bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community emergency medicine throughout the UK and Ireland: a comparison of current national activity
Authors: Hanks Anthony , Ramage Lisa , Leech Caroline 
Published: September 2021

BackgroundCommunity emergency medicine (CEM) aims to bring highly skilled, expert medical care to the patient outside of the traditional ED setting. Currently, there are several different CEM models in existence within the UK and Ireland which confer multiple benefits including provision of a senior clinical decision-maker early in the patient’s journey, frontloading of time-critical interventions, easing pressure on busy EDs and reducing inpatient bed days. This is achieved through increased community-based management supplemented by utilisation of alternative care pathways. This study aimed to undertake a national comparison of CEM services currently in operation.MethodA data collection tool was distributed to CEM services by the Pre-Hospital trainee Operated Research Network in October 2020 which aimed to establish current practice among services in the UK and Ireland. It focused on six key sections: service aims; staffing and training; job tasking and patient selection; funding and vehicles used; equipment and medication; data collection, governance and research activity.ResultsSeven services responded from across England, Wales and Ireland. Similarities were found with the aims of each service, staffing structures and operational times. There were large differences in equipment carried, categories of patient targeted and with governance and research activity.ConclusionWhile some national variations in services are explained by funding and geographical location, this review process revealed several differences in practice under the umbrella term of CEM. A national definition of CEM and its aim, with guidance on scope of practice and measurable outcomes, should be generated to ensure high standard and cost-effective emergency care is delivered in the community.
Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis
Authors: Kaiser Yannick , Nurmohamed Nick S , Kroon Jeffrey , Verberne Hein J , Tzolos Evangelos , Dweck Marc R , Somsen Aernout G , Arsenault Benoit J , Stroes Erik S G , Zheng Kang H , Boekholdt S Matthijs 
Published: September 2021

ObjectiveTo assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).MethodsWe performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18F-NaF uptake.Results52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group).ConclusionAmong patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.
Elucidating mechanisms of antitumor immunity mediated by live oncolytic vaccinia and heat-inactivated vaccinia
Authors: Wang Weiyi , Liu Shuaitong , Dai Peihong , Yang Ning , Wang Yi , Giese Rachel A , Merghoub Taha , Wolchok Jedd , Deng Liang 
Published: September 2021

BackgroundViral-based immunotherapy can overcome resistance to immune checkpoint blockade (ICB) and fill the unmet needs of many patients with cancer. Oncolytic viruses (OVs) are defined as engineered or naturally occurring viruses that selectively replicate in and kill cancer cells. OVs also induce antitumor immunity. The purpose of this study was to compare the antitumor effects of live oncolytic vaccinia viruses versus the inactivated versions and elucidate their underlying immunological mechanisms.MethodsWe engineered a replication-competent, oncolytic vaccinia virus (OV-GM) by inserting a murine GM-CSF gene into the thymidine kinase locus of a mutant vaccinia E3L∆83N, which lacks the Z-DNA-binding domain of vaccinia virulence factor E3. We compared the antitumor effects of intratumoral (IT) delivery of live OV-GM versus heat-inactivated OV-GM (heat-iOV-GM) in a murine B16-F10 melanoma bilateral implantation model. We also generated vvDD, a well-studied oncolytic vaccinia virus, and compared the antitumor effects of live vvDD vs heat-inactivated vvDD (heat-ivvDD) in a murine A20 B-cell lymphoma bilateral tumor implantation model.ResultsHeat-iOV-GM infection of dendritic cells (DCs) and tumor cells in vitro induced type I interferon and proinflammatory cytokines and chemokines, whereas live OV-GM did not. IT live OV-GM was less effective in generating systemic antitumor immunity compared with heat-iOV-GM. Similar to heat-iOV-GM, the antitumor effects of live OV-GM also require Batf3-dependent CD103+ dendritic cells. When combined with systemic delivery of ICB, IT heat-iOV-GM was more effective in eradicating tumors, compared with live OV-GM. IT heat-ivvDD was also more effective in treating murine A20 B-cell lymphoma, compared with live vvDD.ConclusionsTumor lysis induced by the replication of oncolytic vaccinia virus has a limited effect on the generation of systemic antitumor immunity. The activation of Batf3-dependent CD103+ DCs is critical for antitumor effects induced by both live OV-GM and heat-iOV-GM, with the latter being more potent than live OV-GM in inducing innate and adaptive immunity in both locally injected and distant, non-injected tumors. We propose that evaluations of both innate and adaptive immunity, induced by IT oncolytic viral immunotherapy at injected and non-injected tumors, should be included as potential biomarkers for host responses to viral therapy.
Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.
Authors: Pinato David J. , Murray Sam M , Forner Alejandro , Kaneko Takahiro , Fessas Petros , Toniutto Pierluigi , Mínguez Beatriz , Cacciato Valentina , Avellini Claudio , Diaz Alba , Boyton Rosemary J. , Altmann Daniel M. , Goldin Robert D , Akarca Ayse U , Marafioti Teresa , Mauri Francesco A , Casagrande Edoardo , Grillo Federica , Giannini Edoardo , Bhoori Sherrie , Mazzaferro Vincenzo 
Published: September 2021

BackgroundModulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.MethodsWe profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163.ResultsWe analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T−. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T−.ConclusionsTACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
Residential extremely low frequency magnetic fields and skin cancer
Authors: Khan Muhammad Waseem , Juutilainen Jukka , Naarala Jonne , Roivainen Päivi 
Published: September 2021

ObjectivePhotoinduced radical reactions have a fundamental role in skin cancer induced by ultraviolet radiation, and changes in radical reactions have also been proposed as a mechanism for the putative carcinogenic effects of extremely low frequency (ELF) magnetic fields (MFs). We assessed the association of melanoma and squamous cell carcinoma with residential MF exposure.MethodsAll cohort members had lived in buildings with indoor transformer stations (TSs) during the period from 1971 to 2016. MF exposure was assessed based on apartment location. Out of the 225 492 individuals, 8617 (149 291 person-years of follow-up) living in apartments next to TSs were considered as exposed, while individuals living on higher floors of the same buildings were considered as referents. Associations between MF exposure and skin cancers were examined using Cox proportional hazard models.ResultsThe HR for MF exposure ≥6 month was 1.05 (95% CI 0.72 to 1.53) for melanoma and 0.94 (95% CI 0.55 to 1.61) for squamous cell carcinoma. Analysis of the age at the start of residence showed an elevated HR (2.55, 95% CI 1.15 to 5.69) for melanoma among those who lived in the apartments when they were less than 15 years old. This finding was based on seven exposed cases.ConclusionsThe results of this study suggested an association between childhood ELF MF exposure and adult melanoma. This is in agreement with previous findings suggesting that the carcinogenic effects of ELF MFs may be associated particularly with childhood exposure.
Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis
Authors: Chen Yue , Cheng Xingyu , Sun Chenyu , Kim Na Hyun , Kailas Sujatha , Qureshi Faisal , Karadsheh Zeid , Wu Yile , Hu Lei , Zhou Zhen , Bhan Chandur , Kim Keun Young , Manem Raveena , Cheng Ce , Zhou Qin 
Published: September 2021

AbstractObjectivesStudies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC.MethodsA comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed.ResultsSeven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p&lt;0.001). Sensitivity analysis suggested that the results were relatively stable.ConclusionMetformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations.PROSPERO registration numberCRD42021237127.
Trends in amyloidosis in spondyloarthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999–2015)—TREND-EspA study
Authors: Mazzucchelli Ramon , Almodovar-González Raquel , Dieguez-Costa Elisa , Crespí-Villarías Natalia , Pérez-Fernández Elia , García-Zamora Elena , Garcia Vadillo Alberto 
Published: September 2021

ObjectiveTo assess the incidence of amyloidosis and trends therein in patients with spondyloarthritis (SpA) over a long period (17 years).MethodsAn observational retrospective population-based matched cohort study was conducted. All the admissions of patients with SpA, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (SpA-IBD) and reactive arthritis (ReA), reported between 1999 and 2015, were analysed and a control group matched by age, sex and year of admission was selected. Incidence rates for amyloidosis were calculated. Generalised linear models were used for trend analysis and unconditional logistic regression for calculating crude and adjusted ORs (AOR) to assess the association between amyloidosis and SpA.ResultsThe study database contained data on 107 140 admissions in each group. Between 1999 and 2015, 792 patients in the SpA cohort (0.7% of all admissions) had a diagnosis of amyloidosis versus 68 in the non-SpA cohort (0.1%) (p<0.001). From 1999 to 2015, incidence rates of amyloidosis tended to decrease in the SpA cohort (−4.63%/year overall), while they increased in the Non-SpA cohort (+10.25%/year overall). We found strong associations of amyloidosis with all SpAs (AOR 10.4; 95% CI 8.2 to 13.3) and with each type studied (AORs 10.05 (7.84 to 12. 88) for AS, 9.5 (7.3 to 12.4) for PsA, 22.9 (16.6 to 31.7) for SpA-IBD and 10.1 (6.1 to 16.7) for ReA).ConclusionsIncidence of amyloidosis among patients with SpA has strongly decreased in Spain. Amyloidosis is most strongly associated with SpA-IBD while the strength of association with PsA and ReA is similar to that with AS.
SYNTHESIS AND CHARACTERIZATION OF NANOCRYSTALLINE Co-DOPED ZnO THIN FILMS PREPARED BY CHEMICAL SPRAY PYROLYSIS FOR OPTOELECTRONIC APPLICATIONS
Authors: HASSAN FAEZ M. , NAJIM AUS A. 
Published: September 2021

ZnO:Co thin films were synthesized by the chemical spray pyrolysis (CSP) on glass substrates. Then, investigated the impact of Co doping concentration on its physical properties. XRD analyses show that all films have a polycrystalline structure of hexagonal ZnO. The crystallite size increased from 18[Formula: see text]nm to 25[Formula: see text]nm with Co doping concentrations. Furthermore, the unit cell volume increased from 47.485[Formula: see text]Å to 47.831[Formula: see text]Å, and the Zn–O bond length expanded from 1.97588[Formula: see text]Å to 1.98071[Formula: see text]Å. SEM observations reveal the formation of fiber-like nanostructures in the Co-doped thin films. The diameter of nanofibers increased with Co doping concentration from 260[Formula: see text]nm to 700[Formula: see text]nm. The optical characteristics were studied by the UV-Visible spectrophotometer and manifest the optical transparency vary with Co doping. In addition, the band gap decreases from 3.27[Formula: see text]eV to 2.73[Formula: see text]eV with increasing Co doping concentrations. The conductivity varied from 3.35[Formula: see text]S[Formula: see text][Formula: see text][Formula: see text]m[Formula: see text] to 19.88[Formula: see text]S[Formula: see text][Formula: see text][Formula: see text]m[Formula: see text] with Co doping concentrations. Empirical models were proposed to evaluate the correlated variables with excellent accuracy with the experimental data. The best result was accomplished in ZnO:Co1% films, where good transparency and high conductivity were achieved.
FOREIGN CAPITAL AND DOMESTIC FUNDING CONDITIONS: A MUNDELLIAN TRILEMMA PERSPECTIVE
Authors: STOJKOV ALEKSANDAR , WARIN THIERRY 
Published: September 2021

This study investigates and evaluates the impact of global funding conditions on private sector credit growth and controlling for the Mundellian Trilemma configuration. We contribute to the empirical literature by investigating the role of other conditioning factors such as the size of economies and their level of economic development. The more specific research goals are as follows: (i) To explore the different Trilemma configurations by income group and size of the economies; (ii) to enrich international macroeconomics literature on the role of Trilemma configurations and countries’ idiosyncrasies in assessing the impact of global financial conditions; and (iii) to formulate policy-relevant conclusions. We argue that — when assessing the impact of global financial conditions — the exchange rate regime and financial openness matter and the size of the economy and its income level. The high volatility in gross and net international capital flows redefined many trilemma configurations in the Great Recession aftermath. Many countries decided to shield their financial markets by reducing the degree of financial openness and moving toward intermediate or middle-ground positions in their Trilemma configurations.
#PrettyFlyForAWiFi
Authors: Birnbach Simon , Baker Richard , Eberz Simon , Martinovic Ivan 
Published: September 2021

Drones are becoming increasingly popular for hobbyists and recreational use. But with this surge in popularity comes increased risk to privacy as the technology makes it easy to spy on people in otherwise-private environments, such as an individual’s home. An attacker can fly a drone over fences and walls to observe the inside of a house, without having physical access. Existing drone detection systems require specialist hardware and expensive deployment efforts, making them inaccessible to the general public.
In this work, we present a drone detection system that requires minimal prior configuration and uses inexpensive commercial off-the-shelf hardware to detect drones that are carrying out privacy invasion attacks. We use a model of the attack structure to derive statistical metrics for movement and proximity that are then applied to received communications between a drone and its controller. We test our system in real-world experiments with two popular consumer drone models mounting privacy invasion attacks using a range of flight patterns. We are able both to detect the presence of a drone and to identify which phase of the privacy attack was in progress while being resistant to false positives from other mobile transmitters. For line-of-sight approaches using our kurtosis-based method, we are able to detect all drones at a distance of 6 m, with the majority of approaches detected at 25 m or farther from the target window without suffering false positives for stationary or mobile non-drone transmitters.
MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia
Authors: Sanjiv Kumar , Calderón-Montaño José Manuel , Pham Therese M. , Erkers Tom , Tsuber Viktoriia , Almlöf Ingrid , Höglund Andreas , Heshmati Yaser , Seashore-Ludlow Brinton , Nagesh Danda Akhilesh , Gad Helge , Wiita Elisee , Göktürk Camilla , Rasti Azita , Friedrich Stefanie , Centio Anders , Estruch Montserrat , Våtsveen Thea Kristin , Struyf Nona , Visnes Torkild , Scobie Martin , Koolmeister Tobias , Henriksson Martin , Wallner Olov , Sandvall Teresa , Lehmann Sören , Theilgaard-Mönch Kim , Garnett Mathew J. , Östling Päivi , Walfridsson Julian , Helleday Thomas , Warpman Berglund Ulrika 
Published: September 2021

AbstractAcute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin−CD34+CD38−), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial.Significance:The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.
A Modified Nucleoside 6-Thio-2′-Deoxyguanosine Exhibits Antitumor Activity in Gliomas
Authors: Yu Shengnan , Wei Shiyou , Savani Milan , Lin Xiang , Du Kuang , Mender Ilgen , Siteni Silvia , Vasilopoulos Themistoklis , Reitman Zachary J. , Ku Yin , Wu Di , Liu Hao , Tian Meng , Chen Yaohui , Labrie Marilyne , Charbonneau Casey M. , Sugarman Eric , Bowie Michelle , Hariharan Seethalakshmi , Waitkus Matthew , Jiang Wen , McLendon Roger E. , Pan Edward , Khasraw Mustafa , Walsh Kyle M. , Lu Yiling , Herlyn Meenhard , Mills Gordon , Herbig Utz , Wei Zhi , Keir Stephen T. , Flaherty Keith , Liu Lunxu , Wu Kongming , Shay Jerry W. , Abdullah Kalil , Zhang Gao , Ashley David M. 
Published: September 2021

Abstract

Purpose:
To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2′-deoxyguanosine (THIO) in gliomas both in vitro and in vivo.

Experimental Design:
A panel of human and mouse glioma cell lines was used to test therapeutic efficacy of THIO using cell viability assays, flow cytometric analyses, and immunofluorescence. Integrated analyses of RNA sequencing and reverse-phase protein array data revealed the potential antitumor mechanisms of THIO. Four patient-derived xenografts (PDX), two patient-derived organoids (PDO), and two xenografts of human glioma cell lines were used to further investigate the therapeutic efficacy of THIO.

Results:
THIO was effective in the majority of human and mouse glioma cell lines with no obvious toxicity against normal astrocytes. THIO as a monotherapy demonstrated efficacy in three glioma cell lines that had acquired resistance to temozolomide. In addition, THIO showed efficacy in four human glioma cell lines grown as neurospheres by inducing apoptotic cell death. Mechanistically, THIO induced telomeric DNA damage not only in glioma cell lines but also in PDX tumor specimens. Integrated computational analyses of transcriptomic and proteomic data indicated that THIO significantly inhibited cell invasion, stem cell, and proliferation pathways while triggering DNA damage and apoptosis. Importantly, THIO significantly decreased tumor proliferation in two PDO models and reduced the tumor size of a glioblastoma xenograft and a PDX model.

Conclusions:
The current study established the therapeutic role of THIO in primary and recurrent gliomas and revealed the acute induction of telomeric DNA damage as a primary antitumor mechanism of THIO in gliomas.