bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phenomenological analysis of medical tourism: Investigating the lived experience of returning to Canada after osseointegration abroad
Authors: Bedore Christopher D. , Woodend A. Kirsten 
Published: October 2023

Background:
Travel out of country for medical care is increasing for many reasons including costs, wait-lists, and availability of procedures. Until 2018, when the surgery was offered in only 1 province, Canadians with amputation wanting osseointegration (OI) had to travel out of country for the surgery. The purpose of this study was to understand the lived experience of accessing health care in Canada after having a procedure performed out of country.

Methods:
This is a phenomenological study of persons with amputation who had OI outside of Canada. The grand tour interview question was “What was it like travelling to another country for OI surgery and then returning to access follow-up care in Canada?”

Results:
There were 5 participants, and 5 themes emerged: (1) lack of support from Canadian physicians; (2) exceptional support from prosthetists and other members of the health care team; (3) continued reliance on the country where the procedure was initially performed; (4) self-advocacy for access to care; and (5) benefits of travelling outweighing the problems faced.

Conclusions:
These themes are not unique to OI, but to medical tourism as a whole. The lack of support was countered partly by a strong sense of self-advocacy from the participants and support from other members of the health care team.
Ischemia-Induced Metabolic Patterns Associate With Kidney Function During Normothermic Kidney Perfusion, a Preclinical Study
Authors: De Beule Julie , De Craemer Sam , Verstraeten Laurence , Ghesquière Bart , Jochmans Ina 
Published: October 2023

Objective:
To investigate if ischemia alters donor kidney metabolism and whether these changes associate with organ function.

Summary Background Data:
An unmet need in kidney transplantation is the ability to predict post-transplant organ function before transplantation. Key to such viability testing is a profound understanding of the organ’s complex biochemistry and how ischemia, inevitable during the transplantation process, influences this.

Methods:
First, metabolic changes in glucose, lactate and 20 amino acids induced by no, 1h of warm, or 22h of cold ischemia were investigated during 4h perfusion of pig kidneys with autologous whole blood (n=6/group), simulating the ischemia-reperfusion phase of transplantation. Next, we confirmed similar metabolic changes during normothermic preservation of pig (n=3/group; n=4 for cold ischemia) and discarded human kidneys (n=6) perfused with a red-blood cell based perfusate.

Results:
At 2h of perfusion with autologous whole blood, abundances of 17/20 amino acids were significantly different between groups, reflecting the type of ischemia. Amino acid changes at 15 min and 2h of perfusion correlated with future kidney function during perfusion. Similar metabolic patterns were observed during perfusion preservation of pig and discarded human donor kidneys, suggesting an opportunity to assess kidney viability before transplantation.

Conclusions:
Perfusate metabolite changes during normothermic kidney perfusion represent a unique non-invasive opportunity to assess graft viability. These findings now need validation in transplant studies.
Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase
Authors: Duan Ruifeng , von Ehrlich-Treuenstätt Viktor H , Kakoschke Sara C , Schardey Josefine , Wirth Ulrich , Albertsmeier Markus , Renz Bernhard W , Andrassy Joachim , Bazhin Alexandr V , Hodin Richard A , Werner Jens , Ilmer Matthias , Kühn Florian 
Published: October 2023

BACKGROUND:
Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery.

STUDY DESIGN:
Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para-nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS.

RESULTS:
Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = −0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP—also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009).

CONCLUSIONS:
Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.
Effect of Oral Chondroitin Sulfate Supplementation on Acute Brain Injury in a Murine Necrotizing Enterocolitis Model
Authors: Manohar Krishna , Mesfin Fikir M , Liu Jianyun , Shelley W Christopher , Brokaw John P , Markel Troy A 
Published: October 2023

BACKGROUND:
Necrotizing enterocolitis (NEC) is a devastating condition where inflammatory changes and necrosis in the gut results in activation of brain microglia and subsequent neurodevelopmental impairment. Chondroitin sulfate (CS) is a glycosaminoglycan in human breast milk that is absent in conventional formulas. We hypothesized that oral formula supplementation with CS during a murine model of experimental NEC would not only attenuate intestinal injury, but also brain injury.

STUDY DESIGN:
NEC was induced in mouse pups on postnatal days (PNDs) 5 to 8. Three conditions were studied: (1) breastfed controls, (2) NEC, and (3) NEC+enteral CS (formula+200 mg/kg/d of CS). Pups were euthanized on PND 9 or reunited with dams by the evening of PND 8. Intestinal segments were H&E stained, and immunohistochemistry was performed on brain tissue for Iba-1 to assess for microglial morphology and cortical changes. Neurodevelopmental assays were performed on mice reunited with foster dams on PND 9. Single-cell RNA-sequencing analysis was performed on human intestinal epithelial cells exposed to (1) nothing, (2) hydrogen peroxide (H2O2) alone, or (3) H2O2 + CS to look at the differential gene expression between groups. Groups were compared with ANOVA or Kruskal–Wallis tests as appropriate with p < 0.05 considered significant.

