bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the prehospital use of a Valsalva assist device in the emergency treatment of supraventricular tachycardia (EVADE SVT): study protocol for a stepped wedge cluster randomised controlled trial
Authors: Appelboam Andrew , Osborne Ria , Ukoumunne Obioha , Black Sarah , Boot Suzanne , Richards Nicholas , Scotney Natalie , Rhodes Shelley , Cranston Tim , Hawker Ruth , Gillett Annette , Jones Ben , Hawton Annie , Dayer Mark , Creanor Siobhan 
Published: June 2023

IntroductionPatients with episodes of supraventricular tachycardia (SVT), a common heart arrhythmia, are often attended by ambulance services. International guidelines advocate treatment with the Valsalva manoeuvre (VM), but this simple physical treatment has a low success rate, with most patients requiring conveyance to hospital. The Valsalva Assist Device (VAD) is a simple device that might help practitioners and patients perform a more effective VM and reduce the need for patients to be taken to hospital.Methods and analysisThis stepped wedge cluster randomised controlled trial, conducted within a UK ambulance service, compares the current standard VM with a VAD-delivered VM in stable adult patients presenting to the ambulance service with SVT. The primary outcome is conveyance to hospital; secondary outcomes measures include cardioversion rates, duration of ambulance care and number of subsequent episodes of SVT requiring ambulance service care. We plan to recruit approximately 800 patients, to have 90% power to detect an absolute reduction in conveyance rate of 10% (from 90% to 80%) between the standard VM (control) and VAD-delivered VM (intervention). Such a reduction in conveyance would benefit patients, the ambulance service and receiving emergency departments. It is estimated potential savings would pay for devices for the entire ambulance trust within 7 months.Ethics and disseminationThe study has been approved by the Oxford Research Ethics Committee (reference 22/SC/0032). Dissemination will be through peer-reviewed journal publication, presentation at national and international conferences and by the Arrhythmia Alliance, a patient support charity.Trial registration numberISRCTN16145266.
Impact of personal protective equipment on the clarity of vision among trachoma survey graders and trichiasis surgeons in the context of COVID-19
Authors: Ul Hassan Ehtisham , Apadinuwe Sue-Chen , Bisanzio Donal , Dejene Michael , Downs Philip , Harding-Esch Emma M , Jimenez Cristina , Kabona George , Kebede Biruck Negash , Kelly Michaela , Kivumbi Peter , Millar Tom , Mosher Aryc W , Mpyet Caleb , Mkocha Harran , Ngondi Jeremiah M , Olobio Nicholas , Palmer Stephanie , Teyil Wamyil-Mshelia , Courtright Paul 
Published: June 2023

Background/aimsThe COVID-19 pandemic necessitated the use of personal protective equipment for those involved in trachoma survey grading and trichiasis surgery. We sought to determine which configuration of a face shield would be less likely to impact grading accuracy and ability to conduct trichiasis surgery. The research also included assessment of comfort, ease of cleaning and robustness.MethodsThere were three research phases. In phase 1, assessment of four potential face shield configurations was undertaken with principal trachoma graders and trichiasis surgeon trainers to decide which two options should undergo further testing. In phase 2, clarity of vision and comfort (in a classroom environment) of the two configurations were assessed compared with no face shield (control), while grading trachomatous inflammation—follicular (TF). The second phase also included the assessment of impact of the configurations while performing trichiasis surgery using a training model. In phase 3, face shield ease of use was evaluated during routine surgical programmes.ResultsIn phase 2, 124 trachoma graders and 28 trichiasis surgeons evaluated the 2 face shield configurations selected in phase 1. TF agreement was high (kappa=0.83 and 0.82) for both configurations compared with not wearing a face shield. Comfort was reported as good by 51% and 32% of graders using the two configurations. Trichiasis skill scores were similar for both configurations.ConclusionThe face shield configuration that includes a cut-out for mounting the 2.5× magnifying loupes does not appear to impact the ability or comfort of trachoma graders or trichiasis surgeons to carry out their work.
Factors of a physician quality improvement leadership coalition that influence physician behaviour: a mixed methods study
Authors: Mathura Pamela , Marini Sandra , Hagtvedt Reidar , Spalding Karen , Duhn Lenora , Kassam Narmin , Medves Jennifer 
Published: June 2023

BackgroundA coalition (Strategic Clinical Improvement Committee), with a mandate to promote physician quality improvement (QI) involvement, identified hospital laboratory test overuse as a priority. The coalition developed and supported the spread of a multicomponent initiative about reducing repetitive laboratory testing and blood urea nitrogen (BUN) ordering across one Canadian province. This study’s purpose was to identify coalition factors enabling medicine and emergency department (ED) physicians to lead, participate and influence appropriate BUN test ordering.MethodsUsing sequential explanatory mixed methods, intervention components were grouped as person focused or system focused. Quantitative phase/analyses included: monthly total and average of the BUN test for six hospitals (medicine programme and two EDs) were compared pre initiative and post initiative; a cost avoidance calculation and an interrupted time series analysis were performed (participants were divided into two groups: high (>50%) and low (<50%) BUN test reduction based on these findings). Qualitative phase/analyses included: structured virtual interviews with 12 physicians/participants; a content analysis aligned to the Theoretical Domains Framework and the Behaviour Change Wheel. Quotes from participants representing high and low groups were integrated into a joint display.ResultsMonthly BUN test ordering was significantly reduced in 5 of 6 participating hospital medicine programmes and in both EDs (33% to 76%), resulting in monthly cost avoidance (CAN$900–CAN$7285). Physicians had similar perceptions of the coalition’s characteristics enabling their QI involvement and the factors influencing BUN test reduction.ConclusionsTo enable physician confidence to lead and participate, the coalition used the following: a simply designed QI initiative, partnership with a coalition physician leader and/or member; credibility and mentorship; support personnel; QI education and hands-on training; minimal physician effort; and no clinical workflow disruption. Implementing person-focused and system-focused intervention components, and communication from a trusted local physician—who shared data, physician QI initiative role/contribution and responsibility, best practices, and past project successes—were factors influencing appropriate BUN test ordering.
Body mass index and survival in people with heart failure
Authors: Jones Nicholas R , Ordóñez-Mena José M , Roalfe Andrea K , Taylor Kathryn S , Goyder Clare R , Hobbs FD Richard , Taylor Clare J 
Published: June 2023

AimsIn people with heart failure (HF), a high body mass index (BMI) has been linked with better outcomes (‘obesity paradox’), but there is limited evidence in community populations across long-term follow-up. We aimed to examine the association between BMI and long-term survival in patients with HF in a large primary care cohort.MethodsWe included patients with incident HF aged ≥45 years from the Clinical Practice Research Datalink (2000–2017). We used Kaplan-Meier curves, Cox regression and penalised spline methods to assess the association of pre-diagnostic BMI, based on WHO classification, with all-cause mortality.ResultsThere were 47 531 participants with HF (median age 78.0 years (IQR 70–84), 45.8% female, 79.0% white ethnicity, median BMI 27.1 (IQR 23.9–31.0)) and 25 013 (52.6%) died during follow-up. Compared with healthy weight, people with overweight (HR 0.78, 95% CI 0.75 to 0.81, risk difference (RD) −4.1%), obesity class I (HR 0.76, 95% CI 0.73 to 0.80, RD −4.5%) and class II (HR 0.76, 95% CI 0.71 to 0.81, RD −4.5%) were at decreased risk of death, whereas people with underweight were at increased risk (HR 1.59, 95% CI 1.45 to 1.75, RD 11.2%). In those underweight, this risk was greater among men than women (p value for interaction=0.02). Class III obesity was associated with increased risk of all-cause mortality compared with overweight (HR 1.23, 95% CI 1.17 to 1.29).ConclusionThe U-shaped relationship between BMI and long-term all-cause mortality suggests a personalised approach to identifying optimal weight may be needed for patients with HF in primary care. Underweight people have the poorest prognosis and should be recognised as high-risk.
Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node
Authors: AlJabban Ali , Evans Mark G , Fell Geoffrey G , Guccione Jack P , Edwards Robert A , Pinkus Geraldine S , Padera Robert F , Pozdnyakova Olga , Kim Annette S 
Published: June 2023

AimsThe identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this disease; however, only a limited number of case series have focused on lymphoid or haematopoietic tissues.MethodsBM and lymph node (LN) specimens were obtained from adult autopsies performed between 1 April 2020 and 1 June 2020, for which the decedent had tested positive for SARS-CoV-2. Tissue sections (H&E, CD3, CD20, CD21, CD138, CD163, MUM1, kappa/lambda light chains in situ hybridisation) were examined by two haematopathologists, who recorded morphological features in a blinded fashion. Haemophagocytic lymphohistiocytosis (HLH) was assessed based on HLH 2004 criteria.ResultsThe BM demonstrated a haemophagocytic pattern in 9 out of 25 patients (36%). The HLH pattern was associated with longer hospitalisation, BM plasmacytosis, LN follicular hyperplasia and lower aspartate aminotransferase (AST), as well as ferritin at demise. LN examination showed increased plasmacytoid cells in 20 of 25 patients (80%). This pattern was associated with a low absolute monocyte count at diagnosis, lower white cell count and lower absolute neutrophil count at demise, and lower ferritin and AST at demise.ConclusionsAutopsy results demonstrate distinct morphological patterns in BM, with or without haemophagocytic macrophages, and in LN, with or without increased plasmacytoid cells. Since only a minority of patients met diagnostic criteria for HLH, the observed BM haemophagocytic macrophages may be more indicative of an overall inflammatory state.
Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors
Authors: Reil Katherine A , Tsuji Shingo , Molina Elsa , Nelson Kinsey L , McGuire Kathleen L , Giacalone Matthew J 
Published: June 2023

BackgroundImmunologically cold tumors with an ‘immune desert’ phenotype lack tumor-infiltrating lymphocytes (TILs) and are typically impervious to systemic immune checkpoint blockade (ICB). Intratumoral treatment of tumors with immunomodulatory agents can promote local tumor inflammation leading to improved T cell responses in injected tumors. Addition of systemic ICB increases response frequency and immune-mediated clearance of injected and distal non-injected lesions, and this promising approach is being widely investigated clinically. In this work, we evaluate and characterize the local and systemic antitumor immunotherapeutic activity of VAX014, a novel non-viral targeted oncolytic agent based on recombinant bacterial minicells, following intratumoral administration and in combination with systemic ICB.MethodsThe immunotherapeutic activity of VAX014 following weekly intratumoral administration was investigated in multiple preclinical tumor models with B16F10 murine melanoma serving as the primary model for evaluation of immune desert tumors. Mice bearing a single intradermal tumor were used to evaluate tumor response and overall survival (OS), assess changes in immune cell populations, and explore global changes to immunotranscriptomes of injected tumors. Mice bearing bilateral intradermal tumors were then used to evaluate non-injected tumors for changes in TIL populations and phenotypes, compare immunotranscriptomes across treatment groups, and assess distal non-injected tumor response in the context of monotherapy or in combination with ICB.ResultsVAX014 demonstrated strong immune-mediated tumor clearance of injected tumors coinciding with significantly elevated CD8+TILs and upregulation of multiple immune pathways essential for antitumor immune responses. Modest activity against distal non-injected immune desert tumors was observed despite elevated levels of systemic antitumor lymphocytes. Combination with systemic CTLA-4 blockade improved survival and elevated TILs but did not improve clearance rates of non-injected tumors. Immunotranscriptomes of non-injected tumors from this treatment combination group exhibited upregulation of multiple immune pathways but also identified upregulation of PD-1. Further addition of systemic PD-1 blockade led to rapid clearance of non-injected tumors, enhanced OS, and provided durable protective immunological memory.ConclusionsIntratumoral administration of VAX014 stimulates local immune activation and robust systemic antitumor lymphocytic responses. Combination with systemic ICB deepens systemic antitumor responses to mediate clearance of injected and distal non-injected tumors.
Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial
Authors: Appleton Jason Philip , Woodhouse Lisa J , Anderson Craig S , Ankolekar Sandeep , Cala Lesley , Dixon Mark , England Timothy J , Krishnan Kailash , Mair Grant , Muir Keith W , Potter John , Price Christopher I , Randall Marc , Robinson Thompson G , Roffe Christine , Sandset Else C , Saver Jeffrey L , Shone Angela , Siriwardena Aloysius Niroshan , Wardlaw Joanna M , Sprigg Nikola , Bath Philip M 
Published: June 2023

BackgroundThe effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2).MethodsRIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined ‘brain frailty’ markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI.Results597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging ‘brain frailty’ was common: median score 2 [2, 3] (range 0–3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI −0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke.ConclusionsIn patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.
Higher-group structure in lattice Abelian gauge theory under instanton-sum modification
Authors: Kan Naoto , Morikawa Okuto , Nagoya Yuta , Wada Hiroki 
Published: June 2023

AbstractWe consider the U(1) gauge theory on a four-dimensional torus, where the instanton number is restricted to an integral multiple of p. This theory possesses the nontrivial higher-group structure, which can be regarded as a generalization of the Green–Schwarz mechanism, between $$\mathbb {Z}_q$$

Z
q

1-form and $$\mathbb {Z}_p$$

Z
p

3-form symmetries. Here, $$\mathbb {Z}_q$$

Z
q

is a subgroup of the center of U(1). Following the recent study of the lattice construction of the $$U(1)/\mathbb {Z}_q$$

U

(
1
)

/

Z
q

principal bundle, we examine how such a structure is realized on the basis of lattice regularization.
Revisiting the universal texture zero of flavour: a Markov chain Monte Carlo analysis
Authors: Bernigaud Jordan , de Medeiros Varzielas Ivo , Levy Miguel , Talbert Jim 
Published: June 2023

AbstractWe revisit the phenomenological predictions of the Universal Texture Zero (UTZ) model of flavour originally presented in [1], and update them in light of both improved experimental constraints and numerical analysis techniques. In particular, we have developed an in-house Markov Chain Monte Carlo (MCMC) algorithm to exhaustively explore the UTZ’s viable parameter space, considering both leading- and next-to-leading contributions in the model’s effective operator product expansion. We also extract – for the first time – reliable UTZ predictions for the (poorly constrained) leptonic CP-violating phases, and ratio observables that characterize neutrino masses probed by (e.g.) oscillation, $$\beta $$
β
-decay, and cosmological processes. We therefore dramatically improve on the proof-in-principle phenomenological analysis originally presented in [1], and ultimately show that the UTZ remains a minimal, viable, and appealing theory of flavour. Our results also further demonstrate the potential of robustly examining multi-parameter flavour models with MCMC routines.
Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer
Authors: Ramkumar Kavya , Tanimoto Azusa , Della Corte Carminia M. , Stewart C. Allison , Wang Qi , Shen Li , Cardnell Robert J. , Wang Jing , Polanska Urszula M. , Andersen Courtney , Saeh Jamal , Pease J. Elizabeth , Travers Jon , Fabbri Giulia , Gay Carl M. , Urosevic Jelena , Byers Lauren A. 
Published: June 2023

AbstractPurpose:Therapeutic resistance to frontline therapy develops rapidly in small cell lung cancer (SCLC). Treatment options are also limited by the lack of targetable driver mutations. Therefore, there is an unmet need for developing better therapeutic strategies and biomarkers of response. Aurora kinase B (AURKB) inhibition exploits an inherent genomic vulnerability in SCLC and is a promising therapeutic approach. Here, we identify biomarkers of response and develop rational combinations with AURKB inhibition to improve treatment efficacy.Experimental Design:Selective AURKB inhibitor AZD2811 was profiled in a large panel of SCLC cell lines (n = 57) and patient-derived xenograft (PDX) models. Proteomic and transcriptomic profiles were analyzed to identify candidate biomarkers of response and resistance. Effects on polyploidy, DNA damage, and apoptosis were measured by flow cytometry and Western blotting. Rational drug combinations were validated in SCLC cell lines and PDX models.Results:AZD2811 showed potent growth inhibitory activity in a subset of SCLC, often characterized by, but not limited to, high cMYC expression. Importantly, high BCL2 expression predicted resistance to AURKB inhibitor response in SCLC, independent of cMYC status. AZD2811-induced DNA damage and apoptosis were suppressed by high BCL2 levels, while combining AZD2811 with a BCL2 inhibitor significantly sensitized resistant models. In vivo, sustained tumor growth reduction and regression was achieved even with intermittent dosing of AZD2811 and venetoclax, an FDA-approved BCL2 inhibitor.Conclusions:BCL2 inhibition overcomes intrinsic resistance and enhances sensitivity to AURKB inhibition in SCLC preclinical models.
Design and Evaluation of Virtual Reality Environments for Claustrophobia
Authors: Francová Anna , Jablonská Markéta , Fajnerová Iveta 
Published: June 2023

Abstract
Claustrophobia is a specific phobia characterized by fear of enclosed spaces (such as elevators, subway tunnels, etc.). While some individuals with claustrophobia might experience only mild anxiety and discomfort in enclosed spaces, others might suffer from panic attacks usually triggered by a fear of losing control or being unable to escape when needed. One of the most recent and successful treatment methods applied in specific phobias are virtual reality (VR)-based exposure therapy techniques. This feasibility study aimed to design and validate a set of immersive virtual environments (VEs) for exposure therapy in claustrophobia, with interactive scenarios enabling systematic, gradual, and controlled induction of claustrophobic fear. In total, eighteen individuals participated in the feasibility study. Participants were recruited from a general population and divided into two groups (phobic vs. control group). Each participant was asked to evaluate a set of various virtual environments. The study results indicate that the designed virtual environments have the potential to induce claustrophobic fear and are thus considered suitable for use in the exposure therapy of claustrophobia. These virtual environments also evoked a sense of presence, particularly the spatial presence component, while the reported cybersickness symptoms were none or minimal.
Queer Mediated Practices as a Method to Center and Sustain Critical Health and Media Literacies
Authors: Vera A. Nick , Kitzie Vanessa L. , Wagner Travis L. 
Published: June 2023

Abstract
Queer communities experience challenges when accessing accurate and comprehensive health information. These challenges span across media and information environments and threaten queer health promotion. This paper explored how 11 queer community health workers (chw s) in a Southeastern US state respond to, subvert, and resist these challenges when creating digital health information resources for their queer communities. This longitudinal action research occurred over two years and included multiple qualitative data types. We analyzed these data using qualitative coding, following deductive and inductive strategies. Findings demonstrate how queer chw s: 1) identified risks and barriers to health promotion their communities experienced; 2) created health information resources that proactively guarded against risks and reactively resisted barriers; 3) borrowed content, format, and logic from other digital media sources, remixing and repurposing them in ways relevant to their communities. Findings denote implications for decentering deficit-based approaches to framing the health and media literacies of queer populations.