bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-378a inhibits glucose metabolism by suppressing GLUT1 in prostate cancer
Authors: Cannistraci A. , Hascoet P. , Ali A. , Mundra P. , Clarke N. W. , Pavet V. , Marais R. 
Published: January 2022

AbstractProstate cancer (PCa) is the fifth leading cause of cancer related deaths worldwide, in part due to a lack of molecular stratification tools that can distinguish primary tumours that will remain indolent from those that will metastasise. Amongst potential molecular biomarkers, microRNAs (miRs) have attracted particular interest because of their high stability in body fluids and fixed tissues. These small non-coding RNAs modulate several physiological and pathological processes, including cancer progression. Herein we explore the prognostic potential and the functional role of miRs in localised PCa and their relation to nodal metastasis. We define a 7-miR signature that is associated with poor survival independently of age, Gleason score, pathological T state, N stage and surgical margin status and that is also prognostic for disease-free survival in patients with intermediate-risk localised disease. Within our 7-miR signature, we show that miR-378a-3p (hereafter miR-378a) levels are low in primary tumours compared to benign prostate tissue, and also lower in Gleason score 8–9 compared to Gleason 6–7 PCa. We demonstrate that miR-378a impairs glucose metabolism and reduces proliferation in PCa cells through independent mechanisms, and we identify glucose transporter 1 (GLUT1) messenger RNA as a direct target of miR-378a. We show that GLUT1 inhibition hampers glycolysis, leading to cell death. Our data provides a rational for a new PCa stratification strategy based on miR expression, and it reveals that miR-378a and GLUT1 are potential therapeutic targets in highly aggressive glycolytic PCa.
A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis
Authors: Schack Line M. H. , Naderi Elnaz , Fachal Laura , Dorling Leila , Luccarini Craig , Dunning Alison M. ,   The Head and Neck Group of the Radiogenomics Consortium, Barnett Gill , Barrera Miguel Elías Aguado , Burnet Neil G. , Calvo Laura M. , Diergaarde Brenda , Dudding Tom , Dunning Alison , Duprez Fréderic , Kerns Sarah L. , Kiang Melvin C. L. , Langendijk Hans , Mehanna Hisham , Ness Andy , Sim Adelene Y. L. , Spiessens An , Summersgill Holly R. , Tajes Juan F. , Vega Ana , Welsh Ceilidh , Wen Enya O. H. , West Catharine ,   The Danish Head and Neck Cancer Group (DAHANCA), Ong Enya H. W. , Chua Melvin L. K. , Langendijk Johannes A. , Alizadeh Behrooz Z. , Overgaard Jens , Eriksen Jesper Grau , Andreassen Christian Nicolaj , Alsner Jan 
Published: January 2022

Abstract
Purpose
A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT.

Materials and methods
The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site.

Results
We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48–2.41; ppooled = 4.34 × 10−16).

Conclusion
This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.
Integration of tumour sequencing and case–control data to assess pathogenicity of RAD51C missense variants in familial breast cancer
Authors: Lim Belle W. X. , Li Na , Rowley Simone M. , Thompson Ella R. , McInerny Simone , Zethoven Magnus , Scott Rodney J. , Devereux Lisa , Sloan Erica K. , James Paul A. , Campbell Ian G. 
Published: January 2022

AbstractWhile protein-truncating variants in RAD51C have been shown to predispose to triple-negative (TN) breast cancer (BC) and ovarian cancer, little is known about the pathogenicity of missense (MS) variants. The frequency of rare RAD51C MS variants was assessed in the BEACCON study of 5734 familial BC cases and 14,382 population controls, and findings were integrated with tumour sequencing data from 21 cases carrying a candidate variant. Collectively, a significant enrichment of rare MS variants was detected in cases (MAF < 0.001, OR 1.57, 95% CI 1.00–2.44, p = 0.05), particularly for variants with a REVEL score >0.5 (OR 3.95, 95% CI 1.40–12.01, p = 0.006). Sequencing of 21 tumours from 20 heterozygous and 1 homozygous carriers of nine candidate MS variants identified four cases with biallelic inactivation through loss of the wild-type allele, while six lost the variant allele and ten that remained heterozygous. Biallelic loss of the wild-type alleles corresponded strongly with ER- and TN breast tumours, high homologous recombination deficiency scores and mutational signature 3. Using this approach, the p.Gly264Ser variant, which was previously suspected to be pathogenic based on small case–control analyses and loss of activity in in vitro functional assays, was shown to be benign with similar prevalence in cases and controls and seven out of eight tumours showing no biallelic inactivation or characteristic mutational signature. Conversely, evaluation of case–control findings and tumour sequencing data identified p.Ile144Thr, p.Arg212His, p.Gln143Arg and p.Gly114Arg as variants warranting further investigation.
Irgm1 regulates metabolism and function in T cell subsets
Authors: Alwarawrah Yazan , Danzaki Keiko , Nichols Amanda G. , Fee Brian E. , Bock Cheryl , Kucera Gary , Hale Laura P. , Taylor Gregory A. , MacIver Nancie J. 
Published: January 2022

