bluuebunny/crossref_metadata_2025_split huggingface dataset:
LPS preconditioning of MSC‐CM improves protection against hypoxia/reoxygenation‐induced damage in H9c2 cells partly via HMGB1/Bach1 signalling
Authors: Wang Dan , Xie Yu , Peng Hui‐Qian , Wen Zhi‐Min , Ying Zi‐Yue , Geng Cong , Wu Jun , Lv Hui‐Yi , Xu Bing 
Published: September 2022

AbstractMesenchymal stem cell‐derived conditioned medium (MSC‐CM) improves cardiac function after myocardial infarction; however, this cardioprotective effect is moderate and transient. Lipopolysaccharide (LPS) pretreatment partially improves MSC‐CM‐mediated cardioprotective effects owing to the presence of paracrine factors. However, the mechanism underlying these improved effects remains unknown. To study the effect of LPS‐pretreated MSC‐CM on hypoxia/reoxygenation (H/R)‐induced injury, MSCs were treated with or without LPS (400 ng/mL) for 48 h, and the supernatant was collected (MSC‐CM). Subsequently, H9c2 cells were co‐cultured with Nor‐CM (CM derived from LPS‐untreated MSCs) and LPS‐CM (CM derived from LPS‐pretreated MSCs) for 24 h and subjected to H/R. MSC‐CM inhibited the progression of H/R‐induced injury in H9c2 cells, and this protective effect was enhanced via LPS pretreatment as evidenced by the improved apoptosis assessment index (i.e. caspase‐3 and B‐cell lymphoma‐2 [Bcl‐2] expression) and decreased levels of lactic dehydrogenase (LDH) and cardiac troponin (cTn). In addition, the results of haematoxylin–eosin staining (H&E), transmission electron microscopy (TEM) and TdT‐mediated dUTP nick‐end labelling (TUNEL) validated that MSC‐CM inhibited H/R‐induced injury in H9c2 cardiomyocytes. LPS pretreatment downregulated the expression of high mobility group box‐1 (HMGB1) and BTB and CNC homology‐1 (Bach1) proteins in MSCs but upregulated the expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and insulin‐like growth factor (IGF). HMGB1 knockdown (MSC/siHMGB1‐CM) significantly decreased the expression of Bach1 and increased the expression of VEGF, HGF and IGF. Bach1 knockdown (MSC/siBach1‐CM) did not alter the production of HMGB1 but increased the expression of VEGF and IGF. LPS pretreatment did not alter the expression of the paracrine factors VEGF and HGF in the MSC/siHMGB1 group but increased their expression in the MSC/siBach1 group. The myocyte anti‐apoptotic effects of MSCs/siBach1‐CM were similar to those of untreated MSCs, which were not enhanced by LPS. LPS‐pretreated MSC‐CM protects H9c2 cells against H/R‐induced injury partly through the HMGB1/Bach1 signalling pathway.
PD‐L1/PD‐L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK
Authors: Cao Yihui , Liang Weiye , Fang Lian , Liu Ming‐kai , Zuo Jia , Peng Ying‐long , Shan Jia‐jie , Sun Rui‐xia , Zhao Jie , Wang Jian 
Published: September 2022

AbstractProgrammed death ligand 1 (PD‐L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD‐1)/PD‐L1 signalling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) are elusive. We previously found that PD‐L1 can bind to PD‐L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD‐L1 binds to PD‐L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD‐L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD‐L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD‐L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD‐L1 was found to promote epithelial–mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1–86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD‐L1 after binding to PD‐L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti‐PD‐L1 antibodies.
Drivers of fungal diversity and community biogeography differ between green roofs and adjacent ground‐level green space
Authors: Droz Anna G. , Coffman Reid R. , Eagar Andrew C. , Blackwood Christopher B. 
Published: September 2022