RESULTS:
Compared with NEC, mice treated with oral CS showed improved clinical outcomes, decreased intestinal injury, and attenuated microglial activation and deleterious cortical change. Mice with CS performed better on early neurodevelopmental assays when compared with NEC alone. Single-cell analysis of HIEC-6 cells demonstrated that CS treatment down regulated several inflammatory pathways including nuclear factor κB—suggesting an explanation for the improved Th17 intestinal cytokine profile.

CONCLUSIONS:
Oral CS supplementation improved both physiological, clinical, and developmental outcomes. These data suggest that CS is a safe compound for formula supplementation for the prevention of NEC.
Aging and intraocular pressure homeostasis in mice
Authors: Li Guorong , van Batenburg-Sherwood Joseph , Safa Babak N. , Fraticelli Guzmán Nina Sara , Wilson Andrea , Bahrani Fard Mohammad Reza , Choy Kevin , De Ieso Michael L. , Cui J. Serena , Feola Andrew J , Weisz Tara , Kuhn Megan , Rickman Cathy Bowes , Farsiu Sina , Ethier C. Ross , Stamer W. Daniel 
Published: October 2023

AbstractAge and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma.
A fast and reliable larval sampling method for improving the monitoring of fruit flies in soft and stone fruits
Authors: Zriki Ghais , Belois Rémy , Fournier Christine , Tergoat-Bertrand Léa , Poupart Pierre-Yves , Bardel Amélie , Gard Benjamin , Rode Nicolas O. 
Published: October 2023

AbstractThe spotted-wing drosophila,Drosophila suzukii(Matsumura) (Diptera: Drosophilidae), threatens both the soft-skinned and stone fruit industry in Asia, Europe and America. Integrated pest management requires monitoring for infestation rates in real-time. Although baited traps are widely used for field monitoring, trap captures are weakly correlated to infestation rates. Thus, monitoring for larvae instead of adult flies represents the most reliable monitoring technique. Current methods for larval monitoring (e.g. dunk flotation) are both time-consuming and labor-intensive. In this study, we develop the sleeve method, a new method for monitoring larval infestation in strawberries through the inspection of fruits individually crushed within transparent plastic sleeves. Based on count data from both specialist and non-specialist observers, the estimation of larval infestation with the sleeve method is fast, precise and highly repeatable within and among all observers. Mean processing time is twice faster than previous methods and varies from 33 to 80 seconds per sample, depending on infestation levels. As the accuracy of the sleeve method decreases with infestation levels, we suggest ways to improve its accuracy by incubating fruits for 48h and calibrating data with exact counts. This new method is easier to use, faster and more cost-effective than previous monitoring methods. It could be used to monitorD. suzukiiinfestations in various fruit crops and is scalable to the farm-level for fruit growers or for academic research. Finally, the method represents a promising monitoring tool for effective management programs ofD. suzukiiand other insect pests of soft and stone fruits.
Yes1-mediated Cul9 phosphorylation promotes the metabolic reprogramming in gastric cancer
Authors: Wu Youliang , Zhang Heng , Zhang Shangxin , Wang Mingliang , Wang Huizhen , Huang He , Hong Xuehui , Zhang Zhiyong , Li Yongxiang 
Published: October 2023

AbstractAlthough Cul9 has been implicated in human carcinogenesis, its upstream regulators and roles remain unknown. Herein, we indicate that the Cul9 promoter is hypermethylated in GCs. Bioinformatics, mass spectrometry, and unbiased-kinase screen identify the tyrosine kinase Yes1 as a key regulator of Cul9. Yes1 phosphorylates Cul9 at Y1505, promoting its selective autophagy. Patient-associated mutation of Yes1 or helicobacter pylori infection induces Cul9-Y1505 phosphorylation which switches Cul9 from a tumor-suppressor to an oncogene, as evidenced by the fact that Cul9-Y1505D knockin mice are more susceptible to gastric tumorigenesis than wild-type counterparts. Metabolic profiling and ATAC sequencing reveal that Cul9-Y1505D mutant promotes pyrimidine and purine synthesis pathways in GC. DNA-demethylating drug decitabine or HG78 compound upregulates Cul9 expression and limits GC cell proliferation in a Yes1-dependent manner. The Yes1 inhibitor CH6953755 or Leflunomide and Mycophenolate mofetil (MMF) also impair the malignancy of GC with Cul9 dysregulation. Cul9 in turn binds Yes1 and disrupts Yes1 stability, establishing a feedback circuit. Collectively, our project reveals an unrecognized role of the Yes1-Cul9 loop in GC, suggesting potential therapeutic targets.
Towards Parsimonious Generative Modeling of RNA Families
Authors: Calvanese Francesco , Lambert Camille N. , Nghe Philippe , Zamponi Francesco , Weigt Martin 
Published: October 2023

AbstractGenerative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the characteristics of RNA sequences, with a strong emphasis on simplicity, efficiency, and interpretability. eaDCA explicitly constructs sparse coevolutionary models for RNA families, achieving performance levels comparable to more complex methods while utilizing a significantly lower number of parameters. Our approach demonstrates efficiency in generating artificial RNA sequences that closely resemble their natural counterparts in both statistical analyses and SHAPE-MaP experiments, and in predicting the effect of mutations. Notably, eaDCA provides a unique feature: estimating the number of potential functional sequences within a given RNA family. For example, in the case of cyclic di-AMP riboswitches (RF00379), our analysis suggests the existence of approximately 1039functional nucleotide sequences. While huge compared to the known < 4, 000 natural sequences, this number represents only a tiny fraction of the vast pool of nearly 1082possible nucleotide sequences of the same length (136 nucleotides). These results underscore the promise of sparse and interpretable generative models, such as eaDCA, in enhancing our understanding of the expansive RNA sequence space.
Horizontal gene transfer of a key translation protein has shaped the polyproline proteome
Authors: Brewer Tess E. , Wagner Andreas 
Published: October 2023

AbstractProlines take longer than other amino acids to be incorporated into nascent proteins and cause ribosomes to stall during translation. This phenomenon occurs in all domains of life and is exacerbated at polyproline motifs. Such stalling can be eased by elongation factor P (EFP) in bacteria. We discovered a potential connection between horizontally transferred EFP variants and genomic signs of EFP dysfunction. Horizontal transfer of theefpgene has occurred several times throughout the bacterial tree of life, and such transfer events are associated with the loss of otherwise highly conserved polyproline motifs. In this study, we pinpoint cases of horizontal EFP transfer among a diverse set of bacterial genomes and examine the consequences of these events on genome evolution in the phyla Thermotogota and Planctomycetes. In these phyla, horizontal EFP transfer is not only associated with the loss of conserved polyproline motifs, but also with the loss of entire polyproline motif containing proteins, whose expression is likely dependent on EFP. In particular, three proteases (Lon, ClpC, and FtsH) and three tRNA synthetases (ValS, IleS1, IleS2) appear highly sensitive to EFP transfer. The conserved polyproline motifs within these proteins all reside within, or in close proximity to ATP binding regions, some of which have been shown to be crucial to their function. Our work shows that the horizontal transfer of EFP has left genomic traces that persist to this day. It also implies that the process of ‘domesticating’ a horizontally transferredefpgene can perturb the overall function of EFP.
Sealing the deal – Antarctic fur seals’ active hunting tactics to capture small evasive prey revealed by miniature sonar tags
Authors: Chevallay Mathilde , Guinet Christophe , Goulet-Tran Didier , Jeanniard du Dot Tiphaine 
Published: October 2023

AbstractFine-scale interactions between predators and their prey are key factors determining both predators’ hunting efficiency and prey survival. The ability to adopt hunting tactics that minimise the risk of triggering an escape reaction from the prey is crucial for an efficient foraging, and is contingent to detection capabilities and locomotor performances of both predators and prey. In this study, we aimed at describing fine-scale predator-prey interactions in female Antarctic fur seals (Arctocephalus gazella,AFS hereafter), a small pinniped foraging on evasive prey. Our objectives were (1) to describe characteristics of prey targeted by female AFS to assess prey selection in this species; (2) to estimate the timing of prey detection by AFS and prey reaction to the AFS approach, and (3) to describe AFS hunting tactics, i.e. fine-scale AFS posture and swimming activity during prey capture events.In fine, we seek to better understand AFS’s efficiency at exploiting their small prey. To do so, we used data recorded by a newly developed sonar tag that combines active acoustics with ultra-high resolution movement sensors to study simultaneously the fine-scale behaviour of both AFS and prey during predator-prey interactions. We analysed more than 1200 prey capture events in eight female AFS and showed that AFS and their prey detect each other at the same time, i.e. 1-2 seconds before the strike, forcing AFS to display reactive fast-moving chases to capture their prey. Prey detection was consistently followed by bursts of accelerations from AFS, which lasted longer for evasive prey. We suggest that the ability of AFS to perform bursts of accelerations may allow them to target evasive prey. This active hunting tactics is likely very energy-consuming but might be compensated by the consumption of highly nutritious prey.
DNA metabarcoding reveals limited consumption of livestock and black rhinoceros by spotted hyenas in a prey-rich environment
Authors: Dheer Arjun , Danabalan Renita , Pellizzone Antonia , Davidian Eve , Naman Philemon , Mazzoni Camila , Höner Oliver P. 
Published: October 2023

AbstractThe diet of large carnivores is of great interest to conservation managers, as it can reveal the extent of human-carnivore conflict and the impact of carnivores on species of high conservation priority. Metabarcoding of environmental DNA can identify species and is often more reliable in doing so than observational or morphological methods. Metabarcoding is particularly powerful at detecting elusive and rare species and has therefore become a widely applied tool in biodiversity research. Here, we used DNA metabarcoding of fecal samples to determine the diet of spotted hyenas in the Ngorongoro Crater, a protected area in Northern Tanzania surrounded by areas co-inhabited by pastoralists. We assessed which species hyenas preferably consumed over a 24-year period and how frequently they consumed pastoralist livestock and black rhinoceros, a species of high economic value and conservation priority. We further estimated the effects of three key socio-demographic variables – age, social rank, and sex – on the propensity of hyenas to consume livestock. We detected DNA from 20 species in 371 hyena feces. Hyenas preferably consumed blue wildebeest and Grant’s gazelle. Among the detected species were five domestic species and one wild species that lived in the pastoralist-inhabited areas but not the Crater. This shows that resident Crater hyenas undertake foraging trips to areas surrounding the Crater. DNA of domestic species however was rarely detected (4.1% of 434 detections), and predominantly in feces of old hyenas. This suggests that Crater hyenas rarely consume livestock and that livestock is mostly consumed by hyenas less capable of hunting fleet-footed and powerful wild prey. No DNA of black rhinoceros was detected in any of the samples, suggesting that Crater hyenas do not frequently consume rhinoceros. Our findings suggest that the impact of Crater hyenas on livestock and wildlife of high conservation priority is limited. Our study highlights the potential of DNA metabarcoding to assess the extent of human-carnivore conflict and to guide evidence-based conservation efforts to promote coexistence of carnivores, humans and species of high conservation priority.
Introducing Isotòpia: a stable isotope database for Classical Antiquity
Authors: Formichella Giulia , Soncin Silvia , Lubritto Carmine , Tafuri Mary Anne , Fernandes Ricardo , Cocozza Carlo 
Published: October 2023

AbstractWe present Isotòpia, an open-access database compiling over 36,000 stable isotope measurements (δ13C, δ15N, δ18O, δ34S,87Sr/86Sr,206Pb/204Pb,207Pb/204Pb,208Pb/204Pb,207Pb/206Pb, and208Pb/206Pb) on human, animal, and plant bioarchaeological remains dating to Classical Antiquity (approximately 800 BCE - 500 CE). These were recovered from different European regions, particularly from the Mediterranean. Isotòpia provides a comprehensive characterisation of the isotopic data, encompassing various historical, archaeological, biological, and environmental variables. Isotòpia is a resource for meta-analytical research of past human activities and paleoenvironments. The database highlights data gaps in isotopic classical archaeology, such as the limited number of isotopic measurements available for plants and animals, limited number of studies on spatial mobility, and spatial heterogeneity of isotopic research. As such, we emphasise the necessity to address and fill these gaps in order to unlock the reuse potential of this database.
GAS6 and AXL promote insulin resistance by rewiring insulin signaling and increasing insulin receptor trafficking to endosomes
Authors: Schott Céline , Germain Amélie , Lacombe Julie , Pata Monica , Faubert Denis , Boulais Jonathan , Carmeliet Peter , Côté Jean-François , Ferron Mathieu 
Published: October 2023

ABSTRACTGrowth-arrest specific 6 (GAS6) is a secreted protein that acts as a ligand for TAM receptors (TYRO3, AXL and MERTK). In humans, GAS6 circulating levels and genetic variations inGAS6are associated with hyperglycemia and increased risk of type 2 diabetes. However, the mechanisms by which GAS6 influences glucose metabolism are not understood. Here, we show thatGas6deficiency in mice increases insulin sensitivity and protects from diet-induced insulin resistance. Conversely, increasing GAS6 circulating levels is sufficient to reduce insulin sensitivityin vivo. GAS6 inhibits the activation of the insulin receptor (IR) and reduces insulin response in muscle cells in vitro and in vivo. Mechanistically, AXL and IR fom a complex, while GAS6 reprograms signaling pathways downstream of IR. This results in increased IR endocytosis following insulin treatment. This study contributes to a better understanding of the cellular and molecular mechanisms by which GAS6 and AXL influence insulin sensitivity.ARTICLE HIGHLIGHTSGAS6 deficient mice are characterized by improved glucose tolerance, increased insulin sensitivity and are protected from diet-induced insulin resistance.The GAS6 receptor AXL is expressed in muscle cells and forms a complex with the insulin receptor.GAS6 reprograms insulin signaling by modulating the phosphorylation of proteins implicated in endocytosis, vesicle-mediated transport, and membrane trafficking.AXL and GAS6 promotes insulin receptor endocytosis following insulin treatment.