bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engagement is a necessary condition to test audit and feedback design features: results of a pragmatic, factorial, cluster-randomized trial with an embedded process evaluation
Authors: McCleary Nicola , Desveaux Laura , Presseau Justin , Reis Catherine , Witteman Holly O. , Taljaard Monica , Linklater Stefanie , Thavorn Kednapa , Dobell Gail , Mulhall Cara L. , Lam Jonathan M. C. , Grimshaw Jeremy M. , Ivers Noah M. 
Published: May 2023

Abstract
Background
While audit & feedback (A&F) is an effective implementation intervention, the design elements which maximize effectiveness are unclear. Partnering with a healthcare quality advisory organization already delivering feedback, we conducted a pragmatic, 2 × 2 factorial, cluster-randomized trial to test the impact of variations in two factors: (A) the benchmark used for comparison and (B) information framing. An embedded process evaluation explored hypothesized mechanisms of effect.

Methods
Eligible physicians worked in nursing homes in Ontario, Canada, and had voluntarily signed up to receive the report. Groups of nursing homes sharing physicians were randomized to (A) physicians’ individual prescribing rates compared to top-performing peers (the top quartile) or the provincial median and (B) risk-framed information (reporting the number of patients prescribed high-risk medication) or benefit-framed information (reporting the number of patients not prescribed). We hypothesized that the top quartile comparator and risk-framing would lead to greater practice improvements. The primary outcome was the mean number of central nervous system-active medications per resident per month. Primary analyses compared the four arms at 6 months post-intervention. Factorial analyses were secondary. The process evaluation comprised a follow-up questionnaire and semi-structured interviews.

Results
Two hundred sixty-seven physicians (152 clusters) were randomized: 67 to arm 1 (median benchmark, benefit framing), 65 to arm 2 (top quartile benchmark, benefit framing), 75 to arm 3 (median benchmark, risk framing), and 60 to arm 4 (top quartile benchmark, risk framing). There were no significant differences in the primary outcome across arms or for each factor. However, engagement was low (27–31% of physicians across arms downloaded the report). The process evaluation indicated that both factors minimally impacted the proposed mechanisms. However, risk-framed feedback was perceived as more actionable and more compatible with current workflows, whilst a higher target might encourage behaviour change when physicians identified with the comparator.

Conclusions
Risk framing and a top quartile comparator have the potential to achieve change. Further work to establish the strategies most likely to enhance A&F engagement, particularly with physicians who may be most likely to benefit from feedback, is required to support meaningfully addressing intricate research questions concerning the design of A&F.

Trial registration
ClinicalTrials.gov, NCT02979964. Registered 29 November 2016.
Surgical treatment of double aortic arch malformation combined with descending aortic arch dissection in adults: a case series
Authors: Min Xinping , Hu Zhipeng , Wang Zhiwei , Xia Jun 
Published: May 2023

Abstract
Background
Double aortic arch (DAA) combined with descending aortic arch dissection (DAAD) in adults is a rare aorta vascular disease. Due to the abnormal anatomy of the double arch and arch vessels, the clinical symptoms and surgical methods differ from those of typical aortic dissection.

Methods
This study was retrospective analysis of a case series involving three patients (mean age, 47.3 years) with DAA combined DAAD underwent total arch replacement or hybrid aortic repair from September 2010 to June 2019. The patients’ demographics, initial symptoms, comorbidities, surgical procedures, and outcomes are summarized.

Results
Total arch replacement plus frozen stent implantation under deep hypothermic circulatory arrest was performed for 2 patients, one of them developed disseminated intravascular coagulation and multiple organ failure postoperatively. Case 3 underwent a hybrid procedure with left subclavian artery revascularization and thoracic endovascular aortic repair. The symptoms of hoarseness and dysphagia were obviously improved during the follow up.

Conclusion
In addition to typical sudden chest and back pain, patients with DAA and DAAD may have hoarseness and dysphagia. Based on the development of DAA, total arch replacement or hybrid surgery may be is an optional treatment.
Towards the international interoperability of clinical research networks for rare diseases: recommendations from the IRDiRC Task Force
Authors: Nabbout Rima , Zanello Galliano , Baker Dixie , Black Lora , Brambilla Isabella , Buske Orion J. , Conklin Laurie S. , Davies Elin Haf , Julkowska Daria , Kim Yeonju , Klopstock Thomas , Nakamura Harumasa , Nielsen Kim G. , Pariser Anne R. , Pastor Jose Carlos , Scarpa Maurizio , Smith Maureen , Taruscio Domenica , Groft Stephen 
Published: May 2023

Abstract
Background
Many patients with rare diseases are still lacking a timely diagnosis and approved therapies for their condition despite the tremendous efforts of the research community, biopharmaceutical, medical device industries, and patient support groups. The development of clinical research networks for rare diseases offers a tremendous opportunity for patients and multi-disciplinary teams to collaborate, share expertise, gain better understanding on specific rare diseases, and accelerate clinical research and innovation. Clinical Research Networks have been developed at a national or continental level, but global collaborative efforts to connect them are still lacking. The International Rare Diseases Research Consortium set a Task Force on Clinical Research Networks for Rare Diseases with the objective to analyse the structure and attributes of these networks and to identify the barriers and needs preventing their international collaboration. The Task Force created a survey and sent it to pre-identified clinical research networks located worldwide.

Results
A total of 34 responses were received. The survey analysis demonstrated that clinical research networks are diverse in their membership composition and emphasize community partnerships including patient groups, health care providers and researchers. The sustainability of the networks is mostly supported by public funding. Activities and research carried out at the networks span the research continuum from basic to clinical to translational research studies. Key elements and infrastructures conducive to collaboration are well adopted by the networks, but barriers to international interoperability are clearly identified. These hurdles can be grouped into five categories: funding limitation; lack of harmonization in regulatory and contracting process; need for common tools and data standards; need for a governance framework and coordination structures; and lack of awareness and robust interactions between networks.

Conclusions
Through this analysis, the Task Force identified key elements that should support both developing and established clinical research networks for rare diseases in implementing the appropriate structures to achieve international interoperability worldwide. A global roadmap of actions and a specific research agenda, as suggested by this group, provides a platform to identify common goals between these networks.
The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva
Authors: Ye Zhengqin , Wang Siyi , Shan Chang , Zhu Qi , Xue Ying , Zhang Keqin 
Published: May 2023

Abstract
Background
Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients.

Results
We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients.

Conclusions
There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis.
Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: a pragmatic performance evaluation
Authors: Moyo Sikhulile , Ramogola-Masire Doreen , Moraka Natasha O. , Tawe Leabaneng , Noubary Farzad , Motsumi Kesego , Manowe Godiraone , Zuze Boitumelo , Radibe Botshelo , Hungwe Faith T. T. , Mohammed Terence , Maphorisa Comfort , Shapiro Roger , Gaseitsiwe Simani , Luckett Rebecca 
Published: May 2023

Abstract
Background
Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease.

Methods
We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia.

Results
63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3–98.1) and negative percent agreement was 79.3% (95% CI 60.3–92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia.

Conclusions
The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.
Epitranscriptome marks detection and localization of RNA modifying proteins in mammalian ovarian follicles
Authors: Dubuc Karine , Marchais Mathilde , Gilbert Isabelle , Bastien Alexandre , Nenonene Karen E. , Khandjian Edward W. , Viger Robert S. , Delbes Géraldine , Robert Claude 
Published: May 2023

AbstractBackgroundMost of the resources that support the early development of the embryo are stored in the oocyte. Clearing of maternal resources and activation of the embryonic genome to produce its own mRNA transcripts marks the maternal-to-embryo transition. Dependence on stored mRNA can last from a few hours to several days, depending on animal species. The mechanisms regulating stabilization and recruitment of stored maternal transcripts have not yet been described in full detail but are known to involve reversible polyadenylation and modulation of 3’UTR-mediated elements. RNA epigenetic modifications, new players in this field, have an important role in RNA regulation and stabilization.ResultsThe objectives of this study were first to determine if some of post-transcriptional methylation of stored mRNA is greater in oocytes than in somatic cells. We found that m6A, known to be the most prevalent and involved in various aspects of RNA metabolism and physiological functions, is particularly abundant in porcine oocyte mRNA compared to liver used as a somatic tissue reference. The second objective was to compare the epitranscriptome machinery, such as methyltransferases (“writers”), binding proteins (“readers”) and demethylases (“erasers”) catalyzing the different process, in follicles and oocytes of different mammalian species by immunofluorescence and confocal microscopy. The expression and localization patterns of these proteins differ between mice, pigs and cows ovaries and oocytes. m5C-associated proteins were generally less abundant. In contrast, m6A-associated proteins were expressed strongly during the early and late stages of folliculogenesis. Transzonal projections were found to contain more granules bearing the m5C mark in mice but both m5C and m6A methylation marks in association with mature oocytes of pigs and cows. Eraser proteins showed the greatest interspecies diversity in terms of distribution in the germinal tissues.ConclusionsSo far, few studies have looked at the oocyte and ovarian epitranscriptomic profile. Our findings indicate that a hitherto unrecognized species-specific layer of transcript regulation occurs at the RNA level and might be consequential during the oocyte transcriptional silencing period.
The association between the presence and burden of periodic discharges and outcome in septic patients: an observational prospective study
Authors: Ferlini Lorenzo , Maenhout Christelle , Crippa Ilaria Alice , Quispe-Cornejo Armin Alvaro , Creteur Jacques , Taccone Fabio Silvio , Gaspard Nicolas 
Published: May 2023

Abstract
Background
Sepsis-associated encephalopathy (SAE) is frequent in septic patients. Electroencephalography (EEG) is very sensitive to detect early epileptic abnormalities, such as seizures and periodic discharges (PDs), and to quantify their duration (the so-called burden). However, the prevalence of these EEG abnormalities in septic patients, as well as their effect on morbidity and mortality, are still unclear. The aims of this study were to assess whether the presence of electrographic abnormalities (i.e. the absence of reactivity, the presence and burden of seizures and PDs) was associated with functional outcome and mortality in septic patients and whether these abnormalities were associated with sepsis-associated encephalopathy (SAE).

Methods
We prospectively included septic patients, without known chronic or acute intracranial disease or pre-existing acute encephalopathy, requiring ICU admission in a tertiary academic centre. Continuous EEG monitoring was started within 72 h after inclusion and performed for up to 7 days. A comprehensive assessment of consciousness and delirium was performed twice daily by a trained neuropsychologist. Primary endpoints were unfavourable functional outcome (UO, defined as a Glasgow Outcome Scale-Extended—GOSE—score < 5), and mortality collected at hospital discharge and secondary endpoint was the association of PDs with SAE. Mann–Whitney, Fisher’s exact and χ2 tests were used to assess differences in variables between groups, as appropriate. Multivariable logistic regression analysis with in-hospital mortality, functional outcome, SAE or PDs as the dependent variables were performed.

Results
We included 92 patients. No seizures were identified. Nearly 25% of patients had PDs. The presence of PDs and PDs burden was associated with UO in univariate (n = 15 [41%], p = 0.005 and p = 0.008, respectively) and, for PDs presence, also in multivariate analysis after correcting for disease severity (OR 3.82, IC 95% [1.27–11.49], p = 0.02). The PDs burden negatively correlated with GOSE (Spearman’s coefficient ρ = − 0.2, p = 0.047). The presence of PDs was also independently associated with SAE (OR 8.98 [1.11–72.8], p = 0.04). Reactivity was observed in the majority of patients and was associated with outcomes (p = 0.044 for both functional outcome and mortality).

Conclusion
Our findings suggest that PDs and PDs burden are associated with SAE and might affect outcome in septic patients.
Breast cancer genomes from CHEK2 c.1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile
Authors: Smid Marcel , Schmidt Marjanka K. , Prager-van der Smissen Wendy J. C. , Ruigrok-Ritstier Kirsten , Schreurs Maartje A. C. , Cornelissen Sten , Garcia Aida Marsal , Broeks Annegien , Timmermans A. Mieke , Trapman-Jansen Anita M. A. C. , Collée J. Margriet , Adank Muriel A. , Hooning Maartje J. , Martens John W. M. , Hollestelle Antoinette 
Published: May 2023

Abstract
Background
CHEK2 c.1100delC was the first moderate-risk breast cancer (BC) susceptibility allele discovered. Despite several genomic, transcriptomic and functional studies, however, it is still unclear how exactly CHEK2 c.1100delC promotes tumorigenesis. Since the mutational landscape of a tumor reflects the processes that have operated on its development, the aim of this study was to uncover the somatic genomic landscape of CHEK2-associated BC.

Methods
We sequenced primary BC (pBC) and normal genomes of 20 CHEK2 c.1100delC mutation carriers as well as their pBC transcriptomes. Including pre-existing cohorts, we exhaustively compared CHEK2 pBC genomes to those from BRCA1/2 mutation carriers, those that displayed homologous recombination deficiency (HRD) and ER− and ER+ pBCs, totaling to 574 pBC genomes. Findings were validated in 517 metastatic BC genomes subdivided into the same subgroups. Transcriptome data from 168 ER+ pBCs were used to derive a TP53-mutant gene expression signature and perform cluster analysis with CHEK2 BC transcriptomes. Finally, clinical outcome of CHEK2 c.1100delC carriers was compared with BC patients displaying somatic TP53 mutations in two well-described retrospective cohorts totaling to 942 independent pBC cases.

Results
BC genomes from CHEK2 mutation carriers were most similar to ER+ BC genomes and least similar to those of BRCA1/2 mutation carriers in terms of tumor mutational burden as well as mutational signatures. Moreover, CHEK2 BC genomes did not show any evidence of HRD. Somatic TP53 mutation frequency and the size distribution of structural variants (SVs), however, were different compared to ER+ BC. Interestingly, BC genomes with bi-allelic CHEK2 inactivation lacked somatic TP53 mutations and transcriptomic analysis indicated a shared biology with TP53 mutant BC. Moreover, CHEK2 BC genomes had an increased frequency of > 1 Mb deletions, inversions and tandem duplications with peaks at specific sizes. The high chromothripsis frequency among CHEK2 BC genomes appeared, however, not associated with this unique SV size distribution profile.

Conclusions
CHEK2 BC genomes are most similar to ER+ BC genomes, but display unique features that may further unravel CHEK2-driven tumorigenesis. Increased insight into this mechanism could explain the shorter survival of CHEK2 mutation carriers that is likely driven by intrinsic tumor aggressiveness rather than endocrine resistance.
Dynamics of plate equations with time delay driven by additive noise in $\mathbb{R}^{n}$
Authors: Yao Xiaobin 
Published: May 2023

AbstractThis paper is concerned with the asymptotic behavior of solutions for plate equations with delay blurred by additive noise in $\mathbb{R}^{n}$

R
n

. First, we obtain the uniform compactness of pullback random attractors of the problem, then derive the upper semicontinuity of the attractors.
NHS staff awareness, attitudes and actions towards the change in organ donation law in England—results of the #options survey 2020
Authors: Coe Dorothy , Newell Natasha , Jones Mark , Robb Matthew , Clark Natalie , Reaich David , Wroe Caroline 
Published: May 2023

Abstract
Background
In Spring 2020 there was a change in organ donation legislation in England (UK). Much is known about public opinions to organ donation and the change in legislation, however, there is little evidence about the opinions of the NHS workforce. This study set out to understand the levels of awareness, support and action of NHS staff to this change and explore the impact of respondent demographics, place and type of work on awareness, support and action.

Methods
An online survey was offered to all NHS organisations in North Thames and the North East and North Cumbria through the NIHR Clinical Research Network between July and December 2020. Participating organisations were provided with an information package and promoted the survey via email and internal staff communications. Associations were compared univariately using chi-square tests and logistic regression was used for multivariable analysis to compare findings with NHS Blood and Transplant public Kantar survey data.

Results
A total of 5789 staff participated in the survey. They were more aware, more supportive, more likely to have discussed their organ donation choices with family and more likely to be on the organ donor register than the public. This increased awareness and support was found across minority ethnic and religious groups. Those working in a transplanting centre were most aware and supportive and those working in the ambulance service were most likely to ‘opt-in’ following the change in legislation.

Conclusions
NHS staff in England were well informed about the change in organ donation legislation and levels of support were high. NHS staff were six times more likely than the public to have a conversation with their family about their organ donation choices. The size and ethnic diversity of the NHS workforce offers an opportunity to enable and support NHS staff to be advocates for organ donation and raise awareness of the change in legislation amongst their communities.