AbstractGreen roof soils are usually engineered for purposes other than urban biodiversity, which may impact their fungal communities, and in turn impact the health of plants in the urban ecosystem. We examined the drivers of fungal diversity and community composition in soil of green roofs and adjacent ground‐level green spaces in three Midwestern USA cities—Chicago, Cleveland, and Minneapolis. Overall, fungal communities on green roofs were more diverse than ground‐level green spaces and were correlated with plant cover (positively) and roof age (negatively) rather than abiotic soil properties. Fungal community composition was distinct between roof and ground environments, among cities, and between sampling sites, but green roofs and their immediately surrounding ground‐level green space showed some similarity. This suggests dispersal limitation may result in geographic structuring at large spatial scales, but dispersal between roofs and their neighbouring sites may be occurring. Different fungal taxonomic and functional groups were better explained when roofs were classified either by depth (extensive or intensive) or functional intent of the roof design (i.e. stormwater/energy, biodiversity, or aesthetics/recreation). Our results demonstrate that green roofs are an important reservoir of fungal diversity in the urban landscape, which should be considered in future green roof design.
The ‘oxygen’ in oxygen minimum zones
Authors: Canfield Don E. , Kraft Beate 
Published: September 2022

AbstractAerobic processes require oxygen, and anaerobic processes are typically hindered by it. In many places in the global ocean, oxygen is completely removed at mid‐water depths forming anoxic oxygen minimum zones (A‐OMZs). Within the oxygen gradients linking oxygenated waters with A‐OMZs, there is a transition from aerobic to anaerobic microbial processes. This transition is not sharp and there is an overlap between processes using oxygen and those using other electron acceptors. This review will focus on the oxygen control of aerobic and anaerobic metabolisms and will explore how this overlap impacts both the carbon and nitrogen cycles in A‐OMZ environments. We will discuss new findings on non‐phototrophic microbial processes that produce oxygen, and we focus on how oxygen impacts the loss of fixed nitrogen (as N2) from A‐OMZ waters. There are both physiological and environmental controls on the activities of microbial processes responsible for N2 loss, and the environmental controls are active at extremely low levels of oxygen. Understanding how these controls function will be critical to understanding and predicting how fixed‐nitrogen loss in the oceans will respond to future global warming.
Multi‐disciplinary, simulation‐based, standardised trauma team training within the Victorian State Trauma System
Authors: Fitzgerald Mark C , Noonan Michael , Lim Emma , Mathew Joseph K , Boo Ellaine , Stergiou Helen E , Kim Yesul , Reilly Stephanie , Groombridge Christopher , Maini Amit , Williams Kim , Mitra Biswadev 
Published: September 2022

AbstractObjectiveInconsistency in the structure and function of team‐based major trauma reception and resuscitation is common. A standardised trauma team training programme was initiated to improve quality and consistency among trauma teams across a large, mature trauma system. The aim of this manuscript is to outline the programme and report on the initial perception of participants.MethodsThe Alfred Trauma Team Reception and Resuscitation Training (TTRRT) programme commenced in March 2019. Participants included critical care and surgical craft group members commonly involved in trauma teams. Training was site‐specific and included rural, urban and tertiary referral centres. The programme consisted of prescribed pre‐learning, didactic lectures, skill stations and simulated team‐based scenarios. Participant perceptions of the programme were collected before and after the programme for analysis.ResultsThe TTRRT was delivered to 252 participants and 120 responses were received. Significant improvement in participant‐reported confidence was identified across all key topic areas. There was also a significant increase in both confidence and clinical exposure to trauma team leadership roles after participation in the programme (from 53 [44.2%] to 74 [61.7%; P = 0.007]). This finding was independent of clinician experience.ConclusionsA team‐based trauma reception and resuscitation education programme, introduced in a large, mature trauma system led to positive participant‐reported outcomes in clinical confidence and real‐life team leadership participation. Wider implementation combined with longitudinal data collection will facilitate correlation with patient and staff‐centred outcomes.
Living on the edge: morphological and behavioral adaptations to a marginal high‐elevation habitat in an arboreal mammal
Authors: TRANQUILLO Claudia , WAUTERS Lucas Armand , SANTICCHIA Francesca , PREATONI Damiano , MARTINOLI Adriano 
Published: September 2022

