bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal assessment of DNA recovery from post-mortem whole blood stored in EDTA, sodium fluoride/potassium oxalate and additive-free tubes
Authors: Grobbelaar Jana , Vuko Loyiso Abongile Marvin , Davies Bronwen , Pearce Brendon , Musiyandaka Fungisai Lorraine , Heathfield Laura Jane 
Published: December 2024

Abstract
Adverse drug reactions and fatalities can result from therapeutic drug use due to genetic deficiencies in drug-metabolizing enzymes. In cases where ancillary testing may not reveal a clear cause of death, molecular autopsies can be valuable. However, forensic mortuaries do not retain DNA samples in all cases, which hinders subsequent genetic testing if it is later deemed necessary. This study aimed to evaluate whether post-mortem whole blood samples collected for toxicological analysis, could provide viable DNA for genetic testing after varying storage periods. Thirty deceased individuals were recruited with informed consent. Blood collected at autopsy from each individual was stored in two sodium fluoride/potassium oxalate (gray-top) tubes, two additive-free (red-top) tubes and one ethylenediaminetetraacetic acid (EDTA; purple-top) tube– the latter recommended for DNA analysis. Blood from one gray-top and one red-top tube were sampled for toxicological analysis prior to DNA analysis, while the remaining samples (acting as controls) underwent DNA analysis immediately. DNA analysis involved DNA extraction and DNA concentration and degradation assessment. Blood samples were stored at 4 °C and DNA extraction and analysis was repeated one year and then five years later. Toxicological sampling did not significantly influence DNA results. DNA concentration and quality significantly decreased over time for all sample types, with DNA from red-top tubes showing the greatest decline. The study showed that DNA testing for drug-metabolizing enzymes was feasible on whole blood that had been stored for five years. This finding supports the potential for retrospective genetic testing in cases of adverse drug reactions and fatalities.
Evaluation of alternative prognostic thresholds for SP142 and 22C3 immunohistochemical PD-L1 expression in triple-negative breast cancer: results from a population-based cohort
Authors: Sigurjonsdottir Gudbjörg , De Marchi Tommaso , Ehinger Anna , Hartman Johan , Ullén Susann , Leandersson Karin , Bosch Ana , Staaf Johan , Killander Fredrika , Niméus Emma 
Published: December 2024

Abstract
Background
Immune checkpoint inhibitors are now a part of the treatment arsenal for triple-negative breast cancer (TNBC) but refinement of PD-L1 as a prognostic and predictive biomarker is a clinical priority. We aimed to evaluate the relevance of novel PD-L1 immunohistochemical (IHC) thresholds in TNBC with regard to PD-L1 gene expression, prognostic value, tumor infiltrating lymphocytes (TILs), and TNBC molecular subtypes.

Material & methods
PD-L1 was scored in a tissue microarray with the SP142 (immune cell (IC) score) and the 22C3 (combined positive score; CPS) IHC assays and TIL abundance evaluated in whole slides in a population-based cohort of 237 early-stage TNBC patients. Survival analysis was performed and RNA sequencing data employed for molecular profiling.

Results
As expected, PD-L1 positivity (IC ≥ 1% and/or CPS ≥ 1) was significantly associated with better prognosis compared to zero PD-L1 expression. Importantly however, also patients with intermediate expression (IC > 0%, < 1%; CPS > 0, < 1) showed a trend toward improved outcome. Tumors with intermediate PD-L1 IHC expression also had intermediate PD-L1 (CD274) gene expression (mRNA). Patients who were both low in TILs (< 30%) and PD-L1 (IC < 1%; CPS < 1) tended to have the poorest prognosis.
PD-L1 positive tumors clustered significantly more often as Immunomodulatory-high and Basal-Like 1-high TNBC molecular subtypes and were enriched in immune response and cell cycle/proliferation signaling pathways. PD-L1-zero tumors on the other hand were enriched in cell growth, differentiation, and metastatic potential pathways and clustered more prevalently as Luminal-Androgen-Receptor-high and Mesenchymal-high. PD-L1-intermediate tumors categorized with neither PD-L1-positive nor PD-L1-zero tumors on the hierarchical clustering level, consigning them as a unique subgroup.

