bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the Overall Fidelity Enactment Scale for Complex Interventions (OFES-CI)
Authors: Ginsburg Liane , Hoben Matthias , Berta Whitney , Doupe Malcolm , Estabrooks Carole A , Norton Peter G , Reid Colin , Geerts Ariane , Wagg Adrian 
Published: August 2023

BackgroundIn many quality improvement (QI) and other complex interventions, assessing the fidelity with which participants ‘enact’ intervention activities (ie, implement them as intended) is underexplored. Adapting the evaluative approach used in objective structured clinical examinations, we aimed to develop and validate a practical approach to assessing fidelity enactment—the Overall Fidelity Enactment Scale for Complex Interventions (OFES-CI).MethodsWe developed the OFES-CI to evaluate enactment of the SCOPE QI intervention, which teaches nursing home teams to use plan-do-study-act (PDSA) cycles. The OFES-CI was piloted and revised early in SCOPE with good inter-rater reliability, so we proceeded with a single rater. An intraclass correlation coefficient (ICC) was used to assess inter-rater reliability. For 27 SCOPE teams, we used ICC to compare two methods for assessing fidelity enactment: (1) OFES-CI ratings provided by one of five trained experts who observed structured 6 min PDSA progress presentations made at the end of SCOPE, (2) average rating of two coders’ deductive content analysis of qualitative process evaluation data collected during the final 3 months of SCOPE (our gold standard).ResultsUsing Cicchetti’s classification, inter-rater reliability between two coders who derived the gold standard enactment score was ‘excellent’ (ICC=0.93, 95% CI=0.85 to 0.97). Inter-rater reliability between the OFES-CI and the gold standard was good (ICC=0.71, 95% CI=0.46 to 0.86), after removing one team where open-text comments were discrepant with the rating. Rater feedback suggests the OFES-CI has strong face validity and positive implementation qualities (acceptability, easy to use, low training requirements).ConclusionsThe OFES-CI provides a promising novel approach for assessing fidelity enactment in QI and other complex interventions. It demonstrates good reliability against our gold standard assessment approach and addresses the practicality problem in fidelity assessment by virtue of its suitable implementation qualities. Steps for adapting the OFES-CI to other complex interventions are offered.
Temporal trends in mortality of aortic dissection and rupture in the UK, Japan, the USA and Canada
Authors: Hibino Makoto , Verma Subodh , Jarret Craig M , Shimamura Junichi , Verma Raj , Hibino Hiromi , Baeza Cristian R , Aune Dagfinn , Yanagawa Bobby , Usui Akihiko , Nienaber Christoph A , Pelletier Marc P 
Published: August 2023

ObjectiveAortic dissection and aortic aneurysm rupture are aortic emergencies and their clinical outcomes have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question. The purpose of this study was to compare mortality trends from aortic dissection and rupture between the UK, Japan, the USA and Canada.MethodsWe analysed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in four countries from 2000 to 2019. Age-standardised mortality rates per 100 000 persons were calculated, and annual percentage change was estimated using joinpoint regression.ResultsAge-standardised mortality rates per 100 000 persons from aortic dissection and rupture in 2019 were 1.04 and 1.80 in the UK, 2.66 and 1.16 in Japan, 0.76 and 0.52 in the USA, and 0.67 and 0.81 in Canada, respectively. There was significantly decreasing trends in age-standardised mortality from aortic rupture in all four countries and decreasing trends in age-standardised mortality from aortic dissection in the UK over the study period. There was significantly increasing trends in mortality from aortic dissection in Japan over the study period. Joinpoint regression identified significant changes in the aortic dissection trends from decreasing to increasing in the USA from 2010 and Canada from 2012. In sensitivity analyses stratified by sex, similar trends were observed.ConclusionsTrends in mortality from aortic rupture are decreasing; however, mortality from aortic dissection is increasing in Japan, the USA and Canada. Further study to explain these trends is warranted.
Location of CD39+T cell subpopulations within tumors predict differential outcomes in non-small cell lung cancer
Authors: Koppensteiner Lilian , Mathieson Layla , Pattle Samuel , Dorward David A , O’Connor Richard , Akram Ahsan R 
Published: August 2023

