. , de Vries Jeanne H. M. , Bredenoord Albert J. , Vlieg‐Boerstra Berber 
Published: March 2024

AbstractBackgroundIn addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response.AimTo explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients.MethodsNutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3‐day food diaries. In this randomized controlled trial, diagnosed patients received either a four‐food elimination diet alone (FFED) or FFED with addition of an amino acid‐based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks.ResultsAt baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full‐fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra‐processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058).ConclusionDietary composition may be related to inflammation in adult EoE patients. High‐quality and anti‐inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.
Regulatory RNAs in immunosenescence
Authors: Talepoor Atefe Ghamar , Doroudchi Mehrnoosh 
Published: March 2024

AbstractBackgroundImmunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration and is accompanied by genomic or epigenomic perturbations. It is now widely recognized that genes and proteins contributing in the process of immunosenescence are regulated by various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, and circular RNAs.AimsThis review article aimed to evaluate the regulatore RNAs roles in the process of immunosenescence.MethodsWe analyzed publications that were focusing on the different roles of regulatory RNAs on the several aspects of immunosenescence.ResultsIn the immunosenescence setting, ncRNAs have been found to play regulatory roles at both transcriptional and post‐transcriptional levels. These factors cooperate to regulate the initiation of gene expression programs and sustaining the senescence phenotype and proinflammatory responses.ConclusionImmunosenescence is a complex process with pivotal alterations in immune function occurring with age. The extensive network that drive immunosenescence‐related features are are mainly directed by a variety of regulatory RNAs such as miRNAs, lncRNAs, and circRNAs. Latest findings about regulation of senescence by ncRNAs in the innate and adaptive immune cells as well as their role in the immunosenescence pathways, provide a better understanding of regulatory RNAs function in the process of immunosenescence.