Conclusion
With both SP142 and 22C3, we identified an intermediate IHC PD-L1 group within TNBCs that was supported on the molecular level. Any PD-L1 IHC expression, even though it is < 1, tended to have positive prognostic impact. We suggest that the generally accepted threshold of PD-L1 IHC positivity in TNBC should be investigated further.
The Swedish Cancerome Analysis Network – Breast (SCAN-B) study was retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.
Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells
Authors: Tsubaki Toshiya , Chijimatsu Ryota , Takeda Taiga , Abe Maki , Ochiya Takahiro , Tsuji Shinsaku , Inoue Keita , Matsuzaki Tokio , Iwanaga Yasuhide , Omata Yasunori , Tanaka Sakae , Saito Taku 
Published: December 2024

AbstractAdipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their tissue repair capabilities. The microRNA (miRNA) content in sEVs varies depending on ASC status; however, the effects of aging and cell passage on miRNA profiles remain unclear. In this study, we examined the effects of donor age and cell expansion on ASC characteristics and transcriptome using ASCs obtained from three young and three old donors. Cell expansion significantly impaired stem cell properties, notably reducing proliferation and differentiation capacities. In contrast, donor age had minimal effects on ASCs. RNA sequencing (RNA-seq) revealed differences in gene expression related to stemness, phagocytosis, and metabolic processes influenced by cell expansion. To investigate miRNA variability, we performed small RNA-seq on sEVs collected from ASCs of all six donors. The miRNA profiles were influenced by donor age and cell passage. Interestingly, functional enrichment analysis indicated that advanced donor age and increased cell passage may enhance the production of miRNAs associated with organ development through various pathways. These findings suggest that donor age and cell expansion differentially influence ASC characteristics and sEV miRNA content, highlighting the need for disease-specific conditioning of ASCs to optimize the therapeutic effects of sEVs in clinical applications.
Circulating small extracellular vesicles as blood-based biomarkers of muscle health in aging nonhuman primates
Authors: Mishra Shalini , Kumar Ashish , He Yangen , Su Yixin , Singh Sangeeta , Santos Mark F. , Singh Rakesh , Lee Jingyun , Furdui Cristina M. , Shively Carol A. , Kritchevsky Stephen B. , Register Thomas C. , Deep Gagan 
Published: December 2024

AbstractAge-associated loss of muscle mass and function and subsequent mobility decline define poor health outcomes, reduced quality of life, and mortality risk. The rate and extent of aging-related muscle loss varies across older adults. It is challenging to understand the molecular pathogenesis of mobility decline, as anthropometric and imaging techniques, primarily used in muscle function assessment, do not offer much molecular information. Small extracellular vesicles (sEV) are lipid membrane-bound, nano-sized (≤ 200 nm) vesicles which carry a wide array of biomolecules as their cargo. sEV contain cell/tissue-specific signatures on their surface and can be isolated from biofluids. These properties pose sEV as a minimally invasive means to monitor the functional and biological health of difficult-to-access tissues, establishing them as a promising liquid biopsy tool. Here, we first isolated skeletal muscle-derived sEV (sEVSKM) from the serum of vervet monkeys (16 to < 25 years old) using alpha sarcoglycan (SGCA) as a muscle-specific sEV surface marker. sEVSKM were extensively characterized for size, concentration, purity, and specificity. Further, sEVSKM isolated from young (11–15 years) and old (25–29 years) monkeys’ serum were characterized for oxidized proteins by mass spectrometry and miRNAs by small-RNAseq. Notably, the analysis of oxidized proteins indicated perturbation of metabolic pathways, actin cytoskeleton, muscle cytoskeleton regulation, and HIF-1 signaling in older monkeys. Furthermore, small-RNAseq analysis identified differential expression of several miRNAs regulating metabolic pathways, inflammation, and stress signaling. Altogether, these results suggest that it is feasible to isolate sEVSKM and use them to identify molecular biomarkers that reflect the physiological state of muscle tissue.
Cascading tipping points of Antarctica and the Southern Ocean
Authors: Kubiszewski Ida , Adams Vanessa M. , Baird Rachel , Boothroyd Anne , Costanza Robert , MacDonald Darla Hatton , Finau Glenn , Fulton Elizabeth A. , King Catherine K. , King Matt A. , Lannuzel Delphine , Leane Elizabeth , Melbourne-Thomas Jess , Ooi Can-Seng , Raghavan Mala , Senigaglia Valeria , Stoeckl Natalie , Tian Jing , Yamazaki Satoshi 
Published: December 2024

