bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of an avatar-based discharge education application on knowledge and behaviour in people after acute coronary syndrome: protocol for a pragmatic prospective randomised controlled trial
Authors: Ellis Tiffany , Cheng Sonia , Zecchin Robert , Zwack Clara , Hyun Karice , Zhang Ling , Gallagher Robyn , Clark Robyn , Redfern Julie 
Published: August 2023

IntroductionMany hospital presentations for acute coronary syndrome (ACS) occur in people previously hospitalised with coronary heart disease (CHD), leading to increased costs and health burden. Secondary prevention education including a prehospital discharge plan is recommended for all individuals to reduce the risk of recurrence. However, many clinicians lack the time or support to provide education, and patients’ uptake of secondary prevention programmes is limited. An avatar-based education app is a novel and engaging way to provide self-delivered, evidence-based secondary prevention information during the hospital admission and remains accessible after discharge. This protocol aims to evaluate the effect of an avatar-based education app on individuals with ACS.Methods and analysisThis protocol describes a prospective, randomised controlled trial with 3-month follow-up and blinded assessment of 72 participants. Intervention group participants will download the app onto their own device during the hospital admission and independently complete six interactive education modules based on the National Heart Foundation’s six steps to cardiac recovery. All participants will receive a text message reminder of the study after 3 weeks. Both groups will receive usual care consisting of bedside education and a pamphlet about cardiac rehabilitation. The primary outcome is knowledge of CHD, assessed using the Coronary Artery Disease Education Questionnaire II. Secondary outcomes include quality of life, response to heart attack symptoms, cardiac-related readmissions and mortality and modifiable cardiac risk factors. Engagement with the app will be evaluated objectively. Intention-to-treat analysis will be conducted, with between-group comparisons and 95% CIs of the primary outcome analysed using analysis of covariance, adjusting for baseline values.Ethics and disseminationThis study protocol has been approved by the Western Sydney Local Health District Human Research Ethics Committee. The results of this study will be disseminated via a peer-reviewed journal and research thesis.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12622001436763).
Absolute cardiovascular risk assessment by Australian early-career general practitioners: a cross-sectional study
Authors: Morgan Toby , Ralston Anna , Davey Andrew , Holliday Elizabeth G , Nelson Mark , Fielding Alison , van Driel Mieke , Tapley Amanda , Moad Dominica , Ball Jean , Presser Jennifer , Spike Neil , Magin Parker 
Published: August 2023

ObjectiveTo determine the prevalence and associations of general practice registrars’ performing absolute cardio-vascular risk (ACVR) assessment (ACVRa).DesignA cross-sectional study employing data (2017–2018) from the Registrar Clinical Encounters in Training project, an ongoing inception cohort study of Australian GP registrars. The outcome measure was whether an ACVRa was performed. Analyses employed univariable and multivariable regression. Analysis was conducted for all patient problems/diagnoses, then for an ‘at-risk’ population (specific problems/diagnoses for which ACVRa is indicated).SettingThree GP regional training organisations (RTOs) across three Australian states.ParticipantsGP registrars training within participating RTOs.Results1003 registrars (response rate 96.8%) recorded details of 69 105 problems either with Aboriginal and/or Torres Strait patients aged 35 years and older or with non-Indigenous patients aged 45 years and older. Of these problems/diagnoses, 1721 (2.5% (95% CI 2.4% to 2.6%)) involved an ACVRa. An ACVRa was ‘plausibly indicated’ in 10 384 problems/diagnoses. Of these, 1228 (11.8% (95% CI 11.2% to 12.4%)) involved ACVRa. For ‘all problems/diagnoses’, on multivariable analysis female gender was associated with reduced odds of ACVRa (OR 0.61 (95% CI 0.54 to 0.68)). There was some evidence for Aboriginal and/or Torres Strait Islander people being more likely to receive ACVRa (OR 1.40 (95% CI 0.94 to 2.08), p=0.10). There were associations with variables related to continuity of care, with reduced odds of ACVRa: if the patient was new to the registrar (OR 0.65 (95% CI 0.57 to 0.75)), new to the practice (OR 0.24 (95% CI 0.15 to 0.38)) or the problem was new (OR 0.68 (95% CI 0.59 to 0.78)); and increased odds if personal follow-up was organised (OR 1.43 (95% CI 1.24 to 1.66)). For ‘ACVRa indicated’ problems/diagnoses, findings were similar to those for ‘all problems/diagnoses’. Association with Aboriginal and/or Torres Strait Islander status, however, was significant at p<0.05 (OR 1.60 (95% CI 1.04 to 2.46)) and association with female gender was attenuated (OR 0.88 (95% CI 0.77 to 1.01)).ConclusionContinuity of care is associated with registrars assessing ACVR, reinforcing the importance of care continuity in general practice. Registrars’ assessment of an individual patient’s ACVR is targeted to patients with individual risk factors, but this may entail ACVRa underutilisation in female patients and younger age groups.
Associations between modifiable risk factors and frailty: a Mendelian randomisation study
Authors: Zhang Nan , Jia Ziheng , Gu Tianshu , Zheng Yi , Zhang Yunpeng , Song Wenhua , Chen Ziliang , Li Guangping , Tse Gary , Liu Tong 
Published: August 2023