AbstractImmunity Related GTPases (IRG) are a family of proteins produced during infection that regulate membrane remodeling events in cells, particularly autophagy and mitophagy. The human IRGM gene has been strongly associated with Crohn’s disease and other inflammatory diseases through Genome-Wide Association studies. Absence of Irgm1 in mice prompts intestinal inflammation, autoimmunity, and impaired immune control of pathogenic bacteria and protozoa. Although prior work has focused on a prominent role for IRGM/Irgm1 in regulating macrophage function, the work described here addresses a potential role of Irgm1 in regulating the function of mature T cells. Irgm1 was found to be highly expressed in T cells in a manner that varied with the particular T cell subset and increased with activation. Mice with a complete lack of Irgm1, or a conditional lack of Irgm1 specifically in T cells, displayed numerous changes in T cell numbers and function in all subsets examined, including CD4+ (Th1 and Treg) and CD8+ T cells. Related to changes in T cell number, apoptosis was found to be increased in Irgm1-deficient CD4+ and CD8+ T cells. Altered T cell metabolism appeared to be a key driver of the phenotypes: Glucose metabolism and glycolysis were increased in Irgm1-deficient CD4+ and CD8+ T cells, and muting these effects with glycolytic inhibitors partially restored T cell function and viability.
Effect of MBE growth conditions on GaAsBi photoluminescence lineshape and localised state filling
Authors: Bailey N. J. , Rockett T. B. O. , Flores S. , Reyes D. F. , David J. P. R. , Richards R. D. 
Published: January 2022

AbstractA series of gallium arsenide bismide device layers covering a range of growth conditions are thoroughly probed by low-temperature, power-dependent photoluminescence measurements. The photoluminescence data is modelled using a localised state profile consisting of two Gaussians. Good agreement with the raw data is achieved for all layers whilst fixing the standard deviation values of the two Gaussians and constraining the band gap using X-ray diffraction data. The effects of growth temperature and bismuth beam equivalent pressure on the localised state distributions, and other model variables, are both shown to be linked to emission linewidth and device properties. It is concluded that bismuth rich surface conditions are preferable during growth in order to produce the narrowest emission linewidths with this material. These results also show how the growth mode of a gallium arsenide bismide layer can be inferred ex-situ from low-temperature photoluminescence measurements.
Low-invasive 5D visualization of mitotic progression by two-photon excitation spinning-disk confocal microscopy
Authors: Kamada Takafumi , Otomo Kohei , Murata Takashi , Nakata Kaito , Hiruma Shota , Uehara Ryota , Hasebe Mitsuyasu , Nemoto Tomomi 
Published: January 2022

AbstractNon-linear microscopy, such as multi-photon excitation microscopy, offers spatial localities of excitations, thereby achieving 3D cross-sectional imaging with low phototoxicity even in thick biological specimens. We had developed a multi-point scanning two-photon excitation microscopy system using a spinning-disk confocal scanning unit. However, its severe color cross-talk has precluded multi-color simultaneous imaging. Therefore, in this study, we introduced a mechanical switching system to select either of two NIR laser light pulses and an image-splitting detection system for 3- or 4-color imaging. As a proof of concept, we performed multi-color fluorescent imaging of actively dividing human HeLa cells and tobacco BY-2 cells. We found that the proposed microscopy system enabled time-lapse multi-color 3D imaging of cell divisions while avoiding photodamage. Moreover, the application of a linear unmixing method to the 5D dataset enabled the precise separation of individual intracellular components in multi-color images. We thus demonstrated the versatility of our new microscopy system in capturing the dynamic processes of cellular components that could have multitudes of application.
AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells
Authors: Izutsu Runa , Osaki Mitsuhiko , Nemoto Hideyuki , Jingu Maho , Sasaki Ryo , Yoshioka Yusuke , Ochiya Takahiro , Okada Futoshi 
Published: January 2022