AbstractHabitats are characterized by different local environmental conditions that influence both behavior and morphology of species, which can result in habitat‐dependent phenotypic differences among animals living in heterogeneous environments. We studied 3 alpine populations of Eurasian red squirrels (Sciurus vulgaris), 1 living in a marginal high‐elevation habitat at the edge of the species’ altitudinal distribution, and 2 occurring in higher‐quality habitats. Here, we investigated whether squirrels living in the marginal area differed in 2 morphological parameters (body size and body mass) and/or in the expression of 4 personality traits estimated with an open field test and a mirror image stimulation test (activity, exploration, activity‐exploration, and social tendency). Furthermore, we tested whether within‐individual variance of the traits (behavioral plasticity) was higher in the edge habitat. Male squirrels in the edge habitat were smaller and weighed less than in the other study areas, while among females, size–habitat relationships were less marked. These sex‐specific patterns were explained by a strong association between body mass and reproductive success in female squirrels. Squirrels in the marginal habitat were more active, explorative, and had a more social personality than in the other habitats. However, in contrast to our predictions, behavioral plasticity was smaller in the marginal habitat, but only for the trait exploration. Our results suggest that animals choose the habitat that best fits their personality, and that habitat‐related differences in selective pressures may shape animals’ morphology.
Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
Authors: Clement James , Yan Qi , Agrawal Megha , Coronado Ramon E. , Sturges John A. , Horvath Markus , Lu Ake T. , Brooke Robert T. , Horvath Steve 
Published: September 2022

AbstractPlasma transfusions are standard treatments to replace missing proteins in people with rare genetic diseases. Prior studies have demonstrated that heterochronic parabiosis has beneficial effects on several tissues of old animals receiving young blood. Human clinical trials are currently underway to investigate whether the infusion of plasma or plasma‐derived factors from young donors can be used to mitigate human age‐related conditions. Here, we use data from a safety study (n = 18, mean age 74) to investigate whether human umbilical cord plasma concentrate (hereinafter Plasma Concentrate) injected weekly (1 ml intramuscular) into elderly human subjects over a 10‐week period affects different biomarkers, including epigenetic age measures, standard clinical biomarkers of organ dysfunction, mitochondrial DNA copy number (mtDNA‐CN), and leukocyte telomere length. This study shows that treatment with plasma concentrate is safe. More than 20 clinical biomarkers were significantly and beneficially altered following the treatments. For example, creatinine was significantly decreased (p = 0.0039), while estimated glomerular filtration rate (eGFR) was increased (p = 0.0044), indicating the treatment may improve biomarkers of kidney function. Three of four immunoglobulin biomarkers decreased, while telomere length and mtDNA‐CN were not significantly affected by the treatment. The treatment reduced DNA methylation‐based GrimAge by an average of 0.82 years (p = 0.0093), suggests a reduction in morbidity and mortality risk. By contrast, no significant results could be observed for epigenetic clocks that estimate chronological age. Our results support the view that plasma concentrate contains youth‐promoting factors.
Distributional overlap and potential competition between a threatened habitat specialist and generalist frog species in coastal wallum habitats ofSouth EastQueensland, Australia
Authors: Filer Alannah , Meyer Edward A. , van Rensburg Berndt J. 
Published: September 2022