BackgroundEarly identification of modifiable risk factors is essential for the prevention of frailty. This study aimed to explore the causal relationships between a spectrum of genetically predicted risk factors and frailty.MethodsUnivariable and multivariable Mendelian randomisation (MR) analyses were performed to explore the relationships between 22 potential risk factors and frailty, using summary genome-wide association statistics. Frailty was accessed by the frailty index.ResultsGenetic liability to coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), ischaemic stroke, atrial fibrillation and regular smoking history, as well as genetically predicted 1-SD increase in body mass index, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, alcohol intake frequency and sleeplessness were significantly associated with increased risk of frailty (all p<0.001). In addition, there was a significant inverse association between genetically predicted college or university degree with risk of frailty (beta −0.474; 95% CI (−0.561 to –0.388); p<0.001), and a suggestive inverse association between high-density lipoprotein cholesterol level with risk of frailty (beta −0.032; 95% CI (−0.055 to –0.010); p=0.004). However, no significant causal associations were observed between coffee consumption, tea consumption, serum level of total testosterone, oestradiol, 25-hydroxyvitamin D, C reactive protein or moderate to vigorous physical activity level with frailty (all p>0.05). Results of the reverse directional MR suggested bidirectional causal associations between T2DM and CAD with frailty.ConclusionsThis study provided genetic evidence for the causal associations between several modifiable risk factors with lifetime frailty risk. A multidimensional approach targeting these factors may hold a promising prospect for prevention frailty.
Long-term outcomes among stable post-acute myocardial infarction patients living in rural versus urban areas: insights from the prospective, observational TIGRIS registry
Authors: Nicolau Jose Carlos , Owen Ruth , Furtado Remo H M , Goodman Shaun G , Granger Christopher B , Cohen Mauricio G , Westermann Dirk , Yasuda Satoshi , Simon Tabassome , Hedman Katarina , Hunt Phillip R , Brieger David B , Pocock Stuart J 
Published: August 2023

BackgroundInsights on the differences in clinical outcomes, quality of life (QoL) and health resource utilisation (HRU) with different levels of care available to post-acute myocardial infarction (AMI) populations in rural and urban settings are limited.MethodsThe long-Term rIsk, clinical manaGement, and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS), a prospective, observational registry, enrolled 8452 patients aged ≥50 years 1–3 years post-AMI from June 2013 to November 2014 from 24 countries in Asia Pacific/Australia, Europe, North America and South America. Differences in QoL (measured using the EuroQol Research Foundation instrument) and HRU between patients in rural and urban settings were evaluated in this post hoc analysis. The incidence of clinical endpoints (cardiovascular (CV) death, AMI, unstable angina with urgent revascularisation and stroke; bleeding; and all-cause mortality) was analysed. Data were collected at baseline and every 6 months for 24 months.ResultsThere were fewer hospitalisations and visits to general practitioners (GPs) and cardiologists in the rural versus urban populations (adjusted event rate ratio (ERR)=0.90 (95% CI, 0.82 to 1.00, p=0.04); ERR=0.84 (95% CI, 0.78 to 0.92, p<0.001); ERR=0.86 (95% CI, 0.81 to 0.92, p<0.001), respectively). No statistically significant differences were observed between rural and urban populations in all-cause death, AMI, unstable angina with urgent revascularisation, CV death, stroke, major bleeding events and health-related QoL. The adjusted incidence rate ratio was 0.92 (95% CI, 0.74 to 1.15) for the composite of CV death, AMI and stroke.ConclusionsLiving in rural areas was associated with fewer GP/cardiologist visits and hospitalisations; no significant differences in clinical outcomes and QoL were observed.Trial registration numberNCT01866904.
Safety profile of baricitinib in patients with systemic lupus erythematosus: an integrated analysis
Authors: Morand Eric , Smolen Josef S , Petri Michelle , Tanaka Yoshiya , Silk Maria , Dickson Christina , Meszaros Gabriella , de la Torre Inmaculada , Issa Maher , Zhang Hong , Dörner Thomas 
Published: August 2023

ObjectivesTo assess the safety of the oral Janus kinase inhibitor baricitinib in adult patients with systemic lupus erythematosus (SLE) receiving stable background therapy. Topics of special interest included infections and cardiovascular and thromboembolic events.MethodsThis analysis included integrated safety data from three randomised, placebo-controlled studies (one phase 2 and two phase 3) and one long-term extension study. Data are reported in three data sets: placebo-controlled, extended exposure and all-baricitinib. Outcomes include treatment-emergent adverse events (AEs), AEs of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IRs) were calculated.ResultsA total of 1655 patients received baricitinib for up to 3.5 years (median duration 473 days). With baricitinib 4 mg, baricitinib 2 mg and placebo, respectively, 50.8%, 50.7% and 49.0% of patients reported at least one infection and 4.4%, 3.4% and 1.9% of patients had a serious infection. The most common treatment-emergent infections included urinary tract infection, COVID-19, upper respiratory tract infection and nasopharyngitis. Herpes zoster was more common with baricitinib 4 mg (4.7%) vs baricitinib 2 mg (2.7%) and placebo (2.8%). Among baricitinib-4 mg, 2 mg and placebo-treated patients, respectively, 4 (IR=0.9), 1 (IR=0.2) and 0 experienced at least one positively adjudicated major adverse cardiovascular event, and 0, 3 (IR=0.6) and 2 (IR=0.4) reported at least one positively adjudicated venous thromboembolism.ConclusionsThe results of this integrated safety analysis in patients with SLE are not substantially different to the established safety profile of baricitinib. No increased venous thromboembolism was found.
A perturbative production of massive Z bosons and fermion–antifermion pairs from the vacuum in the de Sitter Universe
Authors: Dumitrele Diana , Băloi Mihaela-Andreea , Crucean Cosmin 
Published: August 2023

AbstractIn this paper we study the problem of neutral electro-weak interactions in a de Sitter geometry. We develop the formalism of reduction for the Proca field with the help of the solutions for the interacting fields and by using perturbative methods we obtain the definition of the transition amplitudes in the first order of perturbation theory. As an application to our formalism we study the generation of massive fermions and Z bosons from vacuum in the expanding de Sitter universe. Our results are the generalization to the curved geometry of the Weinberg–Salam electro-weak theory for the case of Z boson interaction with leptons. The probability is found to be a quantity that depends on the Hubble parameter and we prove that such perturbative processes are possible only for large expansion regime of the early Universe. The total probability and rate of transition are obtained for the case of large expansion and we use the dimensional regularization for extract finite results from the momenta integrals. In the Minkowski limit we obtain that the probability of particle generation from vacuum is vanishing recovering the well known result that forbids particle production in flat space-time due to the momentum-energy conservation.
Collapsing dynamics of relativistic fluid in modified gravity admitting a conformal Killing vector
Authors: Bamba Kazuharu , Yousaf Z. , Bhatti M. Z. , Nazer R. , Hashimoto Yuki 
Published: August 2023

AbstractThe collapsing dynamics of relativistic fluid are explored in f(R) gravity in detailed systematic manner for the non-static spherically symmetric spacetime satisfying the equation of the conformal Killing vector. With quasi-homologous condition and diminishing complexity factor condition, exact solutions for dissipative as well as for non-dissipative system are found and the astrophysical applications of these exact solutions are discussed. Furthermore, it is demonstrated that $$f(R)=R,$$

f
(
R
)
=
R
,

which is the extensive restriction of f(R) gravity, prior solutions of the collapsing fluid in general relativity, can be retrieved.
The myth of the Highland Cretaceous revealed by the art of palaeogeographic mapping
Authors: Macdonald David I. M. 
Published: August 2023

Abstract
Since the term was coined in 1873, palaeogeography has provided a powerful map-based tool for synthesizing, visualizing, and testing diverse regional data and hypotheses, but there are problems in deducing the palaeogeography of areas with few data points. As an example, the Scottish Highlands are better mapped and more studied than almost any other ancient orogen, yet questions remain on the persistence of topography since the Caledonian orogeny and the possibility of Cretaceous marine inundation. This paper reviews the data available on Scottish Cretaceous outcrops using published geological maps and memoirs to extract data: outcrop length, stratigraphic thickness and component units, elevation range of the outcrop and subcrop formations. All Cretaceous rocks in western Scotland were deposited in shallow marine and shoreline environments; deposits thin northwards and appear to be close to a feather edge. Elevation data are used to construct a Cretaceous surface which intersects present-day topography at low to intermediate altitudes. It is concluded that the Scottish Highlands were largely emergent during the Late Cretaceous, confirming previous palaeogeographic studies.
Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance
Authors: Cotton Jennifer L. , Estrada Diez Javier , Sagar Vivek , Chen Julie , Piquet Michelle , Alford John , Song Youngchul , Li Xiaoyan , Riester Markus , DiMare Matthew T. , Schumacher Katja , Boulay Gaylor , Sprouffske Kathleen , Fan Lin , Burks Tyler , Mansur Leandra , Wagner Joel , Bhang Hyo-eun C. , Iartchouk Oleg , Reece-Hoyes John , Morris Erick J. , Hammerman Peter S. , Ruddy David A. , Korn Joshua M. , Engelman Jeffrey A. , Niederst Matthew J. 
Published: August 2023

Abstract

For a majority of patients with non–small cell lung cancer with EGFR mutations, treatment with EGFR inhibitors (EGFRi) induces a clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to disease relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister cells and deciphering how drug-tolerant cells evolve in response to treatment could help identify strategies to improve the efficacy of EGFRi. In this study, we tracked the origins and clonal evolution of drug-tolerant cells at a high resolution by using an expressed barcoding system coupled with single-cell RNA sequencing. This platform enabled longitudinal profiling of gene expression and drug sensitivity in response to EGFRi across a large number of clones. Drug-tolerant cells had higher expression of key survival pathways such as YAP and EMT at baseline and could also differentially adapt their gene expression following EGFRi treatment compared with sensitive cells. In addition, drug combinations targeting common downstream components (MAPK) or orthogonal factors (chemotherapy) showed greater efficacy than EGFRi alone, which is attributable to broader targeting of the heterogeneous EGFRi-tolerance mechanisms present in tumors. Overall, this approach facilitates thorough examination of clonal evolution in response to therapy that could inform the development of improved diagnostic approaches and treatment strategies for targeting drug-tolerant cells.