Abstract
Antarctica and the Southern Ocean are key elements in the physical and biological Earth system. Human-induced climate change, and other human activities in the region, are leading to several potential interacting tipping points with major and irreversible consequences. Here, we examine eight potential physical, biological, chemical, and social Antarctic tipping points. These include ice sheets, ocean acidification, ocean circulation, species redistribution, invasive species, permafrost melting, local pollution, and the Antarctic Treaty System. We discuss the nature of each potential tipping point, its control variables, thresholds, timescales, and impacts, and focus on the potential for cumulative and cascading effects as a result of their interactions. The analysis provides substantial evidence of the need for more concerted and rapid action to limit climate change and to minimise the impacts of local human activities to avoid these cascading tipping points.
Upcycling of Low Quality Aluminum Automotive Scrap: The DNA of Twitch
Authors: Shankar Shrivatsav , Gois Nicholas , Molstad Emily , Söderhjelm Carl , Apelian Diran 
Published: December 2024

AbstractAs our consumption of aluminum continues to grow, the demand to maximize the use of aluminum scrap grows proportionally. The challenge is to create value from waste, taking low quality scrap and upcycling it to high value “green aluminum alloys.” Automotive aluminum scrap from auto shredders dubbed “Twitch,” is an amalgamation of aluminum alloys which is traditionally melted and downcycled to a low value alloy. The first step in the development of green aluminum alloys is to have an in-depth knowledge of the Twitch feedstock, both geographically and temporally. In this work, Twitch was collected from the two coasts of US over a period of 12 months; a dynamic analysis of Twitch as well as metallurgical pathways to upcycle Twitch are given.
Current challenges in multilayer network engineering
Authors: Panayiotou Georgios , Magnani Matteo , Pinaud Bruno 
Published: December 2024

AbstractMultilayer networks (MLNs) have become a popular choice to model complex systems. However, current MLN engineering solutions, that is, systems and methods to store, manipulate, and support the analysis of MLNs, are challenged by the size and complexity of contemporary sources of network data. We assess the maturity level of the MLN engineering ecosystem through an analysis of software libraries for MLNs, focusing on supported functionality, operators and their scalability. Based on this analysis, we provide an overview of the current status of the MLN engineering landscape, compile a list of current limitations to be addressed and propose future developments for more effective and broadly applicable MLN engineering solutions.
On the Effect of Liquid Crystal Orientation in the Lipid Layer on Tear Film Thinning and Breakup
Authors: Taranchuk M. J. , Braun R. J. 
Published: December 2024