AbstractAdhesion of cancer cells to vascular endothelial cells in target organs is an initial step in cancer metastasis. Our previous studies revealed that amphoterin-induced gene and open reading frame 2 (AMIGO2) promotes the adhesion of tumor cells to liver endothelial cells, followed by the formation of liver metastasis in a mouse model. However, the precise mechanism underlying AMIGO2-promoted the adhesion of tumor cells and liver endothelial cells remains unknown. This study was conducted to explore the role of cancer cell-derived AMIGO2-containing extracellular vesicles (EVs) in the adhesion of cancer cells to human hepatic sinusoidal endothelial cells (HHSECs). Western blotting indicated that AMIGO2 was present in EVs from AMIGO2-overexpressing MKN-28 gastric cancer cells. The efficiency of EV incorporation into HHSECs was independent of the AMIGO2 content in EVs. When EV-derived AMIGO2 was internalized in HHSECs, it significantly enhanced the adhesion of HHSECs to gastric (MKN-28 and MKN-74) and colorectal cancer cells (SW480), all of which lacked AMIGO2 expression. Thus, we identified a novel mechanism by which EV-derived AMIGO2 released from AMIGO2-expressing cancer cells stimulates endothelial cell adhesion to different cancer cells for the initiate step of liver metastasis.
Accounting for variation in temperature and oxygen availability when quantifying marine ecosystem metabolism
Authors: Bracken Matthew E. S. , Miller Luke P. , Mastroni Sarah E. , Lira Stephany M. , Sorte Cascade J. B. 
Published: January 2022

AbstractIt is critical to understand how human modifications of Earth’s ecosystems are influencing ecosystem functioning, including net and gross community production (NCP and GCP, respectively) and community respiration (CR). These responses are often estimated by measuring oxygen production in the light (NCP) and consumption in the dark (CR), which can then be combined to estimate GCP. However, the method used to create “dark” conditions—either experimental darkening during the day or taking measurements at night—could result in different estimates of respiration and production, potentially affecting our ability to make integrative predictions. We tested this possibility by measuring oxygen concentrations under daytime ambient light conditions, in darkened tide pools during the day, and during nighttime low tides. We made measurements every 1–3 months over one year in southeastern Alaska. Daytime respiration rates were substantially higher than those measured at night, associated with higher temperature and oxygen levels during the day and leading to major differences in estimates of GCP calculated using daytime versus nighttime measurements. Our results highlight the potential importance of measuring respiration rates during both day and night to account for effects of temperature and oxygen—especially in shallow-water, constrained systems—with implications for understanding the impacts of global change on ecosystem metabolism.
Individual differences in the experience of body ownership are related to cortical thickness
Authors: Matuz-Budai Timea , Lábadi Beatrix , Kohn Eszter , Matuz András , Zsidó András Norbert , Inhóf Orsolya , Kállai János , Szolcsányi Tibor , Perlaki Gábor , Orsi Gergely , Nagy Szilvia Anett , Janszky József , Darnai Gergely 
Published: January 2022

AbstractThe widely used rubber hand illusion (RHI) paradigm provides insight into how the brain manages conflicting multisensory information regarding bodily self-consciousness. Previous functional neuroimaging studies have revealed that the feeling of body ownership is linked to activity in the premotor cortex, the intraparietal areas, the occipitotemporal cortex, and the insula. The current study investigated whether the individual differences in the sensation of body ownership over a rubber hand, as measured by subjective report and the proprioceptive drift, are associated with structural brain differences in terms of cortical thickness in 67 healthy young adults. We found that individual differences measured by the subjective report of body ownership are associated with the cortical thickness in the somatosensory regions, the temporo-parietal junction, the intraparietal areas, and the occipitotemporal cortex, while the proprioceptive drift is linked to the premotor area and the anterior cingulate cortex. These results are in line with functional neuroimaging studies indicating that these areas are indeed involved in processes such as cognitive-affective perspective taking, visual processing of the body, and the experience of body ownership and bodily awareness. Consequently, these individual differences in the sensation of body ownership are pronounced in both functional and structural differences.
Anti-Pseudomonas aeruginosa activity of a C16-terpene dilactone isolated from the endophytic fungus Neofusicoccum luteum of Kigelia africana (Lam.)
Authors: Bodede Olusola , Kuali Mamokoena , Prinsloo Gerhard , Moodley Roshila , Govinden Roshini 
Published: January 2022

AbstractFungal endophytes have the capacity to biosynthesize secondary metabolites that are produced by their host plants. In this study, a dilactone terpenoid of C16 architecture was isolated from the fungal endophytes of Kigeliaafricana, in our attempt to identify anti-Pseudomonasaeruginosa metabolites. Thirty-eight fungal isolates were cultured for biomolecule production over a period of thirty days. Extracts from three (ZF 34, ZF 52 and ZF 91) of the fungi showed good anti-P.aeruginosa activity, with ZF 52 presenting the best MIC of 19.53 µg/mL and was accordingly subjected to chromatographic separation. Based on nuclear magnetic resonance (NMR) spectroscopy, high resolution mass spectrometry and single crystal X-ray diffraction (XRD) analyses, the isolated compound was identified as a C16-terpene dilactone, with a structure consistent with that of the known diterpene, CJ-14445. The isolated dilactone showed anti-P.aeruginosa activity with MIC of 0.61 µg/mL, signifying the antibacterial potential of the biomolecule. The bioactive fungal isolate (ZF 52) was identified as Neofusicoccumluteum based on genomic DNA sequencing. This is the first report of the endophyte N.luteum from K.africana and the first reported occurrence of CJ-14445 in the fungus.
Variation in community and ambulance care processes for out-of-hospital cardiac arrest during the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Masuda Yoshio , Teoh Seth En , Yeo Jun Wei , Tan Darren Jun Hao , Jimian Daryl Lin , Lim Shir Lynn , Ong Marcus Eng Hock , Blewer Audrey L. , Ho Andrew Fu Wah 
Published: January 2022

AbstractBystander cardiopulmonary resuscitation (BCPR), early defibrillation and timely treatment by emergency medical services (EMS) can double the chance of survival from out-of-hospital sudden cardiac arrest (OHCA). We investigated the effect of the COVID-19 pandemic on the pre-hospital chain of survival. We searched five bibliographical databases for articles that compared prehospital OHCA care processes during and before the COVID-19 pandemic. Random effects meta-analyses were conducted, and meta-regression with mixed-effect models and subgroup analyses were conducted where appropriate. The search yielded 966 articles; 20 articles were included in our analysis. OHCA at home was more common during the pandemic (OR 1.38, 95% CI 1.11–1.71, p = 0.0069). BCPR did not differ during and before the COVID-19 pandemic (OR 0.94, 95% CI 0.80–1.11, p = 0.4631), although bystander defibrillation was significantly lower during the COVID-19 pandemic (OR 0.65, 95% CI 0.48–0.88, p = 0.0107). EMS call-to-arrival time was significantly higher during the COVID-19 pandemic (SMD 0.27, 95% CI 0.13–0.40, p = 0.0006). Resuscitation duration did not differ significantly between pandemic and pre-pandemic timeframes. The COVID-19 pandemic significantly affected prehospital processes for OHCA. These findings may inform future interventions, particularly to consider interventions to increase BCPR and improve the pre-hospital chain of survival.
Plasticity of feeding behaviour traits in response to production environment (temperate vs. tropical) in group-housed growing pigs
Authors: Poullet Nausicaa , Rauw Wendy M. , Renaudeau David , Riquet Juliette , Giorgi Mario , Billon Yvon , Gilbert Hélène , Gourdine Jean-Luc 
Published: January 2022

AbstractHeat stress affects pig metabolism, health and welfare, resulting in reduced growth and important economic losses. The present experiment aimed to evaluate the effects of two climatic environments [temperate (TEMP) vs. tropical humid (TROP)] on feeding behaviour in growing pigs. The feeding behaviour traits were measured with automated feeders and included: daily feed intake, daily eating time, feeding rate, daily number of meals, feed intake per meal, and feeding time per meal. Pigs came from a backcross population between Large White (LW, heat sensitive) and Creole (CR, heat tolerant) pigs. The same 10 F1 LW × CR boars (sire families [SF]) were mated with related LW sows in each environment. Feeding behaviour was recorded for a total of 1,296 pigs (n = 634 pigs for TEMP and n = 662 pigs for TROP) between 11 and 23 weeks of age. Growth performance and thermoregulatory responses (rectal and skin temperatures) were also measured. Results show that TROP conditions affect feeding behaviour traits: animals had more meals per day but these meals were smaller both in duration and in size, resulting in lower daily feed intake and less time eating per day. Significant SF by environment (GxE) interactions were found for all feeding behaviour traits. When SF were distributed into robust and sensitive groups (previously defined according to performance and thermoregulatory traits), results showed group by environment interactions for all feeding traits, except meal frequency. Moreover, a significant difference in feeding rate between robust and sensitive group was detected in TEMP, suggesting that feeding rate may be a good candidate to evaluate heat tolerance.
A mechanistic view on the aging human skin through ex vivo layer-by-layer analysis of mechanics and microstructure of facial and mammary dermis
Authors: Lynch Barbara , Pageon Hervé , Le Blay Heiva , Brizion Sébastien , Bastien Philippe , Bornschlögl Thomas , Domanov Yegor 
Published: January 2022

AbstractAge-related changes in skin mechanics have a major impact on the aesthetic perception of skin. The link between skin microstructure and mechanics is crucial for therapeutic and cosmetic applications as it bridges the micro- and the macro-scale. While our perception is governed by visual and tactile changes at the macroscopic scale, it is the microscopic scale (molecular assemblies, cells) that is targeted by topical treatments including active compounds and energies. We report here a large dataset on freshly excised human skin, and in particular facial skin highly relevant for cosmetics and aesthetic procedures. Detailed layer-by-layer mechanical analysis revealed significant age-dependent decrease in stiffness and elastic recoil of full-thickness skin from two different anatomical areas. In mammary skin, we found that the onset of mechanical degradation was earlier in the superficial papillary layer than in the deeper, reticular dermis. These mechanical data are linked with microstructural alterations observed in the collagen and elastic networks using staining and advanced imaging approaches. Our data suggest that with ageing, the earliest microstructural and mechanical changes occur in the top-most layers of dermis/skin and then propagate deeper, providing an opportunity for preventive topical treatments acting at the level of papillary dermis.
miR-548j-5p regulates angiogenesis in peripheral artery disease
Authors: Lee Chiu-Yang , Lin Shing-Jong , Wu Tao-Cheng 
Published: January 2022

AbstractPeripheral artery disease (PAD) is a vascular disease involving diffuse atherosclerosis, and is associated with increased cardiovascular mortality and morbidity. Critical limb ischemia (CLI) is the most severe complication of PAD. In addition to medical and interventional treatment, therapeutic angiogenesis is a novel therapy for PAD. Circulating microRNAs (miRNAs) are considered key regulators of gene expression, but their role in ischemic-induced angiogenesis is poorly-characterized. There is currently a limited understanding of the specific miRNAs associated with PAD. To determine the regulation of miRNAs, we obtained miRNA profiles using RNA isolated from patients with PAD and a control group. The effects of specific miRNAs on angiogenesis were evaluated by assessing the in vitro angiogenic function of endothelial progenitor cells (EPCs), performing an in vivo angiogenesis assay, and employing a mouse hindlimb ischemic model. Our results demonstrated that circulating miR-548j-5p was significantly reduced in patients with PAD as compared with the controls. miR-548j-5p promoted EPC angiogenesis by enhancing migration and tube formation. The endothelial nitric oxide synthase (NOS) and stromal cell-derived factor (SDF)-1 signaling pathways appeared to be potential targets of miR-548j-5p. Furthermore, the results of a directed in vivo angiogenesis assay of EPCs and a hindlimb ischemia mouse model demonstrated that miR-548j-5p enhanced the capillary density and blood flow recovery in hindlimb ischemia. In conclusion, our data indicated that up-regulation of miR-548j-5p promotes angiogenesis in ischemic tissue and may represent a novel therapeutic approach for PAD.