AbstractCoastal wallum wetlands inhabited by the vulnerable wallum sedgefrog (Litoria olongburensis) are highly susceptible to habitat degradation owing to their unusual hydrology and water chemistry. Anthropogenic impacts on wallum wetland environs pose a significant threat to the wallum sedgefrog by allowing the eastern sedgefrog (Litoria fallax), a habitat generalist and closely related competitor species, to colonise and displace the wallum sedgefrog from disturbed wallum habitat. To identify ‘at risk’ areas, overlapping species distribution models were utilised to highlight areas of sympatry between these species in south east Queensland, where competition with the eastern sedgefrog poses a particular threat to the wallum sedgefrog. Significant areas of distributional overlap (including 47% of the wallum sedgefrog's modelled distribution) were identified, primarily in mainland areas where anthropogenic disturbance is highest. When overlayed with the boundaries of protected areas, 84% of the area exclusively inhabited by the wallum sedgefrog occurs within the bounds of protected lands. In contrast, 74% of overlapping distribution of the two species occurred outside of these parks, highlighting the importance of protected areas in the conservation of the wallum sedgefrog. This study highlights areas where competition with the eastern sedgefrog presents a particular threat to the wallum sedgefrog, helping inform effective conservation initiatives for this species.
‘The best thing since sliced bread’: Patient experiences of teleoncology in western NSW
Authors: Pye Sid , Webster Emma , Zielinski Rob , Honeyball Florian 
Published: September 2022

AbstractObjectiveThis study explored experiences of rural cancer patients who were receiving treatments by remote video‐assisted chemotherapy (RVAC) or participating in clinical trials remotely.SettingParticipants lived in Coonabarabran or Dubbo in western NSW.ParticipantsSeven cancer patients undergoing treatment for breast, bladder or colon cancer, renal cell carcinoma or lymphoma.DesignAppreciative inquiry informed this qualitative study. Semi‐structured interviews were conducted between July 2018 and January 2019 and thematically analysed.ResultsThe patient experience of teleoncology was overwhelmingly positive. Patients explained the value of relationships that developed with the local and virtual care team. Patients felt they received better care if they saw the same oncologist for the duration of their treatment and felt RVAC had accommodated this. Teleoncology allowed patients to remain independent because they were able to maintain their usual support mechanisms including family, friends and health care team. Patients described the reduced physical and emotional travel burden in addition to reduction in travel time and cost.ConclusionsThese findings highlight the acceptability of teleoncology for rural patients as chemotherapy can be added to the health care and social and emotional supports, which exist in their hometown. Expansion of teleoncology should be codesigned with local communities with a focus on establishing care teams with consistent staffing to build trust between the treating team and the patient. These relationships improve the patient experience and enhance patient independence, which is a desirable attribute of cancer survivorship. Recruitment to clinical trials using teleoncology is acceptable and should be factored into trial development.
Robust subtractive stability measures for fast and exhaustive feature importance ranking and selection in generalised linear models
Authors: Smith Connor , Guennewig Boris , Muller Samuel 
Published: September 2022

AbstractWe introduce the relatively new concept of subtractive lack‐of‐fit measures in the context of robust regression, in particular in generalised linear models. We devise a fast and robust feature selection framework for regression that empirically enjoys better performance than other selection methods while remaining computationally feasible when fully exhaustive methods are not. Our method builds on the concepts of model stability, subtractive lack‐of‐fit measures and repeated model identification. We demonstrate how the multiple implementations add value in a robust regression type context, in particular through utilizing a combination of robust regression coefficient and scale estimates. Through resampling, we construct a robust stability matrix, which contains multiple measures of feature importance for each variable. By constructing this stability matrix and using it to rank features based on importance, we are able to reduce the candidate model space and then perform an exhaustive search on the remaining models. We also introduce two different visualisations to better convey information held within the stability matrix; a subtractive Mosaic Probability Plot and a subtractive Variable Inclusion Plot. We demonstrate how these graphics allow for a better understanding of how variable importance changes under small alterations to the underlying data. Our framework is made available in R through the RobStabR package.
Identification of sepsis in paediatric emergency departments: A scoping review
Authors: Oruganti Sivakumar , Evans Jordan , Cromarty Thomas , Javaid Assim , Roland Damian 
Published: September 2022

AbstractAimSepsis is an acute illness associated with significant morbidity and mortality. Early detection and time‐sensitive management of sepsis has been shown to improve outcomes. We report the results of a scoping review to explore methods evaluated for the identification of sepsis in children presenting to emergency departments.MethodsA systematic literature search was carried out on two databases, Medline and Web of Science, to identify relevant studies published from 1990 to 2022. Data were extracted for age groups including study design, reference standard used for comparison, sepsis identification method evaluated and study quality.ResultsA total of 89 studies were identified from the literature search. There was significant heterogeneity in the age groups including study design and reference standards used for evaluating the performance of the sepsis identification methods. There has been a substantial increase in the number of published studies in the last 2 years.ConclusionOur scoping review identifies marked heterogeneity in approaches to identifying sepsis but demonstrates a recent focus of research on patient outcomes. Using appropriate core outcome sets, developing reference standards, monitoring sepsis prevalence via registries and continuously monitoring process measures will provide robust evidence to identify the best performing identification tools and the impact they have on patient‐orientated outcomes.
Petrographic and geochemical characterization of chert artifacts from Middle, Upper, and Epi‐Paleolithic assemblages in the Jebel Qalkha area, southern Jordan
Authors: Ichinose Natsuki , Suga Eiki , Kadowaki Seiji , Tsukada Kazuhiro , Nadmid Bayart , Umeda Kanta , Nuramkhaan Manchuk , Massadeh Sate , Henry Donald O. 
Published: September 2022

AbstractThis study conducted petrographic and geochemical analyses of chert artifacts from the Late Middle Paleolithic, the Initial Upper Paleolithic, the Early Upper Paleolithic, and the Epi‐Paleolithic assemblages in the Jebel Qalkha area, southern Jordan, to examine their correlations with the visual attributes and diachronic variability. The results revealed two different aspects of the petrographic and geochemical signatures. The first aspect showed some correlations with the visual chert types that were characterized by the abundance/preservation of fossils, the enrichment of several elements (i.e., Ca, Sr, and Ba), and the quartz crystallite size.The second aspect of geochemical signatures, such as Fe, Mn, Ni, Cr, and Co, showed no correlation with the visual types but was correlated with the chrono‐cultural groups. Given the chert occurrences and variability in and around the study area, the first aspect of the chert variability likely represents the variations of different chert outcrops as well as the internal variations within the same sources. Whether the second aspect represents chrono‐cultural changes in the use of chert sources needs to be clarified in future by our ongoing examination of geological chert samples in the study area.
Prediction of the pharmacokinetics of pemetrexed with a low test dose: A proof‐of‐concept study
Authors: Boosman René J. , de Rouw Nikki , Huitema Alwin D. R. , Burgers Jacobus A. , ter Heine Rob 
Published: September 2022

PurposePemetrexed is a cytotoxic drug used for the treatment of lung cancer and mesothelioma. The use of a low test dosing of cytotoxic drugs may aid in dose individualization without causing harm. The aim of this proof‐of‐concept study was to assess if the pharmacokinetics (PKs) of a test dose could predict the PKs of a therapeutic pemetrexed dose.MethodsTen patients received both a low test dose (100 μg) and a therapeutic dose of pemetrexed after which plasma concentrations pemetrexed were measured. PK analysis was performed by means of nonlinear mixed‐effects modelling. The predictive performances of test dose clearance and renal function towards a therapeutic dose were assessed.ResultsThe PKs of a pemetrexed test dose were best described by a one‐compartment model with linear elimination. A high variability in the administered dose was observed for the test dose, but not for the therapeutic dose. A statistically significant correlation between test dose clearance and therapeutic dose clearance was observed (Spearman's rho: 0.758, P = 0.02). The predictive performance of test dose clearance was worse than renal function: mean predictive error (+95% confidence interval [CI]) 53.9% (50.1‐57.6%) vs 19.4% (12.4‐26.4%) and normalized root‐mean square error (+95% CI) 57.8% (30.5‐85.1%) vs 25.7% (20.3‐31.0%).ConclusionWe show that test dosing of pemetrexed is feasible, but there seems no added value for a low test dosing in the dose individualization of pemetrexed.