AbstractThe human tear film (TF) is thin multilayer fluid film that is critical for clear vision and ocular surface health. Its dynamics are strongly affected by a floating lipid layer and, in health, that layer slows evaporation and helps create a more uniform tear film over the ocular surface. The tear film lipid layer (LL) may have liquid crystalline characteristics and plays important roles in the health of the tear film. Previous models have treated the lipid layer as a Newtonian fluid in extensional flow. We extend previous models to include extensional flow of a thin nematic liquid crystal atop a Newtonian aqueous layer with insoluble surfactant between them. We derive the resulting system of nonlinear partial differential equations for thickness of the LL and aqueous layers, surfactant transport and velocity in the LL. We find that in the limit used here, the liquid crystal director field becomes orientated at a constant angle through the depth of LL. Evaporation is taken into account, and is affected by the LL thickness, internal arrangement of its rod-like molecules, and external conditions. Despite the complexity, this system still represents a significant reduction of the full system. We solve the system numerically via collocation with finite difference discretization in space together with implicit time stepping. We analyze solutions for different internal LL structures and show significant effect of the orientation. Orienting the molecules close to the normal direction to the TF surface results in slower evaporation, and other orientations have an effect on flow, showing that this type of model has promise for predicting TF dynamics.
Disagreement, retraction, and the importance of perspective
Authors: Zeman Dan 
Published: December 2024

Abstract
In the semantic debate about perspectival expressions—predicates of taste, aesthetic and moral terms, epistemic modals, etc.—intuitions about armchair scenarios (e.g., disagreement, retraction) have played a crucial role. More recently, various experimental studies have been conducted, both in relation to disagreement (e.g., Cova, 2012; Foushee and Srinivasan, 2017; Solt, 2018) and retraction (e.g., Knobe and Yalcin, 2014; Khoo, 2018; Beddor and Egan, 2018; Dinges and Zakkou, 2020; Kneer 2021; 2022; Almagro, Bordonaba Plou, and Villanueva, 2023; Marques, 2024), with the aim of establishing a more solid foundation for semantic theorizing. Both these types of data have been used to argue for or against certain views (e.g., contextualism, relativism). In this talk, I discern a common thread in the use of these data and argue for two claims: (i) which perspective is adopted by those judging the armchair scenarios put forward and by the participants in experimental studies crucially matters for the viability of the intended results; (ii) failure to properly attend to this puts recent experimental work at risk. Finally, I consider the case of cross-linguistic disagreement and retraction and assess their importance for the semantic debate about perspectival expressions, as well as for the claim that perspective matters in putting forward the data on which decisions about the right semantic view are made.
The impact of cues on language switching: do spoken questions reduce the need for bilingual language control?
Authors: Timmer Kalinka , Wolna Agata , Wodniecka Zofia 
Published: December 2024

Abstract
The classical language switching paradigm using arbitrary cues to indicate the language to speak in has revealed switching between languages comes at a cost (i.e., switch cost) and makes one slower in the first than in the second language (i.e., reversed language dominance). However, arbitrary cues can create artificial requirements not present during everyday language interactions. Therefore, we investigated whether simulating elements of real-life conversations with question cues (‘Co?’ versus ‘What?’) facilitates language switching in comparison to the classical paradigm (Experiment 1: red versus blue outline; Experiments 2 and 3: low versus high tone). We revealed a dissociation between the two indices of language control: (1) question cues, compared to arbitrary cues, reduced switch costs but (2) did not modulate (in Experiment 1) or increase the reversed language dominance (Experiments 2 and 3). We propose that this conversational switching paradigm could be used as a conceptually more ‘true’ measure of language control.
Novel neuromuscular controllers with simplified muscle model and enhanced reflex modulation: A comparative study in hip exoskeletons
Authors: Manzoori Ali Reza , Messara Sara , Di Russo Andrea , Ijspeert Auke , Bouri Mohamed 
Published: December 2024