PurposeAn improved mechanistic understanding of immunosuppressive pathways in non-small cell lung cancer (NSCLC) is important to develop novel diagnostic and therapeutic approaches. Here, we investigate the prognostic significance of the ectonucleotidases CD39 and CD73 in NSCLC.Experimental designThe expression and localization of CD39, CD73 and CD103 was digitally quantified in a cohort of 162 early treatment naïve NSCLC patients using multiplex-immunofluorescence and related to patient outcome. Expression among different cell-populations was assessed via flow cytometry. Targeted RNA-Seq was performed on CD4+and CD8+T cells from digested NSCLC tumor tissue and single-cell RNA-Seq data was analyzed to investigate the functional significance of CD39+T cell populations.ResultsWe demonstrate that flow cytometry of early untreated NSCLC patients shows an upregulation of CD39 expression in the tumor tissue among natural killer (NK) cells, fibroblasts and T cells. CD73 expression is mainly found among fibroblasts and Epcam+cells in the tumor tissue. Multiplex Immunofluorescence in a cohort of 162 early untreated NSCLC patients demonstrates that CD39 expression is mainly localized in the tumor stroma while CD73 expression is equally distributed between tumor nest and stroma, and high expression of CD39 and CD73 in the tumor stroma is associated with poor recurrence-free survival (RFS) at 5 years. Additionally, we find that CD8+T cells located in the tumor nest express CD103 and the density of CD39+CD103+CD8+ T cells in the tumor nest predicts improved RFS at 5 years. Targeted RNA-Seq shows that the tumor microenvironment of NSCLC upregulates regulatory pathways in CD4+T cells and exhaustion in CD8+T cells, and analysis of a single cell RNA sequencing dataset shows that CD39+CD4+cells are enriched in Treg signature gene-sets, and CD39+CD103+cytotoxic T lymphocyte show gene signatures indicative of an exhausted cytotoxic phenotype with upregulated expression of CXCL13.ConclusionsKnowledge of patterns of distribution and location are required to understand the prognostic impact of CD39+T cell populations in NSCLC. This study provides an improved understanding of spatial and functional characteristics of CD39+T cells and their significance to patient outcome.
NKG2A gene variant predicts outcome of immunotherapy in AML and modulates the repertoire and function of NK cells
Authors: Hussein Brwa Ali , Kristenson Linnea , Pesce Silvia , Wöhr Anne , Tian Yarong , Hallner Alexander , Brune Mats , Hellstrand Kristoffer , Tang Ka-Wei , Bernson Elin , Thorén Fredrik B 
Published: August 2023

BackgroundThe natural killer (NK) complex (NKC) harbors multiple genes such as KLRC1 (encoding NKG2A) and KLRK1 (encoding NKG2D) that are central to regulation of NK cell function. We aimed at determining to what extent NKC haplotypes impact on NK cell repertoire and function, and whether such gene variants impact on outcome of IL-2-based immunotherapy in acute myeloid leukemia (AML).MethodsGenotype status of NKG2D rs1049174 and NKG2A rs1983526 was determined using the TaqMan-Allelic discrimination approach. To dissect the impact of single nucloetide polymorphim (SNP) on NK cell function, we engineered the K562 cell line with CRISPR to be killed in a highly NKG2D-dependent fashion. NK cells were assayed for degranulation, intracellular cytokine production and cytotoxicity using flow cytometry.ResultsIn AML patients receiving immunotherapy, the NKG2A gene variant, rs1983526, was associated with superior leukemia-free survival and overall survival. We observed that superior NK degranulation from individuals with the high-cytotoxicity NKG2D variant was explained by presence of a larger, highly responsive NKG2A+subset. Notably, NK cells from donors homozygous for a favorable allele encoding NKG2A mounted stronger cytokine responses when challenged with leukemic cells, and NK cells from AML patients with this genotype displayed higher accumulation of granzyme B during histamine dihydrochloride/IL-2 immunotherapy. Additionally, among AML patients, the NKG2A SNP defined a subset of patients with HLA-B-21 TT with a strikingly favorable outcome.ConclusionsThe study results imply that a dimorphism in the NKG2A gene is associated with enhanced NK cell effector function and improved outcome of IL-2-based immunotherapy in AML.
Clinical significance and prevalence of subarachnoid hyperdensities on flat detector CT after mechanical thrombectomy: does it really matter?
Authors: Zidan Mousa , Ghaei Shiwa , Bode Felix J , Weller Johannes M , Krueger Nadine , Lehnen Nils Christian , Petzold Gabor C , Radbruch Alexander , Dorn Franziska , Paech Daniel 
Published: August 2023

BackgroundSubarachnoid hyperdensities after mechanical thrombectomy (MT) are a common finding. However, it is often regarded as clinically insignificant.ObjectiveWith this single-center investigation, to identify the prevalence of subarachnoid hyperdensities following MT, associated predictors, and the impact on the clinical outcome of the patients.Methods383 patients from the stroke registry were analyzed for the presence of subarachnoid hyperdensities on flat detector CT (FDCT) directly after the completion of MT, and on follow-up dual-energy CT, then classified according to a visual grading scale. 178 patients were included with anterior circulation occlusions. Regression analysis was performed to identify significant predictors, and Kruskal-Wallis analysis and Χ2test were performed to test the variables among the different groups. The primary outcome was the modified Rankin Scale (mRS) score at 90 days and was analyzed with the Wilcoxon–Mann-Whitney rank-sum test.ResultsThe prevalence of subarachnoid hyperdensities on FDCT was (66/178, 37.1%) with patients experiencing a significant unfavorable outcome (P=0.035). Significantly fewer patients with subarachnoid hyperdensities achieved a mRS score of ≤3 at 90 days 25/66 (37.9%) vs 60/112 (53.6%), P=0.043). In addition, mortality was significantly higher in the subarachnoid hyperdensities group (34.8% vs 19.6%, P=0.024). Distal occlusions and a higher number of device passes were significantly associated with subarachnoid hyperdensities (P=0.026) and (P=0.001), respectively. Patients who received intravenous tissue plasminogen activator had significantly fewer subarachnoid hyperdensities (P=0.029).ConclusionsPostinterventional subarachnoid hyperdensities are a frequent finding after MT and are associated with neurological decline and worse functional outcome. They are more common with distal occlusions and multiple device passes.
Endovascular therapy for acute intracranial large vessel occlusion due to atherothrombosis: Multicenter historical registry
Authors: Uchida Kazutaka , Yamagami Hiroshi , Sakai Nobuyuki , Shirakawa Manabu , Beppu Mikiya , Toyoda Kazunori , Matsumaru Yuji , Matsumoto Yasushi , Todo Kenichi , Hayakawa Mikito , Shindo Seigo , Ota Shinzo , Morimoto Masafumi , Takeuchi Masataka , Imamura Hirotoshi , Ikeda Hiroyuki , Tanaka Kanta , Ishihara Hideyuki , Kakita Hiroto , Sano Takanori , Araki Hayato , Nomura Tatsufumi , Sakakibara Fumihiro , Yoshimura Shinichi 
Published: August 2023

BackgroundAtherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion or stenosis (tandem group). The prognosis and reocclusion rate of each etiology after endovascular therapy (EVT) is unclear.MethodsWe conducted a historical multicenter registry study at 51 Japanese centers to compare the prognoses of AT-LVO between two etiologies. The primary outcome was the incidence of recurrent ischemic stroke or reocclusion of the treated vessels within 90 days after EVT. Each of the primary outcome means the incidence of recurrent ischemic stroke and reocclusion of the treated vessels within 90 days after EVT.ResultsWe analyzed 582 patients (338 in the intracranial group and 244 in the tandem group). Patients in the intracranial group were younger (mean 71.9 vs 74.5, p=0.003), more of them were female and fewer of them were current smokers than those in the tandem group. In the tandem group, the patients’ National Institutes of Health Stroke Scale score on admission was higher (13 vs 15, p=0.006), onset to puncture time was shorter (299 [145–631] vs 232 [144–459] minutes, p=0.03) and Alberta Stroke Program Early CT Score (ASPECTS) was lower (8 [7–9] vs 8 [6–9], p=0.0002). The primary outcome was higher in the intracranial group (22.5% vs 8.2%, p<0.0001). However, any ICH and death were not significantly different in the two groups.ConclusionsThe incidence of recurrent ischemic stroke or reocclusion after EVT for AT-LVO was higher in the intracranial group.
Long-term effectiveness of a cognitive behavioural therapy (CBT) in the management of fatigue in patients with relapsing remitting multiple sclerosis (RRMS): a multicentre, randomised, open-label, controlled trial versus standard care
Authors: Gay Marie Claire , Cassedanne Fanny , Barbot Frederic , Vaugier Isabelle , Thomas Sarah , Manchon Eric , Bensmail Djamel , Blanchere Marie , Heinzlef Olivier 
Published: August 2023

BackgroundFatigue is a disabling symptom of multiple sclerosis (MS). The lack of effective therapeutics has promoted the development of cognitive behavioural therapy (CBT)-based fatigue management programmes. However, their efficacy does not sustain over time. We proposed to test the long-term effectiveness of a 6-week fatigue programme supplemented with four booster sessions (‘FACETS+’) in patients with relapsing remitting MS (RRMS) and fatigue.MethodsThis multicentre, randomised, controlled, open-label, parallel-group trial versus standard care enrolled patients with RRMS and fatigue. Participants were randomised to either FACETS+ plus standard care or standard care alone. The primary outcome measure was fatigue impact (Modified Fatigue Impact Scale (MFIS) at 12 months) based on intention-to-treat analyses.ResultsFrom May 2017 to September 2020, 162 patients were screened; 105 were randomly assigned to FACETS+ (n=57) or standard care (n=48) and 88 completed the primary outcome assessment for the MFIS. At month 12, participants showed improved MFIS compared with baseline in the intervention group (mean difference (MD)=14.0 points; (95% CI 6.45 to 21.5)) and the control group (MD=6.1 points; (95% CI −0.30 to 12.5)) with a significant between-group difference in favour of the intervention group (adjusted MD=7.89 points; (95% CI 1.26 to 14.52), standardised effect size=0.52, p=0.021). No trial-related serious adverse events were reported.ConclusionsA 6-week CBT-based programme with four booster sessions is superior to standard care alone to treat MS-related fatigue in the long term (12 months follow-up). The results support the use of the FACETS+ programme for the treatment of MS-related fatigue.Trial registration numberNCT03758820.
Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study
Authors: Hestetun Sigrid , Andersen Svend , Sanner Helga , Størdal Ketil 
Published: August 2023

ObjectivesEarly antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA.MethodsWe conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0–24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA.ResultsWe included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0–24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0–6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA.ConclusionsThe novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.
A comprehensive discussion for the identification of cracking points in f(R) theories of gravity
Authors: Malik Adnan , Shafaq Attiya , Naz Tayyaba , Al-khaldi A. H. 
Published: August 2023

AbstractThis paper investigates the concept of cracking and overturning to analyze the impact of local density perturbations on the stability of self-gravitating compact objects in the framework of $$f(R,\phi , X)$$

f
(
R
,
ϕ
,
X
)

theory of gravity, where R, $$\phi $$
ϕ
, and X denote the Ricci scalar, scalar potential, and kinetic term, respectively. In this context, we developed the hydrostatic equilibrium equation for spherically symmetric spacetime with anisotropic matter configuration and subsequently employed the Krori Barua technique. We then perturb the hydrostatic equilibrium state of the configuration by employing the local density perturbation technique, while taking into account the barotropic equation of state. To validate this technique, we employed it on different compact stars namely, Her X-1, SAX J1808.4-3658, 4U 1820-30, PSR J1614-2230, Vela X-1, and Cen X-3, and found that all stars exhibit cracking or overturning for a specific range of model parameters. Conclusively, this study emphasizes that the proposed cracking technique provides significant insights into the stability analysis of self-gravitating compact objects.
Joint UV Optimization and Texture Baking
Authors: Knodt Julian , Pan Zherong , Wu Kui , Gao Xifeng 
Published: August 2023

Level of detail has been widely used in interactive computer graphics. In current industrial 3D modeling pipelines, artists rely on commercial software to generate highly detailed models with UV maps and then bake textures for low-poly counterparts. In these pipelines, each step is performed separately, leading to unsatisfactory visual appearances for low polygon count models. Moreover, existing texture baking techniques assume the low-poly mesh has a small geometric difference from the high-poly, which is often not true in practice, especially with extremely low poly count models.
To alleviate the visual discrepancy of the low-poly mesh, we propose to jointly optimize UV mappings during texture baking, allowing for low-poly models to faithfully replicate the appearance of the high-poly even with large geometric differences. We formulate the optimization within a differentiable rendering framework, allowing the automatic adjustment of texture regions to encode appearance information. To compensate for view parallax when two meshes have large geometric differences, we introduce a spherical harmonic parallax mapping, which uses spherical harmonic functions to modulate per-texel UV coordinates based on the view direction. We evaluate the effectiveness and robustness of our approach on a dataset composed of online downloaded models, with varying complexities and geometric discrepancies. Our method achieves superior quality over state-of-the-art techniques and commercial solutions.
Administrative Burden Associated with Cost-Related Delays in Care in U.S. Cancer Patients
Authors: Doherty Meredith , Thom Bridgette , Gardner Daniel S. 
Published: August 2023

Abstract

Background:
U.S. cancer patients engage in administrative tasks to pay for their healthcare. This study investigated the relationship between payment tasks and timely access to cancer care.

Methods:
We analyzed online survey data from 510 U.S. cancer patients and survivors to understand the relationship between administrative payment tasks and cost-related delays and nonadherence. Two-part modelling was used to determine if, and to what extent, there was a relationship between administrative burden and cost-related delays/nonadherence.

Results:
Younger patients (≤44 years) reported more payment tasks and cost-related delays/nonadherence than older patients (≥ 55 years); African American patients reported more payment tasks and cost-related delays/nonadherence than white patients. After accounting for age, race/ethnicity, education, and out-of-pocket costs, patients who reported engaging in more tasks had greater log odds of delaying/forgoing care [b = 0.18; 95% confidence interval (CI), 0.12–0.24]. Cost-related delays/nonadherence increased by 32% for every unit increase in administrative payment burden (b = 0.32; 95% CI, 0.18–0.46).

Conclusions:
Administrative payment burden increased the odds of cost-related delays and nonadherence by 49%, taking the form of delayed or skipped doctor appointments, tests and bloodwork, and prescription fulfillment. Younger patients and those identifying as African American were more likely to engage in payment tasks and to delay or forgo care due to cost. Administrative burdens can disrupt access to care and traditionally underserved patient populations are disproportionately exposed to these hardships.

Impact:
Reducing the complexity of healthcare through universal, human-centered design could reduce burdens and increase access.