Significance:
The evolution and heterogeneity of EGFR inhibitor tolerance are identified in a large number of clones at enhanced cellular and temporal resolution using an expressed barcode technology coupled with single-cell RNA sequencing.
Fasting-Mimicking Diet Drives Antitumor Immunity against Colorectal Cancer by Reducing IgA-Producing Cells
Authors: Zhong Ziwen , Zhang Hao , Nan Ke , Zhong Jing , Wu Qichao , Lu Lihong , Yue Ying , Zhang Zhenyu , Guo Miaomiao , Wang Zhiqiang , Xia Jie , Xing Yun , Fu Ying , Yu Baichao , Zhou Wenchang , Sun Xingfeng , Shen Yang , Chen Wankun , Zhang Jie , Zhang Jin , Ma Duan , Chu Yiwei , Liu Ronghua , Miao Changhong 
Published: August 2023

Abstract

As a safe, feasible, and inexpensive dietary intervention, fasting-mimicking diet (FMD) exhibits excellent antitumor efficacy by regulating metabolism and boosting antitumor immunity. A better understanding of the specific mechanisms underlying the immunoregulatory functions of FMD could help improve and expand the clinical application of FMD-mediated immunotherapeutic strategies. In this study, we aimed to elucidate the role of metabolic reprogramming induced by FMD in activation of antitumor immunity against colorectal cancer. Single-cell RNA sequencing analysis of intratumoral immune cells revealed that tumor-infiltrating IgA+ B cells were significantly reduced by FMD treatment, leading to the activation of antitumor immunity and tumor regression in murine colorectal cancer models. Mechanistically, FMD delayed tumor growth by repressing B-cell class switching to IgA. Therefore, FMD-induced reduction of IgA+ B cells overcame the suppression of CD8+ T cells. The immunoregulatory and antitumor effects of FMD intervention were reversed by IgA+ B-cell transfer. Moreover, FMD boosted fatty acid oxidation (FAO) to trigger RUNX3 acetylation, thus inactivating Cα gene transcription and IgA class switching. IgA+ B-cell expansion was also impeded in patients placed on FMD, while B-cell expression of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme of FAO, was increased. Furthermore, CPT1A expression was negatively correlated with both IgA+ B cells and IgA secretion within colorectal cancer. Together, these results highlight that FMD holds great promise for treating colorectal cancer. Furthermore, the degree of IgA+ B cell infiltration and FAO-associated metabolic status are potential biomarkers for evaluating FMD efficacy.

Significance:
Metabolic reprogramming of B cells induced by fasting-mimicking diet suppresses IgA class switching and production to activate antitumor immunity and inhibit tumor growth.
See related commentary by Bush and Perry, p. 3493
Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade
Authors: Gao Yaqi , Xu Pingping , Sun Danfeng , Jiang Yi , Lin Xiao-Lin , Han Ting , Yu Jun , Sheng Chunquan , Chen Haoyan , Hong Jie , Chen Yingxuan , Xiao Xiu-Ying , Fang Jing-Yuan 
Published: August 2023

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential. Here, we found that patients receiving ICIs who developed colitis had a lower abundance of F. prausnitzii. In vivo, immunocompetent mice administered with dextran sodium sulfate and immunodeficient NSG mice with human peripheral blood mononuclear cell transfer were treated with ICIs to study ICI-induced colitis. Dual CTLA4 and PD-1 blockade exacerbated autoimmune colitis, activated an inflammatory response, and promoted myeloid cell infiltration, with higher percentages of macrophages, dendritic cells, monocytes, and neutrophils. F. prausnitzii administration mitigated the exacerbated colitis induced by ICIs. Concomitantly, F. prausnitzii enhanced the antitumor immunity elicited by ICIs in tumor-bearing mice while abrogating colitis. In addition, administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. F. prausnitzii abundance was reduced in mice that developed ICI-associated colitis. Together, this study shows that F. prausnitzii administration ameliorates ICI-induced colitis, reshapes the gut microbial composition, and enhances the antitumor activity of immunotherapy.

Significance:
F. prausnitzii alleviates colitis while enhancing the tumor-suppressive effects of immune checkpoint blockade, indicating that supplementation with F. prausnitzii could be a treatment strategy to mitigate immunotherapy toxicity in patients with cancer.