Abstract
Neuromuscular controllers (NMCs) offer a promising approach to adaptive and task-invariant control of exoskeletons for walking assistance, leveraging the bioinspired models based on the peripheral nervous system. This article expands on our previous development of a novel structure for NMCs with modifications to the virtual muscle model and reflex modulation strategy. The modifications consist firstly of simplifications to the Hill-type virtual muscle model, resulting in a more straightforward formulation and reduced number of parameters; and second, using a finer division of gait subphases in the reflex modulation state machine, allowing for a higher degree of control over the shape of the assistive profile. Based on the proposed general structure, we present two controller variants for hip exoskeletons, with four- and five-state reflex modulations (NMC-4 and NMC-5). We used an iterative data-driven approach with two tuning stages (i.e., muscle parameters and reflex gains) to determine the controller parameters. Biological joint torque profiles and optimal torque profiles for metabolic cost reduction were used as references for the final tuning outcome. Experimental testing under various walking conditions demonstrated the capability of both variants for adapting to the locomotion task with minimal parameter adjustments, mostly in terms of timing. Furthermore, NMC-5 exhibited better alignment with biological and optimised torque profiles in terms of timing characteristics and relative magnitudes, resulting in less negative mechanical work. These findings firstly validate the adequacy of the simplified muscle model for assistive controllers, and demonstrate the utility of a more nuanced reflex modulation in improving the assistance quality.
Association between youth blood pressure and exposure to pediatric fruit and vegetable prescriptions
Authors: Saxe-Custack Amy , Todem David , LaChance Jenny , Kerver Jean , Anthony James 
Published: December 2024

Abstract
Background
Health impacts of pediatric fruit and vegetable prescription programs (FVPPs) are unclear. This study assessed whether exposure to an FVPP that provided $15 produce prescriptions during pediatric visits was associated with differences in child diet, food security, physical activity, weight status, and blood pressure.

Methods
This cross-sectional analysis included data from caregiver-child dyads with varying levels of exposure to the FVPP. Dyads completed surveys at pediatric offices. Trained research assistants measured height and weight of children and recorded blood pressure through chart review. Causal inference analyses using propensity score adjustments compared outcomes of exposure groups.

Results
680 dyads enrolled. Youth who received ≥1 prescription (exposed) reported greater physical activity compared to youth who received no prescriptions (unexposed). Blood pressure percentiles were lower among exposed when compared to unexposed youth (63.273 versus 75.060 for SBP; 71.472 versus 77.548 for DBP); and fewer exposed children recorded elevated blood pressure when compared to unexposed (0.141 versus 0.343 for SBP; 0.199 versus 0.344 for DBP; and 0.286 versus 0.531 overall). Similar findings were obtained using duration as a measure of exposure.

Conclusion
Youth exposed to the FVPP experienced greater physical activity and healthier blood pressure. Findings may indicate novel health-promoting effects of pediatric FVPPs.

Impact

When compared to youth with no exposure, youth exposed to a pediatric fruit and vegetable prescription program recorded greater physical activity and healthier blood pressure.

Youth with high exposure (≥24 months) to the fruit and vegetable prescription program experienced greater physical activity and healthier blood pressure when compared to youth with low exposure (<24 months).

This extends evaluation of pediatric fruit and vegetable prescription programs beyond feasibility and preliminary effectiveness to indicate potential of such programs in positively influencing physical activity and blood pressure of participating youth.

Findings indicate novel health-promoting effects of pediatric fruit and vegetable prescription programs.
Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma
Authors: Papargyriou Aristeidis , Najajreh Mulham , Cook David P. , Maurer Carlo H. , Bärthel Stefanie , Messal Hendrik A. , Ravichandran Sakthi K. , Richter Till , Knolle Moritz , Metzler Thomas , Shastri Akul R. , Öllinger Rupert , Jasper Jacob , Schmidleitner Laura , Wang Surui , Schneeweis Christian , Ishikawa-Ankerhold Hellen , Engleitner Thomas , Mataite Laura , Semina Mariia , Trabulssi Hussein , Lange Sebastian , Ravichandra Aashreya , Schuster Maximilian , Mueller Sebastian , Peschke Katja , Schäfer Arlett , Dobiasch Sophie , Combs Stephanie E. , Schmid Roland M. , Bausch Andreas R. , Braren Rickmer , Heid Irina , Scheel Christina H. , Schneider Günter , Zeigerer Anja , Luecken Malte D. , Steiger Katja , Kaissis Georgios , van Rheenen Jacco , Theis Fabian J. , Saur Dieter , Rad Roland , Reichert Maximilian 
Published: December 2024

AbstractIn patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies.