bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synovial fibroblasts regulate the cytotoxicity and osteoclastogenic activity of synovial natural killer cells through the RANKL‐RANK axis in osteoarthritis
Authors: Zhao Wenbin , Liu Yuanfeng , Liu Kang , Tu Feng , Zhang Chen , Wang Hao 
Published: May 2021

AbstractChronic inflammation plays an important role in the progression of osteoarthritis (OA). Cumulative evidence suggests that natural killer (NK) cells potentially participate in OA inflammation. To investigate the regulation of NK cell reactivity in OA synovium, we characterized the phenotypic and functional properties of infiltrating NK cells in the synovial tissue in a rat collagenase‐induced OA model. Our data indicated that in comparison with splenic NK cells, OA synovial NK cells were poorly responsive to the stimulation of IL‐12 plus IL‐15 and IL‐18, as evidenced by lower production of IFN‐γ, perforin and granzyme B. Consistently, synovial NK cells showed lower cytotoxicity to target cells than splenic NK cells. Further investigations revealed that synovial NK cells highly expressed receptor activator of nuclear factor‐κB (RANK), while OA synovial fibroblasts (SFs) upregulated the expression of RANK ligand (RANKL). Co‐culture of OA SFs with RANK‐expressing NK cells inhibited cytokine‐induced production of above cytotoxic mediators in NK cells and subsequently impaired NK cell cytotoxicity. Gene silencing of RANKL expression in SFs partially recovered the cytotoxicity of NK cells after co‐culture. Furthermore, through the RANKL‐RANK axis, OA SFs induced RANKL expression in NK cells and subsequently promoted the osteoclastogenic activity of NK cells in vitro. Taken together, our study showed that OA SF inhibited the cytotoxicity while augmenting the osteoclastogenic activity of NK cells through the RANKL‐RANK axis. This study reveals a novel mechanism by which SFs modulate the reactivity of synovial NK cells in OA.
The Effect of Social Distancing on the Early Spread of the Novel Coronavirus
Authors: Price Gregory , van Holm Eric 
Published: May 2021

AbstractThis article quantifies the effect of individual social distancing on the spread of the novel coronavirus. To do so, we use data on time spent by individuals on activities that would potentially expose them to crowds from the American Time Use Survey linked with state‐level data on positive tests from the COVID Tracking Project. We estimate count data specifications of observed COVID‐19 infections at the state level as a function of control demographic variables, and a measure of social distance that captures the amount of time individuals across the states spend in activities that potentially expose them to crowds. Parameter estimates reveal that the number of state‐level novel coronavirus infections decrease with respect to our measure of individual social distance. From a practical perspective, our parameter estimates suggest that if the typical individual in a U.S. state were to spend eight hours away from crowds completely, this would translate into approximately 240,000 fewer COVID‐19 infections across the states. Our results suggest that, at least in the United States, social distancing policies are effective in slowing the spread of the novel coronavirus.
The hedge asset for BRICS stock markets: Bitcoin, gold or VIX
Authors: Shahzad Syed Jawad Hussain , Bouri Elie , Rehman Mobeen Ur , Roubaud David 
Published: May 2021

AbstractWe compare the weak/strong hedging abilities of three alternative assets, namely bitcoin, gold and US VIX futures, against the downside movements in BRICS stock market indices. Results from the cross‐quantilogram approach indicate that bitcoin and gold are weak hedges. Analysis from the recursive sampling shows that each of bitcoin, gold and VIX futures has a time‐varying hedging role in some BRICS countries, which has been shaped by the COVID‐19 outbreak. Results from the conditional diversification benefits show appealing roles for the three alternative assets for investors in BRICS stock markets. However, gold appears to have higher and more stable diversification benefits in China, especially during the COVID‐19 outbreak. Conversely, VIX futures offer higher diversification benefits in Brazil, Russia, India and South Africa during the abrupt of the COVID‐19 outbreak.
Brief hypoxia in late gestation sheep causes prolonged disruption of fetal electrographic, breathing behaviours and can result in early labour
Authors: Baburamani Ana A. , Tran Nhi T. , Castillo‐Melendez Margie , Yawno Tamara , Walker David W. 
Published: May 2021

Key points
Brief episodes of severe fetal hypoxia can arise in late gestation as a result of interruption of normal umbilical blood flow
Systemic parameters and blood chemistry indicate complete recovery within 1–2 hours, although the long‐term effects on fetal brain functions are unknown
Fetal sheep were subjected to umbilical cord occlusion (UCO) for 10 min at 131 days of gestation, and then monitored intensively until onset of labour or delivery (<145 days of gestation)
Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements and postural (neck) muscle activity, were disrupted for 3–10 days after the UCO
Preterm labour and delivery occurred in a significant number of the pregnancies after UCO compared to the control (sham‐UCO) cohort.
AbstractComplications arising from antepartum events such as impaired umbilical blood flow can cause significant fetal hypoxia. These complications can be unpredictable, as well as difficult to detect, and thus we lack a detailed understanding of the (patho)physiological changes that occur between the antenatal in utero event and birth. In the present study, we assessed the consequences of brief (∼10 min) umbilical cord occlusion (UCO) in fetal sheep at ∼0.88 gestation on fetal plasma cortisol concentrations and fetal behaviour [electrocortical (EcoG), electo‐oculargram (EOG), nuchal muscle electromyography (EMG) and breathing activities] in the days following UCO. UCO caused a rapid onset of fetal hypoxaemia, hypercapnia, and acidosis; however, by 6 h, all blood parameters and cardiovascular status were normalized and not different from the control (Sham‐UCO) cohort. Subsequently, the incidence of fetal breathing movements decreased compared to the control group, and abnormal behavioural patterns developed over the days following UCO and leading up to the onset of labour, which included increased high voltage and sub‐low voltage ECoG and EOG activities, as well as decreased nuchal EMG activity. Fetuses subjected to UCO went into labour 7.9 ± 3.6 days post‐UCO (139.5 ± 3.2 days of gestation) compared to the control group fetuses at 13.6 ± 3.3 days post‐sham UCO (144 ± 2.2 days of gestation; P < 0.05), despite comparable increases in fetal plasma cortisol and a similar body weight at birth. Thus, a single transient episode of complete UCO late in gestation in fetal sheep can result in prolonged effects on fetal brain activity and premature labour, suggesting persisting effects on fetal cerebral metabolism.
Modeling Nanosecond-Pulsed Spark Discharge and Flame Kernel Evolution
Authors: Kim Joohan , Gururajan Vyaas , Scarcelli Riccardo , Biswas Sayan , Ekoto Isaac 
Published: May 2021

Abstract
Dilute combustion, either using exhaust gas recirculation or with excess air, is considered a promising strategy to improve the thermal efficiency of internal combustion engines. However, the dilute air-fuel mixture, especially under intensified turbulence and high-pressure conditions, poses significant challenges for ignitability and combustion stability, which may limit the attainable efficiency benefits. In-depth knowledge of the flame kernel evolution to stabilize ignition and combustion in a challenging environment is crucial for effective engine development and optimization. To date, a comprehensive understanding of ignition processes that result in the development of fully predictive ignition models usable by the automotive industry does not yet exist. Spark-ignition consists of a wide range of physics that includes electrical discharge, plasma evolution, joule-heating of gas, and flame kernel initiation and growth into a self-sustainable flame. In this study, an advanced approach is proposed to model spark-ignition energy deposition and flame kernel growth. To decouple the flame kernel growth from the electrical discharge, a nanosecond-pulsed high-voltage discharge is used to trigger spark-ignition in an optically accessible small ignition test vessel with a quiescent mixture of air and methane. Initial conditions for the flame kernel, including its thermodynamic state and species composition, are derived from a plasma-chemical equilibrium calculation. The geometric shape and dimension of the kernel are characterized using a multi-dimensional thermal plasma solver. The proposed modeling approach is evaluated using a high-fidelity computational fluid dynamics procedure to compare the simulated flame kernel evolution against flame boundaries from companion Schlieren images.
Modeling Dislocation-Mediated Hydrogen Transport and Trapping in Face-Centered Cubic Metals
Authors: Zirkle Theodore , Costello Luke , Zhu Ting , McDowell David L. 
Published: May 2021

Abstract
The diffusion of hydrogen in metals is of interest due to the deleterious influence of hydrogen on material ductility and fracture resistance. It is becoming increasingly clear that hydrogen transport couples significantly with dislocation activity. In this work, we use a coupled diffusion-crystal plasticity model to incorporate hydrogen transport associated with dislocation sweeping and pipe diffusion in addition to standard lattice diffusion. Moreover, we consider generation of vacancies via plastic deformation and stabilization of vacancies via trapping of hydrogen. The proposed hydrogen transport model is implemented in a physically based crystal viscoplasticity framework to model the interaction of dislocation substructure and hydrogen migration. In this study, focus is placed on hydrogen transport and trapping within the intense deformation field of a crack tip plastic zone. We discuss the implications of the model results in terms of constitutive relations that incorporate hydrogen effects on crack tip field behavior and enable exploration of hydrogen embrittlement mechanisms.
Changes in Physical Activity, Sleep, Mental Health, and Social Media Use During COVID-19 Lockdown Among Adolescent Girls: A Mixed-Methods Study
Authors: O’Kane S. Maria , Lahart Ian M. , Gallagher Alison M. , Carlin Angela , Faulkner Maria , Jago Russell , Murphy Marie H. 
Published: May 2021

Background: To suppress the transmission of coronavirus, many governments, including that of the island of Ireland, implemented a societal lockdown, which included school closures, limits on social gatherings, and time outdoors. This study aimed to evaluate changes in physical activity (PA), mental health, sleep, and social media use among adolescent girls during lockdown. Methods: 281 female pupils (12–14 y) taking part in the ongoing Walking In Schools study on the island of Ireland self-reported PA, mental health, sleep, and social media use before (September–October 2019) and during lockdown (May–June 2020), via questionnaires. These were supplemented with open-ended structured interviews conducted with 16 girls during lockdown. Results: During the period of lockdown and school closures, pupils tried new forms of PA and undertook PA with family, but there was no significant change in self-reported PA. There was a decline in health-related quality of life; however, self-efficacy for walking increased. There was no change in sleep quality or social media usage. Conclusions: Despite the many challenges that schools face as they reopen, there is a need to continue to prioritize PA and motivation for exercise to support health and well-being in adolescent girls.
The interfacial energy penalty to crystal growth close to equilibrium
Authors: Gaidies Fred , George Freya R. 
Published: May 2021

AbstractUnderstanding the origin of rock microstructure is critical for refining models of the geodynamics of the Earth. We use the geometry of compositional growth zoning of a population of garnet porphyroblasts in a mica schist to gain quantitative insight into (1) the relative growth rates of individual crystals, (2) the departure from equilibrium during their growth, and (3) the mobility of the porphyroblast-matrix interface. The driving force for garnet growth in the studied sample was exceedingly small and is comparable in magnitude to the interfacial energy associated with the garnet-matrix interface. This resulted in size-dependent garnet growth at macroscopic length scales, with a decrease in radial growth rates for smaller crystals caused by the penalty effect of the interfacial energy. The difference in growth rate between the largest and the smallest crystal is ~45%, and the interface mobility for garnet growth from ~535°C, 480 MPa to 565°C, 560 MPa in the phyllosilicate-dominated rock matrix ranged between ~10−19 and 10−20 m4 J−1 s−1. This is the first estimation of interface mobility in natural rock samples. In addition to the complex structural and chemical reorganization associated with the formation of dodecahedral coordination polyhedra in garnet, the presence of abundant graphite may have exerted drag on the garnet-matrix interface, further decreasing its mobility.
Phantom vision after eye removal: prevalence, features and related risk factors
Authors: Martel Arnaud , Baillif Stephanie , Thomas Pierre , Almairac Fabien , Galatoire Olivier , Hamedani Mehrad , Fontaine Denys , Lanteri-Minet Michel 
Published: May 2021

AimPhantom eye syndrome is a poorly understood and underestimated complication of eye removal (ER). Seeing with the amputated eye, referred to as phantom vision (PV), is undoubtedly the most intriguing and confusing complication experienced by anophthalmic patients. The aim of the study was to assess PV prevalence, clinical features and risk factors after ER.MethodsA multicentric questionnaire-based study was conducted between April 2016 and July 2017. Patients >18 years who underwent ER >3 months ago had a socket examination before inclusion. Data recorded included patients’ demographics, and preoperative, surgical and postoperative features.ResultsOne hundred patients (53 men) with a mean age of 65.1 years (29–92; SD=13.0) were included. ER indications were: uveal melanoma (n=24, 24%), trauma (n=20, 20%), retinal detachment (n=20, 20%), glaucoma (n=14, 14%) and endophthalmitis (n=12, 12%). Thirty (30%) patients experienced PV. Elementary and complex visual hallucinations were experienced by 80% and 20% of patients, respectively. PV usually appeared within the first postoperative month and tended to decrease over time. Risk factors for PV were the preoperative use of proton beam therapy (p=0.006), uveal melanoma (p=0.014), enucleation (p=0.015), anxiety with a Hospital and Anxiety Depression (HAD) score ≥8 (p=0.042), depression with a HAD score ≥8 (p=0.030), phantom eye pain (p=0.044) and phantom eye sensations (p=0.002).ConclusionPV was reported by one-third of our patients. Despite being widely misunderstood, ophthalmologists and neurologists should be aware of this complication to adequately reassure patients.
Development and implementation of a clinician report to reduce unnecessary urine drug screen testing in the ED: a quality improvement initiative
Authors: Vanstone Jason Robert , Patel Shivani , Degelman Michelle L , Abubakari Ibrahim W , McCann Shawn , Parker Robert , Ross Terry 
Published: May 2021

BackgroundUnnecessary testing is a problem-facing healthcare systems around the world striving to achieve sustainable care. Despite knowing this problem exists, clinicians continue to order tests that do not contribute to patient care. Using behavioural and implementation science can help address this problem. Locally, audit and feedback are used to provide information to clinicians about their performance on relevant metrics. However, this is often done without evidence-based methods to optimise uptake. Our objective was to improve the appropriate use of laboratory tests in the ED using evidence-based audit and feedback and behaviour change techniques.MethodsUsing the behaviour change wheel, we implemented an audit and feedback tool that provided information to ED physicians about their use of laboratory tests; specifically, we focused on education and review of the appropriate use of urine drug screen tests. The report was designed in collaboration with end users to help maximise engagement. Following development of the report, audit and feedback sessions were delivered over an 18-month period.ResultsData on urine drug screen testing were collected continually throughout the intervention period and showed a sustained decrease among ED physicians. Test use dropped from a monthly departmental average of 26 urine drug screen tests per 1000 patient visits to only eight tests per 1000 patient visits following the initiation of the audit and feedback intervention.ConclusionAudit and feedback reduced unnecessary urine drug screen testing in the ED. Regular feedback sessions continuously engaged physicians in the audit and feedback intervention and allowed the implementation team to react to changing priorities and feedback from the clinical group. It was important to include the end users in the design of audit and feedback tools to maximise physician engagement. Inclusion in this process can help ensure physicians adopt a sense of ownership regarding which metrics to review and provides a key component for the motivation aspect of behaviour change. Departmental leadership is also critical to the process of implementing a successful audit and feedback initiative and achieving sustained behaviour change.
Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition
Authors: Sharbeen George , McCarroll Joshua A. , Akerman Anouschka , Kopecky Chantal , Youkhana Janet , Kokkinos John , Holst Jeff , Boyer Cyrille , Erkan Mert , Goldstein David , Timpson Paul , Cox Thomas R. , Pereira Brooke A. , Chitty Jessica L. , Fey Sigrid K. , Najumudeen Arafath K. , Campbell Andrew D. , Sansom Owen J. , Ignacio Rosa Mistica C. , Naim Stephanie , Liu Jie , Russia Nelson , Lee Julia , Chou Angela , Johns Amber , Gill Anthony J. , Gonzales-Aloy Estrella , Gebski Val , Guan Yi Fang , Pajic Marina , Turner Nigel , Apte Minoti V. , Davis Thomas P. , Morton Jennifer P. , Haghighi Koroush S. , Kasparian Jorjina , McLean Benjamin J. , Setargew Yordanos F. , Phillips Phoebe A. 
Published: May 2021

Abstract

Cancer-associated fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through protumor signaling and the generation of fibrosis, the latter of which creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11 is a cystine transporter that has been identified as a potential therapeutic target in PDAC cells. However, no prior study has evaluated the role of SLC7A11 in PDAC tumor stroma and its prognostic significance. Here we show that high expression of SLC7A11 in human PDAC tumor stroma, but not tumor cells, is independently prognostic of poorer overall survival. Orthogonal approaches showed that PDAC-derived CAFs are highly dependent on SLC7A11 for cystine uptake and glutathione synthesis and that SLC7A11 inhibition significantly decreases CAF proliferation, reduces their resistance to oxidative stress, and inhibits their ability to remodel collagen and support PDAC cell growth. Importantly, specific ablation of SLC7A11 from the tumor compartment of transgenic mouse PDAC tumors did not affect tumor growth, suggesting the stroma can substantially influence PDAC tumor response to SLC7A11 inhibition. In a mouse orthotopic PDAC model utilizing human PDAC cells and CAFs, stable knockdown of SLC7A11 was required in both cell types to reduce tumor growth, metastatic spread, and intratumoral fibrosis, demonstrating the importance of targeting SLC7A11 in both compartments. Finally, treatment with a nanoparticle gene-silencing drug against SLC7A11, developed by our laboratory, reduced PDAC tumor growth, incidence of metastases, CAF activation, and fibrosis in orthotopic PDAC tumors. Overall, these findings identify an important role of SLC7A11 in PDAC-derived CAFs in supporting tumor growth.

Significance:
This study demonstrates that SLC7A11 in PDAC stromal cells is important for the tumor-promoting activity of CAFs and validates a clinically translatable nanomedicine for therapeutic SLC7A11 inhibition in PDAC.
Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Authors: Sun Guangyan , Shvab Anna , Leclerc Guy J. , Li Bin , Beckedorff Felipe , Shiekhattar Ramin , Barredo Julio C. 
Published: May 2021

Abstract

Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wide metabolic-stress regulated genes, we used RNA-sequencing in ALL cells treated with AICAR, an AMPK activator. RNA-sequencing identified the immediate early genes (IEGs) as a subset of genes downregulated by AICAR. We show that AICAR-induced IEGs downregulation was blocked by an adenosine uptake inhibitor indicating AICAR was responsible for IEGs reprogramming. Using pharmacologic and genetic models we established this mechanism was AMPK-independent. Further investigations using kinase assays, PKD/PKC inhibitors and rescue experiments, demonstrated that AICAR directly inhibited PKD kinase activity and identified PKD as responsible for IEGs downregulation. Mechanistically, PKD inhibition suppressed phosphorylation and nuclear export of class IIa HDACs, which lowered histone H3 acetylation and decreased NFκB(p65) recruitment to IEGs promoters. Finally, PKD inhibition induced apoptosis via DUSP1/DUSP6 downregulation eliciting a DNA damage response. More importantly, ALL patient cells exhibited the same PKD-HDACs-IEGs–mediated mechanism. As proof of principle of the therapeutic potential of targeting PKD, we established the in vivo relevance of our findings using an NSG ALL mouse model. In conclusion, we identified a previously unreported PKD-dependent survival mechanism in response to AICAR-induced cellular stress in ALL through regulation of DUSPs and IEGs' expression.

Implications:
PKD mediates early transcriptional responses in ALL cells as an adaptive survival mechanism to overcome